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Sample records for omental adipose tissue

  1. Characterization and comparison of adipose tissue-derived cells from human subcutaneous and omental adipose tissues.

    Science.gov (United States)

    Toyoda, Mito; Matsubara, Yoshinori; Lin, Konghua; Sugimachi, Keizou; Furue, Masutaka

    2009-10-01

    Different fat depots contribute differently to disease and function. These differences may be due to the regional variation in cell types and inherent properties of fat cell progenitors. To address the differences of cell types in the adipose tissue from different depots, the phenotypes of freshly isolated adipose tissue-derived cells (ATDCs) from subcutaneous (SC) and omental (OM) adipose tissues were compared using flow cytometry. Our results showed that CD31(-)CD34(+)CD45(-)CD90(-)CD105(-)CD146(+) population, containing vascular smooth muscle cells and pericytes, was specifically defined in the SC adipose tissue while no such population was observed in OM adipose tissue. On the other hand, CD31(-)CD34(+)CD45(-)CD90(-)CD105(-)CD146(-) population, which is an undefined cell population, were found solely in OM adipose tissue. Overall, the SC adipose tissue contained more ATDCs than OM adipose tissue, while OM adipose tissue contained more blood-derived cells. Regarding to the inherent properties of fat cell progenitors from the two depots, adipose-derived stem cells (ADSCs) from SC had higher capacity to differentiate into both adipogenic and osteogenic lineages than those from OM, regardless of that the proliferation rates of ADSCs from both depots were similar. The higher differentiation capacity of ADSCs from SC adipose tissue suggests that SC tissue is more suitable cell source for regenerative medicine than OM adipose tissue.

  2. Increased Infiltration of Macrophages in Omental Adipose Tissue Is Associated With Marked Hepatic Lesions in Morbid Human Obesity

    National Research Council Canada - National Science Library

    Raffaella Cancello; Joan Tordjman; Christine Poitou; Gaël Guilhem; Jean Luc Bouillot; Danielle Hugol; Christiane Coussieu; Arnaud Basdevant; Avner Bar Hen; Pierre Bedossa; Michèle Guerre-Millo; Karine Clément

    2006-01-01

    Increased Infiltration of Macrophages in Omental Adipose Tissue Is Associated With Marked Hepatic Lesions in Morbid Human Obesity Raffaella Cancello 1 2 3 , Joan Tordjman 1 2 3 , Christine Poitou 1 2 3...

  3. Unique transcriptomic signature of omental adipose tissue in Ossabaw swine: a model of childhood obesity.

    Science.gov (United States)

    Toedebusch, Ryan G; Roberts, Michael D; Wells, Kevin D; Company, Joseph M; Kanosky, Kayla M; Padilla, Jaume; Jenkins, Nathan T; Perfield, James W; Ibdah, Jamal A; Booth, Frank W; Rector, R Scott

    2014-05-15

    To better understand the impact of childhood obesity on intra-abdominal adipose tissue phenotype, a complete transcriptomic analysis using deep RNA-sequencing (RNA-seq) was performed on omental adipose tissue (OMAT) obtained from lean and Western diet-induced obese juvenile Ossabaw swine. Obese animals had 88% greater body mass, 49% greater body fat content, and a 60% increase in OMAT adipocyte area (all P development, 2) cellular function and maintenance, and 3) connective tissue development and function, while transcripts associated with RNA posttranslational modification, lipid metabolism, and small molecule biochemistry were reduced. DAVID and Gene Ontology analyses showed that many of the classically recognized gene pathways associated with adipose tissue dysfunction in obese adults including hypoxia, inflammation, angiogenesis were not altered in OMAT in our model. The current study indicates that obesity in juvenile Ossabaw swine is characterized by increases in overall OMAT transcript number and provides novel data describing early transcriptomic alterations that occur in response to excess caloric intake in visceral adipose tissue in a pig model of childhood obesity.

  4. Discriminatory metabolic and inflammatory parameters in serum and omental adipose tissue of obese patients with different insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Marian Khatib

    2014-09-01

    Conclusions: The study highlighted the predictive value of serum bile acids in identifying obese patients at high risk. Secondly, omental adipose tissue ADAM17 was revealed as a novel and strongest independent predictor for higher insulin resistance in morbidly obese patients.

  5. Identification of a Novel Function of Adipocyte Plasma Membrane-Associated Protein (APMAP) in Gestational Diabetes Mellitus by Proteomic Analysis of Omental Adipose Tissue.

    Science.gov (United States)

    Ma, Yuhang; Gao, Jing; Yin, Jiajing; Gu, Liping; Liu, Xing; Chen, Su; Huang, Qianfang; Lu, Huifang; Yang, Yuemin; Zhou, Hu; Wang, Yufan; Peng, Yongde

    2016-02-05

    Gestational diabetes mellitus (GDM) is considered as an early stage of type 2 diabetes mellitus. In this study, we compared demographic and clinical data between six GDM subjects and six normal glucose tolerance (NGT; healthy controls) subjects and found that homeostasis model of assessment for insulin resistance index (HOMA-IR) increased in GDM. Many previous studies demonstrated that omental adipose tissue dysfunction could induce insulin resistance. Thus, to investigate the cause of insulin resistance in GDM, we used label-free proteomics to identify differentially expressed proteins in omental adipose tissues from GDM and NGT subjects (data are available via ProteomeXchange with identifier PXD003095). A total of 3528 proteins were identified, including 66 significantly changed proteins. Adipocyte plasma membrane-associated protein (APMAP, a.k.a. C20orf3), one of the differentially expressed proteins, was down-regulated in GDM omental adipose tissues. Furthermore, mature 3T3-L1 adipocytes were used to simulate omental adipocytes. The inhibition of APMAP expression by RNAi impaired insulin signaling and activated NFκB signaling in these adipocytes. Our study revealed that the down-regulation of APMAP in omental adipose tissue may play an important role in insulin resistance in the pathophysiology of GDM.

  6. Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects

    Directory of Open Access Journals (Sweden)

    Lu HuiLing

    2010-01-01

    Full Text Available Abstract Background Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP and Triglyceride (TG (LAT vs High ASP and TG (HAT. Subcutaneous (SC and omental (OM adipose tissues (n = 21 were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined. Methods LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1. ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p Results HAT adipose tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL, lipolysis (HSL, CES1, perilipin, fatty acid binding proteins (FABP1, FABP3 and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ. By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7. HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p Conclusion Taken together, the profile of C5L2 receptor, ASP gene expression and metabolic factors in adipose tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG.

  7. Characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat

    Science.gov (United States)

    Bujalska, Iwona J; Durrani, Omar M; Abbott, Joseph; Onyimba, Claire U; Khosla, Pamela; Moosavi, Areeb H; Reuser, Tristan T Q; Stewart, Paul M; Tomlinson, Jeremy W; Walker, Elizabeth A; Rauz, Saaeha

    2007-01-01

    Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that activates cortisol from cortisone has been postulated as a fundamental mechanism underlying the metabolic syndrome mediating adipocyte hyperplasia and hypertrophy in the omental (OM) depot. Orbital adipose tissue (OF) is the site of intense inflammation and tissue remodelling in several orbital inflammatory disease states. In this study, we describe features of the GC metabolic pathways in normal human OF depot and compare it with subcutaneous (SC) and OM depots. Using an automated histological characterisation technique, OF adipocytes were found to be significantly smaller (parameters: area, maximum diameter and perimeter) than OM and SC adipocytes (P<0·001). Although immunohistochemical analyses demonstrated resident CD68+ cells in all three whole tissue adipose depots, OF CD68 mRNA and protein expression exceeded that of OM and SC (mRNA, P<0·05; protein, P<0·001). In addition, there was higher expression of glucocorticoid receptor (GR)α mRNA in the OF whole tissue depot (P<0·05). Conversely, 11β-HSD1 mRNA together with the markers of late adipocyte differentiation (FABP4 and G3PDH) were significantly lower in OF. Primary cultures of OF preadipocytes demonstrated predominant 11β-HSD1 oxo-reductase activity with minimal dehydrogenase activity. Orbital adipocytes are smaller, less differentiated, and express low levels of 11β-HSD1 but abundant GRα compared with SC and OM. OF harbours a large CD68+ population. These characteristics define an orbital microenvironment that has the potential to respond to sight-threatening orbital inflammatory disease. PMID:17283228

  8. Characterisation of 11beta-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat.

    Science.gov (United States)

    Bujalska, Iwona J; Durrani, Omar M; Abbott, Joseph; Onyimba, Claire U; Khosla, Pamela; Moosavi, Areeb H; Reuser, Tristan T Q; Stewart, Paul M; Tomlinson, Jeremy W; Walker, Elizabeth A; Rauz, Saaeha

    2007-02-01

    Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) that activates cortisol from cortisone has been postulated as a fundamental mechanism underlying the metabolic syndrome mediating adipocyte hyperplasia and hypertrophy in the omental (OM) depot. Orbital adipose tissue (OF) is the site of intense inflammation and tissue remodelling in several orbital inflammatory disease states. In this study, we describe features of the GC metabolic pathways in normal human OF depot and compare it with subcutaneous (SC) and OM depots. Using an automated histological characterisation technique, OF adipocytes were found to be significantly smaller (parameters: area, maximum diameter and perimeter) than OM and SC adipocytes (P<0 x 001). Although immunohistochemical analyses demonstrated resident CD68+ cells in all three whole tissue adipose depots, OF CD68 mRNA and protein expression exceeded that of OM and SC (mRNA, P<0 x 05; protein, P<0 x 001). In addition, there was higher expression of glucocorticoid receptor (GR)alpha mRNA in the OF whole tissue depot (P<0 x 05). Conversely, 11beta-HSD1 mRNA together with the markers of late adipocyte differentiation (FABP4 and G3PDH) were significantly lower in OF. Primary cultures of OF preadipocytes demonstrated predominant 11beta-HSD1 oxo-reductase activity with minimal dehydrogenase activity. Orbital adipocytes are smaller, less differentiated, and express low levels of 11beta-HSD1 but abundant GRalpha compared with SC and OM. OF harbours a large CD68+ population. These characteristics define an orbital microenvironment that has the potential to respond to sight-threatening orbital inflammatory disease.

  9. Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects

    Science.gov (United States)

    2010-01-01

    Background Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP) and Triglyceride (TG) (LAT) vs High ASP and TG (HAT). Subcutaneous (SC) and omental (OM) adipose tissues (n = 21) were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined. Methods LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1). ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p tissue, with little difference in OM tissue. Increased C5L2 (p tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL), lipolysis (HSL, CES1, perilipin), fatty acid binding proteins (FABP1, FABP3) and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ). By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7). HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG. PMID:20105310

  10. Expression of Genes Related to Prostaglandin Synthesis or Signaling in Human Subcutaneous and Omental Adipose Tissue: Depot Differences and Modulation by Adipogenesis

    Directory of Open Access Journals (Sweden)

    Andréanne Michaud

    2014-01-01

    Full Text Available Objectives. (1 To examine depot-specific PGE2 and PGF2α release and mRNA expression of enzymes or receptors involved in PG synthesis or signaling in human adipose tissues; (2 to identify changes in expression of these transcripts through preadipocyte differentiation; and (3 to examine associations between adipose tissue mRNA expression of these transcripts and adiposity measurements. Methods. Fat samples were obtained surgically in women. PGE2 and PGF2α release by preadipocytes and adipose tissue explants was measured. Expression levels of mRNA coding for enzymes or receptors involved in PG synthesis or signaling were measured by RT-PCR. Results. Cultured preadipocytes and explants from omental fat released more PGE2 and PGF2α than those from the subcutaneous depot and the corresponding transcripts showed consistent depot differences. Following preadipocyte differentiation, expression of PLA2G16 and PTGER3 mRNA was significantly increased whereas COX-1, COX-2, PTGIS, and PTGES mRNA abundance were decreased in both compartments (P≤0.01 for all. Transcripts that were stimulated during adipogenesis were those that correlated best with adiposity measurements. Conclusion. Cells from the omental fat compartment release more PGE2 and PGF2α than those from the subcutaneous depot. Obesity modulates expression of PG-synthesizing enzymes and PG receptors which likely occurs through adipogenesis-induced changes in expression of these transcripts.

  11. Association of SelS mRNA expression in omental adipose tissue with Homa-IR and serum amyloid A in patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    DU Jian-ling; SUN Chang-kai; L(U) Bo; MEN Li-li; YAO Jun-jie; AN Li-jia; SONG Gui-rong

    2008-01-01

    Background Tanis was repoded as a putative receptor for serum amyloid A(SAA)involving glucose regulated protein in insulin regulated resistance.It was found to be dysregulated in diabetic rats(Psammomys obesus,Israeli sand rat)and its homologue for humans is SelS/AD-015.The present study analyzed mRNA expression of SelS in omental adipose tissue biopsies from patients with type 2 diabetes mellitus (T2DM),and age-and weight-matched nondiabetic patients,the relationship of SelS mRNA with Homa-IR and serum SAA level.Methods Human omental adipose tissues from ten cases of type 2 diabetic patients and twelve cases of nondiabetic individuals were analyzed for the expression level of SelS mRNA by semiquantitative polymerase chain reaction(PCR),Homa-IR estimated by standard formula and SM level by enzyme-linked immunosorbent assay(ELISA).Results SelS mRNA expression.Homa-IR and serum SAA were higher in T2DM sufferers than in nondiabeUc control group.SelS mRNA level was positively correlated with Homa-IR and SAA level in each group.Conclusions SelS protein may be involved in insulin resistarice;in Chinese with T2DM by acting as the SAA receptor,thus playing an important role in the development of T2DM and atherosclerosis.

  12. Microarray analysis of differentially expressed genes and their functions in omental visceral adipose tissues of pregnant women with vs. without gestational diabetes mellitus.

    Science.gov (United States)

    Qian, Yuan; Sun, Hao; Xiao, Hongli; Ma, Meirun; Xiao, Xue; Qu, Qinzai

    2017-05-01

    Increasing evidence has shown that insulin resistance in omental visceral adipose tissue (OVAT) is a characteristic of gestational diabetes mellitus (GDM). The present study aimed to identify differentially expressed genes (DEGs) and their associated functions and pathways involved in the pathogenesis of GDM by comparing the expression profiles of OVATs obtained from pregnant Chinese women with and without GDM during caesarian section. A total of 935 DEGs were identified, including 450 downregulated and 485 upregulated genes. In the gene ontology category cellular components, the DEGs were predominantly associated with functions of the extracellular region, while receptor binding was predominant in the molecular function category and biological process terms included antigen processing and presentation, extracellular matrix organization, positive regulation of cell-substrate adhesion, response to nutrients and response to dietary excess. Functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed and a functional interaction network was constructed. Functions of downregulated genes included antigen processing and presentation as well as cell adhesion molecules, while those of upregulated genes included transforming growth factor (TGF)-β-signaling, focal adhesion, phosphoinositide-3 kinase-Akt-signaling, P53 signaling, extracellular matrix-receptor interaction and regulation of actin cytoskeleton pathway. The five main pathways associated with GDM were antigen processing and presentation, cell adhesion molecules, Type 1 diabetes mellitus, natural killer cell-mediated cytotoxicity and TGF-β signaling. These pathways were included in the KEGG pathway categories of 'signaling molecules and interaction', 'immune system' and 'inflammatory response', suggesting that these processes are involved in GDM. The results of the present study enhanced the present understanding of the mechanisms associated with insulin resistance in

  13. An estimation of diazinon in omental tissue.

    Science.gov (United States)

    Kirkbride, K P

    1987-01-01

    A fatality in which diazinon was the suspected toxic agent was investigated. Samples of omental tissue, blood, and liver tissue were examined by gas chromatography and thin layer chromatography. Diazinon was found in the omentum (at a level of 5.1 mg/kg) and blood (in a trace amount), but no diazinon was found in the liver tissue. Methods are given for the extraction of diazinon from omental fat, the purification of these extracts by sweep co-distillation and fat precipitation, and for an estimation of the amount of diazinon present. It is not possible to determine whether the low level found arose from chronic occupational exposure, accidental dermal contact, or ingestion of a lethal dose.

  14. Adipose tissue fibrosis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The increasing prevalence of obesity causes a majorinterest in white adipose tissue biology. Adipose tissuecells are surrounded by extracellular matrix proteinswhose composition and remodeling is of crucial importancefor cell function. The expansion of adipose tissue inobesity is linked to an inappropriate supply with oxygenand hypoxia development. Subsequent activation ofhypoxia inducible factor 1 (HIF-1) inhibits preadipocytedifferentiation and initiates adipose tissue fibrosis. Therebyadipose tissue growth is limited and excess triglyceridesare stored in ectopic tissues. Stressed adipocytes andhypoxia contribute to immune cell immigration andactivation which further aggravates adipose tissuefibrosis. There is substantial evidence that adipose tissuefibrosis is linked to metabolic dysfunction,both in rodentmodels and in the clinical setting. Peroxisome proliferatoractivated receptor gamma agonists and adiponectin bothreduce adipose tissue fibrosis, inflammation and insulinresistance. Current knowledge suggests that antifibroticdrugs, increasing adipose tissue oxygen supply or HIF-1antagonists will improve adipose tissue function andthereby ameliorate metabolic diseases.

  15. Study on expression of visfatin mRNA in abdominal omental adipose tissue and its relationship with blood lipid in type 2 diabetics%内脂素在2型糖尿病伴高甘油三酯血症患者网膜脂肪组织中的表达及与血脂的关系

    Institute of Scientific and Technical Information of China (English)

    王淑艳; 孟晓梅; 陈述林

    2012-01-01

    目的 探讨内脂素( visfatin)基因在2型糖尿病(T2DM)患者网膜脂肪组织中的表达情况及与血脂的关系.方法 选取2型糖尿病患者161例,分为高甘油三酯及正常甘油三酯两组.采用Northern blot印迹技术研究两组的网膜脂肪组织中visfatin mRNA的表达水平,并测定血清visfatin浓度、空腹血糖、血脂谱及其他生化指标.结果 (1)2型糖尿病伴高甘油三酯血症组血清visfatin增高[( 129.07±21.35) ng/mL vs(101.65±15.23) ng/mL,t =2.295,P<0.05],网膜组织的visfatin mRNA表达量高于正常甘油三酯组(P<0.05).(2)血清visfatin与甘油三酯(β=0.592,P<0.05)及空腹血糖(β=0.763,P<0.01)呈正相关,网膜脂肪组织visfatin与空腹血糖、甘油三酯等均无相关.结论 T2DM患者血清visfatin可能与甘油三酯代谢相关.%Objective To investigate the expression of visfatin mRNA in abdominal omental adipose tissue and its relationship with blood lipid in type 2 diabetes mellitus.Methods 161 type 2 diabetic patients were divided into two groups according to triglyceride ( TG ),high triglyceride group ( TG ≥ 1.7mmol/L) and normal triglyceride group(TG < 1.7 mmol/L).The expression of visfatin mRNA in abdominal omental adipose tissue was measured with Northern Blot.Visfatin plasma concentration,fasting plasma glucose (FPG),blood lipid profiles and other biochemical indicators were also measured.Results Comparing with normal triglyceride group,the diabetic patients in high triglyceride group had significantly increased levels of visfatin plasma concentration [ ( 129.07 ± 21.35)ng/mL vs ( 101.65 ± 15.23 ) ng/mL,t =2.295,P <0.05]and mRNA expression in omental adipose tissue( P <0.05).Visfatin plasma concentration was positively correlated with TG( β =0.592,P <0.05 ) and FPG( β =0.763,P <0.01 ).Visfatin mRNA expression in omental adipose tissue had no correlation with FPG,TG and other biochemical indicators.Conclusions The plasma visfatin level in T2DM

  16. Expression and significance of hemeoxygenase-1 (HO-1) in subcutaneous and omental adipose tissue of type 2 diabetic patients%2型糖尿病患者脂肪组织中的HO-1表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    李倩倩; 李慧敏; 钟继娟; 缪珩

    2012-01-01

    Objective To observe the heme oxygenase-1 (HO-1) mRNA and protein expression in subcutaneous and omental adipose tissue of type 2 diabetic patients and their relation with serum adiponectin level, and other clinical indexes. Methods 23 type 2 diabetic patients with obesity, 23 type 2 diabetic patients, 33 controls with obesity and 23 controls were selected . The HO-1 mRNA expression level in adipose tissue was assayed by RT-PCR, and HO-1 protein expression level was assayed by Western blot. Being usedlinear correlation analysis, their correlations were observed. Results ① The expressions of HO-1 mRNA in subcutaneous adipose tissue of type 2 diabetic patients with obesity were significantly lower ( all P < 0.05), and the level in omental adipose tissue was negatively correlated to BMI (P < 0.01).② Type 2 diabetic patients and those with obesity showed significantly lower expressions of HO-1 protein in subcutaneous and omental adipose tissue comparing with control groups (all P < 0.05) , and the level in omental adipose tissue of type 2 diabetic patients with obesity were negatively correlated to BMI, FPG, TG (all P <0.05). ③The expression level of HO-1 protein in omental adipose tissue of type 2 diabetic patients was positively correlated to the level of serum adiponectin (P < 0.05). Conclusions The levels of HO-1 mRNA and protein in type 2 diabetic patients are significantly lower than those of controls. The higher level of BMI is, the lower of HO-1 expression is. The low expression of HO-1 may be correlated with the occurrence and development of insulin resistance and DM.%目的 探讨2型糖尿病(T2DM)患者脂肪组织中血红素加氧酶-1(HO-1)基因及蛋白表达的临床意义.方法 选择T2DM患者46例(T2DM组),其中伴肥胖者23例(T2DM+ FAT组)、单纯T2DM 23例(单纯T2DM组);非T2DM患者56例(非T2DM组),其中单纯非T2DM患者33例(单纯非T2DM组)、伴肥胖者23例(非T2DM+ FAT组).采用RT-PCR技术检测各组腹部皮下

  17. Visceral fat accumulation is an indicator of adipose tissue macrophage infiltration in women.

    Science.gov (United States)

    Michaud, Andréanne; Drolet, Renée; Noël, Suzanne; Paris, Gaëtan; Tchernof, André

    2012-05-01

    We tested the hypothesis that visceral obesity is the best correlate of abdominal adipose tissue macrophage infiltration in women. Omental and subcutaneous fat samples were surgically obtained from 40 women (age, 47.0 ± 4.0 years; body mass index, 28.4 ± 5.8 kg/m(2)). CD68+ cells were identified using fluorescence immunohistochemistry. Expression of macrophage markers was measured by real-time reverse transcriptase polymerase chain reaction. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography, respectively. Mean CD68+ cell percentage tended to be higher in subcutaneous (18.3%) compared with omental adipose tissue (15.5%, P = .07). Positive correlations were observed between CD68+ cell percentage as well as CD68 messenger RNA expression in a given depot vs the other (P ≤ .01). Visceral adipose tissue area and omental adipocyte diameter were positively related to CD68+ cell percentage in omental fat (r = 0.52 and r = 0.35, P ≤ .05). Total and visceral adipose tissue areas as well as subcutaneous adipocyte diameter were significantly correlated with CD68+ cell percentage in subcutaneous adipose tissue (0.32 ≤ r ≤ 0.40, P ≤ .05). Adipose tissue areas and subcutaneous adipocyte diameter were also significantly associated with expression of commonly used macrophage markers including CD68 in the subcutaneous fat compartment (0.32 ≤ r ≤ 0.57, P ≤ .05). Visceral adipose tissue area was the best correlate of CD68+ cell percentage in both omental and subcutaneous fat tissues, explaining, respectively, 20% and 12% of the variance in models also including subcutaneous adipose tissue area, adipocyte sizes, and total body fat mass. Visceral adipose tissue accumulation is the best correlate of macrophage infiltration in both the subcutaneous and omental fat compartments of lean to obese women.

  18. Adipose tissue macrophages

    NARCIS (Netherlands)

    Boutens, Lily; Stienstra, Rinke

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically

  19. Adipose tissue macrophages

    NARCIS (Netherlands)

    Boutens, Lily; Stienstra, Rinke

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically foc

  20. Adipose tissue macrophages

    NARCIS (Netherlands)

    Boutens, Lily; Stienstra, Rinke

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically foc

  1. Research of resistin protein expression in abdominal omental and subcutaneous adipose tissue in type 2 diabetic patients%2型糖尿病患者大网膜与皮下脂肪组织抵抗素蛋白表达的研究

    Institute of Scientific and Technical Information of China (English)

    许莉军; 张木勋; 杨再刚; 马洪波; 张晶; 周咏明; 张建华

    2004-01-01

    目的了解2型糖尿病(type 2 diabetes mellitus,T2DM)患者大网膜与皮下脂肪组织抵抗素蛋白表达的情况,探讨肥胖和糖尿病间的关系.方法Western bolt法检测大网膜及皮下脂肪组织抵抗素表达情况;磁性分离酶联免疫法测定空腹血胰岛素水平,葡萄糖氧化酶法测定血糖浓度,并计算胰岛素敏感指数;测量身高、体重、臀围、收缩压(SBP)、舒张压(DBP),计算腰臀比(WHR)、体重指数(BMI)、体内脂肪百分比(BF%).结果以OD值表示,正常对照组(57411±1225.59)大网膜与皮下脂肪组织抵抗素蛋白表达明显较单纯肥胖组(41671±884.38)(P<0.01)、非肥胖T2DM组(42132±1286.15)(P<0.01)\\肥胖T2DM组(42677±1751.10)(P<0.05)表达增高,后三组抵抗素蛋白表达差异无显著性.四组自身的大网膜与皮下脂肪组织抵抗素蛋白表达无显著差异.逐步回归分析示WHR、BMI、FBG对抵抗素表达的作用显著,方程为v=116338-38562×WHR-1154.99×BMI-1243.63×FBG.结论正常对照组大网膜与皮下脂肪组织抵抗素蛋白表达明显较单纯肥胖组、非肥胖T2DM组、肥胖T2DM组表达增高,抵抗素与腰臀比、体重指数、空腹血糖呈显著负相关提示人体抵抗素不是肥胖和糖尿病的联系所在.%Objective:To investigate the expression of resistin protein in abdominal omental and subcutaneous adipose tissues in type 2 diabetic patients and the relationship between obesity and diabetes mellitus.Methods: The expression of resistin protein in omental and subcutaneous adipose tissues was measured using Western blot method.Fasting insulin and glucose levels were measured by enzyme immunoassay and glucose oxidase assay respectively to calculate insulin sensitivity index. Height, weight, waist circumference, hip circumference, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured to calculate waist-hip ratio, body mass index (BMI) and body fat percentage (BF%). Results

  2. Childhood giant omental and mesenteric lipoma

    Directory of Open Access Journals (Sweden)

    Hidayatullah Hamidi, MD

    2016-03-01

    Full Text Available Omental and mesenteric lipomas are very rare benign lesions of mature adipose tissue. They are well-defined, noninvasive, and encapsulated masses that can be discovered in asymptomatic patients or may cause variable nonspecific symptoms depending on their size and location. The omental and mesenteric lipoma has confusing features in ultrasound; however, computed tomography and magnetic resonance imaging can well characterize and demarcate these lesions. Though few cases of mesenteric and omental lipomas have been reported in the literature, but because of its large size and childhood presentation, the case we present, can be one of the largest childhood omental and mesenteric lipomas ever reported. A 6-year-old girl presented with slowly progressing abdominal distension and repeated dull abdominal pain for last 4 years. Abdominal and pelvic computed tomography examination revealed a huge mesenteric and omental lipoma that was resected surgically without any complications.

  3. [Human brown adipose tissue].

    Science.gov (United States)

    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.

  4. [Adipose tissue hormones].

    Science.gov (United States)

    Haluzík, M; Trachta, P; Haluzíková, D

    2010-10-01

    Adipose tissue had been traditionally considered a passive energy storage site without direct influence on energy homeostasis regulation. This view has been principally changed during early nineties by the discovery of hormonal production of adipose tissue. At present, the list of hormonally active substances of adipose tissue includes more than one hundred factors with paracrine or endocrine activity that play an important role in metabolic, food intake a inflammatory regulations and many other processes. Only minority of adipose tissue-derived hormones is produced exclusively in fat. Most of these factors is primarily put out by other tissues and organs. Adipose tissue-derived hormones are produced not only by adipocytes but also by preadipocytes, immunocompetent and endothelial cells and other cell types residing in fat. This paper summarizes current knowledge about endocrine function of adipose tissue with special respect to its changes in obesity. It also describes its possible role in the ethiopathogenesis of insulin resistance, atherosclerosis and other obesity-related pathologies.

  5. Adipose Tissue Metabolism During Hypobaria

    Directory of Open Access Journals (Sweden)

    D. P. Chattopadhyay

    1974-10-01

    Full Text Available Possible factors affecting the metabolism of adipose tissue under hypobaric conditions have been reviewed. The hormonal changes brought into play under hypoxic stress generally stress generally increase the adipose tissue lipolysis.

  6. Targeting adipose tissue

    Directory of Open Access Journals (Sweden)

    Haas Bodo

    2012-10-01

    Full Text Available Abstract Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT is generally known and stores excess energy in the form of triacylglycerol (TG, insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP. The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET, however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs, activators of peroxisome proliferator-activated receptor γ (PPARγ a ‘master’ regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity.

  7. Subcutaneous adipose tissue classification

    Directory of Open Access Journals (Sweden)

    A. Sbarbati

    2010-11-01

    Full Text Available The developments in the technologies based on the use of autologous adipose tissue attracted attention to minor depots as possible sampling areas. Some of those depots have never been studied in detail. The present study was performed on subcutaneous adipose depots sampled in different areas with the aim of explaining their morphology, particularly as far as regards stem niches. The results demonstrated that three different types of white adipose tissue (WAT can be differentiated on the basis of structural and ultrastructural features: deposit WAT (dWAT, structural WAT (sWAT and fibrous WAT (fWAT. dWAT can be found essentially in large fatty depots in the abdominal area (periumbilical. In the dWAT, cells are tightly packed and linked by a weak net of isolated collagen fibers. Collagenic components are very poor, cells are large and few blood vessels are present. The deep portion appears more fibrous then the superficial one. The microcirculation is formed by thin walled capillaries with rare stem niches. Reinforcement pericyte elements are rarely evident. The sWAT is more stromal; it is located in some areas in the limbs and in the hips. The stroma is fairly well represented, with a good vascularity and adequate staminality. Cells are wrapped by a basket of collagen fibers. The fatty depots of the knees and of the trochanteric areas have quite loose meshes. The fWAT has a noteworthy fibrous component and can be found in areas where a severe mechanic stress occurs. Adipocytes have an individual thick fibrous shell. In conclusion, the present study demonstrates evident differences among subcutaneous WAT deposits, thus suggesting that in regenerative procedures based on autologous adipose tissues the sampling area should not be randomly chosen, but it should be oriented by evidence based evaluations. The structural peculiarities of the sWAT, and particularly of its microcirculation, suggest that it could represent a privileged source for

  8. Regional differences and up-regulation of progesterone receptors in adipose tissues from oestrogen-treated sheep.

    Science.gov (United States)

    Mayes, J S; McCann, J P; Ownbey, T C; Watson, G H

    1996-01-01

    Differing risk factors between men and women for a number of vascular and metabolic diseases have been linked to regional obesity. The differences in the distribution of adipose tissues between men (abdominal or upper-body obesity) and women (gluteal/femoral or lower body obesity) suggest a role for sex steroids in the regional distribution of fat. Previous work from this laboratory has shown the presence of oestrogen receptor (ER) in gluteal, perirenal and omental adipose tissues of ewes with similar physical characteristics to the ER in uterine tissue. The concentration profile for adipose ER was gluteal > perirenal > omental. In this report, we determined the physiological significance of adipose ERs by showing an up-regulation of the progesterone receptor (PR) in adipose tissues after oestrogen treatment in a fashion similar to that seen in a major responsive tissue such as uterus. Using PR antibodies (PR-6 and C-262), Western blot analysis of PR from oestrogen-treated sheep indicated that PR was induced in uterus > gluteal adipose > perirenal adipose consistent with the concentration of ER contained in these tissues. PR could not be detected by Western blotting in omental adipose tissue from oestrogen-treated animals or in gluteal, perirenal and omental adipose tissues from untreated animals. Sucrose gradient profiles of progestin (R-5020) binding from uterus and gluteal adipose tissues of oestrogen-treated ewes showed specific binding in both the 5S and 9S regions of the gradient, while perirenal and omental adipose tissue had only the 5S peak. The amount of specific binding was increased with oestrogen treatment in all the tissues. When gluteal adipose tissue cytosol was preincubated with PR antibody (C-262) to prevent binding of ligand and subjected to sucrose gradient analysis, both the 5S and 9S regions were diminished, suggesting that both peaks contained PR. Dilution of uterine cytosol resulted in an increase in the ratio of the 5S to the 9S peak

  9. Steroid biosynthesis in adipose tissue.

    Science.gov (United States)

    Li, Jiehan; Papadopoulos, Vassilios; Vihma, Veera

    2015-11-01

    Tissue-specific expression of steroidogenic enzymes allows the modulation of active steroid levels in a local manner. Thus, the measurement of local steroid concentrations, rather than the circulating levels, has been recognized as a more accurate indicator of the steroid action within a specific tissue. Adipose tissue, one of the largest endocrine tissues in the human body, has been established as an important site for steroid storage and metabolism. Locally produced steroids, through the enzymatic conversion from steroid precursors delivered to adipose tissue, have been proven to either functionally regulate adipose tissue metabolism, or quantitatively contribute to the whole body's steroid levels. Most recently, it has been suggested that adipose tissue may contain the steroidogenic machinery necessary for the initiation of steroid biosynthesis de novo from cholesterol. This review summarizes the evidence indicating the presence of the entire steroidogenic apparatus in adipose tissue and discusses the potential roles of local steroid products in modulating adipose tissue activity and other metabolic parameters.

  10. Adipose tissue extract promotes adipose tissue regeneration in an adipose tissue engineering chamber model.

    Science.gov (United States)

    Lu, Zijing; Yuan, Yi; Gao, Jianhua; Lu, Feng

    2016-05-01

    An adipose tissue engineering chamber model of spontaneous adipose tissue generation from an existing fat flap has been described. However, the chamber does not completely fill with adipose tissue in this model. Here, the effect of adipose tissue extract (ATE) on adipose tissue regeneration was investigated. In vitro, the adipogenic and angiogenic capacities of ATE were evaluated using Oil Red O and tube formation assays on adipose-derived stem cells (ASCs) and rat aortic endothelial cells (RAECs), respectively. In vivo, saline or ATE was injected into the adipose tissue engineering chamber 1 week after its implantation. At different time points post-injection, the contents were morphometrically, histologically, and immunohistochemically evaluated, and the expression of growth factors and adipogenic genes was analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. With the exception of the baseline control group, in which fat flaps were not inserted into a chamber, the total volume of fat flap tissue increased significantly in all groups, especially in the ATE group. Better morphology and structure, a thinner capsule, and more vessels were observed in the ATE group than in the control group. Expression of angiogenic growth factors and adipogenic markers were significantly higher in the ATE group. ATE therefore significantly promoted adipose tissue regeneration and reduced capsule formation in an adipose tissue engineering chamber model. These data suggest that ATE provides a more angiogenic and adipogenic microenvironment for adipose tissue formation by releasing various cytokines and growth factors that also inhibit capsule formation.

  11. Bioengineering Beige Adipose Tissue Therapeutics.

    Science.gov (United States)

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and

  12. Adipose tissue lipolysis.

    Science.gov (United States)

    Kolditz, Catherine-Ines; Langin, Dominique

    2010-07-01

    Adipose tissue lipolysis is a critical pathway for the maintenance of energy homeostasis through the degradation of triglycerides and the release of fatty acids into the circulation. The understanding of the cellular factors regulating triglyceride hydrolysis and the metabolic function of lipases has considerably expanded in the last few years, revealing an unexpected complexity. This review aims at describing recent discoveries related to the lipolytic pathway and its regulatory mechanisms. Considerable progress has been made in understanding the role and the mechanisms of activation of the lipolytic enzymes. Recent discoveries have dramatically altered the view of adipose tissue lipolysis and highlighted the importance of additional molecular actors in regulating this process. Catecholamines, natriuretic peptides, and insulin are considered to be the major regulators of lipolysis in humans. However, autocrine/paracrine factors such as metabolites and prostaglandins may also participate in its regulation. The manipulation of lipolysis has therapeutic potential in the metabolic disorders frequently associated with obesity. Unraveling the molecular events occurring during regulation of lipolysis may lead to novel therapeutic targets.

  13. Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity

    OpenAIRE

    Maria Keller; Lydia Hopp; Xuanshi Liu; Tobias Wohland; Kerstin Rohde; Raffaella Cancello; Matthias Klös; Karl Bacos; Matthias Kern; Fabian Eichelmann; Arne Dietrich; Michael R Schön; Daniel Gärtner; Tobias Lohmann; Miriam Dreßler

    2017-01-01

    Objective/methods: DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individuals. Results: We identified negatively correlated methylation and expression of several obesity-associated genes in our discovery dataset and in silico replicated ETV6 in two i...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance.

    Science.gov (United States)

    Sidibeh, Cherno O; Pereira, Maria J; Lau Börjesson, Joey; Kamble, Prasad G; Skrtic, Stanko; Katsogiannos, Petros; Sundbom, Magnus; Svensson, Maria K; Eriksson, Jan W

    2017-03-01

    We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue. Subcutaneous adipose tissue was obtained from well-controlled type 2 diabetes subjects and controls. Subcutaneous adipose tissue gene expression levels of CNR1 and endocannabinoid synthesizing and degrading enzymes were assessed. Furthermore, paired human subcutaneous adipose tissue and omental adipose tissue from non-diabetic volunteers undergoing kidney donation or bariatric surgery, was incubated with or without dexamethasone. Subcutaneous adipose tissue obtained from volunteers through needle biopsy was incubated with or without dexamethasone and in the presence or absence of the CNR1-specific antagonist AM281. CNR1 gene and protein expression, lipolysis and glucose uptake were evaluated. Subcutaneous adipose tissue CNR1 gene expression levels were 2-fold elevated in type 2 diabetes subjects compared with control subjects. Additionally, gene expression levels of CNR1 and endocannabinoid-regulating enzymes from both groups correlated with markers of insulin resistance. Dexamethasone increased CNR1 expression dose-dependently in subcutaneous adipose tissue and omental adipose tissue by up to 25-fold. Dexamethasone pre-treatment of subcutaneous adipose tissue increased lipolysis rate and reduced glucose uptake. Co-incubation with the CNR1 antagonist AM281 prevented the stimulatory effect on lipolysis, but had no effect on glucose uptake. CNR1 is upregulated in states of type 2 diabetes and insulin resistance. Furthermore, CNR1 is involved in glucocorticoid-regulated lipolysis. Peripheral CNR1 could be an interesting drug target in type 2 diabetes and dyslipidemia.

  16. Adipose tissue remodeling and obesity

    National Research Council Canada - National Science Library

    Sun, Kai; Kusminski, Christine M; Scherer, Philipp E

    2011-01-01

    To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited capacity to expand in a non-transformed state...

  17. A chromatin immunoprecipitation (ChIP) protocol for use in whole human adipose tissue.

    Science.gov (United States)

    Haim, Yulia; Tarnovscki, Tanya; Bashari, Dana; Rudich, Assaf

    2013-11-01

    Chromatin immunoprecipitation (ChIP) has become a central method when studying in vivo protein-DNA interactions, with the major challenge being the hope to capture "authentic" interactions. While ChIP protocols have been optimized for use with specific cell types and tissues including adipose tissue-derived cells, a working ChIP protocol addressing the challenges imposed by fresh whole human adipose tissue has not been described. Utilizing human paired omental and subcutaneous adipose tissue obtained during elective abdominal surgeries, we have carefully identified and optimized individual steps in the ChIP protocol employed directly on fresh tissue fragments. We describe a complete working protocol for using ChIP on whole adipose tissue fragments. Specific steps required adaptation of the ChIP protocol to human whole adipose tissue. In particular, a cross-linking step was performed directly on fresh small tissue fragments. Nuclei were isolated before releasing chromatin, allowing better management of fat content; a sonication protocol to obtain fragmented chromatin was optimized. We also demonstrate the high sensitivity of immunoprecipitated chromatin from adipose tissue to freezing. In conclusion, we describe the development of a ChIP protocol optimized for use in studying whole human adipose tissue, providing solutions for the unique challenges imposed by this tissue. Unraveling protein-DNA interaction in whole human adipose tissue will likely contribute to elucidating molecular pathways contributing to common human diseases such as obesity and type 2 diabetes.

  18. Adipose tissues and thyroid hormones

    Directory of Open Access Journals (Sweden)

    Maria-Jesus eObregon

    2014-12-01

    Full Text Available The maintenance of energy balance is regulated by complex homeostatic mechanisms, including those emanating from adipose tissue. The main function of the adipose tissue is to store the excess of metabolic energy in the form of fat. The energy stored as fat can be mobilized during periods of energy deprivation (hunger, fasting, diseases. The adipose tissue has also a homeostatic role regulating energy balance and functioning as endocrine organ that secretes substances that control body homeostasis. Two adipose tissues have been identified: white and brown adipose tissues (WAT and BAT with different phenotype, function and regulation. WAT stores energy, while BAT dissipates energy as heat. Brown and white adipocytes have different ontogenetic origin and lineage and specific markers of WAT and BAT have been identified. Brite or beige adipose tissue has been identified in WAT with some properties of BAT. Thyroid hormones exert pleiotropic actions, regulating the differentiation process in many tissues including the adipose tissue. Adipogenesis gives raise to mature adipocytes and is regulated by several transcription factors (c/EBPs, PPARs that coordinately activate specific genes, resulting in the adipocyte phenotype. T3 regulates several genes involved in lipid mobilization and storage and in thermogenesis. Both WAT and BAT are targets of thyroid hormones, which regulate genes crucial for their proper function: lipogenesis, lipolysis, thermogenesis, mitochondrial function, transcription factors, the availability of nutrients. T3 acts directly through specific TREs in the gene promoters, regulating transcription factors. The deiodinases D3, D2 and D1 regulate the availability of T3. D3 is activated during proliferation, while D2 is linked to the adipocyte differentiation program, providing T3 needed for lipogenesis and thermogenesis. We examine the differences between BAT, WAT and brite/beige adipocytes and the process that activate UCP1 in WAT and

  19. Adipose tissues and thyroid hormones.

    Science.gov (United States)

    Obregon, Maria-Jesus

    2014-01-01

    The maintenance of energy balance is regulated by complex homeostatic mechanisms, including those emanating from adipose tissue. The main function of the adipose tissue is to store the excess of metabolic energy in the form of fat. The energy stored as fat can be mobilized during periods of energy deprivation (hunger, fasting, diseases). The adipose tissue has also a homeostatic role regulating energy balance and functioning as endocrine organ that secretes substances that control body homeostasis. Two adipose tissues have been identified: white and brown adipose tissues (WAT and BAT) with different phenotype, function and regulation. WAT stores energy, while BAT dissipates energy as heat. Brown and white adipocytes have different ontogenetic origin and lineage and specific markers of WAT and BAT have been identified. "Brite" or beige adipose tissue has been identified in WAT with some properties of BAT. Thyroid hormones exert pleiotropic actions, regulating the differentiation process in many tissues including the adipose tissue. Adipogenesis gives raise to mature adipocytes and is regulated by several transcription factors (c/EBPs, PPARs) that coordinately activate specific genes, resulting in the adipocyte phenotype. T3 regulates several genes involved in lipid mobilization and storage and in thermogenesis. Both WAT and BAT are targets of thyroid hormones, which regulate genes crucial for their proper function: lipogenesis, lipolysis, thermogenesis, mitochondrial function, transcription factors, the availability of nutrients. T3 acts directly through specific TREs in the gene promoters, regulating transcription factors. The deiodinases D3, D2, and D1 regulate the availability of T3. D3 is activated during proliferation, while D2 is linked to the adipocyte differentiation program, providing T3 needed for lipogenesis and thermogenesis. We examine the differences between BAT, WAT and brite/beige adipocytes and the process that lead to activation of UCP1 in WAT and

  20. Hormonal control of net glucose-stimulated lipogenesis during transition from brown to white adipose tissue in the goat.

    Science.gov (United States)

    Skarda, J

    2000-01-01

    Perinatal (1-2 days of age) and one-month-old (24-32 days of age) male goats were used to investigate the effect of age and long-term culture (24 h) of perirenal and omental adipose explants in the presence of insulin, cortisol and bovine somatotropin (alone or in different combinations) on net glucose-stimulated lipogenesis (NGSL, i.e. the rate of lipogenesis in the presence of glucose minus the rate of lipogenesis in the absence of glucose) in the absence and in the presence of catecholamines in acute incubations (2 h). Mean values of NGSL in both freshly prepared and cultured explants were consistently lower in perinatal than in one-month-old goats. Cortisol alone decreased and combinations of insulin plus cortisol increased NGSL in perirenal explants of one-month-old animals. When perirenal explants from these one-month-old goats were cultured in the presence of insulin plus cortisol plus bovine somatotropin, the rates of lipogenesis were lower than those in cultures with insulin plus cortisol. No such effects of these hormones were noted in omental explants of both perinatal and one-month-old animals. In freshly prepared perirenal and omental explants, the rates of NGSL were inhibited by isoprenaline in tissues of both groups of animals and by noradrenaline in omental tissues of animals of the older group only. The mean values of NGSL in cultured explants of perinatal animals were not affected by noradrenaline. Isoprenaline inhibited NGSL in omental but not in perirenal tissue. In older animals the rates of NGSL were decreased by both noradrenaline and isoprenaline in perirenal and omental adipose tissues. Isoprenaline was more effective than noradrenaline in perirenal adipose tissue.

  1. Secretory function of adipose tissue.

    Science.gov (United States)

    Kuryszko, J; Sławuta, P; Sapikowski, G

    2016-01-01

    There are two kinds of adipose tissue in mammals: white adipose tissue - WAT and brown adipose tissue - BAT. The main function of WAT is accumulation of triacylglycerols whereas the function of BAT is heat generation. At present, WAT is also considered to be an endocrine gland that produces bioactive adipokines, which take part in glucose and lipid metabolism. Considering its endocrine function, the adipose tissue is not a homogeneous gland but a group of a few glands which act differently. Studies on the secretory function of WAT began in 1994 after discovery of leptin known as the satiation hormone, which regulates body energy homeostasis and maintainence of body mass. Apart from leptin, the following belong to adipokines: adiponectin, resistin, apelin, visfatin and cytokines: TNF and IL 6. Adiponectin is a polypeptide hormone of antidiabetic, anti-inflammatory and anti-atherogenic activity. It plays a key role in carbohydrate and fat metabolism. Resistin exerts a counter effect compared to adiponectin and its physiological role is to maintain fasting glycaemia. Visfatin stimulates insulin secretion and increases insulin sensitivity and glucose uptake by muscle cells and adipocytes. Apelin probably increases the insulin sensitivity of tissues. TNF evokes insulin resistance by blocking insulin receptors and inhibits insulin secretion. Approximately 30% of circulating IL 6 comes from adipose tissue. It causes insulin resistance by decreasing the expression of insulin receptors, decreases adipogenesis and adiponectin and visfatin secretion, and stimulates hepatic gluconeogenesis. In 2004, Bays introduced the notion of adiposopathy, defined as dysfunction of the adipose tissue, whose main feature is insulin and leptin resistance as well as the production of inflammatory cytokines: TNF and IL 6 and monocyte chemoattractant protein. This means that excess of adipose tissue, especially visceral adipose tissue, leads to the development of a chronic subclinical

  2. Effects of catecholamines in vitro on lipogenesis in cultured adipose tissue from young goats.

    Science.gov (United States)

    Skarda, J

    1999-08-01

    Freshly prepared and cultured perirenal and omental adipose tissue explants were used to investigate the effect of age and hormones on lipogenesis in young goats. Perinatal (1-2 days of age) and older (24-32 days of age) male goats were used. Adipose explants were cultured (24 h) in the presence of insulin, cortisol and recombinant bovine growth hormone (bST) and subsequently incubated (2 h) in a glucose-free buffer containing (14C)-acetate in the presence or absence of noradrenaline (Ne) and isoprenaline (Iso) to measure tissue lipogenic responses to hormones added to the culture medium and to measure the responsiveness to catecholamines. Inclusion of hormones in the culture medium did not change lipogenesis during subsequent acute incubation in glucose-free buffer in both perirenal and omental adipose tissue from perinatal goats. On the other hand, in perirenal explants from older animals, insulin alone or insulin plus cortisol increased (P cortisol alone decreased (P cortisol plus bST, the rates of lipogeneses were lower (P cortisol. A similar pattern of the effects of hormones on the rates of fatty acid synthesis was also seen in omental explants; however, these effects were not significant. In vitro rates of lipogeneses were decreased (P effective (P < 0.05) in older but not in perinatal animals.

  3. Downregulation of STEAP4, a highly-expressed TNF-α-inducible gene in adipose tissue, is associated with obesity in humans

    Institute of Scientific and Technical Information of China (English)

    Chun-mei ZHANG; Xia CHI; Bin WANG; Min ZHANG; Yu-hui NI; Rong-hua CHEN; Xiao-nan LI; Xi-rong GUO

    2008-01-01

    Aim: To determine the relationship between six-transmembrane epithelial antigen of the prostate 4 (STEAP4) expression and obesity. Methods: RT-PCR and immunoblot analyses were performed to determine the differential expressions of STEAP4 mRNA and protein, respectively, in human omental adipose tissue from obese patients and normal weight controls. The expression pattern of STEAP4 mRNA in various human tissues was determined by RT-PCR. The subcellular localization of the STEAP4 protein in human adipose tissue was confirmed by immunohistochemistry. Finally, we confirmed that cultured human omental adi- pose tissue undergoes TNF-α-mediated regulation of the STEAP4 expression.Results: STEAP4 mRNA and protein levels were downregulated in omental adi-pose tissue from obese patients relative to normal controls. The STEAP4 expres-sion was most abundant in human adipose tissue. An immunohistochemical analy-sis confirmed that STEAP4 was associated with the plasma membrane of adipocytes. The STEAP4 expression was induced by TNF-α in a dose-dependent manner in human adipose tissue. Conclusion: STEAP4 was abundantly expressed in human adipose tissue, and the STEAP4 expression was significantly downregulated in obese patients. STEAP4 localized to the plasma membrane of adipocytes, and the STEAP4 expression was induced by TNF-α in adipose tissue.These data suggest that STEAP4 may play a significant role in the development of human obesity.

  4. FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance.

    Science.gov (United States)

    Pereira, Maria J; Palming, Jenny; Svensson, Maria K; Rizell, Magnus; Dalenbäck, Jan; Hammar, Mårten; Fall, Tove; Sidibeh, Cherno O; Svensson, Per-Arne; Eriksson, Jan W

    2014-09-01

    To study effects of dexamethasone on gene expression in human adipose tissue aiming to identify potential novel mechanisms for glucocorticoid-induced insulin resistance. Subcutaneous and omental adipose tissue, obtained from non-diabetic donors (10 M/15 F; age: 28-60 years; BMI: 20.7-30.6 kg/m²), was incubated with or without dexamethasone (0.003-3 μmol/L) for 24 h. Gene expression was assessed by microarray and real time-PCR and protein expression by immunoblotting. FKBP5 (FK506-binding protein 5) and CNR1 (cannabinoid receptor 1) were the most responsive genes to dexamethasone in both subcutaneous and omental adipose tissue (~7-fold). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots. The gene product, FKBP51 protein, was 10-fold higher in the omental than in the subcutaneous depot, whereas the mRNA levels were similar. Higher FKBP5 gene expression in omental adipose tissue was associated with reduced insulin effects on glucose uptake in both depots. Furthermore, FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter and negatively with plasma HDL-cholesterol. FKBP5 SNPs were found to be associated with type 2 diabetes and diabetes-related phenotypes in large population-based samples. Dexamethasone exposure promotes expression of FKBP5 in adipose tissue, a gene that may be implicated in glucocorticoid-induced insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Capillary permeability in adipose tissue

    DEFF Research Database (Denmark)

    Paaske, W P; Nielsen, S L

    1976-01-01

    of about 7 ml/100 g-min. This corresponds to a capillary diffusion capacity of 2.0 ml/100 g-min which is half the value reported for vasodilated skeletal muscle having approximately twice as great capillary surface area. Thus, adipose tissue has about the same capillary permeability during slight metabolic...

  6. Glucose transport in adipose tissue

    NARCIS (Netherlands)

    Schoonen, AJM; Wientjes, KJC

    2005-01-01

    Based on the well-known extraction equation and the histology of subcutaneous adipose tissue, transport of glucose from capillary to microdialysis probe is described. Results are evaluated of previous studies by our group and others. Arguments are presented for a simple scheme in which the mean

  7. Hypothalamic control of adipose tissue.

    Science.gov (United States)

    Stefanidis, A; Wiedmann, N M; Adler, E S; Oldfield, B J

    2014-10-01

    A detailed appreciation of the control of adipose tissue whether it be white, brown or brite/beige has never been more important to the development of a framework on which to build therapeutic strategies to combat obesity. This is because 1) the rate of fatty acid release into the circulation from lipolysis in white adipose tissue (WAT) is integrally important to the development of obesity, 2) brown adipose tissue (BAT) has now moved back to center stage with the realization that it is present in adult humans and, in its activated form, is inversely proportional to levels of obesity and 3) the identification and characterization of "brown-like" or brite/beige fat is likely to be one of the most exciting developments in adipose tissue biology in the last decade. Central to all of these developments is the role of the CNS in the control of different fat cell functions and central to CNS control is the integrative capacity of the hypothalamus. In this chapter we will attempt to detail key issues relevant to the structure and function of hypothalamic and downstream control of WAT and BAT and highlight the importance of developing an understanding of the neural input to brite/beige fat cells as a precursor to its recruitment as therapeutic target.

  8. [Omental torsion. Case Report].

    Science.gov (United States)

    Zaleta-Cruz, Janny Lizbeth; Rojas-Méndez, Javier; Garza-Serna, Ulises; González-Ruvalcaba, Román; Ortiz de Elguea-Lizarraga, José; Flores-Villalba, Eduardo

    Omental torsion is an infrequent cause of acute abdomen and its symptoms are non-specific, often presenting with pain at the right iliac fossa as the only symptom. Its aetiology remains unknown, but different risk factors have been associated with the disease, including obesity, congenital malformations, and tumours. These risk factors have been classified as predisposing or triggering, primary or secondary, and external or internal. The is a case of a 24-year-old male who complained about pain in the right iliac fossa without any other symptoms. The diagnosis was acute appendicitis, but during the laparoscopic approach, omental torsion was found. The diagnosis of omental torsion is is complex. However, computed tomography and ultrasound have been used successfully. The treatment for omental torsion is the resection of necrotised tissue by a laparoscopic approach. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  9. Adipose tissue, diet and aging.

    Science.gov (United States)

    Zamboni, Mauro; Rossi, Andrea P; Fantin, Francesco; Zamboni, Giulia; Chirumbolo, Salvatore; Zoico, Elena; Mazzali, Gloria

    2014-01-01

    Age related increase in body fat mass, visceral adipose tissue (AT), and ectopic fat deposition are strongly related to worse health conditions in the elderly. Moreover, with aging higher inflammation in adipose tissue may be observed and may contribute to inflammaging. Aging may significantly affect AT function by modifying the profile of adipokines produced by adipose cells, reducing preadipocytes number and their function and increasing AT macrophages infiltration. The initiating events of the inflammatory cascade promoting a greater AT inflammatory profile are not completely understood. Nutrients may determine changes in the amount of body fat, in its distribution as well as in AT function with some nutrients showing a pro-inflammatory effect on AT. Evidences are sparse and quite controversial with only a few studies performed in older subjects. Different dietary patterns are the result of the complex interaction of foods and nutrients, thus more studies are needed to evaluate the association between dietary patterns and changes in adipose tissue structure, distribution and function in the elderly.

  10. Quantification of adipose tissue insulin sensitivity.

    Science.gov (United States)

    Søndergaard, Esben; Jensen, Michael D

    2016-06-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses. Copyright © 2016 American Federation for Medical Research.

  11. Adipose Tissue Immunity and Cancer

    Directory of Open Access Journals (Sweden)

    Victoria eCatalan

    2013-10-01

    Full Text Available Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete proinflammatory adipokines and cytokines providing a microenvironment favourable for tumour growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching towards M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumour growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumour cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumour microenvironment with more sophisticated and selective anti-tumoural drugs.

  12. Endoplasmic reticulum stress is increased in adipose tissue of women with gestational diabetes.

    Directory of Open Access Journals (Sweden)

    Stella Liong

    Full Text Available Maternal obesity and gestational diabetes mellitus (GDM are two increasingly common and important obstetric complications that are associated with severe long-term health risks to mothers and babies. IL-1β, which is increased in obese and GDM pregnancies, plays an important role in the pathophysiology of these two pregnancy complications. In non-pregnant tissues, endoplasmic (ER stress is increased in diabetes and can induce IL-1β via inflammasome activation. The aim of this study was to determine whether ER stress is increased in omental adipose tissue of women with GDM, and if ER stress can also upregulate inflammasome-dependent secretion of IL-1β. ER stress markers IRE1α, GRP78 and XBP-1s were significantly increased in adipose tissue of obese compared to lean pregnant women. ER stress was also increased in adipose tissue of women with GDM compared to BMI-matched normal glucose tolerant (NGT women. Thapsigargin, an ER stress activator, induced upregulated secretion of mature IL-1α and IL-1β in human omental adipose tissue explants primed with bacterial endotoxin LPS, the viral dsRNA analogue poly(I:C or the pro-inflammatory cytokine TNF-α. Inhibition of capase-1 with Ac-YVAD-CHO resulted in decreased IL-1α and IL-1β secretion, whereas inhibition of pannexin-1 with carbenoxolone suppressed IL-1β secretion only. Treatment with anti-diabetic drugs metformin and glibenclamide also reduced IL-1α and IL-1β secretion in infection and cytokine-primed adipose tissue. In conclusion, this study has demonstrated ER stress to activate the inflammasome in pregnant adipose tissue. Therefore, increased ER stress may contribute towards the pathophysiology of obesity in pregnancy and GDM.

  13. Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance.

    Science.gov (United States)

    Cho, Kae Won; Zamarron, Brian F; Muir, Lindsey A; Singer, Kanakadurga; Porsche, Cara E; DelProposto, Jennifer B; Geletka, Lynn; Meyer, Kevin A; O'Rourke, Robert W; Lumeng, Carey N

    2016-11-01

    Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDCs), contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we use CD64 to distinguish ATM and ATDC, and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80(+)CD11b(+) cells overlaps with other leukocytes and that CD45(+)CD64(+) is specific for ATM. The expression of core dendritic cell genes was enriched in CD11c(+)CD64(-) cells (ATDC), whereas core macrophage genes were enriched in CD45(+)CD64(+) cells (ATM). CD11c(+)CD64(-) ATDCs expressed MHC class II and costimulatory receptors, and had similar capacity to stimulate CD4(+) T cell proliferation as ATMs. ATDCs were predominantly CD11b(+) conventional dendritic cells and made up the bulk of CD11c(+) cells in adipose tissue with moderate high-fat diet exposure. Mixed chimeric experiments with Ccr2(-/-) mice demonstrated that high-fat diet-induced ATM accumulation from monocytes was dependent on CCR2, whereas ATDC accumulation was less CCR2 dependent. ATDC accumulation during obesity was attenuated in Ccr7(-/-) mice and was associated with decreased adipose tissue inflammation and insulin resistance. CD45(+)CD64(+) ATM and CD45(+)CD64(-)CD11c(+) ATDCs were identified in human obese adipose tissue and ATDCs were increased in s.c. adipose tissue compared with omental adipose tissue. These results support a revised strategy for unambiguous delineation of ATM and ATDC, and suggest that ATDCs are independent contributors to adipose tissue inflammation during obesity. Copyright © 2016 by The American Association of Immunologists, Inc.

  14. Hounsfield unit dynamics of adipose tissue and non-adipose soft tissue in growing pigs

    DEFF Research Database (Denmark)

    Mcevoy, Fintan; Madsen, Mads T.; Strathe, Anders Bjerring;

    2008-01-01

    Changes in the Hounsfield Unit value of adipose tissue and of no-adipose soft tissue during growth are poorly documented. This study examines the HU of these tissues in growing pigs.......Changes in the Hounsfield Unit value of adipose tissue and of no-adipose soft tissue during growth are poorly documented. This study examines the HU of these tissues in growing pigs....

  15. Immune response in the adipose tissue of lean mice infected with the protozoan parasite Neospora caninum.

    Science.gov (United States)

    Teixeira, Luzia; Moreira, João; Melo, Joana; Bezerra, Filipa; Marques, Raquel M; Ferreirinha, Pedro; Correia, Alexandra; Monteiro, Mariana P; Ferreira, Paula G; Vilanova, Manuel

    2015-06-01

    The adipose tissue can make important contributions to immune function. Nevertheless, only a limited number of reports have investigated in lean hosts the immune response elicited in this tissue upon infection. Previous studies suggested that the intracellular protozoan Neospora caninum might affect adipose tissue physiology. Therefore, we investigated in mice challenged with this protozoan if immune cell populations within adipose tissue of different anatomical locations could be differently affected. Early in infection, parasites were detected in the adipose tissue and by 7 days of infection increased numbers of macrophages, regulatory T (Treg) cells and T-bet(+) cells were observed in gonadal, mesenteric, omental and subcutaneous adipose tissue. Increased expression of interferon-γ was also detected in gonadal adipose tissue of infected mice. Two months after infection, parasite DNA was no longer detected in these tissues, but T helper type 1 (Th1) cell numbers remained above control levels in the infected mice. Moreover, the Th1/Treg cell ratio was higher than that of controls in the mesenteric and subcutaneous adipose tissue. Interestingly, chronically infected mice presented a marked increase of serum leptin, a molecule that plays a role in energy balance regulation as well as in promoting Th1-type immune responses. Altogether, we show that an apicomplexa parasitic infection influences immune cellular composition of adipose tissue throughout the body as well as adipokine production, still noticed at a chronic phase of infection when parasites were already cleared from that particular tissue. This strengthens the emerging view that infections can have long-term consequences for the physiology of adipose tissue.

  16. MicroRNA-125a-3p expression in abdominal adipose tissues is associated with insulin signalling gene expressions in morbid obesity: observations in Taiwanese.

    Science.gov (United States)

    Yeh, Chiu-Li; Cheng, I-Chi; Hou, Yu-Chen; Wang, Weu; Yeh, Sung-Ling

    2014-01-01

    Micro (mi) RNAs have been found to play an important role in the regulation of adipogenesis and insulin sensitivity. However, associations between miRNA and insulin signalling-related gene expressions in abdominal adipose tissues in obese subjects remain unclear. We used a microarray platform to screen miRNA expressions in abdominal adipose tissues between genders in severely obese subjects and found that the top-ranking miRNA in abdominal omental adipose tissues was miRNA-125a-3p. MicroR-125a-3p and insulin signalling-related gene expressions in abdominal omental adipose tissues of all subjects (11 men and 10 women) were subsequently quantified by a real-time PCR. Also, associations of miR-125a-3p with insulin signalling-related gene expression and biochemical markers in obese subjects were analyzed by a linear regression analysis. miR-125a-3p expressed by abdominal omental adipose tissues was much higher in obese men than women. No gender difference was observed in abdominal subcutaneous adipose tissues. Concomitant with high miR-125a-3p, c-Jun N-terminal kinase gene expression was also higher, whereas insulin receptor was lower in men than women. There were negative associations of miR-125a-3p with the insulin receptor and phosphatidylinositol 3-kinase expressions. Fasting plasma glucose and cholesterol levels were positively associated with miR- 125a-3p expression. These associations were obvious in obese men but not women. Our results support the involvement of miR-125a-3p in regulating the insulin signalling pathway and imply that increased miR- 125a-3p expression in omental adipose tissues may be a characteristic feature of insulin resistance in obese men.

  17. Adipose tissues as endocrine target organs.

    Science.gov (United States)

    Lanthier, Nicolas; Leclercq, Isabelle A

    2014-08-01

    In the context of obesity, white adipocyte hypertrophy and adipose tissue macrophage infiltration result in the production of pro-inflammatory adipocytokines inducing insulin resistance locally but also in distant organs and contributing to low grade inflammatory status associated with the metabolic syndrome. Visceral adipose tissue is believed to play a prominent role. Brown and beige adipose tissues are capable of energy dissipation, but also of cytokine production and their role in dysmetabolic syndrome is emerging. This review focuses on metabolic and inflammatory changes in these adipose depots and contribution to metabolic syndrome. Also we will review surgical and pharmacological procedures to target adiposity as therapeutic interventions to treat obesity-associated disorders.

  18. Age-related changes in the percentage of oleate in adipose tissue of male and female Fischer rats

    DEFF Research Database (Denmark)

    Thorling, E.B.; Hansen, Harald S.

    1995-01-01

    Fischer 344 rats showed sex difference in the percentage of oleate in lipids of the omental adipose tissue (Thorling, E.B. and Overvad, K. (1994) Nutr. Res. 14, 569-576). The development of this difference was studied with respect to time in rats maintained on laboratory chow, from the age of 3...... in the female than in the male rats, and this difference increased with age. The results of the present study suggest that these changes in percentage of oleate in adipose tissue lipids may partly have been caused by an effect of sex steroids on the delta-9-desaturase....

  19. 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.

  20. A novel genetically-obese rat model with elevated 11beta-hydroxysteroid dehydrogenase type 1 activity in subcutaneous adipose tissue

    Directory of Open Access Journals (Sweden)

    Giridharan Nappan V

    2010-11-01

    Full Text Available Abstract 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and plays an important role in the development of obesity and metabolic syndrome. 11β-HSD1 activity is lower in liver and higher in omental adipose tissue of obese rodent models like obese zucker rats, Ob/Ob and db/db mice. Here, we report the 11β-HSD1 activity in liver and adipose tissue of lean and obese rats of WNIN/Ob strain, a new genetic rat model of obesity. 11β-HSD1 activity in liver, omental and subcutaneous adipose tissues of 3 month-old male WNIN/Ob lean and obese rats was assayed. As observed in other rodent models, 11β-HSD1 activity was lower in liver and higher in omental adipose tissue. In contrast to other rodent obese models, WNIN/Ob obese rats had elevated 11β-HSD1 activity in subcutaneous adipose tissue, which is in line with the observation in human obesity. Here, we conclude that dysregulation of 11β-HSD1 in WNIN/Ob obese rat model is identical to human obesity, which makes it an excellent model for studying the effect of 11β-HSD1 inhibitors in ameliorating obesity and metabolic syndrome.

  1. A novel genetically-obese rat model with elevated 11 beta-hydroxysteroid dehydrogenase type 1 activity in subcutaneous adipose tissue.

    Science.gov (United States)

    Prasad, Sakamuri S S Vara; Prashanth, Anamthathmakula; Kumar, Chodavarapu Pavan; Reddy, Sirisha J; Giridharan, Nappan V; Vajreswari, Ayyalasomayajula

    2010-11-17

    11 β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1) catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and plays an important role in the development of obesity and metabolic syndrome. 11 β-HSD1 activity is lower in liver and higher in omental adipose tissue of obese rodent models like obese zucker rats, Ob/Ob and db/db mice. Here, we report the 11 β-HSD1 activity in liver and adipose tissue of lean and obese rats of WNIN/Ob strain, a new genetic rat model of obesity. 11 β-HSD1 activity in liver, omental and subcutaneous adipose tissues of 3 month-old male WNIN/Ob lean and obese rats was assayed. As observed in other rodent models, 11 β-HSD1 activity was lower in liver and higher in omental adipose tissue. In contrast to other rodent obese models, WNIN/Ob obese rats had elevated 11 β-HSD1 activity in subcutaneous adipose tissue, which is in line with the observation in human obesity. Here, we conclude that dysregulation of 11 β-HSD1 in WNIN/Ob obese rat model is identical to human obesity, which makes it an excellent model for studying the effect of 11 β-HSD1 inhibitors in ameliorating obesity and metabolic syndrome.

  2. Lipid metabolism in the adipose tissues of a carnivore, the raccoon dog, during prolonged fasting.

    Science.gov (United States)

    Mustonen, Anne-Mari; Käkelä, Reijo; Käkelä, Anne; Pyykönen, Teija; Aho, Jari; Nieminen, Petteri

    2007-01-01

    Previous studies on laboratory rodents, rabbits, and humans have demonstrated that adipose tissue fatty acid (FA) mobilization is selective, and its efficiency is related to the molecular structure of FAs. This study was undertaken to find out whether such preferences of FA mobilization are a general feature of mammalian white adipose tissue (WAT) and are also manifested in carnivores. Fractional mobilization of a wide spectrum of FAs was studied by gas-liquid chromatography from six subcutaneous (scapular, rump, ventral) and intra-abdominal (omental, mesenteric, retroperitoneal) WAT depots of raccoon dogs (Nyctereutes procyonoides) fed or fasted for 2 months. Fasting stimulated the mobilization of shorter-chain saturated, mono-unsaturated (MUFAs), and polyunsaturated FAs (PUFAs). The effects of unsaturation and the position of the first double bond from the methyl end were more inconsistent. The effect of double-bond position may be due to chain shortening of longer-chain MUFAs and preferential utilization of n-3 PUFAs over n-6 PUFAs. Moreover, there were site-specific differences in fractional mobilization, the omental adipose tissue being the most divergent. The in vivo FA mobilization from the regional WAT depots of a carnivore was selective, and the molecular structure of the FA affected its efficiency.

  3. The Adipose Tissue in Farm Animals

    DEFF Research Database (Denmark)

    Sauerwein, Helga; Bendixen, Emoke; Restelli, Laura

    2014-01-01

    and immune cells. The scientific interest in adipose tissue is largely based on the worldwide increasing prevalence of obesity in humans; in contrast, obesity is hardly an issue for farmed animals that are fed according to their well-defined needs. Adipose tissue is nevertheless of major importance...... in these animals, as the adipose percentage of the bodyweight is a major determinant for the efficiency of transferring nutrients from feed into food products and thus for the economic value from meat producing animals. In dairy animals, the importance of adipose tissue is based on its function as stromal...... and metabolic disorders. We herein provide a general overview of adipose tissue functions and its importance in farm animals. This review will summarize recent achievements in farm animal adipose tissue proteomics, mainly in cattle and pigs, but also in poultry, i.e. chicken and in farmed fish. Proteomics...

  4. Renin dynamics in adipose tissue: adipose tissue control of local renin concentrations

    OpenAIRE

    Fowler, Jason D.; Krueth, Stacy B.; Bernlohr, David A.; Katz, Stephen A.

    2009-01-01

    The renin-angiotensin system (RAS) has been implicated in a variety of adipose tissue functions, including tissue growth, differentiation, metabolism, and inflammation. Although expression of all components necessary for a locally derived adipose tissue RAS has been demonstrated within adipose tissue, independence of local adipose RAS component concentrations from corresponding plasma RAS fluctuations has not been addressed. To analyze this, we varied in vivo rat plasma concentrations of two ...

  5. Adipose tissue: cell heterogeneity and functional diversity.

    Science.gov (United States)

    Esteve Ràfols, Montserrat

    2014-02-01

    There are two types of adipose tissue in the body whose function appears to be clearly differentiated. White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat. A good balance between them is important to maintain energy homeostasis. The concept of white adipose tissue has radically changed in the past decades, and is now considered as an endocrine organ that secretes many factors with autocrine, paracrine, and endocrine functions. In addition, we can no longer consider white adipose tissue as a single tissue, because it shows different metabolic profiles in its different locations, with also different implications. Although the characteristic cell of adipose tissue is the adipocyte, this is not the only cell type present in adipose tissue, neither the most abundant. Other cell types in adipose tissue described include stem cells, preadipocytes, macrophages, neutrophils, lymphocytes, and endothelial cells. The balance between these different cell types and their expression profile is closely related to maintenance of energy homeostasis. Increases in adipocyte size, number and type of lymphocytes, and infiltrated macrophages are closely related to the metabolic syndrome diseases. The study of regulation of proliferation and differentiation of preadipocytes and stem cells, and understanding of the interrelationship between the different cell types will provide new targets for action against these diseases. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  6. Development and differentiation of adipose tissue

    Directory of Open Access Journals (Sweden)

    Ivković-Lazar Tatjana A.

    2003-01-01

    Full Text Available Introduction For years adipose tissue has been considered inert, serving only as a depot of energy surplus. However, there have been recent changes, undoubtedly due to advancement of methods for studying the morphology and metabolic activities of adipose tissue (microdialysis and adipose tissue catheterization. In normal-weight subjects, adipose tissue makes 10-12% with males and 15-20% with females. About 80 % of adipose tissue is located under the skin, and the rest envelops the internal organs. With humans there are white and brown adipose tissues, which is predominant with infants and small children. Histologic characteristics From a histological point of view, it is a special form of reticular connective tissue, which contains adipocytes with netlike structure. Human adipose tissue has four types of adrenergic receptors with different topographic dispositions, which manifest different metabolic activity of adipocytes of particular body organs. Changes in adipose tissue are associated with the process of adipocyte differentiation. Critical moments for this process are last months of pregnancy, the first six months of infancy and then puberty. However, the differentiation process may also begin during maturity. Namely, as size of adipocytes can increase to a certain limit, this process can be activated after reaching a 'critical' adipocyte volume. The differentiation process is affected by a number of hormones (insulin, glucagon, corticosteroids, somatotropin (STH, thyroid gland hormones, prolactin, testosterone, but also by some other substances (fatty acids, prostaglandins, liposoluble vitamins, butyrate, aspirin, indomethacin, metylxanthine, etc..

  7. Mitochondria and endocrine function of adipose tissue.

    Science.gov (United States)

    Medina-Gómez, Gema

    2012-12-01

    Excess of adipose tissue is accompanied by an increase in the risk of developing insulin resistance, type 2 diabetes (T2D) and other complications. Nevertheless, total or partial absence of fat or its accumulation in other tissues (lipotoxicity) is also associated to these complications. White adipose tissue (WAT) was traditionally considered a metabolically active storage tissue for lipids while brown adipose tissue (BAT) was considered as a thermogenic adipose tissue with higher oxidative capacity. Nowadays, WAT is also considered an endocrine organ that contributes to energy homeostasis. Experimental evidence tends to link the malfunction of adipose mitochondria with the development of obesity and T2D. This review discusses the importance of mitochondrial function in adipocyte biology and the increased evidences of mitochondria dysfunction in these epidemics. New strategies targeting adipocyte mitochondria from WAT and BAT are also discussed as therapies against obesity and its complications in the near future.

  8. Adipose and mammary epithelial tissue engineering.

    Science.gov (United States)

    Zhu, Wenting; Nelson, Celeste M

    2013-01-01

    Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast.

  9. Adipose Tissue Biology: An Update Review

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2009-12-01

    Full Text Available BACKGROUND: Obesity is a major health problem in most countries in the world today. It increases the risk of diabetes, heart disease, fatty liver and some form of cancer. Adipose tissue biology is currently one of the “hot” areas of biomedical science, as fundamental for the development of novel therapeutics for obesity and its related disorders.CONTENT: Adipose tissue consist predominantly of adipocytes, adipose-derived stromal cells (ASCs, vascular endothelial cells, pericytes, fibroblast, macrophages, and extracellular matrix. Adipose tissue metabolism is extremely dynamic, and the supply of and removal of substrates in the blood is acutely regulated according to the nutritional state. Adipose tissue possesses the ability to a very large extent to modulate its own metabolic activities including differentiation of new adipocytes and production of blood vessels as necessary to accommodate increasing fat stores. At the same time, adipocytes signal to other tissue to regulate their energy metabolism in accordance with the body's nutritional state. Ultimately adipocyte fat stores have to match the body's overall surplus or deficit of energy. Obesity causes adipose tissue dysfunction and results in obesity-related disorders. SUMMARY: It is now clear that adipose tissue is a complex and highly active metabolic and endocrine organ. Undestanding the molecular mechanisms underlying obesity and its associated disease cluster is also of great significance as the need for new and more effective therapeutic strategies is more urgent than ever.  KEYWORDS: obesity, adipocyte, adipose, tissue, adipogenesis, angiogenesis, lipid droplet, lipolysis, plasticity, dysfunction.

  10. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

    DEFF Research Database (Denmark)

    Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.

    1999-01-01

    Organochlorines are persistent lipophilic compounds that accumulate in Inuit people living in circumpolar countries. Organochlorines accumulate as a result of the Inuits' large consumption of sea mammal fat; however, available data are limited to blood lipids, milk fat, and adipose tissue. We...... report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high......-resolution gas chromatography with electron capture detection. Mean concentrations of polychlorinated biphenyls, 2, 2'-bis(4-chlorophenyl)-1,1-dichloroethylene, ss-hexachlorocyclohexane, hexachlorobenzene, mirex, trans-nonachlor, and oxychlordane in adipose tissue samples from Greenlanders were 3-34-fold higher...

  11. Wrapped omentum with periosteum concurrent with adipose derived adult stem cells for bone tissue engineering in dog model.

    Science.gov (United States)

    Sadegh, Amin Bigham; Basiri, Ehsan; Oryan, Ahmad; Mirshokraei, Pezhman

    2014-03-01

    Adipose derived adult stem cells (ASCs) are multipotent cells that are able to differentiate into osteoblasts in presence of certain factors. The histological characteristics of periosteum makes it a specific tissue with a unique capacity to be engineered. Higher flexibility of the greater omentum is useful for reconstructive surgery. These criteria make it suitable for tissue engineering. The present study was designed to evaluate bone tissue engineering with periosteal free graft concurrent with ASCs and pedicle omentum in dog model. Twelve young female indigenous dogs were used in this experiment. In omental group (n = 4), end of omentum was wrapped by periosteum of the radial bone in abdomen of each dog. In omental-autogenously ASCs group (n = 4), 1 ml of ASCs was injected into the wrapped omentum with periosteum while in omental-allogenously ASCs group (n = 4), 1 ml of allogenous ASCs was injected. Lateral view radiographs were taken from the abdominal cavity postoperatively at the 2nd, 4th, 6th and 8th weeks post-surgery. Eight weeks after operation the dogs were re-anesthetized and the wrapped omenum by periosteum in all groups was found and removed for histopathological evaluation. Our results showed that omentum-periosteum, omental-periosteum-autogenous ASCs and omental-periosteum-allogenous ASCs groups demonstrated bone tissue formation in the abdominal cavity in dog model. The radiological, macroscopical and histological findings of the present study by the end of 8 weeks post-surgery indicate bone tissue engineering in all three groups in an equal level. The present study has shown that the wrapped omentum with periosteum concurrent with ASCs (autogenous or allogenous ASCs) lead to a favorable bone tissue formation. We suggested that it may be useful when pedicle graft omentum used concurrent with periosteum in the bone defect reconstruction, and this phenomenon should be studied in future.

  12. 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...... adipose tissue venous glycerol concentration. Despite several methodological limitations inherent to both techniques, the results strongly suggest that microdialysis and catheterization provide similar estimates of subcutaneous adipose tissue lipolysis in steady-state experimental settings like rest...

  13. Imaging white adipose tissue with confocal microscopy.

    Science.gov (United States)

    Martinez-Santibañez, Gabriel; Cho, Kae Won; Lumeng, Carey N

    2014-01-01

    Adipose tissue is composed of a variety of cell types that include mature adipocytes, endothelial cells, fibroblasts, adipocyte progenitors, and a range of inflammatory leukocytes. These cells work in concert to promote nutrient storage in adipose tissue depots and vary widely based on location. In addition, overnutrition and obesity impart significant changes in the architecture of adipose tissue that are strongly associated with metabolic dysfunction. Recent studies have called attention to the importance of adipose tissue microenvironments in regulating adipocyte function and therefore require techniques that preserve cellular interactions and permit detailed analysis of three-dimensional structures in fat. This chapter summarizes our experience with the use of laser scanning confocal microscopy for imaging adipose tissue in rodents.

  14. Renin dynamics in adipose tissue: adipose tissue control of local renin concentrations.

    Science.gov (United States)

    Fowler, Jason D; Krueth, Stacy B; Bernlohr, David A; Katz, Stephen A

    2009-02-01

    The renin-angiotensin system (RAS) has been implicated in a variety of adipose tissue functions, including tissue growth, differentiation, metabolism, and inflammation. Although expression of all components necessary for a locally derived adipose tissue RAS has been demonstrated within adipose tissue, independence of local adipose RAS component concentrations from corresponding plasma RAS fluctuations has not been addressed. To analyze this, we varied in vivo rat plasma concentrations of two RAS components, renin and angiotensinogen (AGT), to determine the influence of their plasma concentrations on adipose and cardiac tissue levels in both perfused (plasma removed) and nonperfused samples. Variation of plasma RAS components was accomplished by four treatment groups: normal, DOCA salt, bilateral nephrectomy, and losartan. Adipose and cardiac tissue AGT concentrations correlated positively with plasma values. Perfusion of adipose tissue decreased AGT concentrations by 11.1%, indicating that adipose tissue AGT was in equilibrium with plasma. Cardiac tissue renin levels positively correlated with plasma renin concentration for all treatments. In contrast, adipose tissue renin levels did not correlate with plasma renin, with the exception of extremely high plasma renin concentrations achieved in the losartan-treated group. These results suggest that adipose tissue may control its own local renin concentration independently of plasma renin as a potential mechanism for maintaining a functional local adipose RAS.

  15. Lower omental t-regulatory cell count is associated with higher fasting glucose and lower β-cell function in adults with obesity.

    Science.gov (United States)

    Gyllenhammer, Lauren E; Lam, Jonathan; Alderete, Tanya L; Allayee, Hooman; Akbari, Omid; Katkhouda, Namir; Goran, Michael I

    2016-06-01

    T-lymphocytes are potential initiators and regulators of adipose tissue (AT) inflammation, but there is limited human data on omental AT. The aim of this study was to assess the relationship between T cells, particularly Foxp3+ regulatory T (Treg) cells, in human subcutaneous (subQ) and omental AT and type 2 diabetes risk. SubQ and deep subQ (DsubQ) abdominal and omental AT biopsies were collected from 44 patients (body mass index, BMI ≥25) undergoing elective abdominal surgery. Flow cytometry was used to quantify CD4+ T cell (T effector and Treg) and macrophages (M1 and M2), and systemic inflammation was measured in fasting blood. Tregs were significantly lower in omental versus subQ and DsubQ AT, and M1 cell counts were significantly higher in the omental and DsubQ depot relative to the subQ. Only omental AT Tregs were negatively associated with fasting glucose and MCP-1 and positively associated with homeostasis model assessment (HOMA)-β. M1 and M2 cell counts across multiple depots had significant relationships with HOMA-insulin resistance, tumor necrosis factor-α, insulin, and HOMA-β. All relationships were consistent across ethnicities. Tregs were significantly lower in omental versus both subQ adipose depots. Fewer omental Tregs may have metabolic implications based on depot-specific relationships with higher fasting glucose and lower β-cell function. © 2016 The Obesity Society.

  16. Lower Omental T-regulatory Cell Count is Associated with Higher Fasting Glucose and Lower Beta-cell Function in Adults with Obesity

    Science.gov (United States)

    Gyllenhammer, Lauren E.; Lam, Jonathan; Alderete, Tanya L.; Allayee, Hooman; Akbari, Omid; Katkhouda, Namir; Goran, Michael I.

    2016-01-01

    Objective T-lymphocytes are potential initiators and regulators of adipose tissue (AT) inflammation, but there is limited human data on omental AT. Our aim was to assess the relationship between T-cells, particularly Foxp3+ regulatory T (Treg) cells, in human subcutaneous (subQ) and omental AT and type 2 diabetes risk. Methods We collected subQ and deep subcutaneous (DsubQ) abdominal and omental AT biopsies from 44 patients (body mass index (BMI)≥25) undergoing elective abdominal surgery. Flow cytometry was used to quantify CD4+ T-cell (T effector and Treg) and macrophages (M1 and M2), and systemic inflammation was measured in fasting blood. Results Tregs were significantly lower in omental versus subQ and DsubQ AT and M1 cell counts were significantly higher in the omental and DsubQ depot relative to the subQ. Only omental AT Tregs were negatively associated with fasting glucose and MCP-1 and positively associated with HOMA-β. M1 and M2 cell counts across multiple depots had significant relationships with HOMA-IR, TNF-α, insulin and HOMA-β. All relationships were consistent across ethnicities. Conclusions Tregs were significantly lower in omental versus both subQ adipose depots. Fewer omental Tregs may have metabolic implications based on depot specific relationship with higher fasting glucose and lower beta-cell function. PMID:27133873

  17. Inverse regulation of inflammation and mitochondrial function in adipose tissue defines extreme insulin sensitivity in morbidly obese patients.

    Science.gov (United States)

    Qatanani, Mohammed; Tan, Yejun; Dobrin, Radu; Greenawalt, Danielle M; Hu, Guanghui; Zhao, Wenqing; Olefsky, Jerrold M; Sears, Dorothy D; Kaplan, Lee M; Kemp, Daniel M

    2013-03-01

    Obesity is associated with insulin resistance, a major risk factor for type 2 diabetes and cardiovascular disease. However, not all obese individuals are insulin resistant, which confounds our understanding of the mechanistic link between these conditions. We conducted transcriptome analyses on 835 obese subjects with mean BMI of 48.8, on which we have previously reported genetic associations of gene expression. Here, we selected ~320 nondiabetic (HbA(1c) immune response and inflammation-related genes were significantly downregulated in the omental adipose tissue of obese individuals with extreme insulin sensitivity and, to a much lesser extent, in subcutaneous adipose tissue. In contrast, genes related to β-oxidation and the citric acid cycle were relatively overexpressed in adipose of insulin-sensitive patients. These observations were verified by querying an independent cohort of our published dataset of 37 subjects whose subcutaneous adipose tissue was sampled before and after treatment with thiazolidinediones. Whereas the immune response and inflammation pathway genes were downregulated by thiazolidinedione treatment, β-oxidation and citric acid cycle genes were upregulated. This work highlights the critical role that omental adipose inflammatory pathways might play in the pathophysiology of insulin resistance, independent of body weight.

  18. An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss.

    Science.gov (United States)

    Benton, Miles C; Johnstone, Alice; Eccles, David; Harmon, Brennan; Hayes, Mark T; Lea, Rod A; Griffiths, Lyn; Hoffman, Eric P; Stubbs, Richard S; Macartney-Coxson, Donia

    2015-01-22

    Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans. Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3' untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such as CETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose and HDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass. This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.

  19. Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep.

    Science.gov (United States)

    Bloor, Ian D; Sébert, Sylvain P; Saroha, Vivek; Gardner, David S; Keisler, Duane H; Budge, Helen; Symonds, Michael E; Mahajan, Ravi P

    2013-10-01

    Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity.

  20. Hypertrophic Obesity and Subcutaneous Adipose Tissue Dysfunction

    Directory of Open Access Journals (Sweden)

    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.

  1. Cardiac adipose tissue and atrial fibrillation: the perils of adiposity.

    Science.gov (United States)

    Hatem, Stéphane N; Redheuil, Alban; Gandjbakhch, Estelle

    2016-04-01

    The amount of adipose tissue that accumulates around the atria is associated with the risk, persistence, and severity of atrial fibrillation (AF). A strong body of clinical and experimental evidence indicates that this relationship is not an epiphenomenon but is the result of complex crosstalk between the adipose tissue and the neighbouring atrial myocardium. For instance, epicardial adipose tissue is a major source of adipokines, inflammatory cytokines, or reactive oxidative species, which can contribute to the fibrotic remodelling of the atrial myocardium. Fibro-fatty infiltrations of the subepicardium could also contribute to the functional disorganization of the atrial myocardium. The observation that obesity is associated with distinct structural and functional remodelling of the atria has opened new perspectives of treating AF substrate with aggressive risk factor management. Advances in cardiac imaging should lead to an improved ability to visualize myocardial fat depositions and to localize AF substrates.

  2. Brown adipose tissue, thermogenesis, angiogenesis: pathophysiological aspects.

    Science.gov (United States)

    Honek, Jennifer; Lim, Sharon; Fischer, Carina; Iwamoto, Hideki; Seki, Takahiro; Cao, Yihai

    2014-07-01

    The number of obese and overweight individuals is globally rising, and obesity-associated disorders such as type 2 diabetes, cardiovascular disease and certain types of cancer are among the most common causes of death. While white adipose tissue is the key player in the storage of energy, active brown adipose tissue expends energy due to its thermogenic capacity. Expanding and activating brown adipose tissue using pharmacological approaches therefore might offer an attractive possibility for therapeutic intervention to counteract obesity and its consequences for metabolic health.

  3. Adipose tissue as an endocrine organ.

    Science.gov (United States)

    McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

    2014-02-01

    Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling.

  4. Brown adipose tissue and its therapeutic potential.

    Science.gov (United States)

    Lidell, M E; Betz, M J; Enerbäck, S

    2014-10-01

    Obesity and related diseases are a major cause of human morbidity and mortality and constitute a substantial economic burden for society. Effective treatment regimens are scarce, and new therapeutic targets are needed. Brown adipose tissue, an energy-expending tissue that produces heat, represents a potential therapeutic target. Its presence is associated with low body mass index, low total adipose tissue content and a lower risk of type 2 diabetes mellitus. Knowledge about the development and function of thermogenic adipocytes in brown adipose tissue has increased substantially in the last decade. Important transcriptional regulators have been identified, and hormones able to modulate the thermogenic capacity of the tissue have been recognized. Intriguingly, it is now clear that humans, like rodents, possess two types of thermogenic adipocytes: the classical brown adipocytes found in the interscapular brown adipose organ and the so-called beige adipocytes primarily found in subcutaneous white adipose tissue after adrenergic stimulation. The presence of two distinct types of energy-expending adipocytes in humans is conceptually important because these cells might be stimulated and recruited by different signals, raising the possibility that they might be separate potential targets for therapeutic intervention. In this review, we will discuss important features of the energy-expending brown adipose tissue and highlight those that may serve as potential targets for pharmacological intervention aimed at expanding the tissue and/or enhancing its function to counteract obesity.

  5. Adipose tissue and adipocyte dysregulation.

    Science.gov (United States)

    Lafontan, M

    2014-02-01

    Obesity-associated insulin resistance is a complex disorder involving a number of candidate molecules, pathways and transduction systems possessing potential causal actions. Inflammation in adipose tissue (AT) is one mechanism proposed to explain the development of insulin resistance, while identification of factors that lead to or cause AT dysfunction when it reaches its limit of expansion represents an important challenge. Pathological expansion of AT is characterized by changes in its blood flow, and the presence of enlarged and dysfunctional adipocytes that begin an inflammatory campaign of altered adipokine and cytokine secretions. Adipocyte senescence, necrosis and death are associated with increased immune cell and macrophage infiltration of AT in obesity. This can boost inflammation and reinforce fat cell dysfunction and death. In addition, pathological fat mass expansion is also related to limited recruitment of fat cell progenitors able to proliferate and differentiate into healthy small fat cells to compensate for cell death and preserve adipocyte numbers. Limiting vascular development and enhancing fibrotic processes worsen inflammation towards chronic irreversibility. The AT expandability hypothesis states that failure of AT expansion is one of the key factors linking positive energy balance and cardiometabolic risks, not obesity per se. Besides the usual treatment of obesity based on behavioral approaches (specific dietary/nutritional approaches together with increased physical activity), a number of questions remain concerning the possible recovery of metabolic health after inflammation-preventing interventions. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  6. White adipose tissue: getting nervous.

    Science.gov (United States)

    Fliers, E; Kreier, F; Voshol, P J; Havekes, L M; Sauerwein, H P; Kalsbeek, A; Buijs, R M; Romijn, J A

    2003-11-01

    Neuroendocrine research has altered the traditional perspective of white adipose tissue (WAT) as a passive store of triglycerides. In addition to fatty acids, WAT produces many hormones and can therefore be designated as a traditional endocrine gland actively participating in the integrative physiology of fuel and energy metabolism, eating behaviour and the regulation of hormone secretion and sensitivity. WAT is controlled by humoral factors, para- and intracrine factors and by neural regulation. Sympathetic nerve fibres innervate WAT and stimulate lipolysis, leading to the release of glycerol and free fatty acids. In addition, recent research in rats has clearly shown a functional parasympathetic innervation of WAT. There appears to be a distinct somatotopy within the parasympathetic nuclei: separate sets of autonomic neurones in the brain stem innervate either the visceral or the subcutaneous fat compartment. We therefore propose that the central nervous system (CNS) plays a major role in the hitherto unexplained regulation of body fat distribution. Parasympathectomy induces insulin resistance with respect to glucose and fatty acid uptake in the innervated fat depot and has selective effects on local hormone synthesis. Thus, the CNS is involved not only in the regulation of hormone production by WAT, but also in its hormone sensitivity. The developments in this research area are likely to increase our insights in the pathogenesis of metabolic disorders such as hypertriglyceridemia, diabetes mellitus type 2 and lipodystrophy syndromes.

  7. Intermuscular and intramuscular adipose tissues: Bad vs. good adipose tissues.

    Science.gov (United States)

    Hausman, Gary J; Basu, Urmila; Du, Min; Fernyhough-Culver, Melinda; Dodson, Michael V

    2014-01-01

    Human studies of the influence of aging and other factors on intermuscular fat (INTMF) were reviewed. Intermuscular fat increased with weight loss, weight gain, or with no weight change with age in humans. An increase in INTMF represents a similar threat to type 2 diabetes and insulin resistance as does visceral adipose tissue (VAT). Studies of INTMF in animals covered topics such as quantitative deposition and genetic relationships with other fat depots. The relationship between leanness and higher proportions of INTMF fat in pigs was not observed in human studies and was not corroborated by other pig studies. In humans, changes in muscle mass, strength and quality are associated with INTMF accretion with aging. Gene expression profiling and intrinsic methylation differences in pigs demonstrated that INTMF and VAT are primarily associated with inflammatory and immune processes. It seems that in the pig and humans, INTMF and VAT share a similar pattern of distribution and a similar association of components dictating insulin sensitivity. Studies on intramuscular (IM) adipocyte development in meat animals were reviewed. Gene expression analysis and genetic analysis have identified candidate genes involved in IM adipocyte development. Intramuscular (IM) adipocyte development in human muscle is only seen during aging and some pathological circumstance. Several genetic links between human and meat animal adipogenesis have been identified. In pigs, the Lipin1 and Lipin 2 gene have strong genetic effects on IM accumulation. Lipin1 deficiency results in immature adipocyte development in human lipodystrophy. In humans, overexpression of Perilipin 2 (PLIN2) facilitates intramyocellular lipid accretion whereas in pigs PLIN2 gene expression is associated with IM deposition. Lipins and perilipins may influence intramuscular lipid regardless of species.

  8. Adipose Tissue Remodeling as Homeostatic Inflammation

    Directory of Open Access Journals (Sweden)

    Michiko Itoh

    2011-01-01

    Full Text Available Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation. Obese adipose tissue is characterized by dynamic changes in cellular composition and function, which may be referred to as “adipose tissue remodeling”. Among stromal cells in the adipose tissue, infiltrated macrophages play an important role in adipose tissue inflammation and systemic insulin resistance. We have demonstrated that a paracrine loop involving saturated fatty acids and tumor necrosis factor-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 complex, thereby activating macrophages. Such a sustained interaction between endogenous ligands derived from parenchymal cells and pathogen sensors expressed in stromal immune cells should lead to chronic inflammatory responses ranging from the basal homeostatic state to diseased tissue remodeling, which may be referred to as “homeostatic inflammation”. We, therefore, postulate that adipose tissue remodeling may represent a prototypic example of homeostatic inflammation. Understanding the molecular mechanism underlying homeostatic inflammation may lead to the identification of novel therapeutic strategies to prevent or treat obesity-related complications.

  9. Immunological contributions to adipose tissue homeostasis.

    Science.gov (United States)

    DiSpirito, Joanna R; Mathis, Diane

    2015-09-01

    Adipose tissue is composed of many functionally and developmentally distinct cell types, the metabolic core of which is the adipocyte. The classification of "adipocyte" encompasses three primary types - white, brown, and beige - with distinct origins, anatomic distributions, and homeostatic functions. The ability of adipocytes to store and release lipids, respond to insulin, and perform their endocrine functions (via secretion of adipokines) is heavily influenced by the immune system. Various cell populations of the innate and adaptive arms of the immune system can resist or exacerbate the development of the chronic, low-grade inflammation associated with obesity and metabolic dysfunction. Here, we discuss these interactions, with a focus on their consequences for adipocyte and adipose tissue function in the setting of chronic overnutrition. In addition, we will review the effects of diet composition on adipose tissue inflammation and recent evidence suggesting that diet-driven disruption of the gut microbiota can trigger pathologic inflammation of adipose tissue.

  10. Aetiological factors behind adipose tissue inflammation

    DEFF Research Database (Denmark)

    von Scholten, Bernt J; Andresen, Erik N; Sørensen, Thorkild I A

    2013-01-01

    Despite extensive research into the biological mechanisms behind obesity-related inflammation, knowledge of environmental and genetic factors triggering such mechanisms is limited. In the present narrative review we present potential determinants of adipose tissue inflammation and suggest ways...

  11. How to Measure Adipose Tissue Insulin Sensitivity?

    DEFF Research Database (Denmark)

    Søndergaard, Esben; Espinosa De Ycaza, Ana Elena; Morgan-Bathke, Maria

    2017-01-01

    Background: Adipose tissue insulin resistance may be a proximate cause of hepatic and skeletal muscle insulin resistance by releasing excess FFA. However, no consensus exists on how to quantify adipose tissue insulin sensitivity. We compared three methods for measuring adipose tissue insulin...... sensitivity ranging from the complex multistep pancreatic clamp technique to the simple adipose tissue insulin resistance index (Adipo-IR). Methods: We completed studies of 25 adults with a wide range of insulin sensitivity. The insulin dose resulting in a 50% suppression of palmitate flux (IC50) was measured...... using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-13C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations. Results: Adipo-IR was reproducible [sample CV=10...

  12. Glucocorticoids fail to cause insulin resistance in human subcutaneous adipose tissue in vivo.

    Science.gov (United States)

    Hazlehurst, Jonathan M; Gathercole, Laura L; Nasiri, Maryam; Armstrong, Matthew J; Borrows, Sarah; Yu, Jinglei; Wagenmakers, Anton J M; Stewart, Paul M; Tomlinson, Jeremy W

    2013-04-01

    It is widely believed that glucocorticoids cause insulin resistance in all tissues. We have previously demonstrated that glucocorticoids cause insulin sensitization in human adipose tissue in vitro and induce insulin resistance in skeletal muscle. Our aim was to determine whether glucocorticoids have tissue-specific effects on insulin sensitivity in vivo. Fifteen healthy volunteers were recruited into a double-blind, randomized, placebo-controlled, crossover study, receiving both an overnight hydrocortisone and saline infusion. The tissue-specific actions of insulin were determined using paired 2-step hyperinsulinemic euglycemic clamps incorporating stable isotopes with concomitant adipose tissue microdialysis. The study was performed in the Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital, Birmingham, United Kingdom. The sensitivity of sc adipose tissue to insulin action was measured. Hydrocortisone induced systemic insulin resistance but failed to cause sc adipose tissue insulin resistance as measured by suppression of adipose tissue lipolysis and enhanced insulin-stimulated pyruvate generation. In primary cultures of human hepatocytes, glucocorticoids increased insulin-stimulated p-ser473akt/protein kinase B. Similarly, glucocorticoids enhanced insulin-stimulated p-ser473akt/protein kinase B and increased Insulin receptor substrate 2 mRNA expression in sc, but not omental, intact human adipocytes, suggesting a depot-specificity of action. This study represents the first description of sc adipose insulin sensitization by glucocorticoids in vivo and demonstrates tissue-specific actions of glucocorticoids to modify insulin action. It defines an important advance in our understanding of the actions of both endogenous and exogenous glucocorticoids and may have implications for the development and targeting of future glucocorticoid therapies.

  13. Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue[S

    Science.gov (United States)

    Xu, X. Julia; Gauthier, Marie-Soleil; Hess, Donald T.; Apovian, Caroline M.; Cacicedo, Jose M.; Gokce, Noyan; Farb, Melissa; Valentine, Rudy J.; Ruderman, Neil B.

    2012-01-01

    We previously reported that adenosine monophosphate-activated protein kinase (AMPK) activity is lower in adipose tissue of morbidly obese individuals who are insulin resistant than in comparably obese people who are insulin sensitive. However, the number of patients and parameters studied were small. Here, we compared abdominal subcutaneous, epiploic, and omental fat from 16 morbidly obese individuals classified as insulin sensitive or insulin resistant based on the homeostatic model assessment of insulin resistance. We confirmed that AMPK activity is diminished in the insulin resistant group. A custom PCR array revealed increases in mRNA levels of a wide variety of genes associated with inflammation and decreases in PGC-1α and Nampt in omental fat of the insulin resistant group. In contrast, subcutaneous abdominal fat of the same patients showed increases in PTP-1b, VEGFa, IFNγ, PAI-1, and NOS-2 not observed in omental fat. Only angiotensinogen and CD4+ mRNA levels were increased in both depots. Surprisingly, TNFα was only increased in epiploic fat, which otherwise showed very few changes. Protein carbonyl levels, a measure of oxidative stress, were increased in all depots. Thus, adipose tissues of markedly obese insulin resistant individuals uniformly show decreased AMPK activity and increased oxidative stress compared with insulin sensitive patients. However, most changes in gene expression appear to be depot-specific. PMID:22323564

  14. mRNA Expression of Ovine Angiopoietin-like Protein 4 Gene in Adipose Tissues.

    Science.gov (United States)

    Zhang, Jing; Jing, Jiong-Jie; Jia, Xia-Li; Qiao, Li-Ying; Liu, Jian-Hua; Liang, Chen; Liu, Wen-Zhong

    2016-05-01

    Angiopoietin-like protein 4 (ANGPTL4) is involved in a variety of functions, including lipoprotein metabolism and angiogenesis. To reveal the role of ANGPTL4 in fat metabolism of sheep, ovine ANGPTL4 mRNA expression was analyzed in seven adipose tissues from two breeds with distinct tail types. Forty-eight animals with the gender ratio of 1:1 for both Guangling Large Tailed (GLT) and Small Tailed Han (STH) sheep were slaughtered at 2, 4, 6, 8, 10, and 12 months of age, respectively. Adipose tissues were collected from greater and lesser omental, subcutaneous, retroperitoneal, perirenal, mesenteric, and tail fats. Ontogenetic mRNA expression of ANGPTL4 in these adipose tissues from GTL and STH was studied by quantitative real time polymerase chain reaction. The results showed that ANGPTL4 mRNA expressed in all adipose tissues studied with the highest in subcutaneous and the lowest in mesenteric fat depots. Months of age, tissue and breed are the main factors that significantly influence the mRNA expression. These results provide new insights into ovine ANGPTL4 gene expression and clues for its function mechanism.

  15. [Kidney, adipose tissue, adipocytes--what's new?].

    Science.gov (United States)

    Lafontan, Max

    2011-04-01

    Increased evidence suggests that obesity-related glomerulopathy and chronic kidney diseases should be identified as isolated complications of obesity. It is questioned if the numerous adipose tissue productions could play a role in the initiation/maintenance of such kidney diseases. This review will provide a sum-up of recent advances on fat cell metabolism and adipose tissue physiology. The adipose tissue behaves as an endocrine organ with multiple activities. It is secreting hormones (leptin, adiponectin, apelin) and numerous factors with autocrine, paracrine and systemic effects. These secretions are coming from adipocytes themselves or from cells present in the stroma-vascular fraction of the adipose tissue. When expanding, the adipose tissue of the obese is infiltrated by immune cells such as macrophages and lymphocytes; the role of which is not fully clarified. An attempt will be done to delineate if alterations of lipid storage/fatty acid release or of the secretion potencies of adipose tissue could contribute to kidney lipotoxicity and other chronic kidney diseases described in the obese. Copyright © 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  16. How to Measure Adipose Tissue Insulin Sensitivity.

    Science.gov (United States)

    Søndergaard, Esben; Espinosa De Ycaza, Ana Elena; Morgan-Bathke, Maria; Jensen, Michael D

    2017-04-01

    Adipose tissue insulin resistance may cause hepatic and skeletal muscle insulin resistance by releasing excess free fatty acids (FFAs). Because no consensus exists on how to quantify adipose tissue insulin sensitivity we compared three methods for measuring adipose tissue insulin sensitivity: the single step insulin clamp, the multistep pancreatic clamp, and the adipose tissue insulin resistance index (Adipo-IR). We studied insulin sensitivity in 25 adults by measuring the insulin concentration resulting in 50% suppression of palmitate flux (IC50) using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-13C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations. Adipo-IR was reproducible (sample coefficient of variability, 10.0%) and correlated with the IC50 measured by the multistep pancreatic clamp technique (r, 0.86; P adipose tissue insulin sensitivity. However, age and physical fitness systematically affect the predictive values. Although Adipo-IR is suitable for larger population studies, the multistep pancreatic clamp technique is probably needed for mechanistic studies of adipose tissue insulin action.

  17. Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats.

    Directory of Open Access Journals (Sweden)

    Andreea Oana Mocanu

    Full Text Available Obesity is associated with low-grade chronic inflammation. We hypothesized that Roux-en-Y gastric bypass (RYGB surgery would reduce activation of the NLRP3 inflammasome in metabolically active adipose tissue (AT of obese rats, and this change would be related to decreases in body weight and improved glycemic control.Omental, mesenteric and subcutaneous fat depots were collected from Sprague-Dawley rats: Sham control and RYGB; 90-days after surgery. NLRP3, caspase-1, apoptosis-associated speck-like protein (ASC, IL-1β, IL-18, IL-6 and MCP-1 gene and protein expression were quantified. Glucose metabolism was assessed by oral glucose tolerance test (OGTT.Compared to Sham surgery controls, RYGB surgery decreased IL-6, MCP-1, NLRP3, IL-18, caspase-1 and ASC in omental fat, and decreased IL-6, MCP1, IL-1β, IL-18, caspase-1 and ASC gene expression in mesenteric fat. We observed differential gene expression between visceral and subcutaneous fat for IL-6 and IL-1β, both being downregulated by RYGB in visceral, and upregulated in subcutaneous depots. These changes in gene expression were accompanied by a decrease in NLRP3, ASC, IL-18, caspase-1 and IL-1β protein expression in omental tissue. We found a positive correlation between caspase-1, ASC, MCP-1, IL-18 and IL-6 gene expression following surgery and glucose AUC response in omental fat, while the change in glucose AUC response correlated with caspase-1 gene expression in subcutaneous fat.This study demonstrates that bariatric surgery reverses inflammation in visceral adipose tissue by suppressing NLRP3 inflammasome activation. These are the first data to implicate the NLRP3 inflammasome in diabetes remission after RYGB surgery.

  18. Adipose tissue plasticity from WAT to BAT and in between.

    Science.gov (United States)

    Lee, Yun-Hee; Mottillo, Emilio P; Granneman, James G

    2014-03-01

    Adipose tissue plays an essential role in regulating energy balance through its metabolic, cellular and endocrine functions. Adipose tissue has been historically classified into anabolic white adipose tissue and catabolic brown adipose tissue. An explosion of new data, however, points to the remarkable heterogeneity among the cells types that can become adipocytes, as well as the inherent metabolic plasticity of mature cells. These data indicate that targeting cellular and metabolic plasticity of adipose tissue might provide new avenues for treatment of obesity-related diseases. This review will discuss the developmental origins of adipose tissue, the cellular complexity of adipose tissues, and the identification of progenitors that contribute to adipogenesis throughout development. We will touch upon the pathological remodeling of adipose tissue and discuss how our understanding of adipose tissue remodeling can uncover new therapeutic targets. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  19. The mechanical properties of human adipose tissues and their relationships to the structure and composition of the extracellular matrix.

    Science.gov (United States)

    Alkhouli, Nadia; Mansfield, Jessica; Green, Ellen; Bell, James; Knight, Beatrice; Liversedge, Neil; Tham, Ji Chung; Welbourn, Richard; Shore, Angela C; Kos, Katarina; Winlove, C Peter

    2013-12-01

    Adipose tissue (AT) expansion in obesity is characterized by cellular growth and continuous extracellular matrix (ECM) remodeling with increased fibrillar collagen deposition. It is hypothesized that the matrix can inhibit cellular expansion and lipid storage. Therefore, it is important to fully characterize the ECM's biomechanical properties and its interactions with cells. In this study, we characterize and compare the mechanical properties of human subcutaneous and omental tissues, which have different physiological functions. AT was obtained from 44 subjects undergoing surgery. Force/extension and stress/relaxation data were obtained. The effects of osmotic challenge were measured to investigate the cellular contribution to tissue mechanics. Tissue structure and its response to tensile strain were determined using nonlinear microscopy. AT showed nonlinear stress/strain characteristics of up to a 30% strain. Comparing paired subcutaneous and omental samples (n = 19), the moduli were lower in subcutaneous: initial 1.6 ± 0.8 (means ± SD) and 2.9 ± 1.5 kPa (P = 0.001), final 11.7 ± 6.4 and 32 ± 15.6 kPa (P matrix fibers. These results suggest that subcutaneous AT has greater capacity for expansion and recovery from mechanical deformation than omental AT.

  20. Vitamin D signalling in adipose tissue.

    Science.gov (United States)

    Ding, Cherlyn; Gao, Dan; Wilding, John; Trayhurn, Paul; Bing, Chen

    2012-12-14

    Vitamin D deficiency and the rapid increase in the prevalence of obesity are both considered important public health issues. The classical role of vitamin D is in Ca homoeostasis and bone metabolism. Growing evidence suggests that the vitamin D system has a range of physiological functions, with vitamin D deficiency contributing to the pathogenesis of several major diseases, including obesity and the metabolic syndrome. Clinical studies have shown that obese individuals tend to have a low vitamin D status, which may link to the dysregulation of white adipose tissue. Recent studies suggest that adipose tissue may be a direct target of vitamin D. The expression of both the vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) genes has been shown in murine and human adipocytes. There is evidence that vitamin D affects body fat mass by inhibiting adipogenic transcription factors and lipid accumulation during adipocyte differentiation. Some recent studies demonstrate that vitamin D metabolites also influence adipokine production and the inflammatory response in adipose tissue. Therefore, vitamin D deficiency may compromise the normal metabolic functioning of adipose tissue. Given the importance of the tissue in energy balance, lipid metabolism and inflammation in obesity, understanding the mechanisms of vitamin D action in adipocytes may have a significant impact on the maintenance of metabolic health. In the present review, we focus on the signalling role of vitamin D in adipocytes, particularly the potential mechanisms through which vitamin D may influence adipose tissue development and function.

  1. Brown Adipose Tissue Growth and Development

    Directory of Open Access Journals (Sweden)

    Michael E. Symonds

    2013-01-01

    Full Text Available Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle.

  2. Brown adipose tissue growth and development.

    Science.gov (United States)

    Symonds, Michael E

    2013-01-01

    Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle.

  3. Tissue engineering chamber promotes adipose tissue regeneration in adipose tissue engineering models through induced aseptic inflammation.

    Science.gov (United States)

    Peng, Zhangsong; Dong, Ziqing; Chang, Qiang; Zhan, Weiqing; Zeng, Zhaowei; Zhang, Shengchang; Lu, Feng

    2014-11-01

    Tissue engineering chamber (TEC) makes it possible to generate significant amounts of mature, vascularized, stable, and transferable adipose tissue. However, little is known about the role of the chamber in tissue engineering. Therefore, to investigate the role of inflammatory response and the change in mechanotransduction started by TEC after implantation, we placed a unique TEC model on the surface of the groin fat pads in rats to study the expression of cytokines and tissue development in the TEC. The number of infiltrating cells was counted, and vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) expression levels in the chamber at multiple time points postimplantation were analyzed by enzyme-linked immunosorbent assay. Tissue samples were collected at various time points and labeled for specific cell populations. The result showed that new adipose tissue formed in the chamber at day 60. Also, the expression of MCP-1 and VEGF in the chamber decreased slightly from an early stage as well as the number of the infiltrating cells. A large number of CD34+/perilipin- perivascular cells could be detected at day 30. Also, the CD34+/perilipin+ adipose precursor cell numbers increased sharply by day 45 and then decreased by day 60. CD34-/perilipin+ mature adipocytes were hard to detect in the chamber content at day 30, but their number increased and then peaked at day 60. Ki67-positive cells could be found near blood vessels and their number decreased sharply over time. Masson's trichrome showed that collagen was the dominant component of the chamber content at early stage and was replaced by newly formed small adipocytes over time. Our findings suggested that the TEC implantation could promote the proliferation of adipose precursor cells derived from local adipose tissue, increase angiogenesis, and finally lead to spontaneous adipogenesis by inducing aseptic inflammation and changing local mechanotransduction.

  4. A novel genetically-obese rat model with elevated 11beta-hydroxysteroid dehydrogenase type 1 activity in subcutaneous adipose tissue

    OpenAIRE

    Giridharan Nappan V; Reddy Sirisha J; Kumar Chodavarapu; Prashanth Anamthathmakula; Prasad Sakamuri; Vajreswari Ayyalasomayajula

    2010-01-01

    Abstract 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and plays an important role in the development of obesity and metabolic syndrome. 11β-HSD1 activity is lower in liver and higher in omental adipose tissue of obese rodent models like obese zucker rats, Ob/Ob and db/db mice. Here, we report the 11β-HSD1 activity in liver and adipose tissue of lean and obese rats of WNIN/Ob strain, a new genetic rat model of...

  5. Insulin effects in muscle and adipose tissue.

    Science.gov (United States)

    Dimitriadis, George; Mitrou, Panayota; Lambadiari, Vaia; Maratou, Eirini; Raptis, Sotirios A

    2011-08-01

    The major effects of insulin on muscle and adipose tissue are: (1) Carbohydrate metabolism: (a) it increases the rate of glucose transport across the cell membrane, (b) it increases the rate of glycolysis by increasing hexokinase and 6-phosphofructokinase activity, (c) it stimulates the rate of glycogen synthesis and decreases the rate of glycogen breakdown. (2) Lipid metabolism: (a) it decreases the rate of lipolysis in adipose tissue and hence lowers the plasma fatty acid level, (b) it stimulates fatty acid and triacylglycerol synthesis in tissues, (c) it increases the uptake of triglycerides from the blood into adipose tissue and muscle, (d) it decreases the rate of fatty acid oxidation in muscle and liver. (3) Protein metabolism: (a) it increases the rate of transport of some amino acids into tissues, (b) it increases the rate of protein synthesis in muscle, adipose tissue, liver, and other tissues, (c) it decreases the rate of protein degradation in muscle (and perhaps other tissues). These insulin effects serve to encourage the synthesis of carbohydrate, fat and protein, therefore, insulin can be considered to be an anabolic hormone. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Downregulation of complement C3 and C3aR expression in subcutaneous adipose tissue in obese women.

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    Abhishek Gupta

    Full Text Available BACKGROUND: The central component of the complement system, C3, is associated with obesity, metabolic syndrome and cardiovascular disease however the underlying reasons are unknown. In the present study we evaluated gene expression of C3, the cleavage product C3a/C3adesArg and its cognate receptor C3aR in subcutaneous and omental adipose tissue in women. METHODS: Women (n = 140, 21-69 years, BMI 19.5-79 kg/m2 were evaluated for anthropometric and blood parameters, and adipose tissue gene expression. RESULTS: Subjects were separated into groups (n = 34-36 according to obesity: normal/overweight (≤30 kg/m2, obese I (≤45 kg/m2, obese II (≤51 kg/m2, and obese III (≤80 kg/m2. Overall, while omental expression remained unchanged, subcutaneous C3 and C3aR gene expression decreased with increasing adiposity (2-way ANOVA, p<0.01, with a concomitant decrease in SC/OM ratio (p<0.001. In subcutaneous adipose, both C3 and C3aR expression correlated with apoB, and apoA1 and inversely with waist circumference and blood pressure, while C3aR also correlated with glucose (p<0.05-0.0001. While omental C3aR expression did not correlate with any factor, omental C3 correlated with waist circumference, glucose and apoB (all p<0.05. Further, while plasma C3a/C3adesArg increased and adiponectin decreased with increasing BMI, both correlated (C3a negatively and adiponectin positively with subcutaneous C3 and C3aR expression (p<0.05-0.001 or less. CONCLUSIONS: The obesity-induced down-regulation of complement C3 and C3aR which is specific to subcutaneous adipose tissue, coupled to the strong correlations with multiple anthropometric, plasma and adipokine variables support a potential role for complement in immunometabolism.

  7. Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Andrew A. Bremer

    2013-01-01

    Full Text Available The metabolic syndrome (MetS confers an increased risk for both type 2 diabetes mellitus (T2DM and cardiovascular disease (CVD. Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome’s low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin, as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.

  8. Lipophilic Micronutrients and Adipose Tissue Biology

    Directory of Open Access Journals (Sweden)

    Franck Tourniaire

    2012-11-01

    Full Text Available Lipophilic micronutrients (LM constitute a large family of molecules including several vitamins (A, D, E, K and carotenoids. Their ability to regulate gene expression is becoming increasingly clear and constitutes an important part of nutrigenomics. Interestingly, adipose tissue is not only a main storage site for these molecules within the body, but it is also subjected to the regulatory effects of LM. Indeed, several gene regulations have been described in adipose tissue that could strongly impact its biology with respect to the modulation of adipogenesis, inflammatory status, or energy homeostasis and metabolism, among others. The repercussions in terms of health effects of such regulations in the context of obesity and associated pathologies represent an exciting and emerging field of research. The present review will focus on the regulatory effects of vitamin A, D, E and K as well as carotenoids on adipose tissue biology and physiology, notably in the context of obesity and associated disorders.

  9. In vivo determination of subcutaneous and abdominal adipose tissue depots in German Holstein dairy cattle.

    Science.gov (United States)

    Raschka, C; Ruda, L; Wenning, P; von Stemm, C-I; Pfarrer, C; Huber, K; Meyer, U; Dänicke, S; Rehage, J

    2016-07-01

    Ultrasonography was used as a noninvasive method for quantitative estimation of the subcutaneous and abdominal adipose tissue depots in dairy cattle. The prediction model was created and validated with a total of 29 German Holstein cows; 6 were in early lactation (≤100 d in milk [DIM]) and 16 were in advanced lactation (101 to 292 DIM). Seven cows were nonpregnant and nonlactating and had been off milk for 350 to 450 d. Transcutaneous assessment of the thickness of subcutaneous and retroperitoneal adipose tissue was done at 16 sites on the body surface of all cows. After completion of the ultrasonographic measurements, the cows were slaughtered and the adipose depots were separately weighed. A stepwise multivariate regression analysis of the ultrasonographic variables was performed to estimate the slaughter weights of the different fat depots. Slaughter weights of the fat depots ranged from 5.0 to 43.0 kg for subcutaneous adipose tissue (SCAT), from 13.7 to 98.8 kg for abdominal adipose tissue (AAT), from 3.4 to 30.3 kg for retroperitoneal adipose tissue (RPAT), from 5.2 to 39.6 kg for omental adipose tissue (OMAT), and from 4.0 to 35.8 kg for mesenteric adipose tissue (MAT). The relationship between calculated amount of fat and slaughter weight of fat had coefficients of determination () and root mean square errors (kg) of 0.88 and 3.4, respectively, for SCAT; 0.94 and 6.1, respectively, for AAT; 0.94 and 1.7, respectively, for RPAT; 0.83 and 3.2, respectively, for OMAT; and 0.95 and 1.6, respectively, for MAT. The accuracy of ultrasonographic measurement of the different fat depots appears sufficient for the quantitative assessment of internal and subcutaneous fat stores in cows. This method is noninvasive and therefore allows safe and repeated monitoring of the amount of stored fat in different adipose tissue depots of German Holsteins cows.

  10. 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

  11. The endocrine function of adipose tissue

    Directory of Open Access Journals (Sweden)

    Wagner de Jesus Pinto

    2014-09-01

    Full Text Available Currently it is considered the adipose tissue as a dynamic structure involved in many physiological and metabolic processes, produces and releases a variety of active peptides known by the generic name of adipokines that act performing endocrine, paracrine and autocrine. Furthermore, numbers expressed receptors that respond allows the afferent signals from endocrine organs, and also central nervous system. In 1987, the adipose tissue has been identified as the major site of metabolism of steroid hormones, thereafter, in 1994, it was recognized as an endocrine organ and the leptin being an early secretory products identified. In addition other biologically active substances were being isolated, such as adiponectin, resistin, TNF-a, interleukin-6 and others. The adipokines derived from adipose tissue modulate many metabolic parameters such as control of food intake, energy balance and peripheral insulin sensitivity, for example. Thus, the altered secretion of adipokines by adipose tissue may have metabolic effects may present complex relations with the pathophysiological process of obesity, endothelial dysfunction, inflammation, atherosclerosis and Diabetes mellitus. The understanding of the molecular processes occurring in the adipocytes may provide new tools for the treatment of pathophysiological conditions such as, for example, metabolic syndrome, obesity and diabetes mellitus.

  12. Does bariatric surgery improve adipose tissue function?

    Science.gov (United States)

    Frikke-Schmidt, H.; O’Rourke, R. W.; Lumeng, C. N.; Sandoval, D. A.; Seeley, R. J.

    2017-01-01

    Summary Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. PMID:27272117

  13. Browning and thermogenic programing of adipose tissue.

    Science.gov (United States)

    Kiefer, Florian W

    2016-08-01

    The view of adipose tissue as solely a fat storing organ has changed significantly over the past two decades with the discoveries of numerous adipocyte-secreted factors, so called adipokines, and their endocrine functions throughout the body. The newest chapter added to this story is the finding that adipose tissue is also a thermogenic organ contributing to energy expenditure through actions of specialized, heat-producing brown or beige adipocytes. In contrast to bone fide brown adipocytes, beige cells develop within white fat depots in response to various stimuli such as prolonged cold exposure, underscoring the great thermogenic plasticity of adipose tissue. The energy dissipating properties of beige and/or brown adipocytes hold great promise as a novel therapeutic concept against obesity and related complications. Hence, identifying the specific thermogenic adipocyte populations in humans and their pathways of activation are key milestones of current metabolism research. Here we will discuss the recent advances in the understanding of the molecular and physiological mechanisms of adipose tissue browning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Does bariatric surgery improve adipose tissue function?

    Science.gov (United States)

    Frikke-Schmidt, H; O'Rourke, R W; Lumeng, C N; Sandoval, D A; Seeley, R J

    2016-09-01

    Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. © 2016 World Obesity.

  15. [White adipose tissue dysfunction observed in obesity].

    Science.gov (United States)

    Lewandowska, Ewa; Zieliński, Andrzej

    2016-05-01

    Obesity is a disease with continuingly increasing prevalence. It occurs worldwide independently of age group, material status or country of origin. At these times the most common reasons for obesity are bad eating habits and dramatic reduction of physical activity, which cause the energy imbalance of organism. Fundamental alteration observed in obese subjects is white adipose tissue overgrowth, which is linked to increased incidence of obesity-related comorbidities, such as: cardiovascular diseases, type 2 diabetes or digestive tract diseases. What is more, obesity is also a risk factor for some cancers. Special risk for diseases linked to excessive weight is associated with overgrowth of visceral type of adipose tissue. Adipose tissue, which is the main energy storehouse in body and acts also as an endocrine organ, undergoes both the morphological and the functional changes in obesity, having a negative impact on whole body function. In this article we summarize the most important alterations in morphology and function of white adipose tissue, observed in obese subjects.

  16. 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 ...

  17. High-affinity glutamate transporter and glutamine synthetase content in longissimus dorsi and adipose tissues of growing Angus steers differs among suckling, weanling, backgrounding, and finishing production stages.

    Science.gov (United States)

    Matthews, J C; Huang, J; Rentfrow, G

    2016-03-01

    Skeletal muscle and adipose tissues play important roles in maintaining whole-body Glu and N homeostasis by the uptake of Glu and release of Gln. To test the hypothesis that expression of high-affinity Glu transporters (GLAST1, EAAT4, EAAC1, GLT-1) and glutamine synthetase (GS) would increase in longissimus dorsi and adipose tissue of newborn Angus steers randomly assigned ( = 6) to develop through suckling (S; 32 d) and/or weanling (W; 184 d), backgrounding (B; 248 d), and finishing (F; 423 d) production stages. Carcass quality was determined at slaughter to verify shifts in adipose and lean deposition with development. Expression of mRNA (RT-PCR/Southern) and relative protein abundance (Western analysis) were determined in tissue homogenates isolated from longissimus dorsi, and kidney and subcutaneous adipose. The effect of production stage or tissue type on carcass and protein abundance was assessed by 1-way ANOVA using the GLM procedure of SAS, and Fisher's protected LSD procedure was used to separate data means. Neither GLAST1 nor EAAT4 mRNA or protein was detected. EAAC1, GLT-1, and GS mRNA were identified in all tissues, but GLT-1 and GS protein were not detected in kidney or subcutaneous adipose, and GS protein was not detected in longissimus dorsi. The EAAC1 content of subcutaneous ( = 0.06) and kidney ( = 0.02) adipose was 2 times greater in B and F than W steers, whereas GS was 5 times greater ( F). For longissimus dorsi, EAAC1 ( W > B = F, S = W > B = F, respectively). Within F steers, EAAC1 and GLT-1 mRNA was expressed by subcutaneous, kidney, omental, mesenchymal, and intramuscular adipose tissues, whereas GS mRNA was expressed by all except for intramuscular. Only EAAC1 protein was detected in any adipose tissue, with EAAC1 content being 104% and 112% greater ( adipose, respectively, and not differing ( > 0.45) from omental or mesenchymal adipose. These data demonstrate (1) longissimus dorsi and adipose tissues of steers developing through typical

  18. Comparison of Metabolic Network between Muscle and Intramuscular Adipose Tissues in Hanwoo Beef Cattle Using a Systems Biology Approach.

    Science.gov (United States)

    Lee, Hyun-Jeong; Park, Hye-Sun; Kim, Woonsu; Yoon, Duhak; Seo, Seongwon

    2014-01-01

    The interrelationship between muscle and adipose tissues plays a major role in determining the quality of carcass traits. The objective of this study was to compare metabolic differences between muscle and intramuscular adipose (IMA) tissues in the longissimus dorsi (LD) of Hanwoo (Bos taurus coreanae) using the RNA-seq technology and a systems biology approach. The LD sections between the 6th and 7th ribs were removed from nine (each of three cows, steers, and bulls) Hanwoo beef cattle (carcass weight of 430.2 ± 40.66 kg) immediately after slaughter. The total mRNA from muscle, IMA, and subcutaneous adipose and omental adipose tissues were isolated and sequenced. The reads that passed quality control were mapped onto the bovine reference genome (build bosTau6), and differentially expressed genes across tissues were identified. The KEGG pathway enrichment tests revealed the opposite direction of metabolic regulation between muscle and IMA. Metabolic gene network analysis clearly indicated that oxidative metabolism was upregulated in muscle and downregulated in IMA. Interestingly, pathways for regulating cell adhesion, structure, and integrity and chemokine signaling pathway were upregulated in IMA and downregulated in muscle. It is thus inferred that IMA may play an important role in the regulation of development and structure of the LD tissues and muscle/adipose communication.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Sustainable three-dimensional tissue model of human adipose tissue.

    Science.gov (United States)

    Bellas, Evangelia; Marra, Kacey G; Kaplan, David L

    2013-10-01

    The need for physiologically relevant sustainable human adipose tissue models is crucial for understanding tissue development, disease progression, in vitro drug development and soft tissue regeneration. The coculture of adipocytes differentiated from human adipose-derived stem cells, with endothelial cells, on porous silk protein matrices for at least 6 months is reported, while maintaining adipose-like outcomes. Cultures were assessed for structure and morphology (Oil Red O content and CD31 expression), metabolic functions (leptin, glycerol production, gene expression for GLUT4, and PPARγ) and cell replication (DNA content). The cocultures maintained size and shape over this extended period in static cultures, while increasing in diameter by 12.5% in spinner flask culture. Spinner flask cultures yielded improved adipose tissue outcomes overall, based on structure and function, when compared to the static cultures. This work establishes a tissue model system that can be applied to the development of chronic metabolic dysfunction systems associated with human adipose tissue, such as obesity and diabetes, due to the long term sustainable functions demonstrated here.

  1. Human omental adipose-derived mesenchymal stem cell-conditioned medium alters the proteomic profile of epithelial ovarian cancer cell lines in vitro

    Directory of Open Access Journals (Sweden)

    Zhang YL

    2017-03-01

    Full Text Available Yanling Zhang,1,* Weihong Dong,1,* Junjie Wang,2 Jing Cai,1 Zehua Wang1 1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of Obstetrics and Gynecology, Renhe Hospital, China Three Gorges University, Yichang, People’s Republic of China *These authors contributed equally to this work Abstract: Mesenchymal stem cells (MSCs have been reported to participate in the formation of supportive tumor stroma. The abilities of proliferation and invasion of human epithelial ovarian cancer (EOC cells were significantly enhanced when indirectly cocultured with human omental adipose-derived MSCs (O-ADSCs in vitro. However, the underlying mechanisms remain poorly understood. In this study, EOC cells were cultured with conditioned medium (CM from O-ADSCs (O-ADSC, and the effect of O-ADSC CM on the proteomic profile of EOC cells was assessed by two-dimensional gel electrophoresis (2-DE, followed by liquid chromatography and tandem mass spectrometry. The 2-DE assays revealed a global increase in protein expression in the EOC cells treated with CM. Nine proteins were identified from 11 selected protein spots with differential expression after treatment with CM from O-ADSCs. All the nine proteins have been linked to carcinoma and apoptosis, and the migration ability of tumor cells can be regulated by these proteins. Moreover, the upregulation of prohibitin and serine/arginine-rich splicing factor 1 in EOC cells treated with CM was further confirmed by quantitative real-time polymerase chain reaction. These results suggest that O-ADSCs affect the proteomic profile of EOC cells via paracrine mechanism in favor of EOC progression. Keywords: ovarian cancer, mesenchymal stromal cells, mesenchymal stem cells, omentum, proteomic

  2. The Facial Adipose Tissue: A Revision.

    Science.gov (United States)

    Kruglikov, Ilja; Trujillo, Oscar; Kristen, Quick; Isac, Kerelos; Zorko, Julia; Fam, Maria; Okonkwo, Kasie; Mian, Asima; Thanh, Hyunh; Koban, Konstantin; Sclafani, Anthony P; Steinke, Hanno; Cotofana, Sebastian

    2016-12-01

    Recent advantages in the anatomical understanding of the face have turned the focus toward the subcutaneous and deep facial fat compartments. During facial aging, these fat-filled compartments undergo substantial changes along with other structures in the face. Soft tissue filler and fat grafting are valid methods to fight the signs of facial aging, but little is known about their precise effect on the facial fat. This narrative review summarizes the current knowledge about the facial fat compartments in terms of anatomical location, histologic appearance, immune-histochemical characteristics, cellular interactions, and therapeutic options. Three different types of facial adipose tissue can be identified, which are located either superficially (dermal white adipose tissue) or deep (subcutaneous white adipose tissue): fibrous (perioral locations), structural (major parts of the midface), and deposit (buccal fat pad and deep temporal fat pad). These various fat types differ in the size of the adipocytes and the collagenous composition of their extracellular matrix and thus in their mechanical properties. Minimal invasive (e.g., soft tissue fillers or fat grafting) and surgical interventions aiming to restore the youthful face have to account for the different fat properties in various facial areas. However, little is known about the macro- and microscopic characteristics of the facial fat tissue in different compartments and future studies are needed to reveal new insights to better understand the process of aging and how to fight its signs best.

  3. Comparative Transcriptome Analysis of Adipose Tissues Reveals that ECM-Receptor Interaction Is Involved in the Depot-Specific Adipogenesis in Cattle.

    Directory of Open Access Journals (Sweden)

    Hyun-Jeong Lee

    Full Text Available Adipocytes mainly function as energy storage and endocrine cells. Adipose tissues showed the biological and genetic difference based on their depots. The difference of adipocytes between depots might be influenced by the inherent genetic programing for adipogenesis. We used RNA-seq technique to investigate the transcriptomes in 3 adipose tissues of omental (O, subcutaneous (S and intramuscular (I fats in cattle. Sequence reads were obtained from Illumina HiSeq2000 and mapped to the bovine genome using Tophat2. Differentially expressed genes (DEG between adipose tissues were detected by EdgeR. We identified 5797, 2156, and 5455 DEGs in the comparison between OI, OS, and IS respectively and also found 5657 DEGs in the comparison between the intramuscular and the combined omental and subcutaneous fats (C (FDR<0.01. Depot specifically up- and down- regulated DEGs were 853 in S, 48 in I, and 979 in O. The numbers of DEGs and functional annotation studies suggested that I had the different genetic profile compared to other two adipose tissues. In I, DEGs involved in the developmental process (eg. EGR2, FAS, and KLF7 were up-regulated and those in the immune system process were down-regulated. Many DEGs from the adipose tissues were enriched in the various GO terms of developmental process and KEGG pathway analysis showed that the ECM-receptor interaction was one of commonly enriched pathways in all of the 3 adipose tissues and also functioned as a sub-pathway of other enriched pathways. However, genes involved in the ECM-receptor interaction were differentially regulated depending on the depots. Collagens, main ECM constituents, were significantly up-regulated in S and integrins, transmembrane receptors, were up-regulated in I. Different laminins were up-regulated in the different depots. This comparative transcriptome analysis of three adipose tissues suggested that the interactions between ECM components and transmembrane receptors of fat cells

  4. Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle.

    Science.gov (United States)

    Tran, Ha T; Liong, Stella; Lim, Ratana; Barker, Gillian; Lappas, Martha

    2017-01-01

    Gestational diabetes mellitus (GDM), which complicates up to 20% of all pregnancies, is associated with low-grade maternal inflammation and peripheral insulin resistance. Sterile inflammation and infection are key mediators of this inflammation and peripheral insulin resistance. Resveratrol, a stilbene-type phytophenol, has been implicated to exert beneficial properties including potent anti-inflammatory and antidiabetic effects in non-pregnant humans and experimental animal models of GDM. However, studies showing the effects of resveratrol on inflammation and insulin resistance associated with GDM in human tissues have been limited. In this study, human placenta, adipose (omental and subcutaneous) tissue and skeletal muscle were stimulated with pro-inflammatory cytokines TNF-α and IL-1β, the bacterial product lipopolysaccharide (LPS) and the synthetic viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) to induce a GDM-like model. Treatment with resveratrol significantly reduced the expression and secretion of pro-inflammatory cytokines IL-6, IL-1α, IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in human placenta and omental and subcutaneous adipose tissue. Resveratrol also significantly restored the defects in the insulin signalling pathway and glucose uptake induced by TNF-α, LPS and poly(I:C). Collectively, these findings suggest that resveratrol reduces inflammation and insulin resistance induced by chemical and microbial products. Resveratrol may be a useful preventative therapeutic for pregnancies complicated by inflammation and insulin resistance, like GDM.

  5. Adipose tissue remodeling in pathophysiology of obesity.

    Science.gov (United States)

    Lee, Mi-Jeong; Wu, Yuanyuan; Fried, Susan K

    2010-07-01

    Recent studies demonstrate that adipose tissue undergoes a continuous process of remodeling that is pathologically accelerated in the obese state. Contrary to earlier dogma, adipocytes die and are replaced by newly differentiated ones. This review will summarize recent advances of our knowledge of the mechanisms that regulate adipose tissue remodeling and highlight the influences of obesity, depot, and sex, as well as the relevance of rodent models to humans. A substantial literature now points to the importance of dynamic changes in adipocyte and immune cell turnover, angiogenesis, and extracellular matrix remodeling in regulating the expandability and functional integrity of this tissue. In obesity, the macrophages are recruited, surrounding dead adipocytes and polarized toward an inflammatory phenotype. The number of dead adipocytes is closely associated with the pathophysiological consequences of obesity, including insulin resistance and hepatic steatosis. Further, there are substantial depot, sex and species differences in the extent of remodeling. Adipose tissue undergoes a continuous remodeling process that normally maintains tissue health, but may spin out of control and lead to adipocyte death in association with the recruitment and activation of macrophages, and systemic insulin resistance.

  6. Proteomic characterization of adipose tissue constituents, a necessary step for understanding adipose tissue complexity.

    Science.gov (United States)

    Peinado, Juan R; Pardo, María; de la Rosa, Olga; Malagón, Maria M

    2012-02-01

    The original concept of adipose tissue as an inert storage depot for the excess of energy has evolved over the last years and it is now considered as one of the most important organs regulating body homeostasis. This conceptual change has been supported by the demonstration that adipose tissue serves as a major endocrine organ, producing a wide variety of bioactive molecules, collectively termed adipokines, with endocrine, paracrine and autocrine activities. Adipose tissue is indeed a complex organ wherein mature adipocytes coexist with the various cell types comprising the stromal-vascular fraction (SVF), including preadipocytes, adipose-derived stem cells, perivascular cells, and blood cells. It is known that not only mature adipocytes but also the components of SVF produce adipokines. Furthermore, adipokine production, proliferative and metabolic activities and response to regulatory signals (i.e. insulin, catecholamines) differ between the different fat depots, which have been proposed to underlie their distinct association to specific diseases. Herein, we discuss the recent proteomic studies on adipose tissue focused on the analysis of the separate cellular components and their secretory products, with the aim of identifying the basic features and the contribution of each component to different adipose tissue-associated pathologies.

  7. Testosterone stimulates adipose tissue 11beta-hydroxysteroid dehydrogenase type 1 expression in a depot-specific manner in children.

    Science.gov (United States)

    Zhu, Lijun; Hou, Miao; Sun, Bin; Burén, Jonas; Zhang, Li; Yi, Jun; Hernell, Olle; Li, Xiaonan

    2010-07-01

    Activation of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in adipose tissue results in the production of excess tissue glucocorticoids and the induction of adiposity and visceral obesity in particular. Androgens may affect body fat distribution by regulating the local metabolism of cortisol. Our objective was to study 11beta-HSD1 mRNA expression in abdominal sc and omental (om) adipose tissue in children after in vitro testosterone and cortisol treatment. Paired fat biopsies (sc and om) were obtained from 19 boys (age 6-14 yr, body mass index 14.6-25.3 kg/m(2), BMI sd score SDS -1.6-3.1) undergoing open abdominal surgery. Pieces of adipose tissue were incubated with testosterone, cortisol, or both hormones for 24 h, whereupon mRNA expression of 11beta-HSD1 and hexose-6-phosphate dehydrogenase (H6PDH) were measured by real-time PCR, and 11beta-HSD1 enzyme activity was determined. Testosterone treatment up-regulated 11beta-HSD1 mRNA expression compared with control incubations in the absence of testosterone (P tissue. Testosterone and cortisol both increased 11beta-HSD1 mRNA expression in om but not sc adipose tissue in a depot-specific manner by 2.5- and 2.9-fold, respectively (P effect of the two hormones. 11beta-HSD1 enzyme activity correlated positively to mRNA expression (r = 0.610; P = 0.001). Adipose tissue mRNA expression of H6PDH was affected in a similar fashion to 11beta-HSD1 after hormonal treatment. Testosterone and cortisol stimulated 11beta-HSD1 and H6PDH mRNA expression and 11beta-HSD1 activity in om but not in sc adipose tissue. This suggests that these hormones may contribute to fat distribution and accumulation during childhood.

  8. Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue.

    Science.gov (United States)

    Gathercole, Laura L; Morgan, Stuart A; Bujalska, Iwona J; Hauton, David; Stewart, Paul M; Tomlinson, Jeremy W

    2011-01-01

    Patients with glucocorticoid (GC) excess, Cushing's syndrome, develop a classic phenotype characterized by central obesity and insulin resistance. GCs are known to increase the release of fatty acids from adipose, by stimulating lipolysis, however, the impact of GCs on the processes that regulate lipid accumulation has not been explored. Intracellular levels of active GC are dependent upon the activity of 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) and we have hypothesized that 11β-HSD1 activity can regulate lipid homeostasis in human adipose tissue (Chub-S7 cell line and primary cultures of human subcutaneous (sc) and omental (om) adipocytes. Across adipocyte differentiation, lipogenesis increased whilst β-oxidation decreased. GC treatment decreased lipogenesis but did not alter rates of β-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models. Low dose Dexamethasone pre-treatment (5 nM) of Chub-S7 cells augmented the ability of insulin to stimulate lipogenesis and there was no evidence of adipose tissue insulin resistance in primary sc cells. Both cortisol and cortisone decreased lipogenesis; selective 11β-HSD1 inhibition completely abolished cortisone-mediated repression of lipogenesis. GCs have potent actions upon lipid homeostasis and these effects are dependent upon interactions with insulin. These in vitro data suggest that manipulation of GC availability through selective 11β-HSD1 inhibition modifies lipid homeostasis in human adipocytes.

  9. Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue.

    Directory of Open Access Journals (Sweden)

    Laura L Gathercole

    Full Text Available Patients with glucocorticoid (GC excess, Cushing's syndrome, develop a classic phenotype characterized by central obesity and insulin resistance. GCs are known to increase the release of fatty acids from adipose, by stimulating lipolysis, however, the impact of GCs on the processes that regulate lipid accumulation has not been explored. Intracellular levels of active GC are dependent upon the activity of 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 and we have hypothesized that 11β-HSD1 activity can regulate lipid homeostasis in human adipose tissue (Chub-S7 cell line and primary cultures of human subcutaneous (sc and omental (om adipocytes. Across adipocyte differentiation, lipogenesis increased whilst β-oxidation decreased. GC treatment decreased lipogenesis but did not alter rates of β-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models. Low dose Dexamethasone pre-treatment (5 nM of Chub-S7 cells augmented the ability of insulin to stimulate lipogenesis and there was no evidence of adipose tissue insulin resistance in primary sc cells. Both cortisol and cortisone decreased lipogenesis; selective 11β-HSD1 inhibition completely abolished cortisone-mediated repression of lipogenesis. GCs have potent actions upon lipid homeostasis and these effects are dependent upon interactions with insulin. These in vitro data suggest that manipulation of GC availability through selective 11β-HSD1 inhibition modifies lipid homeostasis in human adipocytes.

  10. Influence of adipocyte size and adipose depot on the in vitro lipolytic activity and insulin sensitivity of adipose tissue in dairy cows at the end of the dry period.

    Science.gov (United States)

    De Koster, J; Van den Broeck, W; Hulpio, L; Claeys, E; Van Eetvelde, M; Hermans, K; Hostens, M; Fievez, V; Opsomer, G

    2016-03-01

    The aim of the present research was to describe characteristics of adipose tissue lipolysis in dairy cows with a variable body condition score (BCS). Ten clinically healthy Holstein Friesian cows were selected based on BCS and euthanized 10 to 13 d before the expected parturition date. Immediately after euthanasia, adipose tissue samples were collected from subcutaneous and omental fat depots. In both depots, we observed an increase in adipocyte size with increasing BCS. Using an in vitro explant culture of subcutaneous and omental adipose tissue, we aimed to determine the influence of adipocyte size and localization of adipose depot on the lipolytic activity in basal conditions and after addition of isoproterenol (nonselective β-agonist) and insulin in different concentrations. Glycerol release in the medium was used as a measure for lipolytic activity. We observed that the basal lipolytic activity of subcutaneous and omental adipose tissue increased with adipocyte volume, meaning that larger fat cells have higher basal lipolytic activity independent of the location of the adipose depot. Dose-response curves were created between the concentration of isoproterenol or insulin and the amount of glycerol released. The shape of the dose-response curves is determined by the concentration of isoproterenol and insulin needed to elicit the half-maximal effect and the maximal amount of stimulated glycerol release or the maximal inhibitory effect of insulin. We observed that larger fat cells released more glycerol upon maximal stimulation with isoproterenol and this was more pronounced in subcutaneous adipose tissue. Additionally, larger fat cells had a higher sensitivity toward lipolytic signals. We observed a trend for larger adipocytes to be more resistant to the maximal antilipolytic effect of insulin. The insulin concentration needed to elicit the half-maximal inhibitory effect of insulin was within the physiological range of insulin and was not influenced by adipocyte

  11. Oestrone sulphate, adipose tissue, and breast cancer.

    Science.gov (United States)

    Hawkins, R A; Thomson, M L; Killen, E

    1985-01-01

    Oestrone sulphate, the oestrogen in highest concentration in the plasma, may play a role in the induction and growth of breast cancers. By enzymolysis and radioimmunoassay, oestrone sulphate concentrations were measured in 3 biological fluids. High concentrations of the conjugate (up to 775 nmol/l) were detected in breast cyst fluids from some premenopausal women, the concentrations in blood plasma (0.91-4.45 nmol/l) being much lower. Concentrations in the plasmas from postmenopausal women with (0.23-4.63 nmol/l) or without (0.18-1.27 nmol/l) breast cancer were still lower. Oestrone sulphate concentration in cow's milk or cream (0.49-0.67 nmol/l) was also low: dietary intake in these fluids is probably of little consequence. The capacity of breast tissues for hydrolysis of oestrone sulphate was examined in two ways: In tissue slices incubated with 85 pM (3H) oestrone sulphate solution at 37 degrees C, cancers (131-412 fmol/g tissue/hr) and adipose tissues (23-132 fmol/g tissue/hr) hydrolysed significantly more sulphate than did benign tissues (1-36 fmol/g tissue/hr). In tissue homogenates incubated with 5-25 microM [3H] oestrone sulphate at 37 degrees much higher capacities for hydrolysis (nmol/g tissue/hr) were demonstrated with a Km of 2-16.5 microM: cancers (34-394) and benign tissues (9-485) had significantly higher sulphatase activities than adipose tissues (9-39). On a protein basis, however, the sulphatase activities in the 3 tissues were comparable. It is concluded that oestrone sulphate is present in breast cysts and blood plasma and that in vitro, the conjugated hormone can be hydrolysed by breast tissues. The biological significance of these findings in vivo remains to be established.

  12. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

    DEFF Research Database (Denmark)

    Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.

    1999-01-01

    report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high...

  13. Sex dimorphism and depot differences in adipose tissue function.

    Science.gov (United States)

    White, Ursula A; Tchoukalova, Yourka D

    2014-03-01

    Obesity, characterized by excessive adiposity, is a risk factor for many metabolic pathologies, such as type 2 diabetes mellitus (T2DM). Numerous studies have shown that adipose tissue distribution may be a greater predictor of metabolic health. Upper-body fat (visceral and subcutaneous abdominal) is commonly associated with the unfavorable complications of obesity, while lower-body fat (gluteal-femoral) may be protective. Current research investigations are focused on analyzing the metabolic properties of adipose tissue, in order to better understand the mechanisms that regulate fat distribution in both men and women. This review will highlight the adipose tissue depot- and sex-dependent differences in white adipose tissue function, including adipogenesis, adipose tissue developmental patterning, the storage and release of fatty acids, and secretory function. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

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

    Science.gov (United States)

    Kang, Yea Eun; Kim, Ji Min; Joung, Kyong Hye; Lee, Ju Hee; You, Bo Ram; Choi, Min Jeong; Ryu, Min Jeong; Ko, Young Bok; Lee, Min A; Lee, Junguee; Ku, Bon Jeong; Shong, Minho; Lee, Ki Hwan; Kim, Hyun Jin

    2016-01-01

    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 leptin have specific

  15. Perivascular Adipose Tissue and Cardiometabolic Disease

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2013-04-01

    Full Text Available BACKGROUND: Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity. CONTENT: Perivascular adipose tissue (PVAT is a local deposit of adipose tissue surrounding the vasculature. PVAT is present throughout the body and has been shown to have a local effect on blood vessels. The influence of PVAT on the vasculature changes with increasing adiposity. PVAT similarly to other fat depots, is metabolically active, secreting a wide array of bioactive substances, termed ‘adipokines’. Adipokines include cytokines, chemokines and hormones that can act in a paracrine, autocrine or endocrine fashion. Many of the proinflammatory adipokines upregulated in obesity are known to influence vascular function, including endothelial function, oxidative stress, vascular stiffness and smooth muscle migration. Adipokines also stimulate immune cell migration into the vascular wall, potentially contributing to the inflammation found in atherosclerosis. Finally, adipokines modulate the effect of insulin on the vasculature, thereby decreasing insulin-mediated muscle glucose uptake. This leads to alterations in nitric oxide signaling, insulin resistance and potentially atherogenesis. SUMMARY: PVAT surrounds blood vessels. PVAT and the adventitial layer of blood vessels are in direct contact with each other. Healthy PVAT secretes adipokines and regulates vascular function. Obesity is associated with changes in adipokine secretion and the resultant inflammation of PVAT. The dysregulation of adipokines changes the effect of PVAT on the vasculature. Changes in perivascular adipokines secretion in obesity appear to contribute to the development of obesity-mediated vascular disease. KEYWORDS: obesity, perivascular adipose tissue, PVAT

  16. Differentially expressed genes in adipocytokine signaling pathway of adipose tissue in pregnancy

    OpenAIRE

    Ogunyemi, Dotun; Xu, Jun; Mahesan, Arnold M.; Rad, Steve; Kim, Eric; Yano, Jacqueline; Alexander, Carolyn; Rotter, Jerome I.; Chen, Y.-D. Ida

    2013-01-01

    Objective To profile the differential gene expression of the KEGG Adipocytokine Signaling pathway in omental compared to subcutaneous tissue in normal pregnancy. Study Design Subjects included 14 nonobese, normal glucose tolerant, healthy pregnant women. Matched omental and subcutaneous tissue were obtained at elective cesarean delivery. Gene expression was evaluated using microarray and validated by RT-PCR. Differential gene expression was defined as ≥1.5 fold increase at p < 0.05. Results S...

  17. Glycation and Hypoxia: Two Key Factors for Adipose Tissue Dysfunction.

    Science.gov (United States)

    Matafome, Paulo; Rodrigues, Tiago; Seica, Raquel

    2015-01-01

    Many aspects of adipose tissue pathophysiology in metabolic diseases have been described in the last years. One of such aspects is certainly hypoxia, which was shown to develop in adipose tissue of obese individuals and animal models. Recent data suggest two main factors for adipose tissue hypoxia: adipocyte hypertrophy and vascular dysfunction. In addition, glycation was also shown to induce morphological and functional alterations in adipose tissue. In particular, methylglyoxal directly formed from glucose was shown to potently induce AGE formation in vivo and to contribute to metabolic and vascular alterations in adipose tissue. Glycation and hypoxia are both thought to be on the basis of low grade inflammatory activation, further increasing metabolic dysregulation in adipose tissue. This review summarizes the current knowledge about the factors that contribute for tissue hypoxia and the role of glycation, not only at the vascular level, but also at the metabolic, oxidative and inflammatory levels.

  18. Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines.

    Science.gov (United States)

    Halleux, C M; Declerck, P J; Tran, S L; Detry, R; Brichard, S M

    1999-11-01

    Plasma levels of type 1 plasminogen activator inhibitor (PAI-1), a risk factor for cardiovascular disease, are elevated in obese subjects, especially those with omental fat accumulation. We investigated the hormonal control of PAI-1 gene expression and secretion in cultured human adipose tissue. We more particularly focused on the effects of glucocorticoids, insulin, cAMP, and catecholamines in explants from the omental region. The addition of dexamethasone to the culture medium increased PAI-1 secretion in a time-dependent manner for up to 24 h. The stimulation by the glucocorticoid was preceded by a 2-fold rise in PAI-1 messenger ribonucleic acid levels between 4-8 h of culture. The effectiveness of the glucocorticoid was concentration dependent, with a half-maximal effect within a physiological range. This stimulation was also observed in sc fat, but dexamethasone-stimulated as well as basal PAI-1 secretion rates were always higher in omental fat. Unlike dexamethasone, 24-h insulin did not modify PAI-1 secretion while accelerating glucose consumption. In contrast, 24-h cAMP inhibited PAI-1 gene expression and protein production under basal conditions and in the presence of dexamethasone. This inhibition was already detectable after 1 h and was maximal after 4 h at the level of gene expression. It occurred in both omental and sc adipose tissues. Importantly, epinephrine dose dependently inhibited PAI-1 parameters, an effect that was reproduced by isoproterenol. Dexamethasone- and cAMP-induced changes in PAI-1 messenger ribonucleic acid abundance were similar in explants and isolated fat cells. In isolated stromal-vascular cells, only dexamethasone was effective. In conclusion, we provide evidence for a reciprocal regulation of PAI-1 by dexamethasone (positive effector) and cAMP/catecholamines (negative effectors) in cultured human adipose tissue. The stimulation by glucocorticoids could contribute to enhanced production of PAI-1 by adipose tissue and high plasma

  19. Adipose tissue angiogenesis: impact on obesity and type-2 diabetes.

    Science.gov (United States)

    Corvera, Silvia; Gealekman, Olga

    2014-03-01

    The growth and function of tissues are critically dependent on their vascularization. Adipose tissue is capable of expanding many-fold during adulthood, therefore requiring the formation of new vasculature to supply growing and proliferating adipocytes. The expansion of the vasculature in adipose tissue occurs through angiogenesis, where new blood vessels develop from those pre-existing within the tissue. Inappropriate angiogenesis may underlie adipose tissue dysfunction in obesity, which in turn increases type-2 diabetes risk. In addition, genetic and developmental factors involved in vascular patterning may define the size and expandability of diverse adipose tissue depots, which are also associated with type-2 diabetes risk. Moreover, the adipose tissue vasculature appears to be the niche for pre-adipocyte precursors, and factors that affect angiogenesis may directly impact the generation of new adipocytes. Here we review recent advances on the basic mechanisms of angiogenesis, and on the role of angiogenesis in adipose tissue development and obesity. A substantial amount of data points to a deficit in adipose tissue angiogenesis as a contributing factor to insulin resistance and metabolic disease in obesity. These emerging findings support the concept of the adipose tissue vasculature as a source of new targets for metabolic disease therapies. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  20. The potential roles for adipose tissue in peripheral nerve regeneration.

    Science.gov (United States)

    Walocko, Frances M; Khouri, Roger K; Urbanchek, Melanie G; Levi, Benjamin; Cederna, Paul S

    2016-01-01

    This review summarizes current understanding about the role of adipose-derived tissues in peripheral nerve regeneration and discusses potential advances that would translate this approach into the clinic. We searched PubMed for in vivo, experimental studies on the regenerative effects of adipose-derived tissues on peripheral nerve injuries. We summarized the methods and results for the 42 experiments. Adipose-derived tissues enhanced peripheral nerve regeneration in 86% of the experiments. Ninety-five percent evaluated purified, cultured, or differentiated adipose tissue. These approaches have regulatory and scaling burdens, restricting clinical usage. Only one experiment tested the ability of adipose tissue to enhance nerve regeneration in conjunction with nerve autografts, the clinical gold standard. Scientific studies illustrate that adipose-derived tissues enhance regeneration of peripheral nerves. Before this approach achieves clinical acceptance, fat processing must become automated and regulatory approval achieved. Animal studies using whole fat grafts are greatly needed for clinical translation. © 2015 Wiley Periodicals, Inc.

  1. Adipose tissue and its role in organ crosstalk.

    Science.gov (United States)

    Romacho, T; Elsen, M; Röhrborn, D; Eckel, J

    2014-04-01

    The discovery of adipokines has revealed adipose tissue as a central node in the interorgan crosstalk network, which mediates the regulation of multiple organs and tissues. Adipose tissue is a true endocrine organ that produces and secretes a wide range of mediators regulating adipose tissue function in an auto-/paracrine manner and important distant targets, such as the liver, skeletal muscle, the pancreas and the cardiovascular system. In metabolic disorders such as obesity, enlargement of adipocytes leads to adipose tissue dysfunction and a shift in the secretory profile with an increased release of pro-inflammatory adipokines. Adipose tissue dysfunction has a central role in the development of insulin resistance, type 2 diabetes, and cardiovascular diseases. Besides the well-acknowledged role of adipokines in metabolic diseases, and the increasing number of adipokines being discovered in the last years, the mechanisms underlying the release of many adipokines from adipose tissue remain largely unknown. To combat metabolic diseases, it is crucial to better understand how adipokines can modulate adipose tissue growth and function. Therefore, we will focus on adipokines with a prominent role in auto-/paracrine crosstalk within the adipose tissue such as RBP4, HO-1, WISP2, SFRPs and chemerin. To depict the endocrine crosstalk between adipose tissue with skeletal muscle, the cardiovascular system and the pancreas, we will report the main findings regarding the direct effects of adiponectin, leptin, DPP4 and visfatin on skeletal muscle insulin resistance, cardiovascular function and β-cell growth and function.

  2. Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

    Science.gov (United States)

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

    Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues

  3. Thyroid hormone status defines brown adipose tissue activity and browning of white adipose tissues in mice.

    Science.gov (United States)

    Weiner, Juliane; Kranz, Mathias; Klöting, Nora; Kunath, Anne; Steinhoff, Karen; Rijntjes, Eddy; Köhrle, Josef; Zeisig, Vilia; Hankir, Mohammed; Gebhardt, Claudia; Deuther-Conrad, Winnie; Heiker, John T; Kralisch, Susan; Stumvoll, Michael; Blüher, Matthias; Sabri, Osama; Hesse, Swen; Brust, Peter; Tönjes, Anke; Krause, Kerstin

    2016-12-12

    The present study aimed to determine the effect of thyroid hormone dysfunction on brown adipose tissue activity and white adipose tissue browning in mice. Twenty randomized female C57BL/6NTac mice per treatment group housed at room temperature were rendered hypothyroid or hyperthyroid. In-vivo small animal (18)F-FDG PET/MRI was performed to determine the effects of hypo- and hyperthyroidism on BAT mass and BAT activity. Ex-vivo(14)C-acetate loading assay and assessment of thermogenic gene and protein expression permitted analysis of oxidative and thermogenic capacities of WAT and BAT of eu-, hyper and hypothyroid mice. (18)F-FDG PET/MRI revealed a lack of brown adipose tissue activity in hypothyroid mice, whereas hyperthyroid mice displayed increased BAT mass alongside enhanced (18)F-FDG uptake. In white adipose tissue of both, hyper- and hypothyroid mice, we found a significant induction of thermogenic genes together with multilocular adipocytes expressing UCP1. Taken together, these results suggest that both the hyperthyroid and hypothyroid state stimulate WAT thermogenesis most likely as a consequence of enhanced adrenergic signaling or compensation for impaired BAT function, respectively.

  4. Obesity induces a phenotypic switch in adipose tissue macrophage polarization

    OpenAIRE

    Lumeng, Carey N.; Bodzin, Jennifer L.; Alan R Saltiel

    2007-01-01

    Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80+CD11c+ population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or “alternatively activated” macrophages, i...

  5. Brown adipose tissue in cetacean blubber.

    Directory of Open Access Journals (Sweden)

    Osamu Hashimoto

    Full Text Available Brown adipose tissue (BAT plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall's and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1, within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool

  6. Brown adipose tissue in cetacean blubber.

    Science.gov (United States)

    Hashimoto, Osamu; Ohtsuki, Hirofumi; Kakizaki, Takehiko; Amou, Kento; Sato, Ryo; Doi, Satoru; Kobayashi, Sara; Matsuda, Ayaka; Sugiyama, Makoto; Funaba, Masayuki; Matsuishi, Takashi; Terasawa, Fumio; Shindo, Junji; Endo, Hideki

    2015-01-01

    Brown adipose tissue (BAT) plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall's and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1), within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT) scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool waters during

  7. Brain-adipose tissue neural crosstalk.

    Science.gov (United States)

    Bartness, Timothy J; Song, C Kay

    2007-07-24

    The preponderance of basic obesity research focuses on its development as affected by diet and other environmental factors, genetics and their interactions. By contrast, we have been studying the reversal of a naturally-occurring seasonal obesity in Siberian hamsters. In the course of this work, we determined that the sympathetic innervation of white adipose tissue (WAT) is the principal initiator of lipid mobilization not only in these animals, but in all mammals including humans. We present irrefutable evidence for the sympathetic nervous system (SNS) innervation of WAT with respect to neuroanatomy (including its central origins as revealed by transneuronal viral tract tracers), neurochemistry (norepinephrine turnover studies) and function (surgical and chemical denervation). A relatively unappreciated role of WAT SNS innervation also is reviewed--the control of fat cell proliferation as shown by selective chemical denervation that triggers adipocyte proliferation, although the precise mechanism by which this occurs presently is unknown. There is no, however, equally strong evidence for the parasympathetic innervation of this tissue; indeed, the data largely are negative severely questioning its existence and importance. Convincing evidence also is given for the sensory innervation of WAT (as shown by tract tracing and by markers for sensory nerves in WAT), with suggestive data supporting a possible role in conveying information on the degree of adiposity to the brain. Collectively, these data offer an additional or alternative view to the predominate one of the control of body fat stores via circulating factors that serve as efferent and afferent communicators.

  8. Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation.

    Science.gov (United States)

    Huang, Zhi H; Reardon, Catherine A; Getz, Godfrey S; Maeda, Nobuyo; Mazzone, Theodore

    2015-02-01

    apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state.

  9. Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

    2011-03-04

    Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

  10. Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation

    Science.gov (United States)

    Huang, Zhi H.; Reardon, Catherine A.; Getz, Godfrey S.; Maeda, Nobuyo; Mazzone, Theodore

    2015-01-01

    apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state. PMID:25421060

  11. Macrophage elastase suppresses white adipose tissue expansion with cigarette smoking.

    Science.gov (United States)

    Tsuji, Takao; Kelly, Neil J; Takahashi, Saeko; Leme, Adriana S; Houghton, A McGarry; Shapiro, Steven D

    2014-12-01

    Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced emphysema, yet its role in other smoking related pathologies remains unclear. The weight suppressing effects of smoking are a major hindrance to cessation efforts, and MMP12 is known to suppress the vascularization on which adipose tissue growth depends by catalyzing the formation of antiangiogenic peptides endostatin and angiostatin. The goal of this study was to determine the role of MMP12 in adipose tissue growth and smoking-related suppression of weight gain. Whole body weights and white adipose depots from wild-type and Mmp12-deficient mice were collected during early postnatal development and after chronic CS exposure. Adipose tissue specimens were analyzed for angiogenic and adipocytic markers and for content of the antiangiogenic peptides endostatin and angiostatin. Cultured 3T3-L1 adipocytes were treated with adipose tissue homogenate to examine its effects on vascular endothelial growth factor (VEGF) expression and secretion. MMP12 content and activity were increased in the adipose tissue of wild-type mice at 2 weeks of age, leading to elevated endostatin production, inhibition of VEGF secretion, and decreased adipose tissue vascularity. By 8 weeks of age, adipose MMP12 levels subsided, and the protein was no longer detectable. However, chronic CS exposure led to macrophage accumulation and restored adipose MMP12 activity, thereby suppressing adipose tissue mass and vascularity. Our results reveal a novel systemic role for MMP12 in postnatal adipose tissue expansion and smoking-associated weight loss by suppressing vascularity within the white adipose tissue depots.

  12. Depot-specific Regulation of the Conversion of Cortisone to Cortisol in Human Adipose Tissue

    Science.gov (United States)

    Lee, Mi-Jeong; Fried, Susan K.; Mundt, Steven S.; Wang, Yanxin; Sullivan, Sean; Stefanni, Alice; Daugherty, Bruce L.; Hermanowski-Vosatka, Anne

    2015-01-01

    Objective Our main objective was to compare the regulation of cortisol production within omental (Om) and abdominal subcutaneous (Abd sc) human adipose tissue. Methods and Procedures Om and Abd sc adipose tissue were obtained at surgery from subjects with a wide range of BMI. Hydroxysteroid dehydrogenase (HSD) activity (3H-cortisone and 3H-cortisol interconversion) and expression were measured before and after organ culture with insulin and/or dexamethasone. Results Type 1 HSD (HSD1) mRNA and reductase activity were mainly expressed within adipocytes and tightly correlated with adipocyte size within both depots. There was no depot difference in HSD1 expression or reductase activity, while cortisol inactivation and HSD2 mRNA expression (expressed in stromal cells) were higher in Om suggesting higher cortisol turnover in this depot. Culture with insulin decreased HSD reductase activity in both depots. Culture with dexamethasone plus insulin compared to insulin alone increased HSD reductase activity only in the Om depot. This depot-specific increase in reductase activity could not be explained by an alteration in HSD1 mRNA or protein, which was paradoxically decreased. However, in Om only, hexose-6-phosphate dehydrogenase (H6PDH) mRNA levels were increased by culture with dexamethasone plus insulin compared to insulin alone, suggesting that higher nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) production within the endoplasmic reticulum (ER) contributed to the higher HSD reductase activity. Discussion We conclude that in the presence of insulin, glucocorticoids cause a depot-specific increase in the activation of cortisone within Om adipose tissue, and that this mechanism may contribute to adipocyte hypertrophy and visceral obesity. PMID:18388900

  13. Adipokines and the Endocrine Role of Adipose Tissues.

    Science.gov (United States)

    Giralt, Marta; Cereijo, Rubén; Villarroya, Francesc

    2016-01-01

    The last two decades have witnessed a shift in the consideration of white adipose tissue as a mere repository of fat to be used when food becomes scarce to a true endocrine tissue releasing regulatory signals, the so-called adipokines, to the whole body. The control of eating behavior, the peripheral insulin sensitivity, and even the development of the female reproductive system are among the physiological events controlled by adipokines. Recently, the role of brown adipose tissue in human physiology has been recognized. The metabolic role of brown adipose tissue is opposite to white fat; instead of storing fat, brown adipose tissue is a site of energy expenditure via adaptive thermogenesis. There is growing evidence that brown adipose tissue may have its own pattern of secreted hormonal factors, the so-called brown adipokines, having distinctive biological actions on the overall physiological adaptations to enhance energy expenditure.

  14. Cell supermarket: Adipose tissue as a source of stem cells

    Science.gov (United States)

    Adipose tissue is derived from numerous sources, and in recent years has been shown to provide numerous cells from what seemingly was a population of homogeneous adipocytes. Considering the types of cells that adipose tissue-derived cells may form, these cells may be useful in a variety of clinical ...

  15. Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects

    DEFF Research Database (Denmark)

    Arngrim, N; Simonsen, L; Holst, Jens Juul

    2012-01-01

    The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after ...... online publication, 3 July 2012; doi:10.1038/ijo.2012.98....

  16. Adipose tissue macrophages: going off track during obesity

    NARCIS (Netherlands)

    Boutens, L.; Stienstra, R.

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically

  17. Local and systemic effects of visceral and perivascular adipose tissue

    NARCIS (Netherlands)

    Verhagen, S.N.

    2012-01-01

    Rather than being solely a storage depot for triglycerides, adipose tissue is able to secrete pro- and anti-inflammatory cytokines and adipokines. A state of low grade inflammation associated with excess adipose tissue is involved in the increase in the incidences of atherosclerotic diseases and

  18. Adipose tissue macrophages: going off track during obesity

    NARCIS (Netherlands)

    Boutens, L.; Stienstra, R.

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically focuse

  19. Relations between antioxidant vitamins in adipose tissue, plasma, and diet

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Veer, P. van 't; Brants, H.A.M.; Berg, H. van den; Schoonhoven, J. van; Hermus, R.J.J.

    1995-01-01

    For an evaluation of fat-soluble vitamin concentrations in adipose tissue as biomarkers of intake, estimates of usual intake of β-carotene, total vitamin A, and vitamin E (assessed by food frequency questionnaire) were compared with plasma and adipose tissue concentrations of β-carotene, retinol, an

  20. Characterization of the human visceral adipose tissue secretome

    NARCIS (Netherlands)

    Alvarez Llamas, Gloria; Szalowska, Ewa; de Vries, Marcel P.; Weening, Desiree; Landman, Karloes; Hoek, Annemieke; Wolffenbuttel, Bruce H. R.; Roelofsen, Johan; Vonk, Roel J.

    2007-01-01

    Adipose tissue is an endocrine organ involved in storage and release of energy but also in regulation of energy metabolism in other organs via secretion of peptide and protein hormones (adipokines). Especially visceral adipose tissue has been implicated in the development of metabolic syndrome and t

  1. Involvement of mast cells in adipose tissue fibrosis.

    Science.gov (United States)

    Hirai, Shizuka; Ohyane, Chie; Kim, Young-Il; Lin, Shan; Goto, Tsuyoshi; Takahashi, Nobuyuki; Kim, Chu-Sook; Kang, Jihey; Yu, Rina; Kawada, Teruo

    2014-02-01

    Recently, fibrosis is observed in obese adipose tissue; however, the pathogenesis remains to be clarified. Obese adipose tissue is characterized by chronic inflammation with massive accumulation of immune cells including mast cells. The objective of the present study was to clarify the relationship between fibrosis and mast cells in obese adipose tissue, as well as to determine the origin of infiltrating mast cells. We observed the enhancement of mast cell accumulation and fibrosis in adipose tissue of severely obese diabetic db/db mice. Furthermore, adipose tissue-conditioned medium (ATCM) from severely obese diabetic db/db mice significantly enhanced collagen 5 mRNA expression in NIH-3T3 fibroblasts, and this enhancement was suppressed by the addition of an anti-mast cell protease 6 (MCP-6) antibody. An in vitro study showed that only collagen V among various types of collagen inhibited preadipocyte differentiation. Moreover, we found that ATCM from the nonobese but not obese stages of db/db mice significantly enhanced the migration of bone marrow-derived mast cells (BMMCs). These findings suggest that immature mast cells that infiltrate into adipose tissue at the nonobese stage gradually mature with the progression of obesity and diabetes and that MCP-6 secreted from mature mast cells induces collagen V expression in obese adipose tissue, which may contribute to the process of adipose tissue fibrosis. Induction of collagen V by MCP-6 might accelerate insulin resistance via the suppression of preadipocyte differentiation.

  2. Local and systemic effects of visceral and perivascular adipose tissue

    NARCIS (Netherlands)

    Verhagen, S.N.

    2012-01-01

    Rather than being solely a storage depot for triglycerides, adipose tissue is able to secrete pro- and anti-inflammatory cytokines and adipokines. A state of low grade inflammation associated with excess adipose tissue is involved in the increase in the incidences of atherosclerotic diseases and typ

  3. Characterization of the human visceral adipose tissue secretome

    NARCIS (Netherlands)

    Alvarez Llamas, Gloria; Szalowska, Ewa; de Vries, Marcel P.; Weening, Desiree; Landman, Karloes; Hoek, Annemieke; Wolffenbuttel, Bruce H. R.; Roelofsen, Johan; Vonk, Roel J.

    2007-01-01

    Adipose tissue is an endocrine organ involved in storage and release of energy but also in regulation of energy metabolism in other organs via secretion of peptide and protein hormones (adipokines). Especially visceral adipose tissue has been implicated in the development of metabolic syndrome and t

  4. Mechanisms of inflammatory responses in obese adipose tissue

    NARCIS (Netherlands)

    Sun, S.Y.; Yewei, Ji; Kersten, A.H.; Qi, L.

    2012-01-01

    The fields of immunology and metabolism are rapidly converging on adipose tissue. During obesity, many immune cells infiltrate or populate in adipose tissue and promote a low-grade chronic inflammation. Studies to date have suggested that perturbation of inflammation is critically linked to nutrient

  5. Relations between antioxidant vitamins in adipose tissue, plasma, and diet

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Veer, P. van 't; Brants, H.A.M.; Berg, H. van den; Schoonhoven, J. van; Hermus, R.J.J.

    1995-01-01

    For an evaluation of fat-soluble vitamin concentrations in adipose tissue as biomarkers of intake, estimates of usual intake of β-carotene, total vitamin A, and vitamin E (assessed by food frequency questionnaire) were compared with plasma and adipose tissue concentrations of β-carotene, retinol, an

  6. A hot interaction between immune cells and adipose tissue

    NARCIS (Netherlands)

    van den Berg, S.M.

    2017-01-01

    Systemic as well as adipose tissue inflammation contributes to the development of obesity-associated diseases. This thesis describes three targets to battle this chronic inflammation in a model of diet-induced obesity in mice. First, we studied inflammation in obese white - and brown adipose tissue

  7. Altered autophagy in human adipose tissues in obesity

    Science.gov (United States)

    Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat d...

  8. The role of adipose tissue in cancer-associated cachexia.

    Science.gov (United States)

    Vaitkus, Janina A; Celi, Francesco S

    2017-03-01

    Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing

  9. Automatic Segmentation of Abdominal Adipose Tissue in MRI

    DEFF Research Database (Denmark)

    Mosbech, Thomas Hammershaimb; Pilgaard, Kasper; Vaag, Allan

    2011-01-01

    This paper presents a method for automatically segmenting abdominal adipose tissue from 3-dimensional magnetic resonance images. We distinguish between three types of adipose tissue; visceral, deep subcutaneous and superficial subcutaneous. Images are pre-processed to remove the bias field effect...... of intensity in-homogeneities. This effect is estimated by a thin plate spline extended to fit two classes of automatically sampled intensity points in 3D. Adipose tissue pixels are labelled with fuzzy c-means clustering and locally determined thresholds. The visceral and subcutaneous adipose tissue...... are separated using deformable models, incorporating information from the clustering. The subcutaneous adipose tissue is subdivided into a deep and superficial part by means of dynamic programming applied to a spatial transformation of the image data. Regression analysis shows good correspondences between our...

  10. Regulation of systemic energy homeostasis by serotonin in adipose tissues.

    Science.gov (United States)

    Oh, Chang-Myung; Namkung, Jun; Go, Younghoon; Shong, Ko Eun; Kim, Kyuho; Kim, Hyeongseok; Park, Bo-Yoon; Lee, Ho Won; Jeon, Yong Hyun; Song, Junghan; Shong, Minho; Yadav, Vijay K; Karsenty, Gerard; Kajimura, Shingo; Lee, In-Kyu; Park, Sangkyu; Kim, Hail

    2015-04-13

    Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.

  11. Inflammatory peptides derived from adipose tissue

    Directory of Open Access Journals (Sweden)

    Barzilai Nir

    2005-01-01

    Full Text Available Abstract The low-grade inflammation seen with aging is noted particularly in subjects with the metabolic syndrome of aging. Insulin resistance, obesity/abdominal obesity, and risks for many age-related diseases characterize this common syndrome. It is becoming clear that this increased adipose tissue is not simply a reservoir for excess nutrients, but rather an active and dynamic organ capable of expressing several cytokines and other fat-derived peptides (FDP. Some, but not all, FDP may have a role in development of the metabolic syndrome but there is no evidence that these FDP are causing inflammation directly. We suggest that high levels of inflammatory peptides are markers for obesity/abdominal obesity seen with aging, but some may not necessarily have a causative role in the development of inflammation.

  12. The Ontogeny of Brown Adipose Tissue.

    Science.gov (United States)

    Symonds, Michael E; Pope, Mark; Budge, Helen

    2015-01-01

    There are three different types of adipose tissue (AT)-brown, white, and beige-that differ with stage of development, species, and anatomical location. Of these, brown AT (BAT) is the least abundant but has the greatest potential impact on energy balance. BAT is capable of rapidly producing large amounts of heat through activation of the unique uncoupling protein 1 (UCP1) located within the inner mitochondrial membrane. White AT is an endocrine organ and site of lipid storage, whereas beige AT is primarily white but contains some cells that possess UCP1. BAT first appears in the fetus around mid-gestation and is then gradually lost through childhood, adolescence, and adulthood. We focus on the interrelationships between adipocyte classification, anatomical location, and impact of diet in early life together with the extent to which fat development differs between the major species examined. Ultimately, novel dietary interventions designed to reactivate BAT could be possible.

  13. Breast cancer 1 (BrCa1 may be behind decreased lipogenesis in adipose tissue from obese subjects.

    Directory of Open Access Journals (Sweden)

    Francisco J Ortega

    Full Text Available CONTEXT: Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1 interacts with acetyl-CoA carboxylase (ACC reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. RESEARCH DESIGN AND METHODS: BrCa1 gene expression, total and phosphorylated (P- BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. RESULTS: BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002 and subcutaneous (SC; 1.49-fold, p = 0.001 adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007 as well as in OM (p = 0.010 fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001 and protein (1.2-fold, p = 0.001 were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005 allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium, whereas lipogenic genes significantly decreased. CONCLUSIONS: The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.

  14. FEEDING INFLUENCES ADIPOSE TISSUE RESPONSES TO EXERCISE IN OVERWEIGHT MEN.

    Science.gov (United States)

    Chen, Yung-Chih; Travers, Rebecca L; Walhin, Jean-Philippe; Gonzalez, Javier T; Koumanov, Francoise; Betts, James A; Thompson, Dylan

    2017-03-14

    Feeding profoundly affects metabolic responses to exercise in various tissues but the effect of feeding status on human adipose tissue responses to exercise has never been studied. Ten healthy overweight men aged 26 ± 5 years (mean ± SD) with a waist circumference of 105 ± 10 cm walked at 60% of maximum oxygen uptake under either FASTED or FED conditions in a randomised, counterbalanced design. Feeding comprised 648 ± 115 kcal 2 h before exercise. Blood samples were collected at regular intervals to examine changes in metabolic parameters and adipokine concentrations. Adipose tissue samples were obtained at baseline and one hour post-exercise to examine changes in adipose tissue mRNA expression and secretion of selected adipokines ex-vivo. Adipose tissue mRNA expression of PDK4, ATGL, HSL, FAT/CD36, GLUT4 and IRS2 in response to exercise were lower in FED compared to FASTED conditions (all p ≤ 0.05). Post-exercise adipose IRS2 protein was affected by feeding (p ≤ 0.05), but Akt2, AMPK, IRS1, GLUT4, PDK4 and HSL protein levels were not different. Feeding status did not impact serum and ex-vivo adipose secretion of IL-6, leptin or adiponectin in response to exercise. This is the first study to show that feeding prior to acute exercise affects post-exercise adipose tissue gene expression and we propose that feeding is likely to blunt long-term adipose tissue adaptation to regular exercise.

  15. Porous decellularized adipose tissue foams for soft tissue regeneration.

    Science.gov (United States)

    Yu, Claire; Bianco, Juares; Brown, Cody; Fuetterer, Lydia; Watkins, John F; Samani, Abbas; Flynn, Lauren E

    2013-04-01

    To design tissue-specific bioscaffolds with well-defined properties and 3-D architecture, methods were developed for preparing porous foams from enzyme-solubilized human decellularized adipose tissue (DAT). Additionally, a technique was established for fabricating "bead foams" comprised of interconnected networks of porous DAT beads fused through a controlled freeze-thawing and lyophilization procedure. In characterization studies, the foams were stable without the need for chemical crosslinking, with properties that could be tuned by controlling the protein concentration and freezing rate during synthesis. Adipogenic differentiation studies with human adipose-derived stem cells (ASCs) suggested that stiffness influenced ASC adipogenesis on the foams. In support of our previous work with DAT scaffolds and microcarriers, the DAT foams and bead foams strongly supported adipogenesis and were also adipo-inductive, as demonstrated by glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity, endpoint RT-PCR analysis of adipogenic gene expression, and intracellular lipid accumulation. Adipogenic differentiation was enhanced on the microporous DAT foams, potentially due to increased cell-cell interactions in this group. In vivo assessment in a subcutaneous Wistar rat model demonstrated that the DAT bioscaffolds were well tolerated and integrated into the host tissues, supporting angiogenesis and adipogenesis. The DAT-based foams induced a strong angiogenic response, promoted inflammatory cell migration and gradually resorbed over the course of 12 weeks, demonstrating potential as scaffolds for wound healing and soft tissue regeneration.

  16. AMPK Activation by Metformin Suppresses Abnormal Extracellular Matrix Remodeling in Adipose Tissue and Ameliorates Insulin Resistance in Obesity.

    Science.gov (United States)

    Luo, Ting; Nocon, Allison; Fry, Jessica; Sherban, Alex; Rui, Xianliang; Jiang, Bingbing; Xu, X Julia; Han, Jingyan; Yan, Yun; Yang, Qin; Li, Qifu; Zang, Mengwei

    2016-08-01

    Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix (ECM) remodeling of WAT is initiated during the development of obesity. Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity. The ability of metformin to repress TGF-β1-induced fibrogenesis is abolished by the dominant negative AMPK in primary cells from the stromal vascular fraction. TGF-β1-induced insulin resistance is suppressed by AMPK agonists and the constitutively active AMPK in 3T3L1 adipocytes. In omental fat depots of obese humans, interstitial fibrosis is also associated with AMPK inactivation, TGF-β1/Smad3 induction, aberrant ECM production, myofibroblast activation, and adipocyte apoptosis. Collectively, integrated AMPK activation and TGF-β1/Smad3 inhibition may provide a potential therapeutic approach to maintain ECM flexibility and combat chronically uncontrolled adipose tissue expansion in obesity.

  17. Omental Infarction Mimicking Cholecystitis

    Directory of Open Access Journals (Sweden)

    David Smolilo

    2015-01-01

    Full Text Available Omental infarction can be difficult to diagnose preoperatively as imaging may be inconclusive and patients often present in a way that suggests a more common surgical pathology such as appendicitis. Here, a 40-year-old Caucasian man presented to casualty with shortness of breath and progressive right upper abdominal pain, accompanied with right shoulder and neck pain. Exploratory laparoscopy was eventually utilised to diagnose an atypical form of omental infarction that mimics cholecystitis. The vascular supply along the long axis of the segment was occluded initiating necrosis. In this case, the necrotic segment was adherent with the abdominal wall, a pathology not commonly reported in cases of omental infarction.

  18. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Miroslav Šram

    2015-01-01

    Full Text Available Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT and visceral adipose tissue (VAT, the latter being highly associated with coronary artery disease (CAD. Expansion of epicardial adipose tissue (EAT is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1 the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2 determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value.

  19. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue.

    Science.gov (United States)

    Šram, Miroslav; Vrselja, Zvonimir; Lekšan, Igor; Ćurić, Goran; Selthofer-Relatić, Kristina; Radić, Radivoje

    2015-01-01

    Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value.

  20. The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function.

    Science.gov (United States)

    Conroy, Melissa J; Fitzgerald, Vivienne; Doyle, Suzanne L; Channon, Shauna; Useckaite, Zivile; Gilmartin, Niamh; O'Farrelly, Cliona; Ravi, Narayanasamy; Reynolds, John V; Lysaght, Joanne

    2016-12-01

    The role of NK cells in visceral adipose tissue (VAT) and liver inflammation in obesity is not fully understood. This study investigated the frequency, cytokine expression, chemokine receptor, and cytotoxicity receptor profile of NK cells in the blood, omentum, and liver of patients with the obesity-associated cancer, oesophageal adenocarcinoma (OAC). The effect of chronically inflamed tissue microenvironments on NK cell viability and function was also examined. We identified significantly lower NK cell frequencies in the liver of OAC patients compared with healthy controls and within the omentum and liver of OAC patients compared with blood, whereas IL-10-producing populations were significantly higher. Interestingly, our data suggest that reduced frequencies of NK cells in omentum and liver of OAC patients are not a result of impaired NK cell chemotaxis to these tissues. In fact, our functional data revealed that secreted factors from omentum and liver of OAC patients induce significant levels of NK cell death and lead to reduced percentages of TNF-α(+) and NKP46(+) NK cells and higher frequencies of IL-10-producing NK cells. Together, these data suggest that the omental and hepatic microenvironments of OAC patients alter the NK cell phenotype to a more anti-inflammatory homeostatic role. © Society for Leukocyte Biology.

  1. Hepatic oleate regulates adipose tissue lipogenesis and fatty acid oxidation.

    Science.gov (United States)

    Burhans, Maggie S; Flowers, Matthew T; Harrington, Kristin R; Bond, Laura M; Guo, Chang-An; Anderson, Rozalyn M; Ntambi, James M

    2015-02-01

    Hepatic steatosis is associated with detrimental metabolic phenotypes including enhanced risk for diabetes. Stearoyl-CoA desaturases (SCDs) catalyze the synthesis of MUFAs. In mice, genetic ablation of SCDs reduces hepatic de novo lipogenesis (DNL) and protects against diet-induced hepatic steatosis and adiposity. To understand the mechanism by which hepatic MUFA production influences adipose tissue stores, we created two liver-specific transgenic mouse models in the SCD1 knockout that express either human SCD5 or mouse SCD3, that synthesize oleate and palmitoleate, respectively. We demonstrate that hepatic de novo synthesized oleate, but not palmitoleate, stimulate hepatic lipid accumulation and adiposity, reversing the protective effect of the global SCD1 knockout under lipogenic conditions. Unexpectedly, the accumulation of hepatic lipid occurred without induction of the hepatic DNL program. Changes in hepatic lipid composition were reflected in plasma and in adipose tissue. Importantly, endogenously synthesized hepatic oleate was associated with suppressed DNL and fatty acid oxidation in white adipose tissue. Regression analysis revealed a strong correlation between adipose tissue lipid fuel utilization and hepatic and adipose tissue lipid storage. These data suggest an extrahepatic mechanism where endogenous hepatic oleate regulates lipid homeostasis in adipose tissues.

  2. Role of adipose tissue in the pathogenesis of cardiac arrhythmias.

    Science.gov (United States)

    Samanta, Rahul; Pouliopoulos, Jim; Thiagalingam, Aravinda; Kovoor, Pramesh

    2016-01-01

    Epicardial adipose tissue is present in normal healthy individuals. It is a unique fat depot that, under physiologic conditions, plays a cardioprotective role. However, excess epicardial adipose tissue has been shown to be associated with prevalence and severity of atrial fibrillation. In arrhythmogenic right ventricular cardiomyopathy and myotonic dystrophy, fibrofatty infiltration of the myocardium is associated with ventricular arrhythmias. In the ovine model of ischemic cardiomyopathy, the presence of intramyocardial adipose or lipomatous metaplasia has been associated with increased propensity to ventricular tachycardia. These observations suggest a role of adipose tissue in the pathogenesis of cardiac arrhythmias. In this article, we review the role of cardiac adipose tissue in various cardiac arrhythmias and discuss the possible pathophysiologic mechanisms.

  3. 0Adipose-derived stem cells: Implications in tissue regeneration

    Institute of Scientific and Technical Information of China (English)

    Wakako; Tsuji; J; Peter; Rubin; Kacey; G; Marra

    2014-01-01

    Adipose-derived stem cells(ASCs) are mesenchymal stem cells(MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differ-entiate into multiple cell lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant adipose tissue by a minimally invasive procedure, which results in a high number of cells. Therefore, ASCs are promising for regenerating tissues and organs dam-aged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration.

  4. Is adipose tissue metabolically different at different sites?

    Science.gov (United States)

    Gil, Angel; Olza, Josune; Gil-Campos, Mercedes; Gomez-Llorente, Carolina; Aguilera, Concepción M

    2011-09-01

    This review focuses on metabolic differences of adipose tissue at different sites of the body, with emphasis in pediatrics. Adipose tissue is composed of various cell types, which include adipocytes and other cells of the stromal vascular fraction such as preadipocytes, blood cells, endothelial cells and macrophages. Mammals have two main types of adipose tissue: white adipose tissue (WAT), and brown adipose tissue (BAT), each of which possesses unique cell autonomous properties. WAT and BAT differ at the functional, as well as the morphological and molecular levels. WAT accumulates surplus energy mainly in the form of triacylglycerols and BAT dissipates energy directly as heat. Recently, functional BAT in humans has been located in the neck, supraclavicular, mediastinal and interscapular areas. WAT is distributed throughout the body in the form of two major types: subcutaneous adipose tissue (SWAT) and the intra-abdominal visceral adipose tissue (VWAT). VWAT tissue is associated with insulin resistance, diabetes mellitus, dyslipidaemia, hypertension, atherosclerosis, hepatic steatosis, and overall mortality whereas SWAT and BAT have intrinsic beneficial metabolic properties. Subcutaneous and visceral adipocytes derive from different progenitor cells that exhibit a different gene expression pattern. SWAT responds better to the antilipolytic effects of insulin and other hormones, secrets more adiponectin and less inflammatory cytokines, and is differentially affected by molecules involved in signal transduction as well as drugs compared with VWAT. Current research is investigating various approaches of BAT and SWAT transplantation, including new sources of adipocyte progenitors. This may be important for the potential treatment of childhood obesity.

  5. The mechanism of functional vasodilatation in rabbit epigastric adipose tissue.

    Science.gov (United States)

    Lewis, G P; Mattews, J

    1970-03-01

    1. The effect of close-arterial infusions of fat-mobilizing substances has been examined on the release of free fatty acids and blood flow in the epigastric adipose tissue of rabbits.2. All the fat mobilizers in addition to causing the release of free fatty acids also caused an increased blood flow in the fat tissue.3. Both the fat mobilization and the vasodilatation continued for an hour or so after the end of infusion.4. Although no vasodilator substance could be detected in the venous effluent from the activated adipose tissue, a vasodilator could be detected in acid-ether extracts of adipose tissue excised during a period of fat mobilization.5. It is suggested that a vasodilator substance is released or formed in adipose tissue during fat mobilization and that this substance accounts for the vasodilatation accompanying activity in the tissue.

  6. Does Adipose Tissue Thermogenesis Play a Role in Metabolic Health?

    Directory of Open Access Journals (Sweden)

    Craig Porter

    2013-01-01

    Full Text Available The function ascribed to brown adipose tissue in humans has long been confined to thermoregulation in neonates, where this thermogenic capacity was thought lost with maturation. Recently, brown adipose tissue depots have been identified in adult humans. The significant oxidative capacity of brown adipocytes and the ability of their mitochondria to respire independently of ATP production, has led to renewed interest in the role that these adipocytes play in human energy metabolism. In our view, there is a need for robust physiological studies determining the relationship between molecular signatures of brown adipose tissue, adipose tissue mitochondrial function, and whole body energy metabolism, in order to elucidate the significance of thermogenic adipose tissue in humans. Until such information is available, the role of thermogenic adipose tissue in human metabolism and the potential that these adipocytes may prevent or treat obesity and metabolic diseases in humans will remain unknown. In this article, we summarize the recent literature pertaining to brown adipose tissue function with the aims of drawing the readers’ attention to the lack of data concerning the role of brown adipocytes in human physiology, and to the potential limitations of current research strategies.

  7. Adipose tissue macrophages: the inflammatory link between obesity and cancer?

    Science.gov (United States)

    Wagner, Marek; Samdal Steinskog, Eli Sihn; Wiig, Helge

    2015-04-01

    Obesity has increased dramatically over the last three decades. Thus, epidemiological evidence linking obesity and cancer has ignited our interest in the relationship between adipose tissue mass and cancer development. Obesity is defined as an excess of adipose tissue that is typified by a chronic, low-grade inflammatory response instigated by macrophage infiltration. Therefore, in this review, we will discuss the putative causal relationship between obesity-induced chronic inflammation and cancer with particular focus on adipose tissue macrophages. Chronic, low-grade inflammation has long been associated with cancer initiation, promotion and progression. Therefore, signals derived from adipose tissue macrophages may play a significant role in carcinogenesis. In this review we will discuss the molecular mechanisms of cancer development in obesity and highlight possible therapeutic strategies aiming at adipose tissue macrophages. The strong correlation between tumor-associated macrophage infiltration and tumor growth and progression emphasizes the value of macrophages as an effective therapeutic target. It remains to be deciphered to what extent adipose tissue macrophages contribute to these processes, especially in tumors growing within or adjacent to adipose tissue. More effort should also be placed on elucidating macrophage differences between humans and mice that may lead to the development of more effective diagnostic and therapeutic strategies.

  8. Adipose tissue and skeletal muscle blood flow during mental stress

    Energy Technology Data Exchange (ETDEWEB)

    Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

    1989-01-01

    Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

  9. 2型糖尿病患者皮下、大网膜脂肪组织脂联素mRNA表达变化及意义%Expression and significance of adiponectin mRNA in subcutaneous and omental adipose tissue of type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    李倩倩; 蒋秀琴; 李慧敏; 缪珩

    2011-01-01

    映胰岛素抵抗程度.%Objective: To observe the adiponectin mRNA expression in subcutaneous and omental adipose tissue of type 2 diabetic patients and their relation with serum adiponectin, body mass index(BMI), waist circumference (WC),waist hip ratio (WHR), blood pressure, fasting plasma glucose (FPG), HbA 1 c, blood lipids and uric acid (UA). Methods:Twenty-three T2DM patients with obesity,23 T2DM patients, 33 obesity patients and 23 controls were selected. The adiponectin mRNA expression level in adipose tissue was assayed by RT-PCR. The level of serum adiponectin was measured with ELISA kit. FBG, triglyceride (TG), total cholesterol(TC),high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), HbAlc, UA of all subjects were determined and their blood pressure, height, weight, waist circumference, hip circumference were measured to calculate BMI,WHR.Results: ①The SBP, DBP, FPG, HbA1c, TG, LDL-C, UA were significantly higher, and serum adiponectin, HDL-C and adiponectin mRNA expression level in both subcutaneous and omental adipose tissue were significantly lower in diabetic obesity group than in obesity group (P < 0.05), the adiponectin mRNA expression level in omental were significantly lower than in subcutaneous adipose tissue in both groups (P < 0.01). ②The FPG, HbAlc, TG, UA were higher, serum adiponectin, HDL-C and adiponectin mRNA levels expressed in both subcutaneous and omental adipose tissue were lower in diabetic group without obesity than in control group without obesity (P < 0.05), the adiponectin mRNA expression level in omental was lower than in subcutaneous adipose tissue in both groups (P < 0.01). ③The BMI,WHR,SBP,DBP,FPG,HbA1C,TG,UA were higher, serum adiponectin and adiponectin mRNA level expressed in both subcutaneous and omental adipose tissue were lower in diabetic obese group than in diabetic group without obesity(P < 0.05). ④The adiponectin mRNA expression level in omental adipose tissue of diabetic

  10. Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part I: Rheumatoid adipose tissue.

    Science.gov (United States)

    Sudoł-Szopińska, Iwona; Kontny, Ewa; Zaniewicz-Kaniewska, Katarzyna; Prohorec-Sobieszek, Monika; Saied, Fadhil; Maśliński, Włodzimierz

    2013-06-01

    For many years, it was thought that synovial cells and chondrocytes are the only sources of proinflammatory cytokines and growth factors found in the synovial fluid in patients suffering from osteoarthritis and rheumatoid arthritis. Currently, it is more and more frequently indicated that adipose tissue plays a significant role in the pathogenesis of these diseases as well as that a range of pathological processes that take place in the adipose tissue, synovial membrane and cartilage are interconnected. The adipose tissue is considered a specialized form of the connective tissue containing various types of cells which produce numerous biologically active factors. The latest studies reveal that, similarly to the synovial membrane, articular adipose tissue may take part in the local inflammatory response and affect the metabolism of the cartilage and subchondral osseous tissue. In in vitro conditions, the explants of this tissue obtained from patients suffering from osteoarthritis and rheumatoid arthritis produce similar pro- and anti-inflammatory cytokines to the explants of the synovial membrane. At this stage already, knowledge translates into imaging diagnostics. In radiological images, the shadowing of the periarticular soft tissues may not only reflect synovial membrane pathologies or joint effusion, but may also suggest inflammatory edema of the adipose tissue. On ultrasound examinations, abnormal presentation of the adipose tissue, i.e. increased echogenicity and hyperemia, may indicate its inflammation. Such images have frequently been obtained during ultrasound scanning and have been interpreted as inflammation, edema, hypertrophy or fibrosis of the adipose tissue. At present, when the knowledge concerning pathogenic mechanisms is taken into account, abnormal echogenicity and hyperemia of the adipose tissue may be considered as a proof of its inflammation. In the authors' own practice, the inflammation of the adipose tissue usually accompanies synovitis

  11. Injury-Induced Insulin Resistance in Adipose Tissue

    OpenAIRE

    Williams, Vanessa L.; Martin, Rachel E.; Franklin, John L.; Hardy, Robert. W.; Messina, Joseph L.

    2012-01-01

    Hyperglycemia and insulin resistance are common findings in critical illness. Patients in the surgical ICU are frequently treated for this ‘critical illness diabetes’ with intensive insulin therapy, resulting in a substantial reduction in morbidity and mortality. Adipose tissue is an important insulin target tissue, but it is not known whether adipose tissue is affected by critical illness diabetes. In the present study, a rodent model of critical illness diabetes was used to determine whethe...

  12. Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation.

    Directory of Open Access Journals (Sweden)

    Bong-Sung Kim

    Full Text Available Macrophage migration inhibitory factor (MIF is a pleiotropic cytokine and has been implicated in inflammatory diseases. However, little is known about the regulation of MIF in adipose tissue and its impact on wound healing. The aim of this study was to investigate MIF expression in inflamed adipose and determine its role in inflammatory cell recruitment and wound healing. Adipose tissue was harvested from subcutaneous adipose tissue layers of 24 healthy subjects and from adipose tissue adjacent to acutely inflamed wounds of 21 patients undergoing wound debridement. MIF protein and mRNA expression were measured by ELISA and RT-PCR. Cell-specific MIF expression was visualized by immunohistochemistry. The functional role of MIF in cell recruitment was investigated by a chemotaxis assay and by flow cytometry of labeled macrophages that were injected into Mif-/-and wildtype mice. Wound healing was evaluated by an in vitro scratch assay on human fibroblast monolayers. MIF protein levels of native adipose tissue and supernatants from acutely inflamed wounds were significantly elevated when compared to healthy controls. MIF mRNA expression was increased in acutely inflamed adipose tissue indicating the activation of MIF gene transcription in response to adipose tissue inflammation. MIF is expressed in mature adipocytes and in infiltrated macrophages. Peripheral blood mononuclear cell migration was significantly increased towards supernatants derived from inflamed adipose tissue. This effect was partially abrogated by MIF-neutralizing antibodies. Moreover, when compared to wildtype mice, Mif-/-mice showed reduced infiltration of labeled macrophages into LPS-stimulated epididymal fat pads in vivo. Finally, MIF antibodies partially neutralized the detrimental effect of MIF on fibroblast wound healing. Our results indicate that increased MIF expression and rapid activation of the MIF gene in fat tissue adjacent to acute wound healing disorders may play a

  13. Hypoxia and adipose tissue function and dysfunction in obesity.

    Science.gov (United States)

    Trayhurn, Paul

    2013-01-01

    The rise in the incidence of obesity has led to a major interest in the biology of white adipose tissue. The tissue is a major endocrine and signaling organ, with adipocytes, the characteristic cell type, secreting a multiplicity of protein factors, the adipokines. Increases in the secretion of a number of adipokines occur in obesity, underpinning inflammation in white adipose tissue and the development of obesity-associated diseases. There is substantial evidence, particularly from animal studies, that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in Po(2) is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of >1,000 genes. The secretion of a number of inflammation-related adipokines is upregulated by hypoxia, and there is a switch from oxidative metabolism to anaerobic glycolysis. Glucose utilization is increased in hypoxic adipocytes with corresponding increases in lactate production. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Many of the responses of adipocytes to hypoxia are initiated at Po(2) levels above the normal physiological range for adipose tissue. The other cell types within the tissue also respond to hypoxia, with the differentiation of preadipocytes to adipocytes being inhibited and preadipocytes being transformed into leptin-secreting cells. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity.

  14. TAF7L modulates brown adipose tissue formation

    OpenAIRE

    ZHOU, HAIYING; Wan, Bo; Grubisic, Ivan; Kaplan, Tommy; Tjian, Robert

    2014-01-01

    eLife digest Mammals produce two distinct types of adipose tissue: white adipose tissue (white fat) is the more common type and is used to store energy; brown adipose tissue (brown fat) is mostly found in young animals and infants, and it plays an important role in dissipating energy as heat rather than storing it in fat for future use. In adults, higher levels of brown fat are associated with lower levels of fat overall, so there is considerable interest in learning more about this form of f...

  15. Self-synthesized extracellular matrix contributes to mature adipose tissue regeneration in a tissue engineering chamber.

    Science.gov (United States)

    Zhan, Weiqing; Chang, Qiang; Xiao, Xiaolian; Dong, Ziqing; Zeng, Zhaowei; Gao, Jianhua; Lu, Feng

    2015-01-01

    The development of an engineered adipose tissue substitute capable of supporting reliable, predictable, and complete fat tissue regeneration would be of value in plastic and reconstructive surgery. For adipogenesis, a tissue engineering chamber provides an optimized microenvironment that is both efficacious and reproducible; however, for reasons that remain unclear, tissues regenerated in a tissue engineering chamber consist mostly of connective rather than adipose tissue. Here, we describe a chamber-based system for improving the yield of mature adipose tissue and discuss the potential mechanism of adipogenesis in tissue-chamber models. Adipose tissue flaps with independent vascular pedicles placed in chambers were implanted into rabbits. Adipose volume increased significantly during the observation period (week 1, 2, 3, 4, 16). Histomorphometry revealed mature adipose tissue with signs of adipose tissue remolding. The induced engineered constructs showed high-level expression of adipogenic (peroxisome proliferator-activated receptor γ), chemotactic (stromal cell-derived factor 1a), and inflammatory (interleukin 1 and 6) genes. In our system, the extracellular matrix may have served as a scaffold for cell migration and proliferation, allowing mature adipose tissue to be obtained in a chamber microenvironment without the need for an exogenous scaffold. Our results provide new insights into key elements involved in the early development of adipose tissue regeneration.

  16. Adipose Tissue: Sanctuary for HIV/SIV Persistence and Replication.

    Science.gov (United States)

    Pallikkuth, Suresh; Mohan, Mahesh

    2015-12-01

    This commentary highlights new findings from a recent study identifying adipose tissue as a potential HIV reservoir and a major site of inflammation during chronic human/simian immunodeficiency virus (HIV/SIV) infection. A concise discussion about upcoming challenges and new research avenues for reducing chronic adipose inflammation during HIV/SIV infection is presented.

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

    DEFF Research Database (Denmark)

    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 ti...

  18. Adipose tissue lymphocytes: types and roles.

    Science.gov (United States)

    Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

    2009-12-01

    Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

  19. Brain-adipose tissue cross talk.

    Science.gov (United States)

    Bartness, Timothy J; Kay Song, C; Shi, Haifei; Bowers, Robert R; Foster, Michelle T

    2005-02-01

    While investigating the reversible seasonal obesity of Siberian hamsters, direct sympathetic nervous system (SNS) postganglionic innervation of white adipose tissue (WAT) has been demonstrated using anterograde and retrograde tract tracers. The primary function of this innervation is lipid mobilization. The brain SNS outflow to WAT has been defined using the pseudorabies virus (PRV), a retrograde transneuronal tract tracer. These PRV-labelled SNS outflow neurons are extensively co-localized with melanocortin-4 receptor mRNA, which, combined with functional data, suggests their involvement in lipolysis. The SNS innervation of WAT also regulates fat cell number, as noradrenaline inhibits and WAT denervation stimulates fat cell proliferation in vitro and in vivo respectively. The sensory innervation of WAT has been demonstrated by retrograde tract tracing, electrophysiological recording and labelling of the sensory-associated neuropeptide calcitonin gene-related peptide in WAT. Local injections of the sensory nerve neurotoxin capsaicin into WAT selectively destroy this innervation. Just as surgical removal of WAT pads triggers compensatory increases in lipid accretion by non-excised WAT depots, capsaicin-induced sensory denervation triggers increases in lipid accretion of non-capsaicin-injected WAT depots, suggesting that these nerves convey information about body fat levels to the brain. Finally, parasympathetic nervous system innervation of WAT has been suggested, but the recent finding of no WAT immunoreactivity for the possible parasympathetic marker vesicular acetylcholine transporter (VAChT) argues against this claim. Collectively, these data suggest several roles for efferent and afferent neural innervation of WAT in body fat regulation.

  20. New concepts in white adipose tissue physiology

    Energy Technology Data Exchange (ETDEWEB)

    Proença, A.R.G. [Universidade Estadual de Campinas, Laboratório de Biotecnologia, Faculdade de Ciências Aplicadas, Limeira, SP, Brasil, Laboratório de Biotecnologia, Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, SP (Brazil); Sertié, R.A.L. [Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brasil, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Oliveira, A.C. [Universidade Estadual do Ceará, Instituto Superior de Ciências Biomédicas, Fortaleza, CE, Brasil, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, CE (Brazil); Campaãa, A.B.; Caminhotto, R.O.; Chimin, P.; Lima, F.B. [Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brasil, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-03-03

    Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT.

  1. Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues.

    Science.gov (United States)

    Chen, Yu-Jen; Liu, Hui-Yu; Chang, Yun-Tsui; Cheng, Ying-Hung; Mersmann, Harry J; Kuo, Wen-Hung; Ding, Shih-Torng

    2016-03-31

    Obesity is an unconstrained worldwide epidemic. Unraveling molecular controls in adipose tissue development holds promise to treat obesity or diabetes. Although numerous immortalized adipogenic cell lines have been established, adipose-derived stem cells from the stromal vascular fraction of subcutaneous white adipose tissues provide a reliable cellular system ex vivo much closer to adipose development in vivo. Pig adipose-derived stem cells (pADSC) are isolated from 7- to 9-day old piglets. The dorsal white fat depot of porcine subcutaneous adipose tissues is sliced, minced and collagenase digested. These pADSC exhibit strong potential to differentiate into adipocytes. Moreover, the pADSC also possess multipotency, assessed by selective stem cell markers, to differentiate into various mesenchymal cell types including adipocytes, osteocytes, and chondrocytes. These pADSC can be used for clarification of molecular switches in regulating classical adipocyte differentiation or in direction to other mesenchymal cell types of mesodermal origin. Furthermore, extended lineages into cells of ectodermal and endodermal origin have recently been achieved. Therefore, pADSC derived in this protocol provide an abundant and assessable source of adult mesenchymal stem cells with full multipotency for studying adipose development and application to tissue engineering of regenerative medicine.

  2. The role of dietary fat in adipose tissue metabolism.

    Science.gov (United States)

    Fernández-Quintela, Alfredo; Churruca, Itziar; Portillo, Maria Puy

    2007-10-01

    Energy intake and expenditure tend on average to remain adjusted to each other in order to maintain a stable body weight, which is only likely to be sustained if the fuel mix oxidised is equivalent to the nutrient content of the diet. Whereas protein and carbohydrate degradation and oxidation are closely adjusted to their intakes, fat balance regulation is less precise and that fat is more likely to be stored than oxidised. It has been demonstrated that dietary fatty acids have an influence not only on the fatty acid composition of membrane phospholipids, thus modulating several metabolic processes that take place in the adipocyte, but also on the composition and the quantity of different fatty acids in adipose tissue. Moreover, dietary fatty acids also modulate eicosanoid presence, which have hormone-like activities in lipid metabolism regulation in adipose tissue. Until recently, the adipocyte has been considered to be no more than a passive tissue for storage of excess energy. However, there is now compelling evidence that adipocytes have a role as endocrine secretory cells. Some of the adipokines produced by adipose tissue, such as leptin and adiponectin, act on adipose tissue in an autocrine/paracrine manner to regulate adipocyte metabolism. Furthermore, dietary fatty acids may influence the expression of adipokines. The nutrients are among the most influential of the environmental factors that determine the way adipose tissue genes are expressed by functioning as regulators of gene transcription. Therefore, not only dietary fat amount but also dietary fat composition influence adipose tissue metabolism.

  3. Assessment of in situ adipose tissue inflammation by microdialysis

    DEFF Research Database (Denmark)

    Langkilde, Anne; Andersen, Ove; Henriksen, Jens H;

    2015-01-01

    Inflammation, and specifically adipose tissue (AT) inflammation, is part of the pathophysiology of obesity and HIV-associated lipodystrophy. Local AT protein assessment methods are limited, and AT inflammation studies have therefore primarily examined inflammatory gene expression. We therefore...

  4. Morphological and inflammatory changes in visceral adipose tissue during obesity.

    Science.gov (United States)

    Revelo, Xavier S; Luck, Helen; Winer, Shawn; Winer, Daniel A

    2014-03-01

    Obesity is a major health burden worldwide and is a major factor in the development of insulin resistance and metabolic complications such as type II diabetes. Chronic nutrient excess leads to visceral adipose tissue (VAT) expansion and dysfunction in an active process that involves the adipocytes, their supporting matrix, and immune cell infiltrates. These changes contribute to adipose tissue hypoxia, adipocyte cell stress, and ultimately cell death. Accumulation of lymphocytes, macrophages, and other immune cells around dying adipocytes forms the so-called "crown-like structure", a histological hallmark of VAT in obesity. Cross talk between immune cells in adipose tissue dictates the overall inflammatory response, ultimately leading to the production of pro-inflammatory mediators which directly induce insulin resistance in VAT. In this review, we summarize recent studies demonstrating the dramatic changes that occur in visceral adipose tissue during obesity leading to low-grade chronic inflammation and metabolic disease.

  5. Adipose-derived stem cells and periodontal tissue engineering.

    Science.gov (United States)

    Tobita, Morikuni; Mizuno, Hiroshi

    2013-01-01

    Innovative developments in the multidisciplinary field of tissue engineering have yielded various implementation strategies and the possibility of functional tissue regeneration. Technologic advances in the combination of stem cells, biomaterials, and growth factors have created unique opportunities to fabricate tissues in vivo and in vitro. The therapeutic potential of human multipotent mesenchymal stem cells (MSCs), which are harvested from bone marrow and adipose tissue, has generated increasing interest in a wide variety of biomedical disciplines. These cells can differentiate into a variety of tissue types, including bone, cartilage, fat, and nerve tissue. Adipose-derived stem cells have some advantages compared with other sources of stem cells, most notably that a large number of cells can be easily and quickly isolated from adipose tissue. In current clinical therapy for periodontal tissue regeneration, several methods have been developed and applied either alone or in combination, such as enamel matrix proteins, guided tissue regeneration, autologous/allogeneic/xenogeneic bone grafts, and growth factors. However, there are various limitations and shortcomings for periodontal tissue regeneration using current methods. Recently, periodontal tissue regeneration using MSCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because the various secreted growth factors from MSCs might not only promote the regeneration of periodontal tissue but also encourage neovascularization of the damaged tissues. Adipose-derived stem cells are especially effective for neovascularization compared with other MSC sources. In this review, the possibility and potential of adipose-derived stem cells for regenerative medicine are introduced. Of particular interest, periodontal tissue regeneration with adipose-derived stem cells is discussed.

  6. The adipose tissue in farm animals: a proteomic approach.

    Science.gov (United States)

    Sauerwein, Helga; Bendixen, Emoke; Restelli, Laura; Ceciliani, Fabrizio

    2014-03-01

    Adipose tissue is not only a tissue where energy is stored but is also involved in regulating several body functions such as appetite and energy expenditure via its endocrine activity. Moreover, it thereby modulates complex processes like reproduction, inflammation and immune response. The products secreted from adipose tissue comprise hormones and cytokines that are collectively termed as adipocytokines or "adipokines"; the discovery and characterization of new proteins secreted by adipose tissue is still ongoing and their number is thus increasing. Adipokines act in both endocrine manner as well as locally, as autocrine or paracrine effectors. Proteomics has emerged as a valuable technique to characterize both cellular and secreted proteomes from adipose tissues, including those of main cellular fractions, i.e. the adipocytes or the stromal vascular fraction containing mainly adipocyte precursors and immune cells. The scientific interest in adipose tissue is largely based on the worldwide increasing prevalence of obesity in humans; in contrast, obesity is hardly an issue for farmed animals that are fed according to their well-defined needs. Adipose tissue is nevertheless of major importance in these animals, as the adipose percentage of the bodyweight is a major determinant for the efficiency of transferring nutrients from feed into food products and thus for the economic value from meat producing animals. In dairy animals, the importance of adipose tissue is based on its function as stromal structure for the mammary gland and on its role in participating in and regulating of energy metabolism and other functions. Moreover, as pig has recently become an important model organism to study human diseases, the knowledge of adipose tissue metabolism in pig is relevant for the study of obesity and metabolic disorders. We herein provide a general overview of adipose tissue functions and its importance in farm animals. This review will summarize recent achievements in

  7. Adipose tissue and adipocytes supports tumorigenesis and metastasis#

    OpenAIRE

    Nieman, Kristin M; Romero, Iris L.; Van Houten, Bennett; Lengyel, Ernst

    2013-01-01

    Adipose tissue influences tumor development in two major ways. First, obese individuals have a higher risk of developing certain cancers (endometrial, esophageal, and renal cell cancer). However, the risk of developing other cancers (melanoma, rectal, and ovarian) is not altered by body mass. In obesity, hypertrophied adipose tissue depots are characterized by a state of low grade inflammation. In this activated state, adipocytes and inflammatory cells secrete adipokines and cytokines which a...

  8. The gene expression of the main lipogenic enzymes is downregulated in visceral adipose tissue of obese subjects.

    Science.gov (United States)

    Ortega, Francisco J; Mayas, Dolores; Moreno-Navarrete, José M; Catalán, Victoria; Gómez-Ambrosi, Javier; Esteve, Eduardo; Rodriguez-Hermosa, Jose I; Ruiz, Bartomeu; Ricart, Wifredo; Peral, Belen; Fruhbeck, Gema; Tinahones, Francisco J; Fernández-Real, José M

    2010-01-01

    Contradictory findings regarding the gene expression of the main lipogenic enzymes in human adipose tissue depots have been reported. In this cross-sectional study, we aimed to evaluate the mRNA expression of fatty acid synthase (FAS) and acetyl-CoA carboxilase (ACC) in omental and subcutaneous (SC) fat depots from subjects who varied widely in terms of body fat mass. FAS and ACC gene expression were evaluated by real time-PCR in 188 samples of visceral adipose tissue which were obtained during elective surgical procedures in 119 women and 69 men. Decreased sex-adjusted FAS (-59%) and ACC (-49%) mRNA were found in visceral adipose tissue from obese subjects, with and without diabetes mellitus type 2 (DM-2), compared with lean subjects (both P < 0.0001). FAS mRNA was also decreased (-40%) in fat depots from overweight subjects (P < 0.05). Indeed, FAS mRNA was significantly and positively associated with ACC gene expression (r = 0.316, P < 0.0001) and negatively with BMI (r = -0.274), waist circumference (r = -0.437), systolic blood pressure (r = -0.310), serum glucose (r = -0.277), and fasting triglycerides (r = -0.226), among others (all P < 0.0001). Similar associations were observed for ACC gene expression levels. In a representative subgroup of nonobese (n = 4) and obese women (n = 6), relative FAS gene expression levels significantly correlated (r = 0.657, P = 0.034; n = 10) with FAS protein values. FAS protein levels were also inversely correlated with blood glucose (r = -0.640, P = 0.046) and fasting triglycerides (r = -0.832, P = 0.010). In conclusion, the gene expression of the main lipogenic enzymes is downregulated in visceral adipose tissue from obese subjects.

  9. (Brown) adipose tissue associated metabolic dysfunction and risk of cardiovascular disease in high risk patients

    NARCIS (Netherlands)

    Franssens, BT

    2016-01-01

    In this thesis it was shown that (brown) adipose tissue associated metabolic dysfunction increases the risk on development of cardiovascular disease in high risk patients. Quantity of adipose tissue is an important risk factor for adipose tissue dysfunction but functionality of adipose tissue not so

  10. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI.

    Science.gov (United States)

    Khan, Tayeba; Muise, Eric S; Iyengar, Puneeth; Wang, Zhao V; Chandalia, Manisha; Abate, Nicola; Zhang, Bei B; Bonaldo, Paolo; Chua, Streamson; Scherer, Philipp E

    2009-03-01

    Adipocytes are embedded in a unique extracellular matrix whose main function is to provide mechanical support, in addition to participating in a variety of signaling events. During adipose tissue expansion, the extracellular matrix requires remodeling to accommodate adipocyte growth. Here, we demonstrate a general upregulation of several extracellular matrix components in adipose tissue in the diabetic state, therefore implicating "adipose tissue fibrosis" as a hallmark of metabolically challenged adipocytes. Collagen VI is a highly enriched extracellular matrix component of adipose tissue. The absence of collagen VI results in the uninhibited expansion of individual adipocytes and is paradoxically associated with substantial improvements in whole-body energy homeostasis, both with high-fat diet exposure and in the ob/ob background. Collectively, our data suggest that weakening the extracellular scaffold of adipocytes enables their stress-free expansion during states of positive energy balance, which is consequently associated with an improved inflammatory profile. Therefore, the disproportionate accumulation of extracellular matrix components in adipose tissue may not be merely an epiphenomenon of metabolically challenging conditions but may also directly contribute to a failure to expand adipose tissue mass during states of excess caloric intake.

  11. Exercise and Adipose Tissue Macrophages: New Frontiers in Obesity Research?

    Science.gov (United States)

    Goh, Jorming; Goh, Kian Peng; Abbasi, Asghar

    2016-01-01

    Obesity is a major public health problem in the twenty-first century. Mutations in genes that regulate substrate metabolism, subsequent dysfunction in their protein products, and other factors, such as increased adipose tissue inflammation, are some underlying etiologies of this disease. Increased inflammation in the adipose tissue microenvironment is partly mediated by the presence of cells from the innate and adaptive immune system. A subset of the innate immune population in adipose tissue include macrophages, termed adipose tissue macrophages (ATMs), which are central players in adipose tissue inflammation. Being extremely plastic, their responses to diverse molecular signals in the microenvironment dictate their identity and functional properties, where they become either pro-inflammatory (M1) or anti-inflammatory (M2). Endurance exercise training exerts global anti-inflammatory responses in multiple organs, including skeletal muscle, liver, and adipose tissue. The purpose of this review is to discuss the different mechanisms that drive ATM-mediated inflammation in obesity and present current evidence of how exercise training, specifically endurance exercise training, modulates the polarization of ATMs from an M1 to an M2 anti-inflammatory phenotype.

  12. Endoplasmic reticulum stress in adipose tissue augments lipolysis.

    Science.gov (United States)

    Bogdanovic, Elena; Kraus, Nicole; Patsouris, David; Diao, Li; Wang, Vivian; Abdullahi, Abdikarim; Jeschke, Marc G

    2015-01-01

    The endoplasmic reticulum (ER) is an organelle important for protein synthesis and folding, lipid synthesis and Ca(2+) homoeostasis. Consequently, ER stress or dysfunction affects numerous cellular processes and has been implicated as a contributing factor in several pathophysiological conditions. Tunicamycin induces ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark of tunicamycin administration is the development of fatty livers within 24-48 hrs accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce ER stress in adipose tissue that would lead to increased lipolysis and subsequently to fatty infiltration of the liver and hepatomegaly. Our results show that intraperitoneal administration of tunicamycin rapidly induced an ER stress response in adipose tissue that correlated with increased circulating free fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and lipid droplet size. Furthermore, we found that in addition to fatty infiltration of the liver as well as hepatomegaly, lipid accumulation was also present in the heart, skeletal muscle and kidney. To corroborate our findings to a clinical setting, we examined adipose tissue from burned patients where increases in lipolysis and the development of fatty livers have been well documented. We found that burned patients displayed significant ER stress within adipose tissue and that ER stress augments lipolysis in cultured human adipocytes. Our results indicate a possible role for ER stress induced lipolysis in adipose tissue as an underlying mechanism contributing to increases in circulating FFAs and fatty infiltration into other organs.

  13. Gene Expression Signature in Adipose Tissue of Acromegaly Patients

    Science.gov (United States)

    Hochberg, Irit; Tran, Quynh T.; Barkan, Ariel L.; Saltiel, Alan R.; Chandler, William F.; Bridges, Dave

    2015-01-01

    To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. PMID:26087292

  14. Gene Expression Signature in Adipose Tissue of Acromegaly Patients.

    Science.gov (United States)

    Hochberg, Irit; Tran, Quynh T; Barkan, Ariel L; Saltiel, Alan R; Chandler, William F; Bridges, Dave

    2015-01-01

    To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly.

  15. Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity.

    Science.gov (United States)

    Lee, Byung-Cheol; Kim, Myung-Sunny; Pae, Munkyong; Yamamoto, Yasuhiko; Eberlé, Delphine; Shimada, Takeshi; Kamei, Nozomu; Park, Hee-Sook; Sasorith, Souphatta; Woo, Ju Rang; You, Jia; Mosher, William; Brady, Hugh J M; Shoelson, Steven E; Lee, Jongsoon

    2016-04-12

    Obesity-induced inflammation mediated by immune cells in adipose tissue appears to participate in the pathogenesis of insulin resistance. We show that natural killer (NK) cells in adipose tissue play an important role. High-fat diet (HFD) increases NK cell numbers and the production of proinflammatory cytokines, notably TNFα, in epididymal, but not subcutaneous, fat depots. When NK cells were depleted either with neutralizing antibodies or genetic ablation in E4bp4(+/-) mice, obesity-induced insulin resistance improved in parallel with decreases in both adipose tissue macrophage (ATM) numbers, and ATM and adipose tissue inflammation. Conversely, expansion of NK cells following IL-15 administration or reconstitution of NK cells into E4bp4(-/-) mice increased both ATM numbers and adipose tissue inflammation and exacerbated HFD-induced insulin resistance. These results indicate that adipose NK cells control ATMs as an upstream regulator potentially by producing proinflammatory mediators, including TNFα, and thereby contribute to the development of obesity-induced insulin resistance.

  16. Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth.

    Science.gov (United States)

    Jo, Junghyo; Gavrilova, Oksana; Pack, Stephanie; Jou, William; Mullen, Shawn; Sumner, Anne E; Cushman, Samuel W; Periwal, Vipul

    2009-03-01

    Adipose tissue grows by two mechanisms: hyperplasia (cell number increase) and hypertrophy (cell size increase). Genetics and diet affect the relative contributions of these two mechanisms to the growth of adipose tissue in obesity. In this study, the size distributions of epididymal adipose cells from two mouse strains, obesity-resistant FVB/N and obesity-prone C57BL/6, were measured after 2, 4, and 12 weeks under regular and high-fat feeding conditions. The total cell number in the epididymal fat pad was estimated from the fat pad mass and the normalized cell-size distribution. The cell number and volume-weighted mean cell size increase as a function of fat pad mass. To address adipose tissue growth precisely, we developed a mathematical model describing the evolution of the adipose cell-size distributions as a function of the increasing fat pad mass, instead of the increasing chronological time. Our model describes the recruitment of new adipose cells and their subsequent development in different strains, and with different diet regimens, with common mechanisms, but with diet- and genetics-dependent model parameters. Compared to the FVB/N strain, the C57BL/6 strain has greater recruitment of small adipose cells. Hyperplasia is enhanced by high-fat diet in a strain-dependent way, suggesting a synergistic interaction between genetics and diet. Moreover, high-fat feeding increases the rate of adipose cell size growth, independent of strain, reflecting the increase in calories requiring storage. Additionally, high-fat diet leads to a dramatic spreading of the size distribution of adipose cells in both strains; this implies an increase in size fluctuations of adipose cells through lipid turnover.

  17. Adipose tissue, the skeleton and cardiovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Wiklund, Peder

    2011-07-01

    Cardiovascular disease (CVD) is the leading cause of death in the Western World, although the incidence of myocardial infarction (MI) has declined over the last decades. However, obesity, which is one of the most important risk factors for CVD, is increasingly common. Osteoporosis is also on the rise because of an aging population. Based on considerable overlap in the prevalence of CVD and osteoporosis, a shared etiology has been proposed. Furthermore, the possibility of interplay between the skeleton and adipose tissue has received increasing attention the last few years with the discovery that leptin can influence bone metabolism and that osteocalcin can influence adipose tissue. A main aim of this thesis was to investigate the effects of fat mass distribution and bone mineral density on the risk of MI. Using dual-energy x-ray absorptiometry (DEXA) we measured 592 men and women for regional fat mass in study I. In study II this was expanded to include 3258 men and women. In study III 6872 men and women had their bone mineral density measured in the total hip and femoral neck using DEXA. We found that a fat mass distribution with a higher proportion of abdominal fat mass was associated with both an adverse risk factor profile and an increased risk of MI. In contrast, a higher gynoid fat mass distribution was associated with a more favorable risk factor profile and a decreased risk of MI, highlighting the different properties of abdominal and gynoid fat depots (study I-II). In study III, we investigated the association of bone mineral density and risk factors shared between CVD and osteoporosis, and risk of MI. We found that lower bone mineral density was associated with hypertension, and also tended to be associated to other CVD risk factors. Low bone mineral density was associated with an increased risk of MI in both men and women, apparently independently of the risk factors studied (study III). In study IV, we investigated 50 healthy, young men to determine if

  18. Ghrelin receptor regulates adipose tissue inflammation in aging.

    Science.gov (United States)

    Lin, Ligen; Lee, Jong Han; Buras, Eric D; Yu, Kaijiang; Wang, Ruitao; Smith, C Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance.

  19. From neutrophils to macrophages: differences in regional adipose tissue depots.

    Science.gov (United States)

    Dam, V; Sikder, T; Santosa, S

    2016-01-01

    Currently, we do not fully understand the underlying mechanisms of how regional adiposity promotes metabolic dysregulation. As adipose tissue expands, there is an increase in chronic systemic low-grade inflammation due to greater infiltration of immune cells and production of cytokines. This chronic inflammation is thought to play a major role in the development of metabolic complications and disease such as insulin resistance and diabetes. We know that different adipose tissue depots contribute differently to the risk of metabolic disease. People who have an upper body fat distribution around the abdomen are at greater risk of disease than those who tend to store fat in their lower body around the hips and thighs. Thus, it is conceivable that adipose tissue depots contribute differently to the inflammatory milieu as a result of varied infiltration of immune cell types. In this review, we describe the role and function of major resident immune cells in the development of adipose tissue inflammation and discuss their regional differences in the context of metabolic disease risk. We find that although initial studies have found regional differences, a more comprehensive understanding of how immune cells interrupt adipose tissue homeostasis is needed.

  20. Cold-induced changes in gene expression in brown adipose tissue, white adipose tissue and liver.

    Directory of Open Access Journals (Sweden)

    Andrew M Shore

    Full Text Available Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT, white adipose (WAT and liver of mice in response to 24 h cold exposure at 8°C. Expression of 1895 genes were significantly (P<0.05 up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and 134 genes were common between WAT and BAT, WAT and liver, and BAT and liver, respectively. We confirmed using qRT-PCR, the increased expression of a number of characteristic BAT genes during cold exposure. In both BAT and the liver, the most common direction of change in gene expression was suppression (496 genes in BAT and 590 genes in liver. Gene ontology analysis revealed for the first time significant (P<0.05 down regulation in response to cold, of genes involved in oxidoreductase activity, lipid metabolic processes and protease inhibitor activity, in both BAT and liver, but not WAT. The results reveal an unexpected importance of down regulation of cytochrome P450 gene expression and apolipoprotein, in both BAT and liver, but not WAT, in response to cold exposure. Pathway analysis suggests a model in which down regulation of the nuclear transcription factors HNF4α and PPARα in both BAT and liver may orchestrate the down regulation of genes involved in lipoprotein and steroid metabolism as well as Phase I enzymes belonging to the cytochrome P450 group in response to cold stress in mice. We propose that the response to cold stress involves decreased gene expression in a range of cellular processes in order to maximise pathways involved in heat production.

  1. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

    Directory of Open Access Journals (Sweden)

    Ribeiro Ricardo

    2012-04-01

    Full Text Available Abstract Background Obesity is associated with prostate cancer aggressiveness and mortality. The contribution of periprostatic adipose tissue, which is often infiltrated by malignant cells, to cancer progression is largely unknown. Thus, this study aimed to determine if periprostatic adipose tissue is linked with aggressive tumor biology in prostate cancer. Methods Supernatants of whole adipose tissue (explants or stromal vascular fraction (SVF from paired fat samples of periprostatic (PP and pre-peritoneal visceral (VIS anatomic origin from different donors were prepared and analyzed for matrix metalloproteinases (MMPs 2 and 9 activity. The effects of those conditioned media (CM on growth and migration of hormone-refractory (PC-3 and hormone-sensitive (LNCaP prostate cancer cells were measured. Results We show here that PP adipose tissue of overweight men has higher MMP9 activity in comparison with normal subjects. The observed increased activities of both MMP2 and MMP9 in PP whole adipose tissue explants, likely reveal the contribution of adipocytes plus stromal-vascular fraction (SVF as opposed to SVF alone. MMP2 activity was higher for PP when compared to VIS adipose tissue. When PC-3 cells were stimulated with CM from PP adipose tissue explants, increased proliferative and migratory capacities were observed, but not in the presence of SVF. Conversely, when LNCaP cells were stimulated with PP explants CM, we found enhanced motility despite the inhibition of proliferation, whereas CM derived from SVF increased both cell proliferation and motility. Explants culture and using adipose tissue of PP origin are most effective in promoting proliferation and migration of PC-3 cells, as respectively compared with SVF culture and using adipose tissue of VIS origin. In LNCaP cells, while explants CM cause increased migration compared to SVF, the use of PP adipose tissue to generate CM result in the increase of both cellular proliferation and migration

  2. Exercise Regulation of Marrow Adipose Tissue

    Science.gov (United States)

    Pagnotti, Gabriel M.; Styner, Maya

    2016-01-01

    Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT) remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell (MSC) pool that also gives rise to osteoblasts, chondrocytes, and myocytes, among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here, we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions, and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally supportive tissues, inhibits bone resorption, and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high-fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone – a PPARγ-agonist known to increase MAT and fracture risk – mice demonstrate a fivefold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise

  3. Exercise Regulation of Marrow Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Gabriel M Pagnotti

    2016-07-01

    Full Text Available Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell pool (MSC that gives rise also to osteoblasts, chondrocytes, and myocytes among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally-supportive tissues, inhibits bone resorption and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot, or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone - a PPARγ-agonist known to increase MAT and fracture risk - mice demonstrate a 5-fold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise

  4. Adipose tissues differentiated by adipose-derived stemcells harvested from transgenic mice

    Institute of Scientific and Technical Information of China (English)

    LU Feng; GAO Jian-hua; Rei Ogawa; Hiroshi Mizuro; Hiki Hykusoku

    2006-01-01

    Objective: To induce adipocyte differentiation in vitro by adipose-derived stromal cells (ASCs) harvested from transgenic mice with green fluorescent protein (GFP)and assess the possibility of constructing adipose tissues via attachment of ASCs to type Ⅰ collagen scaffolds.Methods: Inguinal fat pads from GFP transgenic mice were digested by enzymes for isolation of ASCs (primary culture). After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks, and the adipocyte differentiation by ASCs in vitro was assessed by morphological observation and Oil Red O staining. Then they were attached to collagen scaffolds and co-cultured for 12 hours, followed by hypodermic implantation to the dorsal skin of nude mice for 2 months. The newly-formed tissues were detected by HE staining.Results: The cultured primary stem cells were fibroblast-like and showed active proliferation. After being incubated in an adipocyte differentiation medium, the lipid droplets in the cytoplasm accumulated gradually and finally developed into mature adipocytes, which showed positive in Oil Red O staining. A 0.5-cm3 new tissue clot was found under the dorsal skin of the nude mice and it was confirmed as mature adipose tissues by fluorescent observation and HE staining.Conclusions: ASCs can successfully differentiate adipose tissues into mature adipocytes, which exhibit an adipocyte-like morphology and express as intracytoplasmic lipid droplets. It is an efficient model of adipose tissues engineered with ASCs and type Ⅰ collagen scaffolds.

  5. White adipose tissue resilience to insulin deprivation and replacement.

    Science.gov (United States)

    Hadji, Lilas; Berger, Emmanuelle; Soula, Hédi; Vidal, Hubert; Géloën, Alain

    2014-01-01

    Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. The initial body weight of the rats was 465±5.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues.

  6. White Adipose Tissue Resilience to Insulin Deprivation and Replacement

    Science.gov (United States)

    Hadji, Lilas; Berger, Emmanuelle; Soula, Hédi; Vidal, Hubert; Géloën, Alain

    2014-01-01

    Introduction Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Methods Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. Results The initial body weight of the rats was 465±5.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Conclusion Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues. PMID:25170835

  7. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Kumar Sudhesh

    2006-01-01

    Full Text Available Abstract Introduction Inflammation contributes to cardiovascular disease and is exacerbated with increased adiposity, particularly omental adiposity; however, the role of epicardial fat is poorly understood. Methods For these studies the expression of inflammatory markers was assessed in epicardial fat biopsies from coronary artery bypass grafting (CABG patients using quantitative RT-PCR. Further, the effects of chronic medications, including statins, as well as peri-operative glucose, insulin and potassium infusion, on gene expression were also assessed. Circulating resistin, CRP, adiponectin and leptin levels were determined to assess inflammation. Results The expression of adiponectin, resistin and other adipocytokine mRNAs were comparable to that in omental fat. Epicardial CD45 expression was significantly higher than control depots (p Conclusion Epicardial and omental fat exhibit a broadly comparable pathogenic mRNA profile, this may arise in part from macrophage infiltration into the epicardial fat. This study highlights that chronic inflammation occurs locally as well as systemically potentially contributing further to the pathogenesis of coronary artery disease.

  8. Adipocyte pseudohypoxia suppresses lipolysis and facilitates benign adipose tissue expansion.

    Science.gov (United States)

    Michailidou, Zoi; Morton, Nicholas M; Moreno Navarrete, José Maria; West, Christopher C; Stewart, Kenneth J; Fernández-Real, José Manuel; Schofield, Christopher J; Seckl, Jonathan R; Ratcliffe, Peter J

    2015-03-01

    Prolyl hydroxylase enzymes (PHDs) sense cellular oxygen upstream of hypoxia-inducible factor (HIF) signaling, leading to HIF degradation in normoxic conditions. In this study, we demonstrate that adipose PHD2 inhibition plays a key role in the suppression of adipocyte lipolysis. Adipose Phd2 gene ablation in mice enhanced adiposity, with a parallel increase in adipose vascularization associated with reduced circulating nonesterified fatty acid levels and normal glucose homeostasis. Phd2 gene-depleted adipocytes exhibited lower basal lipolysis in normoxia and reduced β-adrenergic-stimulated lipolysis in both normoxia and hypoxia. A selective PHD inhibitor suppressed lipolysis in murine and human adipocytes in vitro and in vivo in mice. PHD2 genetic ablation and pharmacological inhibition attenuated protein levels of the key lipolytic effectors hormone-sensitive lipase and adipose triglyceride lipase (ATGL), suggesting a link between adipocyte oxygen sensing and fatty acid release. PHD2 mRNA levels correlated positively with mRNA levels of AB-hydrolase domain containing-5, an activator of ATGL, and negatively with mRNA levels of lipid droplet proteins, perilipin, and TIP47 in human subcutaneous adipose tissue. Therapeutic pseudohypoxia caused by PHD2 inhibition in adipocytes blunts lipolysis and promotes benign adipose tissue expansion and may have therapeutic applications in obesity or lipodystrophy. © 2015 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.

  9. Under the Surface of Subcutaneous Adipose Tissue Biology.

    Science.gov (United States)

    Pandžić Jakšić, Vlatka; Grizelj, Danijela

    2016-12-01

    The global obesity epidemic enhanced contemporary interest in adipose tissue biology. Two structurally and functionally distinct depots, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), are spread throughout the body. Their distribution was recognized to be a major determinant of metabolic risk. Unlike VAT, SAT showed some protective endocrine and inflammatory features that might explain the occurrence of obese but metabolically healthy persons. The unique developmental gene expression signature, angiogenesis, and adipogenic potential of SAT determines its growth ability under the positive energy balance. The overflow hypothesis suggested that when SAT is unable to expand sufficiently, fat overflows towards metabolically adverse ectopic depots. Besides white adipose tissue, recent studies found important brown adipose tissue activity responsible for thermogenesis and energy dissipation in adults as well. SAT is prone to "browning" - the appearance of particular beige adipocytes that contribute to its favorable metabolic effects. Morbid obesity, aging, hormonal status, nutrition, low physical activity, and other environmental factors impair SAT relative resistance to dysfunctional changes and promote development of metabolic disorders. The popular approach considering SAT mainly as the subject of cosmetic procedures for improving the appearance of body contours should be avoided. Complex heterogeneity of obesity revealed that a tissue of an extreme plasticity and rich interactions with vital functions of the body lies under the surface. Therapeutic manipulations to preserve and enhance healthier fat in order to correct obesity-related metabolic disorders seem to be a relevant but still unexplored opportunity.

  10. High intensity interval training improves liver and adipose tissue insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Katarina Marcinko

    2015-12-01

    Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

  11. Lipolysis and lipases in white adipose tissue – An update

    OpenAIRE

    Bolsoni-Lopes,Andressa; Alonso-Vale, Maria Isabel C.

    2015-01-01

    Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanism...

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  13. Adipose tissue, obesity and adipokines: role in cancer promotion.

    Science.gov (United States)

    Booth, Andrea; Magnuson, Aaron; Fouts, Josephine; Foster, Michelle

    2015-01-01

    Adipose tissue is a complex organ with endocrine, metabolic and immune regulatory roles. Adipose depots have been characterized to release several adipocytokines that work locally in an autocrine and paracrine fashion or peripherally in an endocrine fashion. Adipocyte hypertrophy and excessive adipose tissue accumulation, as occurs during obesity, dysregulates the microenvironment within adipose depots and systemically alters peripheral tissue metabolism. The term "adiposopathy" is used to describe this promotion of pathogenic adipocytes and associated adipose - elated disorders. Numerous epidemiological studies confirm an association between obesity and various cancer forms. Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include, but are not limited to, obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipocktokine production. Several epidemiological studies have demonstrated a relationship between specific circulating adipocytokines and cancer risk. The aim of this review is to define the function, in normal weight and obesity states, of well-characterized and novel adipokines including leptin, adiponectin, apelin, visfatin, resistin, chemerin, omentin, nesfatin and vaspin and summarize the data that relates their dysfunction, whether associated or direct effects, to specific cancer outcomes. Overall research suggests most adipokines promote cancer cell progression via enhancement of cell proliferation and migration, inflammation and anti-apoptosis pathways, which subsequently can prompt cancer metastasis. Further research and longitudinal studies are needed to define the specific independent and additive roles of adipokines in cancer progression and reoccurrence.

  14. Characteristic expression of extracellular matrix in subcutaneous adipose tissue development and adipogenesis; comparison with visceral adipose tissue.

    Science.gov (United States)

    Mori, Shinobu; Kiuchi, Satomi; Ouchi, Atsushi; Hase, Tadashi; Murase, Takatoshi

    2014-01-01

    Adipose tissue is a connective tissue specified for energy metabolism and endocrines, but functional differences between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have not been fully elucidated. To reveal the physiological role of SAT, we characterized in vivo tissue development and in vitro adipocyte differentiation. In a DNA microarray analysis of SAT and VAT in Wistar rats, functional annotation clusters of extracellular matrix (ECM)-related genes were found in SAT, and major ECM molecules expressed in adipose tissues were profiled. In a histological analysis and quantitative expression analysis, ECM expression patterns could be classified into two types: (i) a histogenesis-correlated type such as type IV and XV collagen, and laminin subunits, (ii) a high-SAT expression type such as type I, III, and V collagen and minor characteristic collagens. Type (i) was related to basal membrane and up-regulated in differentiated 3T3-L1 cells and in histogenesis at depot-specific timings. In contrast, type (ii) was related to fibrous forming and highly expressed in 3T3-L1 preadipocytes. Exceptionally, fibronectin was abundant in developed adipose tissue, although it was highly expressed in 3T3-L1 preadipocytes. The present study showed that adipose tissues site-specifically regulate molecular type and timing of ECM expression, and suggests that these characteristic ECM molecules provide a critical microenvironment, which may affect bioactivity of adipocyte itself and interacts with other tissues. It must be important to consider the depot-specific property for the treatment of obesity-related disorders, dermal dysfunction and for the tissue regeneration.

  15. A stringent validation of mouse adipose tissue identity markers.

    Science.gov (United States)

    de Jong, Jasper M A; Larsson, Ola; Cannon, Barbara; Nedergaard, Jan

    2015-06-15

    The nature of brown adipose tissue in humans is presently debated: whether it is classical brown or of brite/beige nature. The dissimilar developmental origins and proposed distinct functions of the brown and brite/beige tissues make it essential to ascertain the identity of human depots with the perspective of recruiting and activating them for the treatment of obesity and type 2 diabetes. For identification of the tissues, a number of marker genes have been proposed, but the validity of the markers has not been well documented. We used established brown (interscapular), brite (inguinal), and white (epididymal) mouse adipose tissues and corresponding primary cell cultures as validators and examined the informative value of a series of suggested markers earlier used in the discussion considering the nature of human brown adipose tissue. Most of these markers unexpectedly turned out to be noninformative concerning tissue classification (Car4, Cited1, Ebf3, Eva1, Fbxo31, Fgf21, Lhx8, Hoxc8, and Hoxc9). Only Zic1 (brown), Cd137, Epsti1, Tbx1, Tmem26 (brite), and Tcf21 (white) proved to be informative in these three tissues. However, the expression of the brite markers was not maintained in cell culture. In a more extensive set of adipose depots, these validated markers provide new information about depot identity. Principal component analysis supported our single-gene conclusions. Furthermore, Zic1, Hoxc8, Hoxc9, and Tcf21 displayed anteroposterior expression patterns, indicating a relationship between anatomic localization and adipose tissue identity (and possibly function). Together, the observed expression patterns of these validated marker genes necessitates reconsideration of adipose depot identity in mice and humans.

  16. Natural killer T cells in adipose tissue prevent insulin resistance.

    Science.gov (United States)

    Schipper, Henk S; Rakhshandehroo, Maryam; van de Graaf, Stan F J; Venken, Koen; Koppen, Arjen; Stienstra, Rinke; Prop, Serge; Meerding, Jenny; Hamers, Nicole; Besra, Gurdyal; Boon, Louis; Nieuwenhuis, Edward E S; Elewaut, Dirk; Prakken, Berent; Kersten, Sander; Boes, Marianne; Kalkhoven, Eric

    2012-09-01

    Lipid overload and adipocyte dysfunction are key to the development of insulin resistance and can be induced by a high-fat diet. CD1d-restricted invariant natural killer T (iNKT) cells have been proposed as mediators between lipid overload and insulin resistance, but recent studies found decreased iNKT cell numbers and marginal effects of iNKT cell depletion on insulin resistance under high-fat diet conditions. Here, we focused on the role of iNKT cells under normal conditions. We showed that iNKT cell-deficient mice on a low-fat diet, considered a normal diet for mice, displayed a distinctive insulin resistance phenotype without overt adipose tissue inflammation. Insulin resistance was characterized by adipocyte dysfunction, including adipocyte hypertrophy, increased leptin, and decreased adiponectin levels. The lack of liver abnormalities in CD1d-null mice together with the enrichment of CD1d-restricted iNKT cells in both mouse and human adipose tissue indicated a specific role for adipose tissue-resident iNKT cells in the development of insulin resistance. Strikingly, iNKT cell function was directly modulated by adipocytes, which acted as lipid antigen-presenting cells in a CD1d-mediated fashion. Based on these findings, we propose that, especially under low-fat diet conditions, adipose tissue-resident iNKT cells maintain healthy adipose tissue through direct interplay with adipocytes and prevent insulin resistance.

  17. Adipose tissue as an immunological organ : implications for childhood obesity

    NARCIS (Netherlands)

    Schipper, H.S.

    2013-01-01

    Obesity is increasingly considered as an inflammatory disorder. In adults, obesity induces inflammation of adipose tissue (AT). Through the release of inflammatory lipids and immune mediating proteins called adipokines, AT inflammation spreads to other tissues ranging from liver and muscle to the

  18. Regulation of brown adipose tissue by stress and sex

    NARCIS (Netherlands)

    J.C. van den Beukel (Anneke)

    2016-01-01

    textabstractDue to the increasing incidence of obesity, more means of treating obesity are necessary. Brown adipose tissue (BAT) is a potential target tissue via which obesity can be treated due to its unique ability to use energy to produce heat. Not much is known however about the mechanisms via w

  19. Regulation of brown adipose tissue by stress and sex

    NARCIS (Netherlands)

    J.C. van den Beukel (Anneke)

    2016-01-01

    textabstractDue to the increasing incidence of obesity, more means of treating obesity are necessary. Brown adipose tissue (BAT) is a potential target tissue via which obesity can be treated due to its unique ability to use energy to produce heat. Not much is known however about the mechanisms via w

  20. NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism.

    Science.gov (United States)

    Park, Seongjoon; Fujishita, Chika; Komatsu, Toshimitsu; Kim, Sang Eun; Chiba, Takuya; Mori, Ryoichi; Shimokawa, Isao

    2014-12-01

    An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPARγ-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases.

  1. 11-Beta hydroxysteroid dehydrogenase type 2 expression in white adipose tissue is strongly correlated with adiposity.

    Science.gov (United States)

    Milagro, Fermin I; Campión, Javier; Martínez, J Alfredo

    2007-04-01

    Glucocorticoid action within the cells is regulated by the levels of glucocorticoid receptor (GR) expression and two enzymes, 11-beta hydroxysteroid dehydrogenase type 1 (11betaHSD1), which converts inactive to active glucocorticoids, and 11-beta hydroxysteroid dehydrogenase type 2 (11betaHSD2), which regulates the access of active glucocorticoids to the receptor by converting cortisol/corticosterone to the glucocorticoid-inactive form cortisone/dehydrocorticosterone. Male Wistar rats developed obesity by being fed a high-fat diet for 56 days, and GR, 11betaHSD1 and 11betaHSD2 gene expression were compared with control-diet fed animals. Gene expression analysis of 11betaHSD1, 11betaHSD2 and GR were performed by RT-PCR in subcutaneous and retroperitoneal adipose tissue. High-fat fed animals overexpressed 11betaHSD2 in subcutaneous but not in retroperitoneal fat. Interestingly, mRNA levels strongly correlated in both tissues with different parameters related to obesity, such as body weight, adiposity and insulin resistance, suggesting that this gene is a reliable marker of adiposity in this rat model of obesity. Thus, 11betaHSD2 is expressed in adipose tissue by both adipocytes and stromal-vascular cells, which suggests that this enzyme may play an important role in preventing fat accumulation in adipose tissue.

  2. Epicardial adipose tissue in endocrine and metabolic diseases.

    Science.gov (United States)

    Iacobellis, Gianluca

    2014-05-01

    Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

  3. MicroRNAs in dysfunctional adipose tissue: cardiovascular implications.

    Science.gov (United States)

    Icli, Basak; Feinberg, Mark W

    2017-07-01

    In this review, we focus on the emerging role of microRNAs, non-coding RNAs that regulate gene expression and signaling pathways, in dysfunctional adipose tissue. We highlight current paradigms of microRNAs involved in adipose differentiation and function in depots such as white, brown, and beige adipose tissues and potential implications of microRNA dysregulation in human disease such as obesity, inflammation, microvasculature dysfunction, and related cardiovascular diseases. We highlight accumulating studies indicating that adipocyte-derived microRNAs may not only serve as biomarkers of cardiometabolic disease, but also may directly regulate gene expression of other tissues. Finally, we discuss the future prospects, challenges, and emerging strategies for microRNA delivery and targeting for therapeutic applications in cardiovascular disease states associated with adipocyte dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  4. The effect of hypokinesia on lipid metabolism in adipose tissue

    Science.gov (United States)

    Macho, Ladislav; Kvetn̆anský, Richard; Ficková, Mária

    The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.

  5. Adipose tissue Fatty Acid patterns and changes in antrhropometry

    DEFF Research Database (Denmark)

    Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre

    2011-01-01

    Introduction Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns...... in adipose tissue fatty acids and changes in anthropometry. Methods 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate...... the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC), and WC controlled for changes in body mass index (WCBMI), adjusting for confounders. Results 7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men...

  6. The effects of adipose tissue and adipocytokines in human pregnancy.

    Science.gov (United States)

    Valsamakis, G; Kumar, S; Creatsas, G; Mastorakos, G

    2010-09-01

    During pregnancy, important changes take place in maternal metabolism because of the growing fetus and placental formation. The increase in insulin resistance during pregnancy is paralleled by the progressive increase of maternal adipose tissue deposition. This review examines the topography of fat mass deposition during pregnancy in relation to factors such as parity and maternal age that might affect this deposition. We also examine adipose tissue markers, such as pregravid weight and weight gain during pregnancy, and their effect on fetal growth and pregnancy outcomes. In addition, this review studies the possible effects of cytokines that are produced by adipose tissue and the placenta on maternal metabolism and its complications. Finally, we also consider the possible role of maternal adipocytokines and fetal adipocytokines on fetal growth. © 2010 New York Academy of Sciences.

  7. In vivo Analysis of White Adipose Tissue in Zebrafish

    Science.gov (United States)

    Minchin, James E.N.; Rawls, John F.

    2016-01-01

    White adipose tissue (WAT) is the major site of energy storage in bony vertebrates, and also serves central roles in the endocrine regulation of energy balance. The cellular and molecular mechanisms underlying WAT development and physiology are not well understood. This is due in part to difficulties associated with imaging adipose tissues in mammalian model systems, especially during early life stages. The zebrafish (Danio rerio) has recently emerged as a new model system for adipose tissue research, in which WAT can be imaged in a transparent living vertebrate at all life stages. Here we present detailed methods for labeling adipocytes in live zebrafish using fluorescent lipophilic dyes, and for in vivo microscopy of zebrafish WAT. PMID:21951526

  8. Bovine dedifferentiated adipose tissue (DFAT) cells

    OpenAIRE

    Wei, Shengjuan; Du, Min; Jiang, Zhihua; Duarte, Marcio S.; Fernyhough-Culver, Melinda; Albrecht, Elke; Will, Katja; Zan, Linsen; Hausman, Gary J.; Elabd, Elham M Youssef; Bergen, Werner G.; Basu, Urmila; Dodson, Michael V.

    2013-01-01

    Dedifferentiated fat cells (DFAT cells) are derived from lipid-containing (mature) adipocytes, which possess the ability to symmetrically or asymmetrically proliferate, replicate, and redifferentiate/transdifferentiate. Robust cell isolation and downstream culture methods are needed to isolate large numbers of DFAT cells from any (one) adipose depot in order to establish population dynamics and regulation of the cells within and across laboratories. In order to establish more consistent/repea...

  9. Resistant starch improves insulin resistance and reduces adipose tissue weight and CD11c expression in rat OLETF adipose tissue.

    Science.gov (United States)

    Harazaki, Tomomi; Inoue, Seiya; Imai, Chihiro; Mochizuki, Kazuki; Goda, Toshinao

    2014-05-01

    CD11s/CD18 dimers induce monocyte/macrophage infiltration into many tissues, including adipose tissues. In particular, it was reported that β2-integrin CD11c-positive macrophages in adipose tissues are closely associated with the development of insulin resistance. The aim of this study was to determine whether intake of resistant starch (RS) reduces macrophage accumulation in adipose tissues and inhibits the development of insulin resistance at an early stage in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Twenty-two-wk-old male OLETF rats were fed a control diet (55% α-corn starch) or an RS diet (55% RS) for 5 wk. An oral glucose tolerance test was performed after 4 wk of feeding; tissues (mesenteric and epididymal adipose tissues, and liver) and tail vein blood were collected after 5 wk of feeding the test diets. Feeding the RS diet to OLETF rats for 5 wk improved insulin resistance, reduced the mesenteric adipose tissue weight, and enhanced the number of small adipocytes. CD68 expression, a macrophage infiltration marker, was not changed by the RS diet, whereas the gene expression levels of integrins such as CD11c, CD11d, and CD18, but not CD11a, and CD11b, were significantly reduced. CD11c protein expression was reduced by the RS diet. These findings suggest that part of the mechanism for the improved insulin resistance by the RS diet involves a reduction of CD11c expression in adipose tissues. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Different adipose tissue depots: Metabolic implications and effects of surgical removal.

    Science.gov (United States)

    Marcadenti, Aline; de Abreu-Silva, Erlon Oliveira

    2015-11-01

    Increased adiposity has been associated to worse metabolic profile, cardiovascular disease, and mortality. There are two main adipose tissue depots in the body, subcutaneous and visceral adipose tissue, which differ in anatomical location. A large body of evidence has shown the metabolic activity of adipose tissue; lipectomy and/or liposuction therefore appear to be alternatives for improving metabolic profile through rapid loss of adipose tissue. However, surgical removal of adipose tissue may be detrimental for metabolism, because subcutaneous adipose tissue has not been associated to metabolic disorders such as insulin resistance and type 2 diabetes mellitus. In addition, animal studies have shown a compensatory growth of adipose tissue in response to lipectomy. This review summarizes the implications of obesity-induced metabolic dysfunction, its relationship with the different adipose tissue depots, and the effects of lipectomy on cardiometabolic risk factors. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  11. Expression of Resistin Protein in Normal Human Subcutaneous Adipose Tissue and Pregnant Women Subcutaneous Adipose Tissue and Placenta

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yongming; GUO Tiecheng; ZHANG Muxun; GUO Wei; YU Meixia; XUE Keying; HUANG Shiang; CHEN Yanhong; ZHU Huanli; XU Lijun

    2006-01-01

    The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabetes mellitus (T2DM), pregnant physiological insulin resistance (IR) and gestational diabetes mellitus (GDM) was investigated. The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta was detected by using Western blotting method.Fasting serum glucose concentration was measured by glucose oxidase assay. Serum cholesterol (CHOL), serum triglycerides (TG), serum HDL cholesterol (HDL-C) and serum LDL cholesterol (LDL-C) were determined by full automatic biochemical instrument. Fasting insulin was measured by enzyme immunoassay to calculate insulin resistance index (IRI). Height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured to calculate body mass index (BMI) and body fat percentage (BF %). Resistin protein expression in pregnant women placental tissue (67 905±8441) (arbitrary A values) was much higher than that in subcutaneous adipose tissue in pregnant women abdomen (40 718 ± 3818, P < 0.01), non-pregnant women abdomen (38 288±2084, P<0.01), normal human abdomen (39 421±6087, P<0.01)and thigh (14 942 ±6706, P<0. 001) respectively. The resistin expression in abdominal subcutaneous adipose tissue showed no significant difference among pregnant, non-pregnant women and normal human, but much higher than that in thigh subcutaneous adipose tissue (P<0. 001). Pearson analysis revealed that resistin protein was correlated with BMI (r=0.42), fasting insulin concentration (r=0.38),IRI (r=0. 34), BF % (r=0.43) and fasting glucose (r=0. 39), but not with blood pressure,CHOL, TG, HDL-C and LDL-C. It was suggested that resistin protein expression in human abdominal subcutaneous adipose tissue was much higher

  12. Adipocyte insulin receptor activity maintains adipose tissue mass and lifespan.

    Science.gov (United States)

    Friesen, Max; Hudak, Carolyn S; Warren, Curtis R; Xia, Fang; Cowan, Chad A

    2016-08-05

    Type 2 diabetes follows a well-defined progressive pathogenesis, beginning with insulin resistance in metabolic tissues such as the adipose. Intracellular signaling downstream of insulin receptor activation regulates critical metabolic functions of adipose tissue, including glucose uptake, lipogenesis, lipolysis and adipokine secretion. Previous studies have used the aP2 promoter to drive Cre recombinase expression in adipose tissue. Insulin receptor (IR) knockout mice created using this aP2-Cre strategy (FIRKO mice) were protected from obesity and glucose intolerance. Later studies demonstrated the promiscuity of the aP2 promoter, casting doubts upon the tissue specificity of aP2-Cre models. It is our goal to use the increased precision of the Adipoq promoter to investigate adipocyte-specific IR function. Towards this end we generated an adipocyte-specific IR knockout (AIRKO) mouse using an Adipoq-driven Cre recombinase. Here we report AIRKO mice are less insulin sensitive throughout life, and less glucose tolerant than wild-type (WT) littermates at the age of 16 weeks. In contrast to WT littermates, the insulin sensitivity of AIRKO mice is unaffected by age or dietary regimen. At any age, AIRKO mice are comparably insulin resistant to old or obese WT mice and have a significantly reduced lifespan. Similar results were obtained when these phenotypes were re-examined in FIRKO mice. We also found that the AIRKO mouse is protected from high-fat diet-induced weight gain, corresponding with a 90% reduction in tissue weight of major adipose depots compared to WT littermates. Adipose tissue mass reduction is accompanied by hepatomegaly and increased hepatic steatosis. These data indicate that adipocyte IR function is crucial to systemic energy metabolism and has profound effects on adiposity, hepatic homeostasis and lifespan. Copyright © 2016. Published by Elsevier Inc.

  13. Food restriction and refeeding induces changes in lipid pathways and fat deposition in the adipose and hepatic tissues in rats with diet-induced obesity.

    Science.gov (United States)

    Duarte, Fernanda Oliveira; Sene-Fiorese, Marcela; Cheik, Nadia Carla; Maria, Adriana Simone Lopes Santa; de Aquino, Antônio Eduardo; Oishi, Jorge Camargo; Rossi, Elizeu Antônio; Garcia de Oliveira Duarte, Ana Cláudia; Dâmaso, Ana Raimunda

    2012-07-01

    The aim of this study was to determine the effects of successive cycles of a moderately restrictive diet and refeeding with a high-fat diet on the metabolism of the adipose and hepatic tissues of obese rats. Rats were assigned to the following groups: a chow diet; a high-fat diet; a moderate caloric restriction; or a moderate caloric restriction plus refeeding. Some animals in each group were given [1-(14)C]triolein intragastrically, while others received an intraperitoneal injection of 3 mCi (3)H(2)O. All animals were killed by decapitation. The retroperitoneal, visceral epididymal and omental white adipose tissues, brown adipose tissue, liver and blood were immediately removed. The lipid uptake from the diet, in vivo rate of lipogenesis, percentage of fat, lipid profile and leptin concentration were analysed. The high-fat diet promoted an increase in fatty liver (P ≤ 0.05), adiposity mass (P ≤ 0.05) and the plasma concentration of leptin (P ≤ 0.05) and a decreased lipid uptake in white adipose tissue depots (P ≤ 0.05) in relation to the chow diet. The moderate caloric restriction did not reverse the changes promoted by the high-fat diet but induced a small decrease in adiposity, which was reversed after refeeding, and the animals maintained a dyslipidaemic profile and high fat deposition in the liver. We can conclude that the high-fat diet and subsequent moderate caloric restriction plus refeeding increased the risks of developing visceral obesity, dyslipidaemia and non-alcoholic fatty liver disease, which suggests that this type of experimental protocol can be used to study mechanisms related to the metabolic syndrome.

  14. Chagas disease, adipose tissue and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Fnu Nagajyothi

    2009-07-01

    Full Text Available Trypanosoma cruzi infection of the adipose tissue of mice triggers the local expression of inflammatory mediators and a reduction in the expression of the adipokine adiponectin. T. cruzi can be detected in adipose tissue by PCR 300 days post-infection. Infection of cultured adipocytes results in increased expression of cytokines and chemokines and a reduction in the expression of adiponectin and the peroxisome proliferator-activated receptor ³, both of which are negative regulators of inflammation. Infection also results in the upregulation of cyclin D1, the Notch pathway, and extracellular signal-regulated kinase and a reduction in the expression of caveolin-1. Thus, T. cruzi infection of cultured adipocytes leads to an upregulation of the inflammatory process. Since adiponectin null mice have a cardiomyopathic phenotype, it is possible that the reduction in adiponectin contributes to the pathogenesis of chagasic cardiomyopathy. Adipose tissue may serve as a reservoir for T. cruzi from which parasites can become reactivated during periods of immunosuppression. T. cruzi infection of mice often results in hypoglycemia. In contrast, hyperglycemia as observed in diabetes results in increased parasitemia and mortality. Adipose tissue is an important target tissue of T. cruzi and the infection of this tissue is associated with a profound impact on systemic metabolism, increasing the risk of metabolic syndrome.

  15. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

    Science.gov (United States)

    Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Valenzano, Anna; Esposito, Teresa; Cibelli, Giuseppe

    2017-01-01

    Osteopontin (OPN) is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it seems to be one of the most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis.

  16. Adipose tissue Fatty Acid patterns and changes in antrhropometry

    DEFF Research Database (Denmark)

    Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre

    2011-01-01

    in adipose tissue fatty acids and changes in anthropometry. Methods 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate......Introduction Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns...

  17. Natural killer T cells in adipose tissue are activated in lean mice.

    Science.gov (United States)

    Kondo, Taisuke; Toyoshima, Yujiro; Ishii, Yoshiyuki; Kyuwa, Shigeru

    2013-01-01

    Adipose tissues are closely connected with the immune system. It has been suggested that metabolic syndromes such as type 2 diabetes, arteriosclerosis and liver steatosis can be attributed to adipose tissue inflammation characterized by macrophage infiltration. To understand a physiological and pathological role of natural killer T (NKT) cells on inflammation in adipose tissue, we characterized a subset of NKT cells in abdominal and subcutaneous adipose tissues in C57BL/6J mice fed normal or high-fat diets. NKT cells comprised a larger portion of lymphocytes in adipose tissues compared with the spleen and peripheral blood, with epididymal adipose tissue having the highest number of NKT cells. Furthermore, some NKT cells in adipose tissues expressed higher levels of CD69 and intracellular interferon-γ, whereas the Vβ repertoires of NKT cells in adipose tissues were similar to other cells. In obese mice fed a high-fat diet, adipose tissue inflammation had little effect on the Vβ repertoire of NKT cells in epididymal adipose tissues. We speculate that the NKT cells in adipose tissues may form an equivalent subset in other tissues and that these subsets are likely to participate in adipose tissue inflammation. Additionally, the high expression level of CD69 and intracellular IFN-γ raises the possibility that NKT cells in adipose tissue may be stimulated by some physiological mechanism.

  18. Giant Omental Fibromatosis Presenting as Pelvic Mass

    Science.gov (United States)

    Singh, Pradyumn; Jain, Neelesh; Jain, Jaswant; Kumar, Vijay

    2015-01-01

    Omental fibromatosis (abdominal desmoids) is a rare benign but locally aggressive neoplasm characterized by mass like or infiltrative growth of fibrous tissue. It usually arises from the abdominal wall or the extremities, however rarely it may also arise in the omentum, ileocolic mesentery, transverse or sigmoid mesocolon and ligamentum teres. Here, we present an 18-year-old male, who presented with lower abdominal pain and palpable lump in hypogastric region. Computed tomography of the abdomen showed large heterogeneous mass in lower abdomen, possibly arising from mesentery with regional adenopathy. Patient underwent exploratory laparotomy with a preoperative diagnosis of mesenteric tumour possibly gastrointestinal stromal tumour (GIST). Histopathological examination revealed the lesion as omental fibromatosis. To the best of our knowledge, very few cases of omental fibromatosis are noted in literature. Here, we describe a rare case of giant omental fibromatosis which resembled mesenteric GIST clinically but finally diagnosed as fibromatosis by histomorphology and immunohistochemistry (IHC). The present article describes fibromatosis of greater omentum and the difficulty in preoperative diagnosis, as it is frequently misdiagnosed as GIST. PMID:25859511

  19. Benefits of healthy adipose tissue in the treatment of diabetes.

    Science.gov (United States)

    Gunawardana, Subhadra C

    2014-08-15

    The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin. Insulin deficiency is either absolute due to destruction or failure of pancreatic β cells, or relative due to decreased sensitivity of peripheral tissues to insulin. The primary lesion being related to insulin, treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin. These therapies have their own limitations and complications, some of which can be life-threatening. For example, exogenous insulin administration can lead to fatal hypoglycemic episodes; islet/pancreas transplantation requires life-long immunosuppressive therapy; and anti-diabetic drugs have dangerous side effects including edema, heart failure and lactic acidosis. Thus the need remains for better safer long term treatments for diabetes. The ultimate goal in treating diabetes is to re-establish glucose homeostasis, preferably through endogenously generated hormones. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism. While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines, healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties, which can complement and/or compensate for the function of insulin. Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes, and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin. Although specific adipokines may correct diabetes, administration of individual adipokines still carries risks similar to those of insulin monotherapy. Thus a

  20. Vitamin D and adipose tissue - more than storage

    Directory of Open Access Journals (Sweden)

    Shivaprakash Jagalur Mutt

    2014-06-01

    Full Text Available The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OHD, no evidence was obtained for a BMI lowering effect by higher 25(OHD. Some of the physiological functions of 1,25(OH2D3 (1,25-dihydroxycholecalciferol or calcitriol via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g. in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH2D3, vitamin D binding proteins (VDBPs and nuclear vitamin D receptor (VDR after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR -/- and CYP27B1 knock out (CYP27B1 -/- mouse models: Both VDR -/- and CYP27B1 -/- models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH2D3. Experimental studies demonstrate that 1,25(OH2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases.

  1. Maternal nutritional manipulations program adipose tissue dysfunction in offspring.

    Science.gov (United States)

    Lecoutre, Simon; Breton, Christophe

    2015-01-01

    Based on the concept of Developmental Origin of Health and Disease, both human and animal studies have demonstrated a close link between nutrient supply perturbations in the fetus or neonate (i.e., maternal undernutrition, obesity, gestational diabetes and/or rapid catch-up growth) and increased risk of adult-onset obesity. Indeed, the adipose tissue has been recognized as a key target of developmental programming in a sex-and depot-specific manner. Despite different developmental time windows, similar mechanisms of adipose tissue programming have been described in rodents and in bigger mammals (sheep, primates). Maternal nutritional manipulations reprogram offspring's adipose tissue resulting in series of alterations: enhanced adipogenesis and lipogenesis, impaired sympathetic activity with reduced noradrenergic innervations and thermogenesis as well as low-grade inflammation. These changes affect adipose tissue development, distribution and composition predisposing offspring to fat accumulation. Modifications of hormonal tissue sensitivity (i.e., leptin, insulin, glucocorticoids) and/or epigenetic mechanisms leading to persistent changes in gene expression may account for long-lasting programming across generations.

  2. Maternal nutritional manipulations program adipose tissue dysfunction in offspring

    Directory of Open Access Journals (Sweden)

    Simon eLecoutre

    2015-05-01

    Full Text Available Based on the concept of Developmental Origin of Health and Disease, both human and animal studies have demonstrated a close link between nutrient supply perturbations in the fetus or neonate (i.e., maternal undernutrition, obesity, gestational diabetes and/or rapid catch-up growth and increased risk of adult-onset obesity. Indeed, the adipose tissue has been recognized as a key target of developmental programming in a sex-and depot-specific manner. Despite different developmental time windows, similar mechanisms of adipose tissue programming have been described in rodents and in bigger mammals (sheep, primates. Maternal nutritional manipulations reprogram offspring’s adipose tissue resulting in series of alterations: enhanced adipogenesis and lipogenesis, impaired sympathetic activity with reduced noradrenergic innervations and thermogenesis as well as low-grade inflammation. These changes affect adipose tissue development, distribution and composition predisposing offspring to fat accumulation. Modifications of hormonal tissue sensitivity (i.e., leptin, insulin, glucocorticoids and/or epigenetic mechanisms leading to persistent changes in gene expression may account for long-lasting programming across generations.

  3. Ontogenetic development of adipose tissue in grass carp (Ctenopharyngodon idellus).

    Science.gov (United States)

    Liu, Pin; Ji, Hong; Li, Chao; Tian, Jingjing; Wang, Yifei; Yu, Ping

    2015-08-01

    To investigate the adipose tissue development process during the early stages of grass carp (Ctenopharyngodon idellus) development, samples were collected from fertilized eggs to 30 days post-fertilization (dpf) of fish. Paraffin and frozen sections were taken to observe the characteristics of adipocytes in vivo by different staining methods, including hematoxylin and eosin (H&E), Oil red O, and BODIPY. The expression of lipogenesis-related genes of the samples at different time points was detected by real-time qPCR. In addition, protein expression level of peroxisome proliferator-activated receptors γ (PPAR γ) was detected by immunohistochemistry. The results showed that the neutral lipid droplets accumulated first in the hepatocytes of 14-dpf fish larvae, and visceral adipocytes appeared around the hepatopancreas on 16 dpf. As grass carp grew, the adipocytes increased in number and spread to other tissues. In 20-dpf fish larvae, the intestine was observed to be covered by adipose tissue. However, there was no significant change in the average size (30.40-40.01 μm) of adipocytes during this period. Accordingly, the gene expression level of PPAR γ and CCAAT/enhancer-binding proteins α (C/EBP α) was significantly elevated after fertilization for 12 days (p adipose tissue is caused by active recruitment of adipocytes as opposed to hypertrophy of the cell. In addition, our study indicated that lipogenesis-related genes might regulate the ongoing development of adipose tissue.

  4. Myocardial regeneration potential of adipose tissue-derived stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xiaowen, E-mail: baixw01@yahoo.com [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States); Alt, Eckhard, E-mail: ealt@mdanderson.org [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States)

    2010-10-22

    Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

  5. Browning of white adipose tissue: role of hypothalamic signaling.

    Science.gov (United States)

    Bi, Sheng; Li, Lin

    2013-10-01

    Two types of fat, white adipose tissue (WAT) and brown adipose tissue (BAT), exist in mammals including adult humans. While WAT stores excess calories and an excessive accumulation of fat causes obesity, BAT dissipates energy to produce heat through nonshivering thermogenesis for protection against cold environments and provides the potential for the development of novel anti-obesity treatments. The hypothalamus plays a central role in the control of energy balance. Specifically, recent observations indicate the importance of the dorsomedial hypothalamus (DMH) in thermoregulation. We have found that the orexigenic neuropeptide Y (NPY) in the DMH has distinct actions in modulating adiposity and BAT thermogenesis. Knockdown of NPY in the DMH elevates the thermogenic activity of classic BAT and promotes the development of brown adipocytes in WAT, leading to increased thermogenesis. These findings identify a novel potential target for combating obesity.

  6. Physiological and pathological impact of exosomes of adipose tissue.

    Science.gov (United States)

    Zhang, Yan; Yu, Mei; Tian, Weidong

    2016-02-01

    Exosomes are nanovesicles that have emerged as a new intercellular communication system for transporting proteins and RNAs; recent studies have shown that they play a role in many physiological and pathological processes such as immune regulation, cell differentiation, infection and cancer. By transferring proteins, mRNAs and microRNAs, exosomes act as information vehicles that alter the behavior of recipient cells. Compared to direct cell-cell contact or secreted factors, exosomes can affect recipient cells in more efficient ways. In whole adipose tissues, it has been shown that exosomes exist in supernatants of adipocytes and adipose stromal cells (ADSCs). Adipocyte exosomes are linked to lipid metabolism and obesity-related insulin resistance and exosomes secreted by ADSCs are involved in angiogenesis, immunomodulation and tumor development. This review introduces characteristics of exosomes in adipose tissue, summarizes their functions in different physiological and pathological processes and provides the further insight into potential application of exosomes to disease diagnosis and treatment.

  7. Lipolysis and lipases in white adipose tissue - An update.

    Science.gov (United States)

    Bolsoni-Lopes, Andressa; Alonso-Vale, Maria Isabel C

    2015-08-01

    Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanisms involved, which reformulated the concept of lipolysis. Novel findings from these studies include the identification of lipolytic products as signaling molecules regulating important metabolic processes in many non-adipose tissues, unveiling a previously underestimated aspect of lipolysis. Thus, we present here an updated review of concepts and regulation of white adipocyte lipolysis with a special emphasis in its role in metabolism homeostasis and as a source of important signaling molecules.

  8. Hkat, a novel nutritionally regulated transmembrane protein in adipose tissues.

    Science.gov (United States)

    Zhang, Ren

    2012-01-01

    White adipose tissue is an active endocrine organ regulating many aspects of whole body physiology and pathology. Adipogenesis, a process in which premature cells differentiate into adipocytes, is a complex process that includes orchestrated changes in gene expression and cell morphology in response to various nutritional and hormonal stimuli. To profile transcriptome changes in response to nutritional stimulation, we performed RNA-seq on fat in mice treated with either a high-fat diet or fasting. We identified a novel nutritionally regulated gene, Gm12824, named Hkat (heart, kidney, adipose-enriched transmembrane protein). We show that both fasting and obesity dramatically reduce Hkat in white adipose tissue, and that fasting reduces while obesity increases its expression in brown fat. Hkat is localized to the plasma membrane and induced during adipogenesis. Therefore, Hkat is a novel nutritionally regulated gene that is potentially involved in metabolism.

  9. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders

    Science.gov (United States)

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response. PMID:27148161

  10. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

    Directory of Open Access Journals (Sweden)

    Sung Sik eChoe

    2016-04-01

    Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  11. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    Science.gov (United States)

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  12. The Combination of Tissue Dissection and External Volume Expansion Generates Large Volumes of Adipose Tissue.

    Science.gov (United States)

    He, Yunfan; Dong, Ziqing; Xie, Gan; Zhou, Tao; Lu, Feng

    2017-04-01

    Noninvasive external volume expansion device has been applied to stimulate nonsurgical breast enlargement in clinical settings. Although previous results demonstrate the capacity of external volume expansion to increase the number of adipocytes, this strategy alone is insufficient to reconstruct soft-tissue defects or increase breast mass. The authors combined a minimally invasive tissue dissection method with external volume expansion to generate large volumes of adipose tissue. In vitro, various densities of adipose-derived stem cells were prepared to evaluate relations between cell contacts and cell proliferation. In vivo, dorsal adipose tissue of rabbits was thoroughly dissected and the external volume expansion device was applied to maintain the released state. External volume expansion without tissue dissection served as the control. In the dissection group, the generated adipose tissue volume was much larger than that in the control group at all time points. A larger number of proliferating cells appeared in the dissection samples than in the control samples at the early stage after tissue dissection. At low cell density, adipose-derived stem cells displayed an increasing proliferation rate compared to high cell density. Protein expression analysis revealed that cell proliferation was mediated by a similar mechanism both in vivo and in vitro, involving the release of cell contact inhibition and Hippo/Yes-associated protein pathway activation. Adipose tissue dissection releases cell-to-cell contacts and induces adipose-derived stem cell proliferation. Preexpanded adipose-derived stem cells undergo adipogenesis under the adipogenic environment created by external volume expansion, leading to better adipose regeneration compared with the control.

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

    Science.gov (United States)

    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.

  14. Insulin receptor signaling in POMC, but Not AgRP, neurons controls adipose tissue insulin action

    National Research Council Canada - National Science Library

    Oberlin, Douglas; Chi, Tiffany; Buettner, Christoph; Shin, Andrew C; Degann, Seta; Filatova, Nika; Lindtner, Claudia

    2017-01-01

    Insulin is a key regulator of adipose tissue lipolysis, and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes...

  15. Subcutaneous abdominal adipose tissue lipolysis during exercise determined by arteriovenous measurements in older women

    DEFF Research Database (Denmark)

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

    2002-01-01

    To characterize the lipolytic response in the subcutaneous abdominal adipose tissue in older women to endurance exercise.......To characterize the lipolytic response in the subcutaneous abdominal adipose tissue in older women to endurance exercise....

  16. Molecular pathways regulating the formation of brown-like adipocytes in white adipose tissue.

    Science.gov (United States)

    Fu, Jianfei; Li, Zhen; Zhang, Huiqin; Mao, Yushan; Wang, Anshi; Wang, Xin; Zou, Zuquan; Zhang, Xiaohong

    2015-07-01

    Adipose tissue is functionally composed of brown adipose tissue and white adipose tissue. The unique thermogenic capacity of brown adipose tissue results from expression of uncoupling protein 1 in the mitochondrial inner membrane. On the basis of recent findings that adult humans have functionally active brown adipose tissue, it is now recognized as playing a much more important role in human metabolism than was previously thought. More importantly, brown-like adipocytes can be recruited in white adipose tissue upon environmental stimulation and pharmacologic treatment, and this change is associated with increased energy expenditure, contributing to a lean and healthy phenotype. Thus, the promotion of brown-like adipocyte development in white adipose tissue offers novel possibilities for the development of therapeutic strategies to combat obesity and related metabolic diseases. In this review, we summarize recent advances in understanding the molecular mechanisms involved in the recruitment of brown-like adipocyte in white adipose tissue.

  17. Metabolic and Vascular Consequences of Adipose Tissue Dysfunction

    NARCIS (Netherlands)

    Westerink, J.|info:eu-repo/dai/nl/343038617

    2012-01-01

    Adipose Tissue Dysfunction (ATD) has been proposed as the pathophysiological route by which obesity confers its associated increased risk for cardiovascular disease and is characterized by an increased secretion of pro-inflammatory cytokines and adipokines and reduced secretion of anti-inflammatory

  18. Adipose Tissue Dysfunction : Clinical Relevance and Diagnostic Possibilities

    NARCIS (Netherlands)

    Schrover, I. M.; Spiering, W.; Leiner, T.; Visseren, F. L J

    2016-01-01

    Adipose tissue dysfunction is defined as an imbalance between pro- and anti-inflammatory adipokines, causing insulin resistance, systemic low-grade inflammation, hypercoagulability, and elevated blood pressure. These can lead to cardiovascular disease and diabetes mellitus type 2. Although quantity

  19. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

    DEFF Research Database (Denmark)

    Sun, Kai; Park, Jiyoung; Gupta, Olga T

    2014-01-01

    We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonst...

  20. Adipose Tissue Dysfunction : Clinical Relevance and Diagnostic Possibilities

    NARCIS (Netherlands)

    Schrover, I. M.; Spiering, W.; Leiner, T.; Visseren, F. L J

    2016-01-01

    Adipose tissue dysfunction is defined as an imbalance between pro- and anti-inflammatory adipokines, causing insulin resistance, systemic low-grade inflammation, hypercoagulability, and elevated blood pressure. These can lead to cardiovascular disease and diabetes mellitus type 2. Although quantity

  1. Obesity induces a phenotypic switch in adipose tissue macrophage polarization.

    Science.gov (United States)

    Lumeng, Carey N; Bodzin, Jennifer L; Saltiel, Alan R

    2007-01-01

    Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.

  2. Spice Up Your Life: Adipose Tissue and Inflammation

    Directory of Open Access Journals (Sweden)

    Anil K. Agarwal

    2014-01-01

    Full Text Available Cells of the immune system are now recognized in the adipose tissue which, in obesity, produces proinflammatory chemokines and cytokines. Several herbs and spices have been in use since ancient times which possess anti-inflammatory properties. In this perspective, I discuss and propose the usage of these culinary delights for the benefit of human health.

  3. Endocrine modulators of mouse subcutaneous adipose tissue beige adipocyte markers

    Science.gov (United States)

    The stromal vascular fraction (SVF) of subcutaneous adipose tissue contains precursors that can give rise to beige adipocytes. Beige adipocytes are characterized by the expression of specific markers, but it is not clear which markers best evaluate beige adipocyte differentiation. Both regulators of...

  4. Browning attenuates murine white adipose tissue expansion during postnatal development.

    Science.gov (United States)

    Lasar, D; Julius, A; Fromme, T; Klingenspor, M

    2013-05-01

    During postnatal development of mice distinct white adipose tissue depots display a transient appearance of brown-like adipocytes. These brite (brown in white) adipocytes share characteristics with classical brown adipocytes including a multilocular appearance and the expression of the thermogenic protein uncoupling protein 1. In this study, we compared two inbred mouse strains 129S6sv/ev and C57BL6/N known for their different propensity to diet-induced obesity. We observed transient browning in retroperitoneal and inguinal adipose tissue depots of these two strains. From postnatal day 10 to 20 the increase in the abundance of multilocular adipocytes and uncoupling protein 1 expression was higher in 129S6sv/ev than in C57BL6/N pups. The parallel increase in the mass of the two fat depots was attenuated during this browning period. Conversely, epididymal white and interscapular brown adipose tissue displayed a steady increase in mass during the first 30 days of life. In this period, 129S6sv/ev mice developed a significantly higher total body fat mass than C57BL6/N. Thus, while on a local depot level a high number of brite cells is associated with the attenuation of adipose tissue expansion the strain comparison reveals no support for a systemic impact on energy balance. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  5. Brown adipose tissue takes up plasma triglycerides mostly after lipolysis

    NARCIS (Netherlands)

    Khedoe, P.P.S.J.; Hoeke, Geerte; Kooijman, Sander; Dijk, Wieneke; Buijs, Jeroen T.; Kersten, Sander; Havekes, Louis M.; Hiemstra, Pieter S.; Berbée, Jimmy F.P.; Boon, Mariëtte R.; Rensen, Patrick C.N.

    2015-01-01

    Brown adipose tissue (BAT) produces heat by burning TGs that are stored within intracellular lipid droplets and need to be replenished by the uptake of TG-derived FA from plasma. It is currently unclear whether BAT takes up FA via uptake of TG-rich lipoproteins (TRLs), after lipolysis-mediated li

  6. The immunosuppressive agents rapamycin, cyclosporin A and tacrolimus increase lipolysis, inhibit lipid storage and alter expression of genes involved in lipid metabolism in human adipose tissue.

    Science.gov (United States)

    Pereira, Maria J; Palming, Jenny; Rizell, Magnus; Aureliano, Manuel; Carvalho, Eugénia; Svensson, Maria K; Eriksson, Jan W

    2013-01-30

    Cyclosporin A (CsA), tacrolimus and rapamycin are immunosuppressive agents (IAs) associated with insulin resistance and dyslipidemia, although their molecular effects on lipid metabolism in adipose tissue are unknown. We explored IAs effects on lipolysis, lipid storage and expression of genes involved on lipid metabolism in isolated human adipocytes and/or adipose tissue obtained via subcutaneous and omental fat biopsies. CsA, tacrolimus and rapamycin increased isoproterenol-stimulated lipolysis and inhibited lipid storage by 20-35% and enhanced isoproterenol-stimulated hormone-sensitive lipase Ser552 phosphorylation. Rapamycin also increased basal lipolysis (~20%) and impaired insulin's antilipolytic effect. Rapamycin, down-regulated the gene expression of perilipin, sterol regulatory element-binding protein 1 (SREBP1) and lipin 1, while tacrolimus down-regulated CD36 and aP2 gene expression. All three IAs increased IL-6 gene expression and secretion, but not expression and secretion of TNF-α or adiponectin. These findings suggest that CsA, tacrolimus and rapamycin enhance lipolysis, inhibit lipid storage and expression of lipogenic genes in adipose tissue, which may contribute to the development of dyslipidemia and insulin resistance associated with immunosuppressive therapy.

  7. Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity

    OpenAIRE

    2010-01-01

    Adipose tissue expresses all components of the renin-angiotensin system including angiotensinogen (AGT). Recent studies have highlighted a potential role of AGT in adipose tissue function and homeostasis. However, some controversies surround the regulatory mechanisms of AGT in obese adipose tissue. In this context, we here demonstrated that the AGT messenger RNA (mRNA) level in human subcutaneous adipose tissue was significantly reduced in obese subjects as compared with nonobese subjects. Ad...

  8. Thematic review series: Adipocyte Biology. Adipose tissue function and plasticity orchestrate nutritional adaptation

    OpenAIRE

    Sethi, Jaswinder K.; Vidal-Puig, Antonio J

    2007-01-01

    This review focuses on adipose tissue biology and introduces the concept of adipose tissue plasticity and expandability as key determinants of obesity-associated metabolic dysregulation. This concept is fundamental to our understanding of adipose tissue as a dynamic organ at the center of nutritional adaptation. Here, we summarize the current knowledge of the mechanisms by which adipose tissue can affect peripheral energy homeostasis, particularly in the context of overnutrition. Two mechanis...

  9. A Story in Brown and White Regulation of Metabolic Homeostasis by Brown Adipose tissue

    OpenAIRE

    Mössenböck, Karin

    2016-01-01

    Adipose tissue exists in three shades: White adipose tissue (WAT), the site of energy storage, brown adipose tissue (BAT), which burns nutrients to generate heat and maintain body temperature, and brown in white adipose tissue (brite AT), which represents WAT adapting BAT features in cold exposure. Thermogenically active BAT has been discovered in adult humans and inversely correlates with obesity and insulin resistance. The link between impaired insulin sensitivity and the browning of adipos...

  10. Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels*

    OpenAIRE

    Herman, Mark A.; She, Pengxiang; Peroni, Odile D.; Lynch, Christopher J.; Kahn, Barbara B.

    2010-01-01

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent obse...

  11. Caspase Induction and BCL2 Inhibition in Human Adipose Tissue

    Science.gov (United States)

    Tinahones, Francisco José; Coín Aragüez, Leticia; Murri, Mora; Oliva Olivera, Wilfredo; Mayas Torres, María Dolores; Barbarroja, Nuria; Gomez Huelgas, Ricardo; Malagón, Maria M.; El Bekay, Rajaa

    2013-01-01

    OBJECTIVE Cell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling. RESEARCH DESIGN AND METHODS The expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-α or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects. RESULTS SAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In obese subjects, CASP3/7 activation and BCL2 downregulation correlated with the IRS-1/2–expression levels. Expression levels of caspases, BCL2, p21, p53, IRS-1/2, GLUT4, protein tyrosine phosphatase 1B, and leukocyte antigen-related phosphatase in TNF-α– or IL-6–treated explants from lean subjects were comparable with those found in adipose tissue samples from morbidly obese subjects. These insulin component expression levels were reverted with CASP3/7 inhibition in these TNF-α– or IL-6–treated explants. CONCLUSIONS Body fat mass increase is associated with CASP3/7 and BCL2 expression in adipose tissue. Moreover, this proapoptotic state correlated with insulin signaling, suggesting its potential contribution to the development of insulin resistance. PMID:23193206

  12. Allergen exposure induces adipose tissue inflammation and insulin resistance.

    Science.gov (United States)

    Jung, Chien-Cheng; Tsai, Yau-Sheng; Chang, Chih-Ching; Cheng, Tsun-Jen; Chang, Ching-Wen; Liu, Ping-Yen; Chiu, Yi-Jen; Su, Huey-Jen

    2014-11-01

    This study investigates whether exposure to allergen elicits insulin resistance as a result of adipose tissue inflammation. Male C57BL/6 mice were challenged with ovalbumin (OVA) allergen for 12 weeks, and blood and adipose tissue samples were collected at 24h after the last challenge. Levels of adhesion molecules, fasting insulin, fasting glucose, and adipokines in the blood were analyzed, and fasting homeostasis model assessment was applied to determine insulin resistance (HOMA-IR). The expression of pro- and anti-inflammatory genes in dissected adipose tissues was analyzed by real-time RT-PCR. Our results showed that OVA exposure increased insulin resistance as well as resistin and E-selectin, but reduced adiponectin in the serum. Resistin level was significantly correlated with HOMA-IR. Moreover, in adipose tissues of OVA-challenged mice, the pro-inflammatory M1 genes were more abundant while the anti-inflammatory M2 genes were less than those of PBS-treated mice. The expressional changes of both M1 and M2 genes were significantly associated with serum levels of adiponectin, resistin, and E-selectin. Hematoxylin and eosin (HE) and immunohistochemistry (IHC) stain also showed that there was more obvious inflammation in OVA-challenged mice. In conclusion, the current study suggests the relationship between allergen-elicited adipose tissue inflammation and circulating inflammatory molecules, which are possible mediators for the development of insulin resistance. Therefore, we propose that allergen exposure might be one risk factor for insulin resistance. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Exercise Effects on White Adipose Tissue: Beiging and Metabolic Adaptations.

    Science.gov (United States)

    Stanford, Kristin I; Middelbeek, Roeland J W; Goodyear, Laurie J

    2015-07-01

    Regular physical activity and exercise training have long been known to cause adaptations to white adipose tissue (WAT), including decreases in cell size and lipid content and increases in mitochondrial proteins. In this article, we discuss recent studies that have investigated the effects of exercise training on mitochondrial function, the "beiging" of WAT, regulation of adipokines, metabolic effects of trained adipose tissue on systemic metabolism, and depot-specific responses to exercise training. The major WAT depots in the body are found in the visceral cavity (vWAT) and subcutaneously (scWAT). In rodent models, exercise training increases mitochondrial biogenesis and activity in both these adipose tissue depots. Exercise training also increases expression of the brown adipocyte marker uncoupling protein 1 (UCP1) in both adipose tissue depots, although these effects are much more pronounced in scWAT. Consistent with the increase in UCP1, exercise training increases the presence of brown-like adipocytes in scWAT, also known as browning or beiging. Training results in changes in the gene expression of thousands of scWAT genes and an altered adipokine profile in both scWAT and vWAT. Transplantation of trained scWAT in sedentary recipient mice results in striking improvements in skeletal muscle glucose uptake and whole-body metabolic homeostasis. Human and rodent exercise studies have indicated that exercise training can alter circulating adipokine concentration as well as adipokine expression in adipose tissue. Thus, the profound changes to WAT in response to exercise training may be part of the mechanism by which exercise improves whole-body metabolic health.

  14. Pharmacological and nutritional agents promoting browning of white adipose tissue.

    Science.gov (United States)

    Bonet, M Luisa; Oliver, Paula; Palou, Andreu

    2013-05-01

    The role of brown adipose tissue in the regulation of energy balance and maintenance of body weight is well known in rodents. Recently, interest in this tissue has re-emerged due to the realization of active brown-like adipose tissue in adult humans and inducible brown-like adipocytes in white adipose tissue depots in response to appropriate stimuli ("browning process"). Brown-like adipocytes that appear in white fat depots have been called "brite" (from brown-in-white) or "beige" adipocytes and have characteristics similar to brown adipocytes, in particular the capacity for uncoupled respiration. There is controversy as to the origin of these brite/beige adipocytes, but regardless of this, induction of the browning of white fat represents an attractive potential strategy for the management and treatment of obesity and related complications. Here, the different physiological, pharmacological and dietary determinants that have been linked to white-to-brown fat remodeling and the molecular mechanisms involved are reviewed in detail. In the light of available data, interesting therapeutic perspectives can be expected from the use of specific drugs or food compounds able to induce a program of brown fat differentiation including uncoupling protein 1 expression and enhancing oxidative metabolism in white adipose cells. However, additional research is needed, mainly focused on the physiological relevance of browning and its dietary control, where the use of ferrets and other non-rodent animal models with a more similar adipose tissue organization and metabolism to humans could be of much help. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

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  16. CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis

    NARCIS (Netherlands)

    Park, Jong-Gil; Xu, Xu; Cho, Sungyun; Hur, Kyu Yeon; Lee, Myung-Shik; Kersten, Sander; Lee, Ann-Hwee

    2016-01-01

    Adipose tissue lipolysis produces glycerol and nonesterified fatty acids (NEFA) that serve as energy sources during nutrient scarcity. Adipose tissue lipolysis is tightly regulated and excessive lipolysis causes hepatic steatosis, as NEFA released from adipose tissue constitutes a major source of TG

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  6. Adipose tissue and metabolic syndrome: too much, too little or neither.

    Science.gov (United States)

    Grundy, Scott M

    2015-11-01

    Obesity is strongly associated with metabolic syndrome. Recent research suggests that excess adipose tissue plays an important role in development of the syndrome. On the other hand, persons with a deficiency of adipose tissue (e.g. lipodystrophy) also manifest the metabolic syndrome. In some animal models, expansion of adipose tissue pools mitigates adverse metabolic components (e.g. insulin resistance, hyperglycaemia and dyslipidemia). Hence, there are conflicting data as to whether adipose tissue worsens the metabolic syndrome or protects against it. This conflict may relate partly to locations of adipose tissue pools. For instance, lower body adipose tissue may be protective whereas upper body adipose tissue may promote the syndrome. One view holds that in either case, the accumulation of ectopic fat in muscle and liver is the driving factor underlying the syndrome. If so, there may be some link between adipose tissue fat and ectopic fat. But the mechanisms underlying this connection are not clear. A stronger association appears to exist between excessive caloric intake and ectopic fat accumulation. Adipose tissue may act as a buffer to reduce the impact of excess energy consumption by fat storage; but once a constant weight has been achieved, it is unclear whether adipose tissue influences levels of ectopic fat. Another mechanism whereby adipose tissue could worsen the metabolic syndrome is through release of adipokines. This is an intriguing mechanism, but the impact of adipokines on metabolic syndrome risk factors is uncertain. Thus, many potential connections between adipose tissue and metabolic syndrome remain to unravelled.

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  1. File list: DNS.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  9. Circadian regulation of lipid mobilization in white adipose tissues.

    Science.gov (United States)

    Shostak, Anton; Meyer-Kovac, Judit; Oster, Henrik

    2013-07-01

    In mammals, a network of circadian clocks regulates 24-h rhythms of behavior and physiology. Circadian disruption promotes obesity and the development of obesity-associated disorders, but it remains unclear to which extent peripheral tissue clocks contribute to this effect. To reveal the impact of the circadian timing system on lipid metabolism, blood and adipose tissue samples from wild-type, ClockΔ19, and Bmal1(-/-) circadian mutant mice were subjected to biochemical assays and gene expression profiling. We show diurnal variations in lipolysis rates and release of free fatty acids (FFAs) and glycerol into the blood correlating with rhythmic regulation of two genes encoding the lipolysis pacemaker enzymes, adipose triglyceride (TG) lipase and hormone-sensitive lipase, by self-sustained adipocyte clocks. Circadian clock mutant mice show low and nonrhythmic FFA and glycerol blood content together with decreased lipolysis rates and increased sensitivity to fasting. Instead circadian clock disruption promotes the accumulation of TGs in white adipose tissue (WAT), leading to increased adiposity and adipocyte hypertrophy. In summary, circadian modulation of lipolysis rates regulates the availability of lipid-derived energy during the day, suggesting a role for WAT clocks in the regulation of energy homeostasis.

  10. 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.

  11. Effects of Exendin-4 on human adipose tissue inflammation and ECM remodelling

    Science.gov (United States)

    Pastel, E; Joshi, S; Knight, B; Liversedge, N; Ward, R; Kos, K

    2016-01-01

    BACKGROUND/OBJECTIVES: Subjects with type-2 diabetes are typically obese with dysfunctional adipose tissue (AT). Glucagon-like peptide-1 (GLP-1) analogues are routinely used to improve glycaemia. Although, they also aid weight loss that improves AT function, their direct effect on AT function is unclear. To explore GLP-1 analogues' influence on human AT's cytokine and extracellular matrix (ECM) regulation, we therefore obtained and treated omental (OMAT) and subcutaneous (SCAT) AT samples with Exendin-4, an agonist of the GLP-1 receptor (GLP-1R). SUBJECTS/METHODS: OMAT and abdominal SCAT samples obtained from women during elective surgery at the Royal Devon & Exeter Hospital (UK) were treated with increasing doses of Exendin-4. Changes in RNA expression of adipokines, inflammatory cytokines, ECM components and their regulators were assessed and protein secretion analysed by ELISA. GLP-1R protein accumulation was compared in paired AT depot samples. RESULTS: Exendin-4 induced an increase in OMAT adiponectin (P=0.02) and decrease in elastin expression (P=0.03) in parallel with reduced elastin secretion (P=0.04). In contrast to OMAT, we did not observe an effect on SCAT. There was no change in the expression of inflammatory markers (CD14, TNFA, MCP-1), collagens, TGFB1 or CTGF. GLP-1R accumulation was higher in SCAT. CONCLUSIONS: Independently of weight loss, which may bias findings of in vivo studies, GLP-1 analogues modify human OMAT physiology favourably by increasing the insulin-sensitising cytokine adiponectin. However, the reduction of elastin and no apparent effect on AT's inflammatory cytokines suggest that GLP-1 analogues may be less beneficial to AT function, especially if there is no associated weight loss. PMID:27941938

  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. Omental Lipid-Coated Mesh

    Science.gov (United States)

    2011-06-16

    civilian medicine. REFERENCES: 1. Takada T, Kamei Y, Iwata T, et al. Effect of Omental Lipid Fraction on Enhancement of Skin Flap Survival. Annals of...Characterization of Feline Omentum Lipids. Lipids, 1987; 22:229-235. 7. Nottebaert M, Lane J, Juhn A, et al. Omental Angiogenic Lipid Fraction and

  14. Adipose tissue partitioning of limit-fed beef cattle and beef cattle with ad libitum access to feed differing in adaptation to heat.

    Science.gov (United States)

    Sprinkle, J E; Ferrell, C L; Holloway, J W; Warrington, B G; Greene, L W; Wu, G; Stuth, J W

    1998-03-01

    We compared fat distribution and lipoprotein lipase (LPL) activity in steers differing in adaptability to the subtropics. Steers were fed a grain diet (3.13 Mcal ME/kg DM) at limited (150 kcal ME x kg[-.75] x d[-1]; .23 kg ADG) or ad libitum levels for 140 d, then slaughtered. Sixteen British- (8 Angus, 8 Hereford; S), 16 Boran- (R), 16 Brahman- (B), and 16 Tuli- (T) cross steers from MARC III composite cows were used. Adipose tissue samples from perirenal, omental, and subcutaneous depots were analyzed for LPL activity. Carcass measurements including omental, external, and seam fat trim from 1/ 2 of the carcass were measured. Subcutaneous fat had greater (P .05) in fat distribution for steers fed at limited levels. Means for ADG, slaughter weights, carcass weights, yield grades, and carcass lipid weights for S and B fed for ad libitum intake were greater (P .05) for the other breeds with ad libitum intake. Factor analysis of fat depots for animals with ad libitum intake indicated that Bos taurus cattle differing in adaptation to heat deposited fat differently; S deposited greater (P carcass fat and T deposited greater (P < .05) proportions of internal fat. It seems that accumulation of internal fat is detrimental for ADG for Bos taurus cattle.

  15. Heterogeneous response of adipose tissue to cancer cachexia

    Directory of Open Access Journals (Sweden)

    P.S. Bertevello

    2001-09-01

    Full Text Available Cancer cachexia causes disruption of lipid metabolism. Since it has been well established that the various adipose tissue depots demonstrate different responses to stimuli, we assessed the effect of cachexia on some biochemical and morphological parameters of adipocytes obtained from the mesenteric (MES, retroperitoneal (RPAT, and epididymal (EAT adipose tissues of rats bearing Walker 256 carcinosarcoma, compared with controls. Relative weight and total fat content of tissues did not differ between tumor-bearing rats and controls, but fatty acid composition was modified by cachexia. Adipocyte dimensions were increased in MES and RPAT from tumor-bearing rats, but not in EAT, in relation to control. Ultrastructural alterations were observed in the adipocytes of tumor-bearing rat RPAT (membrane projections and EAT (nuclear bodies.

  16. Skin Tissue Engineering: Application of Adipose-Derived Stem Cells

    Science.gov (United States)

    Zimoch, Jakub; Biedermann, Thomas

    2017-01-01

    Perception of the adipose tissue has changed dramatically over the last few decades. Identification of adipose-derived stem cells (ASCs) ultimately transformed paradigm of this tissue from a passive energy depot into a promising stem cell source with properties of self-renewal and multipotential differentiation. As compared to bone marrow-derived stem cells (BMSCs), ASCs are more easily accessible and their isolation yields higher amount of stem cells. Therefore, the ASCs are of high interest for stem cell-based therapies and skin tissue engineering. Currently, freshly isolated stromal vascular fraction (SVF), which may be used directly without any expansion, was also assessed to be highly effective in treating skin radiation injuries, burns, or nonhealing wounds such as diabetic ulcers. In this paper, we review the characteristics of SVF and ASCs and the efficacy of their treatment for skin injuries and disorders.

  17. Expression of visfatin mRNA in adipose tissues of subjects with different glucose tolerance%内脂素基因在不同糖耐量个体脂肪组织的表达差异

    Institute of Scientific and Technical Information of China (English)

    姜秀云; 郑冬梅; 庄霞; 张海清; 孔磊; 管庆波; 赵家军

    2009-01-01

    Objective To investigate the difference of visfatin mRNA expression in abdominal subcutaneous and omental adipose tissues of type 2 diabetes and impaired glucose tolerance(the IGT group) and to explore the relationship between visfafin mRNA expression and indexes of correlation metabolism. Methods The subjects were Chinese Han population, including 23 controls with no family history of diabetes(the control group), 18 patients with impaired glucose tolerance(the IGT group) and 22 with type 2 diabetes(T2DM group). The blood pressure, FBG, TC, TG, HDL-C, LDL-C, HbA1c, and Fins were determined, and (T2DM BMI, WHR, and HOMA-IR were calculated. Semi-quantitative RT-PCR was used to determine visfatin mRNA expres-sion in adipose tissues. Results Visfatin mRNA expression of omental adipose tissues in the T2DM group was higher than that in the IGT and control groups(P0.05). There was no statistical difference in visfatin mRNA expression of subcutaneous adipose tissues among the three groups (P>0.05).Visfafin expression of omental adipose tissues in the fat/overweight group was higher than that in the control group (P0.05).对照组、IGT组及T2DM组皮下脂肪组织的内脂素基因表达量无统计学差异(P>0.05).肥胖/超重组网膜脂肪组织的内脂素基因表达量高于体质量正常组(P0.05),而皮下脂肪组织内脂素基因表达则与,TC相关(P<0.05).结论内脂素在汉族人群T2DM、肥胖者中表达增加,且主要在内脏脂肪组织中表达,在维持葡萄糖稳态平衡中发挥作用.

  18. Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

    Science.gov (United States)

    Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

    2010-04-09

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

  19. 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.

  20. Presence of the cannabinoid receptors, CB1 and CB2, in human omental and subcutaneous adipocytes.

    Science.gov (United States)

    Roche, Régis; Hoareau, Laurence; Bes-Houtmann, Sandrine; Gonthier, Marie-Paule; Laborde, Christine; Baron, Jean-François; Haffaf, Yacine; Cesari, Maya; Festy, Franck

    2006-08-01

    To investigate the expression of the endocannabinoid 1 and 2 receptors by human adipocyte cells of omental and subcutaneous fat tissue, as well as to determine whether these receptors are functional. The expression of CB1 and CB2 receptors on human adipocytes was analyzed by western blotting, immunohistology and immunocytology. We also investigated intracytoplasmic cyclic AMP level modulation following CB1 and CB2 receptor stimulation by an enzymatic immuno assay. All mature adipocytes, from visceral (epiploon) and subcutaneous fat tissue, express CB1 and CB2 on their plasma membranes. We also demonstrate in this study that adipocyte precursors (pre-adipocytes) express CB1 and CB2 on their plasma membranes and that both receptors are functional. Activation of CB1 increases intracytoplasmic cyclic AMP whilst CB2 activation leads to a cyclic AMP decrease. Here we demonstrate, for the first time, that adipocytes of human adipose tissue (mature adipocytes and pre-adipocytes) express functional plasma membrane CB1 and CB2 receptors. Their physiological role on the adipose tissue is not known. However, their major involvement in the physiology of other tissues leads us to suppose that they could play a significant role in the homeostasis of the energy balance and/or in the regulation of adipose tissue inflammation.

  1. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) deficiencies affect expression of lipolytic activities in mouse adipose tissues.

    Science.gov (United States)

    Morak, Maria; Schmidinger, Hannes; Riesenhuber, Gernot; Rechberger, Gerald N; Kollroser, Manfred; Haemmerle, Guenter; Zechner, Rudolf; Kronenberg, Florian; Hermetter, Albin

    2012-12-01

    Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patterns of brown and white adipose tissue from ATGL (-/-) and HSL (-/-) mice using differential activity-based gel electrophoresis. This method is based on activity-recognition probes possessing the same substrate analogous structure but carrying different fluorophores for specific detection of the enzyme patterns of two different tissues in one electrophoresis gel. We found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose tissue. Enzyme activities of mouse tissues on acylglycerol substrates were analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for at least in part by other enzymes. The proteins that responded to ATGL-deficiency in brown adipose tissue were overexpressed and their activities on acylglycerols were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase candidates as they catalyze the hydrolysis of long-chain acylglycerols.

  2. [Role of chronic inflammation in adipose tissue in the pathophysiology of obesity].

    Science.gov (United States)

    Suganami, Takayoshi; Ogawa, Yoshihiro

    2013-02-01

    Obesity may be viewed as a chronic low-grade inflammatory disease as well as a metabolic disease. Evidence has accumulated suggesting that chronic inflammation in adipose tissue leads to dramatic changes in number and cell type of stromal cells during the course of obesity, which is referred to as"adipose tissue remodeling". Among stromal cells, macrophages in obese adipose tissue are considered to be crucial for adipose tissue inflammation, which results in dysregulated adipocytokine production and ectopic fat accumulation. Understanding the molecular mechanism underlying adipose tissue inflammation would contribute to the identification of novel therapeutic strategies to prevent or treat obesity-induced metabolic derangements.

  3. Adipose tissue deletion of Gpr116 impairs insulin sensitivity through modulation of adipose function.

    Science.gov (United States)

    Nie, Tao; Hui, Xiaoyan; Gao, Xuefei; Li, Kuai; Lin, Wanhua; Xiang, Xiaoliang; Ding, Mengxiao; Kuang, Ying; Xu, Aimin; Fei, Jian; Wang, Zhugang; Wu, Donghai

    2012-10-19

    G protein-coupled receptor 116 (GPR116) is a novel member of the G protein-coupled receptors and its function is largely unknown. To investigate the physiological function of GPR116 in vivo, we generated adipose tissue specific conditional Gpr116 knockout mice (CKO) and fed them on standard chow or high fat diets. Selective deletion of Gpr116 in adipose tissue caused a pronounced glucose intolerance and insulin resistance in mice, especially when challenged with a high fat diet. Biochemical analysis revealed a more severe hepatosteatosis in CKO mice. Additionally, we found that CKO mice showed a lowered concentration of circulating adiponectin and an increased level of serum resistin. Our study suggests that GPR116 may play a critical role in controlling adipocyte biology and systemic energy homeostasis. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. Succination of Thiol Groups in Adipose Tissue Proteins in Diabetes

    Science.gov (United States)

    Frizzell, Norma; Rajesh, Mathur; Jepson, Matthew J.; Nagai, Ryoji; Carson, James A.; Thorpe, Suzanne R.; Baynes, John W.

    2009-01-01

    S-(2-Succinyl)cysteine (2SC) is formed by reaction of the Krebs cycle intermediate fumarate with cysteine residues in protein, a process termed succination of protein. Both fumarate and succination of proteins are increased in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik, M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and Frizzell, N. (2007) J. Biol. Chem. 282, 34219–34228). We show here that succination of protein is also increased in epididymal, mesenteric, and subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a major target for succination in both adipocytes and adipose tissue. Cys-39, which is involved in cross-linking of adiponectin monomers to form trimers, was identified as a key site of succination of adiponectin in adipocytes. 2SC was detected on two of seven monomeric forms of adiponectin immunoprecipitated from adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin accounted for ∼7 and 8% of total intracellular adiponectin in cells and tissue, respectively. 2SC was found only in the intracellular, monomeric forms of adiponectin and was not detectable in polymeric forms of adiponectin in cell culture medium or plasma. We conclude that succination of adiponectin blocks its incorporation into trimeric and higher molecular weight, secreted forms of adiponectin. We propose that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes. PMID:19592500

  5. [The adipose tissue as a regulatory center of the metabolism].

    Science.gov (United States)

    Fonseca-Alaniz, Miriam H; Takada, Julie; Alonso-Vale, Maria Isabel C; Lima, Fabio Bessa

    2006-04-01

    The recent progress in the research about the metabolic properties of the adipose tissue and the discovery of its ability to produce hormones that are very active in pathophysiologic as well as physiologic processes is rebuilding the concepts about its biology. Its involvement in conditions like obesity, type 2 diabetes mellitus, arterial hypertension, arteriosclerosis, dislipidemias and chronic and acute inflammatory processes indicate that the understanding of its functional capacities may contribute to improve the prognosis of those diseases whose prevalence increased in a preoccupying manner. Here we review some functional aspects of adipocytes, such as the metabolism, its influence on energy homeostasis, its endocrine ability and the adipogenesis, i.e., the potential of pre-adipocytes present in adipose tissue stroma to differentiate into new adipocytes and regenerate the tissue. In addition, we are including some studies on the relationship between the adipose tissue and the pineal gland, a new and poorly known, although, as will be seen, very promising aspect of adipocyte physiology together with its possible favorable repercussions to the therapy of the obesity related diseases.

  6. Bovine dedifferentiated adipose tissue (DFAT) cells

    Science.gov (United States)

    Wei, Shengjuan; Du, Min; Jiang, Zhihua; Duarte, Marcio S; Fernyhough-Culver, Melinda; Albrecht, Elke; Will, Katja; Zan, Linsen; Hausman, Gary J; Elabd, Elham M Youssef; Bergen, Werner G; Basu, Urmila; Dodson, Michael V

    2013-01-01

    Dedifferentiated fat cells (DFAT cells) are derived from lipid-containing (mature) adipocytes, which possess the ability to symmetrically or asymmetrically proliferate, replicate, and redifferentiate/transdifferentiate. Robust cell isolation and downstream culture methods are needed to isolate large numbers of DFAT cells from any (one) adipose depot in order to establish population dynamics and regulation of the cells within and across laboratories. In order to establish more consistent/repeatable methodology here we report on two different methods to establish viable DFAT cell cultures: both traditional cell culture flasks and non-traditional (flat) cell culture plates were used for ceiling culture establishment. Adipocytes (maternal cells of the DFAT cells) were easier to remove from flat culture plates than flasks and the flat plates also allowed cloning rings to be utilized for cell/cell population isolation. While additional aspects of usage of flat-bottomed cell culture plates may yet need to be optimized by definition of optimum bio-coating to enhance cell attachment, utilization of flat plate approaches will allow more efficient study of the dedifferentiation process or the DFAT progeny cells. To extend our preliminary observations, dedifferentiation of Wagyu intramuscular fat (IMF)-derived mature adipocytes and redifferentiation ability of DFAT cells utilizing the aforementioned isolation protocols were examined in traditional basal media/differentiation induction media (DMI) containing adipogenic inducement reagents. In the absence of treatment approximately 10% isolated Wagyu IMF-mature adipocytes dedifferentiated spontaneously and 70% DFAT cells displayed protracted adipogenesis 12 d after confluence in vitro. Lipid-free intracellular vesicles in the cytoplasm (vesicles possessing an intact membrane but with no any observable or stainable lipid inside) were observed during redifferentiation. One to 30% DFAT cells redifferentiated into lipid

  7. The environmental obesogen bisphenol A promotes adipogenesis by increasing the amount of 11β-hydroxysteroid dehydrogenase type 1 in the adipose tissue of children.

    Science.gov (United States)

    Wang, J; Sun, B; Hou, M; Pan, X; Li, X

    2013-07-01

    Bisphenol A (BPA) is considered as an environmental obesogen. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts the inactive hormone cortisone to the active hormone cortisol in adipose tissues and promotes adipogenesis. To examine whether environmentally relevant concentrations of BPA could increase the expression of 11β-HSD1, as well as that of the adipogenesis-related genes peroxisome proliferator-activated receptor-γ (PPAR-γ) and lipoprotein lipase (LPL), in the adipose tissue of children. Omental fat biopsies were obtained from 17 children (7 boys and 10 girls between 3 and 13 years of age) undergoing abdominal surgery. The effects of BPA (10 nM, 1 μM, and 80 μM) on 11β-HSD1, PPAR-γ and LPL mRNA expression, and 11β-HSD1 enzymatic activity in adipose tissue and adipocytes were assessed in vitro. Moreover, the effects of carbenoxolone (CBX), an 11β-HSD1 inhibitor, or RU486, a glucocorticoid (GC) receptor antagonist, on 11β-HSD1, PPAR-γ and LPL mRNA expression were assessed in human visceral preadipocytes and adipocytes. BPA, even at the lowest concentration tested (10 nM), increased the mRNA expression and enzymatic activity of 11β-HSD1 in the omental adipose tissue samples and the visceral adipocytes. Similar effects on PPAR-γ and LPL mRNA expression and lipid accumulation were observed in the adipocytes. CBX treatment inhibited the stimulatory effects of BPA (at 10 nM) on PPAR-γ and LPL mRNA expression, whereas RU486 inhibited 11β-HSD1 mRNA expression in the adipocytes. BPA, at environmentally relevant levels, increased the mRNA expression and enzymatic activity of 11β-HSD1 by acting upon a GC receptor, which may lead to the acceleration of adipogenesis.

  8. A role of active brown adipose tissue in cancer cachexia?

    Directory of Open Access Journals (Sweden)

    Emiel Beijer

    2012-06-01

    Full Text Available Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT. Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and socalled brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activation, but its quantitative impact on energy expenditure and weight loss is controversial. Prospective clinical studies can address the potential role of BAT in cancer cachexia using 18F-fluorodeoxyglucose positron emission tomography-computed tomography scanning, with careful consideration of co-factors such as diet, exposure to the cold, physical activity and body mass index, that all seem to act on BAT recruitment and activity.

  9. Browning effects of (-)-epicatechin on adipocytes and white adipose tissue.

    Science.gov (United States)

    Varela, Claudia Elena; Rodriguez, Alonso; Romero-Valdovinos, Mirza; Mendoza-Lorenzo, Patricia; Mansour, Christina; Ceballos, Guillermo; Villarreal, Francisco; Ramirez-Sanchez, Israel

    2017-09-15

    In this study, we demonstrate that (-)-epicatechin (Epi), a cacao flavanol, induces the browning of fat by promoting mitochondrial biogenesis, enhancing indicators of mitochondrial structure and function, increasing fatty acid metabolism and upregulating the expression of brown adipose tissue-specific proteins in a high-fat diet mouse model of obesity and in cultured human adipocytes. Epi treatment significantly improved mitochondrial function, as measured by citrate synthase activity, and also reduced protein acetylation of total and specific regulators in both adipose tissue and human adipocytes. Browning of fat via Epi was evidenced by the increased expression of key thermogenic genes, phosphorylation of upstream regulators of fatty acid oxidation, and reduced triglyceride levels. Properly designed clinical trials are needed to explore the potential of Epi as an agent that promotes the browning of fat. Copyright © 2017. Published by Elsevier B.V.

  10. Endogenous adipose tissue as a hemostatic: use in microsurgery.

    Science.gov (United States)

    Akelina, Yelena; Danilo, Peter

    2008-01-01

    Bleeding is a frequent complication of microsurgical repair of small blood vessels and time is spent while hemostasis is accomplished. We studied the hemostatic effect of endogenous adipose tissue on bleeding from rat femoral arterial anastomoses. We measured bleeding time (time from removal of clamps to cessation of active bleeding) and mean arterial blood velocity (using a micro-Doppler system), the latter immediately after anastomosis, and again 7 days post-anastomosis. Bleeding time for vessels with fat applied to the artery was 50% less than when no fat was applied. Blood velocity by day 7 post-anastomosis returned to values equivalent to those for intact arteries. Histological evaluation of the anastomotic site demonstrated no significant differences in inflammatory response between fat-treated and untreated arteries. These data suggest that endogenous adipose tissue may be a useful hemostatic agent devoid of significant effects on small artery blood velocity or histology. (c) 2008 Wiley-Liss, Inc.

  11. Id transcriptional regulators in adipogenesis and adipose tissue metabolism.

    Science.gov (United States)

    Patil, Mallikarjun; Sharma, Bal Krishan; Satyanarayana, Ande

    2014-06-01

    Id proteins (Id1-Id4) are helix-loop-helix (HLH) transcriptional regulators that lack a basic DNA binding domain. They act as negative regulators of basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibit their DNA binding and transcriptional activity. Id proteins are implicated in the regulation of various cellular mechanisms such as cell proliferation, cellular differentiation, cell fate determination, angiogenesis and tumorigenesis. A handful of recent studies also disclosed that Id proteins have critical functions in adipocyte differentiation and adipose tissue metabolism. Here, we reviewed the progress made thus far in understanding the specific functions of Id proteins in adipose tissue differentiation and metabolism. In addition to reviewing the known mechanisms of action, we also discuss possible additional mechanisms in which Id proteins might participate in regulating adipogenic and metabolic pathways.

  12. Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

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    Delphine Duteil

    2016-10-01

    Full Text Available Previous work indicated that lysine-specific demethylase 1 (Lsd1 can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT and find that BAT-selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1-deficient mice. Further studies show that Lsd1 maintains BAT properties via a dual role. It activates BAT-selective gene expression in concert with the transcription factor Nrf1 and represses WAT-selective genes through recruitment of the CoREST complex. In conclusion, our data uncover Lsd1 as a key regulator of gene expression and metabolic function in BAT.

  13. Mechanisms of perivascular adipose tissue dysfunction in obesity.

    Science.gov (United States)

    Fernández-Alfonso, Maria S; Gil-Ortega, Marta; García-Prieto, Concha F; Aranguez, Isabel; Ruiz-Gayo, Mariano; Somoza, Beatriz

    2013-01-01

    Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT) was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important number of adipocyte-derived factors with physiological and pathophysiological paracrine vasoactive effects have been identified. PVAT undergoes structural and functional changes in obesity. During early diet-induced obesity, an adaptative overproduction of vasodilator factors occurs in PVAT, probably aimed at protecting vascular function. However, in established obesity, PVAT loses its anticontractile properties by an increase of contractile, oxidative, and inflammatory factors, leading to endothelial dysfunction and vascular disease. The aim of this review is to focus on PVAT dysfunction mechanisms in obesity.

  14. Mechanisms of Perivascular Adipose Tissue Dysfunction in Obesity

    Directory of Open Access Journals (Sweden)

    Maria S. Fernández-Alfonso

    2013-01-01

    Full Text Available Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important number of adipocyte-derived factors with physiological and pathophysiological paracrine vasoactive effects have been identified. PVAT undergoes structural and functional changes in obesity. During early diet-induced obesity, an adaptative overproduction of vasodilator factors occurs in PVAT, probably aimed at protecting vascular function. However, in established obesity, PVAT loses its anticontractile properties by an increase of contractile, oxidative, and inflammatory factors, leading to endothelial dysfunction and vascular disease. The aim of this review is to focus on PVAT dysfunction mechanisms in obesity.

  15. Prolactin (PRL) in adipose tissue: regulation and functions.

    Science.gov (United States)

    Ben-Jonathan, Nira; Hugo, Eric

    2015-01-01

    New information concerning the effects of prolactin (PRL) on metabolic processes warrants reevaluation of its overall metabolic actions. PRL affects metabolic homeostasis by regulating key enzymes and transporters associated with glucose and lipid metabolism in several target organs. In the lactating mammary gland, PRL increases the production of milk proteins, lactose, and lipids. In adipose tissue, PRL generally suppresses lipid storage and adipokine release and affect adipogenesis. A specific case is made for PRL in the human breast and adipose tissues, where it acts as a circulating hormone and an autocrine/paracrine factor. Although its overall effects on body composition are both modest and species-specific, PRL may be involved in the manifestation of insulin resistance.

  16. Heterogeneity of white adipose tissue: molecular basis and clinical implications.

    Science.gov (United States)

    Kwok, Kelvin H M; Lam, Karen S L; Xu, Aimin

    2016-03-11

    Adipose tissue is a highly heterogeneous endocrine organ. The heterogeneity among different anatomical depots stems from their intrinsic differences in cellular and physiological properties, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, insulin sensitivity, hormonal control, thermogenic ability and vascularization. Additional factors that influence adipose tissue heterogeneity are genetic predisposition, environment, gender and age. Under obese condition, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. For instance, individuals with central obesity are more susceptible to developing diabetes and cardiovascular complications, whereas those with peripheral obesity are more metabolically healthy. This review summarizes the clinical and mechanistic evidence for the depot-specific differences that give rise to different metabolic consequences, and provides therapeutic insights for targeted treatment of obesity.

  17. Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo

    OpenAIRE

    Scotney, Hannah; Symonds, Michael E; Law, James; Budge, Helen; Sharkey, Don; Manolopoulos, Konstantinos N.

    2017-01-01

    Introduction: Brown adipose tissue (BAT) is a thermogenic organ with substantial metabolic capacity and has important roles in the maintenance of body weight and metabolism. Regulation of BAT is primarily mediated through the ß-adrenoceptor (ß-AR) pathway. The in vivo endocrine regulation of this pathway in humans is unkown. The objective of our study was to assess the in vivo BAT temperature responses to acute glucocorticoid administration.\\ud Methods: We studied 8 healthy male volunteers, n...

  18. Brain–gut–adipose-tissue communication pathways at a glance

    Directory of Open Access Journals (Sweden)

    Chun-Xia Yi

    2012-09-01

    Full Text Available One of the ‘side effects’ of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain’s survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure. Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders.

  19. Sleep deprivation affects inflammatory marker expression in adipose tissue

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    Santos Ronaldo VT

    2010-10-01

    Full Text Available Abstract Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation. Methods The study consisted of two groups: a control (C group and a paradoxical sleep deprivation by 96 h (PSD group. Ten rats were randomly assigned to either the control group (C or the PSD. Mesenteric (MEAT and retroperitoneal (RPAT adipose tissue, liver and serum were collected following completion of the PSD protocol. Levels of interleukin (IL-6, interleukin (IL-10 and tumour necrosis factor (TNF-α were analysed in MEAT and RPAT, and leptin, adiponectin, glucose, corticosterone and lipid profile levels were analysed in serum. Results IL-6 levels were elevated in RPAT but remained unchanged in MEAT after PSD. IL-10 protein concentration was not altered in either depot, and TNF-α levels decreased in MEAT. Glucose, triglycerides (TG, VLDL and leptin decreased in serum after 96 hours of PSD; adiponectin was not altered and corticosterone was increased. Conclusion PSD decreased fat mass and may modulate the cytokine content in different depots of adipose tissue. The inflammatory response was diminished in both depots of adipose tissue, with increased IL-6 levels in RPAT and decreased TNF-α protein concentrations in MEAT and increased levels of corticosterone in serum.

  20. Nitro-fatty acid pharmacokinetics in the adipose tissue compartment.

    Science.gov (United States)

    Fazzari, Marco; Khoo, Nicholas K H; Woodcock, Steven R; Jorkasky, Diane K; Li, Lihua; Schopfer, Francisco J; Freeman, Bruce A

    2017-02-01

    Electrophilic nitro-FAs (NO2-FAs) promote adaptive and anti-inflammatory cell signaling responses as a result of an electrophilic character that supports posttranslational protein modifications. A unique pharmacokinetic profile is expected for NO2-FAs because of an ability to undergo reversible reactions including Michael addition with cysteine-containing proteins and esterification into complex lipids. Herein, we report via quantitative whole-body autoradiography analysis of rats gavaged with radiolabeled 10-nitro-[(14)C]oleic acid, preferential accumulation in adipose tissue over 2 weeks. To better define the metabolism and incorporation of NO2-FAs and their metabolites in adipose tissue lipids, adipocyte cultures were supplemented with 10-nitro-oleic acid (10-NO2-OA), nitro-stearic acid, nitro-conjugated linoleic acid, and nitro-linolenic acid. Then, quantitative HPLC-MS/MS analysis was performed on adipocyte neutral and polar lipid fractions, both before and after acid hydrolysis of esterified FAs. NO2-FAs preferentially incorporated in monoacyl- and diacylglycerides, while reduced metabolites were highly enriched in triacylglycerides. This differential distribution profile was confirmed in vivo in the adipose tissue of NO2-OA-treated mice. This pattern of NO2-FA deposition lends new insight into the unique pharmacokinetics and pharmacologic actions that could be expected for this chemically-reactive class of endogenous signaling mediators and synthetic drug candidates.

  1. Caveolae, lipid droplets, and adipose tissue biology: pathophysiological aspects.

    Science.gov (United States)

    Martin, Sally

    2013-09-01

    Adipocytes are specialized cells that function to store energy in the form of lipids, predominantly triglycerides (TGs), and as a regulatory system contributing to metabolic homoeostasis through the production and secretion of hormones and cytokines. The regulation of lipid homeostasis by adipose tissue is an important aspect of whole-body metabolism. Owing to the central nature of adipose tissue in lipid metabolism, dysregulation has wide-ranging effects, contributing to disorders as diverse as diabetes, cardiovascular disease, cancer, and neurodegeneration. Excess lipids are stored in specialized organelles called lipid droplets (LDs). The surface of the lipid droplet can be considered a highly regulated membrane domain that both protects the contents of the LD from unregulated lipolysis and the cell from the cytotoxic effects of elevated free fatty acids. The surface of the LD is coated with a variety of regulatory proteins, either resident or transiently associated, including enzymes involved in the breakdown of TG, lipid transport proteins, and cofactors. Recent studies have begun to unravel the range of LD-associated proteins and to define their functional significance. Importantly, the involvement of LD proteins in pathophysiological disorders is beginning to be understood. This review will outline recent advances in defining the diversity of LD-associated proteins and their links to metabolic disorders including the integral membrane protein, caveolin-1 (CAV1). Analysis of the role of CAV1 in adipose tissue has highlighted the interconnectedness between the regulation of lipid storage and the function of the adipocyte plasma membrane.

  2. Food consumption and adipose tissue DDT levels in Mexican women

    Directory of Open Access Journals (Sweden)

    Galván-Portillo Marcia

    2002-01-01

    Full Text Available This article analyzes food consumption in relation to levels of DDE (the principal metabolite of DDT in the adipose tissue of 207 Mexican women residing in States with high and low exposure to DDT. Data on the women's dietary habits and childbearing history were obtained from a personal interview. Adipose tissue DDE levels were measured by gas-liquid chromatography and compared by analysis of variance (ANOVA and multiple linear regression. Adipose tissue DDE levels increased significantly with age (p = 0.005 and residence in coastal areas (p = 0.002 and non-significantly with the consumption of onion, cauliflower, prickly pear, squash blossoms, sweet corn, broad beans, chili pepper sauce, ham, and fish. Even so, during breastfeeding there was a non-significant reduction in these levels. The findings suggest that certain foods serve as vehicles for DDE residues and confirm that breastfeeding is a mechanism for the elimination of this insecticide, which accumulates over the years in the human body.

  3. Adipose tissue-derived stromal cells express neuronal phenotypes

    Institute of Scientific and Technical Information of China (English)

    杨立业; 刘相名; 孙兵; 惠国桢; 费俭; 郭礼和

    2004-01-01

    Background Adipose tissue-derived stromal cells (ADSCs) can be greatly expanded in vitro, and induced to differentiate into multiple mesenchymal cell types, including osteogenic, chondrogenic, myogenic, and adipogenic cells. This study was designed to investigate the possibility of ADSCs differentiating into neurons.Methods Adipose tissue from rats was digested with collagenase, and adherent stromal cells were cultured. A medium containing a low concentration of fetal bovine serum was adopted to induce the cells to differentiate. ADSCs were identified by immunocytochemistry, and semi-quantitative RT-PCR was applied to detect mRNA expression of neurofilament 1 (NF1), nestin, and neuron-specific enolase (NSE).Results Nestin-positive cells were found occasionally among ADSCs. ADSCs were found to express NSE mRNA and nestin mRNA, but not NF1 mRNA. ADSCs could differentiate into neuron-like cells in a medium composed of a low concentration of fetal bovine serum, and these differentiated cells displayed complicated neuron-like morphologies.Conclusions The data support the hypothesis that adipose tissue contains stem cells capable of differentiating into neurons. These stem cells can overcome their mesenchymal commitment, and may represent an alternative autologous stem cell source for CNS cell transplantation.

  4. Food consumption and adipose tissue DDT levels in Mexican women

    Directory of Open Access Journals (Sweden)

    Marcia Galván-Portillo

    2002-04-01

    Full Text Available This article analyzes food consumption in relation to levels of DDE (the principal metabolite of DDT in the adipose tissue of 207 Mexican women residing in States with high and low exposure to DDT. Data on the women's dietary habits and childbearing history were obtained from a personal interview. Adipose tissue DDE levels were measured by gas-liquid chromatography and compared by analysis of variance (ANOVA and multiple linear regression. Adipose tissue DDE levels increased significantly with age (p = 0.005 and residence in coastal areas (p = 0.002 and non-significantly with the consumption of onion, cauliflower, prickly pear, squash blossoms, sweet corn, broad beans, chili pepper sauce, ham, and fish. Even so, during breastfeeding there was a non-significant reduction in these levels. The findings suggest that certain foods serve as vehicles for DDE residues and confirm that breastfeeding is a mechanism for the elimination of this insecticide, which accumulates over the years in the human body.

  5. Brown Adipose Tissue: A New Target for Antiobesity Therapy

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2010-08-01

    Full Text Available BACKGROUND: Human fat consist of white and brown adipose tissue (WAT and BAT. Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure. CONTENT: Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT imaging, immunohistochemistry and gene and protein expression assays to prove conclusively that adult humans have functional BAT. BAT is important for thermogenesis and energy balance in small mammals and its induction in mice promotes energy expenditure, reduces adiposity and protects mice from diet-induced obesity. The thermogenic capacity of BAT is impressive. In humans, it has been estimated that as little as 50g of BAT could utilize up to 20% of basal caloric needs if maximally stimulated. SUMMARY: The obesity pandemic requires new and novel treatments. The past few years have witnessed multiple studies conclusively showing that adult humans have functional BAT, a tissue that has a tremendous capacity for obesity-reducing thermogenesis. Novel therapies targeting BAT thermogenesis may be available in the near future as therapeutic options for obesity and diabetes. Thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity. KEYWORDS: brown adipose tissue, thermogenesis, energy expenditure, antiobesity therapy.

  6. Adipose tissue-liver axis in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Alcoholic liver disease (ALD) remains an important healthproblem worldwide. The disease spectrum is featuredby early steatosis, steatohepatitis (steatosis with inflammatorycells infiltration and necrosis), with someindividuals ultimately progressing to fibrosis/cirrhosis.Although the disease progression is well characterized,no effective therapies are currently available for thetreatment in humans. The mechanisms underlying theinitiation and progression of ALD are multifactorial andcomplex. Emerging evidence supports that adiposetissue dysfunction contributes to the pathogenesis ofALD. In the first part of this review, we discuss themechanisms whereby chronic alcohol exposure contributedto adipose tissue dysfunction, including cell death,inflammation and insulin resistance. It has been longknown that aberrant hepatic methionine metabolismis a major metabolic abnormality induced by chronicalcohol exposure and plays an etiological role in thepathogenesis of ALD. The recent studies in our groupdocumented the similar metabolic effect of chronicalcohol drinking on methionine in adipose tissue. Inthe second part of this review, we also briefly discussthe recent research progress in the field with a focuson how abnormal methionine metabolism in adiposetissue contributes to adipose tissue dysfunction and liverdamage.

  7. Exercise and the Regulation of Adipose Tissue Metabolism.

    Science.gov (United States)

    Tsiloulis, Thomas; Watt, Matthew J

    2015-01-01

    Adipose tissue is a major regulator of metabolism in health and disease. The prominent roles of adipose tissue are to sequester fatty acids in times of energy excess and to release fatty acids via the process of lipolysis during times of high-energy demand, such as exercise. The fatty acids released during lipolysis are utilized by skeletal muscle to produce adenosine triphosphate to prevent fatigue during prolonged exercise. Lipolysis is controlled by a complex interplay between neuro-humoral regulators, intracellular signaling networks, phosphorylation events involving protein kinase A, translocation of proteins within the cell, and protein-protein interactions. Herein, we describe in detail the cellular and molecular regulation of lipolysis and how these processes are altered by acute exercise. We also explore the processes that underpin adipocyte adaptation to endurance exercise training, with particular focus on epigenetic modifications, control by microRNAs and mitochondrial adaptations. Finally, we examine recent literature describing how exercise might influence the conversion of traditional white adipose tissue to high energy-consuming "brown-like" adipocytes and the implications that this has on whole-body energy balance. © 2015 Elsevier Inc. All rights reserved.

  8. Broiler chicken adipose tissue dynamics during the first two weeks post-hatch.

    Science.gov (United States)

    Bai, Shiping; Wang, Guoqing; Zhang, Wei; Zhang, Shuai; Rice, Brittany Breon; Cline, Mark Andrew; Gilbert, Elizabeth Ruth

    2015-11-01

    Selection of broiler chickens for growth has led to increased adipose tissue accretion. To investigate the post-hatch development of adipose tissue, the abdominal, clavicular, and subcutaneous adipose tissue depots were collected from broiler chicks at 4 and 14 days post-hatch. As a percent of body weight, abdominal fat increased (Padipose development, with larger adipocytes and greater G3PDH activity in subcutaneous fat at day 4, more rapid growth of abdominal fat, and clavicular fat intermediate for most traits. Adipose tissue expansion was accompanied by changes in gene expression of adipose-associated factors.

  9. Expression and Regulation of Soluble Epoxide Hydrolase in Adipose Tissue

    Science.gov (United States)

    De Taeye, Bart M.; Morisseau, Christophe; Coyle, Julie; Covington, Joseph W.; Luria, Ayala; Yang, Jun; Murphy, Sheila B.; Friedman, David B.; Hammock, Bruce B.; Vaughan, Douglas E.

    2010-01-01

    Obesity is an increasingly important public health issue reaching epidemic proportions. Visceral obesity has been defined as an important element of the metabolic syndrome and expansion of the visceral fat mass has been shown to contribute to the development of insulin resistance and cardiovascular disease. To identify novel contributors to cardiovascular and metabolic abnormalities in obesity, we analyzed the adipose proteome and identified soluble epoxide hydrolase (sEH) in the epididymal fat pad from C57BL/6J mice that received either a regular diet or a “western diet.” sEH was synthesized in adipocytes and expression levels increased upon differentiation of 3T3-L1 preadipocytes. Although normalized sEH mRNA and protein levels did not differ in the fat pads from mice receiving a regular or a “western diet,” total adipose sEH activity was higher in the obese mice, even after normalization for body weight. Furthermore, peroxisome proliferator–activated recetor γ(PPARγ) agonists increased the expression of sEH in mature 3T3-L1 adipocytes in vitro and in adipose tissue in vivo. Considering the established role for sEH in inflammation, cardiovascular diseases, and lipid metabolism, and the suggested involvement of sEH in the development of type 2 diabetes, our study has identified adipose sEH as a potential novel therapeutic target that might affect the development of metabolic and cardiovascular abnormalities in obesity. PMID:19644452

  10. Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment

    DEFF Research Database (Denmark)

    Tobin, L; Simonsen, L; Bülow, J

    2010-01-01

    The adipose tissue metabolism is dependent on its blood perfusion. During lipid mobilization e.g. during exercise and during lipid deposition e.g. postprandial, adipose tissue blood flow is increased. This increase in blood flow may involve capillary recruitment in the tissue. We investigated...... the basic and postprandial microvascular volume in adipose tissue using real-time contrast-enhanced ultrasound (CEU) imaging in healthy normal weight subjects. In nine subjects, CEU was performed in abdominal subcutaneous adipose tissue and in the underlying skeletal muscle after a bolus injection...... of ultrasound contrast agent to establish the reproducibility of the technique. In nine subjects, the effect of an oral glucose load on blood flow and microvascular volume was measured in abdominal subcutaneous adipose tissue and forearm skeletal muscle. ¹³³Xe washout and venous occlusion strain...

  11. Deep sequencing of the transcriptome reveals inflammatory features of porcine visceral adipose tissue.

    Science.gov (United States)

    Wang, Tao; Jiang, Anan; Guo, Yanqin; Tan, Ya; Tang, Guoqing; Mai, Miaomiao; Liu, Haifeng; Xiao, Jian; Li, Mingzhou; Li, Xuewei

    2013-01-01

    Functional differences in the different types of adipose tissue and the impact of their dysfunction on metabolism are associated with the regional distribution of adipose depots. Here we show a genome-wide comparison between the transcriptomes of one source of subcutaneous and two sources of visceral adipose tissue in the pig using an RNA-seq approach. We obtained ~32.3 million unique mapped reads which covered ~80.2% of the current annotated transcripts across these three sources of adipose tissue. We identified various genes differentially expressed between subcutaneous and visceral adipose tissue, which are potentially associated with the inflammatory features of visceral adipose tissue. These results are of benefit for understanding the phenotypic, metabolic and functional differences between different types of adipose tissue that are deposited in different body sites.

  12. Vitamin D in adipose tissue and serum 25-hydroxyvitamin D after roux-en-Y gastric bypass.

    Science.gov (United States)

    Pramyothin, Pornpoj; Biancuzzo, Rachael M; Lu, Zhiren; Hess, Donald T; Apovian, Caroline M; Holick, Michael F

    2011-11-01

    Vitamin D is stored in body fat. The purpose of this study was to determine vitamin D concentration in abdominal fat of obese patients who underwent roux-en-Y gastric bypass (RYGB), and to describe changes in serum 25-hydroxyvitamin D (25(OH)D) levels in relation to loss of body fat. Subjects from a single clinic who were scheduled for RYGB were invited into the study. Abdominal subcutaneous, omental, and mesenteric fat were obtained at time of surgery. Adipose vitamin D(2) and vitamin D(3) concentrations were measured by high-performance liquid chromatography (HPLC). Weight and serum 25(OH)D were assessed at baseline and every 3 months up to 1 year. Seventeen subjects were included, and fat samples were available from eleven. Total vitamin D content in subcutaneous abdominal fat was 297.2 ± 727.7 ng/g tissue, and a wide range was observed (4-2,470 ng/g). Both vitamin D(2) and vitamin D(3) were detected in some of the fat samples. At baseline, 25(OH)D was 23.1 ± 12.6 ng/ml. Average weight loss was 54.8 kg at 12 months, of which ~40 kg was fat mass. Despite daily vitamin D intake of ≥2,500 IU throughout the study, no significant increase in serum 25(OH)D was observed, with mean serum concentration of 25(OH)D at 1 year of 26.2 ± 5.36 ng/ml (P = 0.58). We conclude that vitamin D in adipose tissue does not significantly contribute to serum 25(OH)D despite dramatic loss of fat mass after RYGB.

  13. Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism.

    Science.gov (United States)

    Zhang, Wei; Cline, Mark A; Gilbert, Elizabeth R

    2014-01-01

    Neuropeptide Y (NPY) is an orexigenic neuropeptide that plays a role in regulating adiposity by promoting energy storage in white adipose tissue and inhibiting brown adipose tissue activation in mammals. This review describes mechanisms underlying NPY's effects on adipose tissue energy metabolism, with an emphasis on cellular proliferation, adipogenesis, lipid deposition, and lipolysis in white adipose tissue, and brown fat activation and thermogenesis. In general, NPY promotes adipocyte differentiation and lipid accumulation, leading to energy storage in adipose tissue, with effects mediated mainly through NPY receptor sub-types 1 and 2. This review highlights hypothalamus-sympathetic nervous system-adipose tissue innervation and adipose tissue-hypothalamus feedback loops as pathways underlying these effects. Potential sources of NPY that mediate adipose effects include the bloodstream, sympathetic nerve terminals that innervate the adipose tissue, as well as adipose tissue-derived cells. Understanding the role of central vs. peripherally-derived NPY in whole-body energy balance could shed light on mechanisms underlying the pathogenesis of obesity. This information may provide some insight into searching for alternative therapeutic strategies for the treatment of obesity and associated diseases.

  14. Laser light propagation in adipose tissue and laser effects on adipose cell membranes

    Science.gov (United States)

    Solarte, Efraín; Rebolledo, Aldo; Gutierrez, Oscar; Criollo, William; Neira, Rodrigo; Arroyave, José; Ramírez, Hugo

    2006-01-01

    Recently Neira et al. have presented a new liposuction technique that demonstrated the movement of fat from inside to outside of the cell, using a low-level laser device during a liposuction procedure with Ultrawet solution. The clinical observations, allowed this new surgical development, started a set of physical, histological and pharmacological studies aimed to determine the mechanisms involved in the observed fat mobilization concomitant to external laser application in liposuction procedures. Scanning and Transmission Electron Microscopy, studies show that the cellular arrangement of normal adipose tissue changes when laser light from a diode laser: 10 mW, 635 nm is applied. Laser exposures longer than 6 minutes cause the total destruction of the adipocyte panicles. Detailed observation of the adipose cells show that by short irradiation times (less than four minutes) the cell membrane exhibits dark zones, that collapse by longer laser exposures. Optical measurements show that effective penetration length depends on the laser intensity. Moreover, the light scattering is enhanced by diffraction and subsequent interference effects, and the tumescent solution produces a clearing of the tissue optical medium. Finally, isolate adipose cell observation show that fat release from adipocytes is a concomitant effect between the tumescent solution (adrenaline) and laser light, revealing a synergism which conduces to the aperture, and maybe the disruption, of the cell membrane. All these studies were consistent with a laser induced cellular process, which causes fat release from inside the adipocytes into the intercellular space, besides a strong modification of the cellular membranes.

  15. Intrinsic regulation of blood flow in adipose tissue

    DEFF Research Database (Denmark)

    Henriksen, O; Nielsen, Steen Levin; Paaske, W

    1976-01-01

    Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called autoregulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated...... subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an autoregulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g-min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue....... Following total ischemia all experiments showed a period with reactive hyperemia, and both duration of hyperemia and excess flow was related to the duration of the ischemia. This response therefore seems more resistant to the experimental procedure, while autoregulation of blood flow to lowered pressure...

  16. Adipose-derived stromal cells mediate in vivo adipogenesis, angiogenesis and inflammation in decellularized adipose tissue bioscaffolds.

    Science.gov (United States)

    Han, Tim Tian Y; Toutounji, Sandra; Amsden, Brian G; Flynn, Lauren E

    2015-12-01

    Decellularized adipose tissue (DAT) has shown promise as an adipogenic bioscaffold for soft tissue augmentation and reconstruction. The objective of the current study was to investigate the effects of allogeneic adipose-derived stem/stromal cells (ASCs) on in vivo fat regeneration in DAT bioscaffolds using an immunocompetent rat model. ASC seeding significantly enhanced angiogenesis and adipogenesis, with cell tracking studies indicating that the newly-forming tissues were host-derived. Incorporating ASCs also mediated the inflammatory response and promoted a more constructive macrophage phenotype. A fraction of the CD163(+) macrophages in the implants expressed adipogenic markers, with higher levels of this "adipocyte-like" phenotype in proximity to the developing adipose tissues. Our results indicate that the combination of ASCs and adipose extracellular matrix (ECM) provides an inductive microenvironment for adipose regeneration mediated by infiltrating host cell populations. The DAT scaffolds are a useful tissue-specific model system for investigating the mechanisms of in vivo adipogenesis that may help to develop a better understanding of this complex process in the context of both regeneration and disease. Overall, combining adipose-derived matrices with ASCs is a highly promising approach for the in situ regeneration of host-derived adipose tissue.

  17. Increased peroxisome proliferator-activated receptor γ expression levels in visceral adipose tissue, and serum CCL2 and interleukin-6 levels during visceral adipose tissue accumulation.

    Science.gov (United States)

    Yogarajah, Thaneswary; Bee, Yvonne-Tee Get; Noordin, Rahmah; Yin, Khoo Boon

    2015-01-01

    This study was conducted to determine the mRNA and protein expression levels of peroxisome proliferator-activated receptors (PPARs) in visceral adipose tissue, as well as serum adipokine levels, in Sprague Dawley rats. The rats were fed either a normal (control rats) or excessive (experimental rats) intake of food for 8 or 16 weeks, then sacrificed, at which time visceral and subcutaneous adipose tissues, as well as blood samples, were collected. The mRNA and protein expression levels of PPARs in the visceral adipose tissues were determined using reverse transcription-polymerase chain reaction and Western blotting, respectively. In addition, the levels of adipokines in the serum samples were determined using commercial ELISA kits. The results revealed that at 8 weeks, the mass of subcutaneous adipose tissue was higher than that of the visceral adipose tissue in the experimental rats, but the reverse occurred at 16 weeks. Furthermore, at 16 weeks the experimental rats exhibited an upregulation of PPARγ mRNA and protein expression levels in the visceral adipose tissues, and significant increases in the serum levels of CCL2 and interleukin (IL)-6 were observed, compared with those measured at 8 weeks. In conclusion, this study demonstrated that the PPARγ expression level was likely correlated with serum levels of CCL2 and IL-6, molecules that may facilitate visceral adipose tissue accumulation. In addition, the levels of the two adipokines in the serum may be useful as surrogate biomarkers for the expression levels of PPARγ in accumulated visceral adipose tissues.

  18. Identification of cathepsin K as a novel marker of adiposity in white adipose tissue.

    Science.gov (United States)

    Chiellini, Chiara; Costa, Mario; Novelli, Silvia E; Amri, Ez-Zoubir; Benzi, Luca; Bertacca, Anna; Cohen, Paul; Del Prato, Stefano; Friedman, Jeffrey M; Maffei, Margherita

    2003-05-01

    In obesity, adipocytes undergo dramatic morphological and molecular changes associated with alterations in their gene expression profile. To identify genes differentially modulated in white adipose tissue (WAT) of obese db/db mice compared to wild type (wt) mice, we utilized RNA fingerprinting. Among the 52 candidates that we identified, we focused here on cathepsin K (ctsk), a cysteine protease, prevalently localized in lysosomes and involved in bone extracellular matrix degradation. In db/db mice, WAT ctsk mRNA was elevated 5.9-fold, as were Mitf and TFE3 (2- and 3.3-fold respectively), two transcription factors involved in ctsk induction in osteoclasts. Moreover, the level of WAT ctsk mRNA was increased in other obese models including A(y), fat, and tubby (2.8-, 3.2-, and 4.9-fold respectively) and decreased in mice undergoing weight loss. Despite the ubiquitous distribution of the ctsk transcript, we demonstrated that the obesity related increase is specific to the adipocytes. Further, in vitro experiments proved that the abundance of ctsk transcript increases upon adipose conversion of the established cell line of preadipocytes 3T3-F442A. In addition, ctsk gene expression was examined in adipose tissue of 21 lean and obese male subjects and significant correlations with BMI (r = 0.54, P = 0.012) and plasma leptin levels (r = 0.54, P = 0.015) were found. In conclusion, the WAT of obese db/db mice exhibits a different expression profile from that of the wt mice, and cathepsin K can be considered a novel marker of obesity and a target for the inhibition of adipose mass growth.

  19. Berberine activates thermogenesis in white and brown adipose tissue.

    Science.gov (United States)

    Zhang, Zhiguo; Zhang, Huizhi; Li, Bo; Meng, Xiangjian; Wang, Jiqiu; Zhang, Yifei; Yao, Shuangshuang; Ma, Qinyun; Jin, Lina; Yang, Jian; Wang, Weiqing; Ning, Guang

    2014-11-25

    Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue formation and function increases energy expenditure and hence may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicinal plant Coptis chinensis. Here we show that BBR increases energy expenditure, limits weight gain, improves cold tolerance and enhances brown adipose tissue (BAT) activity in obese db/db mice. BBR markedly induces the development of brown-like adipocytes in inguinal, but not epididymal adipose depots. BBR also increases expression of UCP1 and other thermogenic genes in white and BAT and primary adipocytes via a mechanism involving AMPK and PGC-1α. BBR treatment also inhibits AMPK activity in the hypothalamus, but genetic activation of AMPK in the ventromedial nucleus of the hypothalamus does not prevent BBR-induced weight loss and activation of the thermogenic programme. Our findings establish a role for BBR in regulating organismal energy balance, which may have potential therapeutic implications for the treatment of obesity.

  20. Adipose tissue and ceramide biosynthesis in the pathogenesis of obesity.

    Science.gov (United States)

    Samad, Fahumiya; Badeanlou, Leylla; Shah, Charmi; Yang, Guang

    2011-01-01

    Although obesity is a complex metabolic disorder often associated with insulin resistance, hyperinsulinemia and Type 2 diabetes, as well as with accelerated atherosclerosis, the molecular changes in obesity that promote these disorders are not completely understood. Several mechanisms have been proposed to explain how increased adipose tissue mass affects whole body insulin resistance and cardiovascular risk. One theory is that increased adipose derived inflammatory cytokines induces a chronic inflammatory state that not only increases cardiovascular risk, but also antagonizes insulin signaling and mitochondrial function and thereby impair glucose hemostasis. Another suggests that lipid accumulation in nonadipose tissues not suited for fat storage leads to the buildup of bioactive lipids that inhibit insulin signaling and metabolism. Recent evidence demonstrates that sphingolipid metabolism is dysregulated in obesity and specific sphingolipids may provide a common pathway that link excess nutrients and inflammation to increased metabolic and cardiovascular risk. This chapter will focus primarily on the expression and regulation of adipose and plasma ceramide biosynthesis in obesity and, its potential contribution to the pathogenesis of obesity and the metabolic syndrome.

  1. Adipose tissue and vascular inflammation in coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    Enrica; Golia; Giuseppe; Limongelli; Francesco; Natale; Fabio; Fimiani; Valeria; Maddaloni; Pina; Elvira; Russo; Lucia; Riegler; Renatomaria; Bianchi; Mario; Crisci; Gaetano; Di; Palma; Paolo; Golino; Maria; Giovanna; Russo; Raffaele; Calabrò; Paolo; Calabrò

    2014-01-01

    Obesity has become an important public health issue in Western and developing countries,with well known metabolic and cardiovascular complications.In the last decades,evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences.As a consequence of the expansion of fat depots,in obese subjects,adipose tissue cells develope a phenotypic modification,which turns into a change of the secretory output.Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling,vascular biology and,moreover,participate to the systemic inflammatory response,which characterizes obesity and metabolic syndrome.This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events.A great number of adipocytokines have been described recently,linking inflammatory mileu and vascular pathology.The understanding of these pathways is crucial not only from a pathophysiological point of view,but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets.The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease.

  2. Mechanobiology and Mechanotherapy of Adipose Tissue-Effect of Mechanical Force on Fat Tissue Engineering.

    Science.gov (United States)

    Yuan, Yi; Gao, Jianhua; Ogawa, Rei

    2015-12-01

    Our bodies are subjected to various mechanical forces, which in turn affect both the structure and function of our bodies. In particular, these mechanical forces play an important role in tissue growth and regeneration. Adipocytes and adipose-derived stem cells are both mechanosensitive and mechanoresponsive. The aim of this review is to summarize the relationship between mechanobiology and adipogenesis. PubMed was used to search for articles using the following keywords: mechanobiology, adipogenesis, adipose-derived stem cells, and cytoskeleton. In vitro and in vivo experiments have shown that adipogenesis is strongly promoted/inhibited by various internal and external mechanical forces, and that these effects are mediated by changes in the cytoskeleton of adipose-derived stem cells and/or various signaling pathways. Thus, adipose tissue engineering could be enhanced by the careful application of mechanical forces. It was shown recently that mature adipose tissue regenerates in an adipose tissue-engineering chamber. This observation has great potential for the reconstruction of soft tissue deficiencies, but the mechanisms behind it remain to be elucidated. On the basis of our understanding of mechanobiology, we hypothesize that the chamber removes mechanical force on the fat that normally impose high cytoskeletal tension. The reduction in tension in adipose stem cells triggers their differentiation into adipocytes. The improvement in our understanding of the relationship between mechanobiology and adipogenesis means that in the near future, we may be able to increase or decrease body fat, as needed in the clinic, by controlling the tension that is loaded onto fat.

  3. Supercritical carbon dioxide extracted extracellular matrix material from adipose tissue.

    Science.gov (United States)

    Wang, Jun Kit; Luo, Baiwen; Guneta, Vipra; Li, Liang; Foo, Selin Ee Min; Dai, Yun; Tan, Timothy Thatt Yang; Tan, Nguan Soon; Choong, Cleo; Wong, Marcus Thien Chong

    2017-06-01

    Adipose tissue is a rich source of extracellular matrix (ECM) material that can be isolated by delipidating and decellularizing the tissue. However, the current delipidation and decellularization methods either involve tedious and lengthy processes or require toxic chemicals, which may result in the elimination of vital proteins and growth factors found in the ECM. Hence, an alternative delipidation and decellularization method for adipose tissue was developed using supercritical carbon dioxide (SC-CO2) that eliminates the need of any harsh chemicals and also reduces the amount of processing time required. The resultant SC-CO2-treated ECM material showed an absence of nuclear content but the preservation of key proteins such as collagen Type I, collagen Type III, collagen Type IV, elastin, fibronectin and laminin. In addition, other biological factors such as glycosaminoglycans (GAGs) and growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were also retained. Subsequently, the resulting SC-CO2-treated ECM material was used as a bioactive coating on tissue culture plastic (TCP). Four different cell types including adipose tissue-derived mesenchymal stem cells (ASCs), human umbilical vein endothelial cells (HUVECs), immortalized human keratinocyte (HaCaT) cells and human monocytic leukemia cells (THP-1) were used in this study to show that the SC-CO2-treated ECM coating can be potentially used for various biomedical applications. The SC-CO2-treated ECM material showed improved cell-material interactions for all cell types tested. In addition, in vitro scratch wound assay using HaCaT cells showed that the presence of SC-CO2-treated ECM material enhanced keratinocyte migration whilst the in vitro cellular studies using THP-1-derived macrophages showed that the SC-CO2-treated ECM material did not evoke pro-inflammatory responses from the THP-1-derived macrophages. Overall, this study shows the efficacy of SC-CO2

  4. Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment

    DEFF Research Database (Denmark)

    Tobin, L; Simonsen, L; Bülow, J

    2010-01-01

    the basic and postprandial microvascular volume in adipose tissue using real-time contrast-enhanced ultrasound (CEU) imaging in healthy normal weight subjects. In nine subjects, CEU was performed in abdominal subcutaneous adipose tissue and in the underlying skeletal muscle after a bolus injection...... of ultrasound contrast agent to establish the reproducibility of the technique. In nine subjects, the effect of an oral glucose load on blood flow and microvascular volume was measured in abdominal subcutaneous adipose tissue and forearm skeletal muscle. ¹³³Xe washout and venous occlusion strain......-gauge plethysmography was used to measure the adipose tissue and forearm blood flow, respectively. Ultrasound signal intensity of the first plateau phases was 27 ± dB in the abdominal subcutaneous adipose tissue and 18 ± 2 dB (P muscle. The reproducibility of the measurements was good...

  5. Regional differences in perivascular adipose tissue impacting vascular homeostasis.

    Science.gov (United States)

    Gil-Ortega, Marta; Somoza, Beatriz; Huang, Yu; Gollasch, Maik; Fernández-Alfonso, Maria S

    2015-07-01

    Perivascular adipose tissue (PVAT) releases several important vasoactive factors with physiological and pathophysiological paracrine effects. A large body of evidence suggests regional phenotypic and functional differences among PVAT depots, depending on the specific vascular bed or different regions in the vascular bed where the PVAT is located. These non-uniform and separate PVATs exert various paracrine effects on vascular structure and function that largely impact disease states, such as endothelial dysfunction, atherosclerosis, or insulin resistance. This emerging view of PVAT function requires considering heterogeneous PVAT as a specialized organ that can differentially regulate vascular function depending on its anatomical location. In this context, the adipose-vascular axis may represent a novel target for pharmacological intervention in vasculopathy in cardiometabolic disorders.

  6. Weight cycling enhances adipose tissue inflammatory responses in male mice.

    Directory of Open Access Journals (Sweden)

    Sandra Barbosa-da-Silva

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

  7. Deletion of CD1d in Adipocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity.

    Science.gov (United States)

    Huh, Jin Young; Park, Jeu; Kim, Jong In; Park, Yoon Jeong; Lee, Yun Kyung; Kim, Jae Bum

    2017-04-01

    Adipose tissue inflammation is an important factor in obesity that promotes insulin resistance. Among various cell types in adipose tissue, immune cells actively regulate inflammatory responses and affect whole-body energy metabolism. In particular, invariant natural killer T (iNKT) cells contribute to mitigating dysregulation of systemic energy homeostasis by counteracting obesity-induced inflammation in adipose tissue. However, the molecular mechanisms by which adipose iNKT cells become activated and mediate anti-inflammatory roles in obese adipose tissue have not been thoroughly understood yet. In the current study, we demonstrate that adipocyte CD1d plays a key role in the stimulation of adipose iNKT cells, leading to anti-inflammatory responses in high-fat diet (HFD)-fed mice. Accordingly, adipocyte-specific CD1d-knockout (CD1d(ADKO)) mice showed reduced numbers of iNKT cells in adipose tissues and decreased responses to α-galactosylceramide-induced iNKT cell activation. Additionally, HFD-fed CD1d(ADKO) mice revealed reduced interleukin-4 expression in adipose iNKT cells and aggravated adipose tissue inflammation and insulin resistance. Collectively, these data suggest that adipocytes could selectively stimulate adipose iNKT cells to mediate anti-inflammatory responses and attenuate excess proinflammatory responses in obese adipose tissue. © 2017 by the American Diabetes Association.

  8. Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells

    National Research Council Canada - National Science Library

    Hammarstedt, Ann; Graham, Timothy E; Kahn, Barbara B

    2012-01-01

    Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver...

  9. Brown Adipose Tissue Bioenergetics: A New Methodological Approach

    Science.gov (United States)

    Calderon‐Dominguez, María; Alcalá, Martín; Sebastián, David; Zorzano, Antonio; Viana, Marta; Serra, Dolors

    2017-01-01

    The rediscovery of brown adipose tissue (BAT) in humans and its capacity to oxidize fat and dissipate energy as heat has put the spotlight on its potential as a therapeutic target in the treatment of several metabolic conditions including obesity and diabetes. To date the measurement of bioenergetics parameters has required the use of cultured cells or extracted mitochondria with the corresponding loss of information in the tissue context. Herein, we present a method to quantify mitochondrial bioenergetics directly in BAT. Based on XF Seahorse Technology, we assessed the appropriate weight of the explants, the exact concentration of each inhibitor in the reaction, and the specific incubation time to optimize bioenergetics measurements. Our results show that BAT basal oxygen consumption is mostly due to proton leak. In addition, BAT presents higher basal oxygen consumption than white adipose tissue and a positive response to b‐adrenergic stimulation. Considering the whole tissue and not just subcellular populations is a direct approach that provides a realistic view of physiological respiration. In addition, it can be adapted to analyze the effect of potential activators of thermogenesis, or to assess the use of fatty acids or glucose as a source of energy. PMID:28435771

  10. Two types of brown adipose tissue in humans.

    Science.gov (United States)

    Lidell, Martin E; Betz, Matthias J; Enerbäck, Sven

    2014-01-01

    During the last years the existence of metabolically active brown adipose tissue in adult humans has been widely accepted by the research community. Its unique ability to dissipate chemical energy stored in triglycerides as heat makes it an attractive target for new drugs against obesity and its related diseases. Hence the tissue is now subject to intense research, the hypothesis being that an expansion and/or activation of the tissue is associated with a healthy metabolic phenotype. Animal studies provide evidence for the existence of at least two types of brown adipocytes. Apart from the classical brown adipocyte that is found primarily in the interscapular region where it constitutes a thermogenic organ, a second type of brown adipocyte, the so-called beige adipocyte, can appear within white adipose tissue depots. The fact that the two cell types develop from different precursors suggests that they might be recruited and stimulated by different cues and therefore represent two distinct targets for therapeutic intervention. The aim of this commentary is to discuss recent work addressing the question whether also humans possess two types of brown adipocytes and to highlight some issues when looking for molecular markers for such cells.

  11. 11-Hydroxy-β-steroid dehydrogenase gene expression in canine adipose tissue and adipocytes: stimulation by lipopolysaccharide and tumor necrosis factor α.

    Science.gov (United States)

    Ryan, V H; Trayhurn, P; Hunter, L; Morris, P J; German, A J

    2011-10-01

    The enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD-1) is expressed in a number of tissues in rodents and humans and is responsible for the reactivation of inert cortisone into cortisol. Its gene expression and activity are increased in white adipose tissue (WAT) from obese humans and may contribute to the adverse metabolic consequences of obesity and the metabolic syndrome. The extent to which 11β-HSD-1 contributes to adipose tissue function in dogs is unknown; the aim of the present study was to examine 11β-HSD-1 gene expression and its regulation by proinflammatory and anti-inflammatory agents in canine adipocytes. Real-time PCR was used to examine the expression of 11β-HSD-1 in canine adipose tissue and canine adipocytes differentiated in culture. The mRNA encoding 11β-HSD-1 was identified in all the major WAT depots in dogs and also in liver, kidney, and spleen. Quantification by real-time PCR showed that 11β-HSD-1 mRNA was least in perirenal and falciform depots and greatest in subcutaneous, omental, and gonadal depots. Greater expression was seen in the omental depot in female than in male dogs (P=0.05). Gene expression for 11β-HSD-1 was also seen in adipocytes, from both subcutaneous and visceral depots, differentiated in culture; expression was evident throughout differentiation but was generally greatest in preadipocytes and during early differentiation, declining as cells progressed to maturity. The inflammatory mediators lipopolysaccharide and tumor necrosis factor α had a main stimulatory effect on 11β-HSD-1 gene expression in canine subcutaneous adipocytes, but IL-6 had no significant effect. Treatment with dexamethasone resulted in a significant time- and dose-dependent increase in 11β-HSD-1 gene expression, with greatest effects seen at 24 h (2 nM: approximately 4-fold; 20 nM: approximately 14-fold; P=0.010 for both). When subcutaneous adipocytes were treated with the peroxisome proliferator activated receptor γ agonist rosiglitazone

  12. Adipose Tissue Dysregulation and Reduced Insulin Sensitivity in Non-Obese Individuals with Enlarged Abdominal Adipose Cells

    OpenAIRE

    Hammarstedt Ann; Graham Timothy E; Kahn Barbara B

    2012-01-01

    Abstract Background Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver; these include reduced insulin-stimulated glucose transport, reduced expression of GLUT4, altered expression of adipokines, and adipocyte hypertrophy. Animal studies have shown that expansion of adipose tissue alone is not sufficient to ...

  13. Tissue/blood partition coefficients for xenon in various adipose tissue depots in man

    DEFF Research Database (Denmark)

    Bülow, J; Jelnes, Rolf; Astrup, A

    1987-01-01

    Tissue/blood partition coefficients (lambda) for xenon were calculated for subcutaneous adipose tissue from the abdominal wall and the thigh, and for the perirenal adipose tissue after chemical analysis of the tissues for lipid, water and protein content. The lambda in the perirenal tissue...... was found to correlate linearly to the relative body weight (RBW) in per cent with the regression equation lambda = 0.045 . RBW + 0.99. The subcutaneous lambda on the abdomen correlated linearly to the local skinfold thickness (SFT) with the equation lambda = 0.22 SFT + 2.99. Similarly lambda on the thigh...... correlated to SFT with the equation lambda = 0.20 . SFT + 4.63. It is concluded that the previously accepted lambda value of 10 is generally too high in perirenal as well as in subcutaneous tissue. Thus, by application of the present regression equations, it is possible to obtain more exact estimates...

  14. Adipose tissue and adipocytes support tumorigenesis and metastasis.

    Science.gov (United States)

    Nieman, Kristin M; Romero, Iris L; Van Houten, Bennett; Lengyel, Ernst

    2013-10-01

    Adipose tissue influences tumor development in two major ways. First, obese individuals have a higher risk of developing certain cancers (endometrial, esophageal, and renal cell cancer). However, the risk of developing other cancers (melanoma, rectal, and ovarian) is not altered by body mass. In obesity, hypertrophied adipose tissue depots are characterized by a state of low grade inflammation. In this activated state, adipocytes and inflammatory cells secrete adipokines and cytokines which are known to promote tumor development. In addition, the adipocyte mediated conversion of androgens to estrogen specifically contributes to the development of endometrial cancer, which shows the greatest relative risk (6.3-fold) increase between lean and obese individuals. Second, many tumor types (gastric, breast, colon, renal, and ovarian) grow in the anatomical vicinity of adipose tissue. During their interaction with cancer cells, adipocytes dedifferentiate into pre-adipocytes or are reprogrammed into cancer-associated adipocytes (CAA). CAA secrete adipokines which stimulate the adhesion, migration, and invasion of tumor cells. Cancer cells and CAA also engage in a dynamic exchange of metabolites. Specifically, CAA release fatty acids through lipolysis which are then transferred to cancer cells and used for energy production through β-oxidation. The abundant availability of lipids from adipocytes in the tumor microenvironment, supports tumor progression and uncontrolled growth. Given that adipocytes are a major source of adipokines and energy for the cancer cell, understanding the mechanisms of metabolic symbiosis between cancer cells and adipocytes, should reveal new therapeutic possibilities. This article is part of a Special Issue entitled Lipid Metabolism in Cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Organochlorine pesticide levels in female adipose tissue from Puebla, Mexico.

    Science.gov (United States)

    Waliszewski, Stefan M; Sanchez, K; Caba, M; Saldariaga-Noreña, H; Meza, E; Zepeda, R; Valencia Quintana, R; Infanzon, R

    2012-02-01

    The objective of this study was to determine the levels of organochlorine pesticides HCB, α-β-γ-HCH, pp'DDE, op'DDT and pp'DDT in adipose tissue of females living in Puebla, Mexico. Organochlorine pesticides were analyzed in 75 abdominal adipose tissue samples taken during 2010 by autopsy at the Forensic Services of Puebla. The results were expressed as mg/kg on fat basis. In analyzed samples the following pesticides were detected: p,p'-DDE in 100% of samples at mean 1.464 mg/kg; p,p'-DDT in 96.0.% of samples at mean 0.105 mg/kg; op'DDT in 89.3% of monitored samples at mean 0.025 mg/kg and β-HCH in 94.7% of the samples at mean 0.108 mg/kg. To show if organochlorine pesticide levels in monitored female's adipose tissues are age dependant, the group was divided in three ages ranges (13-26, 26-57 and 57-96 years). The mean and median levels of all organochlorine pesticides increase significantly (p 0.05). The present results compared to previous ones from 2008 indicates an increase in the concentrations during the 2010 study, but only the differences for pp'DDE and op'DDT were statistically significant. The 2010 group of females was older compared to the 2008 group. The presence of organochlorine pesticide residues is still observed, indicating uniform and permanent exposure to the pesticides by Puebla inhabitants.

  16. Laminin α4 deficient mice exhibit decreased capacity for adipose tissue expansion and weight gain.

    Directory of Open Access Journals (Sweden)

    Marcella K Vaicik

    Full Text Available Obesity is a global epidemic that contributes to the increasing medical burdens related to type 2 diabetes, cardiovascular disease and cancer. A better understanding of the mechanisms regulating adipose tissue expansion could lead to therapeutics that eliminate or reduce obesity-associated morbidity and mortality. The extracellular matrix (ECM has been shown to regulate the development and function of numerous tissues and organs. However, there is little understanding of its function in adipose tissue. In this manuscript we describe the role of laminin α4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin α4 gene (Lama4-/- and compared to wild-type (Lama4+/+ control animals. Lama4-/- mice exhibited reduced weight gain in response to both age and high fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin α4 influences adipose tissue structure and function in a depot-specific manner. Alterations in laminin composition offers insight into the roll the ECM potentially plays in modulating cellular behavior in adipose tissue expansion.

  17. Laminin α4 deficient mice exhibit decreased capacity for adipose tissue expansion and weight gain.

    Science.gov (United States)

    Vaicik, Marcella K; Thyboll Kortesmaa, Jill; Movérare-Skrtic, Sofia; Kortesmaa, Jarkko; Soininen, Raija; Bergström, Göran; Ohlsson, Claes; Chong, Li Yen; Rozell, Björn; Emont, Margo; Cohen, Ronald N; Brey, Eric M; Tryggvason, Karl

    2014-01-01

    Obesity is a global epidemic that contributes to the increasing medical burdens related to type 2 diabetes, cardiovascular disease and cancer. A better understanding of the mechanisms regulating adipose tissue expansion could lead to therapeutics that eliminate or reduce obesity-associated morbidity and mortality. The extracellular matrix (ECM) has been shown to regulate the development and function of numerous tissues and organs. However, there is little understanding of its function in adipose tissue. In this manuscript we describe the role of laminin α4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin α4 gene (Lama4-/-) and compared to wild-type (Lama4+/+) control animals. Lama4-/- mice exhibited reduced weight gain in response to both age and high fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin α4 influences adipose tissue structure and function in a depot-specific manner. Alterations in laminin composition offers insight into the roll the ECM potentially plays in modulating cellular behavior in adipose tissue expansion.

  18. Cross-sectional associations of acylation stimulating protein (ASP) and adipose tissue gene expression with estradiol and progesterone in pre- and postmenopausal women.

    Science.gov (United States)

    Rezvani, Reza; Gupta, Abhishek; Smith, Jessica; Poursharifi, Pegah; Marceau, Picard; Pérusse, Louis; Bouchard, Claude; Tchernof, André; Cianflone, Katherine

    2014-11-01

    Sex steroid hormones play an important regulatory role in fat metabolism and obesity. We hypothesized involvement of interactions between ovarian hormones with acylation stimulating protein (ASP). In 392 women with wide age (18-69 years) and body size (BMI: 17 to 90 kg/m(2) ) ranges, fasting plasma levels of ASP, ovarian hormones, glucose, adiponectin and lipids/apolipoproteins were assessed, along with determination of metabolic syndrome (MS) features. Gene expression of C3 (ASP precursor) and related receptors C5L2, C3aR and C5aR in subcutaneous and omental adipose tissues was measured in a subset. Acylation stimulating protein correlated negatively with concentrations of estradiol (P ASP levels (P ASP and adipose tissue gene expression of its related proteins in a depot-specific manner. ASP may play a role in the regulation of regional fat metabolism through interactions with sex hormones in women. © 2014 John Wiley & Sons Ltd.

  19. Is Crohn’s creeping fat an adipose tissue?

    OpenAIRE

    Olivier, Isabelle; Theodorou, Vassilia; Valet, Philippe; Castan-Laurell, Isabelle; Guillou, Hervé; Bertrand-Michel, Justine; Cartier, Christel; Bezirard, Valerie; Ducroc, Robert; Segain, Jean-Pierre; Portier, Guillaume; Kirzin, Sylvain; Moreau, Jacques; Duffas, Jean-Pierre; Ferrier, Laurent

    2011-01-01

    Background: In human pathology, the ‘‘creeping fat’’ (CF) ofthe mesentery is unique to Crohn’s disease (CD). CF is usuallyreferred to as an ectopic extension of mesenteric adipose tissue(MAT). However, since no animal model developing CF has everbeen established, very little is known about this type of fat-depotexpansion and its role in the development of the disease.Methods: We developed and standardized an experimental protocolin mice that reproducibly induces CF development when asevere co...

  20. Adipose Tissue-Derived Stem Cells for Myocardial Regeneration

    Science.gov (United States)

    Joo, Hyung Joon; Kim, Jong-Ho

    2017-01-01

    Over the past decade, stem cell therapy has been extensively studied for clinical application for heart diseases. Among various stem cells, adipose tissue-derived stem cell (ADSC) is still an attractive stem cell resource due to its abundance and easy accessibility. In vitro studies showed the multipotent differentiation potentials of ADSC, even differentiation into cardiomyocytes. Many pre-clinical animal studies have also demonstrated promising therapeutic results of ADSC. Furthermore, there were several clinical trials showing the positive results in acute myocardial infarction using ADSC. The present article covers the brief introduction, the suggested therapeutic mechanisms, application methods including cell dose and delivery, and human clinical trials of ADSC for myocardial regeneration.

  1. Metabolic Dysregulation and Adipose Tissue Fibrosis: Role of Collagen VI▿ †

    OpenAIRE

    Khan, Tayeba; Muise, Eric S.; Iyengar, Puneeth; Wang, Zhao V.; Chandalia, Manisha; Abate, Nicola; Zhang, Bei B.; Bonaldo, Paolo; Chua, Streamson; Scherer, Philipp E.

    2008-01-01

    Adipocytes are embedded in a unique extracellular matrix whose main function is to provide mechanical support, in addition to participating in a variety of signaling events. During adipose tissue expansion, the extracellular matrix requires remodeling to accommodate adipocyte growth. Here, we demonstrate a general upregulation of several extracellular matrix components in adipose tissue in the diabetic state, therefore implicating “adipose tissue fibrosis” as a hallmark of metabolically chall...

  2. Role of bioactive lipid mediators in obese adipose tissue inflammation and endocrine dysfunction.

    OpenAIRE

    Lopategi, Aritz; López-Vicario, Cristina; Alcaraz-Quiles, José; García-Alonso, Verónica; Rius, Bibiana; Titos Rodríguez, Esther; Clària i Enrich, Joan

    2015-01-01

    White adipose tissue is recognized as an active endocrine organ implicated in the maintenance of metabolic homeostasis. However, adipose tissue function, which has a crucial role in the development of obesity-related comorbidities including insulin resistance and non-alcoholic fatty liver disease, is dysregulated in obese individuals. This review explores the physiological functions and molecular actions of bioactive lipids biosynthesized in adipose tissue including sphingolipids and phosphol...

  3. Decreased adipose tissue zinc content is associated with metabolic parameters in high fat fed Wistar rats

    OpenAIRE

    Alexey A. Tinkov; Elizaveta V. Popova; Evgenia R. Gatiatulina; Anastasia A. Skalnaya; Elena N. Yakovenko; Irina B. Alchinova; Mikhail Y. Karganov; Anatoly V. Skalny; Nikonorov, Alexandr A.

    2016-01-01

    Background. Limited data on adipose tissue zinc content in obesity exist. At the same time, the association between adipose tissue zinc content and metabolic parameters in dietary-induced obesity is poorly studied. Therefore, the primary objective of this study is to assess adipose tissue zinc content and its association  with morphometric parameters, adipokine spectrum, proinflammatory cytokines, and apolipoprotein profile in high fat fed Wistar rats. Material and method...

  4. Observations on Preadipocytes and Their Distribution Patterns in Rat Adipose Tissue

    Science.gov (United States)

    1981-01-01

    enzyme lipoprotein lipase (Hietanen and viously (Stiles et al., 󈨏) in rat adipose tissue Greenwood, 󈨑). Exercise training initiated and suggest that...Huston, C.G. Plopper, and A.L. Hecker increased hormone sensitivity during in vitro adipocyte (1975) Adipose tissue cellularity and lipolysis : Response to... adipose tissue developing into adipocytes. J. Usuku, G., K. Iyama, and K. Ohzono (1978) Ultrastructural Lipid Res., 19: 316-324. studies on the white

  5. Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity?

    Science.gov (United States)

    Trayhurn, Paul; Wang, Bohan; Wood, I Stuart

    2008-08-01

    White adipose tissue is a key endocrine and secretory organ, releasing multiple adipokines, many of which are linked to inflammation and immunity. During the expansion of adipose tissue mass in obesity there is a major inflammatory response in the tissue with increased expression and release of inflammation-related adipokines, including IL-6, leptin, monocyte chemoattractant protein-1 and TNF-alpha, together with decreased adiponectin production. We proposed in 2004 (Trayhurn & Wood, Br J Nutr 92, 347-355) that inflammation in adipose tissue in obesity is a response to hypoxia in enlarged adipocytes distant from the vasculature. Hypoxia has now been directly demonstrated in adipose tissue of several obese mouse models (ob/ob, KKAy, diet-induced) and molecular studies indicate that the level of the hypoxia-inducible transcription factor, hypoxia-inducible factor-1 alpha, is increased, as is expression of the hypoxia-sensitive marker gene, GLUT1. Cell- culture studies on murine and human adipocytes show that hypoxia (induced by low O2 or chemically) leads to stimulation of the expression and secretion of a number of inflammation-related adipokines, including angiopoietin-like protein 4, IL-6, leptin, macrophage migration inhibitory factor and vascular endothelial growth factor. Hypoxia also stimulates the inflammatory response of macrophages and inhibits adipocyte differentiation from preadipocytes. GLUT1 gene expression, protein level and glucose transport by human adipocytes are markedly increased by hypoxia, indicating that low O2 tension stimulates glucose utilisation. It is suggested that hypoxia has a pervasive effect on adipocyte metabolism and on overall adipose tissue function, underpinning the inflammatory response in the tissue in obesity and the subsequent development of obesity-associated diseases, particularly type 2 diabetes and the metabolic syndrome.

  6. The fractionation of adipose tissue procedure to obtain stromal vascular fractions for regenerative purposes

    NARCIS (Netherlands)

    van Dongen, Joris A.; Stevens, Hieronymus P.; Parvizi, Mojtaba; van der Lei, Berend; Harmsen, Martin C.

    2016-01-01

    Autologous adipose tissue transplantation is clinically used to reduce dermal scarring and to restore volume loss. The therapeutic benefit on tissue damage more likely depends on the stromal vascular fraction of adipose tissue than on the adipocyte fraction. This stromal vascular fraction can be obt

  7. The Secretory Function of Adipocytes in the Physiology of White Adipose Tissue

    NARCIS (Netherlands)

    Wang, P.; Mariman, E.; Renes, J.; Keijer, J.

    2008-01-01

    White adipose tissue, previously regarded as a passive lipid storage site, is now viewed as a dynamic tissue. It has the capacity to actively communicate by sending and receiving different types of signals. An overview of these signals, the external modulators that affect adipose tissue and the secr

  8. The Fractionation of Adipose Tissue (FAT) procedure to obtain stromal vascular fractions for regenerative purposes

    NARCIS (Netherlands)

    van Dongen, Joris A; Stevens, Hieronymus P; Parvizi, Mojtaba; van der Lei, Berend; Harmsen, Martin C

    2016-01-01

    Autologous adipose tissue transplantation is clinically used to reduce dermal scarring and to restore volume loss. The therapeutic benefit on tissue damage more likely depends on the stromal vascular fraction of adipose tissue than on the adipocyte fraction. This stromal vascular fraction can be obt

  9. The fractionation of adipose tissue procedure to obtain stromal vascular fractions for regenerative purposes

    NARCIS (Netherlands)

    van Dongen, Joris A.; Stevens, Hieronymus P.; Parvizi, Mojtaba; van der Lei, Berend; Harmsen, Martin C.

    2016-01-01

    Autologous adipose tissue transplantation is clinically used to reduce dermal scarring and to restore volume loss. The therapeutic benefit on tissue damage more likely depends on the stromal vascular fraction of adipose tissue than on the adipocyte fraction. This stromal vascular fraction can be obt

  10. TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling

    Directory of Open Access Journals (Sweden)

    Nigel Beaton

    2015-11-01

    Conclusions: Collectively, these findings establish TUSC5 as an adipose tissue-specific protein that enables proper protein recycling, linking the ubiquitous vesicle traffic machinery with tissue-specific insulin-mediated glucose uptake into adipose tissue and the maintenance of a healthy metabolic phenotype in mice and humans.

  11. Modal response of a computational vocal fold model with a substrate layer of adipose tissue.

    Science.gov (United States)

    Jones, Cameron L; Achuthan, Ajit; Erath, Byron D

    2015-02-01

    This study demonstrates the effect of a substrate layer of adipose tissue on the modal response of the vocal folds, and hence, on the mechanics of voice production. Modal analysis is performed on the vocal fold structure with a lateral layer of adipose tissue. A finite element model is employed, and the first six mode shapes and modal frequencies are studied. The results show significant changes in modal frequencies and substantial variation in mode shapes depending on the strain rate of the adipose tissue. These findings highlight the importance of considering adipose tissue in computational vocal fold modeling.

  12. Adrenergic regulation of cellular plasticity in brown, beige/brite and white adipose tissues.

    Science.gov (United States)

    Ramseyer, Vanesa D; Granneman, James G

    2016-01-01

    The discovery of brown adipose tissue in adult humans along with the recognition of adipocyte heterogeneity and plasticity of white fat depots has renewed the interest in targeting adipose tissue for therapeutic benefit. Adrenergic activation is a well-established means of recruiting catabolic adipocyte phenotypes in brown and white adipose tissues. In this article, we review mechanisms of brown adipocyte recruitment by the sympathetic nervous system and by direct β-adrenergic receptor activation. We highlight the distinct modes of brown adipocyte recruitment in brown, beige/brite, and white adipose tissues, UCP1-independent thermogenesis, and potential non-thermogenic, metabolically beneficial effects of brown adipocytes.

  13. Prolactin suppresses malonyl-CoA concentration in human adipose tissue

    DEFF Research Database (Denmark)

    Nilsson, L. A.; Roepstorff, Carsten; Kiens, Bente

    2009-01-01

    +/-6% compared to control 100+/-5% (p=0.022) in cultured human adipose tissue. In addition, prolactin was found to decrease glucose transporter 4 ( GLUT4) mRNA expression, which may cause decreased glucose uptake. In conclusion, we propose that prolactin decreases lipogenesis in human adipose tissue...... 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...

  14. Sugar-sweetened and diet beverages in relation to visceral adipose tissue.

    Science.gov (United States)

    Odegaard, Andrew O; Choh, Audrey C; Czerwinski, Stefan A; Towne, Bradford; Demerath, Ellen W

    2012-03-01

    Frequent sugar-sweetened beverage (SSB) intake has been consistently associated with increased adiposity and cardio-metabolic risk, whereas the association with diet beverages is more mixed. We examined how these beverages associate with regional abdominal adiposity measures, specifically visceral adipose tissue (VAT). In a cross-sectional analysis of 791 non-Hispanic white men and women aged 18-70 we examined how beverage consumption habits obtained from a food frequency questionnaire associate with overall and abdominal adiposity measures from MRI. With increasing frequency of SSB intake, we observed increases in waist circumference (WC) and the proportion of visceral to subcutaneous abdominal adipose tissue (VAT%), with no change in total body fat (TBF%) or BMI. Greater frequency of diet beverage intake was associated with greater WC, BMI, and TBF%, but was not associated with variation in visceral adiposity We conclude that increased frequency of SSB consumption is associated with a more adverse abdominal adipose tissue deposition pattern.

  15. Endurance training changes in lipolytic responsiveness of obese adipose tissue.

    Science.gov (United States)

    De Glisezinski, I; Crampes, F; Harant, I; Berlan, M; Hejnova, J; Langin, D; Rivière, D; Stich, V

    1998-12-01

    The aim of this study was to investigate the effect of aerobic exercise training on the lipolytic response of adipose tissue in obese subjects. Thirteen men (body mass index = 36.9 +/- 1.3 kg/m2) were submitted to aerobic physical training on a cycloergometer (30-45 min, 4 days a wk) for 3 mo. Adipocyte sensitivity to the action of catecholamines and insulin was studied in vitro before and after training. Training induced a decrease in the percentage of fat mass (P < 0.05) without changing the body weight. Basal lipolysis and hormone-sensitive lipase activity were significantly decreased after training (P < 0.05). The lipolytic effects of epinephrine, isoprenaline (beta-adrenoceptor agonist), and dobutamine (beta1-adrenoceptor agonist) were significantly increased (P < 0.05) but not those of procaterol (beta2-adrenoceptor agonist). The antilipolytic effects of alpha2-adrenoceptor and insulin were significantly decreased (P < 0.05). Lipolysis stimulation by agents acting at the postreceptor level was unchanged after training. In conclusion, aerobic physical training in obese male subjects modifies adipose tissue lipolysis through an enhancement of beta-adrenergic response and a concomitant blunting of adipocyte antilipolytic activity.

  16. Adipose Tissue-Derived Stem Cells in Regenerative Medicine.

    Science.gov (United States)

    Frese, Laura; Dijkman, Petra E; Hoerstrup, Simon P

    2016-07-01

    In regenerative medicine, adult stem cells are the most promising cell types for cell-based therapies. As a new source for multipotent stem cells, human adipose tissue has been introduced. These so called adipose tissue-derived stem cells (ADSCs) are considered to be ideal for application in regenerative therapies. Their main advantage over mesenchymal stem cells derived from other sources, e.g. from bone marrow, is that they can be easily and repeatable harvested using minimally invasive techniques with low morbidity. ADSCs are multipotent and can differentiate into various cell types of the tri-germ lineages, including e.g. osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Interestingly, ADSCs are characterized by immunosuppressive properties and low immunogenicity. Their secretion of trophic factors enforces the therapeutic and regenerative outcome in a wide range of applications. Taken together, these particular attributes of ADSCs make them highly relevant for clinical applications. Consequently, the therapeutic potential of ADSCs is enormous. Therefore, this review will provide a brief overview of the possible therapeutic applications of ADSCs with regard to their differentiation potential into the tri-germ lineages. Moreover, the relevant advancements made in the field, regulatory aspects as well as other challenges and obstacles will be highlighted.

  17. Characterization of mesenchymal stem cells derived from equine adipose tissue

    Directory of Open Access Journals (Sweden)

    A.M. Carvalho

    2013-08-01

    Full Text Available Stem cell therapy has shown promising results in tendinitis and osteoarthritis in equine medicine. The purpose of this work was to characterize the adipose-derived mesenchymal stem cells (AdMSCs in horses through (1 the assessment of the capacity of progenitor cells to perform adipogenic, osteogenic and chondrogenic differentiation; and (2 flow cytometry analysis using the stemness related markers: CD44, CD90, CD105 and MHC Class II. Five mixed-breed horses, aged 2-4 years-old were used to collect adipose tissue from the base of the tail. After isolation and culture of AdMSCs, immunophenotypic characterization was performed through flow cytometry. There was a high expression of CD44, CD90 and CD105, and no expression of MHC Class II markers. The tri-lineage differentiation was confirmed by specific staining: adipogenic (Oil Red O, osteogenic (Alizarin Red, and chondrogenic (Alcian Blue. The equine AdMSCs are a promising type of adult progenitor cell for tissue engineering in veterinary medicine.

  18. Organotypic culture of human bone marrow adipose tissue.

    Science.gov (United States)

    Uchihashi, Kazuyoshi; Aoki, Shigehisa; Shigematsu, Masamori; Kamochi, Noriyuki; Sonoda, Emiko; Soejima, Hidenobu; Fukudome, Kenji; Sugihara, Hajime; Hotokebuchi, Takao; Toda, Shuji

    2010-04-01

    The precise role of bone marrow adipose tissue (BMAT) in the marrow remains unknown. The purpose of the present study was therefore to describe a novel method for studying BMAT using 3-D collagen gel culture of BMAT fragments, immunohistochemistry, ELISA and real-time reverse transcription-polymerase chain reaction. Mature adipocytes and CD45+ leukocytes were retained for >3 weeks. Bone marrow stromal cells (BMSC) including a small number of lipid-laden preadipocytes and CD44+/CD105+ mesenchymal stem cell (MSC)-like cells, developed from BMAT. Dexamethasone (10 micromol/L), but not insulin (20 mU/mL), significantly increased the number of preadipocytes. Dexamethasone and insulin also promoted leptin production and gene expression in BMAT. Adiponectin production by BMAT was BMAT, in which adiponectin protein secretion is normally very low, and that BMAT may exhibit a different phenotype from that of the visceral and subcutaneous adipose tissues. BMAT-osteoblast interactions were also examined, and it was found that osteoblasts inhibited the development of BMSC and reduced leptin production, while BMAT inhibited the growth and differentiation of osteoblasts. The present novel method proved to be useful for the study of BMAT biology.

  19. Hypothalamic regulation of brown adipose tissue thermogenesis and energy homeostasis

    Directory of Open Access Journals (Sweden)

    Wei eZhang

    2015-08-01

    Full Text Available Obesity and diabetes are increasing at an alarming rate worldwide, but the strategies for the prevention and treatment of these disorders remain inadequate. Brown adipose tissue (BAT is important for cold protection by producing heat using lipids and glucose as metabolic fuels. This thermogenic action causes increased energy expenditure and significant lipid/glucose disposal. In addition, BAT in white adipose tissue (WAT or beige cells have been found and they also exhibit the thermogenic action similar to BAT. These data provide evidence indicating BAT/beige cells as a potential target for combating obesity and diabetes. Recent discoveries of active BAT and beige cells in adult humans have further highlighted this potential. Growing studies have also shown the importance of central nervous system in the control of BAT thermogenesis and WAT browning using animal models. This review is focused on central neural thermoregulation, particularly addressing our current understanding of the importance of hypothalamic neural signaling in the regulation of BAT/beige thermogenesis and energy homeostasis.

  20. Remodeling of adipose tissue at experimental diabetes mellitus

    Directory of Open Access Journals (Sweden)

    O. A. Konovalova

    2013-08-01

    Full Text Available Introduction Diabetes mellitus (DM type 1 is chronіc disease whith progressive selective destruction of β- cells pancreatic islets (of Langerhans and whith development of absolute insulin failure. Active immune mechanisms take part in pathogenesis of this disease. Recently many publication appeared which report about the role of adipose tissue. In such way adipose tissue is not only the main metabolic regulator and endocrine organ synthesizing more than 30 regulatory proteins- adipokines, but it is one of the organs of immune system. Dysregulation of adipose tissue leads to morphological restructuring- remodeling of adipocytes, and the development of inflammation of adipose tissue in its turn is integral component of progression of many diseases. The aim of research The aim of this study was to investigate the morphological and functional state of parapancreatic fibre adipocytes in male Wistar rats in experimental diabetes mellitus. Materials and methods The study has been carried out on 20 male Wistar rats with weight 115-135 g. The animals were divided into 2 groups. The control group, which were injected 0,5 ml 0,1 М citrate buffer intraperitoneally (1group. Rats with 7 day experimental streptozotocin-induced diabetes mellitus were in the 2nd group. Adipose tissue was examined on the seventh day. For histological examination sections were colored with haematoxylin and eosin. Images were taken by using a fluorescence microscope PrimoStar(ZEISS,Germany with a computer-assisted video system AxioCam 5c (ZEISS,Germany including the NIH-Image software (NIH Image version 1·46. All statistical analyses were performed using EXCEL MS Office 2010 (Microsoft Corp., USA, STATISTICA 6.0 (Stat-Soft, 2001 software. Results were expressed as mean values ± SEM. Differences were considered statistically significant if the p value was <0.05. Results Injection of streptozotocin to experimental animals led to the development of experimental diabetes mellitus

  1. Dietary conjugated linoleic acids decrease leptin in porcine adipose tissue.

    Science.gov (United States)

    Di Giancamillo, Alessia; Rossi, Raffaella; Vitari, Francesca; Pastorelli, Grazia; Corino, Carlo; Domeneghini, Cinzia

    2009-10-01

    We investigated the effects of dietary conjugated linoleic acids (CLA) on white adipose tissue (WAT) in heavy pigs. Twelve pigs were assigned to 1 of 2 groups supplemented with either 0 or 0.75% of a CLA preparation (isomeric mixture) and were slaughtered at 159 +/- 2.3 kg live weight. Their subcutaneous WAT was analyzed by both chemical and microanatomical methods. The WAT of CLA-fed pigs tended to have a higher protein content (P = 0.064) and smaller adipocytes (P = 0.053) than that of control (CTR) pigs. The number of proliferating preadipocytes tended to be greater (P = 0.076) in pigs fed CLA, whereas the number of apoptotic adipocytes was greater (P leptin (Ob) expression was lower (P = 0.048) in adipocytes from treated pigs and Western blot quantification of Ob revealed lower levels (P tissue.

  2. Controlled cellular energy conversion in brown adipose tissue thermogenesis

    Science.gov (United States)

    Horowitz, J. M.; Plant, R. E.

    1978-01-01

    Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

  3. Intramuscular Adipose Tissue, Sarcopenia, and Mobility Function in Older Individuals

    Directory of Open Access Journals (Sweden)

    Robin L. Marcus

    2012-01-01

    Full Text Available Objective. Intramuscular adipose tissue (IMAT and sarcopenia may adversely impact mobility function and physical activity. This study determined the association of locomotor muscle structure and function with mobility function in older adults. Method. 109 older adults with a variety of comorbid disease conditions were examined for thigh muscle composition via MRI, knee extensor strength via isometric dynamometry, and mobility function. The contribution of strength, quadriceps lean tissue, and IMAT to explaining the variability in mobility function was examined using multivariate linear regression models. Results. The predictors as a group contributed 27–45% of the variance in all outcome measures; however, IMAT contributed between 8–15% of the variance in all four mobility variables, while lean explained only 5% variance in only one mobility measure. Conclusions. Thigh IMAT, a newly identified muscle impairment appears to be a potent muscle variable related to the ability of older adults to move about in their community.

  4. Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

    DEFF Research Database (Denmark)

    Basse, Astrid L.; Dixen, Karen; Yadav, Rachita

    2015-01-01

    Background: Large mammals are capable of thermoregulation shortly after birth due to the presence of brown adipose tissue (BAT). The majority of BAT disappears after birth and is replaced by white adipose tissue (WAT). Results: We analyzed the postnatal transformation of adipose in sheep....... Conclusions: Using global gene expression profiling of the postnatal BAT to WAT transformation in sheep, we provide novel insight into adipose tissue plasticity in a large mammal, including identification of novel transcriptional components linked to adipose tissue remodeling. Moreover, our data set provides...

  5. Visceral adipose tissue: emerging role of gluco- and mineralocorticoid hormones in the setting of cardiometabolic alterations

    Science.gov (United States)

    Boscaro, Marco; Giacchetti, Gilberta; Ronconi, Vanessa

    2012-01-01

    Several clinical and experimental lines of evidence have highlighted the detrimental effects of visceral adipose tissue excess on cardiometabolic parameters. Besides, recent findings have shown the effects of gluco-and mineralocorticoid hormones on adipose tissue and have also underscored the interplay existing between such adrenal steroids and their respective receptors in the modulation of adipose tissue biology. While the fundamental role played by glucocorticoids on adipocyte differentiation and storage was already well known, the relevance of the mineralocorticoids in the physiology of the adipose organ is of recent acquisition. The local and systemic renin–angiotensin–aldosterone system (RAAS) acting on adipose tissue seems to contribute to the development of the cardiometabolic phenotype so that its modulation can have deep impact on human health. A better understanding of the pathophysiology of the adipose organ is of crucial importance in order to identify possible therapeutic approaches that can avoid the development of such cardiovascular and metabolic sequelae. PMID:22804097

  6. Hedgehog signalling in myeloid cells impacts on body weight, adipose tissue inflammation and glucose metabolism.

    Science.gov (United States)

    Braune, Julia; Weyer, Ulrike; Matz-Soja, Madlen; Hobusch, Constance; Kern, Matthias; Kunath, Anne; Klöting, Nora; Kralisch, Susann; Blüher, Matthias; Gebhardt, Rolf; Zavros, Yana; Bechmann, Ingo; Gericke, Martin

    2017-05-01

    Recently, hedgehog (Hh) was identified as a crucial player in adipose tissue development and energy expenditure. Therefore, we tested whether Hh ligands are regulated in obesity. Further, we aimed at identifying potential target cells of Hh signalling and studied the functional impact of Hh signalling on adipose tissue inflammation and glucose metabolism. Hh ligands and receptors were analysed in adipose tissue or serum from lean and obese mice as well as in humans. To study the impact on adipose tissue inflammation and glucose metabolism, Hh signalling was specifically blocked in myeloid cells using a conditional knockout approach (Lys-Smo (-/-)). Desert Hh (DHH) and Indian Hh (IHH) are local Hh ligands, whereas Sonic Hh is not expressed in adipose tissue from mice or humans. In mice, obesity leads to a preferential upregulation of Hh ligands (Dhh) and signalling components (Ptch1, Smo and Gli1) in subcutaneous adipose tissue. Further, adipose tissue macrophages are Hh target cells owing to the expression of Hh receptors, such as Patched1 and 2. Conditional knockout of Smo (which encodes Smoothened, a mandatory Hh signalling component) in myeloid cells increases body weight and adipose tissue inflammation and attenuates glucose tolerance, suggesting an anti-inflammatory effect of Hh signalling. In humans, adipose tissue expression of DHH and serum IHH decrease with obesity and type 2 diabetes, which might be explained by the intake of metformin. Interestingly, metformin reduced Dhh and Ihh expression in mouse adipose tissue explants. Hh signalling in myeloid cells affects adipose tissue inflammation and glucose metabolism and may be a potential target to treat type 2 diabetes.

  7. Effects of Ang II receptor blocker irbesartan on adipose tissue function in mice with metabolic disorders.

    Science.gov (United States)

    Maeda, Akinobu; Tamura, Kouichi; Wakui, Hiromichi; Ohsawa, Masato; Azushima, Kengo; Uneda, Kazushi; Kobayashi, Ryu; Tsurumi-Ikeya, Yuko; Kanaoka, Tomohiko; Dejima, Toru; Ohki, Koji; Haku, Sona; Yamashita, Akio; Umemura, Satoshi

    2014-01-01

    Recent studies indicate that the functional renin-angiotensin system (RAS) exists in the adipose tissue. The adipose tissue RAS is proposed in the pathophysiology of metabolic disorders. In the present study, we examined therapeutic effects of irbesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders without any dietary loading, with our focus on the analysis on possible effect of irbesartan on the adipose tissue. The treatment with irbesartan significantly lowered systolic blood pressure with a concomitant decrease in body weight in KKAy mice. In addition, irbesartan significantly decreased the adipose leptin mRNA expression and tended to decrease IL-6 mRNA expression in the adipose tissue of KKAy mice. Furthermore irbesartan preserved the adipose gene expression of AT1R-associated protein (ATRAP), an endogenous inhibitory molecule of tissue AT1R signaling, with a concomitant tendency of up-regulation of adipose tissue ATRAP/AT1R ratio. Collectively, these results suggest that the irbesartan-induced beneficial suppressive effect on the leptin-IL-6 axis in the adipose tissue in KKAy mice is partly mediated by a trend of up-regulation of the adipose ATRAP/AT1R ratio as one of pleiotropic effects of irbesartan.

  8. Lipid Profiling of In Vitro Cell Models of Adipogenic Differentiation: Relationships With Mouse Adipose Tissues.

    Science.gov (United States)

    Liaw, Lucy; Prudovsky, Igor; Koza, Robert A; Anunciado-Koza, Rea V; Siviski, Matthew E; Lindner, Volkhard; Friesel, Robert E; Rosen, Clifford J; Baker, Paul R S; Simons, Brigitte; Vary, Calvin P H

    2016-09-01

    Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MS(ALL) . Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-derived BAT-C1 cells were also characterized. Over 3000 unique lipid species were quantified. Principal component analysis showed that perirenal versus inguinal white adipose tissues varied in lipid composition of triacyl- and diacylglycerols, sphingomyelins, glycerophospholipids and, notably, cardiolipin CL 72:3. In contrast, hexosylceramides and sphingomyelins distinguished brown from white adipose. Adipocyte differentiation models showed broad differences in lipid composition among themselves, upon adipogenic differentiation, and with adipose tissues. Palmitoyl triacylglycerides predominate in 3T3-L1 differentiation models, whereas cardiolipin CL 72:1 and SM 45:4 were abundant in brown adipose-derived cell differentiation models, respectively. MS/MS(ALL) data suggest new lipid biomarkers for tissue-specific lipid contributions to adipogenesis, thus providing a foundation for using in vitro models of adipogenesis to reflect potential changes in adipose tissues in vivo. J. Cell. Biochem. 117: 2182-2193, 2016. © 2016 Wiley Periodicals, Inc.

  9. Morcellized Omental Transfer for Severe HIV Facial Wasting

    Directory of Open Access Journals (Sweden)

    David Teplica, MD, MFA

    2013-11-01

    Conclusions: Mechanically morcellized omental fat transfer provides a safe option to restore facial volume in those unusual patients with severe wasting and no available subcutaneous tissue for transfer. Consistent anatomic progression of facial wasting permits preoperative classification, counseling of patients, and postoperative evaluation of surgical improvement.

  10. Androgen effects on adipose tissue architecture and function in nonhuman primates.

    Science.gov (United States)

    Varlamov, Oleg; White, Ashley E; Carroll, Julie M; Bethea, Cynthia L; Reddy, Arubala; Slayden, Ov; O'Rourke, Robert W; Roberts, Charles T

    2012-07-01

    The differential association of hypoandrogenism in men and hyperandrogenism in women with insulin resistance and obesity suggests that androgens may exert sex-specific effects on adipose and other tissues, although the underlying mechanisms remain poorly understood. Moreover, recent studies also suggest that rodents and humans may respond differently to androgen imbalance. To achieve better insight into clinically relevant sex-specific mechanisms of androgen action, we used nonhuman primates to investigate the direct effects of gonadectomy and hormone replacement on white adipose tissue. We also employed a novel ex vivo approach that provides a convenient framework for understanding of adipose tissue physiology under a controlled tissue culture environment. In vivo androgen deprivation of males did not result in overt obesity or insulin resistance but did induce the appearance of very small, multilocular white adipocytes. Testosterone replacement restored normal cell size and a unilocular phenotype and stimulated adipogenic gene transcription and improved insulin sensitivity of male adipose tissue. Ex vivo studies demonstrated sex-specific effects of androgens on adipocyte function. Female adipose tissue treated with androgens displayed elevated basal but reduced insulin-dependent fatty acid uptake. Androgen-stimulated basal uptake was greater in adipose tissue of ovariectomized females than in adipose tissue of intact females and ovariectomized females replaced with estrogen and progesterone in vivo. Collectively, these data demonstrate that androgens are essential for normal adipogenesis in males and can impair essential adipocyte functions in females, thus strengthening the experimental basis for sex-specific effects of androgens in adipose tissue.

  11. Microarray Evidences the Role of Pathologic Adipose Tissue in Insulin Resistance and Their Clinical Implications

    Directory of Open Access Journals (Sweden)

    Sandeep Kumar Mathur

    2011-01-01

    Full Text Available Clustering of insulin resistance and dysmetabolism with obesity is attributed to pathologic adipose tissue. The morphologic hallmarks of this pathology are adipocye hypertrophy and heightened inflammation. However, it's underlying molecular mechanisms remains unknown. Study of gene function in metabolically active tissues like adipose tissue, skeletal muscle and liver is a promising strategy. Microarray is a powerful technique of assessment of gene function by measuring transcription of large number of genes in an array. This technique has several potential applications in understanding pathologic adipose tissue. They are: (1 transcriptomic differences between various depots of adipose tissue, adipose tissue from obese versus lean individuals, high insulin resistant versus low insulin resistance, brown versus white adipose tissue, (2 transcriptomic profiles of various stages of adipogenesis, (3 effect of diet, cytokines, adipokines, hormones, environmental toxins and drugs on transcriptomic profiles, (4 influence of adipokines on transcriptomic profiles in skeletal muscle, hepatocyte, adipose tissue etc., and (5 genetics of gene expression. The microarray evidences of molecular basis of obesity and insulin resistance are presented here. Despite the limitations, microarray has potential clinical applications in finding new molecular targets for treatment of insulin resistance and classification of adipose tissue based on future risk of insulin resistance syndrome.

  12. Study on heterogeneity between visceral adipose tissue and subcutaneous adipose tissue%内脏和皮下脂肪组织的异质性探讨

    Institute of Scientific and Technical Information of China (English)

    李顺昌

    2015-01-01

    [Summary] The increasing prevalence of obesity has led to extensive research on white adipose tissue. Currently ,functional differences among white adipose tissue depots have become clear ,especially between visceral adipose tissue (VAT ) and subcutaneous adipose tissue (SAT ). This article will review the heterogeneity of distribution ,structure ,function ,influence factors ,measurement methods and metabolic properties between VAT and SAT.%随着肥胖患病率的增加,对白色脂肪组织的研究受到关注。不同部位的白色脂肪组织有功能异质性,特别是内脏和皮下脂肪组织。本文从二者的分布、解剖、功能、影响因素及内分泌功能等方面作一综述。

  13. Paracrine and intracrine contributions of androgens and estrogens to adipose tissue biology: physiopathological aspects.

    Science.gov (United States)

    Waraich, Rizwana S; Mauvais-Jarvis, Franck

    2013-08-01

    In mammals, the male and female hormones androgen and estrogen act as endocrine regulators of energy metabolism. However, adipose tissue is also a site of androgen and estrogen synthesis; androgens convert to estrogens in these tissues, and adipose tissue is also a reservoir of steroids that act locally in a paracrine and intracrine manner. Thus, in adipose tissue, the local output of sex hormones is more complex than would be suggested by routine measurement of serum hormone concentrations. This review integrates studies on the effects of androgens and estrogens in the developmental programming of adipose tissue function in early life and addresses the contributions of local androgen and estrogen metabolism on adipose tissue function in adults.

  14. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism.

    Science.gov (United States)

    Cao, Haiming; Gerhold, Kristin; Mayers, Jared R; Wiest, Michelle M; Watkins, Steven M; Hotamisligil, Gökhan S

    2008-09-19

    Dysregulation of lipid metabolism in individual tissues leads to systemic disruption of insulin action and glucose metabolism. Utilizing quantitative lipidomic analyses and mice deficient in adipose tissue lipid chaperones aP2 and mal1, we explored how metabolic alterations in adipose tissue are linked to whole-body metabolism through lipid signals. A robust increase in de novo lipogenesis rendered the adipose tissue of these mice resistant to the deleterious effects of dietary lipid exposure. Systemic lipid profiling also led to identification of C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal a lipid-mediated endocrine network and demonstrate that adipose tissue uses lipokines such as C16:1n7-palmitoleate to communicate with distant organs and regulate systemic metabolic homeostasis.

  15. The contribution of different adipose tissue depots to plasma plasminogen activator inhibitor-1 (PAI-1) levels.

    Science.gov (United States)

    Barnard, Sunelle A; Pieters, Marlien; De Lange, Zelda

    2016-11-01

    Increased plasma plasminogen activator inhibitor-1 (PAI-1) level is considered a mechanistic pathway through which obesity contributes to increased cardiovascular disease risk. Abdominal adipose tissue specifically, is a major PAI-1 source with visceral adipose tissue (VAT), an ectopic fat depot, generally considered to produce more PAI-1 than subcutaneous adipose tissue. However, this does not necessarily lead to increased plasma PAI-1 levels. This review provides an overview of studies investigating the association between body fat distribution and plasma PAI-1 levels. It discusses factors that influence this relationship and also considers the contribution of other tissue to plasma PAI-1 levels, placing the relative contribution of adipose tissue into perspective. In conclusion, the relationship between VAT and plasma PAI-1 levels is not fixed but can be modulated by a number of factors such as the size of the subcutaneous adipose tissue depot, ethnicity, possibly genetics and other obesity-related metabolic abnormalities.

  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. Adipogenesis: new insights into brown adipose tissue differentiation.

    Science.gov (United States)

    Carobbio, Stefania; Rosen, Barry; Vidal-Puig, Antonio

    2013-12-01

    Confirmation of the presence of functional brown adipose tissue (BAT) in humans has renewed interest in investigating the potential therapeutic use of this tissue. The finding that its activity positively correlates with decreased BMI, decreased fat content, and augmented energy expenditure suggests that increasing BAT mass/activity or browning of white adipose tissue (WAT) could be a strategy to prevent or treat obesity and its associated morbidities. The challenge now is to find a safe and efficient way to develop this idea. Whereas BAT has being widely studied in murine models both in vivo and in vitro, there is an urgent need for human cellular models to investigate BAT physiology and functionality from a molecular point of view. In this review, we focus on the latest insights surrounding BAT development and activation in rodents and humans. Then, we discuss how the availability of murine models has been essential to identify BAT progenitors and trace their lineage. Finally, we address how this information can be exploited to develop human cellular models for BAT differentiation/activation. In this context, human embryonic stem and induced pluripotent stem cells-based cellular models represent a resource of great potential value, as they can provide a virtually inexhaustible supply of starting material for functional genetic studies, -omics based analysis and validation of therapeutic approaches. Moreover, these cells can be readily genetically engineered, opening the possibility of generating patient-specific cellular models, allowing the investigation of the influence of different genetic backgrounds on BAT differentiation in pathological or in physiological states.

  18. Insulin action in adipose tissue in type 1 diabetes

    Directory of Open Access Journals (Sweden)

    F Arrieta-Blanco

    2011-02-01

    Full Text Available F Arrieta-Blanco1, JI Botella-Carretero1, P Iglesias1, JA Balsa1, I Zamarrón1, C De la Puerta1, JJ Arrieta2, F Ramos3, C Vázquez1, A Rovira21Unit of Clinical Nutrition and Dietetics, Department of Endocrinology and Nutrition, Hospital Ramóny, Cajal, Madrid, Spain, Irycis, Ciberobn; 2Fundación Jimenez Díaz. Madrid, Spain; 3Hospital Sureste de ArgandaBackground: Insulin action has been reported to be normal in type 1 diabetic patients. However, some studies have reported an insulin resistance state in these patients. The aim of this study was to investigate insulin resistance in a group of type 1 diabetic patients. We studied the insulin action in adipose tissue and analyzed the effects of duration of disease, body mass index (BMI, and glycosylated hemoglobin on insulin action at the receptor and postreceptor levels in adipocytes.Methods: Nine female type 1 diabetic patients with different durations of disease and eight nondiabetic female patients of comparable age and BMI were studied. 125I-insulin binding and U-[14C]-D-glucose transport was measured in a sample of subcutaneous gluteus adipose tissue obtained by open surgical biopsy from each subject.Results: The duration of disease was negatively correlated with both 125I-insulin binding capacity (r = -0.70, P < 0.05 and basal and maximum insulin-stimulated glucose transport (r = -0.87, P < 0.01, and r = -0.88, P < 0.01, respectively. Maximum specific 125I-insulin binding to the receptors in adipocytes was higher in the group of patients with a shorter duration of disease (P < 0.01. Basal and maximum insulin-stimulated glucose transport was significantly higher in the group with less than 5 years of disease (P < 0.01. No correlation was found between BMI and insulin action.Conclusion: Female type 1 diabetic patients have normal insulin action. There is a high glucose uptake in the early phase of the disease, although a longer duration of disease appears to be a contributing factor to a

  19. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

    Directory of Open Access Journals (Sweden)

    Aimee L. Dordevic

    2015-07-01

    Full Text Available Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD; body mass index (BMI 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water, carbohydrate (maltodextrin or lipid (dairy-cream. Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h, as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1, interleukin 6 (IL-6 and tumor necrosis factor-α (TNF-α increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03 and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001 decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

  20. Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo

    DEFF Research Database (Denmark)

    Bülow, J; Madsen, J; Astrup, A;

    1985-01-01

    Subcutaneous or perirenal adipose tissue blood flow was measured with the 133Xe-washout technique before and after intravenous injection or infusion of Intralipid in six anesthetized, otherwise intact mongrel dogs. In four anesthetized mongrel puppies adipose tissue blood flow was measured with t...

  1. Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

    Directory of Open Access Journals (Sweden)

    Byung Young Park

    Full Text Available It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2 and MMPs (MMP-2 and MMP-9, whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2 in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.

  2. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity.

    Science.gov (United States)

    Huh, Jin Young; Park, Yoon Jeong; Ham, Mira; Kim, Jae Bum

    2014-05-01

    Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in adipose tissues are involved in obesity-mediated metabolic complications, including insulin resistance. Here, we summarize recent findings on the key roles of innate (neutrophils, macrophages, mast cells, eosinophils) and adaptive (regulatory T cells, type 1 helper T cells, CD8 T cells, B cells) immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. In particular, the roles of natural killer T cells, one type of innate lymphocyte, in adipose tissue inflammation will be discussed. Finally, a new role of adipocytes as antigen presenting cells to modulate T cell activity and subsequent adipose tissue inflammation will be proposed.

  3. Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

    Science.gov (United States)

    Park, Byung Young; Lee, Hyunghee; Woo, Sangee; Yoon, Miso; Kim, Jeongjun; Hong, Yeonhee; Lee, Hee Suk; Park, Eun Kyu; Hahm, Jong Cheon; Kim, Jin Woo; Shin, Soon Shik; Kim, Min-Young; Yoon, Michung

    2015-01-01

    It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.

  4. N-3 polyunsaturated fatty acids in adipose tissue and depression in different age groups from Crete

    NARCIS (Netherlands)

    Mamalakis, G.

    2007-01-01

    In this thesis, the results of cross-sectional studies on the relationship of depression with adipose tissue n-3 polyunsaturated fatty acids have been described. The aim of this thesis is to investigate whether adipose tissue n-3 fatty acids, an objective index or biomarker of long-term or habitual

  5. Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice

    NARCIS (Netherlands)

    A. Grefhorst (Aldo); J.C. van den Beukel (Anneke); A.F. van Houten (A.); J. Steenbergen (Jacobie); J.A. Visser (Jenny); A.P.N. Themmen (Axel)

    2015-01-01

    textabstractBackground: In mammals, white adipose tissue (WAT) stores fat and brown adipose tissue (BAT) dissipates fat to produce heat. Several studies showed that females have more active BAT. Members of the bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) families are expressed

  6. In vivo human lipolytic activity in preperitoneal and subdivisions of subcutaneous abdominal adipose tissue

    DEFF Research Database (Denmark)

    Enevoldsen, L H; Simonsen, L; Stallknecht, Bente

    2001-01-01

    We studied eight normal-weight male subjects to examine whether the lipolytic rate of deep subcutaneous and preperitoneal adipose tissues differs from that of superficial abdominal subcutaneous adipose tissue. The lipolytic rates in the superficial anterior and deep posterior subcutaneous abdomin...

  7. Role of NKG2D in obesity-induced adipose tissue inflammation and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Jun-Jae Chung

    Full Text Available The early events that initiate inflammation in the adipose tissue during obesity are not well defined. It is unclear whether the recruitment of CD8 T cells to the adipose tissue during onset of obesity occurs through antigen-dependent or -independent processes. We have previously shown that interaction between NKG2D (natural-killer group 2, member D and its ligand Rae-1ε is sufficient to recruit cytotoxic T lymphocytes to the pancreas and induce insulitis. Here, we tested whether NKG2D-NKG2D ligand interaction is also involved in obesity-induced adipose tissue inflammation and insulin resistance. We observed a significant induction of NKG2D ligand expression in the adipose tissue of obese mice, especially during the early stages of obesity. However, mice lacking NKG2D developed similar levels of insulin resistance and adipose tissue inflammation compared to control mice when placed on a high-fat diet. Moreover, overexpression of Rae-1ε in the adipose tissue did not increase immune cell infiltration to the adipose tissue either in the setting of a normal or high-fat diet. These results indicate that, unlike in the pancreas, NKG2D-NKG2D ligand interaction does not play a critical role in obesity-induced inflammation in the adipose tissue.

  8. Contact with existing adipose tissue is inductive for adipogenesis in matrigel.

    LENUS (Irish Health Repository)

    Kelly, John L

    2006-07-01

    The effect of adipose tissue on inductive adipogenesis within Matrigel (BD Biosciences) was assessed by using a murine chamber model containing a vascular pedicle. Three-chamber configurations that varied in the access to an adipose tissue source were used, including sealed- and open-chamber groups that had no access and limited access, respectively, to the surrounding adipose tissue, and a sealed-chamber group in which adipose tissue was placed as an autograft. All groups showed neovascularization, but varied in the amount of adipogenesis seen in direct relation to their access to preexisting adipose tissue: open chambers showed strong adipogenesis, whereas the sealed chambers had little or no adipose tissue; adipogenesis was restored in the autograft chamber group that contained 2- to 5-mg fat autografts. These showed significantly more adipogenesis than the sealed chambers with no autograft ( p < 0.01). Autografts with 1mg of fat were capable of producing adipogenesis but did so less consistently than the larger autografts. These findings have important implications for adipose tissue engineering strategies and for understanding de novo production of adipose tissue.

  9. Role of NKG2D in obesity-induced adipose tissue inflammation and insulin resistance.

    Science.gov (United States)

    Chung, Jun-Jae; Markiewicz, Mary A; Polić, Bojan; Shaw, Andrey S

    2014-01-01

    The early events that initiate inflammation in the adipose tissue during obesity are not well defined. It is unclear whether the recruitment of CD8 T cells to the adipose tissue during onset of obesity occurs through antigen-dependent or -independent processes. We have previously shown that interaction between NKG2D (natural-killer group 2, member D) and its ligand Rae-1ε is sufficient to recruit cytotoxic T lymphocytes to the pancreas and induce insulitis. Here, we tested whether NKG2D-NKG2D ligand interaction is also involved in obesity-induced adipose tissue inflammation and insulin resistance. We observed a significant induction of NKG2D ligand expression in the adipose tissue of obese mice, especially during the early stages of obesity. However, mice lacking NKG2D developed similar levels of insulin resistance and adipose tissue inflammation compared to control mice when placed on a high-fat diet. Moreover, overexpression of Rae-1ε in the adipose tissue did not increase immune cell infiltration to the adipose tissue either in the setting of a normal or high-fat diet. These results indicate that, unlike in the pancreas, NKG2D-NKG2D ligand interaction does not play a critical role in obesity-induced inflammation in the adipose tissue.

  10. Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

    Science.gov (United States)

    Blüher, Matthias

    2016-09-01

    The worldwide obesity epidemic has become a major health concern, because it contributes to higher mortality due to an increased risk for noncommunicable diseases including cardiovascular diseases, type 2 diabetes, musculoskeletal disorders and some cancers. Insulin resistance may link accumulation of adipose tissue in obesity to metabolic diseases, although the underlying mechanisms are not completely understood. In the past decades, data from human studies and transgenic animal models strongly suggested correlative, but also causative associations between activation of proinflammatory pathways and insulin resistance. Particularly chronic inflammation in adipose tissue seems to play an important role in the development of obesity-related insulin resistance. On the other hand, adipose tissue inflammation has been shown to be essential for healthy adipose tissue expansion and remodelling. However, whether adipose tissue inflammation represents a consequence or a cause of impaired insulin sensitivity remains an open question. A better understanding of the molecular pathways linking excess adipose tissue storage to chronic inflammation and insulin resistance may provide the basis for the future development of anti-inflammatory treatment strategies to improve adverse metabolic consequences of obesity. In this review, potential mechanisms of adipose tissue inflammation and how adipose tissue inflammation may cause insulin resistance are discussed. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  11. N-3 polyunsaturated fatty acids in adipose tissue and depression in different age groups from Crete

    NARCIS (Netherlands)

    Mamalakis, G.

    2007-01-01

    In this thesis, the results of cross-sectional studies on the relationship of depression with adipose tissue n-3 polyunsaturated fatty acids have been described. The aim of this thesis is to investigate whether adipose tissue n-3 fatty acids, an objective index or biomarker of long-term or habitual

  12. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults.

    Science.gov (United States)

    Dordevic, Aimee L; Pendergast, Felicity J; Morgan, Han; Villas-Boas, Silas; Caldow, Marissa K; Larsen, Amy E; Sinclair, Andrew J; Cameron-Smith, David

    2015-07-01

    Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD)); body mass index (BMI) 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water), carbohydrate (maltodextrin) or lipid (dairy-cream). Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h), as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03) and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001) decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

  13. Delivery of basic fibroblast growth factors from heparinized decellularized adipose tissue stimulates potent de novo adipogenesis.

    Science.gov (United States)

    Lu, Qiqi; Li, Mingming; Zou, Yu; Cao, Tong

    2014-01-28

    Scaffolds based on decellularized adipose tissue (DAT) are gaining popularity in adipose tissue engineering due to their high biocompatibility and adipogenic inductive property. However, previous studies involving DAT-derived scaffolds have not fully revealed their potentials for in vivo adipose tissue construction. With the aim of developing a more efficient adipose tissue engineering technique based on DAT, in this study, we investigated the in vivo adipogenic potential of a basic fibroblast growth factor (bFGF) delivery system based on heparinized DAT (Hep-DAT). To generate this system, heparins were cross-linked to mouse DATs by using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide and N-Hydroxysuccinimide. The bFGF-binding Hep-DATs were first tested for controlled release ability in vitro and then transplanted subcutaneously. Highly vascularized adipose tissues were formed 6weeks after transplantation. Histology and gene expression analysis revealed that majority of the Hep-DAT scaffolds were infiltrated with host-derived adipose tissues that possessed similar adipogenic and inflammatory gene expression as endogenous adipose tissues. Additionally, strong de novo adipogenesis could also be induced when bFGF-binding Hep-DATs were thoroughly minced and injected subcutaneously. In conclusion, our study demonstrated that bFGF-binding Hep-DAT could be an efficient, biocompatible and injectable adipogenic system for in vivo adipose tissue engineering.

  14. A pilot study of sampling subcutaneous adipose tissue to examine biomarkers of cancer risk

    OpenAIRE

    Campbell, Kristin L.; Makar, Karen W.; Kratz, Mario; Foster-Schubert, Karen E.; McTiernan, Anne; Ulrich, Cornelia M.

    2009-01-01

    Examination of adipose tissue biology may provide important insight into mechanistic links for the observed association between higher body fat and risk of several types of cancer, in particular colorectal and breast cancer. We tested two different methods of obtaining adipose tissue from healthy individuals.

  15. Adipose tissue lipolysis is increased during a repeated bout of aerobic exercise

    DEFF Research Database (Denmark)

    Stich, V; de Glisezinski, I; Berlan, M

    2000-01-01

    The goal of the study was to examine whether lipid mobilization from adipose tissue undergoes changes during repeated bouts of prolonged aerobic exercise. Microdialysis of the subcutaneous adipose tissue was used for the assessment of lipolysis; glycerol concentration was measured in the dialysate...

  16. Predictors of adipose tissue carotenoid and retinol levels in nine countries: The EURAMIC study

    NARCIS (Netherlands)

    Virtanen, S.M.; Veer, P. van 't; Kok, F.; Kardinaal, A.F.M.; Aro, A.

    1996-01-01

    The adipose tissue carotenoid (alpha-carotene, beta-carotene, and lycopene) and retinol levels and their predictors were determined in 686 male and 339 female middle-aged and elderly subjects from eight European countries and Israel during the years 1991 to 1992. Adipose tissue carotenoid levels in

  17. Metabolic inflammation in inflammatory bowel disease: crosstalk between adipose tissue and bowel.

    Science.gov (United States)

    Gonçalves, Pedro; Magro, Fernando; Martel, Fátima

    2015-02-01

    Epidemiological studies show that both the incidence of inflammatory bowel disease (IBD) and the proportion of people with obesity and/or obesity-associated metabolic syndrome increased markedly in developed countries during the past half century. Obesity is also associated with the development of more active IBD and requirement for hospitalization and with a decrease in the time span between diagnosis and surgery. Patients with IBD, especially Crohn's disease, present fat-wrapping or "creeping fat," which corresponds to ectopic adipose tissue extending from the mesenteric attachment and covering the majority of the small and large intestinal surface. Mesenteric adipose tissue in patients with IBD presents several morphological and functional alterations, e.g., it is more infiltrated with immune cells such as macrophages and T cells. All these lines of evidence clearly show an association between obesity, adipose tissue, and functional bowel disorders. In this review, we will show that the mesenteric adipose tissue and creeping fat are not innocent by standers but actively contribute to the intestinal and systemic inflammatory responses in patients with IBD. More specifically, we will review evidence showing that adipose tissue in IBD is associated with major alterations in the secretion of cytokines and adipokines involved in inflammatory process, in adipose tissue mesenchymal stem cells and adipogenesis, and in the interaction between adipose tissue and other intestinal components (immune, lymphatic, neuroendocrine, and intestinal epithelial systems). Collectively, these studies underline the importance of adipose tissue for the identification of novel therapeutic approaches for IBD.

  18. Interstitial concentrations of adipokines in subcutaneous abdominal and femoral adipose tissue

    DEFF Research Database (Denmark)

    Nielsen, Ninna Bo; Højbjerre, Lise; Sonne, Mette P

    2009-01-01

    ) in subcutaneous, abdominal and femoral adipose tissue using calibrated, large-pore microdialysis technique in 8 healthy, lean men on 2 experimental days. The interstitial leptin concentration was 2.5-fold higher in subcutaneous, femoral than abdominal adipose tissue (P... found for the remaining adipokines (P>0.05). Adiponectin and leptin concentrations were higher in plasma than subcutaneous adipose tissue (approximately 25-fold and approximately 2-fold, respectively, Padipose tissue than...... plasma (approximately 100-fold, approximately 200-fold and approximately 1000-fold, respectively, PAdipose tissue blood flow (ATBF) showed no regional difference (P>0.05). The intra- and inter-subject variations of all...

  19. Identification of cyclopropaneoctanoic acid 2-hexyl in human adipose tissue and serum.

    Science.gov (United States)

    Sledzinski, Tomasz; Mika, Adriana; Stepnowski, Piotr; Proczko-Markuszewska, Monika; Kaska, Lukasz; Stefaniak, Tomasz; Swierczynski, Julian

    2013-08-01

    Fatty acids containing a cyclopropane ring in their structure (cyclopropane FA) have been found in a wide variety of bacteria, a number of protozoa, and Myriapoda. Little is known about cyclopropane FA in mammal, especially in human tissues. The present study deals with the identification of cyclopropane FA in adipose tissue and serum of humans and rats. Fatty acids extracted from the adipose tissue and serum obtained from obese women during bariatric surgery were methylated and analyzed on GC-MS. We have identified: cyclopropaneoctanoic acid 2-hexyl, cyclopropaneoctanoic acid 2-octyl, cyclopropanenonanoic acid, and 2-[[2-[(2-ethylcyclopropyl)methyl]cyclopropyl]methyl] acid in human adipose tissue. We confirmed the presence of cyclopropaneoctanoic acid 2-hexyl by derivatization of FA extracted from human adipose tissue to picolinyl esters. Cyclopropaneoctanoic acid 2-hexyl was the main cyclopropane FA (approximately 0.4 % of total fatty acids in human adipose tissue, and about 0.2 % of total fatty acids in the serum). In adipose tissue cyclopropaneoctanoic acid 2-hexyl was found mainly in triacylglycerols, whereas in serum in phospholipids and triacylglycerols. The cyclopropaneoctanoic acid 2-hexyl has also been found in serum, and adipose tissue of rats in amounts comparable to humans. The content of cyclopropaneoctanoic acid 2-hexyl decreased in adipose tissue of rats maintained on a restricted diet for 1 month. In conclusion, we demonstrated that cyclopropaneoctanoic acid 2-hexyl is present in human adipose tissue and serum. Adipose tissue cyclopropaneoctanoic acid 2-hexyl is stored mainly in triacylglycerols and the storage of this cyclopropane FA is affected by food restriction.

  20. In vivo effects of corticotropin-releasing hormone on femoral adipose tissue metabolism in women.

    Science.gov (United States)

    Wellhöner, P; Welzel, M; Rolle, D; Dodt, C

    2007-04-01

    To investigate whether i.v. injected corticotropin-releasing hormone (CRH) (1 microg/kg) has a direct effect on adipose tissue metabolism in humans. Double-blinded, placebo-controlled, crossover study. Twelve healthy normal weight female volunteers (age 20-37 years, body mass index: 22.75+/-1.33 kg/m(2)) Assessment of local generation of glycerol, and glucose in adipose tissue by microdialysis. Measurement of adipose tissue and skin blood flow by laser Doppler flowmetry. Injection of CRH acutely increases interstitial concentrations of glycerol (19.0+/-5.4%, Ptissue blood flow do not explain interstitial metabolite alterations. Initial CRH effects on adipose tissue metabolism are short lasting and disappear after 15 min. The importance of CRH on human energy metabolism is underlined by the present in vivo study demonstrating peptidergic effects on lipolysis and glucose homeostasis in human subcutaneous adipose tissue.

  1. Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation.

    Science.gov (United States)

    Sethi, Jaswinder K; Vidal-Puig, Antonio J

    2007-06-01

    This review focuses on adipose tissue biology and introduces the concept of adipose tissue plasticity and expandability as key determinants of obesity-associated metabolic dysregulation. This concept is fundamental to our understanding of adipose tissue as a dynamic organ at the center of nutritional adaptation. Here, we summarize the current knowledge of the mechanisms by which adipose tissue can affect peripheral energy homeostasis, particularly in the context of overnutrition. Two mechanisms emerge that provide a molecular understanding for obesity-associated insulin resistance. These are a) the dysregulation of adipose tissue expandability and b) the abnormal production of adipokines. This knowledge has the potential to pave the way for novel therapeutic concepts and strategies for managing and/or correcting complications associated with obesity and the metabolic syndrome.

  2. Depot-dependent effects of adipose tissue explants on co-cultured hepatocytes

    DEFF Research Database (Denmark)

    Du, Zhen-Yu; Ma, Tao; Lock, Erik-Jan;

    2011-01-01

    We have developed an in vitro hepatocyte-adipose tissue explant (ATE) co-culture model enabling examination of the effect of visceral and subcutaneous adipose tissues on primary rat hepatocytes. Initial analyses of inflammatory marker genes were performed in fractionated epididymal or inguinal...... levels of IL-6, TNF-a and PGE(2) in the media from inguinal ATEs co-cultured with primary rat hepatocytes were higher than that in the media from epididymal ATEs co-cultured with hepatocytes, although the significant difference was only seen in PGE(2). Lipolysis, measured as glycerol release, was similar...... in the ATEs isolated from inguinal and epididymal adipose tissues when cultured alone, but the glycerol release was higher in the ATEs isolated from epididymal than from inguinal adipose tissue when co-cultured with hepatocytes. Compared to epididymal ATEs, the ATEs from inguinal adipose tissue elicited...

  3. 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......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...... in adipose tissue blood flow in response to adrenaline was also reduced by prior adrenaline exposure, but no consistent desensitization could be demonstrated for whole-body energy expenditure, blood pressure and heart rate. 5. In the basal state, arterial plasma and interstitial adrenaline concentrations did...

  4. Vascular and metabolic effects of adrenaline in adipose tissue in type 2 diabetes

    DEFF Research Database (Denmark)

    Tobin, L; Simonsen, L; Galbo, H

    2012-01-01

    Objective:The aim was to investigate adipose tissue vascular and metabolic effects of an adrenaline infusion in vivo in subjects with and without type 2 diabetes mellitus (T2DM).Design:Clinical intervention study with 1-h intravenous adrenaline infusion.Subjects:Eight male overweight T2DM subjects...... and eight male weight-matched, non-T2DM subjects were studied before, during and after an 1-h intravenous adrenaline infusion. Adipose tissue blood flow (ATBF) was determined by Xenon wash-out technique, and microvascular volume in the adipose tissue was studied by contrast-enhanced ultrasound imaging....... Adipose tissue fluxes of glycerol, non-esterified fatty acids (NEFA), triacylglycerol and glucose were measured by Fick's principle after catherisation of a radial artery and a vein draining the abdominal, subcutaneous adipose tissue.Results:ATBF increased similarly in both groups during the adrenaline...

  5. FGF receptor antagonism does not affect adipose tissue development in nutritionally induced obesity.

    Science.gov (United States)

    Scroyen, Ilse; Vranckx, Christine; Lijnen, Henri Roger

    2014-01-01

    The fibroblast growth factor (FGF)-FGF receptor (FGFR) system plays a role in angiogenesis and maintenance of vascular integrity, but its potential role in adipose tissue related angiogenesis and development is still unknown. Administration of SSR, a low molecular weight inhibitor of multiple FGFRs, did not significantly affect body weight nor weight of subcutaneous or gonadal (GON) fat, as compared with pair-fed control mice. Adipocyte hypertrophy and reduced adipocyte density were only observed in GON adipose tissues of treated mice. Adipose tissue angiogenesis was not affected by SSR treatment, as normalized blood vessel density was comparable in adipose tissues of both groups. Blocking the FGF-FGFR system in vivo does not markedly affect adipose tissue development in mice with nutritionally induced obesity.

  6. Insulin Mediated 14C-Glucose Incorporation Into Adipose Tissue: An Undergraduate Biochemistry Experiment

    Science.gov (United States)

    Landman, A. D.; Eskin, N. A. M.

    1975-01-01

    Describes an experiment in which rat adipose tissue samples are exposed to labeled glucose; insulin is added to one sample. Subsequent scintillation counting demonstrates the ability of insulin to facilitate the entry of glucose into the tissue. (MLH)

  7. The role of brown adipose tissue in temperature regulation. [of hibernating and hypothermic mammals

    Science.gov (United States)

    Smith, R. E.

    1973-01-01

    The thermogenetic capacities of brown adipose tissue were studied on marmots, rats and monkeys in response to cold exposure. All experiments indicated that the brown fat produced heat and slowed the cooling of tissues.

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

    Science.gov (United States)

    Kraunsøe, Regitze; Boushel, Robert; Hansen, Christina Neigaard; Schjerling, Peter; Qvortrup, Klaus; Støckel, Mikael; Mikines, Kári J; Dela, Flemming

    2010-06-15

    Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human 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 were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.

  9. Comparison of fatty acid composition of subcutaneous, pericardial and epicardial adipose tissue and atrial tissue in patients with heart disease

    DEFF Research Database (Denmark)

    Eschen, Rikke Bülow; Gu, Jiwei; Andreasen, Jan Jesper;

    OBJECTIVES The content in adipose tissue of marine n-3 polyunsaturated fatty acids (PUFAs) is a marker of long-term fish consumption and data suggest an antiarrhythmic effect of n-3 PUFAs. We investigated the correlation between adipose tissue content of the major n-3 PUFAs, eicosapentaenoic acid...... (EPA) and docosahexaenoic acid (DHA), from three different adipose tissue compartments [epicardial (EAT), pericardial (PAT) and subcutaneous (SAT)]. Furthermore, we studied the correlation between the content of EPA and DHA in these compartments and in atrial tissue (AT). METHODS We obtained AT from...

  10. Comparison of fatty acid composition of subcutaneous, pericardial and epicardial adipose tissue and atrial tissue in patients with heart disease

    DEFF Research Database (Denmark)

    Eschen, Rikke Bülow; Gu, Jiwei; Andreasen, Jan Jesper;

    2016-01-01

    OBJECTIVES The content in adipose tissue of marine n-3 polyunsaturated fatty acids (PUFAs) is a marker of long-term fish consumption and data suggest an antiarrhythmic effect of n-3 PUFAs. We investigated the correlation between adipose tissue content of the major n-3 PUFAs, eicosapentaenoic acid...... (EPA) and docosahexaenoic acid (DHA), from three different adipose tissue compartments [epicardial (EAT), pericardial (PAT) and subcutaneous (SAT)]. Furthermore, we studied the correlation between the content of EPA and DHA in these compartments and in atrial tissue (AT). METHODS We obtained AT from...

  11. Brown adipose tissue in humans: therapeutic potential to combat obesity.

    Science.gov (United States)

    Carey, Andrew L; Kingwell, Bronwyn A

    2013-10-01

    Harnessing the considerable capacity of brown adipose tissue (BAT) to consume energy was first proposed as a potential target to control obesity nearly 40years ago. The plausibility of this approach was, however, questioned due to the prevailing view that BAT was either not present or not functional in adult humans. Recent definitive identification of functional BAT in adult humans as well as a number of important advances in the understanding of BAT biology has reignited interest in BAT as an anti-obesity target. Proof-of-concept evidence demonstrating drug-induced BAT activation provides an important foundation for development of targeted pharmacological approaches with clinical application. This review considers evidence from both human and relevant animal studies to determine whether harnessing BAT for the treatment of obesity via pharmacological intervention is a realistic goal. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Estradiol Regulates Brown Adipose Tissue Thermogenesis via Hypothalamic AMPK

    Science.gov (United States)

    Martínez de Morentin, Pablo B.; González-García, Ismael; Martins, Luís; Lage, Ricardo; Fernández-Mallo, Diana; Martínez-Sánchez, Noelia; Ruíz-Pino, Francisco; Liu, Ji; Morgan, Donald A.; Pinilla, Leonor; Gallego, Rosalía; Saha, Asish K.; Kalsbeek, Andries; Fliers, Eric; Bisschop, Peter H.; Diéguez, Carlos; Nogueiras, Rubén; Rahmouni, Kamal; Tena-Sempere, Manuel; López, Miguel

    2014-01-01

    Summary Estrogens play a major role in the modulation of energy balance through central and peripheral actions. Here, we demonstrate that central action of estradiol (E2) inhibits AMP-activated protein kinase (AMPK) through estrogen receptor alpha (ERα) selectively in the ventromedial nucleus of the hypothalamus (VMH), leading to activation of thermogenesis in brown adipose tissue (BAT) through the sympathetic nervous system (SNS) in a feeding-independent manner. Genetic activation of AMPK in the VMH prevented E2-induced increase in BAT-mediated thermogenesis and weight loss. Notably, fluctuations in E2 levels during estrous cycle also modulate this integrated physiological network. Together, these findings demonstrate that E2 regulation of the VMH AMPK-SNS-BAT axis is an important determinant of energy balance and suggest that dysregulation in this axis may account for the common changes in energy homeostasis and obesity linked to dysfunction of the female gonadal axis. PMID:24856932

  13. Negative regulators of brown adipose tissue (BAT)-mediated thermogenesis.

    Science.gov (United States)

    Sharma, Bal Krishan; Patil, Mallikarjun; Satyanarayana, Ande

    2014-12-01

    Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. PET-CT scans recently demonstrated the existence of metabolically active BAT in adult humans, which revitalized our interest in BAT. Increasing the amount and/or activity of BAT holds tremendous promise for the treatment of obesity and its associated diseases. PGC1α is the master regulator of UCP1-mediated thermogenesis in BAT. A number of proteins have been identified to influence thermogenesis either positively or negatively through regulating the expression or transcriptional activity of PGC1α. Therefore, BAT activation can be achieved by either inducing the expression of positive regulators of PGC1α or by inhibiting the repressors of the PGC1α/UCP1 pathway. Here, we review the most important negative regulators of PGC1α/UCP1 signaling and their mechanism of action in BAT-mediated thermogenesis.

  14. Evidence for two types of brown adipose tissue in humans.

    Science.gov (United States)

    Lidell, Martin E; Betz, Matthias J; Dahlqvist Leinhard, Olof; Heglind, Mikael; Elander, Louise; Slawik, Marc; Mussack, Thomas; Nilsson, Daniel; Romu, Thobias; Nuutila, Pirjo; Virtanen, Kirsi A; Beuschlein, Felix; Persson, Anders; Borga, Magnus; Enerbäck, Sven

    2013-05-01

    The previously observed supraclavicular depot of brown adipose tissue (BAT) in adult humans was commonly believed to be the equivalent of the interscapular thermogenic organ of small mammals. This view was recently disputed on the basis of the demonstration that this depot consists of beige (also called brite) brown adipocytes, a newly identified type of brown adipocyte that is distinct from the classical brown adipocytes that make up the interscapular thermogenic organs of other mammals. A combination of high-resolution imaging techniques and histological and biochemical analyses showed evidence for an anatomically distinguishable interscapular BAT (iBAT) depot in human infants that consists of classical brown adipocytes, a cell type that has so far not been shown to exist in humans. On the basis of these findings, we conclude that infants, similarly to rodents, have the bona fide iBAT thermogenic organ consisting of classical brown adipocytes that is essential for the survival of small mammals in a cold environment.

  15. Effect of diethylstilboestrol on adipose-tissue lipids.

    Science.gov (United States)

    Sink, J D; Huston, C K; Shigley, J W

    1965-11-01

    1. The effect of diethylstilboestrol on the fatty acid composition of adipose-tissue lipids of the ox (Bos taurus) was studied. 2. The capsula adiposa (perirenal) was shown to contain more total saturated fatty acids, whereas more total unsaturated fatty acids were found in the panniculus adiposus (subcutaneous). 3. Significantly more stearic acid and linolenic acid were obtained from the capsula adiposa, whereas the panniculus adiposus contained more myristoleic acid, palmitoleic acid and oleic acid. 4. Implanting diethylstilboestrol significantly increased the deposition of the saturated fatty acids, particularly stearic acid. 5. A decrease in the deposition of total unsaturated fatty acids, myristoleic acid, palmitoleic acid and linoleic acid can also be attributed to the diethylstilboestrol treatment.

  16. Protein turnover in adipose tissue from fasted or diabetic rats

    Science.gov (United States)

    Tischler, Marc E.; Ost, Alan H.; Coffman, Julia

    1986-01-01

    Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

  17. Adipose tissue resistin gene expression in DIO and DR rats

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Zhao; Yuhui Ni; Xirong Guo; Haixia Gong; Xia Chi; Ronghua Chen

    2006-01-01

    Objective: To investigate the expression of resistin gene in diet-induced obesity (DIO) and diet resistance (DR)rats. Methods: DIO and DR models were prepared with male SD rats after 6 weeks feeding by a diet of relatively high fat, sucrose, and caloric content (HE diet). Body-weight, fat mass, and the concentration of serum insulin were measured, and the expression of resistin and Peroxisome proliferator-activated receptory-γ(PPAR-γ) gene in whit adipose tissue (WAT) was also detected by RT-PCR. Results: ①Body weight, fat mass and the concentration of serum insulin were significantly increased in DIO rats and decreased in DR rats. ② The expression of resistin and PPARγ gene was upregulated in DIO group and supressed in DR group, but the expression of resistin was not detectable in all samples within three groups. Conclusion: Resistin may serve as a link between obesity and insulin resistance, but the individual difference is enormous.

  18. The evolution of the adipose tissue: a neglected enigma.

    Science.gov (United States)

    Ottaviani, Enzo; Malagoli, Davide; Franceschi, Claudio

    2011-10-01

    The complexity of the anatomical distribution and functions of adipose tissue (AT) has been rarely analyzed in an evolutionary perspective. From yeast to man lipid droplets are stored mainly in the form of triglycerides in order to provide energy during periods when energy demands exceed caloric intake. This simple scenario is in agreement with the recent discovery of a highly conserved family of proteins for fat storage in both unicellular and multicellular organisms. However, the evolutionary history of organs such as the fat body in insects, playing a role in immunity and other functions besides energy storage and thermal insulation, and of differently distributed subtypes of AT in vertebrates is much less clear. These topics still await a systematic investigation using up-to-date technologies and approaches that would provide information useful for understanding the role of different AT subtypes in normal/physiological conditions or in metabolic pathologies of humans.

  19. Protein turnover in adipose tissue from fasted or diabetic rats

    Science.gov (United States)

    Tischler, Marc E.; Ost, Alan H.; Coffman, Julia

    1986-01-01

    Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

  20. Acetylation of Cavin-1 Promotes Lipolysis in White Adipose Tissue.

    Science.gov (United States)

    Zhou, Shui-Rong; Guo, Liang; Wang, Xu; Liu, Yang; Peng, Wan-Qiu; Liu, Yuan; Wei, Xiang-Bo; Dou, Xin; Ding, Meng; Lei, Qun-Ying; Qian, Shu-Wen; Li, Xi; Tang, Qi-Qun

    2017-08-15

    White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which were under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1. Acetylation-mimetic 3Q mutants of cavin-1 augmented fat mobilization in 3T3-L1 adipocytes and zebrafish. Mechanistically, acetylated cavin-1 preferentially interacted with hormone-sensitive lipase and recruited it to the caveolae, thereby promoting lipolysis. Our findings shed light on the essential role of cavin-1 in regulating lipolysis in an acetylation-dependent manner in WAT. Copyright © 2017 American Society for Microbiology.

  1. Brain insulin controls adipose tissue lipolysis and lipogenesis.

    Science.gov (United States)

    Scherer, Thomas; O'Hare, James; Diggs-Andrews, Kelly; Schweiger, Martina; Cheng, Bob; Lindtner, Claudia; Zielinski, Elizabeth; Vempati, Prashant; Su, Kai; Dighe, Shveta; Milsom, Thomas; Puchowicz, Michelle; Scheja, Ludger; Zechner, Rudolf; Fisher, Simon J; Previs, Stephen F; Buettner, Christoph

    2011-02-02

    <