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Sample records for human visceral adipose

  1. Arteriolar function in visceral adipose tissue is impaired in human obesity.

    Science.gov (United States)

    Farb, Melissa G; Ganley-Leal, Lisa; Mott, Melanie; Liang, Yanmei; Ercan, Bahadir; Widlansky, Michael E; Bigornia, Sherman J; Fiscale, Antonino J; Apovian, Caroline M; Carmine, Brian; Hess, Donald T; Vita, Joseph A; Gokce, Noyan

    2012-02-01

    The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. In 30 obese subjects (age 42±11 years, body mass index 46±11 kg/m(2)) undergoing bariatric surgery, we intraoperatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75-250 μm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (Peffect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and had a higher capacity for cytokine production ex vivo. Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.

  2. Telomere length differences between subcutaneous and visceral adipose tissue in humans

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    Lakowa, Nicole; Trieu, Nhu; Flehmig, Gesine [Department of Medicine, University of Leipzig, Leipzig (Germany); Lohmann, Tobias [Municipal Clinic Dresden-Neustadt, Dresden (Germany); Schön, Michael R. [Städtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, Karlsruhe (Germany); Dietrich, Arne [Department of Surgery, University of Leipzig, Leipzig (Germany); IFB AdiposityDiseases, University of Leipzig, Leipzig (Germany); Zeplin, Philip Helge; Langer, Stefan [Department of Orthopaedics, Traumatology and Plastic Surgery, University of Leipzig, Leipzig (Germany); Stumvoll, Michael; Blüher, Matthias [Department of Medicine, University of Leipzig, Leipzig (Germany); Klöting, Nora, E-mail: nora.kloeting@medizin.uni-leipzig.de [IFB AdiposityDiseases, Junior Research Group 2 “Animal Models of Obesity”, University of Leipzig, Leipzig (Germany)

    2015-02-13

    Adipocyte hypertrophy and hyperplasia have been shown to be associated with shorter telomere length, which may reflect aging, altered cell proliferation and adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat distribution and AT cellular composition may contribute to obesity related metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are different between: (1) abdominal subcutaneous and omental fat depots, (2) superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and cells of the stromal vascular fraction (SVF). We further asked whether AT TL is related to age, anthropometric and metabolic traits. TL was analyzed by quantitative PCR in total human genomic DNA isolated from paired subcutaneous and visceral AT of 47 lean and 50 obese individuals. In subgroups, we analyzed TL in isolated small and large adipocytes and SVF cells. We find significantly shorter TL in subcutaneous compared to visceral AT (P < 0.001) which is consistent in men and subgroups of lean and obese, and individuals with or without type 2 diabetes (T2D). Shorter TL in SAT is entirely due to shorter TL in the SVF compared to visceral AT (P < 0.01). SAT TL is most strongly correlated with age (r = −0.205, P < 0.05) and independently of age with HbA1c (r = −0.5, P < 0.05). We found significant TL differences between superficial SAT of lean and obese as well as between individuals with our without T2D, but not between the two layers of SAT. Our data indicate that fat depot differences in TL mainly reflect shorter TL of SVF cells. In addition, we found an age and BMI-independent relationship between shorter TL and HbA1c suggesting that chronic hyperglycemia may impair the regenerative capacity of AT more strongly than obesity alone. - Highlights: • Telomere lengths (TL) differ between fat depots mainly due to different lengths in SVF. • TL is not associated with gender, BMI and T2D. • The tendency for

  3. Establishment and molecular characterization of mesenchymal stem cell lines derived from human visceral & subcutaneous adipose tissues.

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    Potdar, Pd; Sutar, Jp

    2010-01-01

    Mesenchymal stem cells (MSCs), are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, myocytes and adipocytes. We utilized adipose tissue as our primary source, since it is a rich source of MSCs as well as it can be harvested using a minimally invasive surgical procedure. Both visceral and subcutaneous adipose tissue (VSAT, SCAT respectively) samples were cultured using growth medium without using any substratum for their attachment. We observed growth of mesenchymal like cells within 15 days of culturing. In spite of the absence of any substratum, the cells adhered to the bottom of the petri dish, and spread out within 2 hours. Presently VSAT cells have reached at passage 10 whereas; SCAT cells have reached at passage 14. Morphologically MSCs obtained from visceral adipose tissue were larger in shape than subcutaneous adipose tissue. We checked these cells for presence or absence of specific stem cell molecular markers. We found that VSAT and SCAT cells confirmed their MSC phenotype by expression of specific MSC markers CD 105 and CD 13 and absence of CD34 and CD 45 markers which are specific for haematopoietic stem cells. These cells also expressed SOX2 gene confirming their ability of self-renewal as well as expressed OCT4, LIF and NANOG for their properties for pluripotency & plasticity. Overall, it was shown that adipose tissue is a good source of mesenchymal stem cells. It was also shown that MSCs, isolated from adipose tissue are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, cardiomyocytes, adipocytes and liver cells which may open a new era for cell based regenerative therapies for bone, cardiac and liver disorders.

  4. Establishment and Molecular Characterization of Mesenchymal Stem Cell Lines Derived From Human Visceral & Subcutaneous Adipose Tissues

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    Jyoti Prakash Sutar

    2010-01-01

    Full Text Available Mesenchymal stem cells (MSCs, are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, myocytes and adipocytes. We utilized adipose tissue as our primary source, since it is a rich source of MSCs as well as it can be harvested using a minimally invasive surgical procedure. Both visceral and subcutaneous adipose tissue (VSAT, SCAT respectively samples were cultured using growth medium without using any substratum for their attachment. We observed growth of mesenchymal like cells within 15 days of culturing. In spite of the absence of any substratum, the cells adhered to the bottom of the petri dish, and spread out within 2 hours. Presently VSAT cells have reached at passage 10 whereas; SCAT cells have reached at passage 14. Morphologically MSCs obtained from visceral adipose tissue were larger in shape than subcutaneous adipose tissue. We checked these cells for presence or absence of specific stem cell molecular markers. We found that VSAT and SCAT cells confirmed their MSC phenotype by expression of specific MSC markers CD 105 and CD13 and absence of CD34 and CD 45 markers which are specific for haematopoietic stem cells. These cells also expressed SOX2 gene confirming their ability of self-renewal as well as expressed OCT4, LIF and NANOG for their properties for pluripotency & plasticity. Overall, it was shown that adipose tissue is a good source of mesenchymal stem cells. It was also shown that MSCs, isolated from adipose tissue are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, cardiomyocytes, adipocytes and liver cells which may open a new era for cell based regenerative therapies for bone, cardiac and liver disorders.

  5. Visceral adiposity, insulin resistance and cancer risk

    LENUS (Irish Health Repository)

    Donohoe, Claire L

    2011-06-22

    Abstract Background There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Methods Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Results Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. Conclusions There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

  6. Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes.

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    Jones, D A; Prior, S L; Barry, J D; Caplin, S; Baxter, J N; Stephens, J W

    2014-12-01

    In the past 30 years, prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus and other co-morbidities. Visceral adipose tissue is believed to play a vital role, but underlying mechanisms remain unclear. Our aim was to investigate changes in markers of oxidative damage in human visceral adipose tissue to determine levels of oxidative burden that may be attributed to obesity and/or diabetes. Visceral adipose tissue samples from 61 subjects undergoing abdominal surgery grouped as lean, obese and obese with type 2 diabetes mellitus, were examined using 3 different markers of oxidative stress. Malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation, telomere length and Comet assay as markers of oxidative DNA damage. No significant difference in MDA concentration, telomere length and DNA damage was observed between groups, although longer telomere lengths were seen in the obese with diabetes group compared to the obese group (Pstress and DNA damage was observed in samples from subjects with type 2 diabetes mellitus. Further work is required to investigate this further, however this phenomenon may be due to an up regulation of antioxidant defences in adipose tissue. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals—Depot differences and dysmetabolism implications

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    Pestana, Diogo, E-mail: diogopestana@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Centro de Investigação Médica, P-4200-450 Porto (Portugal); CINTESIS—Center for Research in Health Technologies and Information Systems, P-4200-450 Porto (Portugal); Faria, Gil [General Surgery Department, S. João Hospital, Faculty of Medicine, University of Porto, P-4200-450 Porto (Portugal); Sá, Carla [Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Centro de Investigação Médica, P-4200-450 Porto (Portugal); Fernandes, Virgínia C. [Chemistry Investigation Centre (CIQ), Department of Chemistry, Faculty of Sciences, University of Porto, P-4169-007 Porto (Portugal); Requimte—Instituto Superior de Engenharia, Instituto Politécnico do Porto, P-4200-072 Porto (Portugal); Teixeira, Diana; Norberto, Sónia [Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Centro de Investigação Médica, P-4200-450 Porto (Portugal); Faria, Ana [Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Centro de Investigação Médica, P-4200-450 Porto (Portugal); Chemistry Investigation Centre (CIQ), Department of Chemistry, Faculty of Sciences, University of Porto, P-4169-007 Porto (Portugal); Faculty of Nutrition and Food Sciences, University of Porto, P-4200-465 Porto (Portugal); and others

    2014-08-15

    Background: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. Objectives: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. Methods: AT samples (n=189) from obese patients (BMI ≥35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. Results: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (R{sub S}=0.310, p<0.01) and duration of obesity (R{sub S}=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9±204.2 compared to 155.1±147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (R{sub S}=0.277, p<0.01), with relevance for vAT (R{sub S}=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. Conclusion: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their

  8. Sirtuins 1-7 expression in human adipose-derived stem cells from subcutaneous and visceral fat depots: influence of obesity and hypoxia.

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    Mariani, Stefania; Di Rocco, Giuliana; Toietta, Gabriele; Russo, Matteo A; Petrangeli, Elisa; Salvatori, Luisa

    2017-09-01

    The sirtuin family comprises seven NAD + -dependent deacetylases which control the overall health of organisms through the regulation of pleiotropic metabolic pathways. Sirtuins are important modulators of adipose tissue metabolism and their expression is higher in lean than obese subjects. At present, the role of sirtuins in adipose-derived stem cells has not been investigated yet. Therefore, in this study, we evaluated the expression of the complete panel of sirtuins in adipose-derived stem cells isolated from both subcutaneous and visceral fat of non-obese and obese subjects. We aimed at investigating the influence of obesity on sirtuins' levels, their role in obesity-associated inflammation, and the relationship with the peroxisome proliferator-activated receptor delta, which also plays functions in adipose tissue metabolism. The mRNA levels in the four types of adipose-derived stem cells were evaluated by quantitative polymerase chain reaction, in untreated cells and also after 8 h of hypoxia exposure. Correlations among sirtuins' expression and clinical and molecular parameters were also analyzed. We found that sirtuin1-6 exhibited significant higher mRNA expression in visceral adipose-derived stem cells compared to subcutaneous adipose-derived stem cells of non-obese subjects. Sirtuin1-6 levels were markedly reduced in visceral adipose-derived stem cells of obese patients. Sirtuins' expression in visceral adipose-derived stem cells correlated negatively with body mass index and C-reactive protein and positively with peroxisome proliferator-activated receptor delta. Finally, only in the visceral adipose-derived stem cells of obese patients hypoxia-induced mRNA expression of all of the sirtuins. Our results highlight that sirtuins' levels in adipose-derived stem cells are consistent with protective effects against visceral obesity and inflammation, and suggest a transcriptional mechanism through which acute hypoxia up-regulates sirtuins in the visceral

  9. Pathophysiology of human visceral obesity: an update

    National Research Council Canada - National Science Library

    Tchernof, André; Després, Jean-Pierre

    2013-01-01

    Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage...

  10. Effects of visceral adiposity on glycerol pathways in gluconeogenesis.

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    Neeland, Ian J; Hughes, Connor; Ayers, Colby R; Malloy, Craig R; Jin, Eunsook S

    2017-02-01

    To determine the feasibility of using oral 13 C labeled glycerol to assess effects of visceral adiposity on gluconeogenic pathways in obese humans. Obese (BMI ≥30kg/m 2 ) participants without type 2 diabetes underwent visceral adipose tissue (VAT) assessment and stratification by median VAT into high VAT-fasting (n=3), low VAT-fasting (n=4), and high VAT-refed (n=2) groups. Participants ingested [U- 13 C 3 ] glycerol and blood samples were subsequently analyzed at multiple time points over 3h by NMR spectroscopy. The fractions of plasma glucose (enrichment) derived from [U- 13 C 3 ] glycerol via hepatic gluconeogenesis, pentose phosphate pathway (PPP), and tricarboxylic acid (TCA) cycle were assessed using 13 C NMR analysis of glucose. Mixed linear models were used to compare 13 C enrichment in glucose between groups. Mean age, BMI, and baseline glucose were 49years, 40.1kg/m 2 , and 98mg/dl, respectively. Up to 20% of glycerol was metabolized in the TCA cycle prior to gluconeogenesis and PPP activity was minor (gluconeogenesis from glycerol in obese humans. Our findings provide preliminary evidence that excess visceral fat disrupts multiple pathways in hepatic gluconeogenesis from glycerol. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Visceral Adiposity Index: An Indicator of Adipose Tissue Dysfunction

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    Marco Calogero Amato

    2014-01-01

    Full Text Available The Visceral Adiposity Index (VAI has recently proven to be an indicator of adipose distribution and function that indirectly expresses cardiometabolic risk. In addition, VAI has been proposed as a useful tool for early detection of a condition of cardiometabolic risk before it develops into an overt metabolic syndrome. The application of the VAI in particular populations of patients (women with polycystic ovary syndrome, patients with acromegaly, patients with NAFLD/NASH, patients with HCV hepatitis, patients with type 2 diabetes, and general population has produced interesting results, which have led to the hypothesis that the VAI could be considered a marker of adipose tissue dysfunction. Unfortunately, in some cases, on the same patient population, there is conflicting evidence. We think that this could be mainly due to a lack of knowledge of the application limits of the index, on the part of various authors, and to having applied the VAI in non-Caucasian populations. Future prospective studies could certainly better define the possible usefulness of the VAI as a predictor of cardiometabolic risk.

  12. Significantly increased visceral adiposity index in prehypertension.

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    Yanan Ding

    Full Text Available The prevalence of prehypertension has increased in China, and prehypertension frequently progress to hypertension over a short time period; both have become public health problems. Therefore, this study was conducted to determine the relationship between the Visceral Adiposity Index (VAI and blood pressure (BP in China.A cross-sectional epidemiological survey was conducted in China using a stratified random cluster sampling method. Sex-specific VAI quartile cut-off points were used as follows: 0.88, 1.41, 2.45 in males and 0.85, 1.33, 2.22 in females. Prehypertension and hypertension were each defined according to The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 guidelines. A multivariate logistic analysis was conducted to analyze the relationship among VAI, prehypertension and hypertension.The ORs for prehypertension and hypertension in the upper quartiles of the VAI were 1.514 (1.074-2.133, P=0.018 and 1.660 (1.084-2.542, P=0.020, in males, after adjusting for age, education, smoking habits, alcohol consumption, physical activity, serum creatinine, fasting glucose, and plasma insulin. Following further adjustments for the above confounders, chronic kidney disease, and diabetes, the ORs for prehypertension and hypertension in the upper quartile of the VAI were 1.660 1.533 (1.086-2.165, P=0.015, and 1.743 (1.133-2.680, P=0.011, in males. The ORs for prehypertension and hypertension in the upper quartile of the VAI were 1.691 (1.223-2.338, P=0.001, and 1.682 (1.162-2.435, P=0.006, in females, after adjusting for age, education, smoking habits, alcohol consumption, physical activity, serum creatinine, fasting glucose, and plasma insulin. Following further adjustments for the above confounders, chronic kidney disease, and diabetes, the ORs for prehypertension and hypertension in the upper quartile of the VAI were 1.688 (1.220-2.334, P=0.002, and 1.657 (1

  13. Visceral Adiposity and Sarcopenic Visceral Obesity are Associated with Poor Prognosis After Resection of Pancreatic Cancer.

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    Okumura, Shinya; Kaido, Toshimi; Hamaguchi, Yuhei; Kobayashi, Atsushi; Shirai, Hisaya; Yao, Siyuan; Yagi, Shintaro; Kamo, Naoko; Hatano, Etsuro; Okajima, Hideaki; Takaori, Kyoichi; Uemoto, Shinji

    2017-11-01

    Visceral fat accumulation and muscle depletion have been identified as poor prognostic factors for various cancers. However, the significance of visceral adiposity and sarcopenic visceral obesity on outcomes after resection of pancreatic cancer remains unclear. A retrospective analysis of 301 patients who underwent resection for localized pancreatic cancer between 2004 and 2015 was performed. The extent of visceral adiposity [visceral to subcutaneous adipose tissue area ratio (VSR)] and visceral obesity [visceral fat area (VFA)] were measured on preoperative computed tomography images, together with skeletal muscle index (SMI) and muscle attenuation (MA). The impacts of these body composition parameters on outcomes after pancreatic resection were investigated. The overall survival (OS) and recurrence-free survival (RFS) rates in patients with high VSR were significantly lower than those in patients with low VSR (P = 0.001, P = 0.007, respectively). There were no differences in OS and RFS between high VFA and low VFA group; however, when analyzed together with sarcopenic factors, OS and RFS rates of the patients with sarcopenic visceral obesity were significantly lower compared with those of the others. Multivariate analyses revealed that high VSR was an independent risk factor for mortality (hazard ratio (HR) 1.58, P = 0.009) and recurrence (HR 1.41, P = 0.026) together with low SMI, low MA, high CA19-9, microvascular invasion, and nodal metastasis. Visceral adiposity and sarcopenic visceral obesity, as well as low muscle mass and quality, were closely associated with mortality and recurrence after resection of pancreatic cancer.

  14. Expression of S6K1 in human visceral adipose tissue is upregulated in obesity and related to insulin resistance and inflammation.

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    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Andrada, Patricia; Rotellar, Fernando; Valentí, Víctor; Moncada, Rafael; Martí, Pablo; Silva, Camilo; Salvador, Javier; Frühbeck, Gema

    2015-04-01

    The ribosomal protein S6 kinase 1 (S6K1) is a component of the insulin signalling pathway that has been proposed as a key molecular factor in insulin resistance development under conditions of nutrient overload. The aim was to evaluate the involvement of S6K1 in obesity as well as to explore their association with visceral adipose tissue (VAT) inflammation. Samples obtained from 40 subjects were used. Gene expression levels of RPS6KB1 and key inflammatory markers were analysed in VAT. The effect of insulin on transcript levels of RPS6KB1 in human differentiated adipocytes was also explored. RPS6KB1 mRNA levels in VAT were increased (P obese patients. Insulin treatment significantly enhanced (P insulin resistance was observed. Moreover, RPS6KB1 gene expression levels were positively correlated with VAT gene expression levels of the inflammatory markers CCL2, CD68, MMP2, MMP9, VEGFA and CHI3L1 as well as with mRNA levels of MTOR and MAPK8, representative players involved in signalling pathways related to S6K1. The increased levels of S6K1 in obesity and its positive association with insulin resistance and inflammation suggest a role for this protein in the changes that take place in VAT in obesity establishing a link between inflammation and a higher risk for the development of metabolic diseases.

  15. Quantification of visceral adipose tissue in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Frøssing, Signe; Nylander, Malin Chatarina; Chabanova, Elizaveta

    2018-01-01

    Background Polycystic ovary syndrome (PCOS) is associated with frequent overweight and abdominal obesity. Quantifying visceral adipose tissue (VAT) in PCOS patients can be a tool to assess metabolic risk and monitor effects of treatment. The latest dual-energy X-ray absorptiometry (DXA) technology...

  16. Visceral adipose tissue area measurement at a single level: can it represent visceral adipose tissue volume?

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    Noumura, Yusuke; Kamishima, Tamotsu; Sutherland, Kenneth; Nishimura, Hideho

    2017-08-01

    Measurement of visceral adipose tissue (VAT) needs to be accurate and sensitive to change for risk monitoring. The purpose of this study is to determine the CT slice location where VAT area can best reflect changes in VAT volume and body weight. 60 plain abdominal CT images from 30 males [mean age (range) 51 (41-68) years, mean body weight (range) 71.1 (101.9-50.9) kg] who underwent workplace screenings twice within a 1-year interval were evaluated. Automatically calculated and manually corrected areas of the VAT of various scan levels using "freeform curve" region of interest on CT were recorded and compared with body weight changes. The strongest correlations of VAT area with VAT volume and body weight changes were shown in a slice 3 cm above the lower margin of L3 with r values of 0.853 and 0.902, respectively. VAT area measurement at a single level 3 cm above the lower margin of the L3 vertebra is feasible and can reflect changes in VAT volume and body weight. Advances in knowledge: As VAT area at a CT slice 3cm above the lower margin of L3 can best reflect interval changes in VAT volume and body weight, VAT area measurement should be selected at this location.

  17. Exenatide with Metformin Ameliorated Visceral Adiposity and Insulin Resistance

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    Xuan Du

    2018-01-01

    Full Text Available Background. To study the effectiveness of exenatide with metformin and sequential treatment with exenatide and glargine added to metformin and their influence on insulin sensitivity and adipose distribution. Methods. 20 newly diagnosed obese type 2 diabetic patients were enrolled, and 2-month washout treatment of metformin, 6-month exenatide treatment, and 6-month glargine treatment were administrated sequentially accompanied with previous metformin. Glucolipid metabolic parameters were compared among groups. Adipose distribution was quantified with computerized tomography according to anatomy, dividing into visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT, adding up to total adipose tissue (TAT. Results. The 6-month exenatide treatment dramatically ameliorated the glucose and lipid profile, improved insulin sensitivity, and mainly decreased VAT and also the ratio of VAT/SAT (RVS. The following 6-month glargine treatment increased VAT. The whole 12-month sequential treatment with exenatide and glargine added to metformin basically improved the insulin sensitivity and glucolipid control though VAT rebounded at the end, however without deteriorating the other parameters. Conclusion. Exenatide is an ideal treatment for obese type 2 diabetic patients in the aspect of adipose tissue distribution. Sequential treatment of exenatide and glargine could be an alternative for low-income patients who cannot afford GLP-1 agonist for long time. This trial is registered with ChiCTR-OOC-17013679.

  18. Adipose tissue in muscle : a novel depot similar in size to visceral adipose tissue

    NARCIS (Netherlands)

    Gallagher, Dympna; Kuznia, Patrick; Heshka, Stanley; Albu, Jeanine; Heymsfield, Steven B; Goodpaster, Bret H; Visser, Marjolein; Harris, Tamara B

    BACKGROUND: The manner in which fat depot volumes and distributions, particularly the adipose tissue (AT) between the muscles, vary by race is unknown. OBJECTIVE: The objective was to quantify a previously unstudied and novel intermuscular AT (IMAT) depot and subcutaneous AT, visceral AT (VAT), and

  19. Visceral adipose tissue is associated with microstructural brain tissue damage.

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    Widya, Ralph L; Kroft, Lucia J M; Altmann-Schneider, Irmhild; van den Berg-Huysmans, Annette A; van der Bijl, Noortje; de Roos, Albert; Lamb, Hildo J; van Buchem, Mark A; Slagboom, P Eline; van Heemst, Diana; van der Grond, Jeroen

    2015-05-01

    Obesity has been associated with microstructural brain tissue damage. Different fat compartments demonstrate different metabolic and endocrine behaviors. The aim was to investigate the individual associations between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and microstructural integrity in the brain. This study comprised 243 subjects aged 65.4 ± 6.7 years. The associations between abdominal VAT and SAT, assessed by CT, and magnetization transfer imaging markers of brain microstructure for gray and white matter were analyzed and adjusted for confounding factors. VAT was associated with normalized MTR peak height in gray (β -0.216) and white matter (β -0.240) (both P  0.05). Stepwise linear regression analysis showed that only VAT was associated with normalized MTR peak height in gray and white matter (both P VAT rather than SAT is associated with microstructural brain tissue damage in elderly individuals. © 2015 The Obesity Society.

  20. Role of Nampt and Visceral Adiposity in Esophagogastric Junction Adenocarcinoma

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    Haijun Li

    2017-01-01

    Full Text Available Nampt including eNampt and iNampt may contribute to mediating obesity-associated cancers. This study investigated the role of Nampt in esophagogastric junction adenocarcinoma (EGA, a cancer strongly correlated with obesity. Visceral adiposity was defined by waist circumference or VFA. eNampt in sera were measured by enzyme-linked immunosorbent assay. iNampt expression in EGA was determined by PCR, western blot, and immunohistochemistry. Sera eNampt were significantly elevated in these overweight and obese patients, especially for viscerally obese patients, and positively correlated with BMI, waist circumference, VFA, and also primary tumor, regional lymph nodes, and TNM stage (P<0.05. iNampt expression in both the mRNA and protein levels was upregulated in EGAs (P<0.05. iNampt staining was found primarily in the cytoplasm and nuclei and significantly associated with tumor, lymph nodes, and TNM stage and also correlated positively with serum eNampt, BMI, total fat area, VFA, superficial fat area, and waist circumference (P<0.05. iNampt, eNampt, tumor, lymph nodes, and TNM stage correlated to the survival of EGAs, and iNampt expression and TNM stage affected the prognosis independently (P<0.05. This study highlighted the association of eNampt/iNampt with visceral obesity and a potential impact on the biology of EGA.

  1. [Human brown adipose tissue].

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    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  2. So as we worry we weigh: Visible burrow system stress and visceral adiposity.

    Science.gov (United States)

    Foster, Michelle T

    2017-09-01

    The visible borrow system (VBS) simulates a natural rodent habitat that supports genuine stress provoking social interactions. This model allows investigation of behavioral, neural and endocrine alterations caused by chronic stress. The Sakai lab further used this model to investigate metabolic outcomes of stress in relation to dominance hierarchies formed within the VBS. Communal social conflict occurs among all VBS rats, but only the SUB rats succumb to the redistribution of lipids in the visceral cavity and consequent metabolic dysregulation, such as hyper-insulinemia. These increases in visceral adipose tissue occur after two cycles of VBS stress and recovery bouts and are associated with decreases in subcutaneous adipose tissue. Traditionally, distribution shift in lipid deposition is predominately thought to occur by characteristics specific to the visceral depot, but evidence supports that decreased subcutaneous adipose tissue deposition may be linked to enhanced visceral adipose expansion. This review will discuss VBS stress and redirection of adipose tissue in SUB rats. There will be specific focus on the enhanced adipogenic capacity of visceral adipose tissue as driven by glucocorticoid receptor density, 11-hydroxysteroid dehydrogenase type 1 (11-HSD1) and lipoprotein lipase (LPL). Additionally, the proposed contribution of decreased subcutaneous adipose expansion via stress-induced inhibition of lipid uptake, storage and cellularity will be discussed. Overall, this review will summarize how stress-induced visceral obesity may result from a combination of maladaptive responses within the visceral and subcutaneous depot. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Association of visceral adiposity with oesophageal and junctional adenocarcinomas.

    LENUS (Irish Health Repository)

    Beddy, P

    2012-02-01

    BACKGROUND: Obesity is associated with an increased incidence of oesophageal and oesophagogastric junction adenocarcinoma, in particular Siewert types I and II. This study compared abdominal fat composition in patients with oesophageal\\/junctional adenocarcinoma with that in patients with oesophageal squamous cell carcinoma and gastric adenocarcinoma, and in controls. METHOD: In total, 194 patients (110 with oesophageal\\/junctional adenocarcinoma, 38 with gastric adenocarcinoma and 46 with oesophageal squamous cell carcinoma) and 90 matched control subjects were recruited. The abdominal fat area was assessed using computed tomography (CT), and the total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) were calculated. RESULTS: Patients with oesophageal\\/junctional adenocarcinoma had significantly higher TFA and VFA values compared with controls (both P < 0.001), patients with gastric adenocarcinoma (P = 0.013 and P = 0.006 respectively) and patients with oesophageal squamous cell carcinoma (both P < 0.001). For junctional tumours, the highest TFA and VFA values were seen in patients with Siewert type I tumours (respectively P = 0.041 and P = 0.033 versus type III; P = 0.332 and P = 0.152 versus type II). CONCLUSION: Patients with oesophageal\\/junctional adenocarcinoma, in particular oesophageal and Siewert type I junctional tumours, have greater CT-defined visceral adiposity than patients with gastric adenocarcinoma or oesophageal squamous cell carcinoma, or controls.

  4. Clodronate liposomes improve metabolic profile and reduce visceral adipose macrophage content in diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Bin Feng

    Full Text Available BACKGROUND: Obesity-related adipose inflammation has been thought to be a causal factor for the development of insulin resistance and type 2 diabetes. Infiltrated macrophages in adipose tissue of obese animals and humans are an important source for inflammatory cytokines. Clodronate liposomes can ablate macrophages by inducing apoptosis. In this study, we aim to determine whether peritoneal injection of clodronate liposomes has any beneficial effect on systemic glucose homeostasis/insulin sensitivity and whether macrophage content in visceral adipose tissue will be reduced in diet-induced obese (DIO mice. METHODOLOGY/PRINCIPAL FINDINGS: Clodronate liposomes were used to deplete macrophages in lean and DIO mice. Macrophage content in visceral adipose tissue, metabolic parameters, glucose and insulin tolerance, adipose and liver histology, adipokine and cytokine production were examined. Hyperinsulinemic-euglycemic clamp study was also performed to assess systemic insulin sensitivity. Peritoneal injection of clodronate liposomes significantly reduced blood glucose and insulin levels in DIO mice. Systemic glucose tolerance and insulin sensitivity were mildly improved in both lean and DIO mice treated with clodronate liposomes by intraperitoneal (i.p. injection. Hepatosteatosis was dramatically alleviated and suppression of hepatic glucose output was markedly increased in DIO mice treated with clodronate liposomes. Macrophage content in visceral adipose tissue of DIO mice was effectively decreased without affecting subcutaneous adipose tissue. Interestingly, levels of insulin sensitizing hormone adiponectin, including the high molecular weight form, were significantly elevated in circulation. CONCLUSIONS/SIGNIFICANCE: Intraperitoneal injection of clodronate liposomes reduces visceral adipose tissue macrophages, improves systemic glucose homeostasis and insulin sensitivity in DIO mice, which can be partially attributable to increased adiponectin

  5. Pathophysiology of human visceral obesity: an update.

    Science.gov (United States)

    Tchernof, André; Després, Jean-Pierre

    2013-01-01

    Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese

  6. The association of visceral adiposity with cardiovascular events in patients with peripheral artery disease.

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    Oliver Cronin

    Full Text Available BACKGROUND: Previous studies have suggested that patients with peripheral artery disease (PAD suffer from a high incidence of cardiovascular events (CVE. Visceral adiposity has been implicated in promoting CVEs. This study aimed to assess the association of relative visceral adipose volume with incident cardiovascular events in patients with peripheral artery disease. METHODS: This was a prospective cohort study including 260 patients with PAD who presented between 2003 and 2012. Cases were patients with diagnosed PAD including symptomatic lower limb athero-thrombosis and asymptomatic abdominal aortic aneurysm. All patients underwent computed tomography angiography (CTA. Abdominal visceral to total adipose volume ratio (relative visceral adipose volume was estimated from CTAs using a previously validated workstation protocol. Cardiovascular risk factors were recorded at entry. The association of visceral adiposity with major CVEs (death, non-fatal myocardial infarction or stroke was examined using Kaplan Meier and Cox proportional hazard analyses. RESULTS: A total of 92 major CVEs were recorded in 76 patients during a median follow-up of 2.8 (IQR 1.2 to 4.8 years, including myocardial infarction (n = 26, stroke (n = 10 and death (n = 56. At 3 years the incidence of major CVEs stratified by relative visceral adipose volume quartiles were 15% [Quartile (Q 1], 17% (Q2, 11% (Q3 and 15% (Q4 (P = 0.517. Relative visceral adipose volume was not associated with major CVEs after adjustment for other risk factors. CONCLUSION: This study suggests that visceral adiposity does not play a central role in the predisposition for major CVEs in patients with PAD.

  7. Surrogate markers of visceral adiposity in young adults: waist circumference and body mass index are more accurate than waist hip ratio, model of adipose distribution and visceral adiposity index.

    Science.gov (United States)

    Borruel, Susana; Moltó, José F; Alpañés, Macarena; Fernández-Durán, Elena; Álvarez-Blasco, Francisco; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

    2014-01-01

    Surrogate indexes of visceral adiposity, a major risk factor for metabolic and cardiovascular disorders, are routinely used in clinical practice because objective measurements of visceral adiposity are expensive, may involve exposure to radiation, and their availability is limited. We compared several surrogate indexes of visceral adiposity with ultrasound assessment of subcutaneous and visceral adipose tissue depots in 99 young Caucasian adults, including 20 women without androgen excess, 53 women with polycystic ovary syndrome, and 26 men. Obesity was present in 7, 21, and 7 subjects, respectively. We obtained body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), model of adipose distribution (MOAD), visceral adiposity index (VAI), and ultrasound measurements of subcutaneous and visceral adipose tissue depots and hepatic steatosis. WC and BMI showed the strongest correlations with ultrasound measurements of visceral adiposity. Only WHR correlated with sex hormones. Linear stepwise regression models including VAI were only slightly stronger than models including BMI or WC in explaining the variability in the insulin sensitivity index (yet BMI and WC had higher individual standardized coefficients of regression), and these models were superior to those including WHR and MOAD. WC showed 0.94 (95% confidence interval 0.88-0.99) and BMI showed 0.91 (0.85-0.98) probability of identifying the presence of hepatic steatosis according to receiver operating characteristic curve analysis. In conclusion, WC and BMI not only the simplest to obtain, but are also the most accurate surrogate markers of visceral adiposity in young adults, and are good indicators of insulin resistance and powerful predictors of the presence of hepatic steatosis.

  8. Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity

    DEFF Research Database (Denmark)

    Kraunsøe, Regitze; Boushel, Robert Christopher; Hansen, Christina Neigaard

    2010-01-01

    abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples...

  9. Visceral Adiposity, Genetic Susceptibility, and Risk of Complications Among Individuals with Crohn's Disease

    NARCIS (Netherlands)

    van der Sloot, Kimberley; Ziad Alizadeh, Behrooz

    INTRODUCTION: Adipose tissue in mesenteric fat plays a key role in systemic and luminal inflammation. However, little is known about the role of visceral adipose tissue (VAT) and its interaction with genetic predisposition in Crohn's disease (CD) progression. METHODS: Our study population included

  10. Visceral Adiposity, Genetic Susceptibility, and Risk of Complications Among Individuals with Crohn's Disease

    NARCIS (Netherlands)

    Van Der Sloot, Kimberley W. J.; Joshi, Amit D.; Bellavance, Danielle R.; Gilpin, Katherine K.; Stewart, Kathleen O.; Lochhead, Paul; Garber, John J.; Giallourakis, Cosmas; Yajnik, Vijay; Ananthakrishnan, Ashwin N.; Alizadeh, Behrooz Z.; Xavier, Ramnik J.; Khalili, Hamed

    Introduction: Adipose tissue in mesenteric fat plays a key role in systemic and luminal inflammation. However, little is known about the role of visceral adipose tissue (VAT) and its interaction with genetic predisposition in Crohn's disease (CD) progression. Methods: Our study population included

  11. Sleep and birthweight predict visceral adiposity in overweight/obese children.

    Science.gov (United States)

    Sokolovic, N; Kuriyan, R; Kurpad, A V; Thomas, T

    2013-06-01

    Visceral adiposity poses significant consequences for long-term health and it is important to identify methods that can be used to prevent fat deposition in visceral adipose tissue. To identify the factors contributing to differential fat distribution in overweight/obese children. Demographic, dietary and lifestyle factors potentially associated with increased visceral adipose tissue in overweight and obese South-Indian children aged 3 to 16 years. The diagnosis of visceral obesity was based on the waist-to-height ratio (WHtR) cut-off value of 0.5. Exposure variables with statistically different distributions in the two WHtR categories, when examined by Mann-Whitney and chi-square tests, were used to develop a binary logistic regression model of visceral adiposity. Increased birthweight and higher sleep duration were significant predictors of having a healthy WHtR, with odds ratios of 1.30 and 1.26 respectively. Early programming effects associated with low birthweight and current sleep deprivation could promote the storage of excess fat as visceral adipose tissue in overweight and obese children. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

  12. Metabolic response of visceral white adipose tissue of obese mice exposed for 5 days to human room temperature compared to mouse thermoneutrality

    NARCIS (Netherlands)

    Stelt, van der Inge; Hoevenaars, Femke; Široká, Jitka; Ronde, de Lidwien; Friedeckỳ, David; Keijer, Jaap; Schothorst, van Evert

    2017-01-01

    Housing of laboratory mice at room temperature (22°C) might be considered a constant cold stress, which induces a thermogenic program in brown adipose tissue (BAT). However, the early adaptive response of white adipose tissue (WAT), the fat storage organ of the body, to a change from

  13. Predictive performance of the visceral adiposity index for a visceral adiposity-related risk: Type 2 Diabetes

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    Azizi Fereidoun

    2011-05-01

    Full Text Available Abstract Background Visceral adiposity index (VAI has recently been developed based on waist circumference, body mass index (BMI, triglycerides (TGs, and high-density lipoprotein cholesterol (HDL-C. We examined predictive performances for incident diabetes of the VAI per se and as compared to the metabolic syndrome (MetS and waist-to-height-ratio (WHtR. Methods Participants free of diabetes at baseline with at least one follow-up examination (5,964 were included for the current study. Weibull regression models were developed for interval-censored survival data. Absolute and relative integrated discriminatory improvement index (IDI and cut-point-based and cut-point-free net reclassification improvement index (NRI were used as measures of predictive ability for incident diabetes added by VAI, as compared to the MetS and WHtR. Results The annual incidence rate of diabetes was 0.85 per 1000 person. Mean VAI was 3.06 (95%CIs 2.99-3.13. Diabetes risk factors levels increased in stepwise fashion across VAI quintiles. Risk gradient between the highest and lowest quintile of VAI was 4.5 (95%CIs 3.0-6.9. VAI significantly improved predictive ability of the MetS. The relative IDI and cut-point free NRI for predictive ability added to MetS by VAI were 30.3% (95%CIs 18.8-41.8% and 30.7% (95%CIs 20.8-40.7%, respectively. WHtR, outperformed VAI with cut-point-free NRI of 24.6% (95%CIs 14.1-35.2%. Conclusions In conclusion, although VAI could be a prognostic tool for incident diabetes events, gathering information on its components (WC, BMI, TGs, and HDL-C is unlikely to improve the prediction ability beyond what could be achieved by the simply assessable and commonly available information on WHtR.

  14. Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis.

    Science.gov (United States)

    Alexopoulos, Nikolaos; Katritsis, Demosthenes; Raggi, Paolo

    2014-03-01

    The current epidemic of obesity with the associated increasing incidence of insulin resistance, diabetes mellitus and atherosclerosis affecting a large proportion of the North American and Western populations, has generated a strong interest in the potential role of visceral adipose tissue in the development of atherosclerosis and its complications. The intra-abdominal and epicardial space are two compartments that contain visceral adipose tissue with a similar embryological origin. These visceral fats are highly inflamed in obese patients, patients with the metabolic syndrome and in those with established coronary artery disease; additionally they are capable of secreting large quantities of pro-inflammatory cytokines and free fatty acids. There is accumulating evidence to support a direct involvement of these regional adipose tissue deposits in the development of atherosclerosis and its complicating events, as will be reviewed in this article. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Carotid stiffness, extra-media thickness and visceral adiposity in young adults.

    Science.gov (United States)

    Lefferts, Wesley K; Sperry, Susan D; Jorgensen, Randall S; Kasprowicz, Ari G; Skilton, Michael R; Figueroa, Arturo; Heffernan, Kevin S

    2017-10-01

    Carotid extra-media thickness (EMT) encompasses arterial adventitia and perivascular adipose tissue (PAT). Adventitial remodeling and PAT may contribute independently to functional (stiffness) and structural (remodeling) changes in artery wall properties. Visceral adiposity may contribute to PAT, thereby affecting artery stiffness. We investigated the relationships between carotid artery stiffness, EMT, and visceral adiposity in young, healthy individuals. 135 healthy males (20 ± 2 yr, body mass index [BMI] 24.8 ± 3.3 kg/m(2)) underwent anthropometric and vascular measures on two separate days. Visceral adiposity was assessed using waist circumference and sagittal abdominal diameter (SAD). Brachial and carotid systolic, diastolic, and pulsatile (PP) blood pressures were assessed using an oscillometric cuff and applanation tonometry, respectively. Carotid intima-media thickness (IMT) and EMT were assessed using Doppler ultrasound. Carotid artery stiffness was calculated as β-stiffness and calibrated to carotid pressures. Separate stepwise multiple regression models demonstrated that carotid PP (β = 0.205) and EMT (β = 0.267) accounted for 12.6% of variance in β-stiffness, while carotid PP (β = 0.195) and SAD (β = 0.226) accounted for 10.5% of variance in EMT (p < 0.05). Mediation analyses revealed carotid PP partially mediated the relationship between a) EMT and β-stiffness, and b) SAD and EMT (p < 0.05). Carotid PP and EMT, but not IMT, are related to carotid β-stiffness. Carotid PP and visceral adiposity (SAD) are related to EMT. Carotid PP partially mediates the association between a) EMT and carotid β-stiffness, and b) SAD and EMT. Our findings suggest visceral adiposity may detrimentally affect subclinical markers of cardiovascular disease risk (carotid PP, EMT) and contribute to artery stiffness. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Metabolic profiling of visceral adipose tissue from obese subjects with or without metabolic syndrome.

    Science.gov (United States)

    Candi, Eleonora; Tesauro, Manfredi; Cardillo, Carmine; Lena, Anna Maria; Schinzari, Francesca; Rodia, Giuseppe; Sica, Giuseppe; Gentileschi, Paolo; Rovella, Valentina; Annicchiarico-Petruzzelli, Margherita; Di Daniele, Nicola; Melino, Gerry

    2018-02-08

    Obesity represents one of the most complex public health challenges and has recently reached epidemic proportions.  Obesity is also considered to be primarily responsible for the rising prevalence of metabolic syndrome, defined as the coexistence in the same individual of several risk factors for atherosclerosis, including dyslipidaemia, hypertension and hyperglycaemia, as well as for cancer. Additionally, the presence of three of the five risk factors (abdominal obesity, low HDL cholesterol, high triglycerides, high fasting glucose and high blood pressure) characterizes metabolic syndrome, which has serious clinical consequences.  The current study was conducted in order to identify metabolic differences in visceral adipose tissue collected from obese (BMI 43-48) human subjects who were diagnosed with metabolic syndrome, obese individuals who were metabolically healthy and non-obese healthy controls. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analyses were used to obtain the untargeted visceral adipose tissue metabolomics profiles of 481 metabolites belonging to all biochemical pathways. Our results indicated consistent increases in oxidative stress markers from the pathologically obese samples in addition to subtle markers of elevated glucose levels that may be consistent with metabolic syndrome. In the tissue derived from the pathologically obese subjects, there were significantly elevated levels of plasmalogens, which may be increased in response to oxidative changes in addition to changes in glycerol-phosphorylcholine, glycerol-phosphorylethanolamine glycerol-phosphorylserine, ceramides and sphingolipids. These data could be potentially helpful for recognizing new pathways that underlie the metabolic-vascular complications of obesity and may lead to the development of innovative targeted therapies. ©2018 The Author(s).

  17. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women

    DEFF Research Database (Denmark)

    Fox, Caroline S; Liu, Yongmei; White, Charles C

    2012-01-01

    of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose...... tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio......-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI...

  18. Novel gender-specific visceral adiposity index for Mexican pediatric population

    Directory of Open Access Journals (Sweden)

    María J. Garcés

    2014-10-01

    Conclusions: VAI formula construction seemed to be different in children compared to adults. In the present study we propose a new gender-specific visceral adipose index for pediatric Mexican population living in urban areas that could be further used to predict abnormal cardiometabolic outcomes.

  19. Influence of Visceral Adiposity on Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Eun-Hee Jang

    2012-08-01

    Full Text Available BackgroundThe aim of this study was to investigate the influences of visceral adiposity on cardiovascular autonomic neuropathy (CAN in patients with type 2 diabetes mellitus.MethodsTwo hundred eleven patients with type 2 diabetes participated in this study. Anthropometric and metabolic parameters were measured, and the visceral fat area was assessed using computed tomography. CAN was diagnosed using a cardiovascular reflex test. We analyzed the correlation between the visceral fat area and each parameter in this test.ResultsThe mean age, body mass index (BMI, and duration of diabetes of the study population were 60±14 years (mean±standard deviation, 25.1±4.2 kg/m2, and 12.3±8.9 years, respectively. The visceral fat area showed positive correlations with age, BMI, waist circumference, and subcutaneous fat area. There was no statistically significant difference in the cardiovascular reflex test outcome between genders. Univariate linear regression analysis showed that an increased visceral fat area diminished good heart rate response to a Valsalva maneuver (R2=4.9%, P=0.013 in an unadjusted model, but only in women. This statistical association was preserved after adjusting for age and BMI (R2=9.8%, P=0.0072.ConclusionThe results of this study suggest that visceral adiposity contributes to an autonomic imbalance to some degree, as demonstrated by the impaired cardiovascular reflex test among women with type 2 diabetes.

  20. Metabolic Response of Visceral White Adipose Tissue of Obese Mice Exposed for 5 Days to Human Room Temperature Compared to Mouse Thermoneutrality.

    Science.gov (United States)

    van der Stelt, Inge; Hoevenaars, Femke; Široká, Jitka; de Ronde, Lidwien; Friedecký, David; Keijer, Jaap; van Schothorst, Evert

    2017-01-01

    Housing of laboratory mice at room temperature (22°C) might be considered a constant cold stress, which induces a thermogenic program in brown adipose tissue (BAT). However, the early adaptive response of white adipose tissue (WAT), the fat storage organ of the body, to a change from thermoneutrality to room temperature is not known. This was investigated here for various WAT depots, focusing on epididymal WAT (eWAT), widely used as reference depot. Male adult diet-induced obese (DIO) C57BL/6JOlaHsd mice housed at thermoneutrality (29°C), were for 5 days either switched to room temperature (22°C) or remained at thermoneutrality. Energy metabolism was continuously measured using indirect calorimetry. At the end of the study, serum metabolomics and WAT transcriptomics were performed. We confirmed activation of the thermogenic program in 22°C housed mice. Body weight and total fat mass were reduced. Whole body energy expenditure (EE) was increased, with a higher fatty acid to carbohydrate oxidation ratio and increased serum acylcarnitine levels, while energy intake was not significantly different between the two groups. Transcriptome analysis of eWAT identified tissue remodeling and inflammation as the most affected processes. Expression of pro-inflammatory M1 macrophage-related genes, and M1 over M2 macrophage ratio were decreased, which might be linked to an increased insulin sensitivity. Markers of thermogenesis were not altered in eWAT. Decreased expression of tryptophan hydroxylase 2 (Tph2) and cholecystokinin (Cck) might represent altered neuroendocrine signaling. eWAT itself does not show increased fatty acid oxidation. The three measured WATs, epididymal, mesenteric, and retroperitoneal, showed mainly similar responses; reduced inflammation (s100a8), decreased carbohydrate oxidation, and no or small differences in fatty acid oxidation. However, Ucp1 was only expressed and increased in rWAT in 22°C housed mice. Cck expression was decreased in the three

  1. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.

    Directory of Open Access Journals (Sweden)

    Caroline S Fox

    Full Text Available Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT, visceral adipose tissue (VAT, VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09, previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08. Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08, but not men (p = 0.75. Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006 but not men (p = 0.24 for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]. Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI; associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a

  2. Differential sympathetic outflow to adipose depots is required for visceral fat loss in response to calorie restriction.

    Science.gov (United States)

    Sipe, L M; Yang, C; Ephrem, J; Garren, E; Hirsh, J; Deppmann, C D

    2017-04-10

    The sympathetic nervous system (SNS) regulates energy homeostasis in part by governing fatty acid liberation from adipose tissue. We first examined whether SNS activity toward discrete adipose depots changes in response to a weight loss diet in mice. We found that SNS activity toward each adipose depot is unique in timing, pattern of activation, and habituation with the most dramatic contrast between visceral and subcutaneous adipose depots. Sympathetic drive toward visceral epididymal adipose is more than doubled early in weight loss and then suppressed later in the diet when weight loss plateaued. Coincident with the decline in SNS activity toward visceral adipose is an increase in activity toward subcutaneous depots indicating a switch in lipolytic sources. In response to calorie restriction, SNS activity toward retroperitoneal and brown adipose depots is unaffected. Finally, pharmacological blockage of sympathetic activity on adipose tissue using the β3-adrenergic receptor antagonist, SR59230a, suppressed loss of visceral adipose mass in response to diet. These findings indicate that SNS activity toward discrete adipose depots is dynamic and potentially hierarchical. This pattern of sympathetic activation is required for energy liberation and loss of adipose tissue in response to calorie-restricted diet.

  3. The potential role of inhibitor of differentiation-3 in human adipose tissue remodeling and metabolic health

    DEFF Research Database (Denmark)

    Svendstrup, Mathilde; Vestergaard, Henrik

    2014-01-01

    Metabolic health in obesity is known to differ among individuals, and the distribution of visceral (VAT) and subcutaneous adipose tissue (SAT) plays an important role in this regard. Adipose tissue expansion is dependent on new blood vessel formation in order to prevent hypoxia and inflammation......-3 (ID3) gene in relation to adipose tissue and angiogenesis in humans in order to determine whether ID3 could be involved in the regulation of adipose tissue expansion and metabolic health in human obesity. We find evidence that ID3 is involved in regulatory mechanisms in adipose tissue...... and regulates angiogenesis in many tissues including adipose tissue. We discuss how this might influence obesity and metabolic health in obesity and further discuss some potential mechanisms by which ID3 might regulate visceral and subcutaneous adipose tissue expansion. The combined results from the reviewed...

  4. Epicardial adipose tissue is associated with visceral fat, metabolic syndrome, and insulin resistance in menopausal women.

    Science.gov (United States)

    Fernández Muñoz, María J; Basurto Acevedo, Lourdes; Córdova Pérez, Nydia; Vázquez Martínez, Ana Laura; Tepach Gutiérrez, Nayive; Vega García, Sara; Rocha Cruz, Alberto; Díaz Martínez, Alma; Saucedo García, Renata; Zárate Treviño, Arturo; González Escudero, Eduardo Alberto; Degollado Córdova, José Antonio

    2014-06-01

    Epicardial adipose tissue has been associated with several obesity-related parameters and with insulin resistance. Echocardiographic assessment of this tissue is an easy and reliable marker of cardiometabolic risk. However, there are insufficient studies on the relationship between epicardial fat and insulin resistance during the postmenopausal period, when cardiovascular risk increases in women. The objective of this study was to examine the association between epicardial adipose tissue and visceral adipose tissue, waist circumference, body mass index, and insulin resistance in postmenopausal women. A cross sectional study was conducted in 34 postmenopausal women with and without metabolic syndrome. All participants underwent a transthoracic echocardiogram and body composition analysis. A positive correlation was observed between epicardial fat and visceral adipose tissue, body mass index, and waist circumference. The values of these correlations of epicardial fat thickness overlying the aorta-right ventricle were r = 0.505 (P < .003), r = 0.545 (P < .001), and r = 0.515 (P < .003), respectively. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome than in those without this syndrome (mean [standard deviation], 544.2 [122.9] vs 363.6 [162.3] mm(2); P = .03). Epicardial fat thickness measured by echocardiography was associated with visceral adipose tissue and other obesity parameters. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome. Therefore, echocardiographic assessment of epicardial fat may be a simple and reliable marker of cardiovascular risk in postmenopausal women. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  5. Low birth weight male guinea pig offspring display increased visceral adiposity in early adulthood.

    Directory of Open Access Journals (Sweden)

    Ousseynou Sarr

    Full Text Available Uteroplacental insufficiency (UPI-induced intrauterine growth restriction (IUGR predisposes individuals to adult visceral obesity. We postulated that low birth weight (LBW offspring, from UPI-induced IUGR pregnancies, would display a visceral adipose lipogenic molecular signature involving altered gene expression, phosphorylation status of proteins of the lipid synthesis pathway and microRNA (miR expression profile, occurring in association with increased visceral adiposity. Normal birth weight (NBW and LBW (obtained by uterine artery ablation male guinea pig pups were fed a control diet from weaning to 145 days and sacrificed. Despite being lighter at birth, LBW pups displayed body weights similar to NBW offspring at 145 days. At this age, which represents young adulthood, the relative weights of LBW epididymal white adipose tissue (EWAT and lipid content were increased; which was consistent with adipocyte hypertrophy in the LBW offspring. Additionally, the mRNA expression of lipid synthesis-related genes including acetyl-CoA carboxylase 1 (ACC1, diglyceride acyltransferase 2 (DGAT2 and peroxisome proliferator-activated receptor gamma 1 (PPARγ1, was increased in LBW EWAT. Further, LBW EWAT displayed decreased phospho-ACC (Ser79 and phospho-PPARγ (Ser273 proteins. Moreover, the mRNA expression of hormone-sensitive lipase (HSL and fatty acid binding protein 4 (FABP4, both involved in promoting adipose lipid storage, was increased in LBW EWAT. Finally, miR-24 and miR-103-2, miRs related to adipocyte development, were both increased in LBW EWAT. These findings indicate that, following an adverse in utero environment, lipid synthesis-related genes and miR expression, along with phosphorylation status of key regulators of lipid synthesis, appear to be chronically altered and occur in association with increased visceral adiposity in young adult IUGR male offspring.

  6. Regulation of visceral and epicardial adipose tissue for preventing cardiovascular injuries associated to obesity and diabetes.

    Science.gov (United States)

    González, N; Moreno-Villegas, Z; González-Bris, A; Egido, J; Lorenzo, Ó

    2017-04-04

    Nowadays, obesity is seriously increasing in most of the populations all over the world, and is associated with the development and progression of high-mortality diseases such as type-2 diabetes mellitus (T2DM) and its subsequent cardiovascular pathologies. Recent data suggest that both body fat distribution and adipocyte phenotype, can be more determinant for fatal outcomes in obese patients than increased general adiposity. In particular, visceral adiposity is significantly linked to long term alterations on different cardiac structures, and in developed forms of myocardial diseases such as hypertensive and ischaemic heart diseases, and diabetic cardiomyopathy. Interestingly, this depot may be also related to epicardial fat accumulation through secretion of lipids, adipokines, and pro-inflammatory and oxidative factors from adipocytes. Thus, visceral adiposity and its white single-lipid-like adipocytes, are risk factors for different forms of heart disease and heart failure, mainly in higher degree obese subjects. However, under specific stimuli, some of these adipocytes can transdifferentiate to brown multi-mitochondrial-like adipocytes with anti-inflammatory and anti-apoptotic proprieties. Accordingly, in order to improve potential cardiovascular abnormalities in obese and T2DM patients, several therapeutic strategies have been addressed to modulate the visceral and epicardial fat volume and phenotypes. In addition to lifestyle modifications, specific genetic manipulations in adipose tissue and administration of PPARγ agonists or statins, have improved fat volume and phenotype, and cardiovascular failures. Furthermore, incretin stimulation reduced visceral and epicardial fat thickness whereas increased formation of brown adipocytes, alleviating insulin resistance and associated cardiovascular pathologies.

  7. Adverse Associations between Visceral Adiposity, Brain Structure, and Cognitive Performance in Healthy Elderly

    OpenAIRE

    Isaac, Vivian; Sim, Sam; Zheng, Hui; Zagorodnov, Vitali; Tai, E. Shyong; Chee, Michael

    2011-01-01

    The link between central adiposity and cognition has been established by indirect measures such as body mass index (BMI) or waist–hip ratio. Magnetic resonance imaging (MRI) quantification of central abdominal fat has been linked to elevated risk of cardiovascular and cerebro-vascular disease. However it is not known how quantification of visceral fat correlates with cognitive performance and measures of brain structure. We filled this gap by characterizing the relationships between MRI measu...

  8. Stromal Cells Derived from Visceral and Obese Adipose Tissue Promote Growth of Ovarian Cancers.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available Obesity, and in particular visceral obesity, has been associated with an increased risk of developing cancers as well as higher rates of mortality following diagnosis. The impact of obesity on adipose-derived stromal cells (ASC, which contribute to the formation of tumor stroma, is unknown. Here we hypothesized that visceral source and diet-induced obesity (DIO changes the ASC phenotype, contributing to the tumor promoting effects of obesity. We found that ASC isolated from subcutaneous (SC-ASC and visceral (V-ASC white adipose tissue(WAT of lean(Le and obese(Ob mice exhibited similar mesenchymal cell surface markers expression, and had comparable effects on ovarian cancer cell proliferation and migration. Obese and visceral derived ASC proliferated slower and exhibited impaired differentiation into adipocytes and osteocytes in vitro as compared to ASC derived from subcutaneous WAT of lean mice. Intraperitoneal co-injection of ovarian cancer cells with obese or visceral derived ASC, but not lean SC-ASC, increased growth of intraperitoneal ID8 tumors as compared to controls. Obese and V-ASC increased stromal infiltration of inflammatory cells, including CD3+ T cells and F4/80+ macrophages. Obese and visceral derived ASC, but not lean SC-ASC, increased expression of chemotactic factors IL-6, MIP-2, and MCP-1 when cultured with tumor cells. Overall, these results demonstrate that obese and V-ASC have a unique phenotype, with more limited proliferation and differentiation capacity but enhanced expression of chemotactic factors in response to malignant cells which support infiltration of inflammatory cells and support tumor growth and dissemination.

  9. Stromal Cells Derived from Visceral and Obese Adipose Tissue Promote Growth of Ovarian Cancers.

    Science.gov (United States)

    Zhang, Yan; Nowicka, Aleksandra; Solley, Travis N; Wei, Caimiao; Parikh, Aaroh; Court, Laurence; Burks, Jared K; Andreeff, Michael; Woodward, Wendy A; Dadbin, Ali; Kolonin, Mikhail G; Lu, Karen H; Klopp, Ann H

    2015-01-01

    Obesity, and in particular visceral obesity, has been associated with an increased risk of developing cancers as well as higher rates of mortality following diagnosis. The impact of obesity on adipose-derived stromal cells (ASC), which contribute to the formation of tumor stroma, is unknown. Here we hypothesized that visceral source and diet-induced obesity (DIO) changes the ASC phenotype, contributing to the tumor promoting effects of obesity. We found that ASC isolated from subcutaneous (SC-ASC) and visceral (V-ASC) white adipose tissue(WAT) of lean(Le) and obese(Ob) mice exhibited similar mesenchymal cell surface markers expression, and had comparable effects on ovarian cancer cell proliferation and migration. Obese and visceral derived ASC proliferated slower and exhibited impaired differentiation into adipocytes and osteocytes in vitro as compared to ASC derived from subcutaneous WAT of lean mice. Intraperitoneal co-injection of ovarian cancer cells with obese or visceral derived ASC, but not lean SC-ASC, increased growth of intraperitoneal ID8 tumors as compared to controls. Obese and V-ASC increased stromal infiltration of inflammatory cells, including CD3+ T cells and F4/80+ macrophages. Obese and visceral derived ASC, but not lean SC-ASC, increased expression of chemotactic factors IL-6, MIP-2, and MCP-1 when cultured with tumor cells. Overall, these results demonstrate that obese and V-ASC have a unique phenotype, with more limited proliferation and differentiation capacity but enhanced expression of chemotactic factors in response to malignant cells which support infiltration of inflammatory cells and support tumor growth and dissemination.

  10. Altered clock gene expression in obese visceral adipose tissue is associated with metabolic syndrome.

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    Elaine Vieira

    Full Text Available Clock gene expression was associated with different components of metabolic syndrome (MS in human adipose tissue. However, no study has been done to compare the expression of clock genes in visceral adipose tissue (VAT from lean and obese subjects and its clinical implications. Therefore, we studied in lean and obese women the endogenous 24 h expression of clock genes in isolated adipocytes and its association with MS components. VAT was obtained from lean (BMI 21-25 kg/m2; n = 21 and morbidly obese women (BMI >40 kg/m2; n = 28. The 24 h pattern of clock genes was analyzed every 6 hours using RT-PCR. Correlation of clinical data was studied by Spearman analysis. The 24 h pattern of clock genes showed that obesity alters the expression of CLOCK, BMAL1, PER1, CRY2 and REV-ERB ALPHA in adipocytes with changes found in CRY2 and REV-ERB ALPHA throughout the 24 h period. The same results were confirmed in VAT and stromal cells (SC showing an upregulation of CRY2 and REV-ERB ALPHA from obese women. A positive correlation was observed for REV-ERB ALPHA gene expression with BMI and waist circumference in the obese population. Expression of ROR ALPHA was correlated with HDL levels and CLOCK with LDL. Obese subjects with MS exhibited positive correlation in the PER2 gene with LDL cholesterol, whereas REV-ERB ALPHA was correlated with waist circumference. We identified CRY2 and REV-ERB ALPHA as the clock genes upregulated in obesity during the 24 h period and that REV-ERB ALPHA is an important gene associated with MS.

  11. Circulating Blood Monocyte Subclasses and Lipid-Laden Adipose Tissue Macrophages in Human Obesity.

    Science.gov (United States)

    Pecht, Tal; Haim, Yulia; Bashan, Nava; Shapiro, Hagit; Harman-Boehm, Ilana; Kirshtein, Boris; Clément, Karine; Shai, Iris; Rudich, Assaf

    2016-01-01

    Visceral adipose tissue foam cells are increased in human obesity, and were implicated in adipose dysfunction and increased cardio-metabolic risk. In the circulation, non-classical monocytes (NCM) are elevated in obesity and associate with atherosclerosis and type 2 diabetes. We hypothesized that circulating NCM correlate and/or are functionally linked to visceral adipose tissue foam cells in obesity, potentially providing an approach to estimate visceral adipose tissue status in the non-surgical obese patient. We preformed ex-vivo functional studies utilizing sorted monocyte subclasses from healthy donors. Moreover, we assessed circulating blood monocyte subclasses and visceral fat adipose tissue macrophage (ATM) lipid content by flow-cytometry in paired blood and omental-fat samples collected from patients (n = 65) undergoing elective abdominal surgery. Ex-vivo, NCM and NCM-derived macrophages exhibited lower lipid accumulation capacity compared to classical or intermediate monocytes/-derived macrophages. Moreover, of the three subclasses, NCM exhibited the lowest migration towards adipose tissue conditioned-media. In a cohort of n = 65, increased %NCM associated with higher BMI (r = 0.250,plipid content (r = 0.303,plipid content, particularly in men. Collectively, although circulating blood NCM are unlikely direct functional precursor cells for adipose tissue foam cells, their increased percentage in the circulation may clinically reflect higher lipid content in visceral ATMs.

  12. Measures of body adiposity and visceral adiposity index as predictors of metabolic syndrome among Thai women with PCOS.

    Science.gov (United States)

    Techatraisak, Kitirat; Wongmeerit, Krissanee; Dangrat, Chongdee; Wongwananuruk, Thanyarat; Indhavivadhana, Suchada

    2016-01-01

    To evaluate the relationship between measures of body adiposity and visceral adiposity index (VAI) and risk of metabolic syndrome (MS) and to identify the optimal cut-off points of each measurement in Thai polycystic ovary syndrome (PCOS). A cross-sectional study was completed physical examination, fasting plasma glucose, lipid profiles of 399 PCOS and 42 age-matched normal controls. Body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and VAI were calculated. Associations between different measures and MS were evaluated and the receiver-operating characteristic (ROC) curve was performed to determine appropriate cut-off points for identifying MS. Percentage of MS in PCOS was 24.6%, whereas none MS in controls. Previously recommended cut-off values for body adiposity and VAI were significantly associated with MS. ROC curve analysis of the only PCOS showed newly obtained optimal cut-off points for BMI and VAI of ≥28 kg/m(2) (AUC = 0.90) and >5.6 (AUC = 0.94), respectively. Values found to be more accurate than the original ones. VAI was the best predictor, followed by BMI and WHtR. All body adiposity and VAI parameters can predict the risk of MS. Optimal values for Thai PCOS were ≥28 kg/m(2) for BMI, ≥0.85 for WHR, ≥0.5 for WHtR and >5.6 for VAI.

  13. Epicardial Adipose Tissue Thickness in Patients With Subclinical Hypothyroidism and the Relationship Thereof With Visceral Adipose Tissue Thickness.

    Science.gov (United States)

    Arpaci, Dilek; Gurkan Tocoglu, Aysel; Yilmaz, Sabiye; Korkmaz, Sumeyye; Ergenc, Hasan; Gunduz, Huseyin; Keser, Nurgul; Tamer, Ali

    2016-03-01

    Subclinical hypothyroidism (SH) is associated with cardiovascular metabolic syndromes, especially dislipidemia and abdominal obesity. Visceral abdominal adipose tissue (VAAT) and epicardial adipose tissue (EAT) have the same ontogenic origin and produce many proinflammatory and proatherogenic cytokines. We evaluated EAT and VAAT thickness in patients with SH. Forty-one patients with SH and 35 controls were included in the study. Demographical and anthropometric features of both patients and controls were recorded. Thyroid and metabolic parameters were measured. EAT was measured using 2D-transthoracic echocardiography. The age and gender distributions were similar in the two groups (P = 0.998 and P = 0.121, respectively). Body mass index (BMI), fat mass, waist circumference (WC), hip circumference (HC), the WC/HC ratio, and the thicknesses of VAAT and abdominal subcutaneous adipose tissue were higher in the case group than the control group (all P values 0.05). We found no difference between the two groups in fasting plasma glucose (FPG) level (P = 0.780), but the levels of LDL-C and TG differed significantly (P = 0.002 and P = 0.026, respectively). The serum TSH level was higher and the FT4 level was lower in the case than the control group (both P values <0.01). Increased abdominal adipose tissue thickness in patients with SH is associated with atherosclerosis. To detemine the risk of atherosclerosis in such patients, EAT measurements are valuable; such assessment is simple to perform.

  14. Inverse relation between dietary fiber intake and visceral adiposity in overweight Latino youth.

    Science.gov (United States)

    Davis, Jaimie N; Alexander, Katharine E; Ventura, Emily E; Toledo-Corral, Claudia M; Goran, Michael I

    2009-11-01

    To date, no studies have assessed the longitudinal changes of dietary intake on metabolic risk factors in Latino youth. We assessed the relation between changes in dietary intake, specifically sugar and fiber intakes, with changes in adiposity and risk factors for type 2 diabetes in a longitudinal analysis of overweight Latino youth. Overweight Latino youth (n = 85; aged 11-17 y) underwent the following measures over 2 y [mean (+/-SD) time difference was 1.5 +/- 0.5 y]: dietary intake by 2-d diet recalls, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and glucose and insulin indexes by oral- and intravenous-glucose-tolerance tests. Partial correlations and repeated-measures analysis of covariance assessed the relation between changes in dietary intake with changes in adiposity and glucose and insulin indexes, independent of the following a priori covariates: sex, Tanner stage, time between visits, and baseline dietary and metabolic variables of interest. Increases in total dietary fiber (g/1000 kcal) and insoluble fiber (g/1000 kcal) were associated with decreases in visceral adipose tissue (VAT) (r = -0.29, P = 0.02, and r = -0.27, P = 0.03, for total dietary and insoluble fiber, respectively), independent of baseline covariates and change in subcutaneous abdominal adipose tissue. Participants who had decreased total dietary fiber (mean decrease of 3 g . 1000 kcal(-1) x d(-1)) had significant increases in VAT compared with participants who had increased total dietary fiber (21% compared with -4%; P = 0.02). No other changes in dietary variables were related to changes in adiposity or metabolic variables. Small reductions in dietary fiber intake over 1-2 y can have profound effects on increasing visceral adiposity in a high-risk Latino youth population.

  15. The effect of exercise on visceral adipose tissue in overweight adults: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Dirk Vissers

    Full Text Available Excessive visceral adipose tissue appears to trigger a cascade of metabolic disturbances that seem to coexist with ectopic fat storage in muscle, liver, heart and the ß-cell. Therefore, the reduction of visceral adipose tissue potentially plays a pivotal role in the treatment of the metabolic syndrome. The purpose of this systematic review and meta-analysis is to describe the overall effect of exercise on visceral adipose tissue and to provide an overview of the effect of different exercise regimes, without caloric restriction, on visceral adipose tissue in obese persons. A systematic literature search was performed according to the PRISMA statement for reporting systematic reviews and meta-analyses. The initial search resulted in 87 articles after removing duplicates. After screening on title, abstract and full-text 15 articles (totalling 852 subjects fulfilled the a priori inclusion criteria. The quality of each eligible study was assessed in duplicate with "The Critical Review Form for Quantitative Studies". Using random-effects weights, the standardized mean difference (Hedge's g of the change in visceral adipose tissue was -0.497 with a 95% confidence interval of -0.655 to -0.340. The Z-value was -6.183 and the p-value (two tailed was <0.001. A subgroup analysis was performed based on gender, type of training and intensity. Aerobic training of moderate or high intensity has the highest potential to reduce visceral adipose tissue in overweight males and females. These results suggest that an aerobic exercise program, without hypocaloric diet, can show beneficial effects to reduce visceral adipose tissue with more than 30 cm(2 (on CT analysis in women and more than 40 cm(2 in men, even after 12 weeks.

  16. Prediction of total and visceral fat contents using anthropometric measures of adiposity in women.

    Science.gov (United States)

    Weerarathna, T P; Lekamwasam, S; Rodrigo, M

    2008-12-01

    Although techniques such as dual energy xray absorptiometry (DXA) and quantitative CT are available to estimate global and regional adiposity, anthropometric measurements are often used to detect adiposity in clinical practice. To assess the association between the anthropometric measurements of obesity with total and regional fat mass determined by DXA. A cross-sectional, descriptive study. Patients and method 106 healthy women volunteers, aged between 30 and 54 years were studied. Anthropometric measurements including body mass index (BMI), waist circumference (WC), hip circumference (HC), height adjusted WC (WC/HT), waist-hip ratio (WHR), and skin-fold thickness (SFT) over triceps, infrascapular, and iliac regions were made. All women underwent assessment of total fat mass (TFM) and visceral fat mass (VFM) using a Hologic DXA scan. TFM and VFM showed positive correlations with all the anthropometric measurements examined, the strongest correlation was with BMI (r = 0.89 and 0.77 for TFM and VFM respectively, p measured at three sites showed less strong correlations with TFM and VFM (r = 0.48 to 0.69, p < 0.001). BMI has the strongest association with total and visceral fat mass among these women. Waist and hip circumferences showed high correlations with total and visceral fat mass, but adjusting waist circumference for height did not improve the correlation.

  17. Adverse Associations between Visceral Adiposity, Brain Structure, and Cognitive Performance in Healthy Elderly.

    Science.gov (United States)

    Isaac, Vivian; Sim, Sam; Zheng, Hui; Zagorodnov, Vitali; Tai, E Shyong; Chee, Michael

    2011-01-01

    The link between central adiposity and cognition has been established by indirect measures such as body mass index (BMI) or waist-hip ratio. Magnetic resonance imaging (MRI) quantification of central abdominal fat has been linked to elevated risk of cardiovascular and cerebro-vascular disease. However it is not known how quantification of visceral fat correlates with cognitive performance and measures of brain structure. We filled this gap by characterizing the relationships between MRI measures of abdominal adiposity, brain morphometry, and cognition, in healthy elderly. A total of 184 healthy community dwelling elderly subjects without cognitive impairment participated in this study. Anthropometric and biochemical markers of cardiovascular risk, neuropsychological measurements as well as MRI of the brain and abdomen fat were obtained. Abdominal images were segmented into subcutaneous adipose tissue and visceral adipose tissue (VAT) adipose tissue compartments. Brain MRI measures were analyzed quantitatively to determine total brain volume, hippocampal volume, ventricular volume, and cortical thickness. VAT showed negative association with verbal memory (r = 0.21, p = 0.005) and attention (r = 0.18, p = 0.01). Higher VAT was associated with lower hippocampal volume (F = 5.39, p = 0.02) and larger ventricular volume (F = 6.07, p = 0.02). The participants in the upper quartile of VAT had the lowest hippocampal volume even after adjusting for age, gender, hypertension, and BMI (b = -0.28, p = 0.005). There was a significant age by VAT interaction for cortical thickness in the left prefrontal region. In healthy older adults, elevated VAT is associated with negative effects on cognition, and brain morphometry.

  18. ADAMTS18 Deficiency Leads to Visceral Adiposity and Associated Metabolic Syndrome in Mice.

    Science.gov (United States)

    Zhu, Rui; Cheng, Mengting; Lu, Tiantian; Yang, Ning; Ye, Shuai; Pan, Yi-Hsuan; Hong, Tao; Dang, Suying; Zhang, Wei

    2017-11-20

    Visceral adiposity is of greater risk than obesity in subcutaneous adipose tissue for diabetes and cardiovascular disease. Its pathogenesis remains unclear, but it is associated with extracellular matrix (ECM) remodeling. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are a family of secreted Zn-dependent metalloproteinases that play crucial roles in development and various diseases owing to their ECM remodeling activity. ADAMTS18 is an "orphan ADAMTS" whose function and substrate remain unclear. Here, we showed that Adamts18 mRNA was abundantly expressed in visceral (gonadal) white adipose tissue (vWAT) during the early stage of development after birth. Adamts18 knockout (KO) mice showed increased body fat percentage and larger adipocyte size in vWAT relative to WT littermates, which may be partly attributed to ECM remodeling, especially increased expression of laminin1 and adipokine thrombospondin1 in vWAT. Attenuated ERK1/2 activity, along with increased expression of adipocyte-specific transcription factors PPARγ, C/EBPβ, and marker gene Fabp4 were detected in vWAT of Adamts18 KO mice. Furthermore, Adamts18 KO mice showed early metabolic syndrome including hyperlipidemia, blood glucose metabolic disorder, and hypertension. ADAMTS18 deficiency promotes atherosclerosis in apolipoprotein E-deficient (Apoe-/-) mice. These results indicate a novel function of ADAMTS18 in vWAT development and associated metabolic disorders. Copyright © 2017. Published by Elsevier Inc.

  19. Anthropometric predictors of visceral adiposity in normal-weight and obese adolescents.

    Science.gov (United States)

    Koren, Dorit; Marcus, Carole L; Kim, Christopher; Gallagher, Paul R; Schwab, Richard; Bradford, Ruth M; Zemel, Babette S

    2013-12-01

    Obesity and fat distribution patterns [subcutaneous vs. visceral adipose tissue (VAT)] are important predictors of future cardiometabolic risk. As accurate VAT measurement entails imaging, surrogate anthropometric measurements that would be cheaper and quicker to obtain would be highly desirable. Sagittal abdominal diameter (SAD) may be better than other VAT surrogate measures in adults, but the value of SAD to predict magnetic resonance imaging (MRI)-determined VAT in adolescents of different races, sexes, and pubertal stages has not been determined. To test the hypothesis that SAD correlates more strongly with volumetric VAT than other anthropometric measurements, independent of age, sex, race, and Tanner stage. Twenty-eight normal-weight and 44 obese adolescents underwent Tanner staging, anthropometric examinations, and abdominal MRI for volumetric partitioned fat calculation. VAT increased exponentially in the body mass index (BMI) > 97th percentile range. SAD, waist circumference (WC), BMI, and BMI Z-score correlated strongly with VAT (correlation coefficients of 0.85-0.86, all p-values < 0.0005); waist-hip ratio was less predictive of VAT (r = 0.68, p < 0.0005). On hierarchical regression, the strongest predictors of VAT in obese subjects were BMI Z-score and SAD (R(2)  = 0.34 vs. 0.31, respectively, p < 0.0005); in normal-weight subjects, most anthropometric measures predicted VAT equally (R(2)  = 0.16-0.18, p-values = 0.018-0.026). Unlike adults, in obese adolescents, SAD is not the strongest predictor of visceral adiposity. BMI Z-score is equivalently predictive and, together with BMI, provides sufficient information to assess visceral adiposity; more specialized anthropometric measurements (e.g., SAD and WC) do not add additional predictive value. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. The Associations between Various Ectopic Visceral Adiposity and Body Surface Electrocardiographic Alterations: Potential Differences between Local and Remote Systemic Effects.

    Directory of Open Access Journals (Sweden)

    Po-Ching Chi

    Full Text Available The associations between pericardial adiposity and altered atrial conduction had been demonstrated. However, data comparing differential effects of various body sites visceral adiposity on atrial and ventricular electrocardiographic alterations remains largely unknown.We assessed both peri-cardial fat (PCF and peri-aortic visceral adiposity (TAT using dedicated computed tomography (CT software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA, with anthropometrics including body mass index (BMI and biochemical data obtained. We further related PCF and TAT data to standardized 12-leads electrocardiogram (ECG, including P and QRS wave morphologies. Among 3,087 study subjects (mean age, 49.6 years; 28% women, we observed a linear association among greater visceral adiposity burden, leftward deviation of P and QRS axes, longer PR interval and widened QRS duration (all p200ms, likelihood-ratio: 33.17 to 41.4 & 39.03 for PCF and TAT and widened QRS duration (>100ms, likelihood-ratio: 55.67 to 65.4 & 61.94 for PCF and TAT, all X2 p<0.05 when superimposed on age and BMI.We show in our data greater visceral fat burden may have differential associations on several body surface electrocardiographic parameters. Compared to remote adiposity, those surrounding the heart tissue demonstrated greater influences on altered cardiac activation or conduction, indicating a possible local biological effect.

  1. Automated segmentation of visceral and subcutaneous (deep and superficial) adipose tissues in normal and overweight men.

    Science.gov (United States)

    Sadananthan, Suresh Anand; Prakash, Bhanu; Leow, Melvin Khee-Shing; Khoo, Chin Meng; Chou, Hong; Venkataraman, Kavita; Khoo, Eric Y H; Lee, Yung Seng; Gluckman, Peter D; Tai, E Shyong; Velan, S Sendhil

    2015-04-01

    To develop an automatic segmentation algorithm to classify abdominal adipose tissues into visceral fat (VAT), deep (DSAT), and superficial (SSAT) subcutaneous fat compartments and evaluate its performance against manual segmentation. Data were acquired from 44 normal (BMI 18.0-22.9 kg/m(2) ) and 38 overweight (BMI 23.0-29.9 kg/m(2) ) subjects at 3T using a two-point Dixon sequence. A fully automatic segmentation algorithm was developed to segment the fat depots. The first part of the segmentation used graph cuts to separate the subcutaneous and visceral adipose tissues and the second step employed a modified level sets approach to classify deep and superficial subcutaneous tissues. The algorithmic results of segmentation were validated against the ground truth generated by manual segmentation. The proposed algorithm showed good performance with Dice similarity indices of VAT/DSAT/SSAT: 0.92/0.82/0.88 against the ground truth. The study of the fat distribution showed that there is a steady increase in the proportion of DSAT and a decrease in the proportion of SSAT with increasing obesity. The presented technique provides an accurate approach for the segmentation and quantification of abdominal fat depots. © 2014 Wiley Periodicals, Inc.

  2. The impact of visceral adipose tissue and high-molecular weight adiponectin on cardio-ankle vascular index in asymptomatic Japanese subjects.

    Science.gov (United States)

    Ohashi, Norihiko; Ito, Chikako; Fujikawa, Rumi; Yamamoto, Hideya; Kihara, Yasuki; Kohno, Nobuoki

    2009-07-01

    Few studies addressed the relation of visceral adiposity and high-molecular weight (HMW) adiponectin to arterial stiffness. We investigated the impact of visceral adipose tissue (VAT) and HMW adiponectin on cardio-ankle vascular index (CAVI) in asymptomatic Japanese subjects. We studied 487 consecutive subjects (271 men and 216 women) who underwent general health examination between October 2005 and May 2008. The abdominal, visceral, and subcutaneous adipose tissue areas were determined by low-dose x-ray computed tomography. Serum levels of total and HMW adiponectin were measured using the enzyme-linked immunosorbent assay system based on a monoclonal antibody to humans. Cardio-ankle vascular index was positively correlated with VAT area and negatively correlated with HMW adiponectin levels. We also found the positive association of the number of metabolic syndrome components with CAVI in both sexes. A stepwise multiple regression analysis revealed that age, VAT area, serum HMW adiponectin levels, and homeostasis model assessment of insulin resistance were independent determinants of CAVI. Receiver operating characteristic analyses demonstrated that the predictive value of the VAT area for the extent of CAVI (mild: 75th percentile) exceeded that of total or HMW adiponectin levels in both sexes. In conclusion, increased CAVI is associated with both amounts of VAT measured by computed tomography and serum HMW adiponectin levels in asymptomatic Japanese subjects. Receiver operating characteristic analysis indicates that the VAT area is a lot better predictor of arterial stiffness than adiponectin levels.

  3. Visceral adiposity and metabolic syndrome after very high-fat and low-fat isocaloric diets: a randomized controlled trial.

    Science.gov (United States)

    Veum, Vivian L; Laupsa-Borge, Johnny; Eng, Øyvin; Rostrup, Espen; Larsen, Terje H; Nordrehaug, Jan Erik; Nygård, Ottar K; Sagen, Jørn V; Gudbrandsen, Oddrun A; Dankel, Simon N; Mellgren, Gunnar

    2017-01-01

    not differentially influence visceral fat and metabolic syndrome in a low-processed, lower-glycemic dietary context. Our data do not support the idea that dietary fat per se promotes ectopic adiposity and cardiometabolic syndrome in humans. This study was registered at clinicaltrials.gov as NCT01750021. © 2017 American Society for Nutrition.

  4. Subcutaneous rather than visceral adipose tissue is associated with adiponectin levels and insulin resistance in young men

    DEFF Research Database (Denmark)

    Frederiksen, L; Nielsen, T L; Wraae, K

    2009-01-01

    regression analysis, adiponectin correlated negatively with CFM (r = -0.27; P multiple linear regression analysis, HOMA-IR (dependent variable......, and IR was determined using HOMA. Central fat mass (CFM) and lower extremity fat mass (LEFM) was measured by dual-energy x-ray absorptiometry, and visceral adipose tissue (VAT), sc adipose tissue (SAT), and thigh fat area (TFA) were assessed by magnetic resonance imaging. RESULTS: Using multiple linear...

  5. Discriminatory power of indicators predictors of visceral adiposity evaluated by computed tomography in adults and elderly individuals

    OpenAIRE

    Anna Karla Cameiro Roriz; Luiz Carlos Santana Passos; Carolina Cunha de Oliveira; Michaela Eickemberg; Pricilia de Almeida Moreira; Lilian Ramos Sampaio

    2014-01-01

    Introduction: Identifying anthropometric methods of abdominal adiposity, predictors of excess area of visceral adipose tissue (VAT) allows rapid and low cost evaluation for the risk of cardiovascular diseases in the elderly. Objective: To evaluate the discriminatory power of anthropometric indicators for detection of excess of the area of VAT. Methods: Cross-sectional study comprising 194 adults and elderly individuals for comparison of both sexes and age groups. Anthropometric variables: wai...

  6. Relationships between exercise-induced reductions in thigh intermuscular adipose tissue, changes in lipoprotein particle size, and visceral adiposity

    Science.gov (United States)

    Durheim, Michael T.; Slentz, Cris A.; Bateman, Lori A.; Mabe, Stephanie K.; Kraus, William E.

    2008-01-01

    Small LDL and HDL particle size are characteristic of a proatherogenic lipoprotein profile. Aerobic exercise increases these particle sizes. Although visceral adipose tissue (VAT) has been strongly linked with dyslipidemia, the importance of intermuscular adipose tissue (IMAT) to dyslipidemia and exercise responses is less well understood. We measured exercise-associated changes in thigh IMAT and VAT and examined their relationships with changes in LDL and HDL particle size. Sedentary, dyslipidemic, overweight subjects (n = 73) completed 8–9 mo of aerobic training. Linear regression models were used to compare the power of IMAT change and VAT change to predict lipoprotein size changes. In men alone (n = 40), IMAT change correlated inversely with both HDL size change (r = −0.42, P = 0.007) and LDL size change (r = −0.52, P exercise-associated change in thigh IMAT was inversely correlated with both HDL and LDL size change and was more predictive of these lipoprotein changes than was change in VAT. Reducing IMAT through aerobic exercise may be functionally related to some improvements in atherogenic dyslipidemia in men. PMID:18544640

  7. Pregnancy in obese mice protects selectively against visceral adiposity and is associated with increased adipocyte estrogen signalling.

    Directory of Open Access Journals (Sweden)

    Silvia M A Pedroni

    Full Text Available Maternal obesity is linked with increased adverse pregnancy outcomes for both mother and child. The metabolic impact of excessive fat within the context of pregnancy is not fully understood. We used a mouse model of high fat (HF feeding to induce maternal obesity to identify adipose tissue-mediated mechanisms driving metabolic dysfunction in pregnant and non-pregnant obese mice. As expected, chronic HF-feeding for 12 weeks preceding pregnancy increased peripheral (subcutaneous and visceral (mesenteric fat mass. However, unexpectedly at late gestation (E18.5 HF-fed mice exhibited a remarkable normalization of visceral but not peripheral adiposity, with a 53% reduction in non-pregnant visceral fat mass expressed as a proportion of body weight (P<0.001. In contrast, in control animals, pregnancy had no effect on visceral fat mass proportion. Obesity exaggerated glucose intolerance at mid-pregnancy (E14.5. However by E18.5, there were no differences, in glucose tolerance between obese and control mice. Transcriptomic analysis of visceral fat from HF-fed dams at E18.5 revealed reduced expression of genes involved in de novo lipogenesis (diacylglycerol O-acyltransferase 2--Dgat2 and inflammation (chemokine C-C motif ligand 20--Ccl2 and upregulation of estrogen receptor α (ERα compared to HF non pregnant. Attenuation of adipose inflammation was functionally confirmed by a 45% reduction of CD11b+CD11c+ adipose tissue macrophages (expressed as a proportion of all stromal vascular fraction cells in HF pregnant compared to HF non pregnant animals (P<0.001. An ERα selective agonist suppressed both de novo lipogenesis and expression of lipogenic genes in adipocytes in vitro. These data show that, in a HF model of maternal obesity, late gestation is associated with amelioration of visceral fat hypertrophy, inflammation and glucose intolerance, and suggest that these effects are mediated in part by elevated visceral adipocyte ERα signaling.

  8. Adverse associations between visceral adiposity, brain structure and cognitive performance in healthy elderly

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    Vivian eIsaac

    2011-09-01

    Full Text Available The link between central adiposity and cognition has been established by indirect measures such as BMI or waist-hip ratio. Magnetic resonance imaging (MRI quantification of central abdominal fat has been linked to elevated risk of cardio-vascular and cerebro-vascular disease. However it is not known how quantification of visceral fat correlates with cognitive performance and measures of brain structure. We filled this gap by characterizing the relationships between MRI measures of abdominal adiposity, brain morphometry and cognition, in healthy elderly. Methods: A total of 184 healthy community dwelling elderly subjects without cognitive impairment participated in this study. Anthropometric and biochemical markers of cardio-vascular risk, neuropsychological measurements as well as MRI of the brain and abdomen fat were obtained. Abdominal images were segmented into subcutaneous (SAT and visceral (VAT adipose tissue compartments. Brain MRI measures were analyzed quantitatively to determine total brain volume, hippocampal volume, ventricular volume and cortical thickness. Results: VAT showed negative association with verbal memory (r=0.21, p=0.005 and attention (r=0.18, p=0.01. Higher VAT was associated with lower hippocampal volume (F=5.39, p=0.02 and larger ventricular volume (F=6.07, p=0.02. The participants in the upper quartile of VAT had the lowest hippocampal volume even after adjusting for age, gender, hypertension and BMI (b=-0.28, p=0.005. There was a significant age by VAT interaction for cortical thickness in the left prefrontal region. Conclusions: In healthy older adults, elevated VAT is associated with negative effects on cognition, and brain morphometry.

  9. Inflammation mediates the association between visceral adiposity and obstructive sleep apnea in adolescents.

    Science.gov (United States)

    Gaines, Jordan; Vgontzas, Alexandros N; Fernandez-Mendoza, Julio; Calhoun, Susan L; He, Fan; Liao, Duanping; Sawyer, Marjorie D; Bixler, Edward O

    2016-11-01

    Only a handful of studies, primarily in clinical samples, have reported an association between obesity, inflammation, and obstructive sleep apnea (OSA) in children and adolescents. No studies, however, have examined the pathogenetic link between visceral adiposity, systemic inflammation, and incident OSA in a large general population sample using objective measures of sleep and body fat. Adolescents (n = 392; mean age 17.0 ± 2.2 yr, 54.0% male) from the Penn State Child Cohort (PSCC) underwent 9-h overnight polysomnography; a DXA scan to assess body fat distribution; and a single fasting blood draw for the assessment of plasma interleukin-6 (IL-6), IL-6 soluble receptor (IL-6 sR), tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1A (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels via ELISA. Visceral fat area was significantly elevated in moderate OSA (AHI ≥ 5), especially in boys. IL-6, CRP, and leptin were highest in adolescents with moderate OSA, even after adjusting for BMI percentile. Mediation analysis revealed that 42% of the association between visceral fat and OSA in adolescents was mediated by IL-6 (p = 0.03), while 82% of the association was mediated by CRP (p = 0.01). These data are consistent with the model of a feed-forward, vicious cycle, in which the release of proinflammatory cytokines by visceral adipocytes largely explains the association between central obesity and OSA; in turn, inflammation is also elevated in OSA independent of BMI. These findings, in a large, representative, non-clinical sample of young people, add to our understanding of the developmental pathogenesis of sleep apnea. Copyright © 2016 the American Physiological Society.

  10. Correlation between pre-pregnancy body mass index and maternal visceral adiposity with fetal biometry during the second trimester.

    Science.gov (United States)

    Lopes, Karina R M; Souza, Alex Sandro R; Figueiroa, José N; Alves, João Guilherme B

    2017-08-01

    To determine the correlation between pre-pregnancy body mass index (BMI) and maternal visceral adiposity with fetal biometry during the second trimester. A cross-sectional observational study was conducted among pregnant women who received prenatal care at a center in Recife, Brazil, between October 3, 2011, and September 27, 2013. Pre-pregnancy BMI was determined at the first prenatal care visit. Maternal visceral adiposity and fetal biometry were measured at the same ultrasonography session. The associations between maternal and fetal variables were evaluated using the Pearson correlation coefficient (R). The Student t test was used to test the null hypothesis of adjusted correlation coefficients. Overall, 740 women were included. No correlation was found between pre-pregnancy BMI and any of the fetal biometric variables assessed. By contrast, maternal visceral adiposity positively correlated with fetal abdominal circumference (R=0.529), estimated fetal weight (R=0.524), head circumference (R=0.521), femur length (R=0.521), and biparietal diameter (R=0.524; Ppregnancy length. Maternal visceral adiposity, but not pre-pregnancy BMI, positively correlated with fetal biometry during the second trimester. © 2017 International Federation of Gynecology and Obstetrics.

  11. Higher visceral adiposity is associated with an enhanced early thermogenic response to carbohydrate-rich food.

    Science.gov (United States)

    Gepner, Yftach; Bril, Nitzan; Shelef, Ilan; Schwarzfuchs, Dan; Serfaty, Dana; Rein, Michal; Cohen, Noa; Shemesh, Elad; Tangi-Rosental, Osnat; Sarusi, Benjamin; Goshen, Eyal; Kenigsbuch, Shira; Chassidim, Yoash; Golan, Rachel; Witkow, Shula; Henkin, Yaakov; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

    2016-04-01

    Studies examining the dynamics of the thermic effect of feeding (TEF) of specific food items and the relationship of TEF to visceral adiposity are limited. We measured resting energy expenditure (REE) and early-TEF (40-min postprandial, e-TEF) after 8-h fast by indirect calorimetry in 40 obese men, and imaged abdominal fat tissues by magnetic resonance imaging. Each participant was examined on two occasions, 3-weeks apart. At each examination we measured fasting REE and then postprandial REE following the isocaloric [∼380 kcal] consumption of either 56 gr walnuts [(8% carbohydrates; 84% fat, of which 72% polyunsaturated fat)], or 5-slices (150gr) of whole-grain bread (48% carbohydrates; 32% fat). e-TEF was calculated as the area under the curve between the fasting and postprandial tests. Participants had a mean age of 45 ± 8 years, body-mass-index (BMI) = 31.1 ± 3.8 kg/m(2), total abdominal fat area = 901.4 ± 240 cm(2), visceral fat area (VAT) = 260 ± 102.9 cm(2), fasting REE = 1854 ± 205 kcal, REE/kg = 19.39 ± 1.73 kcal/kg, and respiratory quotient (RQ, CO2 eliminated/O2 consumed) = 0.82 ± 0.04. Individuals who exhibited increased e-TEF (top ΔAUC median) to bread had higher VAT (299 cm(2) vs. 223 cm(2); p = 0.024) and higher BMI (32.4 kg/m(2) vs. 30.0 kg/m(2); p = 0.013), compared to their peers with the lower e-TEF response (ΔAUC below median). As expected, postprandial e-TEF was higher after whole-grain bread consumption [ΔAUC = +14 kcal/40min] compared to walnuts [ΔAUC = -2 kcal/40 min; p food, likely reflecting digestion, early absorption and/or sympathetic tone (rather than metabolic utilization (oxidation)), associates with visceral adiposity. Future studies are required to determine if this association represents an added causality between early carbohydrate processing and visceral fat accumulation. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All

  12. Expression profiling of PPARγ-regulated microRNAs in human subcutaneous and visceral adipogenesis in both genders.

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    Yu, Jing; Kong, Xiaocen; Liu, Juan; Lv, Yifan; Sheng, Yunlu; Lv, Shan; Di, Wenjuan; Wang, Chen; Zhang, Feng; Ding, Guoxian

    2014-06-01

    Clinical evidence shows that visceral fat accumulation decreases whereas sc fat increases in patients treated with thiazolidinediones (TZDs), a type of peroxisome proliferator-activated receptor (PPAR)γ agonist. To clarify the molecular mechanism of the differential effects of PPARγ agonists on sc and visceral adipose, we investigated expression profiling of PPARγ-regulated micro-RNAs (miRNAs) using miRNA microarray. The level of 182 miRNAs changed in human sc adipose treated with pioglitazone, whereas only 46 miRNAs changed in visceral adipose. Among these miRNAs, 27 miRNAs changed in both human sc and visceral adipocytes. Specifically, 7 miRNAs changed at the same direction in sc and visceral adipocytes, whereas 20 miRNAs changed at opposite directions in these two fat depots. Bioinformatics analysis showed that these miRNAs and the predicted target genes were involved in TGF-β-, Wnt/β-catenin-, and insulin-signaling pathways and related to metabolic regulation or cell cycle. Among the miRNAs changed at the same direction in sc and visceral adipocytes, miR-378, located in the first intron of PPARγ coactivator 1β (PGC1β), was coordinately expressed with PGC1β during adipogenesis. Moreover, miR-378 and PGC1β were both up-regulated by PPARγ agonist. We also provided evidence that miR-378 promoted adipogenesis in sc fat, but not in visceral fat. These results display miRNAs expression profiling altered in sc and visceral adipogenesis regulated by PPARγ and suggest a potential mechanism underlying the differential effects of TZDs on the 2 fat depot accumulations.

  13. Subsets of Visceral Adipose Tissue Nuclei with Distinct Levels of 5-Hydroxymethylcytosine.

    Directory of Open Access Journals (Sweden)

    Ping Yu

    Full Text Available The reprogramming of cellular memory in specific cell types, and in visceral adipocytes in particular, appears to be a fundamental aspect of obesity and its related negative health outcomes. We explored the hypothesis that adipose tissue contains epigenetically distinct subpopulations of adipocytes that are differentially potentiated to record cellular memories of their environment. Adipocytes are large, fragile, and technically difficult to efficiently isolate and fractionate. We developed fluorescence nuclear cytometry (FNC and fluorescence activated nuclear sorting (FANS of cellular nuclei from visceral adipose tissue (VAT using the levels of the pan-adipocyte protein, peroxisome proliferator-activated receptor gamma-2 (PPARg2, to distinguish classes of PPARg2-Positive (PPARg2-Pos adipocyte nuclei from PPARg2-Negative (PPARg2-Neg leukocyte and endothelial cell nuclei. PPARg2-Pos nuclei were 10-fold enriched for most adipocyte marker transcripts relative to PPARg2-Neg nuclei. PPARg2-Pos nuclei showed 2- to 50-fold higher levels of transcripts encoding most of the chromatin-remodeling factors assayed, which regulate the methylation of histones and DNA cytosine (e.g., DNMT1, TET1, TET2, KDM4A, KMT2C, SETDB1, PAXIP1, ARID1A, JMJD6, CARM1, and PRMT5. PPARg2-Pos nuclei were large with decondensed chromatin. TAB-seq demonstrated 5-hydroxymethylcytosine (5hmC levels were remarkably dynamic in gene bodies of various classes of VAT nuclei, dropping 3.8-fold from the highest quintile of expressed genes to the lowest. In short, VAT-derived adipocytes appear to be more actively remodeling their chromatin than non-adipocytes.

  14. Subsets of Visceral Adipose Tissue Nuclei with Distinct Levels of 5-Hydroxymethylcytosine.

    Science.gov (United States)

    Yu, Ping; Ji, Lexiang; Lee, Kevin J; Yu, Miao; He, Chuan; Ambati, Suresh; McKinney, Elizabeth C; Jackson, Crystal; Baile, Clifton A; Schmitz, Robert J; Meagher, Richard B

    2016-01-01

    The reprogramming of cellular memory in specific cell types, and in visceral adipocytes in particular, appears to be a fundamental aspect of obesity and its related negative health outcomes. We explored the hypothesis that adipose tissue contains epigenetically distinct subpopulations of adipocytes that are differentially potentiated to record cellular memories of their environment. Adipocytes are large, fragile, and technically difficult to efficiently isolate and fractionate. We developed fluorescence nuclear cytometry (FNC) and fluorescence activated nuclear sorting (FANS) of cellular nuclei from visceral adipose tissue (VAT) using the levels of the pan-adipocyte protein, peroxisome proliferator-activated receptor gamma-2 (PPARg2), to distinguish classes of PPARg2-Positive (PPARg2-Pos) adipocyte nuclei from PPARg2-Negative (PPARg2-Neg) leukocyte and endothelial cell nuclei. PPARg2-Pos nuclei were 10-fold enriched for most adipocyte marker transcripts relative to PPARg2-Neg nuclei. PPARg2-Pos nuclei showed 2- to 50-fold higher levels of transcripts encoding most of the chromatin-remodeling factors assayed, which regulate the methylation of histones and DNA cytosine (e.g., DNMT1, TET1, TET2, KDM4A, KMT2C, SETDB1, PAXIP1, ARID1A, JMJD6, CARM1, and PRMT5). PPARg2-Pos nuclei were large with decondensed chromatin. TAB-seq demonstrated 5-hydroxymethylcytosine (5hmC) levels were remarkably dynamic in gene bodies of various classes of VAT nuclei, dropping 3.8-fold from the highest quintile of expressed genes to the lowest. In short, VAT-derived adipocytes appear to be more actively remodeling their chromatin than non-adipocytes.

  15. A comparative assessment of adipose-derived stem cells from subcutaneous and visceral fat as a potential cell source for knee osteoarthritis treatment.

    Science.gov (United States)

    Tang, Yan; Pan, Zhang-Yi; Zou, Ying; He, Yi; Yang, Peng-Yuan; Tang, Qi-Qun; Yin, Feng

    2017-09-01

    The intra-articular injection of adipose-derived stem cells (ASCs) is a novel potential therapy for patients with osteoarthritis (OA). However, the efficacy of ASCs from different regions of the body remains unknown. This study investigated whether ASCs from subcutaneous or visceral adipose tissue provide the same improvement of OA. Mouse and human subcutaneous and visceral adipose tissue were excised for ASC isolation. Morphology, proliferation, surface markers and adipocyte differentiation of subcutaneous ASCs (S-ASCs) and visceral ASCs (V-ASCs) were analysed. A surgically induced rat model of OA was established, and 4 weeks after the operation, S-ASCs, V-ASCs or phosphate-buffered saline (PBS, control) were injected into the articular cavity. Histology, immunohistochemistry and gene expression analyses were performed 6 weeks after ASC injection. The ability of ASCs to differentiate into chondrocytes was assessed by in vitro chondrogenesis, and the immunosuppressive activity of ASCs was evaluated by co-culturing with macrophages. The proliferation of V-ASCs was significantly greater than that of S-ASCs, but S-ASCs had the greater adipogenic capacity than V-ASCs. In addition, the infracted cartilage treated with S-ASCs showed significantly greater improvement than cartilage treated with PBS or V-ASCs. Moreover, S-ASCs showed better chondrogenic potential and immunosuppression in vitro. Subcutaneous adipose tissue is an effective cell source for cell therapy of OA as it promotes stem cell differentiation into chondrocytes and inhibits immunological reactions. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. Robust Early Inflammation of the Peripancreatic Visceral Adipose Tissue During Diet-Induced Obesity in the KrasG12D Model of Pancreatic Cancer.

    Science.gov (United States)

    Hertzer, Kathleen M; Xu, Mu; Moro, Aune; Dawson, David W; Du, Lin; Li, Gang; Chang, Hui-Hua; Stark, Alexander P; Jung, Xiaoman; Hines, Oscar Joe; Eibl, Guido

    2016-03-01

    Obesity increases the incidence of multiple types of cancer. Our previous work has shown that a high-fat, high-calorie diet (HFCD) leads to visceral obesity, pancreatic inflammation, and accelerated pancreatic neoplasia in KrasG12D (KC) mice. In this study, we aimed to investigate the effects of an HFCD on visceral adipose inflammation with emphasis on potential differences between distinct visceral adipose depots. We examined the weight and visceral obesity in both wild-type and KC mice on either control diet (CD) or HFCD. After 3 months, mice were killed for histological examination. Multiplex assays were also performed to obtain cytokine profiles between different adipose depots. Both wild-type and KC mice on an HFCD exhibited significantly increased inflammation in the visceral adipose tissue, particularly in the peripancreatic fat (PPF), compared with animals on a CD. This was associated with significantly increased inflammation in the pancreas. Cytokine profiles were different between visceral adipose depots and between mice on the HFCD and CD. Our results clearly demonstrate that an HFCD leads to obesity and inflammation in the visceral adipose tissue, particularly the PPF. These data suggest that obesity-associated inflammation in PPF may accelerate pancreatic neoplasia in KC mice.

  17. Continued Loss in Visceral and Intermuscular Adipose Tissue in Weight-Stable Women Following Bariatric Surgery

    Science.gov (United States)

    Toro-Ramos, Tatiana; Goodpaster, Bret H.; Janumala, Isaiah; Lin, Susan; Strain, Gladys W.; Thornton, John C.; Kang, Patrick; Courcoulas, Anita P.; Pomp, Alfons; Gallagher, Dympna

    2014-01-01

    Objective To assess changes in total adipose tissue (TAT), subcutaneous (SAT), visceral (VAT), and intermuscular (IMAT) by whole-body MRI before surgery, at 12 months and 24 months post-surgery in a subset of participants of the Longitudinal Assessment of Bariatric Surgery-2. Design and Methods From 0 to 12 months, n=20F and 3M; from 12 to 24 months, n=42F and 7M. Paired t-tests and GLM repeated measures examined changes in TAT, SAT, VAT, and IMAT at 12 and 24 months, with sex and age as covariates. Results Changes from 0 to 12 months, included weight (−41.9±12.1kg; −36%), TAT (−33.5±9.6kg; −56%), SAT (−29.2±8.2kg; −55%), VAT (−3.3±1.6kg; −73%), and IMAT (−0.99±0.68kg; −50%), all pBariatric surgery continues to induce favorable changes in body composition, i.e., persistent adipose tissue loss at 24 months in the absence of further significant weight loss. PMID:25384375

  18. Data set for renal sinus fat volume and visceral adipose tissue volume on computed tomography

    Directory of Open Access Journals (Sweden)

    Yoko Murakami

    2016-06-01

    Full Text Available Renal sinus fat is partially characteristic of peri-vascular adipose tissue, however, RSF volume (RSFV is associated with visceral adipose tissue (VATV. Therefore, the ratio of RSFV to VATV (RSFV/VATV ratio can distinguish the importance of RSF as an extension of VAT versus its perivascular effects. We assessed the association of RSFV/VATV ratio with coronary artery calcification score (CACS in 189 patients with suspected coronary artery disease. RSFV of the right kidney and VATV were quantified by using image data of unenhanced abdominal CT. CACS were measured on unenhanced ECG-gated CT images. This article contains data on explanatory scheme of how to measure RSFV on unenhanced abdominal CT, CT indication and exclusion criteria of study population, sex-adjusted association between RSFV with risk factors of coronary vascular diseases and metabolic indices, multivariate linear regression analysis with CACS as the dependent variable in the total study population. The data are supplemental to our original research article describing detailed association between RSFV/VATV ratio and CACS including sub-groups analyses classified by the age of 70 “Renal sinus fat volume on computed tomography in middle-aged patients at risk for cardiovascular disease and its association with coronary artery calcification” Murakami et al. [1].

  19. Dietary stearic acid leads to a reduction of visceral adipose tissue in athymic nude mice.

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    Ming-Che Shen

    Full Text Available Stearic acid (C18:0 is a long chain dietary saturated fatty acid that has been shown to reduce metastatic tumor burden. Based on preliminary observations and the growing evidence that visceral fat is related to metastasis and decreased survival, we hypothesized that dietary stearic acid may reduce visceral fat. Athymic nude mice, which are used in models of human breast cancer metastasis, were fed a stearic acid, linoleic acid (safflower oil, or oleic acid (corn oil enriched diet or a low fat diet ad libitum. Total body weight did not differ significantly between dietary groups over the course of the experiment. However visceral fat was reduced by ∼70% in the stearic acid fed group compared to other diets. In contrast total body fat was only slightly reduced in the stearic acid diet fed mice when measured by dual-energy x-ray absorptiometry and quantitative magnetic resonance. Lean body mass was increased in the stearic acid fed group compared to all other groups by dual-energy x-ray absorptiometry. Dietary stearic acid significantly reduced serum glucose compared to all other diets and increased monocyte chemotactic protein-1 (MCP-1 compared to the low fat control. The low fat control diet had increased serum leptin compared to all other diets. To investigate possible mechanisms whereby stearic acid reduced visceral fat we used 3T3L1 fibroblasts/preadipocytes. Stearic acid had no direct effects on the process of differentiation or on the viability of mature adipocytes. However, unlike oleic acid and linoleic acid, stearic acid caused increased apoptosis (programmed cell death and cytotoxicity in preadipocytes. The apoptosis was, at least in part, due to increased caspase-3 activity and was associated with decreased cellular inhibitor of apoptosis protein-2 (cIAP2 and increased Bax gene expression. In conclusion, dietary stearic acid leads to dramatically reduced visceral fat likely by causing the apoptosis of preadipocytes.

  20. Does measurement site for visceral and abdominal subcutaneous adipose tissue alter associations with the metabolic syndrome?

    Science.gov (United States)

    Kuk, Jennifer L; Church, Timothy S; Blair, Steven N; Ross, Robert

    2006-03-01

    To determine whether the associations between visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), and the metabolic syndrome are altered depending on measurement site for VAT and ASAT and the definition used to identify the metabolic syndrome. Total VAT and ASAT volume was derived using approximately 37 contiguous computed tomography (CT) images from T10-T11 to L5-S1 in 85 men. CT images obtained at eight intervertebral locations (e.g., L4-L5, L3-L4, etc.) were used to determine the associations between partial volumes (single images) and metabolic syndrome. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. Logistic regression was used to calculate the odds ratio (OR) per SD increase in adipose tissue. For total and all partial volumes, VAT was more strongly associated with metabolic syndrome than ASAT independent of metabolic syndrome criteria. The OR (per SD) for NCEP metabolic syndrome was higher for total VAT volume (OR = 7.26) and for the partial volumes at T12-L1 (7.46) and L1-L2 (8.77) than those at the L4-L5 level (3.94). The OR for metabolic syndrome ( approximately 2.6) was not substantially different among the ASAT measures. A similar pattern of association was observed using the IDF metabolic syndrome criteria. The measurement site for VAT, but not for ASAT, has a substantial influence on the magnitude of the association with both metabolic syndrome definitions. However, because VAT remained significantly associated with metabolic syndrome regardless of measurement site, the clinical interpretation was unaltered by measurement protocol or metabolic syndrome definition.

  1. Deletion of the Androgen Receptor in Adipose Tissue in Male Mice Elevates Retinol Binding Protein 4 and Reveals Independent Effects on Visceral Fat Mass and on Glucose Homeostasis

    Science.gov (United States)

    McInnes, Kerry J.; Smith, Lee B.; Hunger, Nicole I.; Saunders, Philippa T.K.; Andrew, Ruth; Walker, Brian R.

    2012-01-01

    Testosterone deficiency is epidemic in obese ageing males with type 2 diabetes, but the direction of causality remains unclear. Testosterone-deficient males and global androgen receptor (AR) knockout mice are insulin resistant with increased fat, but it is unclear whether AR signaling in adipose tissue mediates body fat redistribution and alters glucose homoeostasis. To investigate this, mice with selective knockdown of AR in adipocytes (fARKO) were generated. Male fARKO mice on normal diet had reduced perigonadal fat but were hyperinsulinemic and by age 12 months, were insulin deficient in the absence of obesity. On high-fat diet, fARKO mice had impaired compensatory insulin secretion and hyperglycemia, with increased susceptibility to visceral obesity. Adipokine screening in fARKO mice revealed a selective increase in plasma and intra-adipose retinol binding protein 4 (RBP4) that preceded obesity. AR activation in murine 3T3 adipocytes downregulated RBP4 mRNA. We conclude that AR signaling in adipocytes not only protects against high-fat diet–induced visceral obesity but also regulates insulin action and glucose homeostasis, independently of adiposity. Androgen deficiency in adipocytes in mice resembles human type 2 diabetes, with early insulin resistance and evolving insulin deficiency. PMID:22415878

  2. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

    Science.gov (United States)

    Carrasco-Benso, Maria P; Rivero-Gutierrez, Belen; Lopez-Minguez, Jesus; Anzola, Andrea; Diez-Noguera, Antoni; Madrid, Juan A; Lujan, Juan A; Martínez-Augustin, Olga; Scheer, Frank A J L; Garaulet, Marta

    2016-09-01

    In humans, insulin sensitivity varies according to time of day, with decreased values in the evening and at night. Mechanisms responsible for the diurnal variation in insulin sensitivity are unclear. We investigated whether human adipose tissue (AT) expresses intrinsic circadian rhythms in insulin sensitivity that could contribute to this phenomenon. Subcutaneous and visceral AT biopsies were obtained from extremely obese participants (body mass index, 41.8 ± 6.3 kg/m(2); 46 ± 11 y) during gastric-bypass surgery. To assess the rhythm in insulin signaling, AKT phosphorylation was determined every 4 h over 24 h in vitro in response to different insulin concentrations (0, 1, 10, and 100 nM). Data revealed that subcutaneous AT exhibited robust circadian rhythms in insulin signaling (P circadian rhythms were detected in visceral AT (P = 0.643). Here, we demonstrate the relevance of the time of the day for how sensitive AT is to the effects of insulin. Subcutaneous AT shows an endogenous circadian rhythm in insulin sensitivity that could provide an underlying mechanism for the daily rhythm in systemic insulin sensitivity.-Carrasco-Benso, M. P., Rivero-Gutierrez, B., Lopez-Minguez, J., Anzola, A., Diez-Noguera, A., Madrid, J. A., Lujan, J. A., Martínez-Augustin, O., Scheer, F. A. J. L., Garaulet, M. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity. © FASEB.

  3. Effects of exercise training on subcutaneous and visceral adipose tissue in normal- and high-fat diet-fed rats

    OpenAIRE

    Gollisch, Katja S. C.; Brandauer, Josef; Jessen, Niels; Toyoda, Taro; Nayer, Ali; Hirshman, Michael F.; Goodyear, Laurie J.

    2009-01-01

    Regular physical activity improves glucose tolerance and decreases adiposity. Our aim was to investigate the effects of exercise training on subcutaneous (inguinal) and visceral (parametrial) adipose tissue in rats that were fed a chow diet (13% fat) or made insulin resistant by a high-fat diet (60% fat). Sprague-Dawley rats performed 4 wk of voluntary wheel running or were kept as sedentary controls. The training groups fed chow and the high-fat diet achieved similar running distances (8.8 ±...

  4. Anthropometry, DXA and leptin reflect subcutaneous but not visceral abdominal adipose tissue by MRI in 197 healthy adolescents

    DEFF Research Database (Denmark)

    Tinggaard, Jeanette; Hagen, Casper P; Christensen, Anders Nymark

    2017-01-01

    magnetic resonance imaging (MRI). Methods We performed a cross-sectional study that included 197 healthy adolescents (114 boys) aged 10–15 years nested within a longitudinal population-based cohort. Clinical examination, blood sampling, DXA, and abdominal MRI were performed. SAT% and VAT% were adjusted......Background Abdominal fat distribution is associated with the development of cardio-metabolic disease independently of body mass index (BMI). We assessed anthropometry, serum adipokines, and DXA as markers of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) using...

  5. Prediction of whole-body fat percentage and visceral adipose tissue mass from five anthropometric variables.

    Directory of Open Access Journals (Sweden)

    Michelle G Swainson

    Full Text Available The conventional measurement of obesity utilises the body mass index (BMI criterion. Although there are benefits to this method, there is concern that not all individuals at risk of obesity-associated medical conditions are being identified. Whole-body fat percentage (%FM, and specifically visceral adipose tissue (VAT mass, are correlated with and potentially implicated in disease trajectories, but are not fully accounted for through BMI evaluation. The aims of this study were (a to compare five anthropometric predictors of %FM and VAT mass, and (b to explore new cut-points for the best of these predictors to improve the characterisation of obesity.BMI, waist circumference (WC, waist-to-hip ratio (WHR, waist-to-height ratio (WHtR and waist/height0.5 (WHT.5R were measured and calculated for 81 adults (40 women, 41 men; mean (SD age: 38.4 (17.5 years; 94% Caucasian. Total body dual energy X-ray absorptiometry with Corescan (GE Lunar iDXA, Encore version 15.0 was also performed to quantify %FM and VAT mass. Linear regression analysis, stratified by sex, was applied to predict both %FM and VAT mass for each anthropometric variable. Within each sex, we used information theoretic methods (Akaike Information Criterion; AIC to compare models. For the best anthropometric predictor, we derived tentative cut-points for classifying individuals as obese (>25% FM for men or >35% FM for women, or > highest tertile for VAT mass.The best predictor of both %FM and VAT mass in men and women was WHtR. Derived cut-points for predicting whole body obesity were 0.53 in men and 0.54 in women. The cut-point for predicting visceral obesity was 0.59 in both sexes.In the absence of more objective measures of central obesity and adiposity, WHtR is a suitable proxy measure in both women and men. The proposed DXA-%FM and VAT mass cut-offs require validation in larger studies, but offer potential for improvement of obesity characterisation and the identification of individuals

  6. Discriminatory Ability of Visceral Adiposity Index (VAI) in Diagnosis of Metabolic Syndrome: A Population Based Study.

    Science.gov (United States)

    Motamed, N; Khonsari, M R; Rabiee, B; Ajdarkosh, H; Hemasi, G R; Sohrabi, M R; Maadi, M; Zamani, F

    2017-03-01

    Background Visceral adiposity index (VAI) has been suggested as an index of visceral adiposity. This study was conducted to determine the discriminatory ability of VAI in diagnosis of metabolic syndrome (MetS). Methods and materials We used the data of 5 312 subjects aged 18-74 years of a cohort study conducted among 6 140 individuals aged 10-90 years in Amol, northern Iran. The city population was divided into 16 strata based on gender and age groups in 10-year intervals. The subjects were randomly selected from each stratum. MetS was defined based on National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII), American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) update of Adult Treatment Panel III (ATPIII), International Diabetes Federation (IDF) and joint interim statement (JIS) definitions. The discriminatory ability of VAI and other obesity measures were evaluated using receiver operating characteristic (ROC) curves. Results While waist circumference (WC) showed the highest discriminatory ability for MetS in IDF definition in men (AUC=0.899 [CI=0.888-0.910]), VAI had the greatest discriminatory ability according to other definitions in men and women. The related AUCs of VAI were 0.866 (95%CI: 0.850-0.881), 0.829 (95%CI: 0.813-0.846), 0.859 (95%CI: 0.844-0.873) and 0.876 (95%CI: 0.863-0.889) based on NCEP/ATPIII, AHA/NHLBI update of ATPIII, IDF and JIS definition in men, and also 0.888 (95%CI: 0.875-0.902), 0.894 (95%CI: 0.881-0.907), 0.883 (95%CI: 0.869-0.897) and 0.879 (95%CI: 0.864-0.894) in women, respectively. Conclusion VAI showed an excellent discriminatory ability in diagnosis of MetS. Considering its relatively simple calculation, this index could be suggested as a reliable tool in medical practice. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women

    NARCIS (Netherlands)

    Fox, C.S.; Liu, Y.; White, C.C.; Feitosa, M.; Smith, A.V.; Heard-Costa, N.; Lohman, K.; Hottenga, J.J.; de Geus, E.J.C.; Willemsen, G.; Boomsma, D.I.; Johnson, A.D.; Foster, M.C.; Greenawalt, D.M.; Griffin, P.; Ding, J.; Newman, A.B.; Tylavsky, F.; Miljkovic, I.; Kritchevsky, S.B.; Launer, L.; Garcia, M.; Eiriksdottir, G.; Posthuma, D.; Carr, J.J.; Gudnason, V.; Harris, T.B.; Cupples, L.A.; Borecki, I.B.

    2012-01-01

    Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants

  8. Role of Micro RNA-205 in Promoting Visceral Adiposity of NZ10 Mice with Polygenic Susceptibility for Type 2 Diabetes.

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    Adi, Nikhil; Adi, Jennipher; Cesar, Liliana; Kurlansky, Paul; Agatston, Arthur; Webster, Keith A

    2015-07-01

    To characterize diet-dependent miRNA profiles and their targets in the visceral adipose of mice with polygenic susceptibility to type 2 diabetes. Six-week NONcNZO10/LtJ (NZ10) and control SWR/J mice were subjected to high protein-fish oil or control diets for 19 weeks and micro-RNA microarray analyses were implemented on visceral adipose RNA. We found that 27 miRNAs were significantly induced and 10 significantly repressed in the VA of obese NZ10 mice compared with controls. 12 selected regulated miRNAs were confirmed by RT-PCR based on the microarray data and we demonstrated that the expression of these miRNAs remained unaltered in the VA of control SWR mice. To assess the possible functional roles of miRNAs in adipogenesis, we also analyzed their expression in 3T3-L1 cells during growth and differentiation. This revealed that suppression of miRNA-205 alone correlated selectively with increased cell proliferation and lipid formation of adipocytes. Diet and genetics control the expression of obesity-regulated miRNAs in the visceral adipose of NZ10 mice.

  9. Congenitally transmitted visceral leishmaniasis: report of two brazilian human cases

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    Myrlena Regina Machado Mescouto-Borges

    2013-04-01

    Full Text Available Visceral leishmaniasis is a relevant public health problem worldwide. Most of the reported cases in Latin America are from Brazil. Herein we report two human cases of congenitally transmitted visceral leishmaniasis in two patients who developed symptoms during pregnancy. The diagnosis was made by visual examination of Leishmania parasites in bone marrow aspirates of the mothers and by detecting parasite kDNA in bone marrow samples of the newborn children using polymerase chain reaction.

  10. APMAP interacts with lysyl oxidase-like proteins, and disruption of Apmap leads to beneficial visceral adipose tissue expansion.

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    Pessentheiner, Ariane R; Huber, Katharina; Pelzmann, Helmut J; Prokesch, Andreas; Radner, Franz P W; Wolinski, Heimo; Lindroos-Christensen, Josefine; Hoefler, Gerald; Rülicke, Thomas; Birner-Gruenberger, Ruth; Bilban, Martin; Bogner-Strauss, Juliane G

    2017-09-01

    Adipocyte plasma membrane-associated protein (APMAP) has been described as an adipogenic factor in 3T3-L1 cells with unknown biochemical function; we therefore aimed to investigate the physiologic function of APMAP in vivo We generated Apmap-knockout mice and challenged them with an obesogenic diet to investigate their metabolic phenotype. We identified a novel truncated adipocyte-specific isoform of APMAP in mice that is produced by alternative transcription. Mice lacking the full-length APMAP protein, the only isoform that is expressed in humans, have an improved metabolic phenotype upon diet-induced obesity, indicated by enhanced insulin sensitivity, preserved glucose tolerance, increased respiratory exchange ratio, decreased inflammatory marker gene expression, and reduced adipocyte size. At the molecular level, APMAP interacts with the extracellular collagen cross-linking matrix proteins lysyl oxidase-like 1 and 3. On a high-fat diet, the expression of lysyl oxidase-like 1 and 3 is strongly decreased in Apmap-knockout mice, paralleled by reduced expression of profibrotic collagens and total collagen content in epididymal white adipose tissue, indicating decreased fibrotic potential. Together, our data suggest that APMAP is a novel regulator of extracellular matrix components, and establish that APMAP is a potential target to mitigate obesity-associated insulin resistance.-Pessentheiner, A. R., Huber, K., Pelzmann, H. J., Prokesch, A., Radner, F. P. W., Wolinski, H., Lindroos-Christensen, J., Hoefler, G., Rülicke, T., Birner-Gruenberger, R., Bilban, M., Bogner-Strauss, J. G. APMAP interacts with lysyl oxidase-like proteins, and disruption of Apmap leads to beneficial visceral adipose tissue expansion. © The Author(s).

  11. Depletion of Regulatory T Cells in Visceral Adipose Tissues Contributes to Insulin Resistance in Hashimoto's Thyroiditis

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    Min Yang

    2018-02-01

    Full Text Available Hashimoto's Thyroiditis (HT is a common organ-specific autoimmune disorder associated with a high incidence, and insulin resistance is highly related to autoimmune. Here, we examined the insulin sensitivity in HT patients and found decreased insulin sensitivity occurred in HT patients. To explore the relationship between impaired insulin sensitivity and immune status, we established HT model mice which showed similar pathological features and immune features to HT patients. In HT model mice, reinfusion of regulatory T cells (Tregs from peripheral blood of normal mice could improve insulin sensitivity and decrease the inflammation. Anti-CD25 antibodies blocked beneficial effects from reinfusion of Tregs, but delayed administration of anti-CD25 antibodies could not abolished the effect from Tregs. Delayed administration of anti-CD25 antibodies abolished exogenous Tregs in peripheral blood, but there were increased exogenous Tregs located to visceral adipose tissues (VATs which modulated the expression of cytokines in VATs. These findings suggest that insulin resistance exists in HT patients and it associates with the decreased Tregs and increased inflammation in the VATs.

  12. The Effect of Diet or Exercise on Visceral Adipose Tissue in Overweight Youth.

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    Vissers, Dirk; Hens, Wendy; Hansen, Dominique; Taeymans, Jan

    2016-07-01

    Excess visceral adipose tissue (VAT) in children with obesity is associated with the development of cardiovascular and metabolic disease. This meta-analysis investigated if lifestyle interventions can reduce VAT in overweight and obese youth. Pubmed, Cochrane, and PEDro were searched for clinical trials that objectively assessed VAT and included study arms with supervised diet, exercise, or a combination of both. If there was a no-therapy control group, the data of the control group and the intervention groups were used to meta-analyze the data. In all other cases, the preintervention and the postintervention data were used to meta-analyze. Effect sizes were calculated as standardized mean differences or changes of VAT and expressed as Hedges' g. The overall weighted mean effect size on VAT of all included interventions was -0.69 (95% confidence interval [CI] = -0.90 to -0.48) (P effect size of diet-only interventions on VAT was 0.23 (95% CI = -0.22 to 0.68) (P = 0.311). Interventions that combined diet and exercise showed a pooled effect size on VAT of -0.55 (95% CI = -0.75 to -0.39) (P effect size of exercise-only interventions on VAT was -0.85 (95% CI = -1.20 to -0.57) (P effect was found in exercise-only groups. However, high-quality randomized controlled trials describing the effect of supervised dietary interventions on VAT in children are lacking.

  13. Gender differences in the association of visceral and subcutaneous adiposity with adiponectin in African Americans: the Jackson Heart Study

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    Bidulescu Aurelian

    2013-02-01

    Full Text Available Abstract Background Adiponectin, paradoxically reduced in obesity and with lower levels in African Americans (AA, modulates several cardiometabolic risk factors. Because abdominal visceral adipose tissue (VAT, known to be reduced in AA, and subcutaneous adipose tissue (SAT compartments may confer differential metabolic risk profiles, we investigated the associations of VAT and SAT with serum adiponectin, separately by gender, with the hypothesis that VAT is more strongly inversely associated with adiponectin than SAT. Methods Participants from the Jackson Heart Study, an ongoing cohort of AA (n = 2,799; 64% women; mean age, 55 ± 11 years underwent computer tomography assessment of SAT and VAT volumes, and had stored serum specimens analyzed for adiponectin levels. These levels were examined by gender in relation to increments of VAT and SAT. Results Compared to women, men had significantly lower mean levels of adiponectin (3.9 ± 3.0 μg/mL vs. 6.0 ± 4.4 μg/mL; p 3 vs. 2,668 ± 968 cm3; p 3 vs. 801 ± 363 cm3; p  Conclusion In African Americans, abdominal visceral adipose tissue had an inverse association with serum adiponectin concentrations only among women. Abdominal subcutaneous adipose tissue appeared as a protective fat depot in men.

  14. Robust Early Inflammation of the Peri-pancreatic Visceral Adipose Tissue During Diet-Induced Obesity in the KrasG12D Model of Pancreatic Cancer

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    Hertzer, Kathleen M.; Xu, Mu; Moro, Aune; Dawson, David W.; Du, Lin; Li, Gang; Chang, Hui-Hua; Stark, Alexander P.; Jung, Xiaoman; Hines, O. Joe; Eibl, Guido

    2016-01-01

    Objectives Obesity increases the incidence of multiple types of cancer. Our previous work has shown that a high fat, high calorie diet (HFCD) leads to visceral obesity, pancreatic inflammation, and accelerated pancreatic neoplasia in KrasG12D (KC) mice. In this study we aimed to investigate the effects of a HFCD on visceral adipose inflammation with emphasis on potential differences between distinct visceral adipose depots. Methods We examined the weight and visceral obesity in both wild-type (WT) and KC mice on either control diet (CD) or HFCD. After three months, mice were sacrificed for histological examination. Multiplex assays were also performed to obtain cytokine profiles between different adipose depots. Results Both WT and KC mice on a HFCD exhibited significantly increased inflammation in the visceral adipose tissue (VAT), particularly in the peri-pancreatic fat (PPF), compared to animals on a CD. This was associated with significantly increased inflammation in the pancreas. Cytokine profiles were different between visceral adipose depots, and between mice on the HFCD and CD. Conclusions Our results clearly demonstrate that a HFCD leads to obesity and inflammation in the VAT, particularly the PPF. These data suggest that obesity-associated inflammation in PPF may accelerate pancreatic neoplasia in KC mouse. PMID:26495779

  15. Ethnic influences on the relations between abdominal subcutaneous and visceral adiposity, liver fat, and cardiometabolic risk profile: the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity.

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    Nazare, Julie-Anne; Smith, Jessica D; Borel, Anne-Laure; Haffner, Steven M; Balkau, Beverley; Ross, Robert; Massien, Christine; Alméras, Natalie; Després, Jean-Pierre

    2012-10-01

    Ethnic differences in cardiometabolic risk (CMR) may be related to patterns of ethnic-specific body fat distribution. We aimed to identify differences across ethnic groups in interrelations between BMI, abdominal adiposity, liver fat, and CMR profile. In the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity, 297 physicians recruited 4504 patients (from 29 countries). In the current cross-sectional analyses, 2011 whites, 166 African Caribbean blacks, 381 Hispanics, 1192 East Asians, and 347 Southeast Asians were included. Computed tomography was used to assess abdominal fat distribution and to estimate liver fat content. Anthropometric variables and CMR profile were measured. Higher ranges of BMI were associated with higher levels of visceral [visceral adipose tissue (VAT)] and deep subcutaneous [deep subcutaneous adipose tissue (DSAT)] adiposity, with significant ethnic differences regarding the slope of these relations. Despite lower absolute BMI values, East Asians presented the largest accumulation of VAT but the lowest accumulation of DSAT with increasing adiposity. The association of BMI with liver fat did not differ between ethnic groups. Liver fat and DSAT were positively correlated with VAT with no ethnic variation. All ethnic groups had a similar association between a 1-SD increase in VAT, DSAT, or liver fat with hypertension, type 2 diabetes, hypertriglyceridemia, low HDL-cholesterol concentration, or high C-reactive protein concentration. Ethnicity significantly affects abdominal adiposity and liver fat partitioning, and East Asians have the most deleterious abdominal fat distribution. Irrespective of ethnicity, abdominal and hepatic fat depots are strongly interrelated and increased with obesity. Higher amounts of VAT or liver fat are associated with a more deteriorated CMR profile in all ethnic groups.

  16. Diet Quality in Midadulthood Predicts Visceral Adiposity and Liver Fatness in Older Ages: The Multiethnic Cohort Study.

    Science.gov (United States)

    Maskarinec, Gertraud; Lim, Unhee; Jacobs, Simone; Monroe, Kristine R; Ernst, Thomas; Buchthal, Steven D; Shepherd, John A; Wilkens, Lynne R; Le Marchand, Loïc; Boushey, Carol J

    2017-08-01

    The relationship of diet quality assessed by established indices (HEI-2010, AHEI-2010, aMED, DASH) with adiposity measures was examined, especially visceral adipose tissue (VAT) and nonalcoholic fatty liver (NAFL). Close to 2,000 participants of the Multiethnic Cohort completed validated food frequency questionnaires at cohort entry (1993-1996) and clinic visit (2013-2016) when they underwent whole-body dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging scans. Linear regression was used to estimate mean values of adiposity measures by dietary index tertiles at baseline and standardized regression coefficients (βs ) after adjusting for total adiposity and other covariates. Logistic regression of VAT and NAFL on dietary indices was also performed. Higher dietary quality scores at cohort entry were inversely related to all adiposity measures, with the strongest associations for percent liver fat (βs  = -0.14 to -0.08), followed by VAT (βs  = -0.11 to -0.05), BMI (βs  = -0.11 to -0.06), and total body fat (βs  = -0.09 to -0.05). Odds ratios adjusted for total adiposity ranged between 0.57 and 0.77 for NAFL and between 0.41 and 0.65 for high VAT when comparing the highest versus lowest tertiles of diet quality. These longitudinal findings indicate that maintaining a high-quality diet during mid-to-late adulthood may prevent adverse metabolic consequences related to VAT and NAFL. © 2017 The Obesity Society.

  17. Visceral adiposity and cardiometabolic risks: epidemic of abdominal obesity in North America

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    Wimalawansa SJ

    2013-05-01

    Full Text Available Sunil J WimalawansaRobert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USAAbstract: Over the past 40 years, the prevalence of obesity has more than doubled in the United States. Approximately 67% of American adults older than 20 years of age are either obese or overweight. Obesity has now become a critically important issue facing more than 40% of Americans and has become a major burden on the American health care system. Today, obesity cannot be considered a simple lifestyle issue; it is a disease with major public health and economic consequences that requires serious attention by all stakeholders. Each individual has different causes and risk factors that lead to obesity and its associated complications. In addition to preventing becoming overweight, focusing on identifying the causes of obesity and then individualizing care and treatment plans to targeting weight loss, particularly intra-abdominal fat, could potentially generate huge cost savings. Excess intra-abdominal fat (visceral adiposity is linked to excess morbidity and mortality, and positively correlates with the risks of insulin resistance, type 2 diabetes, cardiovascular diseases, certain cancers, and premature death. Therefore, overweight and obese patients should be offered healthy lifestyle changes including education about causes leading to excess weight, weight-reducing diets, physical activity regimens, and monitoring for progress. Medications and bariatric surgery are effective but are the last options and should be complementary to lifestyle and behavioral changes. The costs associated with managing obesity-related disorders and their complications are astounding; unless we intervene now, these are likely to triple over the next 2 decades. Thus, policymakers must pay serious attention to this progressive, insidious epidemic and determine the right paths for tackling obesity, which requires a paradigm shift in thinking

  18. [Relationship between glycemic control and visceral adiposity index among the patients with type 2 diabetes mellitus].

    Science.gov (United States)

    Cao, Y Y; Tang, X; Sun, K X; Liu, Z K; Xiang, X; Juan, J; Song, J; Duan, Q Z; Zhaxi, D J; Hu, Y N; Yang, Y F; Shi, M Y; Tian, Y H; Huang, S P; Liu, X F; Li, N; Li, J; Wu, T; Chen, D F; Hu, Y H

    2017-06-18

    To explore the relationship between glycemic control and visceral adiposity index (VAI) among type 2 diabetes mellitus (T2DM) patients. A community-based epidemiological field study for patients with T2DM aged ≥ 40 years was conducted in China.Every participant underwent physical examinations, biochemical tests of fasting glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and so on, and a questionnaire, including anthropometric characteristics, lifestyle, disease history, family history, and medication use. Those participants with HbA1c ≥7.0% were classified as the poorly controlled in our analysis of relationship between glycemic control and VAI. Anthropometric characteristics, lifestyle, and biochemical indexes of the participants were compared among the groups of different VAI levels. Logistic models were applied in multiple analysis adjusting for possible confounders. A total of 1 607 patients with T2DM were recruited in our analysis with a mean age of (59.4±8.1) years and an average T2DM duration of (7.0±6.4) years. Among them, 78.3% were on hypoglycemic therapy. The cutoff points of quartiles of VAI were calculated for the males and females, respectively. According to the ascending order of the quartiles of VAI, the participants were divided into four groups, i.e. Q1, Q2, Q3, and Q4. The poor glycemic control rate for these groups were 60.6%, 65.7%, 70.1%, and 71.0%, respectively (Trend χ2=12.20, Pglycemic control rate was significantly associated with VAI levels among the patients with T2DM. Compared with the participants in group Q1, the ORs of poor glycemic control for those in groups Q2, Q3, and Q4 were 1.239 (95%CI 0.918 to 1.672), 1.513 (95%CI 1.117 to 2.050), and 1.535 (95%CI 1.128 to 2.088), respectively (trend P=0.003). With each quartile increase in VAI, the OR of poor glycemic control was 1.162 (95%CI 1.054 to 1

  19. Implications of Pericardial, Visceral and Subcutaneous Adipose Tissue on Vascular Inflammation Measured Using 18FDG-PET/CT.

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    Ho Cheol Hong

    Full Text Available Pericardial adipose tissue (PAT is associated with adverse cardiometabolic risk factors and cardiovascular disease (CVD. However, the relative implications of PAT, abdominal visceral and subcutaneous adipose tissue on vascular inflammation have not been explored.We compared the association of PAT, abdominal visceral fat area (VFA, and subcutaneous fat area (SFA with vascular inflammation, represented as the target-to-background ratio (TBR, the blood-normalized standardized uptake value measured using 18F-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET in 93 men and women without diabetes or CVD. Age- and sex-adjusted correlation analysis showed that PAT, VFA, and SFA were positively associated with most cardiometabolic risk factors, including systolic blood pressure, LDL-cholesterol, triglycerides, glucose, insulin resistance and high sensitive C-reactive proteins (hsCRP, whereas they were negatively associated with HDL-cholesterol. In particular, the maximum TBR (maxTBR values were positively correlated with PAT and VFA (r = 0.48 and r = 0.45, respectively; both P <0.001, whereas SFA showed a relatively weak positive relationship with maxTBR level (r = 0.31, P = 0.003.This study demonstrated that both PAT and VFA are significantly and similarly associated with vascular inflammation and various cardiometabolic risk profiles.

  20. Dietary determinants of changes in waist circumference adjusted for body mass index - a proxy measure of visceral adiposity.

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    Dora Romaguera

    2010-07-01

    Full Text Available Given the recognized health effects of visceral fat, the understanding of how diet can modulate changes in the phenotype "waist circumference for a given body mass index (WC(BMI", a proxy measure of visceral adiposity, is deemed necessary. Hence, the objective of the present study was to assess the association between dietary factors and prospective changes in visceral adiposity as measured by changes in the phenotype WC(BMI.We analyzed data from 48,631 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC study. Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years. WC(BMI was defined as the residuals of waist circumference regressed on body mass index, and annual change in WC(BMI (DeltaWC(BMI, cm/y was defined as the difference between residuals at follow-up and baseline, divided by follow-up time. The association between energy, energy density (ED, macronutrients, alcohol, glycemic index (GI, glycemic load (GL, fibre and DeltaWC(BMI was modelled using centre-specific adjusted linear regression, and random-effects meta-analyses to obtain pooled estimates. Men and women with higher ED and GI diets showed significant increases in their WC(BMI, compared to those with lower ED and GI [1 kcal/g greater ED predicted a DeltaWC(BMI of 0.09 cm (95% CI 0.05 to 0.13 in men and 0.15 cm (95% CI 0.09 to 0.21 in women; 10 units greater GI predicted a DeltaWC(BMI of 0.07 cm (95% CI 0.03 to 0.12 in men and 0.06 cm (95% CI 0.03 to 0.10 in women]. Among women, lower fibre intake, higher GL, and higher alcohol consumption also predicted a higher DeltaWC(BMI.Results of this study suggest that a diet with low GI and ED may prevent visceral adiposity, defined as the prospective changes in WC(BMI. Additional effects may be obtained among women of low alcohol, low GL, and high fibre intake.

  1. Human visceral leishmaniasis: a picture from Italy.

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    Abdalmaula, Giuma Harun; Barbadoro, Pamela; Marigliano, Anna; Illuminati, Diego; Di Stanislao, Francesco; D'Errico, Marcello Mario; Prospero, Emilia

    2013-12-01

    The aim of our study was to describe the distribution of Visceral Leishmaniasis (VL) in Italy, focusing on HIV-infected patients, to estimate the burden of the disease and the public health actions that should be undertaken. A review of official notifications and hospitalization data has been performed. From 2006 to 2008, a total of 289 cases of VL were notified; the overall notification rate was 1.63/1,000,000 (95% CI 1.45-1.83). In total, 1192 VL-associated hospitalizations were detected, with a hospitalization rate of 6.71/1,000,000 (95% CI 6.34-7.10). For the age group "≤ 24 years", a statistically significant increase was detected (p<0.05). A total of 68.9% (n = 821) of hospitalizations were detected in HIV-positive patients. The geographic distribution of rates revealed a significant increase in the north-eastern area of the country. Our study confirms that the epidemiological pattern of VL is changing and that, in Italy, control measures and preventive strategies should be based on not only the official notification system but also hospital data. This would lead to the identification of areas of parasite spread and to the creation of awareness campaigns geared toward general practitioners in the affected areas. Easy case detection would allow for timely public health actions and strategies for the implementation of more effective interventions for reservoir control. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  2. Physical training improves visceral adipose tissue health by remodelling extracellular matrix in rats with estrogen absence: a gene expression analysis.

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    Duarte, Fernanda O; Gomes-Gatto, Camila do Valle; Oishi, Jorge C; Lino, Anderson Diogo de S; Stotzer, Uliana S; Rodrigues, Maria Fernanda C; Gatti da Silva, Guilherme H; Selistre-de-Araújo, Heloisa S

    2017-08-01

    Adipose tissue development is associated with modifications involving extracellular matrix remodelling, and metalloproteinases play a significant role in this process. Reduced circulating sexual hormones cause impacts on the size, morphology and functions of the adipose tissue, increasing susceptibility to diseases. This study investigated whether exercise training may be an alternative strategy to combat the effects promoted by estrogen decay through modulation in gene expression patterns in the extracellular matrix (ECM) of visceral adipose tissue of ovariectomized rats. Nulliparous rats (n = 40) were randomly distributed into four groups (n = 10/group): sham sedentary (Sh-S), sham resistance training (Sh-Rt), ovariectomized sedentary (Ovx-S) and ovariectomized resistance training (Ovx-Rt). The Sh-S animals did not have any type of training. The body mass and food intake, ECM gene expression, gelatinase MMP-2 activity and adipocyte area were measured. A lack of estrogen promoted an increase in body mass, food intake and the visceral, parametrial and subcutaneous adipocyte areas. The ovariectomy upregulated the expression of MMP-2, MMP-9, TGF-β, CTGF, VEGF-A and MMP-2 activity. On the other hand, resistance training decreased the body mass, food intake and the adipocyte area of the three fat depots analysed; upregulated TIMP-1, VEGF-A and MMP-2 gene expression; downregulated MMP-9, TGF-β and CTGF gene expression; and decreased the MMP-2 activity. We speculate that resistance training on a vertical ladder could play an important role in maintaining and remodelling ECM by modulation in the ECM gene expression and MMP-2 activity, avoiding its destabilization which is impaired by the lack of estrogen. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

  3. A systematic review and meta-analysis on the effects of exercise training versus hypocaloric diet: distinct effects on body weight and visceral adipose tissue.

    NARCIS (Netherlands)

    Verheggen, R.J.; Maessen, M.F.; Green, D.J.; Hermus, A.R.M.M.; Hopman, M.T.E.; Thijssen, D.H.J.

    2016-01-01

    Exercise training ('exercise') and hypocaloric diet ('diet') are frequently prescribed for weight loss in obesity. Whilst body weight changes are commonly used to evaluate lifestyle interventions, visceral adiposity (VAT) is a more relevant and stronger predictor for morbidity and mortality. A

  4. Intrinsic features in microRNA transcriptomes link porcine visceral rather than subcutaneous adipose tissues to metabolic risk.

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    Jideng Ma

    Full Text Available MicroRNAs (miRNAs are non-coding small RNA ∼22 nucleotides in length that can regulate the expression of a wide range of coding genes at the post-transcriptional level. Visceral adipose tissues (VATs and subcutaneous adipose tissues (SATs, the two main fat compartments in mammals, are anatomically, physiologically, metabolically, and clinically distinct. Various studies of adipose tissues have focused mainly on DNA methylation, and mRNA and protein expression, nonetheless little research sheds directly light on the miRNA transcriptome differences between these two distinct adipose tissue types. Here, we present a comprehensive investigation of miRNA transcriptomes across six variant porcine adipose tissues by small RNA-sequencing. We identified 219 known porcine miRNAs, 97 novel miRNA*s, and 124 miRNAs that are conserved to other mammals. A set of universally abundant miRNAs (i.e., miR-148a-3p, miR-143-3p, miR-27b-3p, miR-let-7a-1-5p, and miR-let-7f-5p across the distinct adipose tissues was found. This set of miRNAs may play important housekeeping roles that are involved in adipogenesis. Clustering analysis indicated significant variations in miRNA expression between the VATs and SATs, and highlighted the role of the greater omentum in responding to potential metabolic risk because of the observed enrichment in this tissue of the immune- and inflammation-related miRNAs, such as the members of miR-17-92 cluster and miR-181 family. Differential expression of the miRNAs between the VATs and SATs, and miRNA target prediction analysis revealed that the VATs-specific enriched miRNAs were associated mainly with immune and inflammation responses. In summary, the differences of miRNA expression between the VATs and SATs revealed some of their intrinsic differences and indicated that the VATs might be closely associated with increased risk of metabolic disorders.

  5. Prognostic significance of the complex "Visceral Adiposity Index" vs. simple anthropometric measures: Tehran lipid and glucose study.

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    Mohammadreza, Bozorgmanesh; Farzad, Hadaegh; Davoud, Khalili; Fereidoun Prof, Azizi Fereidoun

    2012-03-07

    Visceral adiposity index (VAI) has recently been suggested to be used as a surrogate of visceral adiposity. We examined if VAI could improve predictive performances for CVD of the Framingham's general CVD algorithm (a multivariate model incorporating established CVD risk factors). We compared the predictive abilities of the VAI with those of simple anthropometric measures i.e. BMI, waist-to-height ratio (WHtR) or waist-to-hip ratio (WHpR). In a nine-year population-based follow-up, 6,407 (2,778 men) participants, free of CVD at baseline, aged≥30 years were eligible for the current analysis. The risk of CVD was estimated by incorporating VAI, BMI, WHpR, and WHtR, one at a time, into multivariate accelerated failure time models. We documented 534 CVD events with the annual incidence rate (95%CIs) being 7.3 (6.4-8.3) among women and 13.0 (11.7-14.6) among men. Risk of future CVD increased with increasing levels of VAI among both men and women. VAI was associated with multivariate-adjusted increased risk of incident CVD among women. However, the magnitude of risk conferred by VAI was not significantly higher than those conferred by BMI, WHpR, or WHtR. Among men, after adjustment for established CVD risk factors, VAI was no longer associated with increased risk of CVD. VAI failed to add to the predictive ability of the Framingham general CVD algorithm. Using VAI instead of simple anthropometric measures may lead to loss of much information needed for predicting incident CVD.

  6. Improved insulin sensitivity despite increased visceral adiposity in mice deficient for the immune cell transcription factor T-bet.

    Science.gov (United States)

    Stolarczyk, Emilie; Vong, Chi Teng; Perucha, Esperanza; Jackson, Ian; Cawthorne, Michael A; Wargent, Edward T; Powell, Nick; Canavan, James B; Lord, Graham M; Howard, Jane K

    2013-04-02

    Low-grade inflammation in fat is associated with insulin resistance, although the mechanisms are unclear. We report that mice deficient in the immune cell transcription factor T-bet have lower energy expenditure and increased visceral fat compared with wild-type mice, yet paradoxically are more insulin sensitive. This striking phenotype, present in young T-bet(-/-) mice, persisted with high-fat diet and increasing host age and was associated with altered immune cell numbers and cytokine secretion specifically in visceral adipose tissue. However, the favorable metabolic phenotype observed in T-bet-deficient hosts was lost in T-bet(-/-) mice also lacking adaptive immunity (T-bet(-/-)xRag2(-/-)), demonstrating that T-bet expression in the adaptive rather than the innate immune system impacts host glucose homeostasis. Indeed, adoptive transfer of T-bet-deficient, but not wild-type, CD4(+) T cells to Rag2(-/-) mice improved insulin sensitivity. Our results reveal a role for T-bet in metabolic physiology and obesity-associated insulin resistance. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Visceral Abdominal and Subfascial Femoral Adipose Tissue Have Opposite Associations with Liver Fat in Overweight and Obese Premenopausal Caucasian Women

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    Paulo M. Rocha

    2011-01-01

    Full Text Available Abdominal obesity has been associated with liver fat storage. However, the relationships between other body composition depots and metabolic syndrome features with hepatic fat are still unclear. We examined abdominal and thigh adipose tissue (AT compartments associations with liver fat in 140 overweight and obese premenopausal Caucasian women. Blood lipids and, proinflammatory and atherothrombotic markers associations with hepatic fat were also analyzed. A larger visceral AT (VAT was related with liver fat (P<0.05. Contrarily, thigh subfascial AT was inversely related to liver fat (P<0.05. Increased fasting insulin, triglycerides, PAI-1 concentrations, and a higher total-cholesterol/HDL-cholesterol ratio were also associated with hepatic fat, even after adjustment for VAT (P<0.05. Thigh subfascial adiposity was inversely associated with liver fat, suggesting a potential preventive role against ectopic fat storage in overweight and obese women. These results reinforce the contribution of an abdominal obesity phenotype associated with a diabetogenic and atherothrombotic profile to liver lipotoxicity.

  8. Hepatic and visceral adipose tissue 11βHSD1 expressions are markers of body weight loss after bariatric surgery.

    Science.gov (United States)

    Pardina, Eva; Baena-Fustegueras, Juan Antonio; Fort, José Manuel; Ferrer, Roser; Rossell, Joana; Esteve, Montserrat; Peinado-Onsurbe, Julia; Grasa, Mar

    2015-09-01

    Cortisolemia and 11βHSD1 in liver and adipose tissue are altered in obesity. However, their participation in the development of obesity remains unclear. This study analyzed these parameters in the transition from morbid to type 1 obesity after bariatric surgery. A group of 34 patients with morbid obesity and 22 nonobese subjects were recruited. Initial hypothalamus-pituitary-adrenal (HPA) basal activity and 11βHSD1 mRNA expression in liver, subcutaneous (SAT), and visceral adipose tissue (VAT) were evaluated. A year after bariatric surgery (weight loss of 48 kg), these parameters were reappraised in plasma, SAT, and liver. Body weight loss was accompanied by a downshift in basal HPA activity and 11βHSD1 expression in SAT. In patients with morbid obesity, 11βHSD1 expression correlated positively with BMI in VAT and negatively in liver at 6 and 12 months after surgery. In SAT, a correlation was observed with body weight only when patients showed type 1 obesity. Insulin, glucose, and HOMA correlated positively with all the HPA indicators and 11βHSD1 expression in SAT. Body weight loss after bariatric surgery is accompanied by a downshift in basal HPA activity. Hepatic and VAT 11βHSD1 expressions in morbid obesity are predictors of body weight loss. © 2015 The Obesity Society.

  9. Difference by sex but not by race/ethnicity in the visceral adipose tissue-depressive symptoms association: the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Remigio-Baker, Rosemay A; Allison, Matthew A; Schreiner, Pamela J; Szklo, Moyses; Crum, Rosa M; Leoutsakos, Jeannie-Marie; Franco, Manuel; Carnethon, Mercedes R; Nettleton, Jennifer A; Mujahid, Mahasin S; Diez Roux, Ana V; Jensky, Nicole; Golden, Sherita H

    2014-09-01

    Prior studies have investigated the association of clinical depression and depressive symptoms with body weight (i.e. body mass index (BMI) and waist circumference), but few have examined the association between depressive symptoms and intra-abdominal fat. Of these a limited number assessed the relationship in a multi-racial/ethnic population. Using data on 1017 men and women (45-84 years) from the Multi-Ethnic Study of Atherosclerosis (MESA) Body Composition, Inflammation and Cardiovascular Disease Study, we examined the cross-sectional association between elevated depressive symptoms (EDS) and CT-measured visceral fat mass at L2-L5 with multivariable linear regression models. EDS were defined as a Center for Epidemiological Studies Depression score ≥16 and/or anti-depressant use. Covariates included socio-demographics, inflammatory markers, health behaviors, comorbidities, and body mass index (BMI). Race/ethnicity (Whites [referent group], Chinese, Blacks and Hispanics) and sex were also assessed as potential modifiers. The association between depressive symptoms and visceral fat differed significantly by sex (p=0.007), but not by race/ethnicity. Among men, compared to participants without EDS, those with EDS had greater visceral adiposity adjusted for BMI and age (difference=122.5 cm2, 95% CI=34.3, 210.7, p=0.007). Estimates were attenuated but remained significant after further adjustment by socio-demographics, inflammatory markers, health behaviors and co-morbidities (difference=94.7 cm2, 95% CI=10.5, 178.9, p=0.028). Among women, EDS was not significantly related to visceral adiposity in the fully adjusted model. Sex, but not race/ethnicity, was found to modify the relationship between EDS and visceral fat mass. Among men, a significant positive association was found between depressive symptoms and visceral adiposity. No significant relationship was found among women. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

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    Chu-Lin Chou

    Full Text Available Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group. Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L. These results suggest a protective role of calcitriol treatment on endothelial

  11. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    Science.gov (United States)

    Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J F; Fang, Te-Chao

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

  12. Visceral adiposity, genetic susceptibility, and risk of complications among individuals with crohn's disease

    NARCIS (Netherlands)

    Van Der Sloot, Kimberley W.; Bellavance, Danielle; Gilpin, Katherine; Stewart, Kathleen; Joshi, Amit D.; Garber, John; Giallourakis, Comas; Yajnik, Vijay; Ananthakrishnan, Ashwin N.; Alizadeh, Behrooz; Xavier, Ramnik; Khalili, Hamed

    2016-01-01

    Introduction: Adipose tissue in mesenteric fat plays a key role in systemic and luminal inflammation through production of Tumor Necrosis Factor-α (TNF-α) and inhibition of adiponectin, an anti-inflammatory cytokine, in patients with Crohn's disease (CD). However, little is known about the role of

  13. Visceral adiposity index (VAI is predictive of an altered adipokine profile in patients with type 2 diabetes.

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    Marco C Amato

    Full Text Available AIMS: Although there is still no clear definition of "adipose tissue dysfunction" or ATD, the identification of a clinical marker of altered fat distribution and function may provide the needed tools for early identification of a condition of cardiometabolic risk. Our aim was to evaluate the correlations among various anthropometric indices [BMI, Waist Circumference (WC, Hip Circumference (HC, Waist/Hip ratio (WHR, Body Adiposity Index (BAI and Visceral adiposity Index (VAI] and several adipocytokines [Visfatin, Resistin, Leptin, Soluble leptin receptors (sOB-R, Adiponectin, Ghrelin, Adipsin, PAI-1, vascular endothelial growth factor (VEGF, Hepatocyte growth factor (HGF TNF-α, hs-CRP, IL-6, IL-18] in patients with type 2 diabetes (DM2. MATERIALS AND METHODS: Ninety-one DM2 patients (age: 65.25 ± 6.38 years; 42 men and 49 women in stable treatment for the last six months with metformin in monotherapy (1.5-2 g/day were cross-sectionally studied. Clinical, anthropometric, and metabolic parameters were evaluated. Serum adipocytokine levels were assayed with Luminex based kits. RESULTS: At the Pearson's correlation, among all the indices investigated, VAI showed a significant correlation with almost all adipocytokines analyzed [Visfatin, Resistin and hsCRP (all p<0.001; Adiponectin, sOb-R, IL-6, IL-18, HGF (all p<0.010; Ghrelin and VEGF (both p<0.05]. Through a two-step cluster analysis, 55 patients were identified with the most altered adipocytokine profile (patients with ATD. At a ROC analysis, VAI showed the highest C-statistic [0.767 (95% CI 0.66-0.84] of all the indices. CONCLUSIONS: Our study suggests that the VAI, among the most common indexes of adiposity assessment, shows the best correlation with the best known adipocytokines and cardiometabolic risk serum markers. Although to date we are still far from clearly identifying an ATD, the VAI would be an easy tool for clearly mirroring a condition of cardiometabolic risk, in the absence of an

  14. BMI changes during childhood and adolescence as predictors of amount of adult subcutaneous and visceral adipose tissue in men: the GOOD Study

    DEFF Research Database (Denmark)

    Kindblom, Jenny M; Lorentzon, Mattias; Hellqvist, Asa

    2009-01-01

    and visceral fat mass by BMI changes during childhood and adolescence. RESEARCH DESIGN AND METHODS: Detailed growth charts were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study (n = 612). Body composition was analyzed using dual-energy X......OBJECTIVE: The amount of visceral adipose tissue is a risk factor for the metabolic syndrome. It is unclear how BMI changes during childhood and adolescence predict adult fat distribution. We hypothesized that there are critical periods during development for the prediction of adult subcutaneous......-ray absorptiometry and adipose tissue areas using abdominal computed tomography at 18 to 20 years of age. RESULTS: The main finding in the present study was that subjects with increases in BMI Z score of more than 1 SD during adolescence had, independent of prepubertal BMI, both larger subcutaneous (+138%; P

  15. Lifestyle Intervention Involving Calorie Restriction with or without Aerobic Exercise Training Improves Liver Fat in Adults with Visceral Adiposity

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    Eiichi Yoshimura

    2014-01-01

    Full Text Available Objective. To evaluate the effect of calorie restriction-induced weight loss with or without aerobic exercise on liver fat. Methods. Thirty-three adults with visceral adiposity were divided into calorie restriction (CR; n = 18 or CR and aerobic exercise (CR + Ex; n = 15 groups. Target energy intake was 25 kcal/kg of ideal body weight. The CR + Ex group had a targeted exercise time of 300 min/wk or more at lactate threshold intensity for 12 weeks. Results. Reductions in body weight (CR, -5.3 ± 0.8 kg; CR + Ex, -5.1 ± 0.7 kg, fat mass (CR, -4.9± 0.9 kg; CR + Ex, -4.4 ± 0.6 kg, and visceral fat (CR, -24 ± 5 cm2; CR + Ex, -37 ± 5 cm2 were not statistically different between groups. Liver fat decreased significantly in both groups, with no difference between groups. Change in maximal oxygen uptake was significantly greater in the CR + Ex group than in the CR group (CR, -0.7 ± 0.7 mL/kg/min; CR + Ex, 2.9 ± 1.0 mL/kg/min. Conclusion. Both CR and CR + Ex resulted in an improved reduction in liver fat; however, there was no additive effect of exercise training.

  16. A visceral adiposity index-related dietary pattern and the cardiometabolic profiles in women with polycystic ovary syndrome.

    Science.gov (United States)

    Ehsani, Behnaz; Moslehi, Nazanin; Mirmiran, Parvin; Ramezani Tehrani, Fahimeh; Tahmasebinejad, Zhale; Azizi, Fereidoun

    2016-10-01

    Visceral adiposity index (VAI), an indicator of visceral adiposity, has been found to be associated with cardiometabolic disturbances in women with polycystic ovary syndrome (PCOS). The association of dietary intakes with VAI, and subsequently cardiometabolic variables is still unclear. The aims of this study were to identify a dietary pattern associated with VAI and to investigate whether this pattern is associated with cardiometabolic variables in PCOS women. The study was conducted on 53 PCOS women, aged 18-45 years, diagnosed according to National Institutes of Health (NIH) criteria, and 167 age-matched normo-ovulatory women who were recruited from the Tehran Lipid and Glucose Study. Reduced rank regression was applied to determine a dietary pattern that explains the maximum variation of the VAI. Associations between the dietary pattern and cardiometabolic profiles were investigated using linear and logistic regression, adjusted for age and BMI. A VAI dietary pattern was identified characterized by high consumption of fried vegetables, vegetable oils (except olive oil), salty snacks, legumes, eggs, fast foods and low consumption of traditional sweets, high and low fat dairy, cruciferous vegetables, sugars and honey. A one standard deviation (SD) increase in dietary pattern score was significantly associated with higher triglycerides (TGs) (βcontrol = 0.22, p = 0.003; βcase = 0.48, p = 0.001) and TGs/HDL-C ratio (βcontrol = 0.23, p = 0.002; βcase = 0.52, p = 0.001) in both groups. After adjusting for age and BMI, a 1-SD increase in dietary pattern score was associated with increased risk of VAD in PCOS (OR 2.77; 95% CI 1.15, 6.66) and control groups (OR 2.41; 95% CI 1.41-4.12). In the control group, the risk of hypercholesterolemia, hypertriglyceridemia, high LDL-C, low HDL-C, hyperglycemia and IGT + IFG increased significantly per 1-SD increase in dietary pattern score, which all remained significant after adjusting for age and BMI, except

  17. GQ-16, a TZD-Derived Partial PPARγ Agonist, Induces the Expression of Thermogenesis-Related Genes in Brown Fat and Visceral White Fat and Decreases Visceral Adiposity in Obese and Hyperglycemic Mice.

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    Michella S Coelho

    Full Text Available Beige adipocytes comprise a unique thermogenic cell type in the white adipose tissue (WAT of rodents and humans, and play a critical role in energy homeostasis. In this scenario, recruitment of beige cells has been an important focus of interest for the development of novel therapeutic strategies to treat obesity. PPARγ activation by full agonists (thiazolidinediones, TZDs drives the appearance of beige cells, a process so-called browning of WAT. However, this does not translate into increased energy expenditure, and TZDs are associated with weight gain. Partial PPARγ agonists, on the other hand, do not induce weight gain, but have not been shown to drive WAT browning. The present study was designed to investigate the effects of GQ-16 on BAT and on browning of WAT in obese mice.Male Swiss mice with obesity and hyperglycemia induced by high fat diet were treated with vehicle, rosiglitazone (4 mg/kg/d or the TZD-derived partial PPARγ agonist GQ-16 (40 mg/kg/d for 14 days. Fasting blood glucose, aspartate aminotransferase, alanine aminotransferase and lipid profile were measured. WAT and brown adipose tissue (BAT depots were excised for determination of adiposity, relative expression of Ucp-1, Cidea, Prdm16, Cd40 and Tmem26 by RT-qPCR, histological analysis, and UCP-1 protein expression analysis by immunohistochemistry. Liver samples were also removed for histological analysis and determination of hepatic triglyceride content.GQ-16 treatment reduced high fat diet-induced weight gain in mice despite increasing energy intake. This was accompanied by reduced epididymal fat mass, reduced liver triglyceride content, morphological signs of increased BAT activity, increased expression of thermogenesis-related genes in interscapular BAT and epididymal WAT, and increased UCP-1 protein expression in interscapular BAT and in epididymal and inguinal WAT.This study suggests for the first time that a partial PPARγ agonist may increase BAT activity and induce

  18. Relationships between rodent white adipose fat pads and human white adipose fat depots

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    Daniella E. Chusyd

    2016-04-01

    Full Text Available The objective of this review was to compare and contrast the physiological and metabolic profiles of rodent white adipose fat pads with white adipose fat depots in humans. Human fat distribution and its metabolic consequences have received extensive attention, but much of what has been tested in translational research has relied heavily on rodents. Unfortunately, the validity of using rodent fat pads as a model of human adiposity has received less attention. There is a surprisingly lack of studies demonstrating an analogous relationship between rodent and human adiposity on obesity-related comorbidities. Therefore, we aimed to compare known similarities and disparities in terms of white adipose tissue development and distribution, sexual dimorphism, weight loss, adipokine secretion, and aging. While the literature supports the notion that many similarities exist between rodents and humans, notable differences emerge related to fat deposition and function of white adipose tissue. Thus, further research is warranted to more carefully define the strengths and limitations of rodent white adipose tissue as a model for humans, with a particular emphasis on comparable fat depots, such as mesenteric fat.

  19. Multiple-slice magnetic resonance imaging can detect visceral adipose tissue reduction more accurately than single-slice imaging.

    Science.gov (United States)

    So, R; Sasai, H; Matsuo, T; Tsujimoto, T; Eto, M; Saotome, K; Tanaka, K

    2012-12-01

    Imaging methods by magnetic resonance imaging are being increasingly used to quantify visceral adipose tissue (VAT), but there is no clear consensus as to a standardized protocol. We compared the ability of two commonly used imaging protocols (multiple slice versus single slice) to detect changes in VAT with diet or exercise. We utilized data from the participants who completed our diet (n=22) or exercise (n=35) based weight-loss interventions. The intervention mainly comprised of weekly dietary modification sessions or aerobic exercise sessions over 12 weeks. Multiple-slice images obtained from T9 to S1 and a single-slice image at L4-L5 were compared using the effect size of the VAT change. In addition, we calculated the sample size needed to compare the two imaging protocols' ability to detect significant changes in VAT. VAT and subcutaneous adipose tissue volumes and areas, and other anthropometry decreased significantly after both the diet and exercise interventions. For VAT, a single-slice image had a lower effect size (diet: 1.23; exercise: 0.49) than the multiple-slice images (diet: 1.81; exercise: 0.90). The sample size required for multiple slice was substantially lower than for the single-slice with both weight-loss interventions. The different image protocols may lead to different results in relative VAT changes. Furthermore, single-slice imaging required a substantially larger sample size than multiple-slice imaging, and for researchers to detect smaller changes in VAT with single-slice imaging, a larger sample size would be needed. Thus, multiple-slice imaging has advantages for assessing VAT change in future clinical research.

  20. Routine clinical measures of adiposity as predictors of visceral fat in adolescence: a population-based magnetic resonance imaging study.

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    Katie Goodwin

    Full Text Available OBJECTIVE: Visceral fat (VF increases cardiometabolic risk more than fat stored subcutaneously. Here, we investigated how well routine clinical measures of adiposity, namely body mass index (BMI and waist circumference (waist, predict VF and subcutaneous fat (SF in a large population-based sample of adolescents. As body-fat distribution differs between males and females, we performed these analyses separately in each sex. DESIGN AND METHODS: VF and SF were measured by magnetic resonance imaging in 1,002 adolescents (482 males, age 12-18 years. Relationships of BMI and waist with VF and SF were tested in multivariable analyses, which adjusted for potentially confounding effects of age and height. RESULTS: In both males and females, BMI and waist were highly correlated with VF and SF, and explained 55-76% of their total variance. When VF was adjusted for SF, however, BMI and waist explained, respectively, only 0% and 4% of VF variance in males, and 4% and 11% of VF variance in females. In contrast, when SF was adjusted for VF, BMI and waist explained, respectively, 36% and 21% of SF variance in males, and 48% and 23% of SF variance in females. These relationships were similar during early and late puberty. CONCLUSIONS AND RELEVANCE: During adolescence, routine clinical measures of adiposity predict well SF but not VF. This holds for both sexes and throughout puberty. Further longitudinal studies are required to assess how well these measures predict changes of VF and SF over time. Given the clinical importance of VF, development of cost-effective imaging techniques and/or robust biomarkers of VF accumulation that would be suitable in everyday clinical practice is warranted.

  1. Physical exercise remodels visceral adipose tissue and mitochondrial lipid metabolism in rats fed a high-fat diet.

    Science.gov (United States)

    Rocha-Rodrigues, Sílvia; Rodríguez, Amaia; Becerril, Sara; Ramírez, Beatriz; Gonçalves, Inês O; Beleza, Jorge; Frühbeck, Gema; Ascensão, António; Magalhães, José

    2017-03-01

    We aimed to investigate the effects of two physical exercise models, voluntary physical activity (VPA) and endurance training (ET) as preventive and therapeutic strategies, respectively, on lipid accumulation regulators and mitochondrial content in VAT of rats fed a high-fat diet (HFD). Sprague-Dawley rats (6 weeks old, n=60) were assigned into sedentary and VPA groups fed isoenergetic diets: standard (S, 35 kcal% fat) or HFD (71 kcal% fat). The VPA groups had free access to wheel running during the entire protocol. After 9 weeks, half of the sedentary animals were exercised on a treadmill while maintaining the dietary treatments. The HFD induced no changes in plasma non-esterified fatty acids (NEFA) and glycerol levels and decreased oxidative phosphorylation (OXPHOS) subunit IV and increased truncated/full-length sterol regulatory element-binding transcription factor 1c (SREBP1c) ratio in epididymal white adipose tissue (eWAT). VPA decreased plasma glycerol levels, aquaglyceroporin 7 (AQP7) and increased subunit I of cytochrome c oxidase (COX) protein, in standard diet fed animals. Eight weeks of ET decreased body weight, visceral adiposity and adipocyte size and plasma NEFA and glycerol levels, as well as AQP7 protein expression in eWAT. ET increased fatty acid translocase (FAT/CD36), mitochondrial content of complexes IV and V subunits, mitochondrial biogenesis and dynamic (mitofusins and optic atrophy 1)-related proteins. Moreover, lipogenesis-related markers (SREBP1c and acetyl CoA carboxylase) were reduced after 8 weeks of ET. In conclusion, ET-induced alterations reflect a positive effect on mitochondrial function and the overall VAT metabolism of HFD-induced obese rats. © 2016 John Wiley & Sons Australia, Ltd.

  2. Progression from high insulin resistance to type 2 diabetes does not entail additional visceral adipose tissue inflammation.

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    Nuria Barbarroja

    Full Text Available Obesity is associated with a low-grade chronic inflammation state. As a consequence, adipose tissue expresses pro-inflammatory cytokines that propagate inflammatory responses systemically elsewhere, promoting whole-body insulin resistance and consequential islet β-cell exhaustation. Thus, insulin resistance is considered the early stage of type 2 diabetes. However, there is evidence of obese individuals that never develop diabetes indicating that the mechanisms governing the association between the increase of inflammatory factors and type 2 diabetes are much more complex and deserve further investigation. We studied for the first time the differences in insulin signalling and inflammatory pathways in blood and visceral adipose tissue (VAT of 20 lean healthy donors and 40 equal morbidly obese (MO patients classified in high insulin resistance (high IR degree and diabetes state. We studied the changes in proinflammatory markers and lipid content from serum; macrophage infiltration, mRNA expression of inflammatory cytokines and transcription factors, activation of kinases involved in inflammation and expression of insulin signalling molecules in VAT. VAT comparison of these experimental groups revealed that type 2 diabetic-MO subjects exhibit the same pro-inflammatory profile than the high IR-MO patients, characterized by elevated levels of IL-1β, IL-6, TNFα, JNK1/2, ERK1/2, STAT3 and NFκB. Our work rules out the assumption that the inflammation should be increased in obese people with type 2 diabetes compared to high IR obese. These findings indicate that some mechanisms, other than systemic and VAT inflammation must be involved in the development of type 2 diabetes in obesity.

  3. Does obesity play a major role in the pathogenesis of sleep apnoea and its associated manifestations via inflammation, visceral adiposity, and insulin resistance?

    Science.gov (United States)

    Vgontzas, Alexandros N

    2008-10-01

    , supports the hypothesis that cytokines and insulin resistance are mediators of EDS and sleep apnoea in humans. Finally, our recent finding that in obese, hypothalamic CRH neuron is hypoactive, provides additional evidence on the potential central neural mechanisms for depressed ventilation and consequent development of sleep apnoea in obese individuals. In conclusion, accumulating evidence provides support to our thesis that obesity via inflammation, insulin resistance, visceral adiposity, and central neural mechanisms, e.g. hypofunctioning hypothalamic CRH, play a major role in the pathogenesis of sleep apnoea, sleepiness, and the associated cardiovascular co-morbidities.

  4. Extracellular matrix remodeling and matrix metalloproteinase inhibition in visceral adipose during weight cycling in mice.

    Science.gov (United States)

    Caria, Cíntia Rabelo E Paiva; Gotardo, Érica Martins Ferreira; Santos, Paola Souza; Acedo, Simone Coghetto; de Morais, Thainá Rodrigues; Ribeiro, Marcelo Lima; Gambero, Alessandra

    2017-10-15

    Extracellular matrix (ECM) remodeling is necessary for a health adipose tissue (AT) expansion and also has a role during weight loss. We investigate the ECM alteration during weight cycling (WC) in mice and the role of matrix metalloproteinases (MMPs) was assessed using GM6001, an MMP inhibitor, during weight loss (WL). Obesity was induced in mice by a high-fat diet. Obese mice were subject to caloric restriction for WL followed by reintroduction to high-fat diet for weight regain (WR), resulting in a WC protocol. In addition, mice were treated with GM6001 during WL period and the effects were observed after WR. Activity and expression of MMPs was intense during WL. MMP inhibition during WL results in inflammation and collagen content reduction. MMP inhibition during WL period interferes with the period of subsequent expansion of AT resulting in improvements in local inflammation and systemic metabolic alterations induced by obesity. Our results suggest that MMPs inhibition could be an interesting target to improve adipose tissue inflammation during WL and to support weight cyclers. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Protein-Tyrosine Phosphatase-1B Mediates Sleep Fragmentation-Induced Insulin Resistance and Visceral Adipose Tissue Inflammation in Mice.

    Science.gov (United States)

    Gozal, David; Khalyfa, Abdelnaby; Qiao, Zhuanghong; Akbarpour, Mahzad; Maccari, Rosanna; Ottanà, Rosaria

    2017-09-01

    Sleep fragmentation (SF) is highly prevalent and has emerged as an important contributing factor to obesity and metabolic syndrome. We hypothesized that SF-induced increases in protein tyrosine phosphatase-1B (PTP-1B) expression and activity underlie increased food intake, inflammation, and leptin and insulin resistance. Wild-type (WT) and ObR-PTP-1b-/- mice (Tg) were exposed to SF and control sleep (SC), and food intake was monitored. WT mice received a PTP-1B inhibitor (RO-7d; Tx) or vehicle (Veh). Upon completion of exposures, systemic insulin and leptin sensitivity tests were performed as well as assessment of visceral white adipose tissue (vWAT) insulin receptor sensitivity and macrophages (ATM) polarity. SF increased food intake in either untreated or Veh-treated WT mice. Leptin-induced hypothalamic STAT3 phosphorylation was decreased, PTP-1B activity was increased, and reduced insulin sensitivity emerged both systemic and in vWAT, with the latter displaying proinflammatory ATM polarity changes. All of the SF-induced effects were abrogated following PTP-1B inhibitor treatment and in Tg mice. SF induces increased food intake, reduced leptin signaling in hypothalamus, systemic insulin resistance, and reduced vWAT insulin sensitivity and inflammation that are mediated by increased PTP-1B activity. Thus, PTP-1B may represent a viable therapeutic target in the context of SF-induced weight gain and metabolic dysfunction.

  6. Low skeletal muscle radiation attenuation and visceral adiposity are associated with overall survival and surgical site infections in patients with pancreatic cancer.

    Science.gov (United States)

    van Dijk, David P J; Bakens, Maikel J A M; Coolsen, Mariëlle M E; Rensen, Sander S; van Dam, Ronald M; Bours, Martijn J L; Weijenberg, Matty P; Dejong, Cornelis H C; Olde Damink, Steven W M

    2017-04-01

    Cancer cachexia and skeletal muscle wasting are related to poor survival. In this study, quantitative body composition measurements using computed tomography (CT) were investigated in relation to survival, post-operative complications, and surgical site infections in surgical patients with cancer of the head of the pancreas. A prospective cohort of 199 patients with cancer of the head of the pancreas was analysed by CT imaging at the L3 level to determine (i) muscle radiation attenuation (average Hounsfield units of total L3 skeletal muscle); (ii) visceral adipose tissue area; (iii) subcutaneous adipose tissue area; (iv) intermuscular adipose tissue area; and (v) skeletal muscle area. Sex-specific cut-offs were determined at the lower tertile for muscle radiation attenuation and skeletal muscle area and the higher tertile for adipose tissues. These variables of body composition were related to overall survival, severe post-operative complications (Dindo-Clavien ≥ 3), and surgical site infections (wounds inspected daily by an independent trial nurse) using Cox-regression analysis and multivariable logistic regression analysis, respectively. Low muscle radiation attenuation was associated with shorter survival in comparison with moderate and high muscle radiation attenuation [median survival 10.8 (95% CI: 8.8-12.8) vs. 17.4 (95% CI: 14.7-20.1), and 18.5 (95% CI: 9.2-27.8) months, respectively; P attenuation combined with either low visceral adipose tissue or age attenuation was inversely correlated with intermuscular adipose tissue (rp  = -0.697, P attenuation was associated with reduced survival, and high visceral adiposity was associated with an increase in surgical site infections. The strong correlation between muscle radiation attenuation and intermuscular adipose tissue suggests the presence of ectopic fat in muscle, warranting further investigation. CT image analysis could be implemented in pre-operative risk assessment to assist in treatment

  7. Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats

    DEFF Research Database (Denmark)

    Liaset, Bjørn; Madsen, Lise; Hao, Qin

    2009-01-01

    Conjugation of bile acids (BAs) to the amino acids taurine or glycine increases their solubility and promotes liver BA secretion. Supplementing diets with taurine or glycine modulates BA metabolism and enhances fecal BA excretion in rats. However, it is still unclear whether dietary proteins....../retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism....... varying in taurine and glycine contents alter BA metabolism, and thereby modulate the recently discovered systemic effects of BAs. Here we show that rats fed a diet containing saithe fish protein hydrolysate (saithe FPH), rich in taurine and glycine, for 26 days had markedly elevated fasting plasma BA...

  8. The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease through Regulating the Visceral Adipose-Tissue Function.

    Science.gov (United States)

    Kim, Jeongjun; Lee, Haerim; Lim, Jonghoon; Oh, Jaeho; Shin, Soon Shik; Yoon, Michung

    2017-04-17

    Similar to neoplastic tissues, growth and development of adipose tissue are thought to be angiogenesis-dependent. Since visceral adipose tissue (VAT) is associated with development and progression of nonalcoholic fatty liver disease (NAFLD), we hypothesized that angiogenesis inhibition would attenuate obesity-induced NAFLD. We fed C57BL/6J mice a low-fat diet (LFD, chow 10% kcal fat), a high-fat diet (HFD, 45% kcal fat) or HFD supplemented with the lemon-balm extract ALS-L1023 (HFD-ALS) for 15 weeks. ALS-L1023 reduced endothelial cell-tube formation in vitro. HFD increased VAT angiogenesis and induced weight gains including body weight, VAT mass and visceral adipocyte size compared with LFD. However, HFD-ALS led to weight reductions without affecting calorie intake compared with HFD. HFD-ALS also reduced serum ALT and AST levels and improved lipid metabolism. HFD-ALS suppressed steatosis, infiltration of inflammatory cells, and accumulation of collagen in livers. HFD-ALS modulated hepatic expression of genes involved in lipid metabolism, inflammation, fibrosis, antioxidation, and apoptosis. Concomitantly, analysis of VAT function revealed that HFD-ALS led to fewer CD68-positive macrophage numbers and lower expression of inflammatory cytokines compared with HFD. Our findings show that the anti-angiogenic herbal extract ALS-L1023 attenuates NAFLD by targeting VAT during obesity, suggesting that angiogenesis inhibitors could aid in the treatment and prevention of obesity-induced human NAFLD.

  9. Is visceral adiposity a modifier for the impact of blood pressure on arterial stiffness and albuminuria in patients with type 2 diabetes?

    Science.gov (United States)

    Bouchi, Ryotaro; Ohara, Norihiko; Asakawa, Masahiro; Nakano, Yujiro; Takeuchi, Takato; Murakami, Masanori; Sasahara, Yuriko; Numasawa, Mitsuyuki; Minami, Isao; Izumiyama, Hajime; Hashimoto, Koshi; Yoshimoto, Takanobu; Ogawa, Yoshihiro

    2016-01-21

    We aimed to investigate whether visceral adiposity could modify the impact of blood pressure on arterial stiffness and albuminuria in patients with type 2 diabetes. This cross-sectional study examines the interaction of visceral adiposity with increased blood pressure on arterial stiffness and albuminuria. 638 patients with type 2 diabetes (mean age 64 ± 12 years; 40 % female) were enrolled. Visceral fat area (VFA, cm(2)) was assessed by a dual-impedance analyzer, whereby patients were divided into those with VFA Albuminuria was measured in a single 24-h urine collection (UAE, mg/day) and brachial-ankle pulse wave velocity (ba-PWV, cm/s) was used for the assessment of arterial stiffening. Linear regression analyses were used to investigate the association of systolic blood pressure (SBP) and VFA with UAE and baPWV. Patients with VFA ≥ 100 were significantly younger, had higher SBP, HbA1c, triglycerides, UAE, alanine aminotransferase, C-reactive protein and lower high-density lipoprotein and shorter duration of diabetes than those with VFA albuminuria is stronger in the latter.

  10. Visceral fat is associated with brain structure independent of human immunodeficiency virus infection status.

    Science.gov (United States)

    Lake, Jordan E; Popov, Mikhail; Post, Wendy S; Palella, Frank J; Sacktor, Ned; Miller, Eric N; Brown, Todd T; Becker, James T

    2017-06-01

    The combined effects of human immunodeficiency virus (HIV), obesity, and elevated visceral adipose tissue (VAT) on brain structure are unknown. In a cross-sectional analysis of Multicenter AIDS Cohort Study (MACS) participants, we determined associations between HIV serostatus, adiposity, and brain structure. Men (133 HIV+, 84 HIV-) in the MACS Cardiovascular 2 and magnetic resonance imaging (MRI) sub-studies with CT-quantified VAT and whole brain MRI measured within 1 year were assessed. Voxel-based morphometry analyzed brain volumes. Men were stratified by elevated (eVAT, ≥100cm2) or "normal" (nVAT, VAT. Forward stepwise modeling determined associations between clinical and demographic variables and regional brain volumes. eVAT was present in 67% of men. Groups were similar in age and education, but eVAT men were more likely to be HIV+ and have hypertension, diabetes mellitus, body mass index >25 kg/m2, smaller gray and white matter volumes, and larger cerebrospinal fluid volume than nVAT men. In multivariate analysis, hypertension, higher adiponectin, higher interleukin-6, age, diabetes mellitus, higher body mass index, and eVAT were associated with brain atrophy (p VAT was associated with smaller bilateral posterior hippocampus and left mesial temporal lobe and temporal stem white matter volume. Traditional risk factors are more strongly associated with brain atrophy than HIV serostatus, with VAT having the strongest association. However, HIV+ MACS men had disproportionately greater VAT, suggesting the risk for central nervous system effects may be amplified in this population.

  11. Resveratrol Attenuates Intermittent Hypoxia-Induced Macrophage Migration to Visceral White Adipose Tissue and Insulin Resistance in Male Mice

    Science.gov (United States)

    Carreras, Alba; Zhang, Shelley X. L.; Almendros, Isaac; Wang, Yang; Peris, Eduard; Qiao, Zhuanhong

    2015-01-01

    Chronic intermittent hypoxia during sleep (IH), as occurs in sleep apnea, promotes systemic insulin resistance. Resveratrol (Resv) has been reported to ameliorate high-fat diet-induced obesity, inflammation, and insulin resistance. To examine the effect of Resv on IH-induced metabolic dysfunction, male mice were subjected to IH or room air conditions for 8 weeks and treated with either Resv or vehicle (Veh). Fasting plasma levels of glucose, insulin, and leptin were obtained, homeostatic model assessment of insulin resistance index levels were calculated, and insulin sensitivity tests (phosphorylated AKT [also known as protein kinase B]/total AKT) were performed in 2 visceral white adipose tissue (VWAT) depots (epididymal [Epi] and mesenteric [Mes]) along with flow cytometry assessments for VWAT macrophages and phenotypes (M1 and M2). IH-Veh and IH-Resv mice showed initial reductions in food intake with later recovery, with resultant lower body weights after 8 weeks but with IH-Resv showing better increases in body weight vs IH-Veh. IH-Veh and IH-Resv mice exhibited lower fasting glucose levels, but only IH-Veh had increased homeostatic model assessment of insulin resistance index vs all 3 other groups. Leptin levels were preserved in IH-Veh but were significantly lower in IH-Resv. Reduced VWAT phosphorylated-AKT/AKT responses to insulin emerged in both Mes and Epi in IH-Veh but normalized in IH-Resv. Increases total macrophage counts and in M1 to M2 ratios occurred in IH-Veh Mes and Epi compared all other 3 groups. Thus, Resv ameliorates food intake and weight gain during IH exposures and markedly attenuates VWAT inflammation and insulin resistance, thereby providing a potentially useful adjunctive therapy for metabolic morbidity in the context of sleep apnea. PMID:25406018

  12. Predictive value of visceral adiposity index for type 2 diabetes mellitus: A 15-year prospective cohort study.

    Science.gov (United States)

    Wang, Y; He, S; He, J; Wang, S; Liu, K; Chen, X

    2015-05-01

    The emerging term "visceral adiposity index (VAI)" was reported to be closely correlated with glycemic disturbances and diabetes risk. However, whether VAI could predict future type 2 diabetes mellitus (DM) is unknown. Here, we aimed to assess the predictive value of VAI for DM in a Chinese population via a prospective cohort study. This prospective cohort study was conducted based on a 15-year follow-up in a general Chinese population from an urban community. In all, 711 subjects underwent a health examination in 1992, and in 2007 the same examination was repeated. Twenty-four subjects were excluded from the analysis because DM was diagnosed at baseline. Waist circumference (WC), body mass index (BMI), VAI, and cardiovascular risk factors were collected at baseline. Hazard ratios (HRs) for DM incidence were estimated applying Cox proportional hazards models. Paired homogeneity tests were used to explore whether there was a statistical difference between the HRs of VAI and the other two indicators. In all, 74 individuals developed DM during a follow-up of 15 years. The risk of future DM increased with increasing levels of VAI. After adjusting for confounders, for each SD increment in natural logarithm-transformed VAI, BMI, and WC the HRs were 1.538 (95 % CI: 1.225-1.930), 1.639 (95 % CI: 1.289-2.084) and 1.858 (95 % CI: 1.458-2.369), respectively. However, paired homogeneity tests showed no statistical difference among the HRs. VAI could independently predict DM in the Chinese study population, although the predictive power was not higher than that of simple anthropometric measures (BMI and WC). Our study does not support the clinical application of VAI; however, more studies based on different ethnic groups still need to be performed.

  13. Increased visceral adipose tissue as a potential risk factor in patients with embolic stroke of undetermined source (ESUS.

    Directory of Open Access Journals (Sweden)

    Antti T Muuronen

    Full Text Available The etiology of an ischemic stroke remains undetermined in 20-35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT is a suggested new risk factor for both carotid artery atherosclerosis (CAA and atrial fibrillation (AF, but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke.Altogether 58 patients (mean age 57.7 ± 10.2 years, 44 men with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol were also registered.Mean VAT area was significantly higher in stroke patients (205 ± 103 cm2 for men and 168 ± 99 cm2 for women compared to all reference populations (P < 0.01. 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI. Increased VAT was more common than any of the conventional risk factors.Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients.

  14. Increased risk of subclinical atherosclerosis associated with high visceral adiposity index in apparently healthy Korean adults: the Kangbuk Samsung Health Study.

    Science.gov (United States)

    Park, Hye-Jeong; Kim, Jihyun; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

    2016-09-01

    The visceral adiposity index (VAI) is a mathematical tool that reflects a patient's visceral adiposity and insulin resistance. Recent studies have noted an association between VAI and cardiovascular event. We analyzed the association between VAI and coronary artery calcium score (CACS) in Korean adults. For 33,468 participants (mean age 42 yrs) in a health screening program, VAI was calculated using the following formulae: [waist circumference (WC)/{39.68 + (1.88 * body mass index (BMI))}] * (triglyceride/1.03) * {1.31/high-density lipoprotein cholesterol (HDL-C)} for men and [WC/{36.58 + (1.89 * BMI)}] * (triglyceride/0.81) * (1.52/HDL-C) for women. Coronary artery calcium scores were measured with multi-detector computed tomography. CACS was positively correlated with VAI (r = 0.027, p 0 as the dependent variable, subjects in the highest tertile of VAI (>1.777) had significantly increased odds ratio for CACS >0 compared to subjects in the lowest tertile (<0.967), even after adjusting for confounding variables, including BMI (OR 1.26, 95% CI 1.147-1.381). Subjects with high VAI had increased risk for subclinical atherosclerosis, as assessed by CACS. Key messages Recent studies have noted an association between visceral adiposity index (VAI) and cardiovascular event. Subjects with coronary artery calcification (CAC) showed significantly higher VAI compared to those without CAC. The subjects with high VAI showed increased odds ratio for CAC as compared to subjects with low VAI, suggesting high VAI reflects increased risk for subclinical atherosclerosis.

  15. Vulnerability to the transmission of human visceral leishmaniasis in a Brazilian urban area

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    Celina Roma Sánchez de Toledo

    Full Text Available ABSTRACT OBJECTIVE To analyze the determinants for the occurrence of human visceral leishmaniasis linked to the conditions of vulnerability. METHODS This is an ecological study, whose spatial analysis unit was the Territorial Analysis Unit in Araguaína, State of Tocantins, Brazil, from 2007 to 2012. We have carried out an analysis of the sociodemographic and urban infrastructure situation of the municipality. Normalized primary indicators were calculated and used to construct the indicators of vulnerability of the social structure, household structure, and urban infrastructure. From them, we have composed a vulnerability index. Kernel density estimation was used to evaluate the density of cases of human visceral leishmaniasis, based on the coordinates of the cases. Bivariate global Moran’s I was used to verify the existence of spatial autocorrelation between the incidence of human visceral leishmaniasis and the indicators and index of vulnerability. Bivariate local Moran’s I was used to identify spatial clusters. RESULTS We have observed a pattern of centrifugal spread of human visceral leishmaniasis in the municipality, where outbreaks of the disease have progressively reached central and peri-urban areas. There has been no correlation between higher incidences of human visceral leishmaniasis and worse living conditions. Statistically significant clusters have been observed between the incidences of human visceral leishmaniasis in both periods analyzed (2007 to 2009 and 2010 to 2012 and the indicators and index of vulnerability. CONCLUSIONS The environment in circumscribed areas helps as protection factor or increases the local vulnerability to the occurrence of human visceral leishmaniasis. The use of methodology that analyzes the conditions of life of the population and the spatial distribution of human visceral leishmaniasis is essential to identify the most vulnerable areas to the spread/maintenance of the disease.

  16. Lipolysis in human adipose tissue during exercise

    DEFF Research Database (Denmark)

    Lange, Kai Henrik Wiborg; Lorentsen, Jeanne; Isaksson, Fredrik

    2002-01-01

    Subcutaneous adipose tissue lipolysis was studied in vivo by Fick's arteriovenous (a-v) principle using either calculated (microdialysis) or directly measured (catheterization) adipose tissue venous glycerol concentration. We compared results during steady-state (rest and prolonged continuous...... exercise), as well as during non-steady-state (onset of exercise and early exercise) experimental settings. Fourteen healthy women [age: 74 +/- 1 (SE) yr] were studied at rest and during 60-min continuous bicycling at 60% of peak O(2) uptake. Calculated and measured subcutaneous abdominal adipose tissue...

  17. LINE-1 methylation in visceral adipose tissue of severely obese individuals is associated with metabolic syndrome status and related phenotypes

    Directory of Open Access Journals (Sweden)

    Turcot Valérie

    2012-07-01

    Full Text Available Abstract Background Epigenetic mechanisms may be involved in the regulation of genes found to be differentially expressed in the visceral adipose tissue (VAT of severely obese subjects with (MetS+ versus without (MetS- metabolic syndrome (MetS. Long interspersed nuclear element 1 (LINE-1 elements DNA methylation levels (%meth in blood, a marker of global DNA methylation, have recently been associated with fasting glucose, blood lipids, heart diseases and stroke. Aim To test whether LINE-1%meth levels in VAT are associated with MetS phenotypes and whether they can predict MetS risk in severely obese individuals. Methods DNA was extracted from VAT of 34 men (MetS-: n = 14, MetS+: n = 20 and 152 premenopausal women (MetS-: n = 84; MetS+: n = 68 undergoing biliopancreatic diversion for the treatment of obesity. LINE-1%meth levels were assessed by pyrosequencing of sodium bisulfite-treated DNA. Results The mean LINE-1%meth in VAT was of 75.8% (SD = 3.0%. Multiple linear regression analyses revealed that LINE-1%meth was negatively associated with fasting glucose levels (β = -0.04; P = 0.03, diastolic blood pressure (β =  -0.65; P = 0.03 and MetS status (β = -0.04; P = 0.004 after adjustments for the effects of age, sex, waist circumference (except for MetS status and smoking. While dividing subjects into quartiles based on their LINE-1%meth (Q1 to Q4: lower %meth to higher %meth levels, greater risk were observed in the first (Q1: odds ratio (OR = 4.37, P = 0.004 and the second (Q2: OR = 4.76, P = 0.002 quartiles compared to Q4 (1.00 when adjusting for age, sex and smoking. Conclusions These results suggest that lower global DNA methylation, assessed by LINE-1 repetitive elements methylation analysis, would be associated with a greater risk for MetS in the presence of obesity.

  18. Sex differences in the associations of visceral adiposity, HOMA-IR, and BMI with lipoprotein subclass analysis in obese adolescents

    Science.gov (United States)

    Hatch-Stein, Jacquelyn A; Kelly, Andrea; Gidding, Samuel S; Zemel, Babette S; Magge, Sheela N

    2016-01-01

    Background The relationship of lipoprotein particle subclasses to visceral adipose tissue area (VAT-area) in obese children has not been examined previously. Objectives The study aims were to compare the relationships of VAT-area, homeostatic model assessment of insulin resistance (HOMA-IR), and body mass index (BMI) with lipids and lipoprotein subclasses in obese adolescents, and to determine if these relationships vary by sex. Methods This cross-sectional study of obese adolescents (BMI≥95th percentile), ages 12-18y, measured VAT-area by dual energy x-ray absorptiometry (DXA), BMI, fasting lipids, lipoprotein subclasses, and HOMA-IR. Linear regression models evaluated the associations of VAT-area, HOMA-IR, and BMI with lipid cardiometabolic risk factors. Sex-stratified analyses further explored these associations. Results Included were 127 adolescents (age=14.4±1.5 years; 53.5% female; 88.2% African-American), mean BMI=34.0±5.1 kg/m2. VAT-area was negatively associated with LDL particle (−P) size (β=−0.28, p=0.0001), HDL-P size (β=−0.33, p<0.0001) and large HDL-P concentration (β=−0.29, p<0.0001), and positively associated with small LDL-P concentration (β=0.23, p=0.0005) and small HDL-P concentration (β=0.25, p=0.05). When VAT-area, HOMA-IR, and BMI associations were compared, VAT-area had the strongest associations with most of the lipoprotein subclasses. After sex-stratification, the associations of VAT-area with HDL cholesterol, LDL-P size, and large LDL-P concentration were significant only for females (all p<0.05). Conclusions In a cohort of largely African-American obese adolescents, VAT-area was associated with a more atherogenic lipoprotein subclass profile. When compared to HOMA-IR and BMI, VAT-area had the strongest associations with most lipoprotein subclasses. The relationships between VAT-area and certain lipoprotein subclasses are significantly different in males versus females. PMID:27578105

  19. Eight weeks of a combination of high intensity interval training and conventional training reduce visceral adiposity and improve physical fitness: a group-based intervention.

    Science.gov (United States)

    Giannaki, Christoforos D; Aphamis, George; Sakkis, Panikos; Hadjicharalambous, Marios

    2016-04-01

    High intensity interval training (HIIT) has been recently promoted as an effective, low volume and time-efficient training method for improving fitness and health related parameters. The aim of the current study was to examine the effect of a combination of a group-based HIIT and conventional gym training on physical fitness and body composition parameters in healthy adults. Thirty nine healthy adults volunteered to participate in this eight-week intervention study. Twenty three participants performed regular gym training 4 days a week (C group), whereas the remaining 16 participants engaged twice a week in HIIT and twice in regular gym training (HIIT-C group) as the other group. Total body fat and visceral adiposity levels were calculated using bioelectrical impedance analysis. Physical fitness parameters such as cardiorespiratory fitness, speed, lower limb explosiveness, flexibility and isometric arm strength were assessed through a battery of field tests. Both exercise programs were effective in reducing total body fat and visceral adiposity (Pflexibility (Pgyms and craving to acquire significant fitness benefits in relatively short period of time.

  20. Correlation of visceral adiposity index with chronic kidney disease in the People’s Republic of China: to rediscover the new clinical potential of an old indicator for visceral obesity

    Directory of Open Access Journals (Sweden)

    Xu XM

    2016-03-01

    Full Text Available Xiaomeng Xu,1 Yan Zhao,2 Zhihong Zhao,1 Shuangshuang Zhu,1 Xinyu Liu,1 Chaomin Zhou,3 Xiaofei Shao,1 Yan Liang,1 Chongyang Duan,4 Harry Holthöfer,5 Hequn Zou1 1Department of Nephrology, The Third Affiliated Hospital of Southern Medical University, 2Blood Purification Center, The Third Hospital of Zhengzhou, 3Department of Nephrology, Guizhou Provincial People’s Hospital, 4Department of Biostatistics, Southern Medical University, Guangzhou, People’s Republic of China; 5Centre for BioAnalytical Sciences, Dublin City University, Dublin, Ireland Aim: To validate the association between visceral obesity and pathogenesis of chronic kidney disease (CKD among individuals aged 40 years and above, and the potential of visceral adiposity index (VAI to predict CKD.Methods: This study was based on a cross-sectional epidemiologic study in the People’s Republic of China. A total of 1,581 residents aged over 40 years were included and divided into four groups based on VAI quartile intervals, namely, Groups I, II, III, and IV (eg, Group I included patients with their VAIs in the lowest quartile. Logistic regression analysis was performed. Results: VAI is positively correlated with the albumin-to-creatinine ratio and the prevalence of CKD (P<0.001, and is inversely related to estimated glomerular filtration rate (P<0.001. Using Group I as control, odds ratios (ORs were calculated to quantify the risk of developing CKD as VAI increased (Group II 1.08 [P>0.05], Group III 1.57 [P<0.05], Group IV 2.31 [P<0.001]. Related factors like age and sex were normalized in the logistic model before calculation. ORs became 1.16 (P>0.05, 1.59 (P<0.05, and 2.14 (P<0.05, respectively, for each group after further normalization considering smoking, drinking, physical activity, education, and the history of hypertension, coronary heart disease, and diabetes. The same results were not observed after fasting blood glucose and blood pressure levels were included in the

  1. Short-term effects of liraglutide on visceral fat adiposity, appetite, and food preference: a pilot study of obese Japanese patients with type 2 diabetes

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    Inoue Kana

    2011-12-01

    Full Text Available Abstract Background To examine the effects of liraglutide, a glucagon-like peptide-1 (GLP-1 analogue, on visceral fat adiposity, appetite, food preference, and biomarkers of cardiovascular system in Japanese patients with type 2 diabetes. Methods The study subjects were 20 inpatients with type 2 diabetes treated with liraglutide [age; 61.2 ± 14.0 years, duration of diabetes; 16.9 ± 6.6 years, glycated hemoglobin (HbA1c; 9.1 ± 1.2%, body mass index (BMI; 28.3 ± 5.2 kg/m2, mean ± SD]. After improvement in glycemic control by insulin or oral glucose-lowering agents, patients were switched to liraglutide. We assessed the estimated visceral fat area (eVFA by abdominal bioelectrical impedance analysis, glycemic control by the 75-g oral glucose tolerance test (OGTT and eating behavior by the Japan Society for the Study of Obesity questionnaire. Results Treatment with liraglutide (dose range: 0.3 to 0.9 mg/day for 20.0 ± 6.4 days significantly reduced waist circumference, waist/hip ratio, eVFA. It also significantly improved the scores of eating behavior, food preference and the urge for fat intake and tended to reduce scores for sense of hunger. Liraglutide increased serum C-peptide immunoreactivity and disposition index. Conclusions Short-term treatment with liraglutide improved visceral fat adiposity, appetite, food preference and the urge for fat intake in obese Japanese patients with type 2 diabetes.

  2. Ultrasound measurements of visceral and subcutaneous abdominal thickness to predict abdominal adiposity among older men and women

    NARCIS (Netherlands)

    Rolfe, Ema De Lucia; Sleigh, Alison; Finucane, Francis M.; Brage, Soren; Stolk, Ronald P.; Cooper, Cyrus; Sharp, Stephen J.; Wareham, Nicholas J.; Ong, Ken K.

    Accurate measures of visceral and abdominal subcutaneous fat are essential for investigating the pathophysiology of obesity. Classical anthropometric measures such as waist and hip circumference cannot distinguish between these two fat depots. Direct imaging methods such as computed tomography and

  3. Determinants of human adipose tissue gene expression

    DEFF Research Database (Denmark)

    Viguerie, Nathalie; Montastier, Emilie; Maoret, Jean-José

    2012-01-01

    Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT) are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification ...

  4. Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Luo, Zhi, E-mail: luozhi99@yahoo.com.cn; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

    2013-07-15

    Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

  5. Visceral Adiposity Measurements, Metabolic and Inflammatory Profi le in Obese Patients with and Without Type 2 Diabetes Mellitus: A Crosssectional Analysis.

    Science.gov (United States)

    Wanderley Rocha, Denise Rosso Tenório; Jorge, André Rocha; Braulio, Valeria Bender; Arbex, Alberto Krayyem; Marcadenti, Aline

    2017-01-01

    Waist circumference does not distinguish subcutaneous from visceral adipose tissue, which is highly associated with impaired cardiometabolic profile and type-2 diabetes mellitus (T2DM). Because of the complexity of the assessment of visceral fat with imaging techniques, easy-to-apply and low-cost anthropometric measures have been proposed. The aim of the study was to show a possible association between Lipid Accumulation Product Index (LAP Index), Deep-abdominal adiposity tissue Index (DAAT) and Visceral Adiposity Index (VAI) with metabolic profile and adipokines in obese subjects with and without T2DM, and to compare the results with the use of waist circumference isolated. In this cross-sectional study, we enrolled 101 outpatients with obesity (BMI ≥ 30 kg/m2) of which 48% with diabetes and aged 48.9 ±13.3 years. Demographic, clinical and anthropometric data were collected. Plasma C-reactive protein, interleukin-6, vascular adhesion molecule type 1 and adiponectin levels, lipid profile and fasting glucose were assessed. LAP Index, DAAT and VAI were calculated and body composition was evaluated by bioelectric impedance analyses. Continuous variables were described as mean ±standard deviation, and categorical variables as absolute numbers and percentages. Nonparametric data were log-transformed and Student's t test, Wilcoxon-Mann-Whitney and chi-squared test, Pearson correlation and multiple linear regression were used for statistical analyses. In total, 31 men and 70 women were evaluated. Individuals with T2DM showed higher LAP values and percentage of body fat and lower waist circumference and BMI values. DAAT and LAP were positively correlated with BMI, waist circumference, percentage of body fat and free fat mass. After adjustment for age, sex and total body fat, both LAP Index and VAI were associated with plasma adiponectin, LDL-cholesterol, non-HDL cholesterol and VLDL-cholesterol in obese with and without T2DM (all P values ≤ 0.02); fasting glucose

  6. Ultrasound measurements of visceral and subcutaneous abdominal thickness to predict abdominal adiposity among older men and women.

    Science.gov (United States)

    De Lucia Rolfe, Ema; Sleigh, Alison; Finucane, Francis M; Brage, Soren; Stolk, Ronald P; Cooper, Cyrus; Sharp, Stephen J; Wareham, Nicholas J; Ong, Ken K

    2010-03-01

    Accurate measures of visceral and abdominal subcutaneous fat are essential for investigating the pathophysiology of obesity. Classical anthropometric measures such as waist and hip circumference cannot distinguish between these two fat depots. Direct imaging methods such as computed tomography and magnetic resonance imaging (MRI) are restricted in large-scale studies due to practical and ethical issues. We aimed to establish whether ultrasound is a valid alternative method to MRI for the quantitative assessment of abdominal fat depots in older individuals. The study population comprised 74 white individuals (41 men and 33 women, aged 67-76 years) participating in the Hertfordshire Birth Cohort Physical Activity trial. Anthropometry included height, weight, waist and hip circumferences. Abdominal fat was measured by ultrasound in two compartments: visceral fat defined as the depth from the peritoneum to the lumbar spine; and subcutaneous fat defined as the depth from the skin to the abdominal muscles and compared to reference measures by MRI (10-mm single-slice image). Ultrasound measures were positively correlated with MRI measures of visceral and subcutaneous fat (visceral: r = 0.82 and r = 0.80 in men and women, respectively; subcutaneous: r = 0.63 and 0.68 in men and women, respectively). In multiple regression models, the addition of ultrasound measures significantly improved the prediction of visceral fat and subcutaneous fat in both men and women over and above the contribution of standard anthropometric variables. In conclusion, ultrasound is a valid method to estimate visceral fat in epidemiological studies of older men and women when MRI and computed tomography are not feasible.

  7. Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans.

    Science.gov (United States)

    McLaughlin, Tracey; Craig, Colleen; Liu, Li-Fen; Perelman, Dalia; Allister, Candice; Spielman, Daniel; Cushman, Samuel W

    2016-05-01

    Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 ± 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. Risk factors, representations and practices associated with emerging urban human visceral leishmaniasis in Posadas, Argentina.

    Science.gov (United States)

    López, Karen; Tartaglino, Lilian Catalina; Steinhorst, Ingrid Iris; Santini, María Soledad; Salomon, Oscar Daniel

    2016-02-23

    Visceral leishmaniasis is an often overlooked disease with high lethality rates about which there is need of additional local studies to inform the design of effective control strategies. The urbanization of its transmission has already been verified in America, with domestic dogs being the primary reservoirs and vectors of the disease. Socio-economic conditions, demographics and practices of domestic groups typically present in urban settings may play a specific role in the transmission of the infection, which is still poorly understood.  To analyze the sociodemographic characteristics, risk factors and overall practices concerning prevention and coping strategies of visceral leishmaniasis, in both human beings and canines.  This study utilized a cross-sectional case-control design. Cases were defined as a domestic group where the Public Health Ministry had at least one record of a member with human visceral leishmaniasis. Control cases were defined as a domestic group without a clinical record of the disease. The populations were characterized demographically and socially using primary information sources. Measures of household quality and a ranking of knowledge and attitudes towards visceral leishmaniasis were constructed, and practices associated with the presence, and the risk for canine visceral leishmaniasis were described.  Low household quality (p≤0.001), a member of the domestic group out of the household after 6:00 pm (OR=4.4; 95% CI: 1.69-12.18), the uncontrolled racial breeding of dogs (OR=15.7; 95% CI: 3.91-63.2), and the presence of infected dogs infected in the household (OR=120.3; 95% CI: 18.51-728.3) were variables positively associated with the risk of infection.  We observed certain social risk factors, primarily low household quality and overcrowding, associated with structural poverty that could increase human-vector contact probability. The most important risk factor for human visceral leishmaniasis was the possession of infected dogs

  9. Changes in both global diet quality and physical activity level synergistically reduce visceral adiposity in men with features of metabolic syndrome.

    Science.gov (United States)

    Nazare, Julie-Anne; Smith, Jessica; Borel, Anne-Laure; Alméras, Natalie; Tremblay, Angelo; Bergeron, Jean; Poirier, Paul; Després, Jean-Pierre

    2013-07-01

    With regard to the beneficial impact of lifestyle interventions on weight and abdominal obesity management, our objective was to identify which components of a lifestyle-intervention program [physical activity (PA), energy and macronutrient intake, diet quality] had an influence on visceral adipose tissue (VAT) loss. The present lifestyle intervention targeted a daily energy deficit (500 kcal), coupled with a PA program (160 min/wk). From the 144 participants initially recruited, 93 viscerally obese men (age: 49 ± 1 y; waist circumference: 108 ± 9 cm; plasma triglyceride concentration: 2.46 ± 0.09 mmol/L) who completed a 3-d dietary journal both at baseline and after 1 y of intervention and a daily PA journal for 1 y were considered in the present analyses. Body composition and fat distribution were assessed by using dual-energy X-ray absorptiometry and computed tomography. After 1 y, abdominally obese men significantly improved their diet quality, as assessed by the Dietary Approaches to Stop Hypertension (DASH)-derived diet quality (DQ) score (P metabolic syndrome.

  10. [EATING DISORDERS AND VISCERAL ADIPOSE TISSUE - TWO INTERCONNECTED INFORMATIVE MARKERS OF PROGNOSIS OF DISORDERS OF NUTRITIONAL STATUS AND RISK OF DEVELOPMENT OF COMORBIDITY CHRONIC NON-COMMUNICABLE DISEASES].

    Science.gov (United States)

    Fadieienko, G; Nikiforova, Y

    2017-01-01

    The purpose of research was to study the characteristics of eating behaviour (EB) and indicators visceral adipose tissue (VAT) in patients with NAFLD and obesity stage of 1-2 or excessive body mass on the background of hypertension (H). We examined 100 patients with NAFLD in combination with overweight and obesity of 1-2 degrees (body mass index - BMI ≥25 kg/m2) on the background of H I-II stage. Patients with NAFLD and visceral obesity on the background of stage H of I-II the identified three types of violations of EB with a significant predominance of external breach type EB (pnutritional status and risk of development of metabolic disorders, which depends on EB. Identified isolated cases of violations of EB among patients in the control group indicate the possible risk of increase VAT and the development of hormonal and metabolic disorders. Therefore, it is necessary to study the violations of EB on a larger scale to diagnose possible disorders of nutritional status, and to measure these standard anthropometric indicators such as BMI, WC, HC, WC/HC it is advisable to further carry out the measurement % VАT and IVO.

  11. Comparison of Methods for Analyzing Human Adipose Tissue Macrophage Content

    DEFF Research Database (Denmark)

    Morgan-Bathke, Maria; Harteneck, Debra; Jaeger, Philippa

    2017-01-01

    OBJECTIVE: The relationship between inflammation, obesity, and adverse metabolic conditions is associated with adipose tissue macrophages (ATM). This study compared the measurements of human ATM using flow cytometry, immunohistochemistry (IHC), and real-time polymerase chain reaction (RT-PCR) of ...

  12. HMOX1 as a marker of iron excess-induced adipose tissue dysfunction, affecting glucose uptake and respiratory capacity in human adipocytes.

    Science.gov (United States)

    Moreno-Navarrete, José María; Ortega, Francisco; Rodríguez, Amaia; Latorre, Jèssica; Becerril, Sara; Sabater-Masdeu, Mònica; Ricart, Wifredo; Frühbeck, Gema; Fernández-Real, José Manuel

    2017-05-01

    Iron excess in adipose tissue is known to promote adipose tissue dysfunction. Here, we aimed to investigate the possible role of haem oxygenase 1 (HMOX1) in iron excess-induced adipose tissue dysfunction. Cross-sectionally, HMOX1 gene expression in subcutaneous and visceral adipose tissue was analysed in two independent cohorts (n = 234 and 40) in relation to obesity. We also evaluated the impact of weight loss (n = 21), weight gain (in rats, n = 20) on HMOX1 mRNA; HMOX1 mRNA levels during human adipocyte differentiation; the effects of inflammation and iron on adipocyte HMOX1; and the effects of HMOX1-induced activity on adipocyte mitochondrial respiratory function, glucose uptake and adipogenesis. Adipose tissue HMOX1 was increased in obese participants (p = 0.01) and positively associated with obesity-related metabolic disturbances, and markers of iron accumulation, inflammation and oxidative stress (p iron excess, adipogenesis and inflammation. In human adipocytes, iron excess and inflammation led to increased HMOX1 mRNA levels. HMOX1 induction (by haem arginate [hemin] administration), resulted in a significant reduction of mitochondrial respiratory capacity (including basal respiration and spare respiratory capacity), glucose uptake and adipogenesis in parallel with increased expression of inflammatory- and iron excess-related genes. HMOX1 is an important marker of iron excess-induced adipose tissue dysfunction and metabolic disturbances in human obesity.

  13. Occurrence of diabetes mellitus in obese nondiabetic patients, with correlative analysis of visceral fat, fasting insulin, and insulin resistance: A 3-year follow-up study (mysore visceral adiposity in diabetes follow-up study

    Directory of Open Access Journals (Sweden)

    M Premanath

    2017-01-01

    Full Text Available Objective: To assess the occurrence of diabetes in obese nondiabetic patients over a 3-year follow-up period with a correlative analysis of visceral fat (VF, fasting insulin levels, (FILs and insulin resistance (IR. Material and Methods: Thirty-seven obese and nineteen nonobese nondiabetics of our previous study, Mysore Visceral Adiposity in Diabetes were followed for the next 3 years. Their blood pressure, body mass index, waist circumference (WC, fasting blood sugar (FBS, FIL, lipid profile and subcutaneous fat (SCF, and VF measurement by US method were repeated every 6 months for the next 3 years. The findings were analyzed with appropriate statistical methods. Results: Twenty-three obese and 18 nonobese nondiabetics completed the study. There were 17 dropouts. The changes in the physical and biochemical characteristics of the two groups before and after the study were not significant. SCF had no correlation with IR whereas VF correlated with FIL and IR. There were three diabetics in the obese group and two from the control group at the end of the study. There were 12 impaired glucose tolerance (IGT in the test group and 2 in the control group. Those who developed diabetes had higher VF, WC, FBS, FIL, and IR. Those who showed IGT also had these at higher levels compared to others. There was no change in the VF at the end of the study. Conclusions: This follow-up study on South Indians has shown that VF is a significant risk factor for the development of IR. IR can develop without any increase in the volume of the VF, is the essential finding of this study. SCF has not shown any significant relationship with IR. We recommend FBS and FIL in all the obese nondiabetics to calculate IR, which has given much insight in the development of IGT and diabetes. Large multicentric, longitudinal studies are required to establish the cause of IR.

  14. Fructose and stress induce opposite effects on lipid metabolism in the visceral adipose tissue of adult female rats through glucocorticoid action.

    Science.gov (United States)

    Kovačević, Sanja; Nestorov, Jelena; Matić, Gordana; Elaković, Ivana

    2017-09-01

    Daily exposure to stress and excessive fructose intake coincides with the growing rate of obesity and related disorders, to which women are more prone than men. Glucocorticoids, the main regulators of energy balance and response to stress, have been associated with the development of metabolic disturbances. The aim of the present study was to examine the effects of fructose overconsumption and/or chronic stress on glucocorticoid signalization and lipid metabolism in female rat adipose tissue. We examined the effects of fructose-enriched diet and chronic unpredictable stress, separately and in combination, on glucocorticoid signaling in terms of 11β-hydroxysteroid dehydrogenase 1 (HSD1)-catalyzed corticosterone regeneration, glucocorticoid receptor (GR) intracellular distribution, hormone binding and transcriptional regulation of genes involved in lipolysis (hormone-sensitive lipase) and lipogenesis (lipoprotein lipase, acetyl-CoA carboxylase, fatty acid synthase and phosphoenolpyruvate carboxykinase) in the visceral adipose tissue (VAT) of adult female rats. Additionally, the nuclear level of the peroxisomal proliferator-activated receptor γ (PPARγ) was analyzed. The combination of stress and fructose-enriched diet led to an elevation in HSD1 expression and intracellular corticosterone concentration, whereas GR nuclear accumulation was enhanced after separate treatments. Furthermore, fructose was shown to induce the expression of all examined lipogenic genes and nuclear accumulation of PPARγ, thereby stimulating adipogenesis, while stress upregulated HSL, reducing the adipose tissue mass regardless of fructose consumption. Prolonged overconsumption of fructose and chronic exposure to stress promote opposite effects on lipid metabolism in the VAT of adult female rats and suggest that these effects could be mediated by glucocorticoids.

  15. From bench to bedside: use of human adipose-derived stem cells

    National Research Council Canada - National Science Library

    Feisst, Vaughan; Meidinger, Sarah; Locke, Michelle B

    2015-01-01

    Since the discovery of adipose-derived stem cells (ASC) in human adipose tissue nearly 15 years ago, significant advances have been made in progressing this promising cell therapy tool from the laboratory bench to bedside usage...

  16. Mutant Wars2 gene in spontaneously hypertensive rats impairs brown adipose tissue function and predisposes to visceral obesity

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Trnovská, J.; Škop, V.; Marková, I.; Malínská, H.; Hüttl, M.; Kazdová, L.; Bardová, Kristina; Tauchmannová, Kateřina; Vrbacký, Marek; Nůsková, Hana; Mráček, Tomáš; Kopecký, Jan; Houštěk, Josef

    2017-01-01

    Roč. 66, č. 6 (2017), s. 917-924 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 Keywords : brown adipose tissue * spontaneously hypertensive rat * quantitative trait loci * transgenic * Wars2 gene * mitochondrial proteosynthesis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.461, year: 2016

  17. Vulnerability to the transmission of human visceral leishmaniasis in a Brazilian urban area.

    Science.gov (United States)

    Toledo, Celina Roma Sánchez de; Almeida, Andréa Sobral de; Chaves, Sergio Augusto de Miranda; Sabroza, Paulo Chagastelles; Toledo, Luciano Medeiros; Caldas, Jefferson Pereira

    2017-05-15

    To analyze the determinants for the occurrence of human visceral leishmaniasis linked to the conditions of vulnerability. This is an ecological study, whose spatial analysis unit was the Territorial Analysis Unit in Araguaína, State of Tocantins, Brazil, from 2007 to 2012. We have carried out an analysis of the sociodemographic and urban infrastructure situation of the municipality. Normalized primary indicators were calculated and used to construct the indicators of vulnerability of the social structure, household structure, and urban infrastructure. From them, we have composed a vulnerability index. Kernel density estimation was used to evaluate the density of cases of human visceral leishmaniasis, based on the coordinates of the cases. Bivariate global Moran's I was used to verify the existence of spatial autocorrelation between the incidence of human visceral leishmaniasis and the indicators and index of vulnerability. Bivariate local Moran's I was used to identify spatial clusters. We have observed a pattern of centrifugal spread of human visceral leishmaniasis in the municipality, where outbreaks of the disease have progressively reached central and peri-urban areas. There has been no correlation between higher incidences of human visceral leishmaniasis and worse living conditions. Statistically significant clusters have been observed between the incidences of human visceral leishmaniasis in both periods analyzed (2007 to 2009 and 2010 to 2012) and the indicators and index of vulnerability. The environment in circumscribed areas helps as protection factor or increases the local vulnerability to the occurrence of human visceral leishmaniasis. The use of methodology that analyzes the conditions of life of the population and the spatial distribution of human visceral leishmaniasis is essential to identify the most vulnerable areas to the spread/maintenance of the disease. Analisar determinantes para a ocorrência da leishmaniose visceral humana vinculados

  18. Study of caveolin-1 gene expression in whole adipose tissue and its subfractions and during differentiation of human adipocytes

    Directory of Open Access Journals (Sweden)

    Rodriguez-Hermosa Jose I

    2010-03-01

    Full Text Available Abstract Context Caveolins are 21-24 kDa integral membrane proteins that serve as scaffolds to recruit numerous signaling molecules. Specific subclasses of caveolae carry out specific functions in cell metabolism. In particular, triglycerides are synthesized at the site of fatty acid entry in one of these caveolae classes. Objective and Methods We studied the expression of caveolin-1 (CAV-1 gene in association with metabolic variables in 90 visceral and 55 subcutaneous adipose tissue samples from subjects with a wide range of fat mass, in the stromovascular fraction (SVC and isolated adipocytes, and during differentiation of human adipocytes. Results CAV-1 gene expression was significantly decreased in visceral adipose tissue (v-CAV-1 of obese subjects. v-CAV-1 was positively associated with several lipogenic genes such as acetyl-coA carboxylase (ACACA, r = 0.34, p = 0.004 and spot-14 (r = 0.33, p = 0.004. In non-obese subjects v-CAV-1 also correlated with fatty acid synthase (FAS, r = 0.60, p c-CAV-1 gene expression was not associated with these lipogenic factors when obese and non-obese subjects were studied together. In obese subjects, however, sc-CAV-1 was associated with fatty acid synthase (FAS, r = 0.36, p = 0.02, sterol regulatory element binding protein-1c (SREBP-1c (r = 0.58, p ACACA (r = 0.33, p = 0.03, spot-14 (r = 0.36, p = 0.02, PPAR-γ co-activator-1 (PGC-1, r = 0.88, n = 19. In these obese subjects, sc-CAV-1 was also associated with fasting triglycerides (r = -0.50, p CAV-1 expression in mature adipocytes was significantly higher than in stromal vascular cells. CAV-1 gene expression in adipocytes from subcutaneous adipose tissue (but not in adipocytes from visceral adipose tissue was significatively associated with fasting triglycerides. CAV-1 gene expression did not change significantly during differentiation of human preadipocytes from lean or obese subjects despite significant increase of FAS gene expression. Conclusion

  19. Adipose Stromal Cells from Visceral and Subcutaneous Fat Facilitate Migration of Ovarian Cancer Cells via IL-6/JAK2/STAT3 Pathway.

    Science.gov (United States)

    Kim, Boyun; Kim, Hee Seung; Kim, Soochi; Haegeman, Guy; Tsang, Benjamin K; Dhanasekaran, Danny N; Song, Yong Sang

    2017-04-01

    Adipose stromal cells (ASCs) play an important regulatory role in cancer progression and metastasis by regulating systemic inflammation and tissue metabolism. This study examined whether visceral and subcutaneous ASCs (V- and S-ASCs) facilitate the growth and migration of ovarian cancer cells. CD45(-) and CD31(-) double-negative ASCs were isolated from the subcutaneous and visceral fat using magnetic-activated cell sorting. Ovarian cancer cells were cultured in conditioned media (CM) obtained from ASCs to determine the cancer-promoting effects of ASCs. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, Boyden chamber assay, and western blotting were performed to determine the proliferative activity, migration ability, and activation of the JAK2/STAT3 pathway, respectively. CM from ASCs enhanced the migration of the ovarian cancer line, SKOV3, via activation of the JAK2/STAT3 signaling pathway. Interestingly, in response to ASC-CM, the ascites cells derived from an ovarian cancer patient showed an increase in growth and migration. The migration of ovarian cancer cells was suppressed by blocking the activation of JAK2 and STAT3 using a neutralizing antibody against interleukin 6, small molecular inhibitors (e.g., WP1066 and TG101348), and silencing of STAT3 using siRNA. Anatomical differences between S- and V-ASCs did not affect the growth and migration of the ovarian cancer cell line and ascites cells from the ovarian cancer patients. ASCs may regulate the progression of ovarian cancer, and possibly provide a potential target for anticancer therapy.

  20. Bofu-tsu-shosan, an oriental herbal medicine, exerts a combinatorial favorable metabolic modulation including antihypertensive effect on a mouse model of human metabolic disorders with visceral obesity.

    Directory of Open Access Journals (Sweden)

    Kengo Azushima

    Full Text Available Accumulating evidence indicates that metabolic dysfunction with visceral obesity is a major medical problem associated with the development of hypertension, type 2 diabetes (T2DM and dyslipidemia, and ultimately severe cardiovascular and renal disease. Therefore, an effective anti-obesity treatment with a concomitant improvement in metabolic profile is important for the treatment of metabolic dysfunction with visceral obesity. Bofu-tsu-shosan (BOF is one of oriental herbal medicine and is clinically available to treat obesity in Japan. Although BOF is a candidate as a novel therapeutic strategy to improve metabolic dysfunction with obesity, the mechanism of its beneficial effect is not fully elucidated. Here, we investigated mechanism of therapeutic effects of BOF on KKAy mice, a model of human metabolic disorders with obesity. Chronic treatment of KKAy mice with BOF persistently decreased food intake, body weight gain, low-density lipoprotein cholesterol and systolic blood pressure. In addition, both tissue weight and cell size of white adipose tissue (WAT were decreased, with concomitant increases in the expression of adiponectin and peroxisome proliferator-activated receptors genes in WAT as well as the circulating adiponectin level by BOF treatment. Furthermore, gene expression of uncoupling protein-1, a thermogenesis factor, in brown adipose tissue and rectal temperature were both elevated by BOF. Intriguingly, plasma acylated-ghrelin, an active form of orexigenic hormone, and short-term food intake were significantly decreased by single bolus administration of BOF. These results indicate that BOF exerts a combinatorial favorable metabolic modulation including antihypertensive effect, at least partially, via its beneficial effect on adipose tissue function and its appetite-inhibitory property through suppression on the ghrelin system.

  1. Effects of dietary restriction on adipose mass and biomarkers of healthy aging in human.

    Science.gov (United States)

    Lettieri-Barbato, Daniele; Giovannetti, Esmeralda; Aquilano, Katia

    2016-11-29

    In developing countries the rise of obesity and obesity-related metabolic disorders, such as cardiovascular diseases and type 2 diabetes, reflects the changes in lifestyle habits and wrong dietary choices. Dietary restriction (DR) regimens have been shown to extend health span and lifespan in many animal models including primates. Identifying biomarkers predictive of clinical benefits of treatment is one of the primary goals of precision medicine. To monitor the clinical outcomes of DR interventions in humans, several biomarkers are commonly adopted. However, a validated link between the behaviors of such biomarkers and DR effects is lacking at present time. Through a systematic analysis of human intervention studies, we evaluated the effect size of DR (i.e. calorie restriction, very low calorie diet, intermittent fasting, alternate day fasting) on health-related biomarkers. We found that DR is effective in reducing total and visceral adipose mass and improving inflammatory cytokines profile and adiponectin/leptin ratio. By analysing the levels of canonical biomarkers of healthy aging, we also validated the changes of insulin, IGF-1 and IGFBP-1,2 to monitor DR effects. Collectively, we developed a useful platform to evaluate the human responses to dietary regimens low in calories.

  2. Ultrasonography modifications of visceral and subcutaneous adipose tissue after pioglitazone or glibenclamide therapy combined with rosuvastatin in type 2 diabetic patients not well controlled by metformin.

    Science.gov (United States)

    Maffioli, Pamela; Fogari, Elena; D'Angelo, Angela; Perrone, Tiziano; Derosa, Giuseppe

    2013-09-01

    To compare pioglitazone or glibenclamide alone and in combination with rosuvastatin on hepatic steatosis in type 2 diabetic patients. After 3 months of metformin, patients were randomized to add pioglitazone 15 mg twice a day or glibenclamide 5 mg twice a day for 6 months, and then rosuvastatin 5 mg was added for other 6 months. Patients underwent an ultrasound examination for evaluation of steatosis degree, subcutaneous adipose tissue, and visceral adipose tissue diameter, an euglycemic hyperinsulinemic clamp, and blood sample collection for evaluation of glycemic control, fasting plasma insulin, lipid profile, adipocytokines at randomization, and after 6 and 12 months. Both pioglitazone and glibenclamide improved glycemic control. Pioglitazone reduced fasting plasma insulin, whereas glibenclamide increased it. Pioglitazone increased the glucose infusion rate compared with glibenclamide. Pioglitazone, but not glibenclamide, improved the lipid profile, and, when rosuvastatin was added, there was a greater improvement with pioglitazone and rosuvastatin. Adiponectin was increased by pioglitazone (+0.5 μg/ml), with a further increase (+0.4 μg/ml) when rosuvastatin was added. A significant decrease in leptin (-3.1 ng/ml) and interleukin-6 (-0.4 pg/ml) was found only with pioglitazone; a similar trend (-2.5 ng/ml and -0.3 pg/ml, respectively) was maintained after the addition of rosuvastatin.Rosuvastatin+pioglitazone decreased tumor necrosis factor-α (-0.3 ng/ml) and were superior to glibenclamide+rosuvastatin in reducing high-sensitivity C-reactive protein (-0.4 mg/l).Pioglitazone decreased ultrasound parameters, and the addition of rosuvastatin further decreased them both compared with randomization and glibenclamide. Pioglitazone was more effective than glibenclamide in improving inflammation and hepatic steatosis indices.

  3. Pu'erh tea extract-mediated protection against hepatosteatosis and insulin resistance in mice with diet-induced obesity is associated with the induction of de novo lipogenesis in visceral adipose tissue.

    Science.gov (United States)

    Cai, Xianbin; Hayashi, Shuhei; Fang, Chongye; Hao, Shumei; Wang, Xuanjun; Nishiguchi, Shuhei; Tsutsui, Hiroko; Sheng, Jun

    2017-12-01

    White adipose tissue (WAT) is important for the maintenance of metabolic homeostasis, and metabolic syndrome is sometimes associated with WAT dysfunction in humans and animals. WAT reportedly plays a key, beneficial role in the maintenance of glucose and lipid homeostasis during de novo lipogenesis (DNL). Pu'erh tea extract (PTE) can inhibit harmful, ectopic DNL in the liver, thus protecting against hepatosteatosis, in mice with diet-induced obesity. We examined whether PTE could induce DNL in WAT and consequently protect against hepatosteatosis. C57BL/6 male mice were fed a high-fat diet (HFD) with/without PTE for 16 weeks. Systemic insulin sensitivity was determined using HOMA-IR, insulin- and glucose-tolerance tests, and WAT adipogenesis was evaluated by histological analysis. Adipogenesis-, inflammation-, and DNL-related gene expression in visceral AT (VAT) and subcutaneous AT (SAT) was measured using quantitative reverse transcription-PCR. Regression analysis was used to investigate the association between DNL in WAT and systemic insulin resistance or hepatosteatosis. Pu'erh tea extract significantly reduced the gain of body weight and SAT, but not VAT adiposity, in mice fed the high-fat diet and induced adipogenesis in VAT. The expression of DNL-related genes, including Glut4, encoding an important insulin-regulated glucose transporter (GLUT4), were highly elevated in VAT. Moreover, PTE inhibited VAT inflammation by simultaneously downregulating inflammatory molecules and inducing expression of Gpr120 that encodes an anti-inflammatory and pro-adipogenesis receptor (GPR-120) that recognizes unsaturated long-chain fatty acids, including DNL products. The expression of DNL-related genes in VAT was inversely correlated with hepatosteatosis and systemic insulin resistance. Activation of DNL in VAT may explain PTE-mediated alleviation of hepatosteatosis symptoms and systemic insulin resistance.

  4. Peripheral KV7 channels regulate visceral sensory function in mouse and human colon.

    Science.gov (United States)

    Peiris, Madusha; Hockley, James Rf; Reed, David E; Smith, Ewan St John; Bulmer, David C; Blackshaw, L Ashley

    2017-01-01

    Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The KV7 family (KV7.1-KV7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral KV7 channels to visceral nociception. Results Immunohistochemical staining of mouse colon revealed labelling of KV7 subtypes (KV7.3 and KV7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the KV7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B2 bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0-80 mmHg) in a concentration-dependent manner, whereas the KV7 blocker XE991 potentiated such responses. In human bowel tissues, KV7.3 and KV7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon. Conclusions We show that KV7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted KV7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies.

  5. Glucocorticoids affect 24 h clock genes expression in human adipose tissue explant cultures.

    Directory of Open Access Journals (Sweden)

    Purificación Gómez-Abellán

    Full Text Available to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V and subcutaneous (S adipose tissue (AT in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX on positive and negative clock genes expression.VAT and SAT biopsies were obtained from morbid obese women (body mass index ≥ 40 kg/m(2 (n = 6. In order to investigate rhythmic expression pattern of clock genes and the effect of DEX on CLOCK, PER2 and BMAL1 expression, control AT (without DEX and AT explants treated with DEX (2 hours were cultured during 24 h and gene expression was analyzed at the following times: 10:00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h, using qRT-PCR.CLOCK, BMAL1 and PER2 expression exhibited circadian patterns in both VAT and SAT explants that were adjusted to a typical 24 h sinusoidal curve. PER2 expression (negative element was in antiphase with respect to CLOCK and in phase with BMAL1 expression (both positive elements in the SAT (situation not present in VAT. A marked effect of DEX exposure on both positive and negative clock genes expression patterns was observed. Indeed, DEX treatment modified the rhythmicity pattern towards altered patterns with a period lower than 24 hours in all genes and in both tissues.24 h patterns in CLOCK and BMAL1 (positive clock elements and PER2 (negative element mRNA levels were observed in human adipose explants. These patterns were altered by dexamethasone exposure.

  6. The Impact of Blood Pressure and Visceral Adiposity on the Association of Serum Uric Acid With Albuminuria in Adults Without Full Metabolic Syndrome.

    Science.gov (United States)

    Krajcoviechova, Alena; Tremblay, Johanne; Wohlfahrt, Peter; Bruthans, Jan; Tahir, Muhmmad Ramzan; Hamet, Pavel; Cifkova, Renata

    2016-12-01

    The impact of metabolic phenotypes on the association of uricemia with urinary albumin/creatinine ratio (uACR) remains unresolved. We evaluated the association between serum uric acid and uACR in persons with 0, and 1-2 metabolic syndrome (MetS) components and determined the modification effects of visceral adiposity index (VAI), mean arterial pressure (MAP), and fasting glucose on this association. Using data from a cross-sectional survey of a representative Czech population aged 25-64 years (n = 3612), we analyzed 1,832 persons without decreased glomerular filtration rate uric acid levels only in persons with 1-2 MetS components (standardized beta (Sβ) 0.048; P = 0.024); however, not in those without any component (Sβ 0.030; P = 0.264). Uric acid levels increased by the interaction of uACR with VAI (Sβ 0.06; P = 0.012), and of uACR with MAP (Sβ 0.05; P = 0.009). Finally, the association of uACR with uricemia was confined to persons whose VAI together with MAP were ≥the median of 1.35 and 98mm Hg, respectively (Sβ 0.190; P < 0.001). We demonstrated a strong modification effect of VAI and MAP on the association between uACR and uricemia, which suggests obesity-related hypertension as the underlying mechanism.

  7. Anthropometrically-predicted visceral adipose tissue and mortality among men and women in the third national health and nutrition examination survey (NHANES III).

    Science.gov (United States)

    Brown, Justin C; Harhay, Michael O; Harhay, Meera N

    2017-01-01

    This study seeks to quantify the relationship between anthropometrically-predicted visceral adipose tissue (apVAT) and all-cause and cause-specific mortality among individuals of European descent in a population-based prospective cohort study of 10,624 participants. The apVAT with a validated regression equation that included age, body mass index, and waist and thigh circumferences were predicted. During a median of 18.8 years, 3531 participants died with 1153 and 741 deaths attributable to cardiovascular disease and cancer, respectively. In multivariable-adjusted analyses that accounted for demographic, clinical, and behavioral characteristics, higher apVAT was associated with an increased risk of all-cause (Ptrend  cardiovascular-specific (Ptrend  effect estimates. apVAT more accurately predicted all-cause, cardiovascular-specific, and cancer-specific mortality than body mass index (P < .001), waist circumference (P < .001), or the combination of body mass index and waist circumference (P < .001). These data provide evidence that apVAT is associated with all-cause and cause-specific mortality in a large population-based sample of men and women of European descent. These results support the use of apVAT to risk-stratify individuals for premature mortality when imaging data are not available such as in routine clinical practice or in large clinical trials. © 2016 Wiley Periodicals, Inc.

  8. A systematic review and meta-analysis on the effects of exercise training versus hypocaloric diet: distinct effects on body weight and visceral adipose tissue.

    Science.gov (United States)

    Verheggen, R J H M; Maessen, M F H; Green, D J; Hermus, A R M M; Hopman, M T E; Thijssen, D H T

    2016-08-01

    Exercise training ('exercise') and hypocaloric diet ('diet') are frequently prescribed for weight loss in obesity. Whilst body weight changes are commonly used to evaluate lifestyle interventions, visceral adiposity (VAT) is a more relevant and stronger predictor for morbidity and mortality. A meta-analysis was performed to assess the effects of exercise or diet on VAT (quantified by radiographic imaging). Relevant databases were searched through May 2014. One hundred seventeen studies (n = 4,815) were included. We found that both exercise and diet cause VAT loss (P weight loss (P = 0.04). In contrast, a trend was observed towards a larger VAT decrease in exercise (P = 0.08). Changes in weight and VAT showed a strong correlation after diet (R(2)  = 0.737, P weight loss, exercise is related to 6.1% decrease in VAT, whilst diet showed virtually no change (1.1%). In conclusion, both exercise and diet reduce VAT. Despite a larger effect of diet on total body weight loss, exercise tends to have superior effects in reducing VAT. Finally, total body weight loss does not necessarily reflect changes in VAT and may represent a poor marker when evaluating benefits of lifestyle-interventions. © 2016 World Obesity.

  9. Volume-dependent effect of supervised exercise training on fatty liver and visceral adiposity index in subjects with type 2 diabetes The Italian Diabetes Exercise Study (IDES).

    Science.gov (United States)

    Balducci, Stefano; Cardelli, Patrizia; Pugliese, Luca; D'Errico, Valeria; Haxhi, Jonida; Alessi, Elena; Iacobini, Carla; Menini, Stefano; Bollanti, Lucilla; Conti, Francesco G; Nicolucci, Antonio; Pugliese, Giuseppe

    2015-08-01

    This study evaluated the effect of supervised exercise training on liver enzymes and two surrogate measures of non-alcoholic fatty liver disease (NAFLD) in subjects with type 2 diabetes. Sedentary patients from 22 outpatient diabetes clinics were randomized by center, age and treatment to twice-a-week supervised aerobic and resistance training plus structured exercise counseling (exercise group, EXE; n=303) versus counseling alone (control group, CON; n=303) for 12 months. EXE participants were further randomized to low-to-moderate (n=142) or moderate-to-high (n=161) intensity training of equal energy cost. Baseline and end-of-study levels of liver enzymes, fatty liver index (FLI) and visceral adiposity index (VAI) were obtained. Enzyme levels did not change, whereas FLI and VAI decreased significantly in EXE, but not CON participants. Physical activity (PA) volume was an independent predictor of both FLI and VAI reductions, the extent of which increased from the 1st to the 4th quintile of PA volume and baseline to end-of-study changes in fitness parameters. Differences in the effect of LI versus HI training were negligible. Data from this large cohort of subjects with type 2 diabetes indicate that FLI and VAI decrease with supervised training in a volume-dependent manner. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Entomological investigation following the resurgence of human visceral leishmaniasis in southern Algeria.

    Science.gov (United States)

    Benallal, K; Gassen, B; Bouiba, L; Depaquit, J; Harrat, Z

    2013-12-01

    Visceral and cutaneous leishmaniasis are the main endemic vector born diseases in Algeria. In the Hoggar region (extreme south of the country) human visceral leishmaniasis (HVL) is known to be sporadic but during the last decade the number of cases has increased significantly. In 2010, a peak of HVL cases was registered mostly among children. Therefore an entomological survey and a retrospective study on HVL cases were carried out in order to explore the transmission of the disease. Among the sand fly caught Phlebotomus bergeroti was the most frequent species (68%) followed by Sergentomyia schwetzi (22%). In this work we describe the presence of Phlebotomus (Paraphlebotomus) kazeruni for the first time in the Hoggar region. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Variability in responses observed in human white adipose tissue models.

    Science.gov (United States)

    Abbott, Rosalyn D; Borowsky, Francis E; Alonzo, Carlo A; Zieba, Adam; Georgakoudi, Irene; Kaplan, David L

    2017-09-06

    Obesity is a risk factor for a myriad of diseases including diabetes, cardiovascular dysfunction, cirrhosis, and cancer, and there is a need for new systems to study how excess adipose tissue relates to the onset of disease processes. This study provides proof-of-concept patient-specific tissue models of human white adipose tissue to accommodate the variability in human samples. Our 3D tissue engineering approach established lipolytic responses and changes in insulin-stimulated glucose uptake from small volumes of human lipoaspirate, making this methodology useful for patient specific sample source assessments of treatment strategies, drug responses, disease mechanisms, and other responses that vary between patients. Mature unilocular cells were maintained ex vivo in silk porous scaffolds for up to a month of culture and imaged non-invasively with coherent anti-Stokes Raman scattering. Interestingly, differences in responsiveness between tissues were observed in terms of magnitude of lipolysis, ability to suppress lipolysis, differences in glucose uptake, and lipid droplet size. Body mass index was not a factor in determining tissue responsiveness; rather, it is speculated that other unknown variables in the backgrounds of different patients (ethnicity, athleticism, disease history, lifestyle choices, etc.) likely had a more significant effect on the observed differences. This study reinforces the need to account for the variability in backgrounds and genetics within the human population to determine adipose tissue responsiveness. In the future, this tissue system could be used to inform individualized care strategies-enhancing therapeutic precision, improving patient outcomes, and reducing clinical costs. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Flavanol metabolites distribute in visceral adipose depots after a long-term intake of grape seed proanthocyanidin extract in rats.

    Science.gov (United States)

    Serra, Aida; Bladé, Cinta; Arola, Lluís; Macià, Alba; Motilva, Maria-José

    2013-10-01

    A considerable number of epidemiological investigations and intervention studies have supported an association between the intake of flavanol- and proanthocyanidin-containing foods and a decreased risk of metabolic diseases. Nonetheless, less is know about the capacity of tissues to accumulate flavanols and/or their metabolites. The main objective of the present study was to determine (n 20) plasma bioavailability and disposition in the liver, muscle, brown adipose tissue (BAT) and white adipose tissues (mesenteric and perirenal) in rats after a long-term consumption of three doses of grape seed phenolic extract (5, 25 and 50 mg/kg body weight) for 21 d in order to determine whether there is a dose-response relationship. Glucuronidated conjugates (total glucuronidated conjugates: C(5 mg/kg) 1·9; C(25 mg/kg) 6·4; C(50 mg/kg) 27·7 μmol/l plasma) followed by methyl glucuronidated conjugates (total methyl glucuronidated conjugates: C(5 mg/kg) 1·98; C(25 mg/kg) 4·48; C(50 mg/kg) 12·5 μmol/l plasma) were the main flavanol metabolites quantified in plasma, also detecting a dimer in its free form (C(25 mg/kg) 0·74; C(50 mg/kg) 0·79 μmol/l plasma). Each of the studied organs has a particular behaviour of accumulation and response to the assayed grape seed extract doses, with an exponential bioavailability-dose relationship in BAT, in which flavanols could play an important role in the reduction or prevention of obesity, modulating the functionality of that tissue.

  13. Magnetic Resonance Imaging of Human Tissue-Engineered Adipose Substitutes

    Science.gov (United States)

    Proulx, Maryse; Aubin, Kim; Lagueux, Jean; Audet, Pierre; Auger, Michèle

    2015-01-01

    Adipose tissue (AT) substitutes are being developed to answer the strong demand in reconstructive surgery. To facilitate the validation of their functional performance in vivo, and to avoid resorting to excessive number of animals, it is crucial at this stage to develop biomedical imaging methodologies, enabling the follow-up of reconstructed AT substitutes. Until now, biomedical imaging of AT substitutes has scarcely been reported in the literature. Therefore, the optimal parameters enabling good resolution, appropriate contrast, and graft delineation, as well as blood perfusion validation, must be studied and reported. In this study, human adipose substitutes produced from adipose-derived stem/stromal cells using the self-assembly approach of tissue engineering were implanted into athymic mice. The fate of the reconstructed AT substitutes implanted in vivo was successfully followed by magnetic resonance imaging (MRI), which is the imaging modality of choice for visualizing soft ATs. T1-weighted images allowed clear delineation of the grafts, followed by volume integration. The magnetic resonance (MR) signal of reconstructed AT was studied in vitro by proton nuclear magnetic resonance (1H-NMR). This confirmed the presence of a strong triglyceride peak of short longitudinal proton relaxation time (T1) values (200±53 ms) in reconstructed AT substitutes (total T1=813±76 ms), which establishes a clear signal difference between adjacent muscle, connective tissue, and native fat (total T1 ∼300 ms). Graft volume retention was followed up to 6 weeks after implantation, revealing a gradual resorption rate averaging at 44% of initial substitute's volume. In addition, vascular perfusion measured by dynamic contrast-enhanced-MRI confirmed the graft's vascularization postimplantation (14 and 21 days after grafting). Histological analysis of the grafted tissues revealed the persistence of numerous adipocytes without evidence of cysts or tissue necrosis. This study

  14. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways

    OpenAIRE

    M?ller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. ...

  15. Relevance of omental pericellular adipose tissue collagen in the pathophysiology of human abdominal obesity and related cardiometabolic risk.

    Science.gov (United States)

    Michaud, A; Tordjman, J; Pelletier, M; Liu, Y; Laforest, S; Noël, S; Le Naour, G; Bouchard, C; Clément, K; Tchernof, A

    2016-12-01

    Adipose tissue fibrosis is a relatively new notion and its relationship with visceral obesity and cardiometabolic alterations remains unclear, particularly in moderate obesity. Our objective was to examine if total and pericellular collagen accumulation are relevant for the pathophysiology of visceral obesity and related cardiometabolic risk. Surgical omental (OM) and subcutaneous (SC) fat samples were obtained in 56 women (age: 47.2±5.8 years; body mass index (BMI): 27.1±4.4 kg/m2). Body composition and fat distribution were measured by dual-energy X-ray absorptiometry and computed tomography, respectively. Total and pericellular collagen were measured using picrosirius red staining. CD68+ cells (total macrophages) and CD163+ cells (M2-macrophages) were identified using immunohistochemistry. We found that only pericellular collagen percentage, especially in OM fat, was associated with higher BMI, body fat mass and adipose tissue areas as well as lower radiologic attenuation of visceral adipose tissue and altered cardiometabolic risk variables. Strong correlations between peri-adipocyte collagen percentage and total or M2-macrophage percentages were observed in both depots. Total collagen percentage in either compartment was not related to adiposity, fat distribution or cardiometabolic risk. As opposed to whole tissue-based assessments of adipose tissue fibrosis, collagen deposition around the adipocyte, especially in the OM fat compartment is related to total and regional adiposity as well as altered cardiometabolic risk profile.

  16. Effect of functional sympathetic nervous system impairment of the liver and abdominal visceral adipose tissue on circulating triglyceride-rich lipoproteins.

    Science.gov (United States)

    La Fountaine, Michael F; Cirnigliaro, Christopher M; Kirshblum, Steven C; McKenna, Cristin; Bauman, William A

    2017-01-01

    Interruption of sympathetic innervation to the liver and visceral adipose tissue (VAT) in animal models has been reported to reduce VAT lipolysis and hepatic secretion of very low density lipoprotein (VLDL) and concentrations of triglyceride-rich lipoprotein particles. Whether functional impairment of sympathetic nervous system (SNS) innervation to tissues of the abdominal cavity reduce circulating concentrations of triglyceride (TG) and VLDL particles (VLDL-P) was tested in men with spinal cord injury (SCI). One hundred-three non-ambulatory men with SCI [55 subjects with neurologic injury at or proximal to the 4th thoracic vertebrae (↑T4); 48 subjects with SCI at or distal to the 5th thoracic vertebrae (↓T5)] and 53 able-bodied (AB) subjects were studied. Fasting blood samples were obtained for determination of TG, VLDL-P concentration by NMR spectroscopy, serum glucose by autoanalyzer, and plasma insulin by radioimmunoassay. VAT volume was determined by dual energy x-ray absorptiometry imaging with calculation by a validated proprietary software package. Significant group main effects for TG and VLDL-P were present; post-hoc tests revealed that serum TG concentrations were significantly higher in ↓T5 group compared to AB and ↑T4 groups [150±9 vs. 101±8 (plipoproteins (i.e., TG or Large VLDL-P) and VAT volume or HOMA-IR was significant only in the ↓T5 group. Despite a similar VAT volume and insulin resistance in both SCI groups, the ↓T5 group had significantly higher serum TG and VLDL-P values than that observed in the ↑T4 and the AB control groups. Thus, level of injury is an important determinate of the concentration of circulating triglyceride rich lipoproteins, which may play a role in the genesis of cardiometabolic dysfunction.

  17. Glucose intolerance and the amount of visceral adipose tissue contribute to an increase in circulating triglyceride concentrations in Caucasian obese females.

    Directory of Open Access Journals (Sweden)

    Margot Berings

    Full Text Available CONTEXT: Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2, cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2. METHODS: 913 obese females unknown to have diabetes were recruited (mean age: 41.2 ± SD 12.3; median BMI: 36.2, IQR 32.9-40.2. Visceral (VAT and subcutaneous abdominal adipose tissue volumes were quantified with computed tomography. Glucose, insulin, and triglyceride concentrations were determined in fasting state and following a 75 gram oral glucose tolerance test. RESULTS: Based on fasting and 2 h post-load glucose levels, 27% of the women had impaired glucose tolerance (IGT, and 8% had newly diagnosed DM2. Fasting TG concentrations were similar between the IGT- and DM2-groups, and increased as compared to women with normal glucose tolerance (NGT. Even when adjusting for age, hip circumference and VAT, fasting TG concentrations remained elevated as compared to NGT. Mixed modelling analysis of post-load responses showed that TG concentrations declined more slowly in the DM2-group as compared to IGT and NGT. However, when adjusting for VAT the difference in decline between the glucose tolerance groups disappeared. CONCLUSIONS: Glucose intolerance associates with elevated fasting TG concentrations in obese Caucasian women. We propose that glucose intolerance and increased VAT reduce lipid disposal mechanisms and may accelerate lipotoxicity.

  18. Prolonged Exposures to Intermittent Hypoxia Promote Visceral White Adipose Tissue Inflammation in a Murine Model of Severe Sleep Apnea: Effect of Normoxic Recovery.

    Science.gov (United States)

    Gileles-Hillel, Alex; Almendros, Isaac; Khalyfa, Abdelnaby; Nigdelioglu, Recep; Qiao, Zhuanhong; Hamanaka, Robert B; Mutlu, Gökhan M; Akbarpour, Mahzad; Gozal, David

    2017-03-01

    Increased visceral white adipose tissue (vWAT) mass results in infiltration of inflammatory macrophages that drive inflammation and insulin resistance. Patients with obstructive sleep apnea (OSA) suffer from increased prevalence of obesity, insulin resistance, and metabolic syndrome. Murine models of intermittent hypoxia (IH) mimicking moderate-severe OSA manifest insulin resistance following short-term IH. We examined in mice the effect of long-term IH on the inflammatory cellular changes within vWAT and the potential effect of normoxic recovery (IH-R). Male C57BL/6J mice were subjected to IH for 20 weeks, and a subset was allowed to recover in room air (RA) for 6 or 12 weeks (IH-R). Stromal vascular fraction was isolated from epididymal vWAT and mesenteric vWAT depots, and single-cell suspensions were prepared for flow cytometry analyses, reactive oxygen species (ROS), and metabolic assays. IH reduced body weight and vWAT mass and IH-R resulted in catch-up weight and vWAT mass. IH-exposed vWAT exhibited increased macrophage counts (ATMs) that were only partially improved in IH-R. IH also caused a proinflammatory shift in ATMs (increased Ly6c(hi)(+) and CD36(+) ATMs). These changes were accompanied by increased vWAT insulin resistance with only partial improvements in IH-R. In addition, ATMs exhibited increased ROS production, altered metabolism, and changes in electron transport chain, which were only partially improved in IH-R. Prolonged exposures to IH during the sleep period induce pronounced vWAT inflammation and insulin resistance despite concomitant vWAT mass reductions. These changes are only partially reversible after 3 months of normoxic recovery. Thus, long-lasting OSA may preclude complete reversibility of metabolic changes.

  19. Desensitization of human adipose tissue to adrenaline stimulation studied by microdialysis

    DEFF Research Database (Denmark)

    Stallknecht, Bente; Bülow, J; Frandsen, E

    1997-01-01

    1. Desensitization of fat cell lipolysis to catecholamine exposure has been studied extensively in vitro but only to a small extent in human adipose tissue in vivo. 2. We measured interstitial glycerol concentrations by microdialysis in subcutaneous, abdominal adipose tissue in healthy humans dur...

  20. Adaptation of human adipose tissue to hypocaloric diet.

    Science.gov (United States)

    Rossmeislová, L; Mališová, L; Kračmerová, J; Štich, V

    2013-05-01

    Hypocaloric diet is a key component of the weight-reducing treatment of obesity and obesity-related disorders. Hypocaloric diets and the associated weight reduction promote improvement of metabolic profile of obese individuals. Among the mechanisms that underlie this beneficial metabolic outcome, the diet-induced modifications of morphological and functional characteristics of human adipose tissue (AT) are believed to have an important role. Prospective studies of hypocaloric weight-reducing dietary intervention demonstrate effects on adipocyte metabolism, namely lipolysis and lipogenesis, and associated changes of the adipocyte size. The endocrine function of AT, which involves cytokine and adipokine production by adipocytes, as well as by cells of stromavascular fraction, is also regulated by dietary intervention. Related inflammatory status of AT is modulated also as a consequence of the changes in recruitment of immune cells, mainly macrophages, in AT. Here, we give an overview of metabolic and endocrine modifications in human AT induced by a variety of hypocaloric diets.

  1. Estimated Visceral Adipose Tissue, but Not Body Mass Index, Is Associated with Reductions in Glomerular Filtration Rate Based on Cystatin C in the Early Stages of Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ana Karina Teixeira da Cunha França

    2014-01-01

    Full Text Available Information on the association between obesity and initial phases of chronic kidney disease (CKD is still limited, principally those regarding the influence of visceral adipose tissue. We investigated whether the visceral adipose tissue is more associated with reductions in glomerular filtration rate (GFR than total and abdominal obesity in hypertensive individuals with stage 1-2 CKD. A cross-sectional study was implemented which involved 241 hypertensive patients undergoing treatment at a primary health care facility. GFR was estimated using equations based on creatinine and cystatin C levels. Explanatory variables included body mass index (BMI, waist circumference (WC, and estimated visceral adipose tissue (eVAT. The mean age was 59.6±9.2 years old and 75.9% were female. According to BMI, 28.2% of subjects were obese. Prevalence of increased WC and eVAT was 63.9% and 58.5%, respectively. Results from the assessment of GFR by BMI, WC, and eVAT categories showed that only women with increased eVAT (≥150 cm2 had a lower mean GFR by Larsson (P=0.016, Levey 2 (P=0.005, and Levey 3 (P=0.008 equations. The same result was not observed when the MDRD equation was employed. No association was found between BMI, WC, eVAT, and GFR using only serum creatinine. In the early stages of CKD, increased eVAT in hypertensive women was associated with decreased GFR based on cystatin C.

  2. Evaluation of three recombinant Leishmania infantum antigens in human and canine visceral leishmaniasis diagnosis.

    Science.gov (United States)

    Fonseca, Aliani Moura; Faria, Angélica Rosa; Rodrigues, Fernandes Tenório Gomes; Nagem, Ronaldo Alves Pinto; Magalhães, Rubens Daniel Miserani; Cunha, João Luís Reis; Bartholomeu, Daniella Castanheira; de Andrade, Hélida Monteiro

    2014-09-01

    Visceral leishmaniasis (VL) is a neglected disease and is fatal if untreated. Dogs serve as reservoirs for Leishmania infantum (syn. L. chagasi) due to their susceptibility to infection and high skin parasitism. Therefore, VL control in Brazil involves the elimination of seropositive dogs, among other actions. However, the most frequently used serological tests have limitations regarding sensitivity and specificity. In this study, we have selected three Leishmania antigens (C1, C8 and C9) and have produced them as recombinant proteins using pET-28a-TEV vector and Escherichia coli BL-21 as expression system. When tested in ELISA with human samples, the C9 antigen was the one showing the most promising results, with 68% sensitivity and 78% specificity. When testing canine samples, the C1, C8 and C9 antigens showed a sensitivity range from 70% to 80% and specificity range from 60% to 90%. The C1 antigen presented higher sensitivity (80%) and the C8 antigen presented higher specificity (90%). Due to it, we decided to mix and test C1 and C8 antigens together, resulting in the C18 antigen. The mix also yielded high percentages of detected symptomatic and asymptomatic dogs however it did not improve the performance of the diagnostic. Comparison of our tests with the tests recommended by the Brazilian Ministry of Health revealed that our antigens' sensitivities and the percentage of detected asymptomatic dogs were much higher. Our results suggest that the C1, C8, C18 and C9 recombinant proteins are good antigens to diagnose canine visceral leishmaniasis and could potentially be used in screening tests. To diagnose human visceral leishmaniasis, the C9 antigen presented reasonable results, but more optimization must be performed for this antigen to provide better performance. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Effects of Two Different Rhodiola rosea Extracts on Primary Human Visceral Adipocytes.

    Science.gov (United States)

    Pomari, Elena; Stefanon, Bruno; Colitti, Monica

    2015-05-11

    Rhodiola rosea (Rro) has been reported to have various pharmacological properties, including anti-fatigue, anti-stress and anti-inflammatory activity. It is also known to improve glucose and lipid metabolism, but the effects of Rhodiola rosea on adipocyte differentiation and metabolism are not still elucidated. In this study the anti-adipogenic and lipolytic activity of two extracts of Rhodiola rosea, containing 3% salidroside (RS) or 1% salidroside and 3% rosavines (RR) on primary human visceral adipocytes was investigated. Pre-adipocytes were analyzed after 10 and 20 days of treatment during differentiation and after 7 days of treatment when they reached mature shape. The RS extract significantly induced higher apoptosis and lipolysis in comparison to control cells and to RR extract. In contrast, RR extract significantly reduced triglyceride incorporation during maturation. Differentiation of pre-adipocytes in the presence of RS and RR extracts showed a significant decrease in expression of genes involved in adipocyte function such as SLC2A4 and the adipogenic factor FGF2 and significant increase in expression of genes involved in inhibition of adipogenesis, such as GATA3, WNT3A, WNT10B. Furthermore RR extract, in contrast to RS, significantly down-regulates PPARG, the master regulator of adipogenesis and FABP4. These data support the lipolytic and anti-adipogenetic activity of two different commercial extracts of Rhodiola rosea in primary human visceral pre-adipocytes during differentiation.

  4. Effects of Two Different Rhodiola rosea Extracts on Primary Human Visceral Adipocytes

    Directory of Open Access Journals (Sweden)

    Elena Pomari

    2015-05-01

    Full Text Available Rhodiola rosea (Rro has been reported to have various pharmacological properties, including anti-fatigue, anti-stress and anti-inflammatory activity. It is also known to improve glucose and lipid metabolism, but the effects of Rhodiola rosea on adipocyte differentiation and metabolism are not still elucidated. In this study the anti-adipogenic and lipolytic activity of two extracts of Rhodiola rosea, containing 3% salidroside (RS or 1% salidroside and 3% rosavines (RR on primary human visceral adipocytes was investigated. Pre-adipocytes were analyzed after 10 and 20 days of treatment during differentiation and after 7 days of treatment when they reached mature shape. The RS extract significantly induced higher apoptosis and lipolysis in comparison to control cells and to RR extract. In contrast, RR extract significantly reduced triglyceride incorporation during maturation. Differentiation of pre-adipocytes in the presence of RS and RR extracts showed a significant decrease in expression of genes involved in adipocyte function such as SLC2A4 and the adipogenic factor FGF2 and significant increase in expression of genes involved in inhibition of adipogenesis, such as GATA3, WNT3A, WNT10B. Furthermore RR extract, in contrast to RS, significantly down-regulates PPARG, the master regulator of adipogenesis and FABP4. These data support the lipolytic and anti-adipogenetic activity of two different commercial extracts of Rhodiola rosea in primary human visceral pre-adipocytes during differentiation.

  5. AA-amyloidosis caused by visceral leishmaniasis in a human immunodeficiency virus-infected patient.

    Science.gov (United States)

    de Vallière, Serge; Mary, Charles; Joneberg, Jeanna E; Rotman, Samuel; Bullani, Roberto; Greub, Gilbert; Gillmore, Julian D; Buffet, Pierre A; Tarr, Philip E

    2009-08-01

    AA-amyloidosis in the setting of chronic visceral leishmaniasis (VL) has been reported in animal models but documentation in humans is unavailable. Here, we report on a Portuguese man who in 1996 was diagnosed with both human immunodeficiency virus (HIV)-infection and VL. Antiretroviral treatment led to sustained suppression of HIV viremia but CD4+ lymphocytes rose from 8 to only 160 cells/mL. Several courses of antimony treatment did not prevent VL relapses. Renal failure developed in 2006 and renal biopsy revealed AA-amyloidosis. The patient had cryoglobulinemia and serum immune complexes containing antibodies directed against seven leishmanial antigens. Antimony plus amphotericin B, followed by oral miltefosine resulted in a sustained VL treatment response with elimination of circulating Leishmania infantum DNA and CD4+ recovery. The concomitant reduction of serum AA levels and disappearance of circulating leishmanial immune complexes suggests that prolonged VL may lead to AA-amyloidosis in immunocompromised humans.

  6. Changes in adenosine 5'-monophosphate-activated protein kinase as a mechanism of visceral obesity in Cushing's syndrome.

    Science.gov (United States)

    Kola, Blerina; Christ-Crain, Mirjam; Lolli, Francesca; Arnaldi, Giorgio; Giacchetti, Gilberta; Boscaro, Marco; Grossman, Ashley B; Korbonits, Márta

    2008-12-01

    Features of the metabolic syndrome such as central obesity with insulin resistance and dyslipidemia are typical signs of Cushing's syndrome and common side effects of prolonged glucocorticoid treatment. AMP-activated protein kinase (AMPK), a key regulatory enzyme of lipid and carbohydrate metabolism as well as appetite, is involved in the development of the deleterious metabolic effects of excess glucocorticoids, but no data are available in humans. In the current study, we demonstrate the effect of high glucocorticoid levels on AMPK activity of human adipose tissue samples from patients with Cushing's syndrome. AMPK activity and mRNA expression of genes involved in lipid metabolism were assessed in visceral adipose tissue removed at abdominal surgery of 11 patients with Cushing's syndrome, nine sex-, age-, and weight-matched patients with adrenal incidentalomas, and in visceral adipose tissue from four patients with non-endocrine-related abdominal surgery. The patients with Cushing's syndrome exhibited a 70% lower AMPK activity in visceral adipose tissue as compared with both incidentalomas and control patients (P = 0.007 and P Cushing's syndrome. AMPK activity was inversely correlated with 0900 h serum cortisol and with urinary free cortisol. Our data suggest that glucocorticoids inhibit AMPK activity in adipose tissue, suggesting a novel mechanism to explain the deposition of visceral adipose tissue and the consequent central obesity observed in patients with iatrogenic or endogenous Cushing's syndrome.

  7. Nanomechanics of human adipose-derived stem cells

    DEFF Research Database (Denmark)

    Jungmann, Pia M; Mehlhorn, Alexander T; Schmal, Hagen

    2012-01-01

    OBJECTIVES: Human adipose-derived stem cells (ASCs) show gene expression of chondrogenic markers after three-dimensional cultivation. However, hypertrophy and osteogenic transdifferentiation are still limiting clinical applications. The aim of this study was to investigate the impact of small...... stem cells by single-cell elasticity measurements using atomic force microscopy. Results were matched with single-cell size measurements (diameter and volume) and quantitative real time-polymerase chain reaction for osteogenic and hypertrophic (alkaline phosphatase [ALP], collagen type X) as well...... a significantly lower deformability than chondrocytes (Young's modulus: 294.4 vs. 225.1 Pa; ANOVA: pstem cell elasticity to chondrocyte values (221.7 Pa). All other chondrogenic differentiated ASCs presented intermediate elasticity (BMP-2 stimulation: 269.1 Pa...

  8. Hypertrophic Obesity and Subcutaneous Adipose Tissue Dysfunction

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    Anna Meiliana

    2014-08-01

    Full Text Available BACKGROUND: Over the past 50 years, scientists have recognized that not all adipose tissue is alike, and that health risk is associated with the location as well as the amount of body fat. Different depots are sufficiently distinct with respect to fatty-acid storage and release as to probably play unique roles in human physiology. Whether fat redistribution causes metabolic disease or whether it is a marker of underlying processes that are primarily responsible is an open question. CONTENT: The limited expandability of the subcutaneous adipose tissue leads to inappropriate adipose cell expansion (hypertrophic obesity with local inflammation and a dysregulated and insulin-resistant adipose tissue. The inability to store excess fat in the subcutaneous adipose tissue is a likely key mechanism for promoting ectopic fat accumulation in tissues and areas where fat can be stored, including the intra-abdominal and visceral areas, in the liver, epi/pericardial area, around vessels, in the myocardium, and in the skeletal muscles. Many studies have implicated ectopic fat accumulation and the associated lipotoxicity as the major determinant of the metabolic complications of obesity driving systemic insulin resistance, inflammation, hepatic glucose production, and dyslipidemia. SUMMARY: In summary, hypertrophic obesity is due to an impaired ability to recruit and differentiate available adipose precursor cells in the subcutaneous adipose tissue. Thus, the subcutaneous adipose tissue may be particular in its limited ability in certain individuals to undergo adipogenesis during weight increase. Inability to promote subcutaneous adipogenesis under periods of affluence would favor lipid overlow and ectopic fat accumulation with negative metabolic consequences. KEYWORDS: obesity, adipogenesis, subcutaneous adipose tissue, visceral adipose tissue, adipocyte dysfunction.

  9. Visceral Leishmaniasis Treated with Antimonials/Paromomycin followed by Itraconazole/Miltefosine after Standard Therapy Failures in a Human Immunodeficiency Virus–Infected Patient

    OpenAIRE

    Barragán, Patricia; López-Velez, Rogelio; Olmo, Montserrat; Podzamczer, Daniel

    2010-01-01

    Visceral leishmaniasis is an opportunistic infection that affects human immunodeficiency virus–infected persons in leishmaniasis-endemic areas. The standard treatment may not be effective and relapses are common. We report the case of a human immunodeficiency virus-1–infected patient who had several relapses of visceral leishmaniasis after treatment with standard therapies and responded to a combined therapy.

  10. Effect of functional sympathetic nervous system impairment of the liver and abdominal visceral adipose tissue on circulating triglyceride-rich lipoproteins.

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    Michael F La Fountaine

    Full Text Available Interruption of sympathetic innervation to the liver and visceral adipose tissue (VAT in animal models has been reported to reduce VAT lipolysis and hepatic secretion of very low density lipoprotein (VLDL and concentrations of triglyceride-rich lipoprotein particles. Whether functional impairment of sympathetic nervous system (SNS innervation to tissues of the abdominal cavity reduce circulating concentrations of triglyceride (TG and VLDL particles (VLDL-P was tested in men with spinal cord injury (SCI.One hundred-three non-ambulatory men with SCI [55 subjects with neurologic injury at or proximal to the 4th thoracic vertebrae (↑T4; 48 subjects with SCI at or distal to the 5th thoracic vertebrae (↓T5] and 53 able-bodied (AB subjects were studied. Fasting blood samples were obtained for determination of TG, VLDL-P concentration by NMR spectroscopy, serum glucose by autoanalyzer, and plasma insulin by radioimmunoassay. VAT volume was determined by dual energy x-ray absorptiometry imaging with calculation by a validated proprietary software package.Significant group main effects for TG and VLDL-P were present; post-hoc tests revealed that serum TG concentrations were significantly higher in ↓T5 group compared to AB and ↑T4 groups [150±9 vs. 101±8 (p<0.01 and 112±8 mg/dl (p<0.05, respectively]. VLDL-P concentration was significantly elevated in ↓T5 group compared to AB and ↑T4 groups [74±4 vs. 58±4 (p<0.05 and 55±4 μmol/l (p<0.05]. VAT volume was significantly higher in both SCI groups than in the AB group, and HOMA-IR was higher and approached significance in the SCI groups compared to the AB group. A linear relationship between triglyceride rich lipoproteins (i.e., TG or Large VLDL-P and VAT volume or HOMA-IR was significant only in the ↓T5 group.Despite a similar VAT volume and insulin resistance in both SCI groups, the ↓T5 group had significantly higher serum TG and VLDL-P values than that observed in the ↑T4 and the AB

  11. Whole-Body Vibration Partially Reverses Aging-Induced Increases in Visceral Adiposity and Hepatic Lipid Storage in Mice.

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    Aaffien C Reijne

    Full Text Available At old age, humans generally have declining muscle mass and increased fat deposition, which can increase the risk of developing cardiometabolic diseases. While regular physical activity postpones these age-related derangements, this is not always possible in the elderly because of disabilities or risk of injury. Whole-body vibration (WBV training may be considered as an alternative to physical activity particularly in the frail population. To explore this possibility, we characterized whole-body and organ-specific metabolic processes in 6-month and 25-month old mice, over a period of 14 weeks of WBV versus sham training. WBV training tended to increase blood glucose turnover rates and stimulated hepatic glycogen utilization during fasting irrespective of age. WBV was effective in reducing white fat mass and hepatic triglyceride content only in old but not in young mice and these reductions were related to upregulation of hepatic mitochondrial uncoupling of metabolism (assessed by high-resolution respirometry and increased expression of uncoupling protein 2. Because these changes occurred independent of changes in food intake and whole-body metabolic rate (assessed by indirect calorimetry, the liver-specific effects of WBV may be a primary mechanism to improve metabolic health during aging, rather than that it is a consequence of alterations in energy balance.

  12. An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Reducing Visceral Adiposity

    Science.gov (United States)

    Liau, Kai Ming; Lee, Yeong Yeh; Chen, Chee Keong; Rasool, Aida Hanum G.

    2011-01-01

    Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans. PMID:22164340

  13. Interleukin-6 production in human subcutaneous abdominal adipose tissue

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    Lyngsø, Dorthe; Simonsen, Lene; Bülow, Jens

    2002-01-01

    The interleukin-6 (IL-6) output from subcutaneous, abdominal adipose tissue was studied in nine healthy subjects before, during and for 3 h after 1 h two-legged bicycle exercise at 60 % maximal oxygen consumption. Seven subjects were studied in control experiments without exercise. The adipose...

  14. Human case of visceral larva migrans syndrome: pulmonary and hepatic involvement

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    Almatary A. M.

    2016-12-01

    Full Text Available Visceral Larva Migrans (VLM syndrome is commonly caused by larvae of roundworms Toxocara canis or Toxocara cati. Human toxocarosis is a soil-transmitted zoonosis, which may result in partial or general pathological changes in host tissues. We reported a case of 14-year-old boy presented with severe dry cough without dyspnea, mild chest and abdominal pain with general fatigue. Examination of peripheral blood showed marked increase in eosinophils. The chest radiography showed an infiltrative shadow in the lung fields. Chest CT demonstrated multiple opacities in both lungs. Abdominal CT showed multiple low attenuation areas in the liver. Ultrasound guided liver biopsy revealed granulomas with severe eosinophilic infiltration. The boy was treated with albendazole and responded radically. It is worth mentioning that this is the first case of hepato-pulmonary VLM syndrome in Egypt.

  15. Brain-derived neurotrophic factor in VMH as the causal factor for and therapeutic tool to treat visceral adiposity and hyperleptinemia in type 2 diabetic Goto-Kakizaki rats

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    Fumihiko eMaekawa

    2013-10-01

    Full Text Available We previously reported that the type 2 diabetic Goto-Kakizaki (GK rats at young adult ages (6-12 weeks exhibited increased visceral fat mass and hyperleptinemia, due to hyperphagia caused primarily by neuropeptide Y (NPY overexpression in the hypothalamic arcuate nucleus. Later, we found that GK rats continued to exhibit mesenteric fat accumulation and hyperleptinemia at least until 26 weeks of age, while hyperphagia and NPY overexpression ceased at 15 weeks of age. Therefore, we hypothesized that the long-lasting fat accumulation and hyperleptinemia are due to unidentified brain dysfunction other than NPY overexpression. In GK rats aged 26 weeks, glucose transporter-2 (GLUT2 mRNA expression in ventromedial hypothalamus (VMH was markedly reduced in parallel with significant decreases in brain-derived neurotrophic factor (BDNF mRNA level and BDNF-expressing cell numbers in the VMH. Pharmacologic inhibition of glucose utilization reduced BDNF mRNA expression in VMH in vivo and in vitro. The results suggested that impaired glucose utilization caused the reduction of BDNF. On the other hand, intracerebroventricular injection of BDNF for 6 days ameliorated hyperleptinemia in a long-lasting manner concurrently with feeding suppression in GK rats. Restricted feeding paired to BDNF-treated rats reduced plasma leptin level only transiently. BDNF treatment also reduced mesenteric fat mass in GK rats. These results reveal a novel action mode of BDNF to long-lastingly counteract visceral adiposity and hyperleptinemia in addition to and independently of its anorexigenic action. These results suggest that visceral fat accumulation and hyperleptinemia are at least partly due to the reduction of BDNF in VMH primarily caused by impaired glucose utilization in GK rats. The BDNF supplementation could provide an effective treatment of visceral obesity, hyperleptinemia and leptin resistance in type 2 diabetes.

  16. Brain-derived neurotrophic factor in VMH as the causal factor for and therapeutic tool to treat visceral adiposity and hyperleptinemia in type 2 diabetic Goto-Kakizaki rats.

    Science.gov (United States)

    Maekawa, Fumihiko; Fujiwara, Ken; Toriya, Masako; Maejima, Yuko; Nishio, Takashi; Toyoda, Yukiyasu; Nohara, Keiko; Yashiro, Takashi; Yada, Toshihiko

    2013-01-01

    We previously reported that the type 2 diabetic Goto-Kakizaki (GK) rats at young adult ages (6-12 weeks) exhibited increased visceral fat mass and hyperleptinemia, due to hyperphagia caused primarily by neuropeptide Y (NPY) overexpression in the hypothalamic arcuate nucleus. Later, we found that GK rats continued to exhibit mesenteric fat accumulation and hyperleptinemia at least until 26 weeks of age, while hyperphagia and NPY overexpression ceased at 15 weeks of age. Therefore, we hypothesized that the long-lasting fat accumulation and hyperleptinemia are due to unidentified brain dysfunction other than NPY overexpression. In GK rats aged 26 weeks, glucose transporter-2 (GLUT2) mRNA expression in ventromedial hypothalamus (VMH) was markedly reduced in parallel with significant decreases in brain-derived neurotrophic factor (BDNF) mRNA level and BDNF-expressing cell numbers in the VMH. Pharmacologic inhibition of glucose utilization reduced BDNF mRNA expression in VMH in vivo and in vitro. The results suggested that impaired glucose utilization caused the reduction of BDNF. On the other hand, intracerebroventricular injection of BDNF for 6 days ameliorated hyperleptinemia in a long-lasting manner concurrently with feeding suppression in GK rats. Restricted feeding paired to BDNF-treated rats reduced plasma leptin level only transiently. BDNF treatment also reduced mesenteric fat mass in GK rats. These results reveal a novel action mode of BDNF to long-lastingly counteract visceral adiposity and hyperleptinemia in addition to and independently of its anorexigenic action. These results suggest that visceral fat accumulation and hyperleptinemia are at least partly due to the reduction of BDNF in VMH primarily caused by impaired glucose utilization in GK rats. The BDNF supplementation could provide an effective treatment of visceral obesity, hyperleptinemia and leptin resistance in type 2 diabetes.

  17. Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise

    DEFF Research Database (Denmark)

    Frydelund-Larsen, Lone; Åkerström, Thorbjörn; Nielsen, Søren

    2006-01-01

    Visfatin [pre-beta-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression...... by elevated levels of plasma visfatin. Recombinant human IL-6 infusion to mimic the exercise-induced IL-6 response (n = 6) had no effect on visfatin mRNA expression in adipose tissue compared with the effect of placebo infusion (n = 6). The finding that exercise enhances subcutaneous adipose tissue visfatin mRNA...... in abdominal subcutaneous adipose tissue and skeletal muscle biopsies obtained from healthy young men at time points 0, 3, 4.5, 6, 9, and 24 h in relation to either 3 h of ergometer cycle exercise at 60% of Vo(2 max) or rest. Adipose tissue visfatin mRNA expression increased threefold at the time points 3, 4...

  18. Mathematical modelling for Zoonotic Visceral Leishmaniasis dynamics: A new analysis considering updated parameters and notified human Brazilian data

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    Helio Junji Shimozako

    2017-05-01

    Full Text Available Brazil is one of the highest endemic countries for Zoonotic Visceral Leishmaniasis: according to the Brazilian Ministry of Health, the annual number of new human cases and deaths due to this disease has been increasing for the last 20 years. In addition, regarding the Americas, the specific relationship between canine and human for Visceral Leishmaniasis dynamics is still not well understood. In this work we propose a new model for Zoonotic Visceral Leishmaniasis, based on the models previously published by Burattini et al. (1998 and Ribas et al. (2013. Herein, we modeled the disease dynamics using a modified set of differential equations from those two authors, considering the same assumptions (inclusion of human, dog and sandfly populations, all constants over time. From this set of equations we were able to calculate the basic reproduction number R0 and to analyze the stability and sensitivity of the system to the parameters variability. As main result, when the stability of the system is reached, the normalized reporting human cases rate is estimated in 9.12E-08/day. This estimation is very close to the 2015 report from Araçatuba city, 5.69E-08/day. We also observed from stability and sensitivity analysis that the activity of sandfly population is critical to introduction and maintenance of Zoonotic Visceral Leishmaniasis in the population. In addition, the importance of dog as source of infection concentrates on latent dog, since it does not show clinical symptoms and signs and, therefore, has a great contribution to disease dissemination. As conclusion, considering the presently ethical issues regarding to elimination of positive dog in Brazil and the highly sensitivity of disease dynamics on sandfly population, we recommend that the sandfly population control should be prioritized. Keywords: Zoonotic Visceral Leishmaniasis, Disease dynamics, Mathematical modelling, Epidemiology

  19. Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring

    Science.gov (United States)

    Adipose tissue macrophages (ATM) are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. However, it is not known whether maternal undernutrition increases ATM phenotypic expression in F1 offspring. Us...

  20. Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity

    Science.gov (United States)

    Lackey, Denise E.; Lynch, Christopher J.; Olson, Kristine C.; Mostaedi, Rouzbeh; Ali, Mohamed; Smith, William H.; Karpe, Fredrik; Humphreys, Sandy; Bedinger, Daniel H.; Dunn, Tamara N.; Thomas, Anthony P.; Oort, Pieter J.; Kieffer, Dorothy A.; Amin, Rajesh; Bettaieb, Ahmed; Haj, Fawaz G.; Permana, Paska; Anthony, Tracy G.

    2013-01-01

    Elevated blood branched-chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metabolism. We tested if expression of the mitochondrial BCAA oxidation checkpoint, branched-chain α-ketoacid dehydrogenase (BCKD) complex, is reduced in obese WAT and regulated by metabolic signals. WAT BCKD protein (E1α subunit) was significantly reduced by 35–50% in various obesity models (fa/fa rats, db/db mice, diet-induced obese mice), and BCKD component transcripts significantly lower in subcutaneous (SC) adipocytes from obese vs. lean Pima Indians. Treatment of 3T3-L1 adipocytes or mice with peroxisome proliferator-activated receptor-γ agonists increased WAT BCAA catabolism enzyme mRNAs, whereas the nonmetabolizable glucose analog 2-deoxy-d-glucose had the opposite effect. The results support the hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT, as would be seen with insulin resistance/type 2 diabetes, could impair WAT BCAA utilization. However, cross-tissue flux studies comparing lean vs. insulin-sensitive or insulin-resistant obese subjects revealed an unexpected negligible uptake of BCAA from human abdominal SC WAT. This suggests that SC WAT may not be an important contributor to blood BCAA phenotypes associated with insulin resistance in the overnight-fasted state. mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental (but not SC) WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals. PMID:23512805

  1. Avaliação por imagem da área de gordura visceral e suas correlações com alterações metabólicas Evaluación por imagen del área de grasa visceral y sus correlaciones con alteraciones metabólicas Imaging assessment of visceral adipose tissue area and its correlations with metabolic alterations

    Directory of Open Access Journals (Sweden)

    Anna Karla Carneiro Roriz

    2010-12-01

    Full Text Available FUNDAMENTO: A obesidade androgênica está associada a um risco maior de distúrbios metabólicos, favorecendo assim a ocorrência de doenças cardiovasculares e outras morbidades. OBJETIVO: Verificar a influência da área de tecido adiposo visceral (ATAV, medida pela tomografia computadorizada, sobre alterações metabólicas em adultos e idosos. MÉTODOS: Tomografias computadorizadas e valores de lipoproteínas: o colesterol total e frações, os triglicérides, a glicemia e o ácido úrico foram obtidos de 194 indivíduos estratificados por sexo, grupo etário e massa corporal, e analisados utilizando os testes de correlação e de média. RESULTADOS: Os idosos apresentaram maiores valores da ATAV, glicemia, ácido úrico e colesterol total. As maiores correlações foram encontradas entre a ATAV, os triglicérides e o VLDL-c (r > 0,5; p FUNDAMENTO: La obesidad androgénica está asociada a un riesgo mayor de disturbios metabólicos, favoreciendo así la ocurrencia de enfermedades cardiovasculares y otras morbilidades. OBJETIVOS: Verificar la influencia del área de tejido adiposo visceral (ATAV, medida por la tomografía computarizada, sobre alteraciones metabólicas en adultos y adultos mayores. MÉTODOS: Tomografías computarizadas y valores de lipoproteínas: el colesterol total y fracciones, los triglicéridos, la glucemia y el ácido úrico se obtuvieron de 194 individuos estratificados por sexo, grupo de edad y masa corporal, y se analizaron utilizando las pruebas de correlación y de promedio. RESULTADOS: Los adultos mayores presentaron mayores valores de la ATAV, glucemia, ácido úrico y colesterol total. Las mayores correlaciones se encontraron entre la ATAV, los triglicéridos y el VLDL-c (r > 0,5; p BACKGROUND: Androgenic obesity is associated with a higher risk of metabolic disorders, thus favoring the occurrence of cardiovascular diseases and other morbidities. OBJECTIVE: To verify the influence of the visceral adipose tissue

  2. Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue

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    Ribeiro Ricardo

    2012-09-01

    Full Text Available Abstract Background Periprostatic (PP adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW and prostate cancer patients. Methods Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia. Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA was used to investigate gene ontology, canonical pathways and functional networks. Results In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated. Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis, whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH. Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients. Conclusions Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable

  3. Application of Recombinant Proteins for Serodiagnosis of Visceral Leishmaniasis in Humans and Dogs.

    Science.gov (United States)

    Farahmand, Mahin; Nahrevanian, Hossein

    2016-07-01

    Visceral leishmaniasis (VL) is a zoonotic disease caused by leishmania species. Dogs are considered to be the main reservoir of VL. A number of methods and antigen-based assays are used for the diagnosis of leishmaniasis. However, currently available methods are mainly based on direct examination of tissues for the presence of parasites, which is highly invasive. A variety of serological tests are commonly applied for VL diagnosis, including indirect fluorescence antibody test, enzyme-linked immunosorbent assay (ELISA), dot-ELISA, direct agglutination test, Western-blotting, and immunochromatographic test. However, when soluble antigens are used, serological tests are less specific due to cross-reactivity with other parasitic diseases. Several studies have attempted to replace soluble antigens with recombinant proteins to improve the sensitivity and the specificity of the immunodiagnostic tests. Major technological advances in recombinant antigens as reagents for the serological diagnosis of VL have led to high sensitivity and specificity of these serological tests. A great number of recombinant proteins have been shown to be effective for the diagnosis of leishmania infection in dogs, the major reservoir of L. infantum. Although few recombinant proteins with high efficacy provide reasonable results for the diagnosis of human and canine VL, more optimization is still needed for the appropriate antigens to provide high-throughput performance. This review aims to explore the application of different recombinant proteins for the serodiagnosis of VL in humans and dogs.

  4. Epidemiological and immunological aspects of human visceral leishmaniasis on Margarita Island, Venezuela.

    Science.gov (United States)

    Zerpa, Olga; Ulrich, Marian; Benitez, Margarita; Avila, Concepción; Rodríguez, Vestalia; Centeno, Marta; Belizario, Doris; Reed, Steven G; Convit, Jacinto

    2002-12-01

    Sixty-five patients were diagnosed with visceral leishmaniasis (VL) on Margarita Island in the decade from 1990 to1999; 86.2% were <= 3 years old. All were leishmanin-negative at diagnosis. Evaluation of 23 cured patients in 1999 revealed that 22/23 had converted to leishmanin-positive; five had persisting antibodies to rK39 antigen, with no clinical evidence of disease. Leishmanin tests were positive in 20.2% of 1,643 healthy individuals from 417 households in endemic areas. Of the positive reactors, 39.8% were identified in 35 (8.4%) of the households, 15 of which had an antecedent case of VL, a serologically positive dog or both. Weak serological activity to rK39 antigen was detected in 3 of 488 human sera from the endemic areas. The presence of micro-foci of intense peri-urban transmission and the apparent absence of other Trypanosomatidae causing human disease offer a unique opportunity for the study of reservoirs, alternative vectors and evaluation of control measures on the Island.

  5. The evolution of human adiposity and obesity: where did it all go wrong?

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    Jonathan C. K. Wells

    2012-09-01

    Full Text Available Because obesity is associated with diverse chronic diseases, little attention has been directed to the multiple beneficial functions of adipose tissue. Adipose tissue not only provides energy for growth, reproduction and immune function, but also secretes and receives diverse signaling molecules that coordinate energy allocation between these functions in response to ecological conditions. Importantly, many relevant ecological cues act on growth and physique, with adiposity responding as a counterbalancing risk management strategy. The large number of individual alleles associated with adipose tissue illustrates its integration with diverse metabolic pathways. However, phenotypic variation in age, sex, ethnicity and social status is further associated with different strategies for storing and using energy. Adiposity therefore represents a key means of phenotypic flexibility within and across generations, enabling a coherent life-history strategy in the face of ecological stochasticity. The sensitivity of numerous metabolic pathways to ecological cues makes our species vulnerable to manipulative globalized economic forces. The aim of this article is to understand how human adipose tissue biology interacts with modern environmental pressures to generate excess weight gain and obesity. The disease component of obesity might lie not in adipose tissue itself, but in its perturbation by our modern industrialized niche. Efforts to combat obesity could be more effective if they prioritized ‘external’ environmental change rather than attempting to manipulate ‘internal’ biology through pharmaceutical or behavioral means.

  6. Introduction and expansion of human American visceral leishmaniasis in the state of Sao Paulo, Brazil, 1999-2011.

    Science.gov (United States)

    Cardim, Marisa Furtado Mozini; Rodas, Lilian A Colebrusco; Dibo, Margareth Regina; Guirado, Marluci Monteiro; Oliveira, Agda Maria; Chiaravalloti-Neto, Francisco

    2013-08-01

    To analyze the spread of human American visceral leishmaniasis and identify the key municipalities for developing surveillance and control activities. The area of the study was composed of the 316 municipalities in the state of Sao Paulo belonging to the five health districts in which human American visceral leishmaniasis occurs, using data on autochthonous cases and deaths according to the reporting year and municipality in which the death occurred. The incidence, mortality and case fatality rates for each municipality and for the entire area were calculated. An empirical Bayes estimator was used to calculate the local Bayesian incidence and rates of mortality per municipality, and Kriging was used to visualize the spatial distribution of temperature and rainfall. A total of 73 municipalities with transmission of the disease were identified. Human American visceral leishmaniasis was first detected in areas with higher temperatures and lower rainfall, but it also spread in cooler and wetter areas. The expansion of human American visceral leishmaniasis occurred along a main axis of dissemination, from Northwest to Southeast, following the Marechal Rondon highway and the Bolivia-Brazil gas pipeline, and along a secondary axis that was derived from the main axis, which runs both North and South, following the highway network. Rates of incidence according to health district exhibit a peak, followed by a fall, except the Sao Jose do Rio Preto region. Higher concentrations of municipalities with high incidence and mortality rates were observed in the Araçatuba, Presidente Prudente and Marília health districts. This study indicates possible determinants of the spread of disease, including the Marechal Rondon highway and the construction of the Bolivia-Brazil gas pipeline. Climatic factors seemed to play no role in the spread. The use of spatial analysis techniques allowed the municipalities where cases and deaths are possibly underreported to be identified, which

  7. QBC® for the diagnosis of human and canine american visceral leishmaniasis: preliminary data

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    Liarte Daniel B.

    2001-01-01

    Full Text Available "Quantitative Buffy Coat" (QBC® is a direct and fast fluorescent method used for the identification of blood parasites. Since Leishmania chagasi circulates in blood, we decided to test it in American visceral leishmaniasis (AVL. Bone marrow (BM and peripheral blood (PB of 49 persons and PB of 31 dogs were analyzed. QBC® was positive in BM of 11/11 patients with AVL and in 1/6 patients with other diseases. Amastigotes were identified in PB of 18/22 patients with AVL and in none without AVL. The test was positive in 30 out of the 31 seropositive dogs and in 28/28 dogs with Leishmania identified in other tissues. QBC® is a promising method for diagnosis of human AVL, and possibly for the exam of PB of patients with AVL/AIDS, for the control of the cure and for the identification of asymptomatic carriers. Because it is fast and easy to collect and execute, QBC® should be evaluated for programs of reservoir control.

  8. Effect of Bariatric Weight Loss on the Adipose Lipolytic Transcriptome in Obese Humans.

    Science.gov (United States)

    Karki, Shakun; Farb, Melissa G; Myers, Samantha; Apovian, Caroline; Hess, Donald T; Gokce, Noyan

    2015-01-01

    Dysregulated lipolysis has been implicated in mechanisms of cardiometabolic disease and inflammation in obesity. We sought to examine the effect of bariatric weight loss on adipose tissue lipolytic gene expression and their relationship to systemic metabolic parameters in obese subjects. We biopsied subcutaneous adipose tissue in 19 obese individuals (BMI 42 ± 5 kg/m(2), 79% female) at baseline and after a mean period of 8 ± 5 months (range 3-15 months) following bariatric surgery. We performed adipose tissue mRNA expression of proteins involved in triglyceride hydrolysis and correlated their weight loss induced alterations with systemic parameters associated with cardiovascular disease risk. mRNA transcripts of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and lipid droplet proteins comparative gene identification 58 (CGI-58) and perilipin increased significantly after weight loss (p adipose tissue lipolytic genes following bariatric weight loss which correlated inversely with systemic markers of lipid and glucose metabolism. Functional alterations in lipolysis in human adipose tissue may play a role in shaping cardiometabolic phenotypes in human obesity.

  9. Effect of Bariatric Weight Loss on the Adipose Lipolytic Transcriptome in Obese Humans

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    Shakun Karki

    2015-01-01

    Full Text Available Background. Dysregulated lipolysis has been implicated in mechanisms of cardiometabolic disease and inflammation in obesity. Purpose. We sought to examine the effect of bariatric weight loss on adipose tissue lipolytic gene expression and their relationship to systemic metabolic parameters in obese subjects. Methods/Results. We biopsied subcutaneous adipose tissue in 19 obese individuals (BMI 42 ± 5 kg/m2, 79% female at baseline and after a mean period of 8 ± 5 months (range 3–15 months following bariatric surgery. We performed adipose tissue mRNA expression of proteins involved in triglyceride hydrolysis and correlated their weight loss induced alterations with systemic parameters associated with cardiovascular disease risk. mRNA transcripts of adipose triglyceride lipase (ATGL, hormone-sensitive lipase (HSL, and lipid droplet proteins comparative gene identification 58 (CGI-58 and perilipin increased significantly after weight loss (p<0.05 for all. ATGL expression correlated inversely with plasma triglyceride (TG, hemoglobin A1C (HbA1C, and glucose, and HSL expression correlated negatively with glucose, while CGI-58 was inversely associated with HbA1C. Conclusion. We observed increased expression of adipose tissue lipolytic genes following bariatric weight loss which correlated inversely with systemic markers of lipid and glucose metabolism. Functional alterations in lipolysis in human adipose tissue may play a role in shaping cardiometabolic phenotypes in human obesity.

  10. Immunity to Visceral Leishmaniasis

    OpenAIRE

    Ali, Nahid; Mekuria, Asrat Hailu; Requena, José María; Engwerda, Christian

    2012-01-01

    Leishmaniasis is a major vector-borne parasitic disease affecting 12 million people worldwide. With a broad range of clinical manifestations, ranging from self-healing skin ulcers to disfiguring mucosal lesions to life-threatening infections of visceral organs (liver and spleen), the disease has become a serious human health issue, particularly in developing countries. Among all of its forms, visceral leishmaniasis (VL, also known as kala-azar), caused by the Leishmania donovani complex (i.e....

  11. Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring.

    Directory of Open Access Journals (Sweden)

    Linglin Xie

    Full Text Available Adipose tissue macrophages (ATM are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. The study aims to answer whether maternal undernutrition by protein restriction affects the ATM M1 or M2 phenotype under postnatal high fat diet in F1 offspring. Using a rat model of prenatal low protein (LP, 8% protein diet followed by a postnatal high fat energy diet (HE, 45% fat or low fat normal energy diet (NE, 10% fat for 12 weeks, we investigated the effects of these diets on adiposity, programming of the offspring ATM phenotype, and the associated inflammatory response in adipose tissue. Fat mass in newborn and 12-week old LP fed offspring was lower than that of normal protein (20%; NP fed offspring; however, the adipose tissue growth rate was higher compared to the NP fed offspring. While LP did not affect the number of CD68+ or CD206+ cells in adipose tissue of NE offspring, it attenuated the number of these cells in offspring fed HE. In offspring fed HE, LP offspring had a lower percentage of CD11c+CD206+ ATMs, whose abundancy was correlated with the size of the adipocytes. Noteworthy, similar to HE treatment, LP increased gene expression of IL-6 within ATMs. Two-way ANOVA showed an interaction of prenatal LP and postnatal HE on IL-6 and IL-1β transcription. Overall, both LP and HE diets impact ATM phenotype by affecting the ratio of CD11c+CD206+ ATMs and the expression of IL-6.

  12. Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis.

    Science.gov (United States)

    Cecílio, Pedro; Pérez-Cabezas, Begoña; Fernández, Laura; Moreno, Javier; Carrillo, Eugenia; Requena, José M; Fichera, Epifanio; Reed, Steven G; Coler, Rhea N; Kamhawi, Shaden; Oliveira, Fabiano; Valenzuela, Jesus G; Gradoni, Luigi; Glueck, Reinhard; Gupta, Gaurav; Cordeiro-da-Silva, Anabela

    2017-11-01

    The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the "natural infection".

  13. Canine leishmaniosis and its relationship to human visceral leishmaniasis in Eastern Uzbekistan.

    Science.gov (United States)

    Kovalenko, Dmitriy A; Razakov, Shavkat A; Ponirovsky, Evgeny N; Warburg, Alon; Nasyrova, Rokhat M; Ponomareva, Valentina I; Fatullaeva, Aziza A; Nasereddin, Abdelmajeed; Klement, Eyal; Alam, Mohammad Z; Schnur, Lionel F; Jaffe, Charles L; Schönian, Gabriele; Baneth, Gad

    2011-04-13

    The Namangan Region in the Pap District, located in Eastern Uzbekistan is the main focus of visceral leishmaniasis (VL) in Uzbekistan. In total, 28 cases of human VL were registered during 2006-2008 in this region. A study on the epidemiology of VL in this area was carried out in 2007-2008 in the villages of Chodak, Oltinkan, Gulistan and Chorkesar located at elevations of 900-1200 above sea level. A total of 162 dogs were tested for Leishmania infection. Blood was drawn for serology and PCR. When clinical signs of the disease were present, aspirates from lymph nodes and the spleen were taken. Forty-two dogs (25.9%) had clinical signs suggestive of VL and 51 (31.5%) were sero-positive. ITS-1 PCR was performed for 135 dogs using blood and tissue samples and 40 (29.6%) of them were PCR-positive. Leishmanial parasites were cultured from lymph node or spleen aspirates from 10 dogs.Eight Leishmania strains isolated from dogs were typed by multi-locus microsatellite typing (MLMT) and by multilocus enzyme electrophoretic analysis (MLEE), using a 15 enzyme system. These analyses revealed that the strains belong to the most common zymodeme of L. infantum, i.e., MON-1, and form a unique group when compared to MON-1 strains from other geographical regions. The data obtained through this study confirm the existence of an active focus of VL in the Namangan region of Uzbekistan. The fact that L. infantum was the causative agent of canine infection with typical clinical signs, and also of human infection affecting only infants, suggests that a zoonotic form of VL similar in epidemiology to Mediterranean VL is present in Uzbekistan.

  14. Effect of training on epinephrine-stimulated lipolysis determined by microdialysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, B; Simonsen, L; Bülow, J

    1995-01-01

    Trained humans (Tr) have a higher fat oxidation during submaximal physical work than sedentary humans (Sed). To investigate whether this reflects a higher adipose tissue lipolytic sensitivity to catecholamines, we infused epinephrine (0.3 nmol.kg-1.min-1) for 65 min in six athletes and six...

  15. Effect of extracellular vesicles of human adipose tissue on insulin signaling in liver and muscle cells

    NARCIS (Netherlands)

    Kranendonk, Mariëtte E G; Visseren, Frank L J; van Herwaarden, Joost A; Nolte-'t Hoen, Esther N M; de Jager, Wilco; Wauben, Marca H M; Kalkhoven, Eric; Nolte - t Hoen, Esther

    2014-01-01

    OBJECTIVE: Insulin resistance (IR) is a key mechanism in obesity-induced cardiovascular disease. To unravel mechanisms whereby human adipose tissue (AT) contributes to systemic IR, the effect of human AT-extracellular vesicles (EVs) on insulin signaling in liver and muscle cells was determined.

  16. Effect of training on epinephrine-stimulated lipolysis determined by microdialysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, Bente; Simonsen, L; Bülow, J

    1995-01-01

    Trained humans (Tr) have a higher fat oxidation during submaximal physical work than sedentary humans (Sed). To investigate whether this reflects a higher adipose tissue lipolytic sensitivity to catecholamines, we infused epinephrine (0.3 nmol.kg-1.min-1) for 65 min in six athletes and six sedent...

  17. Brown adipose tissue activation is linked to distinct systemic effects on lipid metabolism in humans

    Science.gov (United States)

    Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditio...

  18. Distinct regulation of hypothalamic and brown/beige adipose tissue activities in human obesity.

    Science.gov (United States)

    Rachid, B; van de Sande-Lee, S; Rodovalho, S; Folli, F; Beltramini, G C; Morari, J; Amorim, B J; Pedro, T; Ramalho, A F; Bombassaro, B; Tincani, A J; Chaim, E; Pareja, J C; Geloneze, B; Ramos, C D; Cendes, F; Saad, M J A; Velloso, L A

    2015-10-01

    The identification of brown/beige adipose tissue in adult humans has motivated the search for methods aimed at increasing its thermogenic activity as an approach to treat obesity. In rodents, the brown adipose tissue is under the control of sympathetic signals originating in the hypothalamus. However, the putative connection between the depots of brown/beige adipocytes and the hypothalamus in humans has never been explored. The objective of this study was to evaluate the response of the hypothalamus and brown/beige adipose tissue to cold stimulus in obese subjects undergoing body mass reduction following gastric bypass. We evaluated twelve obese, non-diabetic subjects undergoing Roux-in-Y gastric bypass and 12 lean controls. Obese subjects were evaluated before and approximately 8 months after gastric bypass. Lean subjects were evaluated only at admission. Subjects were evaluated for hypothalamic activity in response to cold by functional magnetic resonance, whereas brown/beige adipose tissue activity was evaluated using a (F 18) fluorodeoxyglucose positron emisson tomography/computed tomography scan and real-time PCR measurement of signature genes. Body mass reduction resulted in a significant increase in brown/beige adipose tissue activity in response to cold; however, no change in cold-induced hypothalamic activity was observed after body mass reduction. No correlation was found between brown/beige adipose tissue activation and hypothalamus activity in obese subjects or in lean controls. In humans, the increase in brown/beige adipose tissue activity related to body mass reduction occurs independently of changes in hypothalamic activity as determined by functional magnetic resonance.

  19. Possibility of Undifferentiated Human Thigh Adipose Stem Cells Differentiating into Functional Hepatocytes

    Directory of Open Access Journals (Sweden)

    Jong Hoon Lee

    2012-11-01

    Full Text Available BackgroundThis study aimed to investigate the possibility of isolating mesenchymal stem cells (MSCs from human thigh adipose tissue and the ability of human thigh adipose stem cells (HTASCs to differentiate into hepatocytes.MethodsThe adipose-derived stem cells (ADSCs were isolated from thigh adipose tissue. Growth factors, cytokines, and hormones were added to the collagen coated dishes to induce the undifferentiated HTASCs to differentiate into hepatocyte-like cells. To confirm the experimental results, the expression of hepatocyte-specific markers on undifferentiated and differentiated HTASCs was analyzed using reverse transcription polymerase chain reaction and immunocytochemical staining. Differentiation efficiency was evaluated using functional tests such as periodic acid schiff (PAS staining and detection of the albumin secretion level using enzyme-linked immunosorbent assay (ELISA.ResultsThe majority of the undifferentiated HTASCs were changed into a more polygonal shape showing tight interactions between the cells. The differentiated HTASCs up-regulated mRNA of hepatocyte markers. Immunocytochemical analysis showed that they were intensely stained with anti-albumin antibody compared with undifferentiated HTASCs. PAS staining showed that HTASCs submitted to the hepatocyte differentiation protocol were able to more specifically store glycogen than undifferentiated HTASCs, displaying a purple color in the cytoplasm of the differentiated HTASCs. ELISA analyses showed that differentiated HTASCs could secrete albumin, which is one of the hepatocyte markers.ConclusionsMSCs were islolated from human thigh adipose tissue differentiate to heapatocytes. The source of ADSCs is not only abundant abdominal adipose tissue, but also thigh adipose tissue for cell therapy in liver regeneration and tissue regeneration.

  20. Normal human adipose tissue functions and differentiation in patients with biallelic LPIN1 inactivating mutations.

    Science.gov (United States)

    Pelosi, Michele; Testet, Eric; Le Lay, Soazig; Dugail, Isabelle; Tang, Xiaoyun; Mabilleau, Guillaume; Hamel, Yamina; Madrange, Marine; Blanc, Thomas; Odent, Thierry; McMullen, Todd P W; Alfò, Marco; Brindley, David N; de Lonlay, Pascale

    2017-12-01

    Lipin-1 is a Mg2+-dependent phosphatidic acid phosphatase (PAP) that in mice is necessary for normal glycerolipid biosynthesis, controlling adipocyte metabolism, and adipogenic differentiation. Mice carrying inactivating mutations in the Lpin1 gene display the characteristic features of human familial lipodystrophy. Very little is known about the roles of lipin-1 in human adipocyte physiology. Apparently, fat distribution and weight is normal in humans carrying LPIN1 inactivating mutations, but a detailed analysis of adipose tissue appearance and functions in these patients has not been available so far. In this study, we performed a systematic histopathological, biochemical, and gene expression analysis of adipose tissue biopsies from human patients harboring LPIN1 biallelic inactivating mutations and affected by recurrent episodes of severe rhabdomyolysis. We also explored the adipogenic differentiation potential of human mesenchymal cell populations derived from lipin-1 defective patients. White adipose tissue from human LPIN1 mutant patients displayed a dramatic decrease in lipin-1 protein levels and PAP activity, with a concomitant moderate reduction of adipocyte size. Nevertheless, the adipose tissue develops without obvious histological signs of lipodystrophy and with normal qualitative composition of storage lipids. The increased expression of key adipogenic determinants such as SREBP1, PPARG, and PGC1A shows that specific compensatory phenomena can be activated in vivo in human adipocytes with deficiency of functional lipin-1. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  1. Decellularized adipose tissue microcarriers as a dynamic culture platform for human adipose-derived stem/stromal cell expansion.

    Science.gov (United States)

    Yu, Claire; Kornmuller, Anna; Brown, Cody; Hoare, Todd; Flynn, Lauren E

    2017-03-01

    With the goal of designing a clinically-relevant expansion strategy for human adipose-derived stem/stromal cells (ASCs), methods were developed to synthesize porous microcarriers derived purely from human decellularized adipose tissue (DAT). An electrospraying approach was applied to generate spherical DAT microcarriers with an average diameter of 428 ± 41 μm, which were soft, compliant, and stable in long-term culture without chemical crosslinking. Human ASCs demonstrated enhanced proliferation on the DAT microcarriers relative to commercially-sourced Cultispher-S microcarriers within a spinner culture system over 1 month. ASC immunophenotype was maintained post expansion, with a trend for reduced expression of the cell adhesion receptors CD73, CD105, and CD29 under dynamic conditions. Upregulation of the early lineage-specific genes PPARγ, LPL, and COMP was observed in the ASCs expanded on the DAT microcarriers, but the cells retained their multilineage differentiation capacity. Comparison of adipogenic and osteogenic differentiation in 2-D cultures prepared with ASCs pre-expanded on the DAT microcarriers or Cultispher-S microcarriers revealed similar adipogenic and enhanced osteogenic marker expression in the DAT microcarrier group, which had undergone a higher population fold change. Further, histological staining results suggested a more homogeneous differentiation response in the ASCs expanded on the DAT microcarriers as compared to either Cultispher-S microcarriers or tissue culture polystyrene. A pilot chondrogenesis study revealed higher levels of chondrogenic gene and protein expression in the ASCs expanded on the DAT microcarriers relative to all other groups, including the baseline controls. Overall, this study demonstrates the promise of applying dynamic culture with tissue-specific DAT microcarriers as a means of deriving regenerative cell populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients

    Directory of Open Access Journals (Sweden)

    Wim Adriaensen

    2018-01-01

    Full Text Available Patients with visceral leishmaniasis (VL–human immunodeficiency virus (HIV coinfection experience increased drug toxicity and treatment failure rates compared to VL patients, with more frequent VL relapse and death. In the era of VL elimination strategies, HIV coinfection is progressively becoming a key challenge, because HIV-coinfected patients respond poorly to conventional VL treatment and play an important role in parasite transmission. With limited chemotherapeutic options and a paucity of novel anti-parasitic drugs, new interventions that target host immunity may offer an effective alternative. In this review, we first summarize current views on how VL immunopathology is significantly affected by HIV coinfection. We then review current clinical and promising preclinical immunomodulatory interventions in the field of VL and discuss how these may operate in the context of a concurrent HIV infection. Caveats are formulated as these interventions may unpredictably impact the delicate balance between boosting of beneficial VL-specific responses and deleterious immune activation/hyperinflammation, activation of latent provirus or increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a target molecule and a more detailed account of the immunological status induced by the coinfection as well as surrogate markers of cure and protection are still required. We do, however, argue that virologically suppressed VL patients with a recovered immune system, in whom effective antiretroviral therapy alone is not able to restore protective immunity, can be considered a relevant target group for an immunomodulatory intervention. Finally, we provide perspectives on the translation of novel theories on synergistic immune cell cross-talk into an effective treatment strategy for VL–HIV-coinfected patients.

  3. Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats.

    Directory of Open Access Journals (Sweden)

    Ichiro Tokubuchi

    Full Text Available Metformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats.In human studies, metformin (1500mg/day was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin. In animal studies, 13 weeks old SD rats were fed 25-26 g of standard chow only during 12-hours dark phase with either treated by metformin (2.5mg/ml in drinking water or not for 2 weeks, and metabolic parameters, anthropometric factors and energy metabolism together with expressions related to fat oxidation and adaptive thermogenesis were measured either in fasting or post-prandial state at 15 weeks old.Post-prandial plasma lactate concentration was significantly increased after the metformin treatment in both healthy subjects and diabetic patients. Although energy expenditure (EE did not change, baseline respiratory quotient (RQ was significantly decreased and post-prandial RQ was significantly increased vice versa following the metformin treatment in both groups. By the administration of metformin to SD rats for 2 weeks, plasma levels of lactate and pyruvate were significantly increased in both fasting and post-prandial states. RQ during a fasting state was significantly decreased in metformin-treated rats compared to controls with no effect on EE. Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle.From the results obtained, beneficial effects of metformin on visceral fat reduction has been

  4. Isolation of Leishmania infantum, zymodeme MON-1 from canine and human visceral leishmaniasis on Margarita Island, Venezuela.

    Science.gov (United States)

    Zerpa, O; Pratlong, F; Ulrich, M; Convit, J

    2001-10-01

    An increase in the incidence of human visceral leishmaniasis (HVL) has been detected in recent years on Margarita Island, located off the NE coast of Venezuela. Recent studies have revealed reactivity to rK39 antigen (Leishmania chagasi) in 20% of 541 sera from domestic dogs in endemic communities; PCR reactions were positive using primers for the L. donovani complex. Here we report that isolates from human and canine infection, identified by isoenzyme analysis, correspond to L. infantum, zymodeme MON-1. This appears to be the first isolation and identification of an isolate from HVL on Margarita Island and demonstrates the presence of this zymodeme in the canine population.

  5. Human breast adipose tissue: characterization of factors that change during tumor progression in human breast cancer.

    Science.gov (United States)

    Fletcher, Sabrina Johanna; Sacca, Paula Alejandra; Pistone-Creydt, Mercedes; Coló, Federico Andrés; Serra, María Florencia; Santino, Flavia Eliana; Sasso, Corina Verónica; Lopez-Fontana, Constanza Matilde; Carón, Rubén Walter; Calvo, Juan Carlos; Pistone-Creydt, Virginia

    2017-02-07

    Adipose microenvironment is involved in signaling pathways that influence breast cancer. We aim to characterize factors that are modified: 1) in tumor and non tumor human breast epithelial cell lines when incubated with conditioned media (CMs) from human breast cancer adipose tissue explants (hATT) or normal breast adipose tissue explants (hATN); 2) in hATN-CMs vs hATT-CMs; 3) in the tumor associated adipocytes vs. non tumor associated adipocytes. We used hATN or hATT- CMs on tumor and non-tumor breast cancer cell lines. We evaluated changes in versican, CD44, ADAMTS1 and Adipo R1 expression on cell lines or in the different CMs. In addition we evaluated changes in the morphology and expression of these factors in slices of the different adipose tissues. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post-hoc tests were performed within each individual treatment. hATT-CMs increase versican, CD44, ADAMTS1 and Adipo R1 expression in breast cancer epithelial cells. Furthermore, hATT-CMs present higher levels of versican expression compared to hATN-CMs. In addition, we observed a loss of effect in cellular migration when we pre-incubated hATT-CMs with chondroitinase ABC, which cleaves GAGs chains bound to the versican core protein, thus losing the ability to bind to CD44. Adipocytes associated with the invasive front are reduced in size compared to adipocytes that are farther away. Also, hATT adipocytes express significantly higher amounts of versican, CD44 and Adipo R1, and significantly lower amounts of adiponectin and perilipin, unlike hATN adipocytes. We conclude that hATT secrete a different set of proteins compared to hATN. Furthermore, versican, a proteoglycan that is overexpressed in hATT-CMs compared to hATN-CMs, might be involved in the tumorogenic behavior observed in both cell lines employed. In addition, we may conclude that adipocytes from the tumor microenvironment show a less differentiated

  6. Comparison of Endothelial Differentiation Capacities of Human and Rat Adipose-Derived Stem Cells.

    Science.gov (United States)

    Orbay, Hakan; Devi, Kamaljit; Williams, Priscilla A; Dehghani, Tima; Silva, Eduardo A; Sahar, David E

    2016-12-01

    The authors compared the endothelial differentiation capacities of human and rat adipose-derived stem cells to determine whether human adipose-derived stem cells can be a source of endothelial cells clinically. Human and rat adipose-derived stem cells were harvested and characterized with flow cytometry and trilineage differentiation. Cells from passages III through V were fed with endothelial cell differentiation medium for up to 3 weeks. Cells were harvested after 1, 2, and 3 weeks, and endothelial differentiation was evaluated with quantitative reverse-transcriptase polymerase chain reaction, flow cytometry, and angiogenic sprouting assays. Both human and rat adipose-derived stem cells were CD90, CD44, and CD31 before differentiation. The cells were successfully differentiated into adipogenic, osteogenic, and chondrogenic lineages. Expression of endothelial cell-specific genes peaked at the second week of differentiation in both human and rat cells. The fold changes in expression of CD31, vascular endothelial growth factor receptor-1, nitric oxide synthase, and von Willebrand factor genes at week 2 were 0.4 ± 0.1, 34.7 ± 0.3, 2.03 ± 0.25, and 12.5 ± 0.3 respectively, in human adipose-derived stem cells; and 1.5 ± 1.01, 21.6 ± 1.7, 17.9 ± 0.6, and 11.2 ± 1.3, respectively, in rat cells. The percentages of CD31 cells were 0.2, 0.64, and 1.6 in human cell populations and 0.5, 5.91, and 11.5 in rat cell populations at weeks 1, 2, and 3, respectively. Rat adipose-derived stem cell-derived endothelial cells displayed enhanced sprouting capability compared with the human cells. Human adipose-derived stem cells responded less strongly to EGM-2MV endothelial differentiation medium than did the rat cells. Still, the human cells have the potential to become a clinical source of endothelial cells with modifications in the differentiation conditions.

  7. Prolactin Promotes Adipose Tissue Fitness and Insulin Sensitivity in Obese Males.

    Science.gov (United States)

    Ruiz-Herrera, Xarubet; de Los Ríos, Ericka A; Díaz, Juan M; Lerma-Alvarado, Ricardo M; Martínez de la Escalera, Lucía; López-Barrera, Fernando; Lemini, María; Arnold, Edith; Martínez de la Escalera, Gonzalo; Clapp, Carmen; Macotela, Yazmín

    2017-01-01

    Excessive accumulation of body fat triggers insulin resistance and features of the metabolic syndrome. Recently, evidence has accumulated that obesity, type 2 diabetes, and metabolic syndrome are associated with reduced levels of serum prolactin (PRL) in humans and rodents, raising the question of whether low PRL levels contribute to metabolic dysfunction. Here, we have addressed this question by investigating the role of PRL in insulin sensitivity and adipose tissue fitness in obese rodents and humans. In diet-induced obese rats, treatment with PRL delivered via osmotic mini-pumps, improved insulin sensitivity, prevented adipocyte hypertrophy, and reduced inflammatory cytokine expression in visceral fat. PRL also induced increased expression of Pparg and Xbp1s in visceral adipose tissue and elevated circulating adiponectin levels. Conversely, PRL receptor null mice challenged with a high-fat diet developed greater insulin resistance, glucose intolerance, and increased adipocyte hypertrophy compared with wild-type mice. In humans, serum PRL values correlated positively with systemic adiponectin levels and were reduced in insulin-resistant patients. Furthermore, PRL circulating levels and PRL produced by adipose tissue correlated directly with the expression of PPARG, ADIPOQ, and GLUT4 in human visceral and sc adipose tissue. Thus, PRL, acting through its cognate receptors, promotes healthy adipose tissue function and systemic insulin sensitivity. Increasing the levels of PRL in the circulation may have therapeutic potential against obesity-induced metabolic diseases. Copyright © 2017 by the Endocrine Society.

  8. Beneficial Effects of Calcitriol on Hypertension, Glucose Intolerance, Impairment of Endothelium-Dependent Vascular Relaxation, and Visceral Adiposity in Fructose-Fed Hypertensive Rats

    OpenAIRE

    Chu-Lin Chou; Cheng-Yoong Pang; Lee, Tony J. F.; Te-Chao Fang

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-f...

  9. Expression of plasminogen activator inhibitor-1 in human adipose tissue: a role for TNF-alpha?

    Science.gov (United States)

    Cigolini, M; Tonoli, M; Borgato, L; Frigotto, L; Manzato, F; Zeminian, S; Cardinale, C; Camin, M; Chiaramonte, E; De Sandre, G; Lunardi, C

    1999-03-01

    Elevated plasminogen activator inhibitor-1 (PAI-1) plasma levels, responsible for reduced fibrinolysis, are associated with animal and human obesity and with increased cardiovascular disease. The expression of PAI-1 has been found recently in animal and human adipose tissue. Factors and mechanisms regulating such an expression remain to be elucidated. In omental and/or subcutaneous biopsies from obese non-diabetic patients, incubated in Medium 199, we have confirmed that human adipose tissue expresses PAI-1 protein and mRNA; furthermore we have demonstrated that such an expression is clearly evident also in collagenase isolated human adipocytes and that it is stimulated by incubation itself and enhanced by exogenous human tumor necrosis factor-alpha (h-TNF-alpha). Since human adipose tissue produces TNF-alpha, to further characterize the relationship of PAI-1 to TNF-alpha, human fat biopsies were also incubated with Pentoxifylline (PTX) or Genistein, both known to inhibit endogenous TNF-alpha through different mechanisms. PTX caused a dose-dependent decrease of basal PAI-1 protein release, reaching 80% maximal inhibitory effect at 10(-3)M, the same inhibitory effect caused by Genistein at 100 microg/ml. This was associated to a marked inhibition of PAI-1 mRNA and of endogenous TNF-alpha production. Furthermore, when human fat biopsies were incubated in the presence of polyclonal rabbit neutralizing anti-human TNF-alpha antibody (at a concentration able to inhibit 100 UI/ml human TNF-alpha activity), a modest but significant decrease of the incubation induced expression of PAI-1 mRNA was observed (19.8+/-19.0% decrease, P = 0.04, n = 7). In conclusion, the results of this study demonstrate that PAI-I expression is present in human isolated adipocytes and that it is enhanced in human adipose tissue in vitro by exogenous TNF-alpha. Furthermore our data support the possibility of a main role of endogenous TNF-alpha on human adipose tissue PAI-1 expression. This

  10. Prolactin expression and secretion by human breast glandular and adipose tissue explants.

    Science.gov (United States)

    Zinger, Michael; McFarland, Molly; Ben-Jonathan, Nira

    2003-02-01

    Prolactin (PRL) is a 23-kDa hormone produced by the pituitary and extrapituitary sites. The main target of PRL is the breast, where it affects cellular growth, differentiation, and milk production. Recent evidence suggests that locally produced PRL plays a role in breast tumorigenesis. Our objective was to examine PRL synthesis/release in different tissues of the human breast and determine the effect of ovarian steroids. Breast tissue, obtained from women undergoing mastectomy or breast reduction, was separated into glandular (nonmalignant) and adipose explants and incubated for 10 d. Conditioned media were analyzed for PRL by a bioassay. PRL release from glandular explants decreased by 60% from d 1-3, followed by a 4-fold increase on d 10. PRL release from adipose explants was unchanged from d 1-3 and increased more than 10-fold by d 10. PRL gene expression, determined by RT-PCR, was low on d 0 and markedly increased on d 10 in both types of explants. De novo synthesis of PRL was confirmed by metabolic labeling. Progesterone suppressed PRL release from glandular explants without affecting adipose explants. Estradiol did not alter PRL release from either tissue. In conclusion, the human breast produces and releases bioactive PRL, with a higher release rate by adipose than glandular tissue. The time-dependent rise in PRL release suggests removal from inhibitory control. Progesterone may be one of the factors that suppresses PRL production in the glandular compartment, whereas the factor(s) that regulate adipose PRL are unknown. These data suggest an autocrine/paracrine role for PRL in human glandular and adipose breast tissue.

  11. Characterization and assessment of hyperelastic and elastic properties of decellularized human adipose tissues.

    Science.gov (United States)

    Omidi, Ehsan; Fuetterer, Lydia; Reza Mousavi, Seyed; Armstrong, Ryan C; Flynn, Lauren E; Samani, Abbas

    2014-11-28

    Decellularized adipose tissue (DAT) has shown potential as a regenerative scaffold for plastic and reconstructive surgery to augment or replace damaged or missing adipose tissue (e.g. following lumpectomy or mastectomy). The mechanical properties of soft tissue substitutes are of paramount importance in restoring the natural shape and appearance of the affected tissues, and mechanical mismatching can lead to unpredictable scar tissue formation and poor implant integration. The goal of this work was to assess the linear elastic and hyperelastic properties of decellularized human adipose tissue and compare them to those of normal breast adipose tissue. To assess the influence of the adipose depot source on the mechanical properties of the resultant decellularized scaffolds, we performed indentation tests on DAT samples sourced from adipose tissue isolated from the breast, subcutaneous abdominal region, omentum, pericardial depot and thymic remnant, and their corresponding force-displacement data were acquired. Elastic and hyperelastic parameters were estimated using inverse finite element algorithms. Subsequently, a simulation was conducted in which the estimated hyperelastic parameters were tested in a real human breast model under gravity loading in order to assess the suitability of the scaffolds for implantation. Results of these tests showed that in the human breast, the DAT would show similar deformability to that of native normal tissue. Using the measured hyperelastic parameters, we were able to assess whether DAT derived from different depots exhibited different intrinsic nonlinearities. Results showed that DAT sourced from varying regions of the body exhibited little intrinsic nonlinearity, with no statistically significant differences between the groups. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Metabolic effects of interleukin-6 in human splanchnic and adipose tissue

    DEFF Research Database (Denmark)

    Lyngsø, Dorthe; Simonsen, Lene; Bülow, Jens

    2002-01-01

    Interleukin-6 (IL-6) was infused intravenously for 2.5 h in seven healthy human volunteers at a dose giving rise to a circulating IL-6 concentration of approximately 35 ng l(-1). The metabolic effects of this infusion were studied in subcutaneous adipose tissue on the anterior abdominal wall...

  13. Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, Bente; Larsen, J J; Mikines, K J

    2000-01-01

    Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men [insu...

  14. Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans

    Science.gov (United States)

    Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. T...

  15. Adipose tissue metabolism in humans determined by vein catheterization and microdialysis techniques

    DEFF Research Database (Denmark)

    Simonsen, L; Bülow, J; Madsen, J

    1994-01-01

    A technique for catheterization of a vein draining abdominal subcutaneous tissue and a microdialysis technique that allows measurements of intercellular water concentrations in adipose tissue in humans have recently been described. In the present study, we compare the two techniques during an ora...

  16. The role of active brown adipose tissue in human metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Ozguven, Salih; Turoglu, H.T. [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Ones, Tunc [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Kozyatagi/Kadikoy, Istanbul (Turkey); Yilmaz, Yusuf; Imeryuz, Nese [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Internal Medicine, Division of Gastroenterology, Istanbul (Turkey)

    2016-02-15

    The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing {sup 18}F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). We retrospectively and prospectively analysed the {sup 18}F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD. (orig.)

  17. RNA-Seq Analysis of Abdominal Fat in Genetically Fat and Lean Chickens Highlights a Divergence in Expression of Genes Controlling Adiposity, Hemostasis, and Lipid Metabolism

    OpenAIRE

    Christopher W Resnyk; Chuming Chen; Hongzhan Huang; Wu, Cathy H.; Jean Simon,; Elisabeth Le Bihan-Duval; Duclos, Michel J.; Cogburn, Larry A.

    2015-01-01

    Genetic selection for enhanced growth rate in meat-type chickens (Gallus domesticus) is usually accompanied by excessive adiposity, which has negative impacts on both feed efficiency and carcass quality. Enhanced visceral fatness and several unique features of avian metabolism (i.e., fasting hyperglycemia and insulin insensitivity) mimic overt symptoms of obesity and related metabolic disorders in humans. Elucidation of the genetic and endocrine factors that contribute to excessive visceral f...

  18. The circulatory and metabolic responses to hypoxia in humans - with special reference to adipose tissue physiology and obesity

    NARCIS (Netherlands)

    I. Heinonen (Ilkka); R. Boushel (Robert); K.K. Kalliokoski (Kari)

    2016-01-01

    textabstractAdipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply

  19. LC-MS/MS analysis of visceral and subcutaneous adipose tissue proteomes in young goats with focus on innate immunity and inflammation related proteins

    DEFF Research Database (Denmark)

    Restelli, Laura; Codrea, Marius Cosmin; Savoini, Giovanni

    2014-01-01

    inflammation, detoxification and coagulation pathways, as well as regulation of body fat mobilization in dairy animals. These findings are of particular interest in farm animals where health and production traits are important for animal welfare and for economic gains. (C) 2014 Elsevier B.V. All rights...... protein and gene expression patterns. In ruminants, fat tissues play important biological roles not only for animal health, but also for quality and gain in meat and milk production. Yet very few studies have explored the ruminant adipose tissue proteomes. The aim of our study was to compare subcutaneous...

  20. Human multipotent adipose-derived stem cells differentiate into functional brown adipocytes

    DEFF Research Database (Denmark)

    Elabd, Christian; Chiellini, Chiara; Carmona, Mamen

    2009-01-01

    adipose-derived stem (hMADS) cells exhibit a normal karyotype and high self-renewal ability; they are known to differentiate into cells that exhibit the key properties of human white adipocytes, that is, uncoupling protein two expression, insulin-stimulated glucose uptake, lipolysis in response to beta......In contrast to the earlier contention, adult humans have been shown recently to possess active brown adipose tissue with a potential of being of metabolic significance. Up to now, brown fat precursor cells have not been available for human studies. We have shown previously that human multipotent......-agonists and atrial natriuretic peptide, and release of adiponectin and leptin. Herein, we show that, upon chronic exposure to a specific PPARgamma but not to a PPARbeta/delta or a PPARalpha agonist, hMADS cell-derived white adipocytes are able to switch to a brown phenotype by expressing both uncoupling protein one...

  1. 11Beta-HSD type 1 expression in human adipose tissue: impact of gender, obesity, and fat localization

    DEFF Research Database (Denmark)

    Paulsen, Søren Kildeberg; Pedersen, Steen Bønløkke; Fisker, Sanne

    2007-01-01

    of the metabolic syndrome. Our objective was to compare 11beta-HSD1 gene expression in different fat depots (visceral, subcutaneous abdominal, and subcutaneous gluteal) in lean and obese men and women. RESEARCH METHODS AND PROCEDURES: A cross-sectional study design was used for healthy patients undergoing minor...... abdominal surgery (lean men, 10), minor gynecological surgery (lean woman, 10), or gastric banding operations (obese men, 10; and obese women, 10). Gene expressions of 11beta-HSD1 in adipose tissue samples were determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Lean...

  2. The MRC1/CD68 ratio is positively associated with adipose tissue lipogenesis and with muscle mitochondrial gene expression in humans.

    Directory of Open Access Journals (Sweden)

    José María Moreno-Navarrete

    Full Text Available BACKGROUND: Alternative macrophages (M2 express the cluster differentiation (CD 206 (MCR1 at high levels. Decreased M2 in adipose tissue is known to be associated with obesity and inflammation-related metabolic disturbances. Here we aimed to investigate MCR1 relative to CD68 (total macrophages gene expression in association with adipogenic and mitochondrial genes, which were measured in human visceral [VWAT, n = 147] and subcutaneous adipose tissue [SWAT, n = 76] and in rectus abdominis muscle (n = 23. The effects of surgery-induced weight loss were also longitudinally evaluated (n = 6. RESULTS: MCR1 and CD68 gene expression levels were similar in VWAT and SWAT. A higher proportion of CD206 relative to total CD68 was present in subjects with less body fat and lower fasting glucose concentrations. The ratio MCR1/CD68was positively associated with IRS1gene expression and with the expression of lipogenic genes such as ACACA, FASN and THRSP, even after adjusting for BMI. The ratio MCR1/CD68 in SWAT increased significantly after the surgery-induced weight loss (+44.7%; p = 0.005 in parallel to the expression of adipogenic genes. In addition, SWAT MCR1/CD68ratio was significantly associated with muscle mitochondrial gene expression (PPARGC1A, TFAM and MT-CO3. AT CD206 was confirmed by immunohistochemistry to be specific of macrophages, especially abundant in crown-like structures. CONCLUSION: A decreased ratio MCR1/CD68 is linked to adipose tissue and muscle mitochondrial dysfunction at least at the level of expression of adipogenic and mitochondrial genes.

  3. The gene expression profile of non-cultured, highly purified human adipose tissue pericytes: Transcriptomic evidence that pericytes are stem cells in human adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Silva Meirelles, Lindolfo da, E-mail: lindolfomeirelles@gmail.com [Center for Cell-Based Therapy (CEPID/FAPESP), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); Laboratory for Stem Cells and Tissue Engineering, PPGBioSaúde, Lutheran University of Brazil, Av. Farroupilha 8001, 92425-900 Canoas, RS (Brazil); Deus Wagatsuma, Virgínia Mara de; Malta, Tathiane Maistro; Bonini Palma, Patrícia Viana [Center for Cell-Based Therapy (CEPID/FAPESP), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); Araújo, Amélia Goes; Panepucci, Rodrigo Alexandre [Laboratory of Large-Scale Functional Biology (LLSFBio), Regional Center for Hemotherapy of Ribeirão Preto, University of São Paulo, Rua Tenente Catão Roxo 2501, 14051-140 Ribeirão Preto, SP (Brazil); and others

    2016-12-10

    Pericytes (PCs) are a subset of perivascular cells that can give rise to mesenchymal stromal cells (MSCs) when culture-expanded, and are postulated to give rise to MSC-like cells during tissue repair in vivo. PCs have been suggested to behave as stem cells (SCs) in situ in animal models, although evidence for this role in humans is lacking. Here, we analyzed the transcriptomes of highly purified, non-cultured adipose tissue (AT)-derived PCs (ATPCs) to detect gene expression changes that occur as they acquire MSC characteristics in vitro, and evaluated the hypothesis that human ATPCs exhibit a gene expression profile compatible with an AT SC phenotype. The results showed ATPCs are non-proliferative and express genes characteristic not only of PCs, but also of AT stem/progenitor cells. Additional analyses defined a gene expression signature for ATPCs, and revealed putative novel ATPC markers. Almost all AT stem/progenitor cell genes differentially expressed by ATPCs were not expressed by ATMSCs or culture-expanded ATPCs. Genes expressed by ATMSCs but not by ATPCs were also identified. These findings strengthen the hypothesis that PCs are SCs in vascularized tissues, highlight gene expression changes they undergo as they assume an MSC phenotype, and provide new insights into PC biology. - Highlights: • Non-cultured adipose tissue-derived human pericytes (ncATPCs) exhibit a distinctive gene expression signature. • ncATPCs express key adipose tissue stem cell genes previously described in vivo in mice. • ncATPCs express message for anti-proliferative and antiangiogenic molecules. • Most ncATPC-specific transcripts are absent in culture-expanded pericytes or ATMSCs • Gene expression changes ncATPCs undergo as they acquire a cultured ATMSC phenotype are pointed out.

  4. Diet-induced weight loss decreases adipose tissue oxygen tension with parallel changes in adipose tissue phenotype and insulin sensitivity in overweight humans

    NARCIS (Netherlands)

    Vink, R.G.; Roumans, N.J.; Čajlaković, M.; Cleutjens, J.P.M.; Boekschoten, M.V.; Fazelzadeh, P.; Vogel, M.A.A.; Blaak, E.E.; Mariman, E.C.; Baak, van M.A.; Goossens, G.H.

    2017-01-01

    Background/objectives: Although adipose tissue (AT) hypoxia is present in rodent models of obesity, evidence for this in humans is limited. Here, we investigated the effects of diet-induced weight loss (WL) on abdominal subcutaneous AT oxygen tension (pO 2), AT blood flow (ATBF), AT capillary

  5. Spatial distribution of human and canine visceral leishmaniasis in Belo Horizonte, Minas Gerais State, Brasil, 1994-1997 Distribuição espacial da leishmaniose visceral humana e canina em Belo Horizonte, Minas Gerais, Brasil, 1994-1997

    Directory of Open Access Journals (Sweden)

    Cláudia Di Lorenzo Oliveira

    2001-10-01

    Full Text Available In this paper, we present spatial analysis of the association between all incidents cases of human Visceral Leishmaniasis and seropositive dogs, from 1994 to 1997 in Belo Horizonte, a large Brazilian city. We geocoded 158 human cases and 11,048 seropositive dogs and compared canine prevalence rates with Human Bayesian Incidence rates in the same areas. We also used Knox's test to evaluate the hypothesis of space-time clustering of human cases in the period. Additionally, we used Kernel's maps for seropositive dogs distribution and located the human cases in the resulting smooth maps. We concluded that human and dog rates are correlated. Also, the Visceral Leishmaniasis in Belo Horizonte spread quickly, but apart from the rates' magnitude, it has kept the same spatial pattern through time. We believe it is possible to use this technique to choose areas to implement control measures against Visceral Leishmaniasis in a more efficient way.Neste artigo, apresentamos uma análise espacial da associação entre todos os casos incidentes de leishmaniose visceral e em cães soropositivos ocorridos em Belo Horizonte no período de 1994 a 1997. Geocodificamos 158 casos humanos e 11.048 cães positivos, comparamos as taxas de prevalência canina por área e as taxas Bayesianas de incidência da doença humana nas mesmas áreas. Usamos o teste de Knox para testar a hipótese de cluster espaço temporal entre os casos humanos no período examinado. Adicionalmente, construímos Mapas de Kernel para cães soropositivos e sobrepusemos os casos humanos em quatro áreas. Os resultados apontam para correlação entre casos humanos e caninos. Além disso, a leishmaniose visceral espalhou-se rapidamente em Belo Horizonte, embora tenha mantido o mesmo padrão durante os anos analisados. Acreditamos ser possível o uso das técnicas empregadas para priorizar áreas onde as medidas de controle devem ser implementadas.

  6. Mechanical characterization of living and dead undifferentiated human adipose-derived stem cells by using atomic force microscopy.

    Science.gov (United States)

    Hu, Kexiang; Zhao, Feihu; Wang, Qingkang

    2013-12-01

    In this article, to map the mechanical properties of undifferentiated human adipose-derived stem cells, local mechanical characterization is carried out on the adipose-derived stem cells. In addition, to distinguish the living and dead human adipose-derived stem cells, mechanical characterization is also implemented on both living and dead adipose-derived stem cells. In this study, Young's modulus of the cell membrane is used for representing the mechanical properties of cells. To obtain Young's modulus of cell membrane, the force-spectroscopy mode of atomic force microscopy is employed to measure the atomic force microscopy tip indentation depth and force on the cells. Then, Young's modulus is obtained through fitting these experimental data to the Hertzian contact mechanics model. The global Young's moduli of living and dead undifferentiated adipose-derived stem cells are about 1.27 and 18.61 kPa, respectively. This displays obvious gap of Young's modulus between the living and dead undifferentiated adipose-derived stem cells. Finally, comparison of the local Young's modulus shows deviation of the local Young's modulus for either living or dead undifferentiated adipose-derived stem cells, and the root-mean-square errors of the global Young's modulus of living and dead undifferentiated adipose-derived stem cells are about 0.48 and 5.05 kPa, respectively.

  7. Adipose tissue-specific regulation of angiotensinogen in obese humans and mice: impact of nutritional status and adipocyte hypertrophy.

    Science.gov (United States)

    Yasue, Shintaro; Masuzaki, Hiroaki; Okada, Sadanori; Ishii, Takako; Kozuka, Chisayo; Tanaka, Tomohiro; Fujikura, Junji; Ebihara, Ken; Hosoda, Kiminori; Katsurada, Akemi; Ohashi, Naro; Urushihara, Maki; Kobori, Hiroyuki; Morimoto, Naoki; Kawazoe, Takeshi; Naitoh, Motoko; Okada, Mitsuru; Sakaue, Hiroshi; Suzuki, Shigehiko; Nakao, Kazuwa

    2010-04-01

    The adipose tissue renin-angiotensin system (RAS) has been implicated in the pathophysiology of obesity and dysfunction of adipose tissue. However, neither regulation of angiotensinogen (AGT) expression in adipose tissue nor secretion of adipose tissue-derived AGT has been fully elucidated in humans. Human subcutaneous abdominal adipose tissue (SAT) biopsies were performed for 46 subjects with a wide range of body mass index (BMI). Considering the mRNA level of AGT and indices of body fat mass, the amount of adipose tissue-derived AGT secretion (A-AGT-S) was estimated. Using a mouse model of obesity and weight reduction, plasma AGT levels were measured with a newly developed enzyme-linked immunosorbent assay (ELISA), and the contribution of A-AGT-S to plasma AGT levels was assessed. A-AGT-S was substantially increased in obese humans and the value was correlated with the plasma AGT level in mice. A-AGT-S and plasma AGT were higher in obese mice, whereas lower in mice with weight reduction. However, the AGT mRNA levels in the liver, kidney, and aorta were not altered in the mouse models. In both humans and mice, the AGT mRNA levels in mature adipocytes (MAs) were comparable to those in stromal-vascular cells. Coulter Multisizer analyses revealed that AGT mRNA levels in the MAs were inversely correlated with the average size of mature adipocytes. This study demonstrates that adipose tissue-derived AGT is substantially augmented in obese humans, which may contribute considerably to elevated levels of circulating AGT. Adipose tissue-specific regulation of AGT provides a novel insight into the clinical implications of adipose tissue RAS in human obesity.

  8. Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates with Active Visceral Disease in Humans

    Directory of Open Access Journals (Sweden)

    Begoña Pérez-Cabezas

    2016-11-01

    Full Text Available The complexity of Leishmania-host interactions, one of the main leishmaniasis issues, is yet to be fully understood. We detected elevated IL-27 plasma levels in European patients with active visceral disease caused by Leishmania infantum, which returned to basal levels after successful treatment, suggesting this cytokine as a probable infection mediator. We further addressed this hypothesis recurring to two classical susceptible visceral leishmaniasis mouse models. BALB/c, but not C57BL/6 mice, showed increased IL-27 systemic levels after infection, which was associated with an upregulation of IL-27p28 expression by dendritic cells and higher parasite burdens. Neutralization of IL-27 in acutely infected BALB/c led to decreased parasite burdens and a transient increase in IFN-γ+ splenic T cells, while administration of IL-27 to C57BL/6 promoted a local anti-inflammatory cytokine response at the site of infection and increased parasite loads. Overall we show that, as in humans, BALB/c IL-27 systemic levels are infection-dependently upregulated and may favor parasite installation by controlling inflammation.

  9. Measures of abdominal adiposity and the risk of stroke

    DEFF Research Database (Denmark)

    Bodenant, Marie; Kuulasmaa, Kari; Wagner, Aline

    2011-01-01

    Excess fat accumulates in the subcutaneous and visceral adipose tissue compartments. We tested the hypothesis that indicators of visceral adiposity, namely, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), are better predictors of stroke risk than body mass in...

  10. Enantioselective gas chromatographic separation of methylsulfonyl PCBs in seal blubber, pelican muscle and human adipose tissues

    Energy Technology Data Exchange (ETDEWEB)

    Karasek, L.; Rosmus, J. [Veterinary Institute Prague (Czech Republic). Dept. of Chemistry; Hajslova, J. [Institute of Chemical Technology (Czech Republic). Dept. of Food Chemistry and Analysis; Huehnerfuss, H. [Hamburg Univ. (Germany). Inst. fuer Organische Chemie

    2004-09-15

    Methyl sulfone derivatives are known to represent primary metabolic products of PCBs (MeSO2- CB) and DDE (MeSO2-DDE). These metabolites are formed via mercapturic acid pathway and belong to persistent, lipophilic compounds which accumulate in the adipose, lung, liver and kidney tissues of mammals exposed to PCBs. In 1976 Jenssen and Jansson reported the identification of PCB methyl sulfones as metabolites of PCBs in Baltic grey seal blubber. Methyl sulfones are moderately polar compounds that are only slightly less hydrophobic than the parent PCBs, and their partition coefficients fulfill the requirements for bioaccumulation. The highest concentrations have been found in kidney and lung tissues of seals, otters, beluga whales, polar bears, fishes and in human tissues. In the present investigation two samples of seal blubber, two pelican muscles and eleven human adipose tissue samples were analysed with regard to their concentrations of PCB parent compounds as well as to the respective chiral methylsulfonyl metabolites.

  11. Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, prespiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues. PMID:24073224

  12. Citrus aurantium and Rhodiola rosea in combination reduce visceral white adipose tissue and increase hypothalamic norepinephrine in a rat model of diet-induced obesity.

    Science.gov (United States)

    Verpeut, Jessica L; Walters, Amy L; Bello, Nicholas T

    2013-06-01

    Extracts from the immature fruit of Citrus aurantium are often used for weight loss but are reported to produce adverse cardiovascular effects. Root extracts of Rhodiola rosea have notable antistress properties. The hypothesis of these studies was that C aurantium (6% synephrine) and R rosea (3% rosavins, 1% salidroside) in combination would improve diet-induced obesity alterations in adult male Sprague-Dawley rats. In normal-weight animals fed standard chow, acute administration of C aurantium (1-10 mg/kg) or R rosea (2-20 mg/kg) alone did not reduce deprivation-induced food intake, but C aurantium (5.6 mg/kg) + R rosea (20 mg/kg) produced a 10.5% feeding suppression. Animals maintained (13 weeks) on a high-fat diet (60% fat) were exposed to 10-day treatments of C aurantium (5.6 mg/kg) or R rosea (20 mg/kg) alone or in combination. Additional groups received vehicle (2% ethanol) or were pair fed to the C aurantium + R rosea group. Although high-fat diet intake and weight loss were not influenced, C aurantium + R rosea had a 30% decrease in visceral fat weight compared with the other treatments. Only the C aurantium group had an increased heart rate (+7%) compared with vehicle. In addition, C aurantium + R rosea administration resulted in an elevation (+15%) in hypothalamic norepinephrine and an elevation (+150%) in frontal cortex dopamine compared with the pair-fed group. These initial findings suggest that treatments of C aurantium + R rosea have actions on central monoamine pathways and have the potential to be beneficial for the treatment of obesity. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Citrus aurantium and Rhodiola rosea in combination reduce visceral white adipose tissue and increase hypothalamic norepinephrine in a rat model of diet-induced obesity

    Science.gov (United States)

    Verpeut, Jessica L.; Walters, Amy L.; Bello, Nicholas T.

    2013-01-01

    Extracts from the immature fruit of Citrus aurantium are often used for weight loss but are reported to produce adverse cardiovascular effects. Root extracts of Rhodiola rosea have notable antistress properties. The hypothesis of these studies was that C aurantium (6% synephrine) and R rosea (3% rosavins, 1% salidroside) in combination would improve diet-induced obesity alterations in adult male Sprague-Dawley rats. In normal-weight animals fed standard chow, acute administration of C aurantium (1-10 mg/kg) or R rosea (2-20 mg/kg) alone did not reduce deprivation-induced food intake, but C aurantium (5.6 mg/kg) + R rosea (20 mg/kg) produced a 10.5% feeding suppression. Animals maintained (13 weeks) on a high-fat diet (60% fat) were exposed to 10-day treatments of C aurantium (5.6 mg/kg) or R rosea (20 mg/kg) alone or in combination. Additional groups received vehicle (2% ethanol) or were pair fed to the C aurantium + R rosea group. Although high-fat diet intake and weight loss were not influenced, C aurantium + R rosea had a 30% decrease in visceral fat weight compared with the other treatments. Only the C aurantium group had an increased heart rate (+7%) compared with vehicle. In addition, C aurantium + R rosea administration resulted in an elevation (+15%) in hypothalamic norepinephrine and an elevation (+150%) in frontal cortex dopamine compared with the pair-fed group. These initial findings suggest that treatments of C aurantium + R rosea have actions on central monoamine pathways and have the potential to be beneficial for the treatment of obesity. PMID:23746567

  14. Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells

    DEFF Research Database (Denmark)

    Pasarica, Magdalena; Mashtalir, Nazar; McAllister, Emily J

    2008-01-01

    Human adenovirus Ad-36 is causatively and correlatively linked with animal and human obesity, respectively. Ad-36 enhances differentiation of rodent preadipocytes, but its effect on adipogenesis in humans is unknown. To indirectly assess the role of Ad-36-induced adipogenesis in human obesity......, the effect of the virus on commitment, differentiation, and lipid accumulation was investigated in vitro in primary human adipose-derived stem/stromal cells (hASC). Ad-36 infected hASC in a time- and dose-dependent manner. Even in the presence of osteogenic media, Ad-36-infected hASC showed significantly...

  15. Diurnal variation of the human adipose transcriptome and the link to metabolic disease

    Directory of Open Access Journals (Sweden)

    Lamb John

    2009-02-01

    Full Text Available Abstract Background Circadian (diurnal rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation. Methods The present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy individuals. In this well-controlled clinical study, adipose biopsies were taken in the morning, afternoon and evening from individuals in three study arms: treatment with the weight loss drug sibutramine/fasted, placebo/fed and placebo/fasted. Results The results indicated that diurnal rhythm was the most significant driver of gene expression variation in the human adipose tissue, with at least 25% of the genes having had significant changes in their expression levels during the course of the day. The mRNA expression levels of core clock genes at a specific time of day were consistent across multiple subjects on different days in all three arms, indicating robust diurnal regulation irrespective of potential confounding factors. The genes essential for energy metabolism and tissue physiology were part of the diurnal signature. We hypothesize that the diurnal transition of the expression of energy metabolism genes reflects the shift in the adipose tissue from an energy-expending state in the morning to an energy-storing state in the evening. Consistent with this hypothesis, the diurnal transition was delayed by fasting and treatment with sibutramine. Finally, an in silico comparison of the diurnal signature with data from the publicly-available Connectivity Map demonstrated a significant association with transcripts that were repressed by mTOR inhibitors, suggesting a possible link between mTOR signaling, diurnal gene expression and metabolic regulation. Conclusion Diurnal rhythm plays an important role in the physiology and regulation of energy metabolism in the adipose

  16. The Effect of Resveratrol and Quercetin Treatment on PPAR Mediated Uncoupling Protein (UCP- 1, 2, and 3 Expression in Visceral White Adipose Tissue from Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Vicente Castrejón-Tellez

    2016-07-01

    Full Text Available Uncoupling proteins (UCPs are members of the mitochondrial anion carrier superfamily involved in the control of body temperature and energy balance regulation. They are currently proposed as therapeutic targets for treating obesity and metabolic syndrome (MetS. We studied the gene expression regulation of UCP1, -2, and -3 in abdominal white adipose tissue (WAT from control and MetS rats treated with two doses of a commercial mixture of resveratrol (RSV and quercetin (QRC. We found that UCP2 was the predominantly expressed isoform, UCP3 was present at very low levels, and UCP1 was undetectable. The treatment with RSV + QRC did not modify UCP3 levels; however, it significantly increased UCP2 mRNA in control and MetS rats in association with an increase in oleic and linoleic fatty acids. WAT from MetS rats showed a significantly increased expression of peroxisome proliferator-activated receptor (PPAR-α and PPAR-γ when compared to the control group. Furthermore, PPAR-α protein levels were increased by the highest dose of RSV + QRC in the control and MetS groups. PPAR-γ expression was only increased in the control group. We conclude that the RSV + QRC treatment leads to overexpression of UCP2, which is associated with an increase in MUFA and PUFA, which might increase PPAR-α expression.

  17. Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis.

    Science.gov (United States)

    García-Alonso, Verónica; Titos, Esther; Alcaraz-Quiles, Jose; Rius, Bibiana; Lopategi, Aritz; López-Vicario, Cristina; Jakobsson, Per-Johan; Delgado, Salvadora; Lozano, Juanjo; Clària, Joan

    2016-01-01

    Obesity induces white adipose tissue (WAT) dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs) are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES). IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1) in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16) in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of interactions

  18. Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis.

    Directory of Open Access Journals (Sweden)

    Verónica García-Alonso

    Full Text Available Obesity induces white adipose tissue (WAT dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES. IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1 in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16 in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of

  19. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

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    Zach S. Templeton

    2015-12-01

    Full Text Available BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014 and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006 and IL-1β (P = .001 in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

  20. Pregnancy complicated by obesity induces global transcript expression alterations in visceral and subcutaneous fat.

    Science.gov (United States)

    Bashiri, Asher; Heo, Hye J; Ben-Avraham, Danny; Mazor, Moshe; Budagov, Temuri; Einstein, Francine H; Atzmon, Gil

    2014-08-01

    Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet not much is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n = 4/group) at the time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations led to identification of indolethylamine N-methyltransferase, tissue factor pathway inhibitor-2, and ephrin type-B receptor 6, not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis as compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity.

  1. Epidemiological aspects and spatial distribution of human and canine visceral leishmaniasis in an endemic area in northeastern Brazil

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    Roseane Campos

    2017-05-01

    Full Text Available Visceral leishmaniasis (VL is a systemic disease endemic in tropical countries and transmitted through sand flies. In particular, Canis familiaris (or domesticated dogs are believed to be a major urban reservoir for the parasite causing the disease Leishmania. The average number of human VL cases was 58 per year in the state of Sergipe. The city of Aracaju, capital of Sergipe in Northeastern Brazil, had 159 cases of VL in humans. Correlatively, the percentage of serologically positive dogs for leishmaniasis increased from 4.73% in 2008 to 12.69% in 2014. Thus, these studies aimed to delineate the spatial distribution and epidemiological aspects of human and canine VL as mutually supportive for increased incidence. The number of human cases of VL and the frequency of canine positive serology for VL both increased between 2008 and 2014. Spatial distribution analyses mapped areas of the city with the highest concentration of human and canine VL cases. The neighbourhoods that showed the highest disease frequency were located on the outskirts of the city and in urbanised areas or subjected to development. Exponential increase in VL-positive dogs further suggests that the disease is expanding in urban areas, where it can serve as a reservoir for transmission of dogs to humans via the sand fly vector.

  2. Inflammatory Role of Toll-Like Receptors in Human and Murine Adipose Tissue

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    Odile Poulain-Godefroy

    2010-01-01

    Full Text Available It was recently demonstrated that TLR4 activation via dietary lipids triggers inflammatory pathway and alters insulin responsiveness in the fat tissue during obesity. Here, we question whether other TLR family members could participate in the TLR-mediated inflammatory processes occurring in the obese adipose tissue. We thus studied the expression of TLR1, TLR2, TLR4, and TLR6 in adipose tissue. These receptors are expressed in omental and subcutaneous human fat tissue, the expression being higher in the omental tissue, independently of the metabolic status of the subject. We demonstrated a correlation of TLRs expression within and between each depot suggesting a coregulation. Murine 3T3-L1 preadipocyte cells stimulated with Pam3CSK4 induced the expression of some proinflammatory markers. Therefore, beside TLR4, other toll-like receptors are differentially expressed in human fat tissue, and functional in an adipocyte cell line, suggesting that they might participate omental adipose tissue-related inflammation that occurs in obesity.

  3. Transcriptomic comparisons between cultured human adipose tissue-derived pericytes and mesenchymal stromal cells

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    Lindolfo da Silva Meirelles

    2016-03-01

    Full Text Available Mesenchymal stromal cells (MSCs, sometimes called mesenchymal stem cells, are cultured cells able to give rise to mature mesenchymal cells such as adipocytes, osteoblasts, and chondrocytes, and to secrete a wide range of trophic and immunomodulatory molecules. Evidence indicates that pericytes, cells that surround and maintain physical connections with endothelial cells in blood vessels, can give rise to MSCs (da Silva Meirelles et al., 2008 [1]; Caplan and Correa, 2011 [2]. We have compared the transcriptomes of highly purified, human adipose tissue pericytes subjected to culture-expansion in pericyte medium or MSC medium, with that of human adipose tissue MSCs isolated with traditional methods to test the hypothesis that their transcriptomes are similar (da Silva Meirelles et al., 2015 [3]. Here, we provide further information and analyses of microarray data from three pericyte populations cultured in pericyte medium, three pericyte populations cultured in MSC medium, and three adipose tissue MSC populations deposited in the Gene Expression Omnibus under accession number GSE67747.

  4. Dynamics of human adipose lipid turnover in health and metabolic disease.

    Science.gov (United States)

    Arner, Peter; Bernard, Samuel; Salehpour, Mehran; Possnert, Göran; Liebl, Jakob; Steier, Peter; Buchholz, Bruce A; Eriksson, Mats; Arner, Erik; Hauner, Hans; Skurk, Thomas; Rydén, Mikael; Frayn, Keith N; Spalding, Kirsty L

    2011-09-25

    Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring (14)C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.

  5. Effects of GSK3 inhibitors on in vitro expansion and differentiation of human adipose-derived stem cells into adipocytes

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    Peraldi Pascal

    2008-02-01

    Full Text Available Abstract Background Multipotent stem cells exist within adipose tissue throughout life. An abnormal recruitment of these adipose precursor cells could participate to hyperplasia of adipose tissue observed in severe obesity or to hypoplasia of adipose tissue observed in lipodystrophy. Therefore, pharmacological molecules that control the pool of stem cells in adipose tissue are of great interest. Glycogen Synthase Kinase (GSK 3 has been previously described as involved in differentiation of preadipose cells and might be a potential therapeutic target to modulate proliferation and differentiation of adipocyte precursors. However, the impact of GSK3 inhibition on human adipose-derived stem cells remained to be investigated. The aim of this study was to investigate GSK3 as a possible target for pharmacological inhibition of stem cell adipogenesis. To reach this goal, we studied the effects of pharmacological inhibitors of GSK3, i.e. lithium chloride (LiCl and BIO on proliferation and adipocyte differentiation of multipotent stem cells derived from human adipose tissue. Results Our results showed that GSK3 inhibitors inhibited proliferation and clonogenicity of human stem cells, strongly suggesting that GSK3 inhibitors could be potent regulators of the pool of adipocyte precursors in adipose tissue. The impact of GSK3 inhibition on differentiation of hMADS cells was also investigated. Adipogenic and osteogenic differentiations were inhibited upon hMADS treatment with BIO. Whereas a chronic treatment was required to inhibit osteogenesis, a treatment that was strictly restricted to the early step of differentiation was sufficient to inhibit adipogenesis. Conclusion These results demonstrated the feasibility of a pharmacological approach to regulate adipose-derived stem cell function and that GSK3 could represent a potential target for controlling adipocyte precursor pool under conditions where fat tissue formation is impaired.

  6. Three-dimensional micro computed tomography analysis of the lung vasculature and differential adipose proteomics in the Sugen/hypoxia rat model of pulmonary arterial hypertension.

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    Shields, Kelly J; Verdelis, Kostas; Passineau, Michael J; Faight, Erin M; Zourelias, Lee; Wu, Changgong; Chong, Rong; Benza, Raymond L

    2016-12-01

    Pulmonary arterial hypertension (PAH) is a rare disease characterized by significant vascular remodeling. The obesity epidemic has produced great interest in the relationship between small visceral adipose tissue depots producing localized inflammatory conditions, which may link metabolism, innate immunity, and vascular remodeling. This study used novel micro computed tomography (microCT) three-dimensional modeling to investigate the degree of remodeling of the lung vasculature and differential proteomics to determine small visceral adipose dysfunction in rats with severe PAH. Sprague-Dawley rats were subjected to a subcutaneous injection of vascular endothelial growth factor receptor blocker (Sugen 5416) with subsequent hypoxia exposure for 3 weeks (SU/hyp). At 12 weeks after hypoxia, microCT analysis showed a decrease in the ratio of vascular to total tissue volume within the SU/hyp group (mean ± standard deviation: 0.27 ± 0.066; P = 0.02) with increased vascular separation (0.37 ± 0.062 mm; P = 0.02) when compared with the control (0.34 ± 0.084 and 0.30 ± 0.072 mm). Differential proteomics detected an up-regulation of complement protein 3 (C3; SU/hyp∶control ratio = 2.86) and the adipose tissue-specific fatty acid binding protein-4 (FABP4, 2.66) in the heart adipose of the SU/hyp. Significant remodeling of the lung vasculature validates the efficacy of the SU/hyp rat for modeling human PAH. The upregulation of C3 and FABP4 within the heart adipose implicates small visceral adipose dysfunction. C3 has been associated with vascular stiffness, and FABP4 suppresses peroxisome proliferator-activated receptor, which is a major regulator of adipose function and known to be downregulated in PAH. These findings reveal that small visceral adipose tissue within the SU/hyp model provides mechanistic links for vascular remodeling and adipose dysfunction in the pathophysiology of PAH.

  7. [Ultrasonic lipoemulsification: a working definition and ex-vivo study on human adipose tissue].

    Science.gov (United States)

    Palmieri, B; Criscuolo, M; Gozzi, G

    1994-01-01

    On the basis of previous reports by other authors which have become increasingly numerous over the past years, we have focused our attention on the use of ultrasonic energy in the medical field to resolve medical and cosmetic problems, such as lipodystrophy and diffuse subcutaneous adiposity. In order to standardise the dissolution times of human subcutaneous adipose tissue we used a ultrasonic generator operating at a constant frequency of 19800 Hz, but which was able to emit a range of power from 0 to 100 Watt. The ultrasounds were applied (according to a scale of power) using a titanium probe to fat samples with a volume of 1 cm until each sample had fully dissolved. This allowed the levels of greatest working efficiency to be established for the most commonly used probes.

  8. Visceral Leishmaniasis

    Science.gov (United States)

    2011-06-01

    Autoclaved Leishmania major vaccine for prevention of visceral leishmaniasis: a randomised, double-blind, BCG -controlled trial in Sudan. Lancet...nitric oxide killing. These properties of sandfly saliva are the focus of current research on an antileishmania vaccine .11 At the site of inoculation...these campaigns, incidence has returned to high levels. No VL vaccine is currently licensed or commercially available. A variety of vaccine

  9. Human brown adipose tissue as a target for obesity management; beyond cold-induced thermogenesis.

    Science.gov (United States)

    Loh, R K C; Kingwell, B A; Carey, A L

    2017-11-01

    Elevating energy expenditure via adaptive thermogenesis in brown adipose tissue (BAT) is a potential strategy to reverse obesity. Much early enthusiasm for this approach, based on rodent studies, was tempered by the belief that BAT was relatively inconsequential in healthy adult humans. Interest was reinvigorated a decade ago when a series of studies re-identified BAT, primarily in upper thoracic regions, in adults. Despite the ensuing explosion of pre-clinical investigations and identification of an extensive list of potential target molecules for BAT recruitment, our understanding of human BAT physiology remains limited, particularly regarding interventions which might hold therapeutic promise. Cold-induced BAT thermogenesis (CIT) has been well studied, although is not readily translatable as an anti-obesity approach, whereas little is known regarding the role of BAT in human diet-induced thermogenesis (DIT). Furthermore, human studies dedicated to translating known pharmacological mechanisms of adipose browning from animal models are sparse. Several lines of recent evidence suggest that molecular regulation and physiology of human BAT differ to that of laboratory rodents, which form the majority of our knowledge base. This review will summarize knowledge on CIT and expand upon the current understanding and evidence gaps related to human adaptive thermogenesis via mechanisms other than cold. © 2017 World Obesity Federation.

  10. Regulation of adipose branched chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity

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    Elevated blood branched chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes. One possibility is that under these conditions there is a reduced cellular utilization and/or lower complete oxidation of BCAAs. White adipose tissue (WAT) has become appreciated as a...

  11. Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs.

    Science.gov (United States)

    Avishek, Kumar; Kaushal, Himanshu; Gannavaram, Sreenivas; Dey, Ranadhir; Selvapandiyan, Angamuthu; Ramesh, V; Negi, Narender Singh; Dubey, Uma S; Nakhasi, Hira L; Salotra, Poonam

    2016-09-14

    Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1(-/-) and Ldp27(-/-)) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1(-/-) and Ldp27(-/-) in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1(-/-) and Ldp27(-/-) strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4(+) and CD8(+) T cells and IL-17 secreting CD4(+) cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1(-/-) and Ldp27(-/-) are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure.

  12. Characterization of human adipose-derived stem cells and expression of chondrogenic genes during induction of cartilage differentiation

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    Adila A Hamid

    2012-01-01

    Full Text Available OBJECTIVES: Understanding the changes in chondrogenic gene expression that are involved in the differentiation of human adipose-derived stem cells to chondrogenic cells is important prior to using this approach for cartilage repair. The aims of the study were to characterize human adipose-derived stem cells and to examine chondrogenic gene expression after one, two, and three weeks of induction. MATERIALS AND METHODS: Human adipose-derived stem cells at passage 4 were evaluated by flow cytometry to examine the expression of surface markers. These adipose-derived stem cells were tested for adipogenic and osteogenic differentiation capacity. Ribonucleic acid was extracted from the cells for quantitative polymerase chain reaction analysis to determine the expression levels of chondrogenic genes after chondrogenic induction. RESULTS: Human adipose-derived stem cells were strongly positive for the mesenchymal markers CD90, CD73, CD44, CD9, and histocompatibility antigen and successfully differentiated into adipogenic and osteogenic lineages. The human adipose-derived stem cells aggregated and formed a dense matrix after chondrogenic induction. The expression of chondrogenic genes (collagen type II, aggrecan core protein, collagen type XI, COMP, and ELASTIN was significantly higher after the first week of induction. However, a significantly elevated expression of collagen type X was observed after three weeks of chondrogenic induction. CONCLUSION: Human adipose-derived stem cells retain stem cell characteristics after expansion in culture to passage 4 and serve as a feasible source of cells for cartilage regeneration. Chondrogenesis in human adiposederived stem cells was most prominent after one week of chondrogenic induction.

  13. Enhanced Adipogenic Differentiation of Human Adipose-Derived Stem Cells in an In Vitro Microenvironment: The Preparation of Adipose-Like Microtissues Using a Three-Dimensional Culture.

    Science.gov (United States)

    Miyamoto, Yoshitaka; Ikeuchi, Masashi; Noguchi, Hirofumi; Yagi, Tohru; Hayashi, Shuji

    2017-01-08

    The application of stem cells for cell therapy has been extensively studied in recent years. Among the various types of stem cells, human adipose tissue-derived stem cells (ASCs) can be obtained in large quantities with relatively few passages, and they possess a stable quality. ASCs can differentiate into a number of cell types, such as adipose cells and ectodermal cells. We therefore focused on the in vitro microenvironment required for such differentiation and attempted to induce the differentiation of human stem cells into microtissues using a microelectromechanical system. We first evaluated the adipogenic differentiation of human ASC spheroids in a three-dimensional (3D) culture. We then created the in vitro microenvironment using a 3D combinatorial TASCL device and attempted to induce the adipogenic differentiation of human ASCs. The differentiation of human ASC spheroids cultured in maintenance medium and those cultured in adipocyte differentiation medium was evaluated via Oil red O staining using lipid droplets based on the quantity of accumulated triglycerides. The differentiation was confirmed in both media, but the human ASCs in the 3D cultures contained higher amounts of triglycerides than those in the 2D cultures. In the short culture period, greater adipogenic differentiation was observed in the 3D cultures than in the 2D cultures. The 3D culture using the TASCL device with adipogenic differentiation medium promoted greater differentiation of human ASCs into adipogenic lineages than either a 2D culture or a culture using a maintenance medium. In summary, the TASCL device created a hospitable in vitro microenvironment and may therefore be a useful tool for the induction of differentiation in 3D culture. The resultant human ASC spheroids were "adipose-like microtissues" that formed spherical aggregation perfectly and are expected to be applicable in regenerative medicine as well as cell transplantation.

  14. The direct agglutination test as an alternative method for the diagnosis of canine and human visceral leishmaniasis

    NARCIS (Netherlands)

    Terán-Angel, Guillermo; Schallig, Henk; Zerpa, Olga; Rodríguez, Vestalia; Ulrich, Marian; Cabrera, Maira

    2007-01-01

    Visceral leishmaniasis is the most severe clinical form of leishmaniasis and is often fatal without proper treatment. Therefore, early and accurate diagnosis is important, but often difficult in endemic areas. The aim was to evaluate a direct agglutination test as a potential visceral leishmaniasis

  15. Human omental-derived adipose stem cells increase ovarian cancer proliferation, migration, and chemoresistance.

    Science.gov (United States)

    Nowicka, Aleksandra; Marini, Frank C; Solley, Travis N; Elizondo, Paula B; Zhang, Yan; Sharp, Hadley J; Broaddus, Russell; Kolonin, Mikhail; Mok, Samuel C; Thompson, Melissa S; Woodward, Wendy A; Lu, Karen; Salimian, Bahar; Nagrath, Deepak; Klopp, Ann H

    2013-01-01

    Adipose tissue contains a population of multipotent adipose stem cells (ASCs) that form tumor stroma and can promote tumor progression. Given the high rate of ovarian cancer metastasis to the omental adipose, we hypothesized that omental-derived ASC may contribute to ovarian cancer growth and dissemination. We isolated ASCs from the omentum of three patients with ovarian cancer, with (O-ASC4, O-ASC5) and without (O-ASC1) omental metastasis. BM-MSCs, SQ-ASCs, O-ASCs were characterized with gene expression arrays and metabolic analysis. Stromal cells effects on ovarian cancer cells proliferation, chemoresistance and radiation resistance was evaluated using co-culture assays with luciferase-labeled human ovarian cancer cell lines. Transwell migration assays were performed with conditioned media from O-ASCs and control cell lines. SKOV3 cells were intraperitionally injected with or without O-ASC1 to track in-vivo engraftment. O-ASCs significantly promoted in vitro proliferation, migration chemotherapy and radiation response of ovarian cancer cell lines. O-ASC4 had more marked effects on migration and chemotherapy response on OVCA 429 and OVCA 433 cells than O-ASC1. Analysis of microarray data revealed that O-ASC4 and O-ASC5 have similar gene expression profiles, in contrast to O-ASC1, which was more similar to BM-MSCs and subcutaneous ASCs in hierarchical clustering. Human O-ASCs were detected in the stroma of human ovarian cancer murine xenografts but not uninvolved ovaries. ASCs derived from the human omentum can promote ovarian cancer proliferation, migration, chemoresistance and radiation resistance in-vitro. Furthermore, clinical O-ASCs isolates demonstrate heterogenous effects on ovarian cancer in-vitro.

  16. Human omental-derived adipose stem cells increase ovarian cancer proliferation, migration, and chemoresistance.

    Directory of Open Access Journals (Sweden)

    Aleksandra Nowicka

    Full Text Available Adipose tissue contains a population of multipotent adipose stem cells (ASCs that form tumor stroma and can promote tumor progression. Given the high rate of ovarian cancer metastasis to the omental adipose, we hypothesized that omental-derived ASC may contribute to ovarian cancer growth and dissemination.We isolated ASCs from the omentum of three patients with ovarian cancer, with (O-ASC4, O-ASC5 and without (O-ASC1 omental metastasis. BM-MSCs, SQ-ASCs, O-ASCs were characterized with gene expression arrays and metabolic analysis. Stromal cells effects on ovarian cancer cells proliferation, chemoresistance and radiation resistance was evaluated using co-culture assays with luciferase-labeled human ovarian cancer cell lines. Transwell migration assays were performed with conditioned media from O-ASCs and control cell lines. SKOV3 cells were intraperitionally injected with or without O-ASC1 to track in-vivo engraftment.O-ASCs significantly promoted in vitro proliferation, migration chemotherapy and radiation response of ovarian cancer cell lines. O-ASC4 had more marked effects on migration and chemotherapy response on OVCA 429 and OVCA 433 cells than O-ASC1. Analysis of microarray data revealed that O-ASC4 and O-ASC5 have similar gene expression profiles, in contrast to O-ASC1, which was more similar to BM-MSCs and subcutaneous ASCs in hierarchical clustering. Human O-ASCs were detected in the stroma of human ovarian cancer murine xenografts but not uninvolved ovaries.ASCs derived from the human omentum can promote ovarian cancer proliferation, migration, chemoresistance and radiation resistance in-vitro. Furthermore, clinical O-ASCs isolates demonstrate heterogenous effects on ovarian cancer in-vitro.

  17. A Defective Oxidative Burst and Impaired Antigen Presentation are Hallmarks of Human Visceral Leishmaniasis.

    Science.gov (United States)

    Roy, Susmita; Mukhopadhyay, Debanjan; Mukherjee, Shibabrata; Ghosh, Susmita; Kumar, Shishir; Sarkar, Kumkum; Pal, Dipankar; Bhowmik, Pratik; Mandal, Kausik; Modak, Dolanchampa; Guha, Subhasish Kamal; Pramanik, Netai; Goswami, Rama Prosad; Saha, Bibhuti; Chatterjee, Mitali

    2015-01-01

    Survival of the Leishmania parasite within monocytes hinges on its ability to effectively nullify their microbicidal effector mechanisms. Accordingly, this study aimed to delineate this biological niche in patients with visceral leishmaniasis (VL). In monocytes, the redox status, antigen presenting capacity, expression of Toll-like receptors (TLRs), co-stimulatory molecules (CD80/86) and generation of intracellular cytokines (IL-8, IL-1β, IL-10 and LAP-TGF-β1) was measured by flow cytometry, levels of circulating cytokines (IL-1β, IL-6, TNF-α, IL-8, IL-4, IL-13, IL-10 and GM-CSF) by ELISA and arginase activity by spectrophotometry. Within monocytes, generation of an oxidative burst was markedly attenuated as evident by decreased generation of nitric oxide and reactive oxygen species, concomitant with raised levels of thiols. This was accompanied by lowered frequency of TLR4(+) monocytes, but the arginase activity remained unaltered. Pathogen persistence was enhanced by the predominance of anti-inflammatory cytokines within monocytes, notably IL-10. Alongside, development of adaptive immunity was severely attenuated as manifested by a pronounced impairment of antigen presentation and co-stimulation evident by down regulation of CD54, HLA-DR and CD86. Treatment corrected the redox imbalance and reversed the impaired antigen presentation. In VL, monocyte functions were severely impaired facilitating parasite persistence; anti-leishmanial chemotherapy mediated parasite elimination through modulation of the macrophage microenvironment by restoring its redox status and antigen presenting capacity.

  18. Non-glycanated Decorin Is a Drug Target on Human Adipose Stromal Cells

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    Alexes C. Daquinag

    2017-09-01

    Full Text Available Adipose stromal cells (ASCs have been identified as a mesenchymal cell population recruited from white adipose tissue (WAT by tumors and supporting cancer progression. We have previously reported the existence of a non-glycanated decorin isoform (ngDCN marking mouse ASCs. We identified a peptide CSWKYWFGEC that binds to ngDCN and hence can serve as a vehicle for ASC-directed therapy delivery. We used hunter-killer peptides composed of CSWKYWFGEC and a pro-apoptotic moiety to deplete ASCs and suppress growth of mouse tumors. Here, we report the discovery of the human non-glycanated decorin isoform. We show that CSWKYWFGEC can be used as a probe to identify ASCs in human WAT and tumors. We demonstrate that human ngDCN is expressed on ASC surface. Finally, we validate ngDCN as a molecular target for pharmacological depletion of human ASCs with hunter-killer peptides. We propose that ngDCN-targeting agents could be developed for obesity and cancer treatment.

  19. Xeno-Free Extraction, Culture, and Cryopreservation of Human Adipose-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Escobar, Carlos Hugo; Chaparro, Orlando

    2016-03-01

    Molecules of animal or bacterial origin, which pose a risk for zoonoses or immune rejection, are commonly used for extraction, culture, and cryopreservation of mesenchymal stem cells. There is no sequential and orderly protocol for producing human adipose-derived stem cells (hASCs) under xeno-free conditions. After standardizing a human platelet lysate (hPL) production protocol, four human adipose tissue samples were processed through explants with fetal bovine serum (FBS)-supplemented or hPL-supplemented media for extracting the adipose-derived stem cells. The cells were cultivated in cell culture medium + hPL (5%) or FBS (10%). The cellular replication rate, immunophenotype, and differentiation potential were evaluated at fourth passage. Cellular viability was evaluated before and after cryopreservation of the cells, with an hPL-based solution compared with an FBS-based solution. The explants cultured in hPL-supplemented media showed earlier and faster hASC proliferation than did those supplemented with FBS. Likewise, cells grown in hPL-supplemented media showed a greater proliferation rate, without losing the immunophenotype. Osteogenic differentiation of xeno-free hASC was higher than the hASC produced in standard conditions. However, adipogenic differentiation was reduced in xeno-free hASC. Finally, the cells cryopreserved in an hPL-based solution showed a higher cellular viability than the cells cryopreserved in an FBS-based. In conclusion, we have developed a complete xeno-free protocol for extracting, culturing, and cryopreserving hASCs that can be safely implemented in clinical studies. ©AlphaMed Press.

  20. Brown adipose tissue: research milestones of a potential player in human energy balance and obesity.

    Science.gov (United States)

    Zafrir, B

    2013-10-01

    Obesity and diabetes mellitus are worldwide epidemics driven by the disruption in energy balance. In recent years, it was discovered that functional brown adipose tissue (BAT), once thought to exist mainly in infants, is present in adults, and can be detected during cold stimulation, and is associated with decreased adiposity. Brown fat pads were shown to be highly vascularized and metabolically active and on stimulation, they caused enhanced energy expenditure and increased glucose and fatty acid uptake. These observations drew attention to the possibility that nonshivering thermogenesis mediated by activation of BAT might be important in human energy balance and a potential tool to counter obesity. Recent investigations have revealed significant advances in the understanding of the role of BAT-mediated thermogenesis, uncovering essential knowledge on the origin, differentiation, activation, and regulation of BAT in both murine models and humans. In addition to classic BAT depots, transformation of white adipocytes into brown-like adipocytes, and the development of "beige" cells from distinct precursors, were demonstrated in different animal models and resulted in increased thermogenic activity. Several transcription factors, activating proteins, and hormones are increasingly identified as regulating the development and function of both brown-like adipocytes and classic brown fat pads. This review will summarize the evolution of research on BAT in humans, in light of the renewed scientific interest and growing body of evidence showing that recruitment and activation of BAT and browning of white adipose tissue can affect energy expenditure and may be a future feasible target in the treatment of metabolic diseases. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Ethanol exerts anti-inflammatory effects in human adipose tissue in vitro.

    Science.gov (United States)

    Wandler, Anne; Bruun, Jens M; Nielsen, Maria P; Richelsen, Bjørn

    2008-12-16

    Moderate alcohol consumption is suggested to be associated with reduced inflammation and morbidity. Human adipose tissue (AT) and obesity is characterised by low-grade inflammation, so the present study wanted to investigate the effects of ethanol on inflammation in human AT in vitro. Subcutaneous human AT was incubated with ethanol [11-88 mM] under non- or LPS-stimulated [50mg/mL] conditions. Protein and mRNA levels of adiponectin, IL-6, IL-8, TNF-alpha, MCP-1, and CD68 were assessed using ELISA and real-time RT-PCR, respectively. Non-stimulated, ethanol incubations up to 24h increased adiponectin release and mRNA expression (p0.05). In conclusion, ethanol exerts anti-inflammatory effects in human AT, suggesting that ethanol may attenuate whole-body inflammation.

  2. Fatty acids do not pay the toll: effect of SFA and PUFA on human adipose tissue and mature adipocytes inflammation

    Directory of Open Access Journals (Sweden)

    Murumalla Ravi Kumar

    2012-12-01

    Full Text Available Abstract Background On the basis that high fat diet induces inflammation in adipose tissue, we wanted to test the effect of dietary saturated and polysunsaturated fatty acids on human adipose tissue and adipocytes inflammation. Moreover we wanted to determine if TLR2 and TLR4 are involved in this pathway. Methods Human adipose tissue and adipocytes primary cultures were treated with endotoxin-free BSA conjugated with SFA (lauric acid and palmitic acid - LA and PA and PUFA (eicosapentaeneic acid, docosahexaenoic acid and oleic acid - EPA, DHA and OA with or without LPS. Cytokines were then assayed by ELISA (TNF-alpha, IL-6 and MCP-1. In order to determine if TLR2 and TLR4 are activated by fatty acid (FA, we used HEK-Blue cells transfected by genes from TLR2 or TLR4 pathways associated with secreted alkaline phosphatase reporter gene. Results None of the FA tested in HEK-Blue cells were able to activate TLR2 or TLR4, which is concordant with the fact that after FA treatment, adipose tissue and adipocytes cytokines levels remain the same as controls. However, all the PUFA tested: DHA, EPA and to a lesser extent OA down-regulated TNF-alpha, IL-6 and MCP-1 secretion in human adipose tissue and adipocytes cultures. Conclusions This study first confirms that FA do not activate TLR2 and TLR4. Moreover by using endotoxin-free BSA, both SFA and PUFA tested were not proinflammatory in human adipose tissue and adipocytes model. More interestingly we showed that some PUFA exert an anti-inflammatory action in human adipose tissue and adipocytes model. These results are important since they clarify the relationship between dietary fatty acids and inflammation linked to obesity.

  3. Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training

    DEFF Research Database (Denmark)

    Alsted, Thomas J; Schweiger, Martina; Nybo, Lars

    2009-01-01

    ) is not changed. Recently, adipose triglyceride lipase (ATGL) was identified as a TG-specific lipase in various rodent tissues. To investigate whether human skeletal muscle ATGL protein is regulated by endurance exercise training, 10 healthy young men completed 8 wk of supervised endurance exercise training...... altogether, indicating an enhanced basal activity of this lipase. No change was found in the expression of diacylglycerol acyl transferase 1 (DGAT1) after training. Inhibition of HSL with a monospecific, small molecule inhibitor (76-0079) and stimulation of ATGL with CGI-58 revealed that significant ATGL...

  4. Serum soluble markers in the evaluation of treatment in human visceral leishmaniasis.

    Science.gov (United States)

    Schriefer, A; Barral, A; Carvalho, E M; Barral-Netto, M

    1995-12-01

    Visceral leishmaniasis (VL) has a fatal course if not properly treated. Recovery from VL is linked to cellular immune response. Unresponsiveness to antimonial therapy reinforces the importance of determining parameters for treatment assessment. We analysed the pre- and post-treatment serum levels of soluble CD4 (sCD4), sCD8, sIL-2R, soluble intercellular adhesion molecule-1 (sICAM-1) and neopterin in groups of VL patients either responsive or not to standard antimonial therapy. Pretreatment serum levels of all markers except for sICAM-1 were significantly higher in VL patients than in healthy subjects from the same area (P antimonial therapy (P = 0.25), but significantly higher in patients responsive to treatment (P = 0.02). The comparison of pre- and post-treatment concentrations showed that all markers, except sCD4 and sICAM-1, presented a significant fall (P antimonial therapy. However, only neopterin presented with levels compatible with those of healthy subjects at the end of treatment (P = 0.30). In refractory patients sICAM-1 presented with post-treatment levels significantly higher than the pretreatment determinations (P = 0.03), while sCD4 experienced a significant drop (P = 0.01). All markers displayed clearly distinct behaviour according to the patient's response to therapy. This makes all soluble molecules studied suitable for use as indicators of antimonial therapy response. Additionally the comparison of pretreatment levels of the markers between responders and refractory patients to antimonial therapy showed that serum concentrations of sIL-2R and sICAM-1 significantly differed among these two groups (P = 0.02 in each case), suggesting that they may be used in future as predictors of antimonial therapy response.

  5. Serum soluble markers in the evaluation of treatment in human visceral leishmaniasis.

    Science.gov (United States)

    Schriefer, A; Barral, A; Carvalho, E M; Barral-Netto, M

    1995-01-01

    Visceral leishmaniasis (VL) has a fatal course if not properly treated. Recovery from VL is linked to cellular immune response. Unresponsiveness to antimonial therapy reinforces the importance of determining parameters for treatment assessment. We analysed the pre- and post-treatment serum levels of soluble CD4 (sCD4), sCD8, sIL-2R, soluble intercellular adhesion molecule-1 (sICAM-1) and neopterin in groups of VL patients either responsive or not to standard antimonial therapy. Pretreatment serum levels of all markers except for sICAM-1 were significantly higher in VL patients than in healthy subjects from the same area (P antimonial therapy (P = 0.25), but significantly higher in patients responsive to treatment (P = 0.02). The comparison of pre- and post-treatment concentrations showed that all markers, except sCD4 and sICAM-1, presented a significant fall (P antimonial therapy. However, only neopterin presented with levels compatible with those of healthy subjects at the end of treatment (P = 0.30). In refractory patients sICAM-1 presented with post-treatment levels significantly higher than the pretreatment determinations (P = 0.03), while sCD4 experienced a significant drop (P = 0.01). All markers displayed clearly distinct behaviour according to the patient's response to therapy. This makes all soluble molecules studied suitable for use as indicators of antimonial therapy response. Additionally the comparison of pretreatment levels of the markers between responders and refractory patients to antimonial therapy showed that serum concentrations of sIL-2R and sICAM-1 significantly differed among these two groups (P = 0.02 in each case), suggesting that they may be used in future as predictors of antimonial therapy response. PMID:8536369

  6. [Human and canine visceral leishmaniasis in the Papsky District, Namangan Region, Uzbekistan: seroepidemiological and seroepizootological surveys].

    Science.gov (United States)

    Kovalenko, D A; Nasyrova, R M; Ponomareva, V I; Fatullaeva, A A; Razakov, Sh A; Ponirovskiĭ, E N; Strelkova, M V; Zhirenkina, E N; Morozov, E N; Dzhaf, Ch; Banet, G; Shnur, L; Varburg, A; Shonian, G

    2011-01-01

    In 2007 - 2008, four (Chodak, Oltinkan, Gulistan, and Chorkesar) of 9 population aggregates in the Papsky District, Namangan Region, Uzbekistan, where visceral leishmaniasis (VL) cases had been registered in the last years were selected to make seroepidemiological and seroepizootological surveys within the international project funded by INTAS grant 05-100006-8043. The surveys of the populations were conducted visiting their homesteads. These additionally included children's and health care facilities where all children aged less than 14 years were examined. On examining the children, their peripheral blood (approximately 0.1 ml) was taken on filter paper for serological assays. Canine blood was sampled from the vein. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect antibodies to VL pathogens. A total of 521 children were examined for two years, by applying ELISA. Five hundred and fourteen blood samples from children younger than 14 years, 162 dogs, 4 foxes, and 1 cat were tested. Testing 514 children's blood samples for VL pathogen antigen ascertained that in the 4 population aggregates there was an average of 10% VL-seropositive children, including those who were ill with VL at the moment of the examination and had been ill. The highest number of VL-seropositive samples (14.9%) was found in the settlement of Chodak. VL pathogen antibodies were detected in 26 (61.9%) of 42 dogs with the clinical signs of VL. VL-positive tests were found in 26 (21.6%) of 120 apparently healthy dogs. The samples from 4 foxes and 1 cat were negative. Immunological findings indicated that 0-3-year-old children were a group that is most susceptible to VL in the study focus of this disease. The high proportion of dogs with VL may account for the rise in infant morbidity and suggests the epizootic strain in the focus of VL in the Papsky District.

  7. Human visceral leishmaniasis in kermanshah province, Western iran, during 2011-2012.

    Science.gov (United States)

    Hamzavi, Y; Hamzeh, B; Mohebali, M; Akhoundi, B; Ajhang, Kh; Khademi, N; Ghadiri, K; Bashiri, H; Pajhouhan, M

    2012-01-01

    Visceral leishmaniasis (VL) or kala-azar is a parasitic disease caused by the species of Leishmania donovani complex. It is endemic in some parts of provinces of Iran. According to the reported cases of VL in Kermanshah Province in recent years, this study was conducted to determine the seroprevalence of VL in high risk villages of the province. Totally, 1622 serum samples obtained from children under 15 years old and 178 from adults in 22 villages of studied areas. Serum samples were examined by direct agglutination test (DAT) for the detection of anti-Leishmania antibodies. Data were analyzed using SPSS software ver.11.5. Only 6 serum samples (0.33%) showed anti-Leishmania antibodies against L.infantum at titers ≥ 1/3200. Four of the seropositive cases had a history of kala-azar and Leishman bodies were seen in their bone marrows. The highest (0.5%) and lowest (0.29%) seroprevalence was seen in the age groups of 5-9 and 10-14 years old, respectively. None of the adults were seropositive. There were not any significant differences between the rate of seropositivity in males (0.36%) and females (0.31%). 66.7% of seropositive individuals showed clinical manifestations. The most important symptoms in Kala-azar patients were fever, hepato-spleenomegally and anemia. Kala-azar is occurred sporadically in Kermanshah Province. But presence of significant number of positive sera confirms the necessity for attention of people and clinicians to kala-azar.

  8. Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats.

    Science.gov (United States)

    Amini, Naser; Vousooghi, Nasim; Hadjighassem, Mahmoudreza; Bakhtiyari, Mehrdad; Mousavi, Neda; Safakheil, Hosein; Jafari, Leila; Sarveazad, Arash; Yari, Abazar; Ramezani, Sara; Faghihi, Faezeh; Joghataei, Mohammad Taghi

    2016-05-01

    Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.

  9. Serum Visfatin and Leptin in Relation to Childhood Adiposity and Body Fat Distribution : The PIAMA Birth Cohort Study

    NARCIS (Netherlands)

    Willers, Saskia M.; Brunekreef, Bert; Abrahamse-Berkeveld, Marieke; van de Heijning, Bert; van der Beek, Eline; Postma, Dirkje S.; Kerkhof, Marjan; Smit, Henriette A.; Wijga, Alet H.

    2015-01-01

    Background/Aims: Visfatin has been suggested as a marker of visceral adiposity. We hypothesized that visfatin, but not leptin, would be specifically associated with visceral adiposity. We investigated the relation of serum visfatin and leptin with measures of adiposity and body fat distribution in

  10. Induction of circadian gene expression in human subcutaneous adipose-derived stem cells.

    Science.gov (United States)

    Wu, Xiying; Zvonic, Sanjin; Floyd, Z Elizabeth; Kilroy, Gail; Goh, Brian C; Hernandez, Teri L; Eckel, Robert H; Mynatt, Randall L; Gimble, Jeffrey M

    2007-11-01

    Genes encoding the circadian transcriptional apparatus exhibit robust oscillatory expression in murine adipose tissues. This study tests the hypothesis that human subcutaneous adipose-derived stem cells (ASCs) provide an in vitro model in which to monitor the activity of the core circadian transcriptional apparatus. Primary cultures of undifferentiated or adipocyte-differentiated ASCs were treated with dexamethasone, rosiglitazone, or 30% fetal bovine serum. The response of undifferentiated ASCs to dexamethasone was further evaluated in the presence of lithium chloride. Lithium inhibits glycogen synthase kinase 3, a key component of the circadian apparatus. Total RNA was harvested at 4-hour intervals over 48 hours and examined by real-time reverse transcription polymerase chain reaction (RT-PCR). Adipocyte-differentiated cells responded more rapidly to treatments than their donor-matched undifferentiated controls; however, the period of the circadian gene oscillation was longer in the adipocyte-differentiated cells. Dexamethasone generated circadian gene expression patterns with mean periods of 25.4 and 26.7 hours in undifferentiated and adipocyte-differentiated ASCs, respectively. Both rosiglitazone and serum shock generated a significantly longer period in adipocyte-differentiated ASCs relative to undifferentiated ASCs. The Bmal1 profile was phase-shifted by approximately 8 to 12 hours relative to Per1, Per3, and Cry2, consistent with their expression in vivo. Lithium chloride inhibited adipogenesis and significantly lengthened the period of Per3 and Rev-erbalpha gene expression profiles by >5 hours in dexamethasone-activated undifferentiated ASCs. These results support the initial hypothesis and validate ASCs as an in vitro model for the analysis of circadian biology in human adipose tissue.

  11. In vitro osteoinductive effects of hydroxycholesterol on human adipose-derived stem cells are mediated through the hedgehog signaling pathway.

    Science.gov (United States)

    Yalom, Anisa; Hokugo, Akishige; Sorice, Sarah; Li, Andrew; Segovia Aguilar, Luis A; Zuk, Patricia; Jarrahy, Reza

    2014-11-01

    Human adipose-derived stem cells have been identified as a potential source of cells for use in bone tissue engineering because of their ready availability, ease of harvest, and susceptibility to osteogenic induction. The authors have previously demonstrated the ability of an osteogenic molecule called hydroxycholesterol, an oxidative derivative of cholesterol, to induce osteogenic differentiation in pluripotent murine and rabbit bone marrow stromal cells. In this study, the authors examine the ability of hydroxycholesterol to induce osteogenesis in human adipose-derived stem cells. Human adipose-derived stem cells were isolated from raw human lipoaspirates through standard isolation and expansion of the stromal vascular fraction. Cells were plated onto tissue culture plates in control medium and harvested between passages 2 and 3, incubated with conventional osteogenic media, and treated with various concentrations (1, 5, and 10 μM) of the 20(S) analogue of hydroxycholesterol. Evaluation of cellular osteogenic activity was performed. The role of the hedgehog signaling pathway in hydroxycholesterol-mediated osteogenesis was evaluated by hedgehog inhibition assays. Alkaline phosphatase activity, bone-related gene expression, and mineralization were all significantly increased in cultures of human adipose-derived stem cells treated with 5 μM of 20(S)-hydroxycholesterol relative to controls. In addition, induction of hydroxycholesterol-mediated osteogenesis was mitigated by the addition of the hedgehog pathway inhibitor to cell cultures, implicating the hedgehog signaling pathway in the osteogenic mechanism on human adipose-derived stem cells by hydroxycholesterol. These in vitro studies demonstrate that hydroxycholesterol exerts an osteoinductive influence on human adipose-derived stem cells and that these effects are mediated at least in part through the hedgehog signaling pathway.

  12. Comparison of T1-weighted 2D TSE, 3D SPGR, and two-point 3D Dixon MRI for automated segmentation of visceral adipose tissue at 3 Tesla.

    Science.gov (United States)

    Fallah, Faezeh; Machann, Jürgen; Martirosian, Petros; Bamberg, Fabian; Schick, Fritz; Yang, Bin

    2017-04-01

    To evaluate and compare conventional T1-weighted 2D turbo spin echo (TSE), T1-weighted 3D volumetric interpolated breath-hold examination (VIBE), and two-point 3D Dixon-VIBE sequences for automatic segmentation of visceral adipose tissue (VAT) volume at 3 Tesla by measuring and compensating for errors arising from intensity nonuniformity (INU) and partial volume effects (PVE). The body trunks of 28 volunteers with body mass index values ranging from 18 to 41.2 kg/m2 (30.02 ± 6.63 kg/m2) were scanned at 3 Tesla using three imaging techniques. Automatic methods were applied to reduce INU and PVE and to segment VAT. The automatically segmented VAT volumes obtained from all acquisitions were then statistically and objectively evaluated against the manually segmented (reference) VAT volumes. Comparing the reference volumes with the VAT volumes automatically segmented over the uncorrected images showed that INU led to an average relative volume difference of -59.22 ± 11.59, 2.21 ± 47.04, and -43.05 ± 5.01 % for the TSE, VIBE, and Dixon images, respectively, while PVE led to average differences of -34.85 ± 19.85, -15.13 ± 11.04, and -33.79 ± 20.38 %. After signal correction, differences of -2.72 ± 6.60, 34.02 ± 36.99, and -2.23 ± 7.58 % were obtained between the reference and the automatically segmented volumes. A paired-sample two-tailed t test revealed no significant difference between the reference and automatically segmented VAT volumes of the corrected TSE (p = 0.614) and Dixon (p = 0.969) images, but showed a significant VAT overestimation using the corrected VIBE images. Under similar imaging conditions and spatial resolution, automatically segmented VAT volumes obtained from the corrected TSE and Dixon images agreed with each other and with the reference volumes. These results demonstrate the efficacy of the signal correction methods and the similar accuracy of TSE and Dixon imaging for automatic volumetry of VAT at 3 Tesla.

  13. Immunobiology of visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Susanne eNylén

    2012-08-01

    Full Text Available Visceral leishmaniasis (VL, commonly known as kala-azar, is caused by Leishmania donovani and Leishmania infantum (Leishmania chagasi in the Americas. These Leishmania species infect macrophages throughout the viscera, and parasites are typically found in the spleen, liver and bone marrow. Patients with active disease typically exhibit marked immunosuppression, lack reactivity to the Leishmania skin test (LST, a delayed type hypersensitivity test, and their peripheral blood mononuclear cells (PBMC fail to respond when stimulated with leishmanial antigens in vitro. However, most people infected with visceralizing species of Leishmania never develop disease. Understanding immune failure and the underlying immune mechanism that lead to disease as well as control of infection are key questions for research in this field. In this review we discuss immunological events described in human and experimental VL and how these can affect the outcome of infection.

  14. Expansion of adipose mesenchymal stromal cells is affected by human platelet lysate and plating density.

    Science.gov (United States)

    Cholewa, Dominik; Stiehl, Thomas; Schellenberg, Anne; Bokermann, Gudrun; Joussen, Sylvia; Koch, Carmen; Walenda, Thomas; Pallua, Norbert; Marciniak-Czochra, Anna; Suschek, Christoph V; Wagner, Wolfgang

    2011-01-01

    The composition of mesenchymal stromal cells (MSCs) changes in the course of in vitro culture expansion. Little is known how these cell preparations are influenced by culture media, plating density, or passaging. In this study, we have isolated MSCs from human adipose tissue in culture medium supplemented with either fetal calf serum (FCS) or human platelet lysate (HPL). In addition, culture expansion was simultaneously performed at plating densities of 10 or 10,000 cells/cm(2). The use of FCS resulted in larger cells, whereas HPL significantly enhanced proliferation. Notably, HPL also facilitated expansion for more population doublings than FCS (43 ± 3 vs. 22 ± 4 population doubling; p < 0.001), while plating density did not have a significant effect on long-term growth curves. To gain further insight into population dynamics, we conceived a cellular automaton model to simulate expansion of MSCS. It is based on the assumptions that the number of cell divisions is limited and that due to contact inhibition proliferation occurs only at the rim of colonies. The model predicts that low plating densities result in more heterogeneity with regard to cell division history, and favor subpopulations of higher migratory activity. In summary, HPL is a suitable serum supplement for isolation of MSC from adipose tissue and facilitates more population doublings than FCS. Cellular automaton computer simulations provided additional insights into how complex population dynamics during long-term expansion are affected by plating density and migration.

  15. Multipotency and cardiomyogenic potential of human adipose-derived stem cells from epicardium, pericardium, and omentum.

    Science.gov (United States)

    Wystrychowski, Wojciech; Patlolla, Bhagat; Zhuge, Yan; Neofytou, Evgenios; Robbins, Robert C; Beygui, Ramin E

    2016-06-13

    Acute myocardial infarction (MI) leads to an irreversible loss of proper cardiac function. Application of stem cell therapy is an attractive option for MI treatment. Adipose tissue has proven to serve as a rich source of stem cells (ADSCs). Taking into account the different morphogenesis, anatomy, and physiology of adipose tissue, we hypothesized that ADSCs from different adipose tissue depots may exert a diverse multipotency and cardiogenic potential. The omental, pericardial, and epicardial adipose tissue samples were obtained from organ donors and patients undergoing heart transplantation at our institution. Human foreskin fibroblasts were used as the control group. Isolated ADSCs were analyzed for adipogenic and osteogenic differentiation capacity and proliferation potential. The immunophenotype and constitutive gene expression of alkaline phosphatase (ALP), GATA4, Nanog, and OCT4 were analyzed. DNA methylation inhibitor 5-azacytidine was exposed to the cells to stimulate the cardiogenesis. Finally, reprogramming towards cardiomyocytes was initiated with exogenous overexpression of seven transcription factors (ESRRG, GATA4, MEF2C, MESP1, MYOCD, TBX5, ZFPM2) previously applied successfully for fibroblast transdifferentiation toward cardiomyocytes. Expression of cardiac troponin T (cTNT) and alpha-actinin (Actn2) was analyzed 3 weeks after initiation of the cardiac differentiation. The multipotent properties of isolated plastic adherent cells were confirmed with expression of CD29, CD44, CD90, and CD105, as well as successful differentiation toward adipocytes and osteocytes; with the highest osteogenic and adipogenic potential for the epicardial and omental ADSCs, respectively. Epicardial ADSCs demonstrated a lower doubling time as compared with the pericardium and omentum-derived cells. Furthermore, epicardial ADSCs revealed higher constitutive expression of ALP and GATA4. Increased Actn2 and cTNT expression was observed after the transduction of seven

  16. The influence of sex steroids on adipose tissue growth and function.

    Science.gov (United States)

    Law, James; Bloor, Ian; Budge, Helen; Symonds, Michael E

    2014-07-01

    Obesity remains a major global health concern. Understanding the metabolic influences of the obesity epidemic in the human population on maintenance of a healthy weight and metabolic profile is still of great significance. The importance and role of white adipose tissue has been long established, particularly with excess adiposity. Brown adipose tissue (BAT), however, has only recently been shown to contribute significantly to the metabolic signature of mammals outside the previously recognised role in small mammals and neonates. BAT's detection in adults has led to a renewed interest and is now considered to be a potential therapeutic target to prevent excess white fat accumulation in obesity, a theory further promoted by the recent discovery of beige fat. Adipose tissue distribution varies significantly between genders. Pre-menopausal females often show enhanced lower and peripheral fat deposition in adiposity deposition compared to the male profile of central and visceral fat accumulation with obesity. This sex disparity is partly attributed to the different effects of sex hormone profiles and interactions on the adipose tissue system. In this review, we explore this intricate relationship and show how modifications in the effects of sex hormones impact on both brown and white adipose tissues. We also discuss the impact of sex hormones on activation of the hypothalamic-pituitary-adrenal (HPA) axis and how the three pathways between adiposity, HPA and sex steroids can have a major contribution to the prevention or maintenance of obesity and therefore on overall health.

  17. MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Francisco J Ortega

    Full Text Available BACKGROUND: Potential regulators of adipogenesis include microRNAs (miRNAs, small non-coding RNAs that have been recently shown related to adiposity and differentially expressed in fat depots. However, to date no study is available, to our knowledge, regarding miRNAs expression profile during human adipogenesis. Thereby, the aim of this study was to investigate whether miRNA pattern in human fat cells and subcutaneous adipose tissue is associated to obesity and co-morbidities and whether miRNA expression profile in adipocytes is linked to adipogenesis. METHODOLOGY/PRINCIPAL FINDINGS: We performed a global miRNA expression microarray of 723 human and 76 viral mature miRNAs in human adipocytes during differentiation and in subcutaneous fat samples from non-obese (n = 6 and obese with (n = 9 and without (n = 13 Type-2 Diabetes Mellitus (DM-2 women. Changes in adipogenesis-related miRNAs were then validated by RT-PCR. Fifty of 799 miRNAs (6.2% significantly differed between fat cells from lean and obese subjects. Seventy miRNAs (8.8% were highly and significantly up or down-regulated in mature adipocytes as compared to pre-adipocytes. Otherwise, 17 of these 799 miRNAs (2.1% were correlated with anthropometrical (BMI and/or metabolic (fasting glucose and/or triglycerides parameters. We identified 11 miRNAs (1.4% significantly deregulated in subcutaneous fat from obese subjects with and without DM-2. Interestingly, most of these changes were associated with miRNAs also significantly deregulated during adipocyte differentiation. CONCLUSIONS/SIGNIFICANCE: The remarkable inverse miRNA profile revealed for human pre-adipocytes and mature adipocytes hints at a closely crosstalk between miRNAs and adipogenesis. Such candidates may represent biomarkers and therapeutic targets for obesity and obesity-related complications.

  18. Adipogenesis of Human Adipose-Derived Stem Cells Within Three-Dimensional Hollow Fiber-Based Bioreactors

    Science.gov (United States)

    Gerlach, Jörg C.; Lin, Yen-Chih; Brayfield, Candace A.; Minteer, Danielle M.; Li, Han; Rubin, J. Peter

    2012-01-01

    To further differentiate adipose-derived stem cells (ASCs) into mature adipocytes and create three-dimensional (3D) adipose tissue in vitro, we applied multicompartment hollow fiber-based bioreactor technology with decentral mass exchange for more physiological substrate gradients and integral oxygenation. We hypothesize that a dynamic 3D perfusion in such a bioreactor will result in longer-term culture of human adipocytes in vitro, thus providing metabolically active tissue serving as a diagnostic model for screening drugs to treat diabetes. ASCs were isolated from discarded human abdominal subcutaneous adipose tissue and then inoculated into dynamic 3D culture bioreactors to undergo adipogenic differentiation. Insulin-stimulated glucose uptake from the medium was assessed with and without TNF-alpha. 3D adipose tissue was generated in the 3D-bioreactors. Immunohistochemical staining indicated that 3D-bioreactor culture displayed multiple mature adipocyte markers with more unilocular morphologies as compared with two-dimensional (2D) cultures. Results of real-time polymerase chain reaction showed 3D-bioreactor treatment had more efficient differentiation in fatty acid-binding protein 4 expression. Repeated insulin stimulation resulted in increased glucose uptake, with a return to baseline between testing. Importantly, TNF-alpha inhibited glucose uptake, an indication of the metabolic activity of the tissue. 3D bioreactors allow more mature adipocyte differentiation of ASCs compared with traditional 2D culture and generate adipose tissue in vitro for up to 2 months. Reproducible metabolic activity of the adipose tissue in the bioreactor was demonstrated, which is potentially useful for drug discovery. We present here, to the best of our knowledge for the first time, the development of a coherent 3D high density fat-like tissue consisting of unilocular structure from primary adipose stem cells in vitro. PMID:21902468

  19. Differentiation of reprogrammed human adipose mesenchymal stem cells toward neural cells with defined transcription factors.

    Science.gov (United States)

    Qu, Xinjian; Liu, Tianqing; Song, Kedong; Li, Xiangqin; Ge, Dan

    2013-10-04

    Somatic cell reprogramming may become a powerful approach to generate specific human cell types for cell-fate determination studies and potential transplantation therapies of neurological diseases. Here we report a reprogramming methodology with which human adipose stem cells (hADSCs) can be differentiated into neural cells. After being reprogrammed with polycistronic plasmid carrying defined factor OCT3/4, SOX2, KLF4 and c-MYC, and further treated with neural induce medium, the hADSCs switched to differentiate toward neural cell lineages. The generated cells had normal karyotypes and exogenous vector sequences were not inserted in the genomes. Therefore, this cell lineage conversion methodology bypasses the risk of mutation and gene instability, and provides a novel strategy to obtain patient-specific neural cells for basic research and therapeutic application. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Activation and recruitment of brown adipose tissue by cold exposure and food ingredients in humans.

    Science.gov (United States)

    Saito, Masayuki; Yoneshiro, Takeshi; Matsushita, Mami

    2016-08-01

    Since the recent re-discovery of brown adipose tissue (BAT) in adult humans, this thermogenic tissue has attracted increasing interest. The inverse relationship between the BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. Cold exposure activates and recruits BAT in association with increased energy expenditure and decreased body fatness. The stimulatory effects of cold are mediated through transient receptor potential channels (TRP), most of which are also chemesthetic receptors for various food ingredients. In fact, capsaicin and its analog capsinoids, representative agonists of TRPV1, mimic the effects of cold to decrease body fatness through the activation and recruitment of BAT. The anti-obesity effect of some other food ingredients including tea catechins may also be attributable to the activation of the TRP-BAT axis. Thus, BAT is a promising target for combating obesity and related metabolic disorders in humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Mechanical properties of cross-linked collagen meshes after human adipose derived stromal cells seeding.

    Science.gov (United States)

    Ochoa, Ignacio; Peña, Estefania; Andreu, Enrique J; Pérez-Ilzarbe, Maitane; Robles, Jose E; Alcaine, Clara; López, Tania; Prósper, Felipe; Doblaré, Manuel

    2011-02-01

    The main goal of this study was to evaluate the potential of collagen meshes derived from porcine dermis as scaffolds for repairing pelvic organ prolapses. Mechanical properties of collagen meshes with different cross-linking percentages before and after Adipose Derived Stromal Cells (ADSC) seeding were studied as well as the cell-scaffold interaction. Uniaxial tensile tests of the collagen meshes with three different cross-linking percentages (full-, partial-, and noncross-linked) were carried out along orthogonal directions. Their mechanical properties were studied with the same tests before and after seeding with human derived adipose stem cells (ADSC) after 1 and 7 days. Histological analyses were performed to determine adhesion and proliferation of ADSC. Significant differences in mechanical properties of the unseeded meshes were observed between each orthogonal direction independently of the cross-linking percentage. A better cell adhesion rate was observed in the cross-linked meshes. An increase in the mechanical properties after cell seeding was observed with a direct relation with the degree of cross-linking. All meshes analyzed showed a marked anisotropy that should be taken into account during the surgical procedure. The cross-linking treatment increased cell adhesion and the mechanical properties of the collagen meshes after seeding. These results suggest that the mechanical properties of this type of collagen mesh could be useful as scaffolds for repair of pelvic organ prolapse. 2010 Wiley Periodicals, Inc.

  2. Characterization of Human Knee and Chin Adipose-Derived Stromal Cells

    Directory of Open Access Journals (Sweden)

    Magali Kouidhi

    2015-01-01

    Full Text Available Animal study findings have revealed that individual fat depots are not functionally equivalent and have different embryonic origins depending on the anatomic location. Mouse bone regeneration studies have also shown that it is essential to match the Hox code of transplanted cells and host tissues to achieve correct repair. However, subcutaneous fat depots from any donor site are often used in autologous fat grafting. Our study was thus carried out to determine the embryonic origins of human facial (chin and limb (knee fat depots and whether they had similar features and molecular matching patterns. Paired chin and knee fat depots were harvested from 11 subjects and gene expression profiles were determined by DNA microarray analyses. Adipose-derived stromal cells (ASCs from both sites were isolated and analyzed for their capacity to proliferate, form clones, and differentiate. Chin and knee fat depots expressed a different HOX code and could have different embryonic origins. ASCs displayed a different phenotype, with chin-ASCs having the potential to differentiate into brown-like adipocytes, whereas knee-ASCs differentiated into white adipocytes. These results highlighted different features for these two fat sites and indicated that donor site selection might be an important factor to be considered when applying adipose tissue in cell-based therapies.

  3. THP-1 macrophages and SGBS adipocytes - a new human in vitro model system of inflamed adipose tissue

    Directory of Open Access Journals (Sweden)

    Michaela eKeuper

    2011-12-01

    Full Text Available Obesity is associated with an accumulation of macrophages in adipose tissue. This inflammation of adipose tissue is a key event in the pathogenesis of several obesity-related disorders, particularly insulin resistance.Here, we summarized existing model systems that mimic the situation of inflamed adipose tissue in vitro, most of them being murine. Importantly, we introduce our newly established human model system which combines the THP-1 monocytic cell line and the preadipocyte cell strain SGBS. THP-1 cells, which originate from an acute monocytic leukemia, differentiate easily into macrophages in vitro. The human preadipocyte cell strain SGBS (Simpson-Golabi-Behmel syndrome was recently introduced as a unique to tool to study human fat cell functions. SGBS cells are characterized by a high capacity for adipogenic differentiation. SGBS adipocytes are capable of fat cell-specific metabolic functions such as insulin-stimulated glucose uptake, insulin-stimulated de novo lipogenesis and beta-adrenergic-stimulated lipolysis and they secrete typical adipokines including leptin, adiponectin, and RBP4. Applying either macrophage-conditioned medium or a direct co-culture of macrophages and fat cells, our model system can be used to distinguish between paracrine and cell-contact dependent effects.In conclusion, we propose this model as a useful tool to study adipose inflammation in vitro. It represents an inexpensive, highly reproducible human system. The methods described here can be easily extended for usage of primary human macrophages and fat cells.

  4. An Adipose Segmentation and Quantification Scheme for the Abdominal Region in Minipigs

    DEFF Research Database (Denmark)

    Engholm, Rasmus; Dubinskiy, Aleks; Larsen, Rasmus

    2006-01-01

    This article describes a method for automatic segmentation of the abdomen into three anatomical regions: subcutaneous, retroperitoneal and visceral. For the last two regions the amount of adipose tissue (fat) is quantified. According to recent medical research, the distinction between...... retroperitoneal and visceral fat is important for studying metabolic syndrome, which is closely related to diabetes.1 However previous work has neglected to address this point, treating the two types of fat together. We use T1-weighted three-dimensional magnetic resonance data of the abdomen of obese minipigs....... The pigs were manually dissected right after the scan, to produce the “ground truth” segmentation. We perform automatic segmentation on a representative slice, which on humans has been shown to correlate with the amount of adipose tissue in the abdomen. The process of automatic fat estimation consists...

  5. The Roles of Adipokines, Proinflammatory Cytokines, and Adipose Tissue Macrophages in Obesity-Associated Insulin Resistance in Modest Obesity and Early Metabolic Dysfunction.

    Directory of Open Access Journals (Sweden)

    Yea Eun Kang

    Full Text Available The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance have been explored in both animal and human studies. However, our current understanding of obesity-associated insulin resistance relies on studies of artificial metabolic extremes. The purpose of this study was to explore the roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in human patients with modest obesity and early metabolic dysfunction. We obtained omental adipose tissue and fasting blood samples from 51 females undergoing gynecologic surgery. We investigated serum concentrations of proinflammatory cytokines and adipokines as well as the mRNA expression of proinflammatory and macrophage phenotype markers in visceral adipose tissue using ELISA and quantitative RT-PCR. We measured adipose tissue inflammation and macrophage infiltration using immunohistochemical analysis. Serum levels of adiponectin and leptin were significantly correlated with HOMA-IR and body mass index. The levels of expression of MCP-1 and TNF-α in visceral adipose tissue were also higher in the obese group (body mass index ≥ 25. The expression of mRNA MCP-1 in visceral adipose tissue was positively correlated with body mass index (r = 0.428, p = 0.037 but not with HOMA-IR, whereas TNF-α in visceral adipose tissue was correlated with HOMA-IR (r = 0.462, p = 0.035 but not with body mass index. There was no obvious change in macrophage phenotype or macrophage infiltration in patients with modest obesity or early metabolic dysfunction. Expression of mRNA CD163/CD68 was significantly related to mitochondrial-associated genes and serum inflammatory cytokine levels of resistin and leptin. These results suggest that changes in the production of inflammatory biomolecules precede increased immune cell infiltration and induction of a macrophage phenotype switch in visceral adipose tissue. Furthermore, serum resistin and

  6. Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells.

    Science.gov (United States)

    Pistone Creydt, Virginia; Fletcher, Sabrina Johanna; Giudice, Jimena; Bruzzone, Ariana; Chasseing, Norma Alejandra; Gonzalez, Eduardo Gustavo; Sacca, Paula Alejandra; Calvo, Juan Carlos

    2013-02-01

    Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

  7. Effects of conditioned medium from LL-37 treated adipose stem cells on human fibroblast migration.

    Science.gov (United States)

    Yang, Eun-Jung; Bang, Sa-Ik

    2017-07-01

    Adipose stem cell-conditioned medium may promote human dermal fibroblast (HDF) proliferation and migration by activating paracrine peptides during the re-epithelization phase of wound healing. Human antimicrobial peptide LL-37 is upregulated in the skin epithelium as part of the normal response to injury. The effects of conditioned medium (CM) from LL-37 treated adipose stem cells (ASCs) on cutaneous wound healing, including the mediation of fibroblast migration, remain to be elucidated, therefore the aim of the present study was to determine how ASCs would react to an LL-37-rich microenvironment and if CM from LL-37 treated ASCs may influence the migration of HDFs. The present study conducted migration assays with HDFs treated with CM from LL-37 treated ASCs. Expression of CXC chemokine receptor 4 (CXCR4), which controls the recruitment of HDFs, was analyzed at the mRNA and protein levels. To further characterize the stimulatory effects of LL-37 on ASCs, the expression of stromal cell-derived factor-1α (SDF-1α), a CXC chemokine, was investigated. CM from LL-37-treated ASCs induced migration of HDFs in a time- and dose-dependent manner, with a maximum difference in migration observed 24 h following stimulation with LL-37 at a concentration of 10 µg/ml. The HDF migration and the expression of CXCR4 in fibroblasts was markedly increased upon treatment with CM from LL-37-treated ASCs compared with CM from untreated ASCs. SDF-1α expression was markedly increased in CM from LL-37 treated ASCs. It was additionally observed that SDF-1α blockade significantly reduced HDF migration. These findings suggest the feasibility of CM from LL-37-treated ASCs as a potential therapeutic for human dermal fibroblast migration.

  8. Adipose tissue autophagy related gene expression is associated with glucometabolic status in human obesity.

    Science.gov (United States)

    Xu, Qing; Mariman, Edwin C M; Roumans, Nadia J T; Vink, Roel G; Goossens, Gijs H; Blaak, Ellen E; Jocken, Johan W E

    2018-02-05

    Adipose tissue autophagy (AT) is associated with human obesity and increased metabolic risk. Recent findings establish a role for autophagy in lipid metabolism. Here, we compared the expression of autophagy-related and lipolysis genes in human abdominal subcutaneous AT (SCAT) in overweight/obese subjects (n = 17) with or without impaired glucose tolerance in comparison with lean normal glucose tolerant individuals (n = 9), and investigated the association between AT autophagy and lipolysis. Human multipotent adipose-derived stem cells (hMADS) were used to investigate the effect of pharmacological HSL inhibition on changes in the autophagic flux. The expression of autophagy-related genes (ATG) 5, 7 and 12 in SCAT was significantly higher (p = 0.043, p = 0.015, p = 0.004, respectively) in overweight/obese compared to lean men, while expression of the classical lipases HSL (p = 0.092) and ATGL (p = 0.084) tended to be lower. ATG12 mRNA was positively correlated with BMI (r = 0.407, p = 0.039). ATG7 mRNA correlated positively with waist/hip ratio (WHR) (r = 0.420, p = 0.041), 2 h glucose concentration (r = 0.488, p = 0.011) and insulin (r = 0.419, p = 0.033). Multiple linear regressions revealed that ATG7 gene expression was positively related to 2 h glucose, independent of BMI, WHR and insulin. Gene expression interaction analysis showed that ATG7 mRNA negatively correlated with HSL (p<0.01) and ATGL mRNA expression (p<0.01). In line, treatment of differentiated hMADS with an HSL inhibitor increased LC3 accumulation, a marker of increased autophagic flux. Collectively, the present study demonstrated that a low expression of classical lipases in abdominal SCAT is accompanied by an increased expression of ATGs in overweight/obese subjects, which seems to be mainly related to glucose tolerance.

  9. Multiple roles for NaV1.9 in the activation of visceral afferents by noxious inflammatory, mechanical, and human disease–derived stimuli

    Science.gov (United States)

    Hockley, James R.F.; Boundouki, George; Cibert-Goton, Vincent; McGuire, Cian; Yip, Ping K.; Chan, Christopher; Tranter, Michael; Wood, John N.; Nassar, Mohammed A.; Blackshaw, L. Ashley; Aziz, Qasim; Michael, Gregory J.; Baker, Mark D.; Winchester, Wendy J.; Knowles, Charles H.; Bulmer, David C.

    2014-01-01

    Chronic visceral pain affects millions of individuals worldwide and remains poorly understood, with current therapeutic options constrained by gastrointestinal adverse effects. Visceral pain is strongly associated with inflammation and distension of the gut. Here we report that the voltage-gated sodium channel subtype NaV1.9 is expressed in half of gut-projecting rodent dorsal root ganglia sensory neurons. We show that NaV1.9 is required for normal mechanosensation, for direct excitation and for sensitization of mouse colonic afferents by mediators from inflammatory bowel disease tissues, and by noxious inflammatory mediators individually. Excitatory responses to ATP or PGE2 were substantially reduced in NaV1.9−/− mice. Deletion of NaV1.9 substantially attenuates excitation and subsequent mechanical hypersensitivity after application of inflammatory soup (IS) (bradykinin, ATP, histamine, PGE2, and 5HT) to visceral nociceptors located in the serosa and mesentery. Responses to mechanical stimulation of mesenteric afferents were also reduced by loss of NaV1.9, and there was a rightward shift in stimulus–response function to ramp colonic distension. By contrast, responses to rapid, high-intensity phasic distension of the colon are initially unaffected; however, run-down of responses to repeat phasic distension were exacerbated in NaV1.9−/− afferents. Finally colonic afferent activation by supernatants derived from inflamed human tissue was greatly reduced in NaV1.9−/− mice. These results demonstrate that NaV1.9 is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity, and is essential for activation by noxious inflammatory mediators, including those from diseased human bowel. These observations indicate that NaV1.9 represents a high-value target for development of visceral analgesics. PMID:24972070

  10. Multiple roles for NaV1.9 in the activation of visceral afferents by noxious inflammatory, mechanical, and human disease-derived stimuli.

    Science.gov (United States)

    Hockley, James R F; Boundouki, George; Cibert-Goton, Vincent; McGuire, Cian; Yip, Ping K; Chan, Christopher; Tranter, Michael; Wood, John N; Nassar, Mohammed A; Blackshaw, L Ashley; Aziz, Qasim; Michael, Gregory J; Baker, Mark D; Winchester, Wendy J; Knowles, Charles H; Bulmer, David C

    2014-10-01

    Chronic visceral pain affects millions of individuals worldwide and remains poorly understood, with current therapeutic options constrained by gastrointestinal adverse effects. Visceral pain is strongly associated with inflammation and distension of the gut. Here we report that the voltage-gated sodium channel subtype NaV1.9 is expressed in half of gut-projecting rodent dorsal root ganglia sensory neurons. We show that NaV1.9 is required for normal mechanosensation, for direct excitation and for sensitization of mouse colonic afferents by mediators from inflammatory bowel disease tissues, and by noxious inflammatory mediators individually. Excitatory responses to ATP or PGE2 were substantially reduced in NaV1.9(-/-) mice. Deletion of NaV1.9 substantially attenuates excitation and subsequent mechanical hypersensitivity after application of inflammatory soup (IS) (bradykinin, ATP, histamine, PGE2, and 5HT) to visceral nociceptors located in the serosa and mesentery. Responses to mechanical stimulation of mesenteric afferents were also reduced by loss of NaV1.9, and there was a rightward shift in stimulus-response function to ramp colonic distension. By contrast, responses to rapid, high-intensity phasic distension of the colon are initially unaffected; however, run-down of responses to repeat phasic distension were exacerbated in NaV1.9(-/-) afferents. Finally colonic afferent activation by supernatants derived from inflamed human tissue was greatly reduced in NaV1.9(-/-) mice. These results demonstrate that NaV1.9 is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity, and is essential for activation by noxious inflammatory mediators, including those from diseased human bowel. These observations indicate that NaV1.9 represents a high-value target for development of visceral analgesics. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  11. Microarray Based Gene Expression Analysis of Murine Brown and Subcutaneous Adipose Tissue: Significance with Human

    Science.gov (United States)

    Boparai, Ravneet K.; Kondepudi, Kanthi Kiran; Mantri, Shrikant; Bishnoi, Mahendra

    2015-01-01

    Background Two types of adipose tissues, white (WAT) and brown (BAT) are found in mammals. Increasingly novel strategies are being proposed for the treatment of obesity and its associated complications by altering amount and/or activity of BAT using mouse models. Methodology/Principle Findings The present study was designed to: (a) investigate the differential expression of genes in LACA mice subcutaneous WAT (sWAT) and BAT using mouse DNA microarray, (b) to compare mouse differential gene expression with previously published human data; to understand any inter- species differences between the two and (c) to make a comparative assessment with C57BL/6 mouse strain. In mouse microarray studies, over 7003, 1176 and 401 probe sets showed more than two-fold, five-fold and ten-fold change respectively in differential expression between murine BAT and WAT. Microarray data was validated using quantitative RT-PCR of key genes showing high expression in BAT (Fabp3, Ucp1, Slc27a1) and sWAT (Ms4a1, H2-Ob, Bank1) or showing relatively low expression in BAT (Pgk1, Cox6b1) and sWAT (Slc20a1, Cd74). Multi-omic pathway analysis was employed to understand possible links between the organisms. When murine two fold data was compared with published human BAT and sWAT data, 90 genes showed parallel differential expression in both mouse and human. Out of these 90 genes, 46 showed same pattern of differential expression whereas the pattern was opposite for the remaining 44 genes. Based on our microarray results and its comparison with human data, we were able to identify genes (targets) (a) which can be studied in mouse model systems to extrapolate results to human (b) where caution should be exercised before extrapolation of murine data to human. Conclusion Our study provides evidence for inter species (mouse vs human) differences in differential gene expression between sWAT and BAT. Critical understanding of this data may help in development of novel ways to engineer one form of adipose

  12. Microarray based gene expression analysis of murine brown and subcutaneous adipose tissue: significance with human.

    Directory of Open Access Journals (Sweden)

    Ritesh K Baboota

    Full Text Available Two types of adipose tissues, white (WAT and brown (BAT are found in mammals. Increasingly novel strategies are being proposed for the treatment of obesity and its associated complications by altering amount and/or activity of BAT using mouse models.The present study was designed to: (a investigate the differential expression of genes in LACA mice subcutaneous WAT (sWAT and BAT using mouse DNA microarray, (b to compare mouse differential gene expression with previously published human data; to understand any inter- species differences between the two and (c to make a comparative assessment with C57BL/6 mouse strain. In mouse microarray studies, over 7003, 1176 and 401 probe sets showed more than two-fold, five-fold and ten-fold change respectively in differential expression between murine BAT and WAT. Microarray data was validated using quantitative RT-PCR of key genes showing high expression in BAT (Fabp3, Ucp1, Slc27a1 and sWAT (Ms4a1, H2-Ob, Bank1 or showing relatively low expression in BAT (Pgk1, Cox6b1 and sWAT (Slc20a1, Cd74. Multi-omic pathway analysis was employed to understand possible links between the organisms. When murine two fold data was compared with published human BAT and sWAT data, 90 genes showed parallel differential expression in both mouse and human. Out of these 90 genes, 46 showed same pattern of differential expression whereas the pattern was opposite for the remaining 44 genes. Based on our microarray results and its comparison with human data, we were able to identify genes (targets (a which can be studied in mouse model systems to extrapolate results to human (b where caution should be exercised before extrapolation of murine data to human.Our study provides evidence for inter species (mouse vs human differences in differential gene expression between sWAT and BAT. Critical understanding of this data may help in development of novel ways to engineer one form of adipose tissue to another using murine model with focus

  13. Subcutaneous adipose tissue zinc-α2-glycoprotein is associated with adipose tissue and whole-body insulin sensitivity.

    Science.gov (United States)

    Balaz, Miroslav; Vician, Marek; Janakova, Zuzana; Kurdiova, Timea; Surova, Martina; Imrich, Richard; Majercikova, Zuzana; Penesova, Adela; Vlcek, Miroslav; Kiss, Alexander; Belan, Vitazoslav; Klimes, Iwar; Olejnik, Juraj; Gasperikova, Daniela; Wolfrum, Christian; Ukropcova, Barbara; Ukropec, Jozef

    2014-08-01

    To examine the regulatory aspects of zinc-α2-glycoprotein (ZAG) association with obesity-related insulin resistance. ZAG mRNA and protein were analyzed in subcutaneous adipose tissue (AT) and circulation of lean, obese, prediabetic, and type 2 diabetic men; both subcutaneous and visceral AT were explored in lean and extremely obese. Clinical and ex vivo findings were corroborated by results of in vitro ZAG silencing experiment. Subcutaneous AT ZAG was reduced in obesity, with a trend to further decrease with prediabetes and type 2 diabetes. ZAG was 3.3-fold higher in subcutaneous than in visceral AT of lean individuals. All differences were lost in extreme obesity. Obesity-associated changes in AT were not paralleled by alterations of circulating ZAG. Subcutaneous AT ZAG correlated with adiposity, adipocyte hypertrophy, whole-body and AT insulin sensitivity, mitochondrial content, expression of GLUT4, PGC1α, and adiponectin. Subcutaneous AT ZAG and adipocyte size were the only predictors of insulin sensitivity, independent on age and BMI. Silencing ZAG resulted in reduced adiponectin, IRS1, GLUT4, and PGC1α gene expression in primary human adipocytes. ZAG in subcutaneous, but not in visceral AT, was markedly reduced in obesity. Clinical, cellular, and molecular evidence indicate that ZAG plays an important role in modulating whole-body and AT insulin sensitivity. Copyright © 2014 The Obesity Society.

  14. WNT5A induces osteogenic differentiation of human adipose stem cells via rho-associated kinase Rock

    NARCIS (Netherlands)

    Santos, A.; Bakker, A.D.; de Blieck-Hogervorst, J.M.A.; Klein-Nulend, J.

    2010-01-01

    Background aims. Human (h) adipose tissue-derived mesenchymal stromal cells (ASC) constitute an interesting cellular source for bone tissue engineering applications. Wnts, for example Wnt5a, are probably important regulators of osteogenic differentiation of stem cells, but the role of Wnt5a in hASC

  15. Glucose-dependent insulinotropic polypeptide may enhance fatty acid re-esterification in subcutaneous abdominal adipose tissue in lean humans

    DEFF Research Database (Denmark)

    Asmar, Meena; Simonsen, Lene; Madsbad, Sten

    2010-01-01

    Glucose-dependent insulinotropic polypeptide (GIP) has been implicated in lipid metabolism in animals. In humans, however, there is no clear evidence of GIP effecting lipid metabolism. The present experiments were performed in order to elucidate the effects of GIP on regional adipose tissue metab...

  16. Lipid mobilization from human abdominal, subcutaneous adipose tissue is independent of sex during steady-state exercise

    DEFF Research Database (Denmark)

    Bülow, Jens; Gjeraa, Kirsten; Enevoldsen, Lotte Hahn

    2006-01-01

    The aim of the study was to elucidate whether there are sex differences of significant biological importance in the human abdominal, subcutaneous adipose tissue lipid metabolism when studied by Fick's Principle during rest and exercise in steady-state conditions. The net mobilization of fatty acids...

  17. Influence of metformin on metabolic effect of insulin in human adipose tissue in vitro.

    Science.gov (United States)

    Cigolini, M; Bosello, O; Zancanaro, C; Orlandi, P G; Fezzi, O; Smith, U

    1984-12-01

    To study the mechanism(s) of action of metformin, fragments of human subcutaneous adipose tissue were incubated with therapeutic blood concentrations of metformin. In the absence of insulin no effect of metformin was seen on either lipolysis or glucose metabolism. When insulin was present, however, metformin stimulated glucose conversion into both triglycerides and CO2. In marked contrast, no effect of metformin was observed on the antilipolytic effect of insulin. In agreement with this selective effect no change in insulin binding was found. In conclusion, metformin seems to exert its effect on glucose metabolism by potentiating the action of insulin at a post-receptor level, possibly on the rate of glucose transport.

  18. Transcriptional dynamics during human adipogenesis and its link to adipose morphology and distribution

    DEFF Research Database (Denmark)

    Ehrlund, Anna; Mejhert, Niklas; Björk, Christel

    2017-01-01

    White adipose tissue (WAT) can develop into several phenotypes with different pathophysiological impact on type 2 diabetes. To better understand the adipogenic process, the transcriptional events that occur during in vitro differentiation of human adipocytes were investigated and the findings...... linked to WAT phenotypes. Single molecule transcriptional profiling provided a detailed map of the expressional changes of genes, enhancers, and long non-coding RNAs, where different types of transcripts share common dynamics during differentiation. Common signatures include early down......-regulated, transient, and late induced transcripts, all of which are linked to distinct developmental processes during adipogenesis. Enhancers expressed during adipogenesis overlap significantly with genetic variants associated with WAT distribution. Transiently and late-induced expressed genes are associated...

  19. Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose-Derived Stem Cells.

    Science.gov (United States)

    Swioklo, Stephen; Constantinescu, Andrei; Connon, Che J

    2016-03-01

    Despite considerable progress within the cell therapy industry, unmet bioprocessing and logistical challenges associated with the storage and distribution of cells between sites of manufacture and the clinic exist. We examined whether hypothermic (4°C-23°C) preservation of human adipose-derived stem cells could be improved through their encapsulation in 1.2% calcium alginate. Alginate encapsulation improved the recovery of viable cells after 72 hours of storage. Viable cell recovery was highly temperature-dependent, with an optimum temperature of 15°C. At this temperature, alginate encapsulation preserved the ability for recovered cells to attach to tissue culture plastic on rewarming, further increasing its effect on total cell recovery. On attachment, the cells were phenotypically normal, displayed normal growth kinetics, and maintained their capacity for trilineage differentiation. The number of cells encapsulated (up to 2 × 10(6) cells per milliliter) did not affect viable cell recovery nor did storage of encapsulated cells in a xeno-free, serum-free,current Good Manufacturing Practice-grade medium. We present a simple, low-cost system capable of enhancing the preservation of human adipose-derived stem cells stored at hypothermic temperatures, while maintaining their normal function. The storage of cells in this manner has great potential for extending the time windows for quality assurance and efficacy testing, distribution between the sites of manufacture and the clinic, and reducing the wastage associated with the limited shelf life of cells stored in their liquid state. ©AlphaMed Press.

  20. Extent, causes, and consequences of small RNA expression variation in human adipose tissue.

    Directory of Open Access Journals (Sweden)

    Leopold Parts

    Full Text Available Small RNAs are functional molecules that modulate mRNA transcripts and have been implicated in the aetiology of several common diseases. However, little is known about the extent of their variability within the human population. Here, we characterise the extent, causes, and effects of naturally occurring variation in expression and sequence of small RNAs from adipose tissue in relation to genotype, gene expression, and metabolic traits in the MuTHER reference cohort. We profiled the expression of 15 to 30 base pair RNA molecules in subcutaneous adipose tissue from 131 individuals using high-throughput sequencing, and quantified levels of 591 microRNAs and small nucleolar RNAs. We identified three genetic variants and three RNA editing events. Highly expressed small RNAs are more conserved within mammals than average, as are those with highly variable expression. We identified 14 genetic loci significantly associated with nearby small RNA expression levels, seven of which also regulate an mRNA transcript level in the same region. In addition, these loci are enriched for variants significant in genome-wide association studies for body mass index. Contrary to expectation, we found no evidence for negative correlation between expression level of a microRNA and its target mRNAs. Trunk fat mass, body mass index, and fasting insulin were associated with more than twenty small RNA expression levels each, while fasting glucose had no significant associations. This study highlights the similar genetic complexity and shared genetic control of small RNA and mRNA transcripts, and gives a quantitative picture of small RNA expression variation in the human population.

  1. Cryopreservation of Human Adipose-Derived Stem Cells in Combination with Trehalose and Reversible Electroporation.

    Science.gov (United States)

    Dovgan, Barbara; Barlič, Ariana; Knežević, Miomir; Miklavčič, Damijan

    2017-02-01

    New cryopreservation approaches for medically applicable cells are of great importance in clinical medicine. Current protocols employ the use of dimethyl sulfoxide (DMSO), which is toxic to cells and causes undesirable side effects in patients, such as cardiac arrhythmias, neurological events, and others. Trehalose, a nontoxic disaccharide, has been already studied as a cryoprotectant. However, an efficient approach for loading this impermeable sugar into mammalian cells is missing. In our study, we assessed the efficiency of combining reversible electroporation and trehalose for cryopreservation of human adipose-derived stem cells. First, we determined reversible electroporation threshold by loading of propidium iodide into cells. The highest permeabilization while maintaining high cell viability was reached at 1.5 kV/cm, at 8 pulses, 100 µs, and 1 Hz. Second, cells were incubated in 250 or 400 mM trehalose and electroporated before cryopreservation. After thawing, 83.8 ± 1.8 % (mean ± SE) cell recovery was obtained at 250 mM trehalose. By using a standard freezing protocol (10 % DMSO in 90 % fetal bovine serum), cell survival after thawing was about 91.5 ± 1.6 %. We also evaluated possible effects of electroporation on cells' functionality before and after thawing. Successful cell growth and efficient adipogenic and osteogenic differentiation were achieved. In conclusion, electroporation seems to be an efficient method for loading nonpermeable trehalose into human adipose-derived stem cells, allowing long-term cryopreservation in DMSO-free and xeno-free conditions.

  2. Human Adipose Tissue Conditioned Media from Lean Subjects Is Protective against H2O2 Induced Neurotoxicity in Human SH-SY5Y Neuronal Cells

    Directory of Open Access Journals (Sweden)

    Zhongxiao Wan

    2015-01-01

    Full Text Available Adipose tissue secretes numerous hormone-like factors, which are known as adipokines. Adipokine receptors have been identified in the central nervous system but the potential role of adipokine signaling in neuroprotection is unclear. The aim of this study is to determine (1 Whether adipokines secreted from cultured adipose tissue of lean humans is protective against oxidative stress-induced neurotoxicity in human SH-SY5Y neuronal cells; and (2 To explore potential signaling pathways involved in these processes. Adipose tissue conditioned media (ATCM from healthy lean subjects completely prevented H2O2 induced neurotoxicity, while this effect is lost after heating ATCM. ATCM activated the phosphorylation of ERK1/2, JNK and Akt at serine 308 in SH-SY5Y cells. PD98059 (25 µM, SP600125 (5 µM and LY29400 (20 µM partially blocked the protective effects of ATCM against H2O2 induced neurotoxicity. Findings demonstrate that heat-sensitive factors secreted from human adipose tissue of lean subjects are protective against H2O2 induced neurotoxicity and ERK1/2, JNK, and PI3K signaling pathways are involved in these processes. In conclusion, this study demonstrates preliminary but encouraging data to further support that adipose tissue secreted factors from lean human subjects might possess neuroprotective properties and unravel the specific roles of ERK1/2, JNK and PI3K in these processes.

  3. Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans

    DEFF Research Database (Denmark)

    Mulla, N A; Simonsen, L; Bülow, J

    2000-01-01

    One purpose of the present experiments was to examine whether the relative workload or the absolute work performed is the major determinant of the lipid mobilization from adipose tissue during exercise. A second purpose was to determine the co-ordination of skeletal muscle and adipose tissue lipid......, a subcutaneous abdominal vein and a femoral vein. Adipose tissue metabolism and skeletal muscle (leg) metabolism were measured using Fick's principle. The results show that the lipolytic rate in adipose tissue during exercise was the same in each experiment. Post-exercise, there was a very fast decrease...... adipose tissue during exercise is the same whether the relative workload is 40% or 60% of maximum. Post-exercise, there is a substantial lipid mobilization from adipose tissue and only a small fraction of this is taken up in the lower extremities. This leaves a substantial amount of NEFAs for either NEFA...

  4. Recent Advances in Human Genetics and Epigenetics of Adiposity: Pathway to Precision Medicine?

    Science.gov (United States)

    Fall, Tove; Mendelson, Michael; Speliotes, Elizabeth K

    2017-05-01

    Obesity is a heritable trait that contributes to substantial global morbidity and mortality. Here, we summarize findings from the past decade of genetic and epigenetic research focused on unravelling the underpinnings of adiposity. More than 140 genetic regions now are known to influence adiposity traits. The genetics of general adiposity, as measured by body mass index, and that of abdominal obesity, as measured by waist-to-hip ratio, have distinct biological backgrounds. Gene expression associated with general adiposity is enriched in the nervous system. In contrast, genes associated with abdominal adiposity function in adipose tissue. Recent population-based epigenetic analyses have highlighted additional distinct loci. We discuss how associated genetic variants can lead to understanding causal mechanisms, and to disentangling reverse causation in epigenetic analyses. Discoveries emerging from population genomics are identifying new disease markers and potential novel drug targets to better define and combat obesity and related diseases. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. Calcium sensing receptor as a novel mediator of adipose tissue dysfunction: mechanisms and potential clinical implications

    Directory of Open Access Journals (Sweden)

    Roberto Bravo

    2016-09-01

    Full Text Available Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue is an active endocrine organ, with a crucial influence on whole-body homeostasis. White adipose tissue dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease and some cancers. Among the regulators of white adipose tissue physiology, the calcium-sensing receptor has arisen as a potential mediator of white adipose tissue dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that calcium-sensing receptor activation in the visceral (i.e. unhealthy white adipose tissue is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to calcium-sensing receptor activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in white adipose tissue plays a key role in the development of white adipose tissue dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that calcium-sensing receptor may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

  6. The Gut and Energy Balance: Visceral Allies in the Obesity Wars

    National Research Council Canada - National Science Library

    Michael K. Badman; Jeffrey S. Flier

    2005-01-01

    .... The gut, the pancreatic islets of Langerhans, elements in the portal vasculature, and even visceral adipose tissue communicate with the controllers of energy balance in the brain by means of neural...

  7. Sex differences in human adipose tissues - the biology of pear shape

    National Research Council Canada - National Science Library

    Karastergiou, Kalypso; Smith, Steven R; Greenberg, Andrew S; Fried, Susan K

    2012-01-01

    .... Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose...

  8. Xenotransplantation of human adipose-derived stem cells in zebrafish embryos.

    Directory of Open Access Journals (Sweden)

    Jin Li

    Full Text Available Zebrafish is a widely used animal model with well-characterized background in developmental biology. The fate of human adipose-derived stem cells (ADSCs after their xenotransplantation into the developing embryos of zebrafish is unknown. Therefore, human ADSCs were firstly isolated, and then transduced with lentiviral vector system carrying a green fluorescent protein (GFP reporter gene, and followed by detection of their cell viability and the expression of cell surface antigens. These GFP-expressing human ADSCs were transplanted into the zebrafish embryos at 3.3-4.3 hour post-fertilization (hpf. Green fluorescent signal, the proliferation and differentiation of human ADSCs in recipient embryos were respectively examined using fluorescent microscopy and immunohistochemical staining. The results indicated that human ADSCs did not change their cell viability and the expression levels of cell surface antigens after GFP transduction. Microscopic examination demonstrated that green fluorescent signals of GFP expressed in the transplanted cells were observed in the embryos and larva fish at post-transplantation. The positive staining of Ki-67 revealed the survival and proliferation of human ADSCs in fish larvae after transplantation. The expression of CD105 was observable in the xenotransplanted ADSCs, but CD31 expression was undetectable. Therefore, our results indicate that human ADSCs xenotransplanted in the zebrafish embryos not only can survive and proliferate at across-species circumstance, but also seem to maintain their undifferentiation status in a short term. This xenograft model of zebrafish embryos may provide a promising and useful technical platform for the investigation of biology and physiology of stem cells in vivo.

  9. Visceral larva migrans

    Science.gov (United States)

    Parasite infection - visceral larva migrans; VLM; Toxocariasis; Ocular larva migrans; Larva migrans visceralis ... Saunders; 2016:chap 39. Nash TE. Visceral larvae migrans and other uncommon helminth infections. In: Bennett JE, ...

  10. The Effect of Secretory Factors of Adipose-Derived Stem Cells on Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Soo-Wan Nam

    2012-01-01

    Full Text Available The beneficial effects of adipose-derived stem cell conditioned medium (ADSC-CM on skin regeneration have been reported. Although the mechanism of how ADSC-CM promotes skin regeneration is unclear, ADSC-CM contained various growth factors and it is an excellent raw material for skin treatment. ADSC-CM produced in a hypoxia condition of ADSC—in other words, Advanced Adipose-Derived Stem cell Protein Extract (AAPE—has great merits for skin regeneration. In this study, human primary keratinocytes (HKs, which play fundamental roles in skin tissue, was used to examine how AAPE affects HK. HK proliferation was significantly higher in the experimental group (1.22 μg/mL than in the control group. DNA gene chip demonstrated that AAPE in keratinocytes (p < 0.05 notably affected expression of 290 identified transcripts, which were associated with cell proliferation, cycle and migration. More keratinocyte wound healing and migration was shown in the experimental group (1.22 μg/mL. AAPE treatment significantly stimulated stress fiber formation, which was linked to the RhoA-ROCK pathway. We identified 48 protein spots in 2-D gel analysis and selected proteins were divided into 64% collagen components and 30% non-collagen components as shown by the MALDI-TOF analysis. Antibody array results contained growth factor/cytokine such as HGF, FGF-1, G-CSF, GM-CSF, IL-6, VEGF, and TGF-β3 differing from that shown by 2-D analysis. Conclusion: AAPE activates HK proliferation and migration. These results highlight the potential of the topical application of AAPE in the treatment of skin regeneration.

  11. From bench to bedside: use of human adipose-derived stem cells

    Directory of Open Access Journals (Sweden)

    Feisst V

    2015-11-01

    Full Text Available Vaughan Feisst,1 Sarah Meidinger,1 Michelle B Locke2 1Dunbar Laboratory, School of Biological Sciences, 2Department of Surgery, Faculty of Medicine and Health Sciences, The University of Auckland, Auckland, New Zealand Abstract: Since the discovery of adipose-derived stem cells (ASC in human adipose tissue nearly 15 years ago, significant advances have been made in progressing this promising cell therapy tool from the laboratory bench to bedside usage. Standardization of nomenclature around the different cell types used is finally being adopted, which facilitates comparison of results between research groups. In vitro studies have assessed the ability of ASC to undergo mesenchymal differentiation as well as differentiation along alternate lineages (transdifferentiation. Recently, focus has shifted to the immune modulatory and paracrine effects of transplanted ASC, with growing interest in the ASC secretome as a source of clinical effect. Bedside use of ASC is advancing alongside basic research. An increasing number of safety-focused Phase I and Phase IIb trials have been published without identifying any significant risks or adverse events in the short term. Phase III trials to assess efficacy are currently underway. In many countries, regulatory frameworks are being developed to monitor their use and assure their safety. As many trials rely on ASC injected at a distant site from the area of clinical need, strategies to improve the homing and efficacy of transplanted cells are also being explored. This review highlights each of these aspects of the bench-to-bedside use of ASC and summarizes their clinical utility across a variety of medical specialties. Keywords: standardization, bystander effect, stromal cells, mesenchymal stem cells, stromal vascular fraction

  12. Standardized Sophora pachycarpa Root Extract Enhances Osteogenic Differentiation in Adipose-derived Human Mesenchymal Stem Cells.

    Science.gov (United States)

    Mollazadeh, Samaneh; Neshati, Vajiheh; Fazly Bazzaz, Bibi Sedigheh; Iranshahi, Mehrdad; Mojarrad, Majid; Naderi-Meshkin, Hojjat; Kerachian, Mohammad Amin

    2017-05-01

    Bone defect is an important topic in public health. Novel therapies are based on osteogenic induction by natural antiosteoporotic compounds including plant-derived estrogens. In the current study, the osteogenic potential of Sophora pachycarpa root extract (SPRE) was explored on human adipose-derived mesenchymal stem cells. Herein, adipose-derived mesenchymal stem cells were osteoinducted in the presence of increased concentrations of the extract for 21 days. Then, cell viability was evaluated by MTT assay, and the differentiated cells were stained by Alizarin Red S for calcium deposition and subjected to alkaline phosphatase (ALP) assay for enzymatic activity. To assess the expression of bone-related genes, treated cells were evaluated by real-time polymerase chain reaction. The MTT test demonstrated that SPRE had no toxic effects on the cell viability. Treating the cells with SPRE noticeably promoted ALP activity, mineralization, and mRNA expression of runt-related transcription factor 2 (RUNX2), bone gamma-carboxyglutamate protein (BGLAP), secreted phosphoprotein 1 (SPP1), and collagen type I alpha 1 (COL1A1). Additionally, cells subjected to 0.1 μg/mL SPRE showed the highest osteogenic effects. According to high-performance liquid chromatography fingerprinting of SPRE, the osteoprotective effects of SPRE is probably due to presence of phytochemicals with estrogen-like activity in the extract. Thus, SPRE might be a suitable therapeutic agent for bone defects therapy in the future research. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Functional polyaniline nanofibre mats for human adipose-derived stem cell proliferation and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Abdul Rahman, Norizah, E-mail: norizah@science.putra.edu.my [Polymer Electronics Research Centre, School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland (New Zealand); Department of Chemistry, University of Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan (Malaysia); Feisst, Vaughan [School of Biological Sciences, The University of Auckland, Private Bag 92019, Auckland (New Zealand); Dickinson, Michelle E. [Department of Chemical and Materials Engineering, The University of Auckland, Private Bag 92019, Auckland (New Zealand); Malmström, Jenny [Polymer Electronics Research Centre, School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland (New Zealand); Dunbar, P. Rod [School of Biological Sciences, The University of Auckland, Private Bag 92019, Auckland (New Zealand); Maurice Wilkins Centre, Private Bag 92019, Auckland (New Zealand); Travas-Sejdic, Jadranka, E-mail: j.travas-sejdic@auckland.ac.nz [Polymer Electronics Research Centre, School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland (New Zealand); MacDiarmid Institute for Advanced Materials and Nanotechnology, P.O. Box 600, Wellington 6140 (New Zealand)

    2013-02-15

    Conductive polymer poly(aniline-co-m-aminobenzoic acid) (P(ANI-co-m-ABA)) and polyaniline (PANI) were blended with a biodegradable, biocompatible polymer, poly(L-lactic acid) and were electrospun into nanofibres to investigate their potential application as a scaffold for human adipose-derived stem cells (hASCs). These polymers, in both conductive and non-conductive form, were electrospun with average fibre diameters of less than 400 nm. Novel nanoindentation results obtained on the individual nanofibres revealed that the elastic moduli of the nanofibres are much higher at the surface (4–10 GPa, h{sub max} <75 nm) than in the inner fibre core (2–4 GPa, h{sub max} >75 nm). The composite nanofibres showed great promise as a scaffold for hASCs as they supported the cell adhesion and proliferation. After 1 week of cell culture hASCs were well spread on the substrates with abundant focal adhesions. The electrospun mats provide the cells with comparably stiff, sub-micron sized fibres as anchoring points on a substrate of high porosity. The conductive nature of these composite nanofibres offers exciting opportunities for electrical stimulation of the cells. - Highlights: ► Polyaniline and its copolymer's nanofibres were prepared by electrospinning. ► The elastic modulus of a single polyaniline composite nanofibres were determined. ► Elastic moduli of the nanofibres are much higher at the surface than the inner core. ► The electrospun mats supported the cell adhesion and proliferation. ► The nanofibres show great promise as a scaffold for adipose derived stem cells.

  14. Expression of Innate Immune Response Genes in Liver and Three Types of Adipose Tissue in Cloned Pigs

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Stagsted, Jan

    2012-01-01

    The pig has been proposed as a relevant model for human obesity-induced inflammation, and cloning may improve the applicability of this model. We tested the assumptions that cloning would reduce interindividual variation in gene expression of innate immune factors and that their expression would...... remain unaffected by the cloning process. We investigated the expression of 40 innate immune factors by high-throughput quantitative real-time PCR in samples from liver, abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and neck SAT in cloned pigs compared to normal outbred pigs...

  15. Human Adipose-Derived Mesenchymal Progenitor Cells Engraft into Rabbit Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Wen Wang

    2015-05-01

    Full Text Available Mesenchymal stem cells (MSCs are known to have the potential for articular cartilage regeneration, and are suggested for the treatment of osteoarthritis (OA. Here, we investigated whether intra-articular injection of xenogeneic human adipose-derived mesenchymal progenitor cells (haMPCs promoted articular cartilage repair in rabbit OA model and engrafted into rabbit articular cartilage. The haMPCs were cultured in vitro, and phenotypes and differentiation characteristics of cells were evaluated. OA was induced surgically by anterior cruciate ligament transection (ACLT and medical meniscectomy of knee joints. At six weeks following surgery, hyaluronic acid (HA or haMPCs was injected into the knee joints, the contralateral knee served as normal control. All animals were sacrificed at the 16th week post-surgery. Assessments were carried out by macroscopic examination, hematoxylin/eosin (HE and Safranin-O/Fast green stainings and immunohistochemistry. The data showed that haMPC treatment promoted cartilage repair. Signals of human mitochondrial can be directly detected in haMPC treated cartilage. The haMPCs expressed human leukocyte antigen I (HLA-I but not HLA-II-DR in vivo. These results suggest that intra-articular injection of haMPCs promotes regeneration of articular cartilage in rabbit OA model, and support the notion that MPCs are transplantable between HLA-incompatible individuals.

  16. The role of dietary fatty acids for early human adipose tissue growth.

    Science.gov (United States)

    Hauner, Hans; Brunner, Stefanie; Amann-Gassner, Ulrike

    2013-08-01

    Childhood obesity is increasing worldwide, and all previous attempts to stop this epidemic have shown little success. There is now growing evidence that the risk of childhood obesity is strongly influenced by perinatal determinants, including prepregnancy body mass index (BMI), gestational weight gain, and—at least in animal studies—dietary factors during pregnancy and lactation. This review addresses the issue of whether modulation of fat intake and its composition in this early-life period has a potential for primary prevention of childhood obesity. Of particular interest is the question of whether supplementation with n–3 long-chain PUFAs (LC-PUFAs) may exert an antiobesity effect. Retrospective analysis of human randomized controlled trials with fish-oil intervention during pregnancy and lactation gave inconsistent results concerning BMI and obesity development in offspring. A recent prospective human intervention study aimed at reducing the n–6:n–3 LC-PUFA ratio did not show an effect on adipose tissue growth in offspring up to the age of 1 y. Therefore, there is currently little evidence to support the hypothesis that dietary intervention to modify fat composition during pregnancy and lactation would be a promising strategy to prevent childhood obesity in humans, but more research is clearly needed to address the question if and how the risk of developing obesity can be modified by dietary intervention early in life.

  17. Long-term in-vivo tumorigenic assessment of human culture-expanded adipose stromal/stem cells

    Energy Technology Data Exchange (ETDEWEB)

    MacIsaac, Zoe Marie, E-mail: zmm4a@virgina.edu [University of Virginia (United States); Shang, Hulan, E-mail: shanghulan@gmail.com [Department of Plastic Surgery, University of Virginia (United States); Agrawal, Hitesh, E-mail: hiteshdos@hotmail.com [Department of Plastic Surgery, University of Virginia (United States); Yang, Ning, E-mail: ny6u@virgina.edu [Department of Plastic Surgery, University of Virginia (United States); Parker, Anna, E-mail: amp4v@virginia.edu [Department of Surgery, University of Virginia (United States); Katz, Adam J., E-mail: ajk2f@virginia.edu [Department of Plastic Surgery, University of Virginia (United States)

    2012-02-15

    After more than a decade of extensive experimentation, the promise of stem cells to revolutionize the field of medicine has negotiated their entry into clinical trial. Adipose tissue specifically holds potential as an attainable and abundant source of stem cells. Currently undergoing investigation are adipose stem cell (ASC) therapies for diabetes and critical limb ischemia, among others. In the enthusiastic pursuit of regenerative therapies, however, questions remain regarding ASC persistence and migration, and, importantly, their safety and potential for neoplasia. To date, assays of in vivo ASC activity have been limited by early end points. We hypothesized that with time, ASCs injected subcutaneously undergo removal by normal tissue turnover and homeostasis, and by the host's immune system. In this study, a high dose of culture expanded ASCs was formulated and implanted as multicellular aggregates into immunocompromised mice, which were maintained for over one year. Animals were monitored for toxicity, and surviving cells quantified at study endpoint. No difference in growth/weight or lifespan was found between cell-treated and vehicle treated animals, and no malignancies were detected in treated animals. Moreover, real-time PCR for a human specific sequence, ERV-3, detected no persistent ASCs. With the advent of clinical application, clarification of currently enigmatic stem cell properties has become imperative. Our study represents the longest duration determination of stem cell activity in vivo, and contributes strong evidence in support of the safety of adipose derived stem cell applications. -- Highlights: Black-Right-Pointing-Pointer Adipose stem cells promise novel clinical therapies. Black-Right-Pointing-Pointer Before clinical translation, safety profiles must be further elucidated. Black-Right-Pointing-Pointer Subcutaneously injected non-autologous adipose stem cells do not form tumors. Black-Right-Pointing-Pointer Subcutaneously injected non

  18. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Jaewoo Pak

    2016-08-01

    Full Text Available This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs and homogenized extracellular matrix (ECM in the form of adipose stromal vascular fraction (SVF, along with hyaluronic acid (HA and platelet-rich plasma (PRP activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI data, functional rating index, range of motion (ROM, and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees.

  19. Abdominal Adiposity Distribution in Diabetic/Prediabetic and Nondiabetic Populations: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Jane J. Lee

    2014-01-01

    Full Text Available Excess fat in the abdomen can be classified generally as visceral and subcutaneous adiposity. Evidence suggests that visceral adiposity has greater implications for diabetes than other fat depots. The purpose of this study is to explore the disparities in the distribution of abdominal adiposity in diabetic/prediabetic and nondiabetic populations and to identify moderators that influence the pattern of central obesity via a meta-analysis technique. The Hedges’ g was used as a measure of effect size and 95% confidence interval was computed. A total of 41 relevant studies with 101 effect sizes were retrieved. Pooled effect sizes for visceral and subcutaneous adiposity were 0.69 and 0.42, respectively. Diabetic/prediabetic populations exhibited greater visceral and subcutaneous adiposity compared to nondiabetic populations (Z=10.35, P<0.05. Significant moderator effects of gender (Z=-2.90 and assessment method of abdominal adiposity (Z=-2.17 were found for visceral fat (P<0.05, but not for subcutaneous fat. Type of health condition influenced both visceral (Z=-5.10 and subcutaneous (Z=-7.09 abdominal adiposity volumes (P<0.05. Abdominal adiposity distributions were significantly altered in the diabetic/prediabetic population compared to the nondiabetic population. Gender, assessment method of abdominal adiposity, and type of health conditions (diabetic/prediabetics were identified as crucial moderators that influence the degree of abdominal adiposity.

  20. Prolactin suppresses malonyl-CoA concentration in human adipose tissue

    DEFF Research Database (Denmark)

    Nilsson, L. A.; Roepstorff, Carsten; Kiens, Bente

    2009-01-01

    as a consequence of suppressed malonyl-CoA concentration in parallel with decreased GLUT-4 expression. In the lactating woman, this regulation in adipose tissue may enhance the provision of nutrients for the infant instead of nutrients being stored in adipose tissue. In hyperprolactinemic individuals, a suppressed...

  1. Comparative analysis of microRNA expression in mouse and human brown adipose tissue.

    Science.gov (United States)

    Güller, Isabelle; McNaughton, Sarah; Crowley, Tamsyn; Gilsanz, Vicente; Kajimura, Shingo; Watt, Matthew; Russell, Aaron P

    2015-10-19

    In small mammals brown adipose tissue (BAT) plays a predominant role in regulating energy expenditure (EE) via adaptive thermogenesis. New-born babies require BAT to control their body temperature, however its relevance in adults has been questioned. Active BAT has recently been observed in adult humans, albeit in much lower relative quantities than small mammals. Comparing and contrasting the molecular mechanisms controlling BAT growth and development in mice and humans will increase our understanding or how human BAT is developed and may identify potential therapeutic targets to increase EE. MicroRNAs are molecular mechanisms involved in mouse BAT development however, little is known about the miRNA profile in human BAT. The aims of this study were to establish a mouse BAT-enriched miRNA profile and compare this with miRNAs measured in human BAT. To achieve this we firstly established a mouse BAT enriched-miRNA profile by comparing miRNAs expressed in mouse BAT, white adipose tissue and skeletal muscle. Following this the BAT-enriched miRNAs predicted to target genes potentially involved in growth and development were identified. MiRNA levels were measured using PCR-based miRNA arrays. Results were analysed using ExpressionSuite software with the global mean expression value of all expressed miRNAs in a givensample used as the normalisation factor. Bio-informatic analyses was used to predict gene targets followed by Ingenuity Pathway Analysis. We identified 35 mouse BAT-enriched miRNAs that were predicted to target genes potentially involved in growth and development. We also identified 145 miRNAs expressed in both mouse and human BAT, of which 25 were enriched in mouse BAT. Of these 25 miRNAs, miR-20a was predicted to target MYF5 and PPARγ, two important genes involved in brown adipogenesis, as well as BMP2 and BMPR2, genes involved in white adipogenesis. For the first time, 69 miRNAs were identified in human BAT but absent in mouse BAT, and 181 miRNAs were

  2. Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome.

    Science.gov (United States)

    Clark, Kaitlin C; Fierro, Fernando A; Ko, Emily Mills; Walker, Naomi J; Arzi, Boaz; Tepper, Clifford G; Dahlenburg, Heather; Cicchetto, Andrew; Kol, Amir; Marsh, Lyndsey; Murphy, William J; Fazel, Nasim; Borjesson, Dori L

    2017-03-20

    Adipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular, and genetic diseases. The objective of this study was to complete a comprehensive side-by-side comparison of human and feline ASCs, with an emphasis on their immunomodulatory capacity and transcriptome. Human and feline ASCs were evaluated for phenotype, immunomodulatory profile, and transcriptome. Additionally, transwells were used to determine the role of cell-cell contact in ASC-mediated inhibition of lymphocyte proliferation in both humans and cats. Similar to human ASCs, feline ASCs were highly proliferative at low passages and fit the minimal criteria of multipotent stem cells including a compatible surface protein phenotype, osteogenic capacity, and normal karyotype. Like ASCs from all species, feline ASCs inhibited mitogen-activated lymphocyte proliferation in vitro, with or without direct ASC-lymphocyte contact. Feline ASCs mimic human ASCs in their mediator secretion pattern, including prostaglandin E2, indoleamine 2,3 dioxygenase, transforming growth factor beta, and interleukin-6, all augmented by interferon gamma secretion by lymphocytes. The transcriptome of three unactivated feline ASC lines were highly similar. Functional analysis of the most highly expressed genes highlighted processes including: 1) the regulation of apoptosis; 2) cell adhesion; 3) response to oxidative stress; and 4) regulation of cell differentiation. Finally, feline ASCs had a similar gene expression profile to noninduced human ASCs. Findings suggest that feline ASCs modulate lymphocyte proliferation using soluble mediators that mirror the human ASC secretion

  3. Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

    Directory of Open Access Journals (Sweden)

    Eva Koellensperger

    2013-01-01

    Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

  4. Cartilage Regeneration in Human with Adipose Tissue-Derived Stem Cells: Current Status in Clinical Implications

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    Jaewoo Pak

    2016-01-01

    Full Text Available Osteoarthritis (OA is one of the most common debilitating disorders among the elderly population. At present, there is no definite cure for the underlying causes of OA. However, adipose tissue-derived stem cells (ADSCs in the form of stromal vascular fraction (SVF may offer an alternative at this time. ADSCs are one type of mesenchymal stem cells that have been utilized and have demonstrated an ability to regenerate cartilage. ADSCs have been shown to regenerate cartilage in a variety of animal models also. Non-culture-expanded ADSCs, in the form of SVF along with platelet rich plasma (PRP, have recently been used in humans to treat OA and other cartilage abnormalities. These ADSCs have demonstrated effectiveness without any serious side effects. However, due to regulatory issues, only ADSCs in the form of SVF are currently allowed for clinical uses in humans. Culture-expanded ADSCs, although more convenient, require clinical trials for a regulatory approval prior to uses in clinical settings. Here we present a systematic review of currently available clinical studies involving ADSCs in the form of SVF and in the culture-expanded form, with or without PRP, highlighting the clinical effectiveness and safety in treating OA.

  5. Overexpressed human heme Oxygenase-1 decreases adipogenesis in pigs and porcine adipose-derived stem cells.

    Science.gov (United States)

    Park, Eun Jung; Koo, Ok Jae; Lee, Byeong Chun

    2015-11-27

    Adipose-derived mesenchymal stem cells (ADSC) are multipotent, which means they are able to differentiate into several lineages in vivo and in vitro under proper conditions. This indicates it is possible to determine the direction of differentiation of ADSC by controlling the microenvironment. Heme oxygenase 1 (HO-1), a type of antioxidant enzyme, attenuates adipogenicity and obesity. We produced transgenic pigs overexpressing human HO-1 (hHO-1-Tg), and found that these animals have little fatty tissue when autopsied. To determine whether overexpressed human HO-1 suppresses adipogenesis in pigs, we analyzed body weight increases of hHO-1-Tg pigs and wild type (WT) pigs of the same strain, and induced adipogenic differentiation of ADSC derived from WT and hHO-1-Tg pigs. The hHO-1-Tg pigs had lower body weights than WT pigs from 16 weeks of age until they died. In addition, hHO-1-Tg ADSC showed reduced adipogenic differentiation and expression of adipogenic molecular markers such as PPARγ and C/EBPα compared to WT ADSC. These results suggest that HO-1 overexpression reduces adipogenesis both in vivo and in vitro, which could support identification of therapeutic targets of obesity and related metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Human Adipose Derived Stem Cells Induced Cell Apoptosis and S Phase Arrest in Bladder Tumor

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    Xi Yu

    2015-01-01

    Full Text Available The aim of this study was to determine the effect of human adipose derived stem cells (ADSCs on the viability and apoptosis of human bladder cancer cells. EJ and T24 cells were cocultured with ADSCs or cultured with conditioned medium of ADSCs (ADSC-CM, respectively. The cell counting and colony formation assay showed ADSCs inhibited the proliferation of EJ and T24 cells. Cell viability assessment revealed that the secretions of ADSCs, in the form of conditioned medium, were able to decrease cancer cell viability. Wound-healing assay suggested ADSC-CM suppressed migration of T24 and EJ cells. Moreover, the results of the flow cytometry indicated that ADSC-CM was capable of inducing apoptosis of T24 cells and inducing S phase cell cycle arrest. Western blot revealed ADSC-CM increased the expression of cleaved caspase-3 and cleaved PARP, indicating that ADSC-CM induced apoptosis in a caspase-dependent way. PTEN/PI3K/Akt pathway and Bcl-2 family proteins were involved in the mechanism of this reaction. Our study indicated that ADSCs may provide a promising and practicable manner for bladder tumor therapy.

  7. Adiposity is associated with DNA methylation profile in adipose tissue.

    Science.gov (United States)

    Agha, Golareh; Houseman, E Andres; Kelsey, Karl T; Eaton, Charles B; Buka, Stephen L; Loucks, Eric B

    2015-08-01

    Adiposity is a risk factor for type 2 diabetes and cardiovascular disease, suggesting an important role for adipose tissue in the development of these conditions. The epigenetic underpinnings of adiposity are not well understood, and studies of DNA methylation in relation to adiposity have rarely focused on target adipose tissue. Objectives were to evaluate whether genome-wide DNA methylation profiles in subcutaneous adipose tissue and peripheral blood leukocytes are associated with measures of adiposity, including central fat mass, body fat distribution and body mass index. Participants were 106 men and women (mean age 47 years) from the New England Family Study. DNA methylation was evaluated using the Infinium HumanMethylation450K BeadChip. Adiposity phenotypes included dual-energy X-ray absorptiometry-assessed android fat mass, android:gynoid fat ratio and trunk:limb fat ratio, as well as body mass index. Adipose tissue genome-wide DNA methylation profiles were associated with all four adiposity phenotypes, after adjusting for race, sex and current smoking (omnibus p-values DNA methylation in several genes that are biologically relevant to the development of adiposity, such as AOC3, LIPE, SOD3, AQP7 and CETP. Blood DNA methylation profiles were not associated with adiposity, before or after adjustment for blood leukocyte cell mixture effects. Findings show that DNA methylation patterns in adipose tissue are associated with adiposity. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

  8. Effect of the anatomical site on telomere length and pref-1 gene expression in bovine adipose tissues

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Tomoya, E-mail: toyamada@affrc.go.jp; Higuchi, Mikito; Nakanishi, Naoto

    2015-08-07

    Adipose tissue growth is associated with preadipocyte proliferation and differentiation. Telomere length is a biological marker for cell proliferation. Preadipocyte factor-1 (pref-1) is specifically expressed in preadipocytes and acts as a molecular gatekeeper of adipogenesis. In the present study, we investigated the fat depot-specific differences in telomere length and pref-1 gene expression in various anatomical sites (subcutaneous, intramuscular and visceral) of fattening Wagyu cattle. Visceral adipose tissue expressed higher pref-1 mRNA than did subcutaneous and intramuscular adipose tissues. The telomere length in visceral adipose tissue tended to be longer than that of subcutaneous and intramuscular adipose tissues. The telomere length of adipose tissue was not associated with adipocyte size from three anatomical sites. No significant correlation was found between the pref-1 mRNA level and the subcutaneous adipocyte size. In contrast, the pref-1 mRNA level was negatively correlated with the intramuscular and visceral adipocyte size. These results suggest that anatomical sites of adipose tissue affect the telomere length and expression pattern of the pref-1 gene in a fat depot-specific manner. - Highlights: • Visceral adipose tissue express higher pref-1 mRNA than other anatomical sites. • Telomere length in visceral adipose tissue is longer than other anatomical sites. • Telomere length of adipose tissue is not associated with adipocyte size. • Pref-1 mRNA is negatively correlated with intramuscular and visceral adipocyte size.

  9. Physical Exercise Reduces the Expression of RANTES and Its CCR5 Receptor in the Adipose Tissue of Obese Humans

    Directory of Open Access Journals (Sweden)

    Engin Baturcam

    2014-01-01

    Full Text Available RANTES and its CCR5 receptor trigger inflammation and its progression to insulin resistance in obese. In the present study, we investigated for the first time the effect of physical exercise on the expression of RANTES and CCR5 in obese humans. Fifty-seven adult nondiabetic subjects (17 lean and 40 obese were enrolled in a 3-month supervised physical exercise. RANTES and CCR5 expressions were measured in PBMCs and subcutaneous adipose tissue before and after exercise. Circulating plasma levels of RANTES were also investigated. There was a significant increase in RANTES and CCR5 expression in the subcutaneous adipose tissue of obese compared to lean. In PBMCs, however, while the levels of RANTES mRNA and protein were comparable between both groups, CCR5 mRNA was downregulated in obese subjects (P<0.05. Physical exercise significantly reduced the expression of both RANTES and CCR5 (P<0.05 in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNF-α, IL-6, and P-JNK. Circulating RANTES correlated negatively with anti-inflammatory IL-1ra (P=0.001 and positively with proinflammatory IP-10 and TBARS levels (P<0.05. Therefore, physical exercise may provide an effective approach for combating the deleterious effects associated with obesity through RANTES signaling in the adipose tissue.

  10. Evaluation of human platelet lysate and dimethyl sulfoxide as cryoprotectants for the cryopreservation of human adipose-derived stem cells.

    Science.gov (United States)

    Wang, Chuan; Xiao, Ran; Cao, Yi-Lin; Yin, Hong-Yu

    2017-09-09

    Cryopreservation provides an effective technique to maintain the functional properties of human adipose-derived stem cells (ASCs). Dimethylsulfoxide (DMSO) and fetal bovine serum (FBS) are frequently used as cryoprotectants for this purpose. However, the use of DMSO can result in adverse effects and toxic reactions and FBS can introduce risks of viral, prion, zoonose contaminations and evoke immune responses after injection. It is therefore crucial to reduce DMSO concentrations and use serum-free solution in the cryopreservation process. Human platelet lysate (PL) is a promising candidate for use as an alternative to DMSO and FBS. Therefore, in this study, with an aim to identify a cryoprotective agent for ASC cryopreservation, we determined the viability, proliferation potential, phenotype, and differentiation potential of fresh ASCs and ASCs cryopreserved using different combinations of three cryoprotective agents: fetal bovine serum (FBS), dimethylsulfoxide (DMSO), and human platelet lysate (PL). The viability of the ASCs cryopreserved with 90% FBS and 10% DMSO, 95% FBS and 5% DMSO, and 97% PL and 3% DMSO was >80%, and the proliferation potentials, cell phenotypes, and differentiation potentials of these groups were similar to those of fresh ASCs. Together, our findings suggest that a combination of 97% PL and 3% DMSO is an ideal cryoprotective agent for the efficient cryopreservation of human ASCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model.

    Science.gov (United States)

    Kuismanen, Kirsi; Juntunen, Miia; Narra Girish, Nathaniel; Tuominen, Heikki; Huhtala, Heini; Nieminen, Kari; Hyttinen, Jari; Miettinen, Susanna

    2018-01-31

    Anal incontinence is a devastating condition that significantly reduces the quality of life. Our aim was to evaluate the effect of human adipose stem cell (hASC) injections in a rat model for anal sphincter injury, which is the main cause of anal incontinence in humans. Furthermore, we tested if the efficacy of hASCs could be improved by combining them with polyacrylamide hydrogel carrier, Bulkamid®. Human ASCs derived from a female donor were culture expanded in DMEM/F12 supplemented with human platelet lysate. Female virgin Sprague-Dawley rats were randomized into four groups (n = 14-15/group): hASCs in saline or Bulkamid® (3 × 105 /60 μl) and saline or Bulkamid® without cells. Anorectal manometry (ARM) was performed before anal sphincter injury, at two (n=58) and at four weeks after (n = 33). Additionally, the anal sphincter tissue was examined by micro-computed tomography (μCT) and the histological parameters were compared between the groups. The median resting and peak pressure during spontaneous contraction measured by ARM were significantly higher in hASC treatment groups compared with the control groups without hASCs. There was no statistical difference in functional results between the hASC-carrier groups (saline vs. Bulkamid®). No difference was detected in the sphincter muscle continuation between the groups in the histology and μCT analysis. More inflammation was discovered in the group receiving saline with hASC. The hASC injection therapy with both saline and Bulkamid® is a promising nonsurgical treatment for acute anal sphincter injury. Traditional histology combined with the 3D μCT image data lends greater confidence in assessing muscle healing and continuity. Stem Cells Translational Medicine 2018. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  12. Effect of extracellular vesicles of human adipose tissue on insulin signaling in liver and muscle cells.

    Science.gov (United States)

    Kranendonk, Mariëtte E G; Visseren, Frank L J; van Herwaarden, Joost A; Nolte-'t Hoen, Esther N M; de Jager, Wilco; Wauben, Marca H M; Kalkhoven, Eric

    2014-10-01

    Insulin resistance (IR) is a key mechanism in obesity-induced cardiovascular disease. To unravel mechanisms whereby human adipose tissue (AT) contributes to systemic IR, the effect of human AT-extracellular vesicles (EVs) on insulin signaling in liver and muscle cells was determined. EVs released from human subcutaneous (SAT) and omental AT (OAT)-explants ex vivo were used for stimulation of hepatocytes and myotubes in vitro. Subsequently, insulin-induced Akt phosphorylation and expression of gluconeogenic genes (G6P, PEPCK) was determined. AT-EV adipokine levels were measured by multiplex immunoassay, and AT-EVs were quantified by high-resolution flow cytometry. In hepatocytes, AT-EVs from the majority of patients inhibited insulin-induced Akt phosphorylation, while EVs from some patients stimulated insulin-induced Akt phosphorylation. In myotubes AT-EVs exerted an ambiguous effect on insulin signaling. Hepatic Akt phosphorylation related negatively to G6P-expression by both SAT-EVs (r = -0.60, P = 0.01) and OAT-EVs (r = -0.74, P = 0.001). MCP-1, IL-6, and MIF concentrations were higher in OAT-EVs compared to SAT-EVs and differently related to lower Akt phosphorylation in hepatocytes. Finally, the number of OAT-EVs correlated positively with liver enzymes indicative for liver dysfunction. Human AT-EVs can stimulate or inhibit insulin signaling in hepatocytes- possibly depending on their adipokine content- and may thereby contribute to systemic IR. Copyright © 2014 The Obesity Society.

  13. Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans).

    Science.gov (United States)

    Cannon, B; Nedergaard, J

    2010-10-01

    Only with the development of the uncoupling protein 1 (UCP1)-ablated mouse has it become possible to strictly delineate the physiological significance of the thermogenic capacity of brown adipose tissue. Considering the presence of active brown adipose tissue in adult humans, these insights may have direct human implications. In addition to classical nonshivering thermogenesis, all adaptive adrenergic thermogeneses, including diet-induced thermogenesis, is fully dependent on brown adipocyte activity. Any weight-reducing effect of β(3)-adrenergic agonists is fully dependent on UCP1 activity, as is any weight-reducing effect of leptin (in excess of its effect on reduction of food intake). Consequently, in the absence of the thermogenic activity of brown adipose tissue, obesity develops spontaneously. The ability of brown adipose tissue to contribute to glucose disposal is also mainly related to thermogenic activity. However, basal metabolic rate, cold-induced thermogenesis, acute cold tolerance, fevers, nonadaptive adrenergic thermogenesis and processes such as angiogenesis in brown adipose tissue itself are not dependent on UCP1 activity. Whereas it is likely that these conclusions are also qualitatively valid for adult humans, the quantitative significance of brown adipose tissue for human metabolism--and the metabolic consequences for a single individual possessing more or less brown adipose tissue--awaits clarification.

  14. Anti-obesity effect of Lactobacillus gasseri SBT2055 accompanied by inhibition of pro-inflammatory gene expression in the visceral adipose tissue in diet-induced obese mice.

    Science.gov (United States)

    Miyoshi, Masaya; Ogawa, Akihiro; Higurashi, Satoshi; Kadooka, Yukio

    2014-01-01

    Probiotic Lactobacillus gasseri SBT2055 (LG2055) has an anti-obesity effect although it is unknown whether the effect influences inflammatory responses in adipose tissue and lipid metabolism in the liver, which are considered substantially relevant to adiposity. C57BL/6 mice were fed a 10%-fat diet containing LG2055 cells for 24 weeks. We then studied body weight, fat tissue mass, liver fat content and inflammatory genes in the adipose tissue, and lipogenic and lipolytic genes in the liver. Consumption of LG2055 resulted in a significant reduction in body weight and fat tissue mass (epididymal and perirenal/retroperitoneal), with a lowered level of triglyceride content in the liver. DNA microarray analysis showed that LG2055 generally inhibited the up-regulation of pro-inflammatory genes, including CCL2 and CCR2, in the epididymal adipose tissue. In the liver, LG2055 tended to inhibit lipogenic gene up-regulation, including ACC1, FAS and SREBP1, but LG2055 did not markedly alter lipolytic genes. Real-time PCR analysis confirmed the DNA microarray results in part, showing a significant reduction in the mRNA expression of CCL2 in the epididymal adipose tissue, and a downward tendency in FAS mRNA expression in the liver, in the LG2055-fed group. LG2055 significantly prevented body weight gain, fat accumulation and pro-inflammatory gene expression in the adipose tissue. Relatively lower triglyceride levels and reduced expression of lipogenic genes were also observed in the liver. It is suggested that improvement in the inflammatory state of the adipose tissue might be a possible mechanism underlying the anti-obesity effect of LG2055.

  15. Deformations experienced in the human skin, adipose tissue, and fascia in osteopathic manipulative medicine.

    Science.gov (United States)

    Chaudhry, Hans; Bukiet, Bruce; Ji, Zhiming; Stecco, Antonio; Findley, Thomas W

    2014-10-01

    Osteopathic manipulative medicine techniques involve compressive and tangential forces to target the fascia. These forces are transmitted to the skin and adipose tissue before the fascia is encountered. Knowing the extent of deformation of these 2 tissue layers relative to the fascia will assist osteopathic physicians in evaluating techniques for manual therapies and adjusting these therapies to reduce patient discomfort and improve results. To determine the magnitude of the forces transmitted to the skin, adipose tissue, and fascia, and to determine the magnitude of deformation produced in the skin and adipose tissue relative to the fascia using a mathematical model. The large deformation theory of elasticity, valid for 3-dimensional deformations, was used to evaluate the forces that need to be applied such that a specified deformation is produced in any region of the skin, adipose tissue, or fascia layers. Similarly, if the forces are specified, then the deformation produced can be determined. The normal and tangential forces required to produce a deformation of 9% compression and 4% shear for the skin were 50 N and 11 N, respectively. Normal and tangential forces of about 100 N and 22 N were found for a similar deformation of fascia. For adipose tissue, these forces were 36 N and 8 N, respectively. In addition, the skin experienced more compression and shear-about 1.5 times as much as the fascia, and the adipose tissue experienced about 2.5 to 3.5 times the deformation of the fascia and 50% more than the skin when a given force was applied to the skin. The forces applied to the surface of the skin were transmitted through this layer and the adipose layer entirely to the fascia. Therefore, the skin and adipose tissue experienced the same magnitude of force as the fascia. However, the skin and adipose tissue experienced more compression and shear than the fascia. © 2014 The American Osteopathic Association.

  16. Leishmania donovani Nucleoside Hydrolase (NH36) Domains Induce T-Cell Cytokine Responses in Human Visceral Leishmaniasis

    Science.gov (United States)

    Barbosa Santos, Micheli Luize; Nico, Dirlei; de Oliveira, Fabrícia Alvisi; Barreto, Aline Silva; Palatnik-de-Sousa, Iam; Carrillo, Eugenia; Moreno, Javier; de Luca, Paula Mello; Morrot, Alexandre; Rosa, Daniela Santoro; Palatnik, Marcos; Bani-Corrêa, Cristiane; de Almeida, Roque Pacheco; Palatnik-de-Sousa, Clarisa Beatriz

    2017-01-01

    Development of immunoprotection against visceral leishmaniasis (VL) focused on the identification of antigens capable of inducing a Th1 immune response. Alternatively, antigens targeting the CD8 and T-regulatory responses are also relevant in VL pathogenesis and worthy of being included in a preventive human vaccine. We assessed in active and cured patients and VL asymptomatic subjects the clinical signs and cytokine responses to the Leishmania donovani nucleoside hydrolase NH36 antigen and its N-(F1), central (F2) and C-terminal (F3) domains. As markers of VL resistance, the F2 induced the highest levels of IFN-γ, IL-1β, and TNF-α and, together with F1, the strongest secretion of IL-17, IL-6, and IL-10 in DTH+ and cured subjects. F2 also promoted the highest frequencies of CD3+CD4+IL-2+TNF-α−IFN-γ−, CD3+CD4+IL-2+TNF-α+IFN-γ−, CD3+CD4+IL-2+TNF-α−IFN-γ+, and CD3+CD4+IL-2+TNF-α+IFN-γ+ T cells in cured and asymptomatic subjects. Consistent with this, the IFN-γ increase was correlated with decreased spleen (R = −0.428, P = 0.05) and liver sizes (R = −0.428, P = 0.05) and with increased hematocrit counts (R = 0.532, P = 0.015) in response to F1 domain, and with increased hematocrit (R = 0.512, P 0.02) and hemoglobin counts (R = 0.434, P = 0.05) in response to F2. Additionally, IL-17 increases were associated with decreased spleen and liver sizes in response to F1 (R = −0.595, P = 0.005) and F2 (R = −0.462, P = 0.04). Conversely, F1 and F3 increased the CD3+CD8+IL-2+TNF-α−IFN-γ−, CD3+CD8+IL-2+TNF-α+IFN-γ−, and CD3+CD8+IL-2+TNF-α+IFN-γ+ T cell frequencies of VL patients correlated with increased spleen and liver sizes and decreased hemoglobin and hematocrit values. Therefore, cure and acquired resistance to VL correlate with the CD4+-Th1 and Th-17 T-cell responses to F2 and F1 domains. Clinical VL outcomes, by contrast, correlate with CD8+ T-cell responses against F3 and F1

  17. Obesity and inflammation: reduced cytokine expression due to resveratrol in a human in vitro model of inflamed adipose tissue

    OpenAIRE

    Ivana eZagotta; Elitsa Y. eDimova; Klaus-Michael eDebatin; Martin eWabitsch; Thomas eKietzmann; Pamela eFischer-Posovszky

    2015-01-01

    Abstract Obesity is associated with an inflammatory status and linked with a number of pathophysiological complications among them cardiovascular disease, type 2 diabetes mellitus, or the metabolic syndrome. Resveratrol was proposed to improve obesity-related inflammatory problems, but the effect of resveratrol on cytokine expression in obesity is not completely understood. In this study, we used an in vitro model of human adipose tissue inflammation to examine the effects of resveratrol o...

  18. The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus

    OpenAIRE

    Catalan, V.; Gomez-Ambrosi, J. (Javier); Rotellar, F.; Silva, C; Gil, M. J.; Rodriguez, A.; J. A. Cienfuegos; Salvador, J.; Frühbeck, G. (Gema)

    2007-01-01

    The G protein-coupled receptor 39 (GPR39) has recently been identified as the receptor for obestatin, a peptidic hormone involved in energy homeostasis. However, the expression levels of this receptor in human adipose tissue in obesity and obesity-associated type 2 diabetes mellitus (T2DM) remain unknown. Therefore, we evaluated the actual presence of GPR39 mRNA in human adipose tissue and whether GPR39 expression levels are altered in obesity and ...

  19. Fascia Origin of Adipose Cells.

    Science.gov (United States)

    Su, Xueying; Lyu, Ying; Wang, Weiyi; Zhang, Yanfei; Li, Danhua; Wei, Suning; Du, Congkuo; Geng, Bin; Sztalryd, Carole; Xu, Guoheng

    2016-05-01

    Adipocytes might arise from vascular stromal cells, pericytes and endothelia within adipose tissue or from bone marrow cells resident in nonadipose tissue. Here, we identified adipose precursor cells resident in fascia, an uninterrupted sheet of connective tissue that extends throughout the body. The cells and fragments of superficial fascia from the rat hindlimb were highly capable of spontaneous and induced adipogenic differentiation but not myogenic and osteogenic differentiation. Fascial preadipocytes expressed multiple markers of adipogenic progenitors, similar to subcutaneous adipose-derived stromal cells (ASCs) but discriminative from visceral ASCs. Such preadipocytes resided in fascial vasculature and were physiologically active in vivo. In growing rats, adipocytes dynamically arose from the adventitia to form a thin adipose layer in the fascia. Later, some adipocytes appeared to overlay on top of other adipocytes, an early sign for the formation of three-dimensional adipose tissue in fascia. The primitive adipose lobules extended invariably along blood vessels toward the distal fascia areas. At the lobule front, nascent capillaries wrapped and passed ahead of mature adipocytes to form the distal neovasculature niche, which might replenish the pool of preadipocytes and supply nutrients and hormones necessary for continuous adipogenesis. Our findings suggest a novel model for the origin of adipocytes from the fascia, which explains both neogenesis and expansion of adipose tissue. Fascial preadipocytes generate adipose cells to form primitive adipose lobules in superficial fascia, a subcutaneous nonadipose tissue. With continuous adipogenesis, these primitive adipose lobules newly formed in superficial fascia may be the rudiment of subcutaneous adipose tissue. Stem Cells 2016;34:1407-1419. © 2016 AlphaMed Press.

  20. Comparison of organochlorine pesticide levels in human adipose tissue of inhabitants from Veracruz and Puebla, Mexico.

    Science.gov (United States)

    Waliszewski, Stefan M; Valencia Quintana, R; Corona, C A; Herrero, M; Sánchez, K; Aguirre, H; Aldave, I A; Gomez Arroyo, S; Villalobos Pietrini, R

    2010-01-01

    Since the discovery of insecticide properties of DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) and HCH (hexachlorocyclohexane), they have provided great benefits to humans in sanitary actions to combat the spread of infection-borne disease vectors. Public Health Programs in Mexico used DDT and HCH until 1999 as the insecticides of choice to control disease-transmitting organisms. Because of their persistence and accumulative properties, organochlorine pesticides bioconcentrate in lipids of the human body, reflecting the rate of environmental exposure. Eighty human abdominal adipose tissue samples from Veracruz and 80 samples from Puebla were analyzed and the obtained results were compared among both populations. The results from Veracruz showed higher contamination levels (mg/kg on lipid base) compared to Puebla: beta-HCH, 0.072 vs. 0.029; pp'DDE (Dichlorodiphenyldichloroethylene), 2.364 vs. 0.726; op'DDT, 0.022 vs. 0.025; pp'DDT, 0.192 vs. 0.061; and Sigma-DDT, 2.589 vs. 0.806. The population from Veracruz and from Puebla divided by sex, origin, and cause of death presented no statistical differences. The comparison between sexes (women and men groups) at Veracruz and Puebla indicated significantly higher levels in Veracruz and statistical significant differences. Calculating possible risks (odds ratios, OR), pp'DDE (OR = 5.04) and op'DDT (OR = 2.93) revealed significantly higher risk for the Veracruz population. The study indicated prolonged DDT exposure of Mexicans caused by the past sanitary use and persistence of its residues in soils and air.

  1. Therapeutic Mechanisms of Human Adipose-Derived Mesenchymal Stem Cells in a Rat Tendon Injury Model.

    Science.gov (United States)

    Lee, Sang Yoon; Kwon, Bomi; Lee, Kyoungbun; Son, Young Hoon; Chung, Sun G

    2017-05-01

    Although survival of transplanted stem cells in vivo and differentiation of stem cells into tenocytes in vitro have been reported, there have been no in vivo studies demonstrating that mesenchymal stem cells (MSCs) could secrete their own proteins as differentiated tenogenic cells. Purpose/Hypothesis: Using a xenogeneic MSC transplantation model, we aimed to investigate whether MSCs could differentiate into the tenogenic lineage and secrete their own proteins. The hypothesis was that human MSCs would differentiate into the human tenogenic lineage and the cells would be able to secrete human-specific proteins in a rat tendon injury model. Controlled laboratory study. The Achilles tendons of 57 Sprague Dawley rats received full-thickness rectangular defects. After the modeling, the defective tendons were randomly assigned to 3 groups: (1) cell group, implantation with human adipose-derived mesenchymal stem cells (hASCs) and fibrin glue (106 cells in 60 μL); (2) fibrin group, implantation with fibrin glue and same volume of cell media; and (3) sham group, identical surgical procedure without any treatment. Gross observation and biomechanical, histopathological, immunohistochemistry, and Western blot analyses were performed at 2 and 4 weeks after modeling. hASCs implanted into the defective rat tendons were viable for 4 weeks as detected by immunofluorescence staining. Tendons treated with hASCs showed better gross morphological and biomechanical recovery than those in the fibrin and sham groups. Furthermore, the expression of both human-specific collagen type I and tenascin-C was significantly higher in the cell group than in the other 2 groups. Transplantation of hASCs enhanced rat tendon healing biomechanically. hASCs implanted into the rat tendon defect model survived for at least 4 weeks and secreted human-specific collagen type I and tenascin-C. These findings suggest that transplanted MSCs may be able to differentiate into the tenogenic lineage and contribute

  2. Human Adipose-Derived Stem Cells on Rapid Prototyped Three-Dimensional Hydroxyapatite/Beta-Tricalcium Phosphate Scaffold.

    Science.gov (United States)

    Canciani, Elena; Dellavia, Claudia; Ferreira, Lorena Maria; Giannasi, Chiara; Carmagnola, Daniela; Carrassi, Antonio; Brini, Anna Teresa

    2016-05-01

    In the study, we assess a rapid prototyped scaffold composed of 30/70 hydroxyapatite (HA) and beta-tricalcium-phosphate (β-TCP) loaded with human adipose-derived stem cells (hASCs) to determine cell proliferation, differentiation toward osteogenic lineage, adhesion and penetration on/into the scaffold.In this in vitro study, hASCs isolated from fat tissue discarded after plastic surgery were expanded, characterized, and then loaded onto the scaffold. Cells were tested for: viability assay (Alamar Blue at days 3, 7 and Live/Dead at day 32), differentiation index (alkaline phosphatase activity at day 14), scaffold adhesion (standard error of the mean analysis at days 5 and 18), and penetration (ground sections at day 32).All the hASC populations displayed stemness markers and the ability to differentiate toward adipogenic and osteogenic lineages.Cellular vitality increased between 3 and 7 days, and no inhibitory effect by HA/β-TCP was observed. Under osteogenic stimuli, scaffold increased alkaline phosphatase activity of +243% compared with undifferentiated samples. Human adipose-derived stem cells adhered on HA/β-TCP surface through citoplasmatic extensions that occupied the macropores and built networks among them. Human adipose derived stem cells were observed in the core of HA/β-TCP. The current combination of hASCs and HA/β-TCP scaffold provided encouraging results. If authors' data will be confirmed in preclinical models, the present engineering approach could represent an interesting tool in treating large bone defects.

  3. Cell culture density affects the proliferation activity of human adipose tissue stem cells.

    Science.gov (United States)

    Kim, Dae Seong; Lee, Myoung Woo; Ko, Young Jong; Chun, Yong Hoon; Kim, Hyung Joon; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2016-01-01

    In this study, we investigated the effect of cell density on the proliferation activity of human mesenchymal stem cells (MSCs) derived from adipose tissue (AT-MSCs) over time in culture. Passage #4 (P4) and #12 (P12) AT-MSCs from two donors were plated at a density of 200 (culture condition 1, CC1) or 5000 (culture condition 2, CC2) cells cm(-2) . After 7 days of incubation, P4 and P12 AT-MSCs cultured in CC1 were thin and spindle-shaped, whereas those cultured in CC2 had extensive cell-to-cell contacts and an expanded cell volume. In addition, P4 and P12 AT-MSCs in CC1 divided more than three times, while those in CC2 divided less than once on average. Flow cytometric analysis using 5(6)-carboxyfluorescein diacetate N-succinimidyl ester dye showed that the fluorescence intensity of AT-MSCs was lower in CC1 than in CC2. Furthermore, expression of proliferation-associated genes, such as CDC45L, CDC20A and KIF20A, in P4 AT-MSCs was higher in CC1 than in CC2, and this difference was also observed in P12 AT-MSCs. These data demonstrated that cell culture density affects the proliferation activity of MSCs, suggesting that it is feasible to design a strategy to prepare suitable MSCs using specific culture conditions. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Collagen-Hydroxyapatite Scaffolds Induce Human Adipose Derived Stem Cells Osteogenic Differentiation In Vitro.

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    Giovanna Calabrese

    Full Text Available Mesenchymal stem cells (MSCs play a crucial role in regulating normal skeletal homeostasis and, in case of injury, in bone healing and reestablishment of skeletal integrity. Recent scientific literature is focused on the development of bone regeneration models where MSCs are combined with biomimetic three-dimensional scaffolds able to direct MSC osteogenesis. In this work the osteogenic potential of human MSCs isolated from adipose tissue (hADSCs has been evaluated in vitro in combination with collagen/Mg doped hydroxyapatite scaffolds. Results demonstrate the high osteogenic potential of hADSCs when cultured in specific differentiation induction medium, as revealed by the Alizarin Red S staining and gene expression profile analysis. In combination with collagen/hydroxyapatite scaffold, hADSCs differentiate into mature osteoblasts even in the absence of specific inducing factors; nevertheless, the supplement of the factors markedly accelerates the osteogenic process, as confirmed by the expression of specific markers of pre-osteoblast and mature osteoblast stages, such as osterix, osteopontin (also known as bone sialoprotein I, osteocalcin and specific markers of extracellular matrix maturation and mineralization stages, such as ALPL and osteonectin. Hence, the present work demonstrates that the scaffold per se is able to induce hADSCs differentiation, while the addition of osteo-inductive factors produces a significant acceleration of the osteogenic process. This observation makes the use of our model potentially interesting in the field of regenerative medicine for the treatment of bone defects.

  5. Enhanced cartilage formation via three-dimensional cell engineering of human adipose-derived stem cells.

    Science.gov (United States)

    Yoon, Hee Hun; Bhang, Suk Ho; Shin, Jung-Youn; Shin, Jaehoon; Kim, Byung-Soo

    2012-10-01

    Autologous chondrocyte implantation is an effective treatment for damaged articular cartilage. However, this method involves surgical procedures that may cause further cartilage degeneration, and in vitro expansion of chondrocytes can result in dedifferentiation. Adipose-derived stem cells (ADSCs) may be an alternative autologous cell source for cartilage regeneration. In this study, we developed an effective method for large-scale in vitro chondrogenic differentiation, which is the procedure that would be required for clinical applications, and the subsequent in vivo cartilage formation of human ADSCs (hADSCs). The spheroid formation and chondrogenic differentiation of hADSCs were induced on a large scale by culturing hADSCs in three-dimensional suspension bioreactors (spinner flasks). In vitro chondrogenic differentiation of hADSCs was enhanced by a spheroid culture compared with a monolayer culture. The enhanced chondrogenesis was probably attributable to hypoxia-related cascades and enhanced cell-cell interactions in hADSC spheroids. On hADSCs loading in fibrin gel and transplantation into subcutaneous space of athymic mice for 4 weeks, the in vivo cartilage formation was enhanced by the transplantation of spheroid-cultured hADSCs compared with that of monolayer-cultured hADSCs. This study shows that the spheroid culture may be an effective method for large-scale in vitro chondrogenic differentiation of hADSCs and subsequent in vivo cartilage formation.

  6. Fluoxetine Decreases the Proliferation and Adipogenic Differentiation of Human Adipose-Derived Stem Cells.

    Science.gov (United States)

    Sun, Bo Kyung; Kim, Ji Hye; Choi, Joon-Seok; Hwang, Sung-Joo; Sung, Jong-Hyuk

    2015-07-22

    Fluoxetine was originally developed as an antidepressant, but it has also been used to treat obesity. Although the anti-appetite effect of fluoxetine is well-documented, its potential effects on human adipose-derived stem cells (ASCs) or mature adipocytes have not been investigated. Therefore, we investigated the mechanisms underlying the inhibitory effects of fluoxetine on the proliferation of ASCs. We also investigated its inhibitory effect on adipogenic differentiation. Fluoxetine significantly decreased ASC proliferation, and signal transduction PCR array analysis showed that it increased expression of autophagy-related genes. In addition, fluoxetine up-regulated SQSTM1 and LC3B protein expression as detected by western blotting and immunofluorescence. The autophagy inhibitor, 3-methyladenine (3-MA), significantly attenuated fluoxetine-mediated effects on ASC proliferation and SQSTM1/LC3B expression. In addition, 3-MA decreased the mRNA expression of two autophagy-related genes, beclin-1 and Atg7, in ASCs. Fluoxetine also significantly inhibited lipid accumulation and down-regulated the levels of PPAR-γ and C/EBP-α in ASCs. Collectively, these results indicate that fluoxetine decreases ASC proliferation and adipogenic differentiation. This is the first in vitro evidence that fluoxetine can reduce fat accumulation by inhibiting ASC proliferation and differentiation.

  7. Fluoxetine Decreases the Proliferation and Adipogenic Differentiation of Human Adipose-Derived Stem Cells

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    Bo Kyung Sun

    2015-07-01

    Full Text Available Fluoxetine was originally developed as an antidepressant, but it has also been used to treat obesity. Although the anti-appetite effect of fluoxetine is well-documented, its potential effects on human adipose-derived stem cells (ASCs or mature adipocytes have not been investigated. Therefore, we investigated the mechanisms underlying the inhibitory effects of fluoxetine on the proliferation of ASCs. We also investigated its inhibitory effect on adipogenic differentiation. Fluoxetine significantly decreased ASC proliferation, and signal transduction PCR array analysis showed that it increased expression of autophagy-related genes. In addition, fluoxetine up-regulated SQSTM1 and LC3B protein expression as detected by western blotting and immunofluorescence. The autophagy inhibitor, 3-methyladenine (3-MA, significantly attenuated fluoxetine-mediated effects on ASC proliferation and SQSTM1/LC3B expression. In addition, 3-MA decreased the mRNA expression of two autophagy-related genes, beclin-1 and Atg7, in ASCs. Fluoxetine also significantly inhibited lipid accumulation and down-regulated the levels of PPAR-γ and C/EBP-α in ASCs. Collectively, these results indicate that fluoxetine decreases ASC proliferation and adipogenic differentiation. This is the first in vitro evidence that fluoxetine can reduce fat accumulation by inhibiting ASC proliferation and differentiation.

  8. Datasets of genes coexpressed with FBN1 in mouse adipose tissue and during human adipogenesis

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    Margaret R. Davis

    2016-09-01

    Full Text Available This article contains data related to the research article entitled “Expression of FBN1 during adipogenesis: relevance to the lipodystrophy phenotype in Marfan syndrome and related conditions” [1]. The article concerns the expression of FBN1, the gene encoding the extracellular matrix protein fibrillin-1, during adipogenesis in vitro and in relation to adipose tissue in vivo. The encoded protein has recently been shown to produce a short glucogenic peptide hormone, (Romere et al., 2016 [2], and this gene is therefore a key gene for regulating blood glucose levels. FBN1 and coexpressed genes were examined in mouse strains and in human cells undergoing adipogenesis. The data show the genes that were coexpressed with FBN1, including genes coding for other connective tissue proteins and the proteases that modify them and for the transcription factors that control their expression. Data analysed were derived from datasets available in the public domain and the analysis highlights the utility of such datasets for ongoing analysis and hence reduction in the use of experimental animals.

  9. Incipient establishment of human adipose-derived mesenchymal stem cells bank

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    Xiao XU

    2017-02-01

    Full Text Available Objective To explore the possibility of establishing the human adipose-derived mesenchymal stem cells (hADSCs bank as to provide an alternative source for the seed cells of tissue engineering. Methods The cell surface antigens of the purified, expanded hADSCs and the ones following cryopreservation were detected by flow cytometry, cultured in an induced culture medium to induce the osteogenic and adipogenic differentiation. The specific marker alkaline phosphatase (ALP in osteogenic special medium was also detected by immunohistochemistry. Results The phenotype and expansion possibility of hADSCs after cryopreservation were remained. It could expand for 10 generations. The doubling time was 48 hours. The 2nd, 6th and 10th generation of hADSCs kept stronger ability of osteogenic and adipogenic differentiation. Conclusion The bank of hADSCs has been incipiently established and can provide eligible seed cells for tissue engineering. DOI: 10.11855/j.issn.0577-7402.2016.12.05

  10. MicroRNA-223 Expression Is Upregulated in Insulin Resistant Human Adipose Tissue

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    Tung-Yueh Chuang

    2015-01-01

    Full Text Available MicroRNAs (miRNAs are short noncoding RNAs involved in posttranscriptional regulation of gene expression and influence many cellular functions including glucose and lipid metabolism. We previously reported that adipose tissue (AT from women with polycystic ovary syndrome (PCOS or controls with insulin resistance (IR revealed a differentially expressed microRNA (miRNA profile, including upregulated miR-93 in PCOS patients and in non-PCOS women with IR. Overexpressed miR-93 directly inhibited glucose transporter isoform 4 (GLUT4 expression, thereby influencing glucose metabolism. We have now studied the role of miR-223, which is also abnormally expressed in the AT of IR subjects. Our data indicates that miR-223 is significantly overexpressed in the AT of IR women, regardless of whether they had PCOS or not. miR-223 expression in AT was positively correlated with HOMA-IR. Unlike what is reported in cardiomyocytes, overexpression of miR-223 in human differentiated adipocytes was associated with a reduction in GLUT4 protein content and insulin-stimulated glucose uptake. In addition, our data suggests miR-223 regulates GLUT4 expression by direct binding to its 3′ untranslated region (3′UTR. In conclusion, in AT miR-223 is an IR-related miRNA that may serve as a potential therapeutic target for the treatment of IR-related disorders.

  11. Human adipose tissue-derived stem cells alleviate radiation-induced xerostomia

    Science.gov (United States)

    XIONG, XUEYAN; SHI, XIUJUAN; CHEN, FENGSHAN

    2014-01-01

    Hyposalivation is an intractable side-effect of radiotherapy for head and neck cancer. It is caused by the irreversible loss of acinar cells and decreased saliva secretion. However, this situation severely compromises the quality of life of affected patients. Currently, there is no effective treatment for this condition. In the present study, we developed a novel approach to regenerate the function of the irradiation-damaged salivary glands using human adipose tissue-derived stem cell (hADSC) intraglandular transplantation. ZsGreen-labeled hADSCs were adoptively transferred into Sprague-Dawley (SD) rat submandibular glands immediately following exposure to 18 Gy irradiation. A higher salivary flow rate (SFR) was observed in the hADSC-treated group. Tissue improvement, including angiogenesis, anti-apoptosis and anti-fibrosis, was detected in the hADSC-treated glands as compared to the untreated glands. Quantitative reverse transcription PCR (RT-qPCR) revealed a significantly higher expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) in the hADSC-treated rats. Furthermore, immunohistochemical analysis indicated that the hADSCs had differentiated into acinar and ductal cells in the rat submandibular glands. Thus, our results suggest that hADSCs are able to regenerate irradiation-damaged salivary glands through glandular transplantation. PMID:25017690

  12. The potentials of human adipose tissue derived mesenchymal stem cells in targeted therapy of experimental glioma

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    FAN Cun-gang

    2012-12-01

    Full Text Available Glioblastoma is the most common primary malignant brain tumor in adults. With current standard therapy which includes extensive microsurgical resection along with concurrent chemoradiotherapy and adjuvant temozolomide (TMZ, the median survival of glioblastoma patients is only 14.60 months nowadays. Recent studies demonstrated that human adipose tissue derived mesenchymal stem cells (hAT-MSCs possessed the glioma-trophic migratory capacity. The engineered hAT-MSCs expressing herpes simplex virus-thymidine kinase (HSV-tk, yeast cytosine deaminase::uracil phosphoribosyltransferase (CDy:: UPRT, and rabbit carboxylesterase (rCE could exert inhibitory effects on glioma when combined with prodrugs, such as ganciclovir (GCV, 5-fluorocytosine (5-FC and irinotecan (CPT-11, respectively. hAT-MSCs carrying the oncolytic virus or expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL also could inhibit the growth of glioma. This paper summarizes the recent progress in this field to pave the way for hAT-MSCs based targeted therapy of glioma in future.

  13. Characterization of electrospun nanocomposite scaffolds and biocompatibility with adipose-derived human mesenchymal stem cells.

    Science.gov (United States)

    McCullen, Seth D; Stevens, Derrick R; Roberts, Wesley A; Clarke, Laura I; Bernacki, Susan H; Gorga, Russell E; Loboa, Elizabeth G

    2007-01-01

    Electrospun nanocomposite scaffolds were fabricated by encapsulating multi-walled carbon nanotubes (MWNT) in poly (lactic acid) (PLA) nanofibers. Scanning electron microscopy (SEM) confirmed the fabrication of nanofibers, and transmission electron microscopy identified the alignment and dispersion of MWNT along the axis of the fibers. Tensile testing showed an increase in the tensile modulus for a MWNT loading of 0.25 wt% compared with electrospun nanofibrous mats without MWNT reinforcement. Conductivity measurements indicated that the confined geometry of the fibrous system requires only minute doping to obtain significant enhancements at 0.32 wt%. Adipose-derived human mesenchymal stem cells (hMSCs) were seeded on electrospun scaffolds containing 1 wt% MWNT and 0 wt% MWNT, to determine the efficacy of the scaffolds for cell growth, and the effect of MWNT on hMSC viability and proliferation over two weeks in culture. Staining for live and dead cells and DNA quantification indicated that the hMSCs were alive and proliferating through day 14. SEM images of hMSCs at 14 days showed morphological differences, with hMSCs on PLA well spread and hMSCs on PLA with 1% MWNT closely packed and longitudinally aligned.

  14. Cellular Behavior of Human Adipose-Derived Stem Cells on Wettable Gradient Polyethylene Surfaces

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    Hyun Hee Ahn

    2014-01-01

    Full Text Available Appropriate surface wettability and roughness of biomaterials is an important factor in cell attachment and proliferation. In this study, we investigated the correlation between surface wettability and roughness, and biological response in human adipose-derived stem cells (hADSCs. We prepared wettable and rough gradient polyethylene (PE surfaces by increasing the power of a radio frequency corona discharge apparatus with knife-type electrodes over a moving sample bed. The PE changed gradually from hydrophobic and smooth surfaces to hydrophilic (water contact angle, 90° to ~50° and rough (80 to ~120 nm surfaces as the power increased. We found that hADSCs adhered better to highly hydrophilic and rough surfaces and showed broadly stretched morphology compared with that on hydrophobic and smooth surfaces. The proliferation of hADSCs on hydrophilic and rough surfaces was also higher than that on hydrophobic and smooth surfaces. Furthermore, integrin beta 1 gene expression, an indicator of attachment, and heat shock protein 70 gene expression were high on hydrophobic and smooth surfaces. These results indicate that the cellular behavior of hADSCs on gradient surface depends on surface properties, wettability and roughness.

  15. Evaluation of two recombinant Leishmania proteins identified by an immunoproteomic approach as tools for the serodiagnosis of canine visceral and human tegumentary leishmaniasis.

    Science.gov (United States)

    Coelho, Eduardo Antonio Ferraz; Costa, Lourena Emanuele; Lage, Daniela Pagliara; Martins, Vívian Tamietti; Garde, Esther; de Jesus Pereira, Nathália Cristina; Lopes, Eliane Gonçalves Paiva; Borges, Luiz Felipe Nunes Menezes; Duarte, Mariana Costa; Menezes-Souza, Daniel; de Magalhães-Soares, Danielle Ferreira; Chávez-Fumagalli, Miguel Angel; Soto, Manuel; Tavares, Carlos Alberto Pereira

    2016-01-15

    Serological diagnostic tests for canine and human leishmaniasis present problems related with their sensitivity and/or specificity. Recently, an immunoproteomic approach performed with Leishmania infantum proteins identified new parasite antigens. In the present study, the diagnostic properties of two of these proteins, cytochrome c oxidase and IgE-dependent histamine-releasing factor, were evaluated for the serodiagnosis of canine visceral (CVL) and human tegumentary (HTL) leishmaniasis. For the CVL diagnosis, sera samples from non-infected dogs living in an endemic or non-endemic area of leishmaniasis, sera from asymptomatic or symptomatic visceral leishmaniasis (VL) dogs, from Leish-Tec(®)-vaccinated dogs, and sera from animals experimentally infected by Trypanosoma cruzi or Ehrlichia canis were used. For the HTL diagnosis, sera from non-infected subjects living in an endemic area of leishmaniasis, sera from active cutaneous or mucosal leishmaniasis patients, as well as those from T. cruzi-infected patients were employed. ELISA assays using the recombinant proteins showed both sensitivity and specificity values of 100% for the serodiagnosis of both forms of disease, with high positive and negative predictive values, showing better diagnostic properties than the parasite recombinant A2 protein or a soluble Leishmania antigen extract. In this context, the two new recombinant proteins could be considered to be used in the serodiagnosis of CVL and HTL. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection

    Science.gov (United States)

    Damouche, Abderaouf; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-01-01

    Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

  17. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

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    Abderaouf Damouche

    2015-09-01

    Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

  18. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

    Science.gov (United States)

    Damouche, Abderaouf; Lazure, Thierry; Avettand-Fènoël, Véronique; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-09-01

    Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

  19. Effect of Bariatric Weight Loss on the Adipose Lipolytic Transcriptome in Obese Humans

    OpenAIRE

    Shakun Karki; Melissa G Farb; Samantha Myers; Caroline Apovian; Hess, Donald T.; Noyan Gokce

    2015-01-01

    Background. Dysregulated lipolysis has been implicated in mechanisms of cardiometabolic disease and inflammation in obesity. Purpose. We sought to examine the effect of bariatric weight loss on adipose tissue lipolytic gene expression and their relationship to systemic metabolic parameters in obese subjects. Methods/Results. We biopsied subcutaneous adipose tissue in 19 obese individuals (BMI 42 ? 5?kg/m2, 79% female) at baseline and after a mean period of 8 ? 5 months (range 3?15 months) fol...

  20. Individual contributions of visceral fat and total body fat to subclinical atherosclerosis: The NEO study

    NARCIS (Netherlands)

    Gast, K.B.; Heijer, M. den; Smit, J.W.A.; Widya, R.L.; Lamb, H.J.; Roos, A. de; Jukema, J.W.; Rosendaal, F.R.; Mutsert, R. de

    2015-01-01

    BACKGROUND: Both overall and abdominal adiposity are established risk factors for cardiovascular disease. Visceral adipose tissue (VAT) and total body fat (TBF) are strongly correlated and previous studies did not make this distinction. OBJECTIVE: We aimed to distinguish individual contributions of

  1. Pro-Inflammatory CD11c+CD206+ Adipose Tissue Macrophages Are Associated With Insulin Resistance in Human Obesity

    Science.gov (United States)

    Wentworth, John M.; Naselli, Gaetano; Brown, Wendy A.; Doyle, Lisa; Phipson, Belinda; Smyth, Gordon K.; Wabitsch, Martin; O'Brien, Paul E.; Harrison, Leonard C.

    2010-01-01

    OBJECTIVE Insulin resistance and other features of the metabolic syndrome have been causally linked to adipose tissue macrophages (ATMs) in mice with diet-induced obesity. We aimed to characterize macrophage phenotype and function in human subcutaneous and omental adipose tissue in relation to insulin resistance in obesity. RESEARCH DESIGN AND METHODS Adipose tissue was obtained from lean and obese women undergoing bariatric surgery. Metabolic markers were measured in fasting serum and ATMs characterized by immunohistology, flow cytometry, and tissue culture studies. RESULTS ATMs comprised CD11c+CD206+ cells in “crown” aggregates and solitary CD11c−CD206+ cells at adipocyte junctions. In obese women, CD11c+ ATM density was greater in subcutaneous than omental adipose tissue and correlated with markers of insulin resistance. CD11c+ ATMs were distinguished by high expression of integrins and antigen presentation molecules; interleukin (IL)-1β, -6, -8, and -10; tumor necrosis factor-α; and CC chemokine ligand-3, indicative of an activated, proinflammatory state. In addition, CD11c+ ATMs were enriched for mitochondria and for RNA transcripts encoding mitochondrial, proteasomal, and lysosomal proteins, fatty acid metabolism enzymes, and T-cell chemoattractants, whereas CD11c− ATMs were enriched for transcripts involved in tissue maintenance and repair. Tissue culture medium conditioned by CD11c+ ATMs, but not CD11c− ATMs or other stromovascular cells, impaired insulin-stimulated glucose uptake by human adipocytes. CONCLUSIONS These findings identify proinflammatory CD11c+ ATMs as markers of insulin resistance in human obesity. In addition, the machinery of CD11c+ ATMs indicates they metabolize lipid and may initiate adaptive immune responses. PMID:20357360

  2. Assessment of tumourigenic potential in long-term cryopreserved human adipose-derived stem cells.

    Science.gov (United States)

    Yong, Kar Wey; Safwani, Wan Kamarul Zaman Wan; Xu, Feng; Zhang, Xiaohui; Choi, Jane Ru; Abas, Wan Abu Bakar Wan; Omar, Siti Zawiah; Azmi, Mat Adenan Noor; Chua, Kien Hui; Pingguan-Murphy, Belinda

    2017-08-01

    Cryopreservation represents an efficient way to preserve human mesenchymal stem cells (hMSCs) at early culture/passage, and allows pooling of cells to achieve sufficient cells required for off-the-shelf use in clinical applications, e.g. cell-based therapies and regenerative medicine. To fully apply cryopreserved hMSCs in a clinical setting, it is necessary to evaluate their biosafety, e.g. chromosomal abnormality and tumourigenic potential. To date, many studies have demonstrated that cryopreserved hMSCs display no chromosomal abnormalities. However, the tumourigenic potential of cryopreserved hMSCs has not yet been evaluated. In the present study, we cryopreserved human adipose-derived mesenchymal stem cells (hASCs) for 3 months, using a slow freezing method with various cryoprotective agents (CPAs), followed by assessment of the tumourigenic potential of the cryopreserved hASCs after thawing and subculture. We found that long-term cryopreserved hASCs maintained normal levels of the tumour suppressor markers p53, p21, p16 and pRb, hTERT, telomerase activity and telomere length. Further, we did not observe significant DNA damage or signs of p53 mutation in cryopreserved hASCs. Our findings suggest that long-term cryopreserved hASCs are at low risk of tumourigenesis. These findings aid in establishing the biosafety profile of cryopreserved hASCs, and thus establishing low hazardous risk perception with the use of long-term cryopreserved hASCs for future clinical applications. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Ectopic Adipose Tissue Storage in the Left and the Right Renal Sinus is Asymmetric and Associated With Serum Kidney Injury Molecule-1 and Fibroblast Growth Factor-21 Levels Increase

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    Gita Krievina, MSc

    2016-11-01

    Conclusions: Regardless of gender adipose tissue in RS accumulates asymmetrically–the left RS accumulates a significantly higher amount of adipose tissue. Thus, primarily RS adipose tissue effects should be assessed on the left kidney. Accumulation of adipose tissue in the RS is related with the visceral adipose amount, KIM-1 and FGF-21 concentration increase in the blood serum.

  4. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue.

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    Tina Rönn

    2013-06-01

    Full Text Available Epigenetic mechanisms are implicated in gene regulation and the development of different diseases. The epigenome differs between cell types and has until now only been characterized for a few human tissues. Environmental factors potentially alter the epigenome. Here we describe the genome-wide pattern of DNA methylation in human adipose tissue from 23 healthy men, with a previous low level of physical activity, before and after a six months exercise intervention. We also investigate the differences in adipose tissue DNA methylation between 31 individuals with or without a family history of type 2 diabetes. DNA methylation was analyzed using Infinium HumanMethylation450 BeadChip, an array containing 485,577 probes covering 99% RefSeq genes. Global DNA methylation changed and 17,975 individual CpG sites in 7,663 unique genes showed altered levels of DNA methylation after the exercise intervention (q<0.05. Differential mRNA expression was present in 1/3 of gene regions with altered DNA methylation, including RALBP1, HDAC4 and NCOR2 (q<0.05. Using a luciferase assay, we could show that increased DNA methylation in vitro of the RALBP1 promoter suppressed the transcriptional activity (p = 0.03. Moreover, 18 obesity and 21 type 2 diabetes candidate genes had CpG sites with differences in adipose tissue DNA methylation in response to exercise (q<0.05, including TCF7L2 (6 CpG sites and KCNQ1 (10 CpG sites. A simultaneous change in mRNA expression was seen for 6 of those genes. To understand if genes that exhibit differential DNA methylation and mRNA expression in human adipose tissue in vivo affect adipocyte metabolism, we silenced Hdac4 and Ncor2 respectively in 3T3-L1 adipocytes, which resulted in increased lipogenesis both in the basal and insulin stimulated state. In conclusion, exercise induces genome-wide changes in DNA methylation in human adipose tissue, potentially affecting adipocyte metabolism.

  5. Forkhead box O-1 modulation improves endothelial insulin resistance in human obesity.

    Science.gov (United States)

    Karki, Shakun; Farb, Melissa G; Ngo, Doan T M; Myers, Samantha; Puri, Vishwajeet; Hamburg, Naomi M; Carmine, Brian; Hess, Donald T; Gokce, Noyan

    2015-06-01

    Increased visceral adiposity has been closely linked to insulin resistance, endothelial dysfunction, and cardiometabolic disease in obesity, but pathophysiological mechanisms are poorly understood. We sought to investigate mechanisms of vascular insulin resistance by characterizing depot-specific insulin responses and gain evidence that altered functionality of transcription factor forkhead box O-1 (FOXO-1) may play an important role in obesity-related endothelial dysfunction. We intraoperatively collected paired subcutaneous and visceral adipose tissue samples from 56 severely obese (body mass index, 43 ± 7 kg/m(2)) and 14 nonobese subjects during planned surgical operations, and characterized depot-specific insulin-mediated responses using Western blot and quantitative immunofluorescence techniques. Insulin signaling via phosphorylation of FOXO-1 and consequent endothelial nitric oxide synthase stimulation was selectively impaired in the visceral compared with subcutaneous adipose tissue and endothelial cells of obese subjects. In contrast, tissue actions of insulin were preserved in nonobese individuals. Pharmacological antagonism with AS1842856 and biological silencing using small interfering RNA-mediated FOXO-1 knockdown reversed insulin resistance and restored endothelial nitric oxide synthase activation in the obese. We observed profound endothelial insulin resistance in the visceral adipose tissue of obese humans which improved with FOXO-1 inhibition. FOXO-1 modulation may represent a novel therapeutic target to diminish vascular insulin resistance. In addition, characterization of endothelial insulin resistance in the adipose microenvironment may provide clues to mechanisms of systemic disease in human obesity. © 2015 American Heart Association, Inc.

  6. Evaluation of adipose tissue volume quantification with IDEAL fat-water separation.

    Science.gov (United States)

    Alabousi, Abdullah; Al-Attar, Salam; Joy, Tisha R; Hegele, Robert A; McKenzie, Charles A

    2011-08-01

    To validate iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) for adipose tissue volume quantification. IDEAL allows MRI images to be produced only from adipose-containing tissues; hence, quantifying adipose tissue should be simpler and more accurate than with current methods. Ten healthy controls were imaged with 1.5 Tesla (T) Spin Echo (SE), 3.0T T1-weighted spoiled gradient echo (SPGR), and 3.0T IDEAL-SPGR. Images were acquired from the abdomen, pelvis, mid-thigh, and mid-calf. Mean subcutaneous and visceral adipose tissue volumes were compared between the three acquisitions for each subject. There were no significant differences (P>0.05) between the three acquisitions for subcutaneous adipose tissue volumes. However, there was a significant difference (P=0.0002) for visceral adipose tissue volumes in the abdomen. Post hoc analysis showed significantly lower visceral adipose tissue volumes measured by IDEAL versus 1.5T (P<0.0001) and 3.0T SPGR (P<0.002). The lower volumes given by IDEAL are due to its ability to differentiate true visceral adipose tissue from other bright structures like blood vessels and bowel content that are mistaken for adipose tissue in non-fat suppressed images. IDEAL measurements of adipose tissue are equivalent to established 1.5T measurement techniques for subcutaneous depots and have improved accuracy for visceral depots, which are more metabolically relevant. Copyright © 2011 Wiley-Liss, Inc.

  7. Adipogenic differentiation of laser-printed 3D tissue grafts consisting of human adipose-derived stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gruene, M; Deiwick, A; Koch, L; Schlie, S; Unger, C; Chichkov, B N [Nanotechnology Department, Laser Zentrum Hannover e.V., Hollerithallee 8, 30419 Hannover (Germany); Pflaum, M; Wilhelmi, M; Haverich, A, E-mail: m.gruene@lzh.de [Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover (Germany)

    2011-03-15

    Laser-assisted bioprinting (LaBP) allows the realization of computer-generated 3D tissue grafts consisting of cells embedded in a hydrogel environment. In this study, human adipose-derived stem cells (hASCs) were printed in a free-scalable 3D grid pattern by means of LaBP. We demonstrate that neither the proliferation ability nor the differentiation behaviour of the stem cells was affected by the LaBP procedure. Furthermore, the 3D grafts were differentiated down the adipogenic lineage pathway for 10 days. We verify by quantitative assessments of adipogenic markers that the 3D grafts resemble cell lineages present in natural adipose tissue. Additionally, we provide the proof that even pre-differentiated hASCs could be utilized for the generation of 3D tissue grafts. These results indicate that the biofabrication of living grafts resembling their complex native origin is within reach.

  8. [Psychophysiology of visceral pain].

    Science.gov (United States)

    Horing, B; Enck, P

    2014-06-01

    The psychophysiology of visceral pain is--different from cardiac psychophysiology--much less well investigated due to the invasiveness of its methods and problems associated with reliably and reproducibly stimulating as well as recording of the gastrointestinal tract. Despite these problems, the last 30 years have documented a number of psychophysiological phenomena such as the perception (interoception) of visceral stimuli, the effect of emotions and stress on visceral sensations, and the effect of visceral processes on cortical processing. This was mainly due to the application of neurophysiological techniques (cortical imaging and stimulation) in these investigations.

  9. Assumed non-persistent environmental chemicals in human adipose tissue; matrix stability and correlation with levels measured in urine and serum.

    Science.gov (United States)

    Artacho-Cordón, F; Arrebola, J P; Nielsen, O; Hernández, P; Skakkebaek, N E; Fernández, M F; Andersson, A M; Olea, N; Frederiksen, H

    2017-07-01

    The aim of this study was to (1) optimize a method for the measurement of parabens and phenols in adipose tissue, (2) evaluate the stability of chemical residues in adipose tissue samples, and (3) study correlations of these compounds in urine, serum, and adipose tissue. Samples were obtained from adults undergoing trauma surgery. Nine phenols and seven parabens were determined by isotope diluted TurboFlow-LC-MS/MS. The analytical method showed good accuracy and precision. Limits of detection (LOD) for parabens and phenols ranged from 0.05 to 1.83ng/g tissue. Good recovery rates were found, even when biological samples remained defrosted up to 24h. Benzophenone-3 (BP-3; range of values: LOD-1.48ng/g tissue) and methylparaben (MeP; LOD-1.78ng/g tissue) were detected in >70% of adipose tissue samples, while bisphenol-A (BPA; LOD-3.28ng/g tissue) and 2-phenylphenol (2-PP; LOD-0.78ng/g tissue) were detected in >40% of adipose tissue samples. In general, levels were similar between adipose tissue and serum, while a correlation between adipose tissue and urine was only found for BP-3. In conclusion, adipose tissue samples in this study were found to contain environmental chemicals considered to be non-persistent, whose levels were weakly or not at all correlated with the urine burden. Therefore, adipose tissue may potentially provide additional information to that obtained from other biological matrices. Further investigations are warranted to explore whether adipose tissue might be a suitable matrix for assessment of the consequences for human health of mid/long-term exposure to these chemicals. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Protective Effects of Diallyl Sulfide Against Ethanol-Induced Injury in Rat Adipose Tissue and Primary Human Adipocytes.

    Science.gov (United States)

    Kema, Venkata Harini; Khan, Imran; Jamal, Reshma; Vishwakarma, Sandeep Kumar; Lakki Reddy, Chandrakala; Parwani, Kirti; Patel, Farhin; Patel, Dhara; Khan, Aleem A; Mandal, Palash

    2017-06-01

    Alcohol consumption is the fourth leading cause of death and disability worldwide. Several cellular pathways contribute to alcohol-mediated tissue injury. Adipose tissue apart from functioning as an endocrine organ secretes several hormones and cytokines known as adipokines that are known to play a significant role in alcohol-induced tissue damage. This study was designed to test the efficacy of diallyl sulfide (DAS) in regulating the alcohol-induced outcomes on adipose tissue. Male Wistar rats were fed with 36% Lieber-DeCarli liquid diet containing ethanol (EtOH) for 4 weeks. Control rats were pair-fed with isocaloric diet containing maltodextrin instead of EtOH. During the last week of feeding protocol, the EtOH-fed rat group was given 200 mg/kg body weight of DAS through diet. We also studied DAS effect on isolated human primary adipocytes. Viability of human primary adipocytes on DAS treatment was assessed by MTT assay. Malondialdehyde (MDA), a marker of oxidative stress, was measured by HPLC and the thiobarbituric acid method. Expression of inflammatory genes and lipogenic genes was studied by qRT-PCR and Western blotting. Serum inflammatory gene expression was studied by ELISA. Our study results showed that DAS could alleviate EtOH-induced expression levels of proinflammatory and endoplasmic reticulum (ER) stress genes and improve adipose tissue mass and adipocyte morphology in male Wistar rats fed Lieber-DeCarli diet containing 6% EtOH. Further, we showed that DAS reduced the expression of lipogenic genes and improved lipid accumulation and adipocyte mass in human primary adipocytes treated with EtOH. Subsequently, we also showed that oxidative stress, as measured by the changes in MDA levels, was reduced in both male Wistar rats and human primary adipocytes treated with EtOH plus DAS. Our study results prove that DAS is effective in ameliorating EtOH-induced damage to adipose tissue as evidenced by the reduction brought about by DAS in oxidative stress

  11. Systemic beta-Adrenergic Stimulation of Thermogenesis Is Not Accompanied by Brown Adipose Tissue Activity in Humans

    OpenAIRE

    Vosselman, M. J.; van der Lans, A. A. J. J.; Brans, B.; Wierts, R.; van Baak, M. A.; Schrauwen, P.; van Marken Lichtenbelt, W. D.

    2012-01-01

    Brown adipose tissue (BAT) is currently considered as a target to combat obesity and diabetes in humans. BAT is densely innervated by the sympathetic nervous system (SNS) and can be stimulated by ?-adrenergic agonists, at least in animals. However, the exact role of the ?-adrenergic part of the SNS in BAT activation in humans is not known yet. In this study, we measured BAT activity by 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography/computed tomography imaging in 10 le...

  12. Human adipose-derived stem cells: definition, isolation, tissue-engineering applications.

    Science.gov (United States)

    Nae, S; Bordeianu, I; Stăncioiu, A T; Antohi, N

    2013-01-01

    Recent researches have demonstrated that the most effective repair system of the body is represented by stem cells - unspecialized cells, capable of self-renewal through successive mitoses, which have also the ability to transform into different cell types through differentiation. The discovery of adult stem cells represented an important step in regenerative medicine because they no longer raises ethical or legal issues and are more accessible. Only in 2002, stem cells isolated from adipose tissue were described as multipotent stem cells. Adipose tissue stem cells benefits in tissue engineering and regenerative medicine are numerous. Development of adipose tissue engineering techniques offers a great potential in surpassing the existing limits faced by the classical approaches used in plastic and reconstructive surgery. Adipose tissue engineering clinical applications are wide and varied, including reconstructive, corrective and cosmetic procedures. Nowadays, adipose tissue engineering is a fast developing field, both in terms of fundamental researches and medical applications, addressing issues related to current clinical pathology or trauma management of soft tissue injuries in different body locations.

  13. Sex differences in human adipose tissues - the biology of pear shape.

    Science.gov (United States)

    Karastergiou, Kalypso; Smith, Steven R; Greenberg, Andrew S; Fried, Susan K

    2012-05-31

    Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant research attention has focused on comparing adipocyte morphological and metabolic properties, as well as the capacity of preadipocytes derived from different depots for proliferation and differentiation. Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose tissue, and developmental factors. Gluteal-femoral adipose tissues of women may simply provide a safe lipid reservoir for excess energy, or they may directly regulate systemic metabolism via release of metabolic products or adipokines. We provide a brief overview of the relationship of fat distribution to metabolic health in men and women, and then focus on mechanisms underlying sex differences in adipose tissue biology.

  14. Sex differences in human adipose tissues – the biology of pear shape

    Directory of Open Access Journals (Sweden)

    Karastergiou Kalypso

    2012-05-01

    Full Text Available Abstract Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant research attention has focused on comparing adipocyte morphological and metabolic properties, as well as the capacity of preadipocytes derived from different depots for proliferation and differentiation. Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose tissue, and developmental factors. Gluteal-femoral adipose tissues of women may simply provide a safe lipid reservoir for excess energy, or they may directly regulate systemic metabolism via release of metabolic products or adipokines. We provide a brief overview of the relationship of fat distribution to metabolic health in men and women, and then focus on mechanisms underlying sex differences in adipose tissue biology.

  15. Human adipose cells in vitro are either refractory or responsive to insulin, reflecting host metabolic state.

    Directory of Open Access Journals (Sweden)

    Vladimir A Lizunov

    Full Text Available While intercellular communication processes are frequently characterized by switch-like transitions, the endocrine system, including the adipose tissue response to insulin, has been characterized by graded responses. Yet here individual cells from adipose tissue biopsies are best described by a switch-like transition between the basal and insulin-stimulated states for the trafficking of the glucose transporter GLUT4. Two statistically-defined populations best describe the observed cellular heterogeneity, representing the fractions of refractive and responsive adipose cells. Furthermore, subjects exhibiting high systemic insulin sensitivity indices (SI have high fractions of responsive adipose cells in vitro, while subjects exhibiting decreasing SI have increasing fractions of refractory cells in vitro. Thus, a two-component model best describes the relationship between cellular refractory fraction and subject SI. Since isolated cells exhibit these different response characteristics in the presence of constant culture conditions and milieu, we suggest that a physiological switching mechanism at the adipose cellular level ultimately drives systemic SI.

  16. Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain Tumor-Initiating Cells.

    Science.gov (United States)

    Choi, Seung Ah; Lee, Ji Yeoun; Kwon, Sung Eun; Wang, Kyu-Chang; Phi, Ji Hoon; Choi, Jung Won; Jin, Xiong; Lim, Ja Yun; Kim, Hyunggee; Kim, Seung-Ki

    2015-01-01

    In neuro-oncology, the biology of neural stem cells (NSCs) has been pursued in two ways: as tumor-initiating cells (TICs) and as a potential cell-based vehicle for gene therapy. NSCs as well as mesenchymal stem cells (MSCs) have been reported to possess tumor tropism capacities. However, there is little data on the migratory capacity of MSCs toward brain tumor-initiating cells (BTICs). This study focuses on the ability of human adipose tissue derived MSCs (hAT-MSCs) to target BTICs and their crosstalk in the microenvironment. BTICs were isolated from three different types of brain tumors. The migration capacities of hAT-MSCs toward BTICs were examined using an in vitro migration assay and in vivo bioluminescence imaging analysis. To investigate the crosstalk between hAT-MSCs and BTICs, we analyzed the mRNA expression patterns of cyto-chemokine receptors by RT-qPCR and the protein level of their ligands in co-cultured medium. The candidate cyto-chemokine receptors were selectively inhibited using siRNAs. Both in vitro and in vivo experiments showed that hAT-MSCs possess migratory abilities to target BTICs isolated from medulloblastoma, atypical teratoid/rhabdoid tumors (AT/RT) and glioblastoma. Different types of cyto-chemokines are involved in the crosstalk between hAT-MSCs and BTICs (medulloblastoma and AT/RT: CXCR4/SDF-1, CCR5/RANTES, IL6R/IL-6 and IL8R/IL8; glioblastoma: CXCR4/SDF-1, IL6R/IL-6, IL8R/IL-8 and IGF1R/IGF-1). Our findings demonstrated the migratory ability of hAT-MSCs for BTICs, implying the potential use of MSCs as a delivery vehicle for gene therapy. This study also confirmed the expression of hAT-MSCs cytokine receptors and the BTIC ligands that play roles in their crosstalk.

  17. Projection Stereolithographic Fabrication of Human Adipose Stem Cell-incorporated Biodegradable Scaffolds for Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Aaron X Sun

    2015-08-01

    Full Text Available Poor self-healing ability of cartilage necessitates the development of methods for cartilage regeneration. Scaffold construction with live stem cell incorporation and subsequent differentiation presents a promising route. Projection stereolithography (PSL offers high resolution and processing speed as well as the ability to fabricate scaffolds that precisely fit the anatomy of cartilage defects using medical imaging as the design template. We report here the use of a visible-light based PSL (VL-PSL system to encapsulate human adipose-derived stem cells (hASCs into a biodegradable polymer (poly-D,L-lactic acid/polyethylene glycol/ poly-D,L-lactic acid (PDLLA-PEG/hyaluronic acid (HA matrix to produce live cell constructs with customized architectures. After fabrication, hASCs showed high viability (84% and were uniformly distributed throughout the constructs, which possessed high mechanical property with a compressive modulus of 780 kPa. The hASC-seeded constructs were then cultured in Control or TGF-β3-containing chondrogenic medium for up to 28 days. In chondrogenic medium treated group (TGF-β3 group hASCs maintained 77% viability and expressed chondrogenic genes Sox9, collagen type II, and aggrecan at 11, 232, and 2.29 x 10(5 fold increases, respectively, compared to levels at day 0 in non-chondrogenic medium. The TGF-β3 group also produced a collagen type II and glycosaminoglycan (GAG-rich extracellular matrix, detected by immunohistochemistry, and Alcian blue and Safranin O staining suggesting robust chondrogenesis within the scaffold. Without chondroinductive addition (Control group, cell viability decreased with time (65% at 28 days and showed poor cartilage matrix deposition. After 28 days, mechanical strength of the TGF-β3 group remained high at 240 kPa. Thus, the PSL- and PLLA-PEG/HA based fabrication method using adult stem cells is a promising approach in producing mechanically competent engineered cartilage for joint cartilage

  18. Endothelial Differentiation of Human Adipose-Derived Stem Cells on Polyglycolic Acid/Polylactic Acid Mesh

    Science.gov (United States)

    Deng, Meng; Gu, Yunpeng; Liu, Zhenjun; Qi, Yue; Ma, Gui E.; Kang, Ning

    2015-01-01

    Adipose-derived stem cell (ADSC) is considered as a cell source potentially useful for angiogenesis in tissue engineering and regenerative medicine. This study investigated the growth and endothelial differentiation of human ADSCs on polyglycolic acid/polylactic acid (PGA/PLA) mesh compared to 2D plastic. Cell adhesion, viability, and distribution of hADSCs on PGA/PLA mesh were observed by CM-Dil labeling, live/dead staining, and SEM examination while endothelial differentiation was evaluated by flow cytometry, Ac-LDL/UEA-1 uptake assay, immunofluorescence stainings, and gene expression analysis of endothelial related markers. Results showed hADSCs gained a mature endothelial phenotype with a positive ratio of 21.4 ± 3.7% for CD31+/CD34− when induced in 3D mesh after 21 days, which was further verified by the expressions of a comprehensive range of endothelial related markers, whereas hADSCs in 2D induced and 2D/3D noninduced groups all failed to differentiate into endothelial cells. Moreover, compared to 2D groups, the expression for α-SMA was markedly suppressed in 3D cultured hADSCs. This study first demonstrated the endothelial differentiation of hADSCs on the PGA/PLA mesh and pointed out the synergistic effect of PGA/PLA 3D culture and growth factors on the acquisition of mature characteristic endothelial phenotype. We believed this study would be the initial step towards the generation of prevascularized tissue engineered constructs. PMID:26106426

  19. Endothelial Differentiation of Human Adipose-Derived Stem Cells on Polyglycolic Acid/Polylactic Acid Mesh

    Directory of Open Access Journals (Sweden)

    Meng Deng

    2015-01-01

    Full Text Available Adipose-derived stem cell (ADSC is considered as a cell source potentially useful for angiogenesis in tissue engineering and regenerative medicine. This study investigated the growth and endothelial differentiation of human ADSCs on polyglycolic acid/polylactic acid (PGA/PLA mesh compared to 2D plastic. Cell adhesion, viability, and distribution of hADSCs on PGA/PLA mesh were observed by CM-Dil labeling, live/dead staining, and SEM examination while endothelial differentiation was evaluated by flow cytometry, Ac-LDL/UEA-1 uptake assay, immunofluorescence stainings, and gene expression analysis of endothelial related markers. Results showed hADSCs gained a mature endothelial phenotype with a positive ratio of 21.4 ± 3.7% for CD31+/CD34− when induced in 3D mesh after 21 days, which was further verified by the expressions of a comprehensive range of endothelial related markers, whereas hADSCs in 2D induced and 2D/3D noninduced groups all failed to differentiate into endothelial cells. Moreover, compared to 2D groups, the expression for α-SMA was markedly suppressed in 3D cultured hADSCs. This study first demonstrated the endothelial differentiation of hADSCs on the PGA/PLA mesh and pointed out the synergistic effect of PGA/PLA 3D culture and growth factors on the acquisition of mature characteristic endothelial phenotype. We believed this study would be the initial step towards the generation of prevascularized tissue engineered constructs.

  20. Brown adipose tissue quantification in human neonates using water-fat separated MRI.

    Directory of Open Access Journals (Sweden)

    Jerod M Rasmussen

    Full Text Available There is a major resurgence of interest in brown adipose tissue (BAT biology, particularly regarding its determinants and consequences in newborns and infants. Reliable methods for non-invasive BAT measurement in human infants have yet to be demonstrated. The current study first validates methods for quantitative BAT imaging of rodents post mortem followed by BAT excision and re-imaging of excised tissues. Identical methods are then employed in a cohort of in vivo infants to establish the reliability of these measures and provide normative statistics for BAT depot volume and fat fraction. Using multi-echo water-fat MRI, fat- and water-based images of rodents and neonates were acquired and ratios of fat to the combined signal from fat and water (fat signal fraction were calculated. Neonatal scans (n = 22 were acquired during natural sleep to quantify BAT and WAT deposits for depot volume and fat fraction. Acquisition repeatability was assessed based on multiple scans from the same neonate. Intra- and inter-rater measures of reliability in regional BAT depot volume and fat fraction quantification were determined based on multiple segmentations by two raters. Rodent BAT was characterized as having significantly higher water content than WAT in both in situ as well as ex vivo imaging assessments. Human neonate deposits indicative of bilateral BAT in spinal, supraclavicular and axillary regions were observed. Pairwise, WAT fat fraction was significantly greater than BAT fat fraction throughout the sample (ΔWAT-BAT = 38 %, p<10(-4. Repeated scans demonstrated a high voxelwise correlation for fat fraction (Rall = 0.99. BAT depot volume and fat fraction measurements showed high intra-rater (ICCBAT,VOL = 0.93, ICCBAT,FF = 0.93 and inter-rater reliability (ICCBAT,VOL = 0.86, ICCBAT,FF = 0.93. This study demonstrates the reliability of using multi-echo water-fat MRI in human neonates for quantification throughout the torso of BAT depot volume and fat

  1. Adiposity, compared with masculinity, serves as a more valid cue to immunocompetence in human mate choice.

    Science.gov (United States)

    Rantala, Markus J; Coetzee, Vinet; Moore, Fhionna R; Skrinda, Ilona; Kecko, Sanita; Krama, Tatjana; Kivleniece, Inese; Krams, Indrikis

    2013-01-22

    According to the 'good genes' hypothesis, females choose males based on traits that indicate the male's genetic quality in terms of disease resistance. The 'immunocompetence handicap hypothesis' proposed that secondary sexual traits serve as indicators of male genetic quality, because they indicate that males can contend with the immunosuppressive effects of testosterone. Masculinity is commonly assumed to serve as such a secondary sexual trait. Yet, women do not consistently prefer masculine looking men, nor is masculinity consistently related to health across studies. Here, we show that adiposity, but not masculinity, significantly mediates the relationship between a direct measure of immune response (hepatitis B antibody response) and attractiveness for both body and facial measurements. In addition, we show that circulating testosterone is more closely associated with adiposity than masculinity. These findings indicate that adiposity, compared with masculinity, serves as a more important cue to immunocompetence in female mate choice.

  2. Impact of glucocorticoid hormones on adipokine secretion and human adipose tissue metabolism.

    Science.gov (United States)

    Fain, John N

    2013-08-01

    The glucocorticoid hormones alter the metabolism of the adipose tissue after an approximately 2-h lag period. The effects are mediated through the nuclear receptors that alter the expression of a wide variety of genes through the mechanisms that are similar to those seen in the other cells. There are many direct metabolic effects of the glucocorticoids on the adipose tissue metabolism, and every year, new effects are added to the list of proteins whose expression is influenced by the glucocorticoids. Furthermore, some enzymatic processes are affected by these hormones only in the presence of the other hormones such as growth hormone (GH) or insulin. Most of the effects of the glucocorticoids are on the gene transcription, and the effects on the mRNA are reflected in the altered levels of the target proteins. The glucocorticoids enhance the leptin release, while reducing that of the inflammatory adipokines and stimulating that of the lipoprotein lipase (LPL) in the presence of insulin. The activity of 11β-hydroxysteroid dehydrogenase type 1 (HSD1) is enhanced by the glucocorticoids along with that of α1 glycoprotein 1 and serum amyloid A release by the adipose tissue. In contrast, the tumor necrosis factor α (TNF)-stimulated lipolysis in the adipose tissue is blocked by the glucocorticoids. It is still unclear which, if any, of these effects account for the insulin resistance due to the glucocorticoids in the adipose tissue. However, recent work suggests that, at least in mice, the reduction in the osteocalcin release by the osteoblasts in the presence of the glucocorticoids accounts for much of the in vivo insulin resistance. In summary, there are multiple direct effects of the glucocorticoids, both anti-inflammatory and proinflammatory, on the adipose tissue.

  3. Effects of Weight Loss and Exercise on Apelin Serum Concentrations and Adipose Tissue Expression in Human Obesity

    Directory of Open Access Journals (Sweden)

    Joanna Krist

    2013-02-01

    Full Text Available Objective: Apelin is an adipokine which plays a role in the regulation of glucose homeostasis and may contribute to the link between increased adipose tissue mass and obesity related metabolic diseases. Here we investigate the role of omental and subcutaneous (SC adipose tissue apelin and its receptor APJ mRNA expression in human obesity and test the hypothesis that changes in circulating apelin are associated with reduced fat mass in three weight loss intervention studies. Methods: Apelin serum concentration was measured in 740 individuals in a cross-sectional (n = 629 study including a subgroup (n = 161 for which omental and SC apelin mRNA expression has been analyzed and in three interventions: 12 weeks exercise (n = 60, 6 months calorie-restricted diet (n = 19, 12 months after bariatric surgery (n = 32. Results: Apelin mRNA is significantly higher expressed in adipose tissue of patients with type 2 diabetes and correlates with circulating apelin, BMI, body fat, C-reactive protein, and insulin sensitivity. Obesity surgery-induced weight loss causes a significant reduction in omental and SC apelin expression. All interventions led to significantly reduced apelin serum concentrations which significantly correlate with improved insulin sensitivity, independently of changes in BMI. Conclusions: Reduced apelin expression and serum concentration may contribute to improved insulin sensitivity beyond significant weight loss.

  4. Human perivascular adipose tissue dysfunction as a cause of vascular disease: Focus on vascular tone and wall remodeling.

    Science.gov (United States)

    Ozen, Gulsev; Daci, Armond; Norel, Xavier; Topal, Gokce

    2015-11-05

    Obesity is one of the major risk factors for the development of cardiovascular diseases. It is characterized by excessive or abnormal accumulation of adipose tissue, including depots which surround the blood vessels named perivascular adipose tissue (PVAT). PVAT plays endocrine and paracrine roles by producing large numbers of metabolically vasoactive adipokines. The present review outlines our current understanding of the beneficial roles of PVAT in vascular tone and remodeling in healthy subjects supported by clinical studies, highlighting different factors or mechanisms that could mediate protective effects of PVAT on vascular function. Most studies in humans show that adiponectin is the best candidate for the advantageous effect of PVAT. However, in pathological conditions especially obesity-related cardiovascular diseases, the beneficial effects of PVAT on vascular functions are impaired and transform into detrimental roles. This change is defined as PVAT dysfunction. In the current review, the contribution of PVAT dysfunction to obesity-related cardiovascular diseases has been discussed with a focus on possible mechanisms including an imbalance between beneficial and detrimental adipokines (commonly described as decreased levels of adiponectin and increased levels of leptin or tumor necrosis factor-alpha (TNFα)), increased quantity of adipose tissue, inflammation, cell proliferation and endothelial dysfunction. Finally, novel pharmacotherapeutic targets for the treatment of cardiovascular and metabolic disorders are addressed. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Regional fat metabolism in human splanchnic and adipose tissues; the effect of exercise

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Bülow, Jens; Sacchetti, Massimo

    2002-01-01

    This study was conducted to investigate the role of splanchnic and adipose tissue in the regulation of fatty acid (FA) metabolism at rest, during 1 h of semi-recumbent cycle exercise at 60 % of maximal power output and 3 h of recovery. In six post-absorptive healthy volunteers catheters were placed...... in a radial artery, hepatic vein and a subcutaneous vein on the anterior abdominal wall. Whole body, and regional splanchnic and adipose tissue FA metabolism were measured by a constant infusion of the stable isotopes [U-(13)C]palmitate and [(2)H(5)]glycerol and according to Fick's principle. The whole body...

  6. Role of the sympathoadrenergic system in adipose tissue metabolism during exercise in humans

    DEFF Research Database (Denmark)

    Stallknecht, Bente; Lorentsen, J; Enevoldsen, L H

    2001-01-01

    1. The relative roles of sympathetic nerve activity and circulating catecholamines for adipose tissue lipolysis during exercise are not known. 2. Seven paraplegic spinal cord injured (SCI, injury level T3-T5) and seven healthy control subjects were studied by microdialysis and (133)xenon washout...... concentrations increased significantly in both groups. Plasma catecholamine levels increased significantly less with exercise in SCI than in healthy subjects. The exercise-induced increase in interstitial glycerol concentration in subcutaneous adipose tissue was significantly lower in SCI compared with healthy...... (P plasma catecholamine concentrations (P

  7. A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH.

    Science.gov (United States)

    Osman, Mohamed; Mistry, Anoop; Keding, Ada; Gabe, Rhian; Cook, Elizabeth; Forrester, Sarah; Wiggins, Rebecca; Di Marco, Stefania; Colloca, Stefano; Siani, Loredana; Cortese, Riccardo; Smith, Deborah F; Aebischer, Toni; Kaye, Paul M; Lacey, Charles J

    2017-05-01

    Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. This

  8. Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source.

    Science.gov (United States)

    Chau, You-Ying; Bandiera, Roberto; Serrels, Alan; Martínez-Estrada, Ofelia M; Qing, Wei; Lee, Martin; Slight, Joan; Thornburn, Anna; Berry, Rachel; McHaffie, Sophie; Stimson, Roland H; Walker, Brian R; Chapuli, Ramon Muñoz; Schedl, Andreas; Hastie, Nick

    2014-04-01

    Fuelled by the obesity epidemic, there is considerable interest in the developmental origins of white adipose tissue (WAT) and the stem and progenitor cells from which it arises. Whereas increased visceral fat mass is associated with metabolic dysfunction, increased subcutaneous WAT is protective. There are six visceral fat depots: perirenal, gonadal, epicardial, retroperitoneal, omental and mesenteric, and it is a subject of much debate whether these have a common developmental origin and whether this differs from that for subcutaneous WAT. Here we show that all six visceral WAT depots receive a significant contribution from cells expressing Wt1 late in gestation. Conversely, no subcutaneous WAT or brown adipose tissue arises from Wt1-expressing cells. Postnatally, a subset of visceral WAT continues to arise from Wt1-expressing cells, consistent with the finding that Wt1 marks a proportion of cell populations enriched in WAT progenitors. We show that all visceral fat depots have a mesothelial layer like the visceral organs with which they are associated, and provide several lines of evidence that Wt1-expressing mesothelium can produce adipocytes. These results reveal a major ontogenetic difference between visceral and subcutaneous WAT, and pinpoint the lateral plate mesoderm as a major source of visceral WAT. They also support the notion that visceral WAT progenitors are heterogeneous, and suggest that mesothelium is a source of adipocytes.

  9. Wnt5a Regulates the Assembly of Human Adipose Derived Stromal Vascular Fraction-Derived Microvasculatures.

    Directory of Open Access Journals (Sweden)

    Venkat M Ramakrishnan

    Full Text Available Human adipose-derived stromal vascular fraction (hSVF cells are an easily accessible, heterogeneous cell system that can spontaneously self-assemble into functional microvasculatures in vivo. However, the mechanisms underlying vascular self-assembly and maturation are poorly understood, therefore we utilized an in vitro model to identify potential in vivo regulatory mechanisms. We utilized passage one (P1 hSVF because of the rapid UEA1+ endothelium (EC loss at even P2 culture. We exposed hSVF cells to a battery of angiogenesis inhibitors and found that the pan-Wnt inhibitor IWP2 produced the most significant hSVF-EC networking decrease (~25%. To determine which Wnt isoform(s and receptor(s may be involved, hSVF was screened by PCR for isoforms associated with angiogenesis, with only WNT5A and its receptor, FZD4, being expressed for all time points observed. Immunocytochemistry confirmed Wnt5a protein expression by hSVF. To see if Wnt5a alone could restore IWP2-induced EC network inhibition, recombinant human Wnt5a (0-150 ng/ml was added to IWP2-treated cultures. The addition of rhWnt5a significantly increased EC network area and significantly decreased the ratio of total EC network length to EC network area compared to untreated controls. To determine if Wnt5a mediates in vivo microvascular self-assembly, 3D hSVF constructs containing an IgG isotype control, anti-Wnt5a neutralizing antibody or rhWnt5a were implanted subcutaneously for 2w in immune compromised mice. Compared to IgG controls, anti-Wnt5a treatment significantly reduced vessel length density by ~41%, while rhWnt5a significantly increased vessel length density by ~62%. However, anti-Wnt5a or rhWnt5a did not significantly affect the density of segments and nodes, both of which measure vascular complexity. Taken together, this data demonstrates that endogenous Wnt5a produced by hSVF plays a regulatory role in microvascular self-assembly in vivo. These findings also suggest that

  10. Modulation of natriuretic peptide receptors in human adipose tissue: molecular mechanisms behind the "natriuretic handicap" in morbidly obese patients.

    Science.gov (United States)

    Gentili, Alessandra; Frangione, Maria Rosaria; Albini, Elisa; Vacca, Carmine; Ricci, Maria Anastasia; De Vuono, Stefano; Boni, Marcello; Rondelli, Fabio; Rotelli, Luciana; Lupattelli, Graziana; Orabona, Ciriana

    2017-08-01

    The B-type natriuretic peptide (BNP) hormone plays a crucial role in the regulation of cardiovascular and energy homeostasis. Obesity is associated with low circulating levels of BNP, a condition known as "natriuretic handicap." Recent evidences suggest an altered expression of BNP receptors-both the signaling natriuretic peptide receptors (NPR)-A and the clearance NPR-C receptor-in adipose tissue (AT) as one of the putative causes of natriuretic handicap. The current study aims at clarifying the molecular mechanisms behind the natriuretic handicap, focusing on NPR modulation in the AT of obese and control subjects. The study enrolled 34 obese and 20 control subjects undergoing bariatric or abdominal surgery, respectively. The main clinical and biochemical parameters, including circulating BNP, were assessed. In visceral (VAT) and subcutaneous AT (SAT) samples, collected during surgery, the adipocytes and stromal vascular fraction (SVF) expression of NPR-A and NPR-C and the SVF secretion of interleukin 6 (IL-6) were determined. Both VAT and SAT from obese patients expressed a lower NPR-A/NPR-C ratio in adipocytes and the SVF secreted a higher level of IL-6, compared with the controls. Moreover, NPR-A/NPR-C ratio expressed by VAT and SAT adipocytes negatively correlated with body mass index, insulin, the Homeostasis Model Assessment of Insulin resistance, and IL-6 secreted by SVF, and the expression of the clearance receptor NPR-C, in both the VAT and SAT adipocytes, showed a negative correlation with circulating BNP. Overall, insulin resistance/hyperinsulinemia and AT inflammation (ie, high level of IL-6) are the major determinants of the lower NPR-A/NPR-C ratio in adipocytes, thus contributing to the natriuretic handicap in obese subjects. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Renin inhibition improves metabolic syndrome, and reduces angiotensin II levels and oxidative stress in visceral fat tissues in fructose-fed rats.

    Science.gov (United States)

    Chou, Chu-Lin; Lin, Heng; Chen, Jin-Shuen; Fang, Te-Chao

    2017-01-01

    Renin-angiotensin system in visceral fat plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats. However, the effects of renin inhibition on visceral adiposity in metabolic syndrome are not fully investigated. We investigated the effects of renin inhibition on visceral adiposity in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups for 8-week experiments: Group Con (standard chow diet), Group Fru (high-fructose diet; 60% fructose), Group FruA (high-fructose diet and concurrent aliskiren treatment; 100 mg/kg body weight [BW] per day), and Group FruB (high-fructose diet and subsequent, i.e. 4 weeks after initiating high-fructose feeding, aliskiren treatment; 100 mg/kg BW per day). The high-fructose diet induced metabolic syndrome, increased visceral fat weights and adipocyte sizes, and augmented angiotensin II (Ang II), NADPH oxidase (NOX) isoforms expressions, oxidative stress, and dysregulated production of adipocytokines from visceral adipose tissues. Concurrent and subsequent aliskiren administration ameliorated metabolic syndrome, dysregulated adipocytokines, and visceral adiposity in high fructose-fed hypertensive rats, and was associated with reducing Ang II levels, NOX isoforms expressions and oxidative stress in visceral fat tissues. Therefore, this study demonstrates renin inhibition could improve metabolic syndrome, and reduce Ang II levels and oxidative stress in visceral fat tissue in fructose-fed rats, and suggests that visceral adipose Ang II plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats.

  12. Common and distinct regulation of human and mouse brown and beige adipose tissues: a promising therapeutic target for obesity.

    Science.gov (United States)

    Liu, Xuejiao; Cervantes, Christopher; Liu, Feng

    2017-06-01

    Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and discuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better understanding of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limitations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing 'metabolic panacea'.

  13. A tale with a Twist: a developmental gene with potential relevance for metabolic dysfunction and inflammation in adipose tissue

    Directory of Open Access Journals (Sweden)

    Anca Dana Dobrian

    2012-08-01

    Full Text Available The Twist proteins (Twist-1 and -2 are highly conserved developmental proteins with key roles for the transcriptional regulation in mesenchymal cell lineages. They belong to the super-family of bHLH proteins and exhibit bi-functional roles as both activators and repressors of gene transcription. The Twist proteins are expressed at low levels in adult tissues but may become abundantly re-expressed in cells undergoing malignant transformation. This observation prompted extensive research on the roles of Twist proteins in cancer progression and metastasis. Very recent studies indicate a novel role for Twist-1 as a potential regulator of adipose tissue remodeling and inflammation. Several studies suggested that developmental genes are important determinants of obesity, fat distribution and remodeling capacity of different adipose depots. Twist-1 is abundantly and selectively expressed in the adult adipose tissue and its constitutive expression is significantly higher in subcutaneous vs. visceral fat in both mice and humans. Moreover, Twist1 expression is strongly correlated with BMI and insulin resistance in humans. However, the functional roles and transcriptional downstream targets of Twist1 in adipose tissue are largely unexplored. The purpose of this review is to highlight the major findings related to Twist1 expression in different fat depots and cellular components of adipose tissue and to discuss the potential mechanisms suggesting a role for Twist1 in adipose tissue metabolism, inflammation and remodeling.

  14. Ageing, adipose tissue, fatty acids and inflammation.

    Science.gov (United States)

    Pararasa, Chathyan; Bailey, Clifford J; Griffiths, Helen R

    2015-04-01

    A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults.

  15. Hormonal regulation of lipoprotein lipase in adipose tissue (studies in the rat and in humans)

    NARCIS (Netherlands)

    M.G.A. Baggen (Marinus)

    1988-01-01

    textabstractCurrent data strongly suggest the most important role for insulin in the hormonal regulation of adipose tissue LPL activity. It is not clear from the literature what the role is of glucocorticoids in the regulation of the enzyme. Stress hormones as ACTH and adrenalin for example seem

  16. Regional fat metabolism in human splanchnic and adipose tissues; the effect of exercise

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Bülow, Jens; Sacchetti, Massimo

    2002-01-01

    This study was conducted to investigate the role of splanchnic and adipose tissue in the regulation of fatty acid (FA) metabolism at rest, during 1 h of semi-recumbent cycle exercise at 60 % of maximal power output and 3 h of recovery. In six post-absorptive healthy volunteers catheters were plac...

  17. Vaccination with liposomal leishmanial antigens adjuvanted with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) confers long-term protection against visceral leishmaniasis through a human administrable route.

    Science.gov (United States)

    Ravindran, Rajesh; Maji, Mithun; Ali, Nahid

    2012-01-01

    The development of a long-term protective subunit vaccine against visceral leishmaniasis depends on antigens and adjuvants that can induce an appropriate immune response. The immunization of leishmanial antigens alone shows limited efficacy in the absence of an appropriate adjuvant. Earlier we demonstrated sustained protection against Leishmania donovani with leishmanial antigens entrapped in cationic liposomes through an intraperitoneal route. However, this route is not applicable for human administration. Herein, we therefore evaluated the immune response and protection induced by liposomal soluble leishmanial antigen (SLA) formulated with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) through a subcutaneous route. Subcutaneous immunization of BALB/c mice with SLA entrapped in liposomes or with MPL-TDM elicited partial protection against experimental visceral leishmaniasis. In contrast, liposomal SLA adjuvanted with MPL-TDM induced significantly higher levels of protection in liver and spleen in BALB/c mice challenged 10 days post-vaccination. Protection conferred by this formulation was sustained up to 12 weeks of immunization, and infection was controlled for at least 4 months of the challenge, similar to liposomal SLA immunization administered intraperitoneally. An analysis of cellular immune responses of liposomal SLA + MPL-TDM immunized mice demonstrated the induction of IFN-γ and IgG2a antibody production not only 10 days or 12 weeks post-vaccination but also 4 months after the challenge infection and a down regulation of IL-4 production after infection. Moreover, long-term immunity elicited by this formulation was associated with IFN-γ production also by CD8⁺ T cells. Taken together, our results suggest that liposomal SLA + MPL-TDM represent a good vaccine formulation for the induction of durable protection against L. donovani through a human administrable route.

  18. In vivo cartilage formation using chondrogenic-differentiated human adipose-derived mesenchymal stem cells mixed with fibrin glue.

    Science.gov (United States)

    Jung, Sung-No; Rhie, Jong Won; Kwon, Ho; Jun, Young Joon; Seo, Je-Won; Yoo, Gyeol; Oh, Deuk Young; Ahn, Sang Tae; Woo, Jihyoun; Oh, Jieun

    2010-03-01

    Human adipose-derived mesenchymal stem cells (MSCs) were differentiated into chondrogenic MSCs, and fibrin glue was used together to explore the feasibility of whether cartilages can be generated in vivo by injecting the differentiated cells. Mesenchymal stem cells extracted from human adipose were differentiated into chondrogenic MSCs, and such differentiated cells mixed with fibrin glue were injected subcutaneously into the back of the nude mouse. In addition to visual evaluation of the tissues formed after 4, 8, and 12 weeks, hematoxylin-eosin staining, Masson trichrome staining, measurement of glycosaminoglycan concentration using dimethylmethylene blue, agreecan through reverse transcriptase-polymerase chain reaction, type II collagen, and expression of SOX-9 were verified. Moreover, the results were compared with 2 groups of controls: 1 control group that received only injection of chondrogenic-differentiated MSC and the supporting control group that received only fibrin glue injection. For the experimental group, cartilage-like tissues were formed after 4, 8, and 12 weeks. Formation of cartilage tissues was not observed in any of 4, 8, and 12 weeks of the control group. The supporting control group had only a small structure formation after 4 weeks, but the formed structure was completely decomposed by the 8th and 12th weeks. The range of staining dramatically increased with time at 4, 8, and 12 weeks in Masson trichrome staining. The concentration of glycosaminoglycan also increased with time. The increased level was statistically significant with more than 3 times more after 8 weeks compared with 4 weeks and more than 2 times more after 12 weeks compared with 8 weeks. Also, in reverse transcriptase-polymerase chain reaction at 4, 8, and 12 weeks, all results expressed a cartilage-specific gene called aggrecan, type II collagen, and SOX-9. The study verified that the chondrogenic-differentiated MSCs derived from human adipose tissues with fibrin glue can

  19. Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis

    Directory of Open Access Journals (Sweden)

    Wang Linjie

    2011-10-01

    Full Text Available Abstract Background Growing evidence suggests that epicardial adipose tissue (EAT may play a key role in the pathogenesis and development of coronary artery disease (CAD by producing several inflammatory adipokines. Chemerin, a novel adipokine, has been reported to be involved in regulating immune responses and glucolipid metabolism. Given these properties, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis. In this study, we sought to determine the relationship of chemerin expression in EAT and the severity of coronary atherosclerosis in Han Chinese patients. Methods Serums and adipose tissue biopsies (epicardial and thoracic subcutaneous were obtained from CAD (n = 37 and NCAD (n = 16 patients undergoing elective cardiac surgery. Gensini score was used to assess the severity of CAD. Serum levels of chemerin, adiponectin and insulin were measured by ELISA. Chemerin protein expression in adipose tissue was detected by immunohistochemistry. The mRNA levels of chemerin, chemR23, adiponectin and TNF-alpha in adipose tissue were detected by RT-PCR. Results We found that EAT of CAD group showed significantly higher levels of chemerin and TNF-alpha mRNA, and significantly lower level of adiponectin mRNA than that of NCAD patients. In CAD group, significantly higher levels of chemerin mRNA and protein were observed in EAT than in paired subcutaneous adipose tissue (SAT, whereas such significant difference was not found in NCAD group. Chemerin mRNA expression in EAT was positively correlated with Gensini score (r = 0.365, P P P P P P P > 0.05. Conclusions The expressions of chemerin mRNA and protein are significantly higher in EAT from patients with CAD in Han Chinese patients. Furthermore, the severity of coronary atherosclerosis is positive correlated with the level of chemerin mRNA in EAT rather than its circulating level.

  20. ACC2 is expressed at high levels in human white adipose and has an isoform with a novel N-terminus [corrected].

    Directory of Open Access Journals (Sweden)

    John C Castle

    Full Text Available Acetyl-CoA carboxylases ACC1 and ACC2 catalyze the carboxylation of acetyl-CoA to malonyl-CoA, regulating fatty-acid synthesis and oxidation, and are potential targets for treatment of metabolic syndrome. Expression of ACC1 in rodent lipogenic tissues and ACC2 in rodent oxidative tissues, coupled with the predicted localization of ACC2 to the mitochondrial membrane, have suggested separate functional roles for ACC1 in lipogenesis and ACC2 in fatty acid oxidation. We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. Human adipose, along with human liver, expresses more ACC2 than ACC1. Using RT-PCR, real-time PCR, and immunoprecipitation we report a novel isoform of ACC2 (ACC2.v2 that is expressed at significant levels in human adipose. The protein generated by this isoform has enzymatic activity, is endogenously expressed in adipose, and lacks the N-terminal sequence. Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis. The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors.

  1. Enhanced biglycan gene expression in the adipose tissues of obese women and its association with obesity-related genes and metabolic parameters.

    Science.gov (United States)

    Kim, Jimin; Lee, Seul Ki; Shin, Ji-Min; Jeoun, Un-Woo; Jang, Yeon Jin; Park, Hye Soon; Kim, Jong-Hyeok; Gong, Gyung-Yub; Lee, Taik Jong; Hong, Joon Pio; Lee, Yeon Ji; Heo, Yoon-Suk

    2016-07-28

    Extracellular matrix (ECM) remodeling dynamically occurs to accommodate adipose tissue expansion during obesity. One non-fibrillar component of ECM, biglycan, is released from the matrix in response to tissue stress; the soluble form of biglycan binds to toll-like receptor 2/4 on macrophages, causing proinflammatory cytokine secretion. To investigate the pattern and regulatory properties of biglycan expression in human adipose tissues in the context of obesity and its related diseases, we recruited 21 non-diabetic obese women, 11 type 2 diabetic obese women, and 59 normal-weight women. Regardless of the presence of diabetes, obese patients had significantly higher biglycan mRNA in both visceral and subcutaneous adipose tissue. Biglycan mRNA was noticeably higher in non-adipocytes than adipocytes and significantly decreased during adipogenesis. Adipose tissue biglycan mRNA positively correlated with adiposity indices and insulin resistance parameters; however, this relationship disappeared after adjusting for BMI. In both fat depots, biglycan mRNA strongly correlated with the expression of genes related to inflammation and endoplasmic reticulum stress. In addition, culture of human preadipocytes and differentiated adipocytes under conditions mimicking the local microenvironments of obese adipose tissues significantly increased biglycan mRNA expression. Our data indicate that biglycan gene expression is increased in obese adipose tissues by altered local conditions.

  2. The effect of low static magnetic field on osteogenic and adipogenic differentiation potential of human adipose stromal/stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Marędziak, Monika, E-mail: monika.maredziak@gmail.com [Faculty of Veterinary Medicine, University of Environmental and Life Sciences, Wrocław (Poland); Wroclaw Research Centre EIT+, Wrocław (Poland); Śmieszek, Agnieszka, E-mail: smieszek.agnieszka@gmail.com [Wroclaw Research Centre EIT+, Wrocław (Poland); Faculty of Biology, University of Environmental and Life Sciences, Wrocław (Poland); Tomaszewski, Krzysztof A., E-mail: krtomaszewski@gmail.com [Department of Anatomy, Jagiellonian University Medical College, Krakow (Poland); Lewandowski, Daniel, E-mail: daniel.lewandowski@pwr.wroc.pl [Institute of Materials Science and Applied Mechanics, Wroclaw University of Technology, Wroclaw (Poland); Marycz, Krzysztof, E-mail: krzysztofmarycz@interia.pl [Wroclaw Research Centre EIT+, Wrocław (Poland); Faculty of Biology, University of Environmental and Life Sciences, Wrocław (Poland)

    2016-01-15

    The aim of this work was to investigate the effects of static magnetic field (SMF) on the osteogenic properties of human adipose derived mesenchymal stem cells (hASCs). In this study in seven days viability assay we examined the impact of SMF on cells proliferation rate, population doubling time, and ability to form single-cell derived colonies. We have also examined cells' morphology, ultrastructure and osteogenic properties on the protein as well as mRNA level. We established a complex approach, which enabled us to obtain information about SMF and hASCs potential in the context of differentiation into osteogenic and adipogenic lineages. We demonstrated that SMF enhances both viability and osteogenic properties of hASCs through higher proliferation factor and shorter population doubling time. We have also observed asymmetrically positioned nuclei and organelles after SMF exposition. With regards to osteogenic properties we observed increased levels of osteogenic markers i.e. osteopontin, osteocalcin and increased ability to form osteonodules with positive reaction to Alizarin Red dye. We have also shown that SMF besides enhancing osteogenic properties of hASCs, simultaneously decreases their ability to differentiate into adipogenic lineage. Our results clearly show a direct influence of SMF on the osteogenic potential of hASCs. These results provide key insights into the role of SMF on their cellular fate and properties. - Graphical abstract: Influence of static magnetic field on viability and differentiation properties of human adipose derived mesenchymal stem cells. Abbreviations: SMF – static magnetic field; hASCs – human adipose derived mesenchymal stem cells; PF – proliferation factor; PDT – population doubling time; CFU-E –> colony forming unit efficiency; OPN – osteopontin; OCL – osteocalcin; Col – collagen type I; BMP-2 – bone morphogenetic protein 2; Ca – calcium; P – phosphorus. - Highlights: • Effects of static

  3. Effects of DHEA on metabolic and endocrine functions of adipose tissue.

    Science.gov (United States)

    Karbowska, Joanna; Kochan, Zdzislaw

    2013-08-01

    Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, are the major circulating adrenal steroids and serve as substrates for sex hormone biosynthesis. DHEA is effectively taken up by adipose tissue, where the concentrations of free DHEA are four to ten times higher than those found in the circulation. DHEA reduces adipose tissue mass and inhibits the proliferation and differentiation of adipocytes; it may also protect against obesity by lowering the activity of stearoyl-CoA desaturase 1 in fat cells. Recent studies demonstrate that DHEA stimulates triacylglycerol hydrolysis in adipose tissue by increasing the expression and activity of adipose triglyceride lipase and hormone-sensitive lipase, the key enzymes of lipolysis. DHEA has been shown to modulate insulin signaling pathways, enhance glucose uptake in adipocytes, and increase insulin sensitivity in patients with DHEA deficiency or abnormal glucose tolerance. Additionally, by suppressing the activity of 11β-hydroxysteroid dehydrogenase 1 in adipocytes, DHEA may promote intra-adipose inactivation of cortisol to cortisone. Several studies have demonstrated that DHEA may also regulate the expression and secretion of adipokines such as leptin, adiponectin, and resistin. The effects of DHEA on adipokine expression in adipose tissue are depot-specific, with visceral fat being the most responsive. The mechanisms underlying DHEA actions in adipose tissue are still unclear; however, they involve nuclear receptors such as androgen receptor and peroxisome proliferator-activated receptors γ and α. Because clinical trials investigating the effects of DHEA failed to yield consistent results, further studies are needed to clarify the role of DHEA in the regulation of human adipose tissue physiology.

  4. Primary cilia: the chemical antenna regulating human adipose-derived stem cell osteogenesis.

    Directory of Open Access Journals (Sweden)

    Josephine C Bodle

    Full Text Available Adipose-derived stem cells (ASC are multipotent stem cells that show great potential as a cell source for osteogenic tissue replacements and it is critical to understand the underlying mechanisms of lineage specification. Here we explore the role of primary cilia in human ASC (hASC differentiation. This study focuses on the chemosensitivity of the primary cilium and the action of its associated proteins: polycystin-1 (PC1, polycystin-2 (PC2 and intraflagellar transport protein-88 (IFT88, in hASC osteogenesis. To elucidate cilia-mediated mechanisms of hASC differentiation, siRNA knockdown of PC1, PC2 and IFT88 was performed to disrupt cilia-associated protein function. Immunostaining of the primary cilium structure indicated phenotypic-dependent changes in cilia morphology. hASC cultured in osteogenic differentiation media yielded cilia of a more elongated conformation than those cultured in expansion media, indicating cilia-sensitivity to the chemical environment and a relationship between the cilium structure and phenotypic determination. Abrogation of PC1, PC2 and IFT88 effected changes in both hASC proliferation and differentiation activity, as measured through proliferative activity, expression of osteogenic gene markers, calcium accretion and endogenous alkaline phosphatase activity. Results indicated that IFT88 may be an early mediator of the hASC differentiation process with its knockdown increasing hASC proliferation and decreasing Runx2, alkaline phosphatase and BMP-2 mRNA expression. PC1 and PC2 knockdown affected later osteogenic gene and end-product expression. PC1 knockdown resulted in downregulation of alkaline phosphatase and osteocalcin gene expression, diminished calcium accretion and reduced alkaline phosphatase enzymatic activity. Taken together our results indicate that the structure of the primary cilium is intimately associated with the process of hASC osteogenic differentiation and that its associated proteins are critical

  5. Visceral sensitivity testing.

    Science.gov (United States)

    Andresen, Viola

    2009-01-01

    Visceral hypersensitivity is regarded as an important factor in the pathogenesis of functional gastrointestinal disorders. Assessment of visceral sensitivity has several important aims: increasing the understanding of normal and abnormal visceral sensory mechanisms and participating sensory pathways, serving as diagnostic tool to detect patients with abnormal visceral sensitivity, and evaluating therapeutic interventions directed towards modification of visceral sensitivity. Current stimulation modes in sensitivity tests include mechanical distension by barostat or tensostat, nutrient drink or water load, chemical stimulation, e.g. acid provocation or capsaicin ingestion, electrical, or thermal stimulation. Multimodal probes incorporating several stimulation modes in one device have recently been developed. Assessment of visceral sensation can be based on subjective responses of conscious perception or on objective parameters such as visceromotoric responses or central sensory processing patterns. All methods face the challenge that visceral sensitivity may be influenced by a wide spectrum of different factors, including the test techniques themselves, and improved, preferably non-invasive sensitivity tests with a greater standardisation and a broader applicability are still needed.

  6. Brown Adipose Tissue Regulates Small Artery Function Through NADPH Oxidase 4-Derived Hydrogen Peroxide and Redox-Sensitive Protein Kinase G-1α.

    Science.gov (United States)

    Friederich-Persson, Malou; Nguyen Dinh Cat, Aurelie; Persson, Patrik; Montezano, Augusto C; Touyz, Rhian M

    2017-03-01

    Biomedical interest in brown adipose tissue (BAT) has increased since the discovery of functionally active BAT in adult humans. Although white adipose tissue (WAT) influences vascular function, vascular effects of BAT are elusive. Thus, we investigated the regulatory role and putative vasoprotective effects of BAT, focusing on hydrogen peroxide, nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4), and redox-sensitive signaling. Vascular reactivity was assessed in wild-type and Nox4-knockout mice (Nox4(-/-)) by wire myography in the absence and presence of perivascular adipose tissue of different phenotypes from various adipose depots: (1) mixed WAT/BAT (inguinal adipose tissue) and (2) WAT (epididymal visceral fat) and BAT (intrascapular fat). In wild-type mice, epididymal visceral fat and perivascular adipose tissue increased EC50 to noradrenaline without affecting maximum contraction. BAT increased EC50 and significantly decreased maximum contraction, which were prevented by a hydrogen peroxide scavenger (polyethylene glycated catalase) and a specific cyclic GMP-dependent protein kinase G type-1α inhibitor (DT-3), but not by inhibition of endothelial nitric oxide synthase or guanylate cyclase. BAT induced dimerization of cyclic GMP-dependent protein kinase G type-1α and reduced phosphorylation of myosin light chain phosphatase subunit 1 and myosin light chain 20. BAT from Nox4-knockout mice displayed reduced hydrogen peroxide levels and no anticontractile effects. Perivascular adipose tissue from β3 agonist-treated mice displayed browned perivascular adipose tissue and an increased anticontractile effect. We identify a novel vasoprotective action of BAT through an anticontractile effect that is mechanistically different to WAT. Specifically, BAT, via Nox4-derived hydrogen peroxide, induces cyclic GMP-dependent protein kinase G type-1α activation, resulting in reduced vascular contractility. BAT may constitute an interesting therapeutic target to

  7. Fetal development of subcutaneous white adipose tissue is dependent on Zfp423

    Directory of Open Access Journals (Sweden)

    Mengle Shao

    2017-01-01

    Conclusions: Our results reveal that Zfp423 is essential for the terminal differentiation of subcutaneous white adipocytes during fetal adipose tissue development. Moreover, our data highlight the striking adverse effects of pathological subcutaneous adipose tissue remodeling on visceral adipose function and systemic nutrient homeostasis in obesity. Importantly, these data reveal the distinct phenotypes that can occur when adiponectin driven transgenes are activated in fetal vs. adult adipose tissue.

  8. Human adipose-derived mesenchymal stem cells as a new model of spinal and bulbar muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Marta Dossena

    Full Text Available Spinal and bulbar muscular atrophy (SBMA or Kennedy's disease is an X-linked CAG/polyglutamine expansion motoneuron disease, in which an elongated polyglutamine tract (polyQ in the N-terminal androgen receptor (ARpolyQ confers toxicity to this protein. Typical markers of SBMA disease are ARpolyQ intranuclear inclusions. These are generated after the ARpolyQ binds to its endogenous ligands, which promotes AR release from chaperones, activation and nuclear translocation, but also cell toxicity. The SBMA mouse models developed so far, and used in preclinical studies, all contain an expanded CAG repeat significantly longer than that of SBMA patients. Here, we propose the use of SBMA patients adipose-derived mesenchymal stem cells (MSCs as a new human in vitro model to study ARpolyQ toxicity. These cells have the advantage to express only ARpolyQ, and not the wild type AR allele. Therefore, we isolated and characterized adipose-derived MSCs from three SBMA patients (ADSC from Kennedy's patients, ADSCK and three control volunteers (ADSCs. We found that both ADSCs and ADSCKs express mesenchymal antigens, even if only ADSCs can differentiate into the three typical cell lineages (adipocytes, chondrocytes and osteocytes, whereas ADSCKs, from SBMA patients, showed a lower growth potential and differentiated only into adipocyte. Moreover, analysing AR expression on our mesenchymal cultures we found lower levels in all ADSCKs than ADSCs, possibly related to negative pressures exerted by toxic ARpolyQ in ADSCKs. In addition, with proteasome inhibition the ARpolyQ levels increased specifically in ADSCKs, inducing the formation of HSP70 and ubiquitin positive nuclear ARpolyQ inclusions. Considering all of this evidence, SBMA patients adipose-derived MSCs cultures should be considered an innovative in vitro human model to understand the molecular mechanisms of ARpolyQ toxicity and to test novel therapeutic approaches in SBMA.

  9. Late gestation over- and undernutrition predispose for visceral adiposity in response to a post-natal obesogenic diet, but with differential impacts on glucose-insulin adaptations during fasting in lambs

    DEFF Research Database (Denmark)

    Khanal, Prabhat; Husted, Sanne Vinter; Axel, Anne Marie Dixen

    2014-01-01

    -fat or a moderate diet until 6 months of age (around puberty), where metabolic and endocrine adaptability to fasting was examined, and subgroups of animals were killed. Results: Animals exposed to either prenatal under- or overnutrition had reduced subcutaneous fat deposition when fed a high-fat diet, resulting...... of subcutaneous adipose tissue and induced differential physiological adaptations to fasting. This study does not suggest that exposure to gestational overnutrition will provide a protective effect against development of hyperglycaemia later in life. © 2013 Scandinavian Physiological Society....

  10. Interferon-gamma released from omental adipose tissue of insulin-resistant humans alters adipocyte phenotype and impairs response to insulin and adiponectin release.

    Science.gov (United States)

    Wentworth, J M; Zhang, J-G; Bandala-Sanchez, E; Naselli, G; Liu, R; Ritchie, M; Smyth, G K; O'Brien, P E; Harrison, L C

    2017-12-01

    Inflammatory factors derived from adipose tissue have been implicated in mediating insulin resistance in obesity. We sought to identify these using explanted human adipose tissue exposed to innate and adaptive immune stimuli. Subcutaneous and omental adipose tissue from obese, insulin-resistant donors was cultured in the presence of macrophage and T-cell stimuli, and the conditioned medium tested for its ability to inhibit insulin-stimulated glucose uptake into human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. The nature of the inhibitory factor in conditioned medium was characterized physicochemically, inferred by gene microarray analysis and confirmed by antibody neutralization. Conditioned medium from omental adipose tissue exposed to a combination of macrophage- and T-cell stimuli inhibited insulin action and adiponectin secretion in SGBS adipocytes. This effect was associated with a pronounced change in adipocyte morphology, characterized by a decreased number of lipid droplets of increased size. The bioactivity of conditioned medium was abolished by trypsin treatment and had a molecular weight of 46 kDa by gel filtration. SGBS adipocytes exposed to a bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-γ). Recombinant human IFN-γ recapitulated the effects of the bioactive medium and neutralizing antibody against IFN-γ but not other candidate factors abrogated medium bioactivity. IFN-γ released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.

  11. Série temporal da leishmaniose visceral em Aracaju, estado de Sergipe, Brasil (1999 a 2008: aspectos humanos e caninos Time series of visceral leishmaniasis in Aracaju, state of Sergipe, Brazil (1999 to 2008: human and canine aspects

    Directory of Open Access Journals (Sweden)

    Marco Aurélio de Oliveira Góes

    2012-06-01

    Full Text Available INTRODUÇÃO: Considerada doença negligenciada pela OMS, a Leishmaniose visceral (LV tem se expandido e urbanizado, sendo sua transmissão e expansão associadas a diversos fatores. OBJETIVO: Avaliar aspectos epidemiológicos da LV no município de Aracaju/SE, por meio de estudo retrospectivo da série histórica de LV humana e canina no período de 1999-2008. MÉTODOS: Foram utilizados dados secundários do SINAN para os casos humanos, e o resultado dos inquéritos caninos e atendimentos da demanda passiva do Centro de Controle de Zoonoses (CCZ. RESULTADOS: Foram notificados 192 casos autóctones de LV humana, sendo 63,5% do gênero masculino. Crianças entre 1 e 4 anos foram mais acometidas (29,2%, seguidas de adultos entre 20-29 anos (15,6% e de crianças entre 5-9 anos (15,1%. A letalidade geral foi de 8,9%, sendo mais acentuada em pessoas entre 60 a 69 anos (60%; 32,3% dos casos autóctones realizaram sorologia para HIV, com positividade de 6,9%. A confirmação laboratorial foi realizada principalmente mediante a imunofluorescência indireta isolada (71,1%. Dos 58.161 cães que realizaram sorologia a positividade foi de 5,4%, sendo 87,0% dos inquéritos realizados anualmente pelo CCZ, com uma positividade de 4,4%. Dos 7.501 cães trazidos ao CCZ por diversas queixas, o exame sorológico foi reagente em 12,0%. CONCLUSÃO: Os dados denotam o caráter endêmico da LV no município, mostrando a necessidade de ações que permitam a diminuição do risco para a população, principalmente aquela onde a incidência e a letalidade são maiores, como melhorias no diagnóstico da LV, assim como na co-infecção com HIV e no monitoramento da população canina, entre outros.INTRODUCTION: Considered as a neglected disease by the WHO, visceral leishmaniasis (VL has expanded and urbanized. Its transmission and expansion have been linked to several factors. OBJECTIVE: To evaluate the epidemiological aspects of VL in the city of Aracaju/SE, through

  12. Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice

    DEFF Research Database (Denmark)

    Niemeyer, P; Vohrer, J; Schmal, H

    2008-01-01

    INTRODUCTION: Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose...... of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice. METHODS: Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were...... transplanted subcutaneously into immunocompetent mice (n=12). Undifferentiated MSC (group A) were compared with osteogenic-induced MSC (group B). Human-specific in situ hybridization and anti-vimentin staining was used to follow MSC after transplantation. Quantitative evaluation of lymphocytes and macrophages...

  13. Desensitization of human adipose tissue to adrenaline stimulation studied by microdialysis

    DEFF Research Database (Denmark)

    Stallknecht, B; Bülow, J; Frandsen, E

    1997-01-01

    during intravenous adrenaline infusion for three 35 min periods with 30 min breaks in between. Local blood flow, interstitial adrenaline and arterial glycerol concentrations were also measured. Adrenaline was infused to result in either a high, a low and a high arterial concentration (5.8, 3.1 and 5.6 n......M, respectively) or a low, a high and a low concentration (2.5, 4.6 and 2.6 nM, respectively) in order to examine both desensitization and the dose dependency of adipose tissue lipolysis to adrenaline. 3. Adipose tissue lipolysis was calculated and was found to vary directly with arterial adrenaline concentration....... However, lipolytic responses to adrenaline decreased markedly during repeated stimulation at a given concentration. Further, arterial glycerol and free fatty acid concentrations varied directly with arterial adrenaline concentrations and showed reduced responses upon repeated exposure. 4. The increase...

  14. Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth; Bojsen-Moller, Kirstine N; Dirksen, Carsten

    2015-01-01

    12 months post-surgery. Adipose tissue from glucose tolerant subjects was the most responsive to RYGB compared to type 2 diabetic patients, whereas changes in skeletal muscle were largely similar in these two groups. In conclusion, an improved molecular insulin sensitive phenotype of skeletal muscle......Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose...... tolerant and type 2 diabetic subjects at fasting and during a hyperinsulinemic-euglycemic clamp before as well as 1 week, 3 and 12 months after RYGB were analyzed for relevant insulin effector proteins/signaling components. Improvement in peripheral insulin sensitivity mainly occurred at 12 months post-surgery...

  15. Content of Trans Fatty Acids in Human Cheek Epithelium: Comparison with Serum and Adipose Tissue

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    Ransi A. Abraham

    2013-01-01

    Full Text Available Studies pertaining to trans fatty acids (TFA, which have been implicated in development of chronic diseases, are more relevant in developing countries where nutrition transition is changing traditional habits and practices. Measuring TFA is an arduous task because of the need for fat biopsies. This study identifies a tissue, which can be easily accessed for analytical measurement of trans fatty acid. In this cross-sectional study, fatty acid in adipose tissue, cheek epithelium, and blood samples were assessed by gas chromatography. Spearman correlation coefficient was computed to study the correlation of fatty acid distribution among the three tissues. The correlation coefficient of total trans fatty acid between cheek epithelium and serum was 0.30 ( and between cheek epithelium and adipose tissue was 0.33 (. This study is the first to report trans fatty acid profile in cheek epithelium giving scope for utilizing the cheek epithelium as a tissue for objective assessment of trans fatty acid intake.

  16. Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis

    OpenAIRE

    Wang Linjie; Zhang Xiaoxia; Gao Feng; Lai Yongqiang; Gong Fengying; Zhang Fuzhuang; Mi Shuhua; Gao Xiuying; Tao Hong

    2011-01-01

    Abstract Background Growing evidence suggests that epicardial adipose tissue (EAT) may play a key role in the pathogenesis and development of coronary artery disease (CAD) by producing several inflammatory adipokines. Chemerin, a novel adipokine, has been reported to be involved in regulating immune responses and glucolipid metabolism. Given these properties, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis. In this study, we sought to determine the r...

  17. Mechanical properties of cross-linked collagen meshes after human adipose derived stromal cells seeding

    OpenAIRE

    Ochoa, I. (Ignacio); Peña, E. (Estefanía); Andreu, E.J. (Enrique José); Perez-Ilzarbe, M. (Maitane);