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Sample records for adipose tissue development

  1. Development and differentiation of adipose tissue

    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..

  2. Brown adipose tissue growth and development.

    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. Brown Adipose Tissue Growth and Development

    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.

  4. Adipose tissue fibrosis

    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.

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

    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.

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

    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.

  7. Adipose tissue macrophages

    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

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

    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.

  9. Fetal development of subcutaneous white adipose tissue is dependent on Zfp423

    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.

  10. FGF receptor antagonism does not affect adipose tissue development in nutritionally induced obesity.

    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.

  11. Adipose tissue and sustainable development: a connection that needs protection

    Angelo eTremblay

    2015-05-01

    Full Text Available Obesity is generally considered as an excess body fat that increases the risk to develop ergonomic, metabolic and psychosocial problems. As suggested in this paper, body fat gain is also a protective adaptation that prevents body lipotoxicity, contributes to the secretion of molecules involved in metabolic regulation, and dilutes lipid soluble persistent organic pollutants (POPs. Recent literature shows that this protective role of adipose tissue is more solicited in a modern context in which unsuspected factors can affect energy balance to a much greater extent than what is generally perceived by health care professionals. These factors include short sleep duration, demanding mental work, and chemical pollution whose impact is more detectable in a context dominated by economic productivity and competitiveness. Since these factors might also include the increase in atmospheric CO2, it is likely that obesity prevention will need the support of a promotion in sustainable development, whether it is for human health and well-being or global ecological protection.

  12. Bioengineering Beige Adipose Tissue Therapeutics.

    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

  13. Targeting adipose tissue

    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.

  14. Development of Synthetic and Natural Materials for Tissue Engineering Applications Using Adipose Stem Cells

    Yunfan He

    2016-01-01

    Full Text Available Adipose stem cells have prominent implications in tissue regeneration due to their abundance and relative ease of harvest from adipose tissue and their abilities to differentiate into mature cells of various tissue lineages and secrete various growth cytokines. Development of tissue engineering techniques in combination with various carrier scaffolds and adipose stem cells offers great potential in overcoming the existing limitations constraining classical approaches used in plastic and reconstructive surgery. However, as most tissue engineering techniques are new and highly experimental, there are still many practical challenges that must be overcome before laboratory research can lead to large-scale clinical applications. Tissue engineering is currently a growing field of medical research; in this review, we will discuss the progress in research on biomaterials and scaffolds for tissue engineering applications using adipose stem cells.

  15. Development of Synthetic and Natural Materials for Tissue Engineering Applications Using Adipose Stem Cells.

    He, Yunfan; Lu, Feng

    2016-01-01

    Adipose stem cells have prominent implications in tissue regeneration due to their abundance and relative ease of harvest from adipose tissue and their abilities to differentiate into mature cells of various tissue lineages and secrete various growth cytokines. Development of tissue engineering techniques in combination with various carrier scaffolds and adipose stem cells offers great potential in overcoming the existing limitations constraining classical approaches used in plastic and reconstructive surgery. However, as most tissue engineering techniques are new and highly experimental, there are still many practical challenges that must be overcome before laboratory research can lead to large-scale clinical applications. Tissue engineering is currently a growing field of medical research; in this review, we will discuss the progress in research on biomaterials and scaffolds for tissue engineering applications using adipose stem cells.

  16. Subcutaneous adipose tissue classification

    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

  17. [Human brown adipose tissue].

    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.

  18. Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4.

    Wojciechowicz, Kamila; Gledhill, Karl; Ambler, Carrie A; Manning, Craig B; Jahoda, Colin A B

    2013-01-01

    The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16) the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis), under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot.

  19. Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4.

    Kamila Wojciechowicz

    Full Text Available The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16 the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis, under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot.

  20. Fat accumulation in adipose tissues as a risk factor for the development of endometrial cancer.

    Nakamura, Keiichiro; Hongo, Atsushi; Kodama, Junichi; Hiramatsu, Yuji

    2011-07-01

    Fat accumulation in adipose tissues is a risk factor for the development of human cancers. However, there are no studies describing the fat accumulation in adipose tissue or its distribution in human endometrial cancer. We first examined fat accumulation in adipose tissues separately on CT images of 122 patients with endometrial cancer, and investigated the correlation of these findings with various histological types of endometrial cancers. Fat accumulation in adipose tissues [subcutaneous fat area (SFA) and/or visceral fat areas (VFA)] was strongly correlated with the group of obesity-related biological parameters (weight, body mass index (BMI), waist and body surface area (BSA)) in endometrial cancer. The incidence of type I endometrial cancer was more closely correlated with an increase in obesity-related parameters such as weight (p=0.011), BMI (p=0.006), waist circumference (p=0.038), BSA (p=0.016), SFA (p=0.005), total fat area (TFA) (p=0.006) and total cholesterol (T.Cho) (P=0.010) than type II endometrial cancer. In particular, the SFA was most strongly correlated with obesity-related biological parameters of type I endometrial cancer. The present findings indicate that type I endometrial cancer has a statistically significant increase in obesity-related biological parameters than type II endometrial cancer. We propose that the subcutaneous fat accumulation in adipose tissue is a strong risk factor for developing type I endometrial cancer.

  1. Quantification of adipose tissue insulin sensitivity.

    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.

  2. Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression.

    Gucalp, Ayca; Iyengar, Neil M; Hudis, Clifford A; Dannenberg, Andrew J

    2016-02-01

    The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies.

  3. Differential effects of a gelatinase inhibitor on adipocyte differentiation and adipose tissue development.

    Van Hul, Matthias; Bauters, Dries; Lijnen, Roger H

    2013-10-01

    (1) A potential role for the gelatinases in adipocyte differentiation in vitro and adipose tissue development in vivo was investigated using the gelatinase inhibitor tolylsam ((R)-3-methyl-2-[4-(3-p-tolyl-[1,2,4]oxadiazol-5-yl)-benzenesulphonylamino]-butyric acid). (2) Differentiation of murine 3T3-F442A preadipocytes (12 days after reaching confluence) into mature adipocytes in vitro was promoted in the presence of tolylsam (10-100 μmol/L). (3) De novo development of fat tissue in nude mice injected with preadipocytes and kept on a high-fat diet was significantly impaired following treatment with tolylsam (100 mg/kg per day for 4 weeks). (4) Adipose tissue development in matrix metalloproteinase (MMP)-2 deficient mice, kept on a high-fat diet, was significantly impaired following administration of tolylsam (100 mg/kg per day for 15 weeks). This was associated with markedly enhanced metabolic rate. (5) Treatment of MMP-2-deficient mice with tolylsam (100 mg/kg per day, 15 weeks) was associated with the preservation of collagen and a reduction in blood vessel size in adipose tissues in vivo. (6) Furthermore, plasma levels of triglycerides and free fatty acids were reduced by tolylsam treatment of MMP-2-deficient mice (100 mg/kg per day, 15 weeks), whereas nutrient adsorption in the intestine was not affected. (7) The results of the present study indicate that tolylsam promotes preadipocyte differentiation in vitro, but impairs adipose tissue development in vivo.

  4. Adipose Tissue Metabolism During Hypobaria

    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.

  5. Hypothalamic control of adipose tissue.

    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.

  6. Roles of FGFs as Adipokines in Adipose Tissue Development, Remodeling, and Metabolism.

    Ohta, Hiroya; Itoh, Nobuyuki

    2014-01-01

    White and brown adipose tissues (BATs), which store and burn lipids, respectively, play critical roles in energy homeostasis. Fibroblast growth factors (FGFs) are signaling proteins with diverse functions in development, metabolism, and neural function. Among 22 FGFs, FGF1, FGF10, and FGF21 play roles as adipokines, adipocyte-secreted proteins, in the development and function of white and BATs. FGF1 is a critical transducer in white adipose tissue (WAT) remodeling. The peroxisome proliferator-activated receptor γ-FGF1 axis is critical for energy homeostasis. FGF10 is essential for embryonic white adipocyte development. FGF21 activates BAT in response to cold exposure. FGF21 also stimulates the accumulation of brown-like cells in WAT during cold exposure and is an upstream effector of adiponectin, which controls systemic energy metabolism. These findings provide new insights into the roles of FGF signaling in white and BATs and potential therapeutic strategies for metabolic disorders.

  7. Steroid biosynthesis in adipose tissue.

    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.

  8. Gene expression profiles reveal effect of a high-fat diet on the development of white and brown adipose tissues.

    Kim, Hyeng-Soo; Ryoo, Zae Young; Choi, Sang Un; Lee, Sanggyu

    2015-07-01

    Because of the recent discovery of brown adipose tissues tissue in adult humans, brown adipose tissues have garnered additional attention. Many studies have attempted to transform the precursor cells within the white adipocyte cultures to Brite (brown-in-white) cells by using genomic modification or pharmacological activation in order to determine the therapeutic effect of obesity. However, genome-scale analysis of the genetic factors governing the development of white and brown adipose tissues remains incomplete. In order to identify the key genes that regulate the development of white and brown adipose tissues in mice, a transcriptome analysis was performed on the adipose tissues. Network analysis of differentially expressed genes indicated that Trim30 and Ucp3 play pivotal roles in energy balance and glucose homeostasis. In addition, it was discovered that identical biological processes and pathways in the white and brown adipose tissues might be regulated by different genes. Trim30 and Ucp3 might be used as genetic markers to precisely represent the stage of obesity during the early and late stages of adipose tissue development, respectively. These results may provide a stepping-stone for future obesity-related studies.

  9. Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology.

    Louveau, I; Perruchot, M-H; Bonnet, M; Gondret, F

    2016-11-01

    Both white and brown adipose tissues are recognized to be differently involved in energy metabolism and are also able to secrete a variety of factors called adipokines that are involved in a wide range of physiological and metabolic functions. Brown adipose tissue is predominant around birth, except in pigs. Irrespective of species, white adipose tissue has a large capacity to expand postnatally and is able to adapt to a variety of factors. The aim of this review is to update the cellular and molecular mechanisms associated with pre- and postnatal adipose tissue development with a special focus on pigs and ruminants. In contrast to other tissues, the embryonic origin of adipose cells remains the subject of debate. Adipose cells arise from the recruitment of specific multipotent stem cells/progenitors named adipose tissue-derived stromal cells. Recent studies have highlighted the existence of a variety of those cells being able to differentiate into white, brown or brown-like/beige adipocytes. After commitment to the adipocyte lineage, progenitors undergo large changes in the expression of many genes involved in cell cycle arrest, lipid accumulation and secretory functions. Early nutrition can affect these processes during fetal and perinatal periods and can also influence or pre-determinate later growth of adipose tissue. How these changes may be related to adipose tissue functional maturity around birth and can influence newborn survival is discussed. Altogether, a better knowledge of fetal and postnatal adipose tissue development is important for various aspects of animal production, including neonatal survival, postnatal growth efficiency and health.

  10. An adipoinductive role of inflammation in adipose tissue engineering: key factors in the early development of engineered soft tissues.

    Lilja, Heidi E; Morrison, Wayne A; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W; Abberton, Keren M

    2013-05-15

    Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

  11. Osteopontin deletion prevents the development of obesity and hepatic steatosis via impaired adipose tissue matrix remodeling and reduced inflammation and fibrosis in adipose tissue and liver in mice.

    Andoni Lancha

    Full Text Available Osteopontin (OPN is a multifunctional extracellular matrix (ECM protein involved in multiple physiological processes. OPN expression is dramatically increased in visceral adipose tissue in obesity and the lack of OPN protects against the development of insulin resistance and inflammation in mice. We sought to unravel the potential mechanisms involved in the beneficial effects of the absence of OPN. We analyzed the effect of the lack of OPN in the development of obesity and hepatic steatosis induced by a high-fat diet (HFD using OPN-KO mice. OPN expression was upregulated in epididymal white adipose tissue (EWAT and liver in wild type (WT mice with HFD. OPN-KO mice had higher insulin sensitivity, lower body weight and fat mass with reduced adipose tissue ECM remodeling and reduced adipocyte size than WT mice under a HFD. Reduced MMP2 and MMP9 activity was involved in the decreased ECM remodeling. Crown-like structure number in EWAT as well as F4/80-positive cells and Emr1 expression in EWAT and liver increased with HFD, while OPN-deficiency blunted the increase. Moreover, our data show for the first time that OPN-KO under a HFD mice display reduced fibrosis in adipose tissue and liver, as well as reduced oxidative stress in adipose tissue. Gene expression of collagens Col1a1, Col6a1 and Col6a3 in EWAT and liver, as well as the profibrotic cytokine Tgfb1 in EWAT were increased with HFD, while OPN-deficiency prevented this increase. OPN deficiency prevented hepatic steatosis via reduction in the expression of molecules involved in the onset of fat accumulation such as Pparg, Srebf1, Fasn, Mogat1, Dgat2 and Cidec. Furthermore, OPN-KO mice exhibited higher body temperature and improved BAT function. The present data reveal novel mechanisms of OPN in the development of obesity, pointing out the inhibition of OPN as a promising target for the treatment of obesity and fatty liver.

  12. Osteopontin deletion prevents the development of obesity and hepatic steatosis via impaired adipose tissue matrix remodeling and reduced inflammation and fibrosis in adipose tissue and liver in mice.

    Lancha, Andoni; Rodríguez, Amaia; Catalán, Victoria; Becerril, Sara; Sáinz, Neira; Ramírez, Beatriz; Burrell, María A; Salvador, Javier; Frühbeck, Gema; Gómez-Ambrosi, Javier

    2014-01-01

    Osteopontin (OPN) is a multifunctional extracellular matrix (ECM) protein involved in multiple physiological processes. OPN expression is dramatically increased in visceral adipose tissue in obesity and the lack of OPN protects against the development of insulin resistance and inflammation in mice. We sought to unravel the potential mechanisms involved in the beneficial effects of the absence of OPN. We analyzed the effect of the lack of OPN in the development of obesity and hepatic steatosis induced by a high-fat diet (HFD) using OPN-KO mice. OPN expression was upregulated in epididymal white adipose tissue (EWAT) and liver in wild type (WT) mice with HFD. OPN-KO mice had higher insulin sensitivity, lower body weight and fat mass with reduced adipose tissue ECM remodeling and reduced adipocyte size than WT mice under a HFD. Reduced MMP2 and MMP9 activity was involved in the decreased ECM remodeling. Crown-like structure number in EWAT as well as F4/80-positive cells and Emr1 expression in EWAT and liver increased with HFD, while OPN-deficiency blunted the increase. Moreover, our data show for the first time that OPN-KO under a HFD mice display reduced fibrosis in adipose tissue and liver, as well as reduced oxidative stress in adipose tissue. Gene expression of collagens Col1a1, Col6a1 and Col6a3 in EWAT and liver, as well as the profibrotic cytokine Tgfb1 in EWAT were increased with HFD, while OPN-deficiency prevented this increase. OPN deficiency prevented hepatic steatosis via reduction in the expression of molecules involved in the onset of fat accumulation such as Pparg, Srebf1, Fasn, Mogat1, Dgat2 and Cidec. Furthermore, OPN-KO mice exhibited higher body temperature and improved BAT function. The present data reveal novel mechanisms of OPN in the development of obesity, pointing out the inhibition of OPN as a promising target for the treatment of obesity and fatty liver.

  13. Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep.

    Satterfield, M Carey; Dunlap, Kathrin A; Keisler, Duane H; Bazer, Fuller W; Wu, Guoyao

    2013-09-01

    Intrauterine growth restriction is a significant problem worldwide, resulting in increased rates of neonatal morbidity and mortality, as well as increased risks for metabolic and cardiovascular disease. The present study investigated the role of maternal undernutrition and L-arginine administration on fetal growth and development. Embryo transfer was utilized to generate genetically similar singleton pregnancies. On Day 35 of gestation, ewes were assigned to receive either 50 or 100% of their nutritional requirements. Ewes received i.v. injections of either saline or L-arginine three times daily from Day 100 to Day 125. Fetal growth was assessed at necropsy on Day 125. Maternal dietary manipulation altered circulating concentrations of leptin, progesterone, and amino acids in maternal plasma. Fetal weight was reduced in nutrient-restricted ewes on Day 125 compared with 100% fed ewes. Compared with saline-treated underfed ewes, maternal L-arginine administration did not affect fetal weight but increased weight of the fetal pancreas by 32% and fetal peri-renal brown adipose tissue mass by 48%. These results indicate that L-arginine administration enhanced fetal pancreatic and brown adipose tissue development. The postnatal effects of increased pancreatic and brown adipose tissue growth warrant further study.

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

    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.

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

    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.

  16. Mitochondria and endocrine function of adipose tissue.

    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.

  17. Differential Roles of Insulin and IGF-1 Receptors in Adipose Tissue Development and Function.

    Boucher, Jeremie; Softic, Samir; El Ouaamari, Abdelfattah; Krumpoch, Megan T; Kleinridders, Andre; Kulkarni, Rohit N; O'Neill, Brian T; Kahn, C Ronald

    2016-08-01

    To determine the roles of insulin and insulin-like growth factor 1 (IGF-1) action in adipose tissue, we created mice lacking the insulin receptor (IR), IGF-1 receptor (IGF1R), or both using Cre-recombinase driven by the adiponectin promoter. Mice lacking IGF1R only (F-IGFRKO) had a ∼25% reduction in white adipose tissue (WAT) and brown adipose tissue (BAT), whereas mice lacking both IR and IGF1R (F-IR/IGFRKO) showed an almost complete absence of WAT and BAT. Interestingly, mice lacking only the IR (F-IRKO) had a 95% reduction in WAT, but a paradoxical 50% increase in BAT with accumulation of large unilocular lipid droplets. Both F-IRKO and F-IR/IGFRKO mice were unable to maintain body temperature in the cold and developed severe diabetes, ectopic lipid accumulation in liver and muscle, and pancreatic islet hyperplasia. Leptin treatment normalized blood glucose levels in both groups. Glucose levels also improved spontaneously by 1 year of age, despite sustained lipodystrophy and insulin resistance. Thus, loss of IR is sufficient to disrupt white fat formation, but not brown fat formation and/or maintenance, although it is required for normal BAT function and temperature homeostasis. IGF1R has only a modest contribution to both WAT and BAT formation and function.

  18. Adipose Tissue Biology: An Update Review

    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.

  19. Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet.

    Kadowaki, Tomoko; Kido, Mizuho A; Hatakeyama, Junko; Okamoto, Kuniaki; Tsukuba, Takayuki; Yamamoto, Kenji

    2014-03-28

    Cathepsin E is an intracellular aspartic proteinase, which is predominantly distributed in immune-related and epithelial cells. However, the role of the enzyme in adipose tissues remains unknown. In this study, we investigated the characteristics of cathepsin E-deficient (CatE(-/-)) mice fed a high-fat diet (HFD), as a mouse model of obesity. HFD-fed CatE(-/-) mice displayed reduced body weight gain and defective development of white adipose tissue (WAT) and brown adipose tissue (BAT), compared with HFD-fed wild-type mice. Moreover, fat-induced CatE(-/-) mice showed abnormal lipid accumulation in non-adipose tissues characterized by hepatomegaly, which is probably due to defective adipose tissue development. Detailed pathological and biochemical analyses showed that hepatomegaly was accompanied by hepatic steatosis and hypercholesterolemia in HFD-induced CatE(-/-) mice. In fat-induced CatE(-/-) mice, the number of macrophages infiltrating into WAT was significantly lower than in fat-induced wild-type mice. Thus, the impaired adipose tissue development in HFD-induced CatE(-/-) mice was probably due to reduced infiltration of macrophages and may lead to hepatomegaly accompanied by hepatic steatosis and hypercholesterolemia.

  20. Adipose Tissue Immunity and Cancer

    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.

  1. Adipose tissue as an endocrine organ.

    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.

  2. Adipose tissue development during early life: novel insights into energy balance from small and large mammals.

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

    2012-08-01

    Since the rediscovery of brown adipose tissue (BAT) in adult human subjects in 2007, there has been a dramatic resurgence in research interest in its role in heat production and energy balance. This has coincided with a reassessment of the origins of BAT and the suggestion that brown preadipocytes could share a common lineage with skeletal myoblasts. In precocial newborns, such as sheep, the onset of non-shivering thermogenesis through activation of the BAT-specific uncoupling protein 1 (UCP1) is essential for effective adaptation to the cold exposure of the extra-uterine environment. This is mediated by a combination of endocrine adaptations which accompany normal parturition at birth and further endocrine stimulation from the mother's milk. Three distinct adipose depots have been identified in all species studied to date. These contain either primarily white, primarily brown or a mix of brown and white adipocytes. The latter tissue type is present, at least, in the fetus and, thereafter, appears to take on the characteristics of white adipose tissue during postnatal development. It is becoming apparent that a range of organ-specific mechanisms can promote UCP1 expression. They include the liver, heart and skeletal muscle, and involve unique endocrine systems that are stimulated by cold exposure and/or exercise. These multiple pathways that promote BAT function vary with age and between species that may determine the potential to be manipulated in early life. Such interventions could modify, or reverse, the normal ontogenic pathway by which BAT disappears after birth, thereby facilitating BAT thermogenesis through the life cycle.

  3. Brown adipose tissue and its therapeutic potential.

    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.

  4. Immunological contributions to adipose tissue homeostasis.

    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.

  5. The role of matrix metalloproteinases in muscle and adipose tissue development and meat quality: A review.

    Christensen, Sara; Purslow, Peter P

    2016-09-01

    Matrix metalloproteinases (MMPs) are a group of enzymes that degrade extracellular matrix components but are also important signaling molecules that regulate many biological processes including muscle, adipose and connective tissue development. Most recently it has been discovered that MMPs act as intracellular signaling molecules inducing gene expression and altering related proteins in the nucleus. Several single nucleotide polymorphisms of MMPs and their inhibitors are known to exist and most of the research on MMPs to date has focused on their activity in relation to human health and disease. Nevertheless there is a growing body of evidence identifying important roles of MMPs as regulators of myogenesis, fibrogenesis and adipogenesis. The aim of this review is to highlight the currently known functions of the MMPs that have a direct bearing on the deposition of meat components and their relationship with meat quality. Some central pathways by which these enzymes can affect the tenderness, the amount and type of fatty acids are highlighted.

  6. Development of automated quantification of visceral and subcutaneous adipose tissue volumes from abdominal CT scans

    Mensink, Sanne D.; Spliethoff, Jarich W.; Belder, Ruben; Klaase, Joost M.; Bezooijen, Roland; Slump, Cornelis H.

    2011-03-01

    This contribution describes a novel algorithm for the automated quantification of visceral and subcutaneous adipose tissue volumes from abdominal CT scans of patients referred for colorectal resection. Visceral and subcutaneous adipose tissue volumes can accurately be measured with errors of 1.2 and 0.5%, respectively. Also the reproducibility of CT measurements is good; a disadvantage is the amount of radiation. In this study the diagnostic CT scans in the work - up of (colorectal) cancer were used. This implied no extra radiation. For the purpose of segmentation alone, a low dose protocol can be applied. Obesity is a well known risk factor for complications in and after surgery. Body Mass Index (BMI) is a widely accepted indicator of obesity, but it is not specific for risk assessment of colorectal surgery. We report on an automated method to quantify visceral and subcutaneous adipose tissue volumes as a basic step in a clinical research project concerning preoperative risk assessment. The outcomes are to be correlated with the surgery results. The hypothesis is that the balance between visceral and subcutaneous adipose tissue together with the presence of calcifications in the major bloodvessels, is a predictive indicator for post - operatieve complications such as anastomotic leak. We start with four different computer simulated humanoid abdominal volumes with tissue values in the appropriate Hounsfield range at different dose levels. With satisfactory numerical results for this test, we have applied the algorithm on over a 100 patient scans and have compared results with manual segmentations by an expert for a smaller pilot group. The results are within a 5% difference. Compared to other studies reported in the literature, reliable values are obtained for visceral and subcutaneous adipose tissue areas.

  7. Cell-autonomous activation of Hedgehog signaling inhibits brown adipose tissue development

    Although recent studies have shown that brown adipose tissue (BAT) arises from progenitor cells that also give rise to skeletal muscle, the developmental signals that control the formation of BAT remain largely unknown. Here, we show that brown preadipocytes possess primary cilia and can respond to ...

  8. AGPAT2 is essential for postnatal development and maintenance of white and brown adipose tissue

    Kelly M. Cautivo

    2016-07-01

    Conclusion: We conclude that lipodystrophy in Agpat2−/− mice results from postnatal cell death of adipose tissue in association with acute local inflammation. It is possible that AGPAT2 deficient adipocytes have an altered lipid filling or a reduced capacity to adapt the massive lipid availability associated with postnatal feeding.

  9. Subcutaneous adipose tissue topography (SAT-Top) development in children and young adults.

    Tafeit, Erwin; Möller, Reinhard; Jurimae, Toivo; Sudi, Karl; Wallner, Sandra Johanna

    2007-06-01

    The importance of body composition measurements to elucidate the dynamics of related diseases in pediatrics is gaining recognition. The methods used should not expose subjects to high doses of radiation and require substantial cooperation. The Lipometer is a new optical device that enables the non-invasive, quick and safe determination of the thickness of subcutaneous adipose tissue (SAT) layers (in mm) at any site of the human body. The topographic specification of 15 evenly distributed body sites, which makes it possible to precisely measure subcutaneous body fat distribution, is called subcutaneous adipose tissue topography (SAT-Top). SAT-Top was determined in more than 1000 children and young adults between the ages of 7 and 21. In this paper we describe the SAT-Top development of these subjects through different age groups and the differences between male and female SAT-Top development in each age group. SAT layer profiles (medians of the 15 body sites) for boys and girls in age group 1 (7-9 yrs) show a very similar pattern for both sexes, followed by slightly decreasing SAT layer thicknesses in boys and increasing values in girls in the subsequent age groups. Between age group 3 (11-13 yrs) and age group 7 (19-21 yrs) male and female SAT-Top is significantly different. The discriminating power between male and female SAT-Top was investigated by stepwise discriminant analysis, which provided no significant results for age group 1 (7-9 yrs), about 73% correct classification for age group 2 (9-11 yrs) and 3 (11-13 yrs), 83% for age group 4 (13-15 yrs), and about 91-93% for the following age groups (15-21 yrs). It is known that SAT development is the same in both sexes until puberty, when girls gain relatively more fat mass than boys to reach a higher body-fat percentage as adults. This paper presents a precise description of SAT development in boys and girls from childhood to adolescence, which provides a basis for further investigations.

  10. Marine n-3 fatty acids in adipose tissue and development of atrial fibrillation

    Rix, Thomas Andersen; Joensen, Albert Marni; Riahi, Sam

    2013-01-01

    OBJECTIVE: Consumption of fish and marine n-3 polyunsaturated fatty acids (PUFA) may be associated with a lower risk of atrial fibrillation (AF), but results have been inconsistent. The aim was to investigate this further by measurements of marine n-3 PUFA in adipose tissue. DESIGN: Cohort study...... of marine n-3 PUFA, which reflects the endogenous exposure and is also an objective marker of the long-term dietary intake. MAIN OUTCOME MEASURES: Incident AF during follow-up. RESULTS: 179 cases of AF occurred over 13.6 years. Multivariate, sex-stratified Cox proportional hazards regression analyses using...... cubic splines showed a monotonic, negative, dose-response trend, but not statistically significant association, between total marine n-3 PUFA in adipose tissue and incident AF. A similar trend towards a lower risk of AF was seen in the second (HR 0.87, 95% CI 0.60 to 1.24) and third tertiles (HR 0...

  11. Lipolysis in human adipose tissue during exercise

    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...

  12. Capillary permeability in adipose tissue

    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...

  13. Vascular endothelial growth factor is important for brown adipose tissue development and maintenance.

    Bagchi, Mandrita; Kim, Leo A; Boucher, Jeremie; Walshe, Tony E; Kahn, C Ronald; D'Amore, Patricia A

    2013-08-01

    Vascular endothelial growth factor (VEGF) is critical for angiogenesis, but also has pleiotropic effects on several nonvascular cells. Our aim was to investigate the role of VEGF in brown adipose tissue (BAT). We show that VEGF expression increases 2.5-fold during differentiation of cultured murine brown adipocytes and that VEGF receptor-2 is phosphorylated, indicating VEGF signaling. VEGF increased proliferation in brown preadipocytes in vitro by 70%, and blockade of VEGF signaling using anti-VEGFR2 antibody DC101 increased brown adipocyte apoptosis, as determined by cell number and activation of caspase 3. Systemic VEGF neutralization in mice, accomplished by adenoviral expression of soluble Flt1, resulted in 7-fold increase in brown adipocyte apoptosis, mitochondrial degeneration, and increased mitophagy compared to control mice expressing a null adenovirus. Absence of the heparan sulfate-binding VEGF isoforms, VEGF164 and VEGF188, resulted in abnormal BAT development in mice at E15.5, with fewer brown adipocytes and lower mitochondrial protein compared to wild-type littermates. These results suggest a role for VEGF in brown adipocytes and preadipocytes to promote survival, proliferation, and normal mitochondria and development.

  14. Adipose tissue, diet and aging.

    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.

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

    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.

  16. Differential Development of Inflammation and Insulin Resistance in Different Adipose Tissue Depots Along Aging in Wistar Rats: Effects of Caloric Restriction.

    Sierra Rojas, Johanna X; García-San Frutos, Miriam; Horrillo, Daniel; Lauzurica, Nuria; Oliveros, Eva; Carrascosa, Jose María; Fernández-Agulló, Teresa; Ros, Manuel

    2016-03-01

    The prevalence of insulin resistance and type 2 diabetes increases with aging and these disorders are associated with inflammation. Insulin resistance and inflammation do not develop at the same time in all tissues. Adipose tissue is one of the tissues where inflammation and insulin resistance are established earlier during aging. Nevertheless, the existence of different fat depots states the possibility of differential roles for these depots in the development of age-associated inflammation and insulin resistance. To explore this, we analyzed insulin signaling and inflammation in epididymal, perirenal, subcutaneous, and brown adipose tissues during aging in Wistar rats. Although all tissues showed signs of inflammation and insulin resistance with aging, epididymal fat was the first to develop signs of inflammation and insulin resistance along aging among white fat tissues. Subcutaneous adipose tissue presented the lowest degree of inflammation and insulin resistance that developed latter with age. Brown adipose tissue also presented latter insulin resistance and inflammation but with lower signs of macrophage infiltration. Caloric restriction ameliorated insulin resistance and inflammation in all tissues, being more effective in subcutaneous and brown adipose tissues. These data demonstrate differential susceptibility of the different adipose depots to the development of age-associated insulin resistance and inflammation.

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

    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.

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

    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.

  19. The impact of diet in early life on adipose tissue growth and development in sheep

    Birtwistle, Mark D.A.

    2016-01-01

    Adipose tissue is found in two main forms: white (WAT), which stores energy; and brown (BAT), which dissipates energy as heat by means of a unique mitochondrial protein, UCP1. In large mammals, BAT is rapidly replaced by WAT after birth, but it has recently been found that functional BAT is present in human adults, which raises the possibility that it could be manipulated to burn off excess fat. The main aim of this thesis was to investigate, using sheep as a model, the effect of early nutrit...

  20. Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice

    Ma, Tao; Liaset, Bjørn; Hao, Qin;

    2011-01-01

    Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity......, adipose tissue inflammation and glucose intolerance....

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

    Franssens, B.T.

    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

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

    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.

  3. Adipose tissue and its role in organ crosstalk.

    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.

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

    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....

  5. Adipose tissues as endocrine target organs.

    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.

  6. Brown Adipose Tissue and Browning Agents: Irisin and FGF21 in the Development of Obesity in Children and Adolescents.

    Pyrżak, B; Demkow, U; Kucharska, A M

    2015-01-01

    In the pediatric population, especially in early infancy, the activity of brown adipose tissue (BAT) is the highest. Further in life BAT is more active in individuals with a lower body mass index and one can expect that BAT is protective against childhood obesity. The development of BAT throughout the whole life can be regulated by genetic, endocrine, and environmental factors. Three distinct adipose depots have been identified: white, brown, and beige adipocytes. The process by which BAT can become beige is still unclear and is an area of intensive research. The "browning agents" increase energy expenditure through the production of heat. Numerous factors known as "browning agents" have currently been described. In humans, recent studies justify a notion of a role of novel myokines: irisin and fibroblast growth factor 21 (FGF21) in the metabolism and development of obesity. This review describes a possible role of irisin and FGF21 in the pathogenesis of obesity in children.

  7. Characterization of the human visceral adipose tissue secretome

    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

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

    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.

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

    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 ...

  10. Adipokines and the Endocrine Role of Adipose Tissues.

    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.

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

    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.

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

    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.

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

    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

  14. Cdkn1c Boosts the Development of Brown Adipose Tissue in a Murine Model of Silver Russell Syndrome.

    Van De Pette, Matthew; Tunster, Simon J; McNamara, Grainne I; Shelkovnikova, Tatyana; Millership, Steven; Benson, Lindsay; Peirson, Stuart; Christian, Mark; Vidal-Puig, Antonio; John, Rosalind M

    2016-03-01

    The accurate diagnosis and clinical management of the growth restriction disorder Silver Russell Syndrome (SRS) has confounded researchers and clinicians for many years due to the myriad of genetic and epigenetic alterations reported in these patients and the lack of suitable animal models to test the contribution of specific gene alterations. Some genetic alterations suggest a role for increased dosage of the imprinted CYCLIN DEPENDENT KINASE INHIBITOR 1C (CDKN1C) gene, often mutated in IMAGe Syndrome and Beckwith-Wiedemann Syndrome (BWS). Cdkn1c encodes a potent negative regulator of fetal growth that also regulates placental development, consistent with a proposed role for CDKN1C in these complex childhood growth disorders. Here, we report that a mouse modelling the rare microduplications present in some SRS patients exhibited phenotypes including low birth weight with relative head sparing, neonatal hypoglycemia, absence of catch-up growth and significantly reduced adiposity as adults, all defining features of SRS. Further investigation revealed the presence of substantially more brown adipose tissue in very young mice, of both the classical or canonical type exemplified by interscapular-type brown fat depot in mice (iBAT) and a second type of non-classic BAT that develops postnatally within white adipose tissue (WAT), genetically attributable to a double dose of Cdkn1c in vivo and ex-vivo. Conversely, loss-of-function of Cdkn1c resulted in the complete developmental failure of the brown adipocyte lineage with a loss of markers of both brown adipose fate and function. We further show that Cdkn1c is required for post-transcriptional accumulation of the brown fat determinant PR domain containing 16 (PRDM16) and that CDKN1C and PRDM16 co-localise to the nucleus of rare label-retaining cell within iBAT. This study reveals a key requirement for Cdkn1c in the early development of the brown adipose lineages. Importantly, active BAT consumes high amounts of energy to

  15. Adipose tissue: cell heterogeneity and functional diversity.

    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.

  16. Adipose and mammary epithelial tissue engineering.

    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.

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

    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...... an oral glucose load. Adipose-tissue blood flow was measured in the anterior subcutaneous abdominal adipose tissue by the (133)Xe-washout technique. ATLD was measured as the disappearance rate of (99m)Tc-labelled nanoaggregated human albumin, during fasting and after an oral glucose load. A significant...... the lymphatic system in obese subjects. Furthermore, they suggest that postprandial changes in ATLD taking place in lean subjects are not observed in obese subjects. This may have a role in the development of obesity-related inflammation in hypertrophic adipose tissue.International Journal of Obesity advance...

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

    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.

  19. DNA甲基化与脂肪组织生长发育%DNA Methylation and Adipose Tissue Development

    高媛; 孙婴宁; 李辉; 王宁

    2012-01-01

    DNA methylation is an important epigenetic modification and plays crucial roles in maintaining normal cellular functions, gene imprinting, embryonic development and human tumorigenesis. The key role of DNA methylation is the regulation of gene expression, and DNA methylation is one of several epigenetic mechanisms that cells use to regulate gene expression. Accumulating evidence has showed that DNA methylation plays an important role in adipose tissue development and obesity. DNA methylation regulates the expression of transcription factors, transcriptional cofactors, and other genes involved in adipose development and adipocyte differentiation. This article reviews recent advances in research on DNA methylation of adipose tissue development, and discusses the ongoing trends and future research directions of DNA methylation in adipose tissue.%DNA甲基化作为一种重要的表观遗传学修饰方式,在维持正常细胞功能、遗传印记、胚胎发育以及人类肿瘤发生中起着重要作用.DNA甲基化最重要的作用是调控基因表达,它是细胞调控基因表达的重要表观遗传机制之一.近年来的研究发现,DNA甲基化在脂肪组织生长发育以及肥胖症发生过程中发挥着重要作用.DNA甲基化通过调控脂肪细胞分化转录因子、转录辅助因子以及其他脂肪代谢相关基因的表达,从而调控脂肪组织的生长发育.该文综述了脂肪组织生长发育过程中DNA甲基化的最新研究进展,探讨了脂肪组织DNA甲基化的研究趋势和未来发展方向.

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

    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.

  1. Imaging white adipose tissue with confocal microscopy.

    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.

  2. Hypertrophic Obesity and Subcutaneous Adipose Tissue Dysfunction

    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.

  3. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance.

    Lee, Byung-Cheol; Lee, Jongsoon

    2014-03-01

    There is increasing evidence showing that inflammation is an important pathogenic mediator of the development of obesity-induced insulin resistance. It is now generally accepted that tissue-resident immune cells play a major role in the regulation of this obesity-induced inflammation. The roles that adipose tissue (AT)-resident immune cells play have been particularly extensively studied. AT contains most types of immune cells and obesity increases their numbers and activation levels, particularly in AT macrophages (ATMs). Other pro-inflammatory cells found in AT include neutrophils, Th1 CD4 T cells, CD8 T cells, B cells, DCs, and mast cells. However, AT also contains anti-inflammatory cells that counter the pro-inflammatory immune cells that are responsible for the obesity-induced inflammation in this tissue. These anti-inflammatory cells include regulatory CD4 T cells (Tregs), Th2 CD4 T cells, and eosinophils. Hence, AT inflammation is shaped by the regulation of pro- and anti-inflammatory immune cell homeostasis, and obesity skews this balance towards a more pro-inflammatory status. Recent genetic studies revealed several molecules that participate in the development of obesity-induced inflammation and insulin resistance. In this review, the cellular and molecular players that participate in the regulation of obesity-induced inflammation and insulin resistance are discussed, with particular attention being placed on the roles of the cellular players in these pathogeneses. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

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

    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

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

    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.

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

    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.

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

    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.

  8. The Adipose Tissue in Farm Animals

    Sauerwein, Helga; Bendixen, Emoke; Restelli, Laura

    2014-01-01

    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...

  9. Development of a System and Method for Automated Isolation of Stromal Vascular Fraction from Adipose Tissue Lipoaspirate

    Swathi SundarRaj

    2015-01-01

    Full Text Available Autologous fat grafting for soft tissue reconstruction is challenged by unpredictable long-term graft survival. Fat derived stromal vascular fraction (SVF is gaining popularity in tissue reconstruction as SVF-enriched fat grafts demonstrate improved engraftment. SVF also has potential in regenerative medicine for remodeling of ischemic tissues by promoting angiogenesis. Since SVF cells do not require culture expansion, attempts are being made to develop automated devices to isolate SVF at the point of care. We report development of a closed, automated system to process up to 500 mL lipoaspirate using cell size-dependent filtration technology. The yield of SVF obtained by automated tissue digestion and filtration (1.17 ± 0.5 × 105 cells/gram was equivalent to that obtained by manual isolation (1.15 ± 0.3 × 105; p = 0.8, and the viability of the cells isolated by both methods was greater than 90%. Cell composition included CD34+CD31− adipose stromal cells, CD34+CD31+ endothelial progenitor cells, and CD34−CD31+ endothelial cells, and their relative percentages were equivalent to SVF isolated by the manual method. CFU-F capacity and expression of angiogenic factors were also comparable with the manual method, establishing proof-of-concept for fully automated SVF isolation, suitable for use in reconstructive surgeries and regenerative medicine applications.

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

    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.

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

    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.

  12. Aetiological factors behind adipose tissue inflammation

    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...

  13. Loss of vitamin D receptor signaling from the mammary epithelium or adipose tissue alters pubertal glandular development.

    Johnson, Abby L; Zinser, Glendon M; Waltz, Susan E

    2014-10-15

    Vitamin D₃ receptor (VDR) signaling within the mammary gland regulates various postnatal stages of glandular development, including puberty, pregnancy, involution, and tumorigenesis. Previous studies have shown that vitamin D₃ treatment induces cell-autonomous growth inhibition and differentiation of mammary epithelial cells in culture. Furthermore, mammary adipose tissue serves as a depot for vitamin D₃ storage, and both epithelial cells and adipocytes are capable of bioactivating vitamin D₃. Despite the pervasiveness of VDR in mammary tissue, individual contributions of epithelial cells and adipocytes, as well as the VDR-regulated cross-talk between these two cell types during pubertal mammary development, have yet to be investigated. To assess the cell-type specific effect of VDR signaling during pubertal mammary development, novel mouse models with mammary epithelial- or adipocyte-specific loss of VDR were generated. Interestingly, loss of VDR in either cellular compartment accelerated ductal morphogenesis with increased epithelial cell proliferation and decreased apoptosis within terminal end buds. Conversely, VDR signaling specifically in the mammary epithelium modulated hormone-induced alveolar growth, as ablation of VDR in this cell type resulted in precocious alveolar development. In examining cellular cross-talk ex vivo, we show that ligand-dependent VDR signaling in adipocytes significantly inhibits mammary epithelial cell growth in part through the vitamin D₃-dependent production of the cytokine IL-6. Collectively, these studies delineate independent roles for vitamin D₃-dependent VDR signaling in mammary adipocytes and epithelial cells in controlling pubertal mammary gland development.

  14. Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood

    Oosting, Annemarie; van Vlies, Naomi; Kegler, Diane; Schipper, Lidewij; Abrahamse-Berkeveld, Marieke; Ringler, Silvia; Verkade, Henkjan J.; van der Beek, Eline M.

    2014-01-01

    Obese individuals have more (hyperplastic) and larger (hypertrophic) adipocytes in their white adipose tissue (WAT) than normal-weight individuals. The difference in cell number emerges early in childhood, suggesting that this is a critical period for being susceptible to obesity. Breast-feeding has

  15. Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood.

    Oosting, Annemarie; van Vlies, Naomi; Kegler, Diane; Schipper, Lidewij; Abrahamse-Berkeveld, Marieke; Ringler, Silvia; Verkade, Henkjan J; van der Beek, Eline M

    2014-01-28

    Obese individuals have more (hyperplastic) and larger (hypertrophic) adipocytes in their white adipose tissue (WAT) than normal-weight individuals. The difference in cell number emerges early in childhood, suggesting that this is a critical period for being susceptible to obesity. Breast-feeding has been shown to be protective against obesity, and we have previously shown in mice that the physical structure of lipids in human milk may contribute to this protective effect. In the present study, we investigated how differences in the physical structure of lipids in the early diet may modulate adipose tissue development. Male mice were fed a diet containing control infant milk formula (Control IMF; Danone Research) or Nuturis® (Concept IMF with large phospholipid-coated lipid droplets; Danone Research) from postnatal day (PN)16 to 42. Subsequently, mice were challenged with a moderate Western-style diet (WSD) until PN98, and body composition was monitored by dual-energy X-ray absorptiometry. Epididymal WAT was analysed for adipocyte size, number and gene expression of metabolic transcription factors. Early Concept IMF exposure reduced fat accumulation during the WSD challenge by 30 % compared with the Control IMF. It reduced adipocyte size without affecting adipocyte number in adult mice. The Concept IMF decreased the expression of PPARγ, CCAAT/enhancer-binding protein and retinoid X receptor α in WAT in adulthood, key regulators of metabolic activity. In conclusion, Concept IMF exposure in early life reduced susceptibility to obesity in adult life, by preventing adipocyte hypertrophia upon adult dietary challenge without affecting adipogenesis. These data emphasise the importance of the physical properties of dietary lipids in early life in obesity risk later in life.

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

    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.

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

    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.

  18. Platelet-derived growth factor and spatiotemporal cues induce development of vascularized bone tissue by adipose-derived stem cells.

    Hutton, Daphne L; Moore, Erika M; Gimble, Jeffrey M; Grayson, Warren L

    2013-09-01

    Vasculature is essential to the functional integration of a tissue-engineered bone graft to enable sufficient nutrient delivery and viability after implantation. Native bone and vasculature develop through intimately coupled, tightly regulated spatiotemporal cell-cell signaling. The complexity of these developmental processes has been a challenge for tissue engineers to recapitulate, resulting in poor codevelopment of both bone and vasculature within a unified graft. To address this, we cultured adipose-derived stromal/stem cells (ASCs), a clinically relevant, single cell source that has been previously investigated for its ability to give rise to vascularized bone grafts, and studied the effects of initial spatial organization of cells, the temporal addition of growth factors, and the presence of exogenous platelet-derived growth factor-BB (PDGF-BB) on the codevelopment of bone and vascular tissue structures. Human ASCs were aggregated into multicellular spheroids via the hanging drop method before encapsulation and subsequent outgrowth in fibrin gels. Cellular aggregation substantially increased vascular network density, interconnectivity, and pericyte coverage compared to monodispersed cultures. To form robust vessel networks, it was essential to culture ASCs in a purely vasculogenic medium for at least 8 days before the addition of osteogenic cues. Physiologically relevant concentrations of exogenous PDGF-BB (20 ng/mL) substantially enhanced both vascular network stability and osteogenic differentiation. Comparisons with the bone morphogenetic protein-2, another pro-osteogenic and proangiogenic growth factor, indicated that this potential to couple the formation of both lineages might be unique to PDGF-BB. Furthermore, the resulting tissue structure demonstrated the close association of mineral deposits with pre-existing vascular structures that have been described for developing tissues. This combination of a single cell source with a potent induction factor

  19. Endoplasmic reticulum stress in adipose tissue augments lipolysis.

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  4. Origins and early development of the concept that brown adipose tissue thermogenesis is linked to energy balance and obesity.

    Trayhurn, Paul

    2017-03-01

    Brown adipose tissue (BAT) was identified as a thermogenic organ in 1961, and in 1978 shown to be the major site of thermoregulatory non-shivering thermogenesis in rats acclimated to the cold. Investigations in the mid-late 1970s established the uncoupling of oxidative phosphorylation through a proton conductance pathway across the mitochondrial inner membrane as the mechanism for heat production in BAT, this being regulated by UCP1 which was first discovered as a 32,000 Mr cold-inducible protein. These developments came when those concerned with nutritional energetics were proposing that thermogenesis is a significant factor in energy balance and the aetiology of obesity. A link with BAT was first demonstrated in obese ob/ob mice, which were shown to have decreased thermogenic activity in the tissue, and in rats exhibiting diet-induced thermogenesis (DIT) during overfeeding on a cafeteria diet where an activation of brown fat was evident. These pioneering observations led to extensive studies on BAT in different animal models of obesity, both genetic (particularly ob/ob and db/db mice, fa/fa rats) and experimentally-induced. In each case, indices of BAT activity and capacity (mitochondrial content, GDP binding, amount of UCP1) indicated that the tissue plays a role in DIT and that obesity is characterised by reduced thermogenesis. Links between BAT and whole-body energetics were also made in physiological situations such as lactation and fasting. Studies in the 1980s also provided clear evidence for the presence of BAT in adult humans, particularly through the detection of UCP1, and its activation in patients with phaeochromocytoma. Interest in BAT in energetics and obesity waned by the 1990s; the current major renewal of interest has undoubtedly been contingent on the pioneering developments that emerged some 40 years ago.

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

    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.

  6. Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

    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.

  7. Effect of human adipose tissue-derived mesenchymal-stem-cell bioactive materials on porcine embryo development.

    Park, Hyo-Young; Kim, Eun-Young; Lee, Seung-Eun; Choi, Hyun-Yong; Moon, Jeremiah Jiman; Park, Min-Jee; Son, Yeo-Jin; Lee, Jun-Beom; Jeong, Chang-Jin; Lee, Dong-Sun; Riu, Key-Jung; Park, Se-Pill

    2013-12-01

    Human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) secrete bioactive materials that are beneficial for tissue repair and regeneration. In this study, we characterized human hAT-MSC bioactive material (hAT-MSC-BM), and examined the effect of hAT-MSC-BM on porcine embryo development. hAT-MSC-BM was enriched with several growth factors and cytokines, including fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA), and interleukin 6 (IL6). Among the various concentrations and days of treatment tested, 10% hAT-MSC-BM treatment beginning on culture Day 4 provided the best environment for the in vitro growth of parthenogenetic porcine embryos. While the addition of 10% fetal bovine serum (FBS) increased the hatching rate and the total cell number of parthenogenetic porcine embryos compared with the control and hAT-MSC culture medium group, the best results were from the group cultured with 10% hAT-MSC-BM. Mitochondrial activity was also higher in the 10% hAT-MSC-BM-treated group. Moreover, the relative mRNA expression levels of development and anti-apoptosis genes were significantly higher in the 10% hAT-MSC-BM-treated group than in control, hAT-MSC culture medium, or 10% FBS groups, whereas the transcript abundance of an apoptosis gene was slightly lower. Treatment with 10% hAT-MSC-BM starting on Day 4 also improved the development rate and the total cell number of in vitro-fertilized embryos. This is the first report on the benefits of hAT-MSC-BM in a porcine embryo in vitro culture system. We conclude that hAT-MSC-BM is a new, alternative supplement that can improve the development of porcine embryos during both parthenogenesis and fertilization in vitro.

  8. PPARgamma activation attenuates T-lymphocyte-dependent inflammation of adipose tissue and development of insulin resistance in obese mice

    Unger Thomas

    2010-10-01

    Full Text Available Abstract Background Inflammation of adipose tissue (AT has been recently accepted as a first step towards obesity-mediated insulin resistance. We could previously show that mice fed with high fat diet (HFD develop systemic insulin resistance (IR and glucose intolerance (GI associated with CD4-positive T-lymphocyte infiltration into visceral AT. These T-lymphocytes, when enriched in AT, participate in the development of fat tissue inflammation and subsequent recruitment of proinflammatory macrophages. The aim of this work was to elucidate the action of the insulin sensitizing PPARgamma on T-lymphocyte infiltration during development of IR, and comparison of the PPARgamma-mediated anti-inflammatory effects of rosiglitazone and telmisartan in diet-induced obesity model (DIO-model in mice. Methods In order to investigate the molecular mechanisms underlying early development of systemic insulin resistance and glucose intolerance male C57BL/6J mice were fed with high fat diet (HFD for 10-weeks in parallel to the pharmacological intervention with rosiglitazone, telmisartan, or vehicle. Results Both rosiglitazone and telmisartan were able to reduce T-lymphocyte infiltration into AT analyzed by quantitative analysis of the T-cell marker CD3gamma and the chemokine SDF1alpha. Subsequently, both PPARgamma agonists were able to attenuate macrophage infiltration into AT, measured by the reduction of MCP1 and F4/80 expression. In parallel to the reduction of AT-inflammation, ligand-activated PPARgamma improved diet-induced IR and GI. Conclusion Together the present study demonstrates a close connection between PPARgamma-mediated anti-inflammation in AT and systemic improvement of glucose metabolism identifying T-lymphocytes as one cellular mediator of PPARgamma´s action.

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

    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.

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

    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.

  11. Inflammatory peptides derived from adipose tissue

    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.

    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. De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development.

    Alvarez-Dominguez, Juan R; Bai, Zhiqiang; Xu, Dan; Yuan, Bingbing; Lo, Kinyui Alice; Yoon, Myeong Jin; Lim, Yen Ching; Knoll, Marko; Slavov, Nikolai; Chen, Shuai; Chen, Peng; Lodish, Harvey F; Sun, Lei

    2015-05-01

    Brown adipose tissue (BAT) protects against obesity by promoting energy expenditure via uncoupled respiration. To uncover BAT-specific long non-coding RNAs (lncRNAs), we used RNA-seq to reconstruct de novo transcriptomes of mouse brown, inguinal white, and epididymal white fat and identified ∼1,500 lncRNAs, including 127 BAT-restricted loci induced during differentiation and often targeted by key regulators PPARγ, C/EBPα, and C/EBPβ. One of them, lnc-BATE1, is required for establishment and maintenance of BAT identity and thermogenic capacity. lnc-BATE1 inhibition impairs concurrent activation of brown fat and repression of white fat genes and is partially rescued by exogenous lnc-BATE1 with mutated siRNA-targeting sites, demonstrating a function in trans. We show that lnc-BATE1 binds heterogeneous nuclear ribonucleoprotein U and that both are required for brown adipogenesis. Our work provides an annotated catalog for the study of fat depot-selective lncRNAs and establishes lnc-BATE1 as a regulator of BAT development and physiology.

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

    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.

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

    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. Does bariatric surgery improve adipose tissue function?

    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.

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

    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.

  18. 11-Beta hydroxysteroid dehydrogenase type 2 expression in white adipose tissue is strongly correlated with adiposity.

    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.

  19. The importance of dietary modulation of cAMP and insulin signaling in adipose tissue and the development of obesity

    Madsen, Lise; Kristiansen, Karsten

    2010-01-01

    Adipose tissue plays a pivotal role in whole body energy homeostasis. In this review, we summarize knowledge of the seemingly paradoxical roles of insulin and cyclic adenosine monophosphate (cAMP) signaling in adipocyte differentiation and function, emphasizing the interplay between the two...... of obesity by changing energy expenditure and/or feed efficiency. We review results demonstrating how the balance between different classes of carbohydrates and proteins modulates the obesigenic action of saturated as well as unsaturated fatty acids pointing to insulin as a key determinant in the regulation...

  20. The Facial Adipose Tissue: A Revision.

    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.

  1. Characterization of the expression profiles of adipogenesis-related factors, ZNF423, KLFs and FGF10, during preadipocyte differentiation and abdominal adipose tissue development in chickens.

    Matsubara, Yusuke; Aoki, Michiru; Endo, Tonami; Sato, Kan

    2013-07-01

    Adipogenesis is controlled by a complicated process involving certain transcriptional events. In chicken adipogenesis, peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of preadipocyte differentiation and abdominal fat accumulation. However, in a recent study in mammals, some novel factors related to regulation of adipogenesis, including preadipocyte differentiation, were identified in mammals. Therefore, in this study, we aimed to determine the expression profiles of these mammalian adipogenesis-related factors, such as zinc-finger protein 423 (ZNF423), Krüppel-like factor -2, -5, and -15 (KLF-2, -5, -15), and FGF10, in the chicken (Gallus gallus). Specifically, we analyzed their expression in primary preadipocyte differentiation in vitro and also analyzed their tissue distribution and their temporal expression in adipose tissue development in vivo. During chicken adipocyte differentiation, the gene expression of ZNF423, KLF-2, KLF-5 and FGF10 was found to rapidly decrease in the early stage of preadipocyte differentiation. Expression of ZNF423 then increased in the late stage of differentiation. KLF-15 expression increased in a time-dependent manner for 48 h. Protein expressions of these factors were reflected by Western blot analysis. High levels of aP2, PPARγ and FGF10 mRNA were found in adipose tissue. In addition, aP2, PPARγ and ZNF423 mRNA levels in the adipose tissue were elevated at days 10 and 20. These expression profiles of the adipogenesis-related factors in chicken are, in part, different from mammalian adipogenesis but this seems to reflect the differences in the regulation of adipogenesis and in adipose tissue functions between avians and mammals.

  2. Epicardial adipose tissue in endocrine and metabolic diseases.

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

    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.

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

    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.

  5. Role of bioactive lipid mediators in obese adipose tissue inflammation and endocrine dysfunction.

    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...

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  12. Adipose tissue lymphocytes: types and roles.

    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.

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

    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.

  14. Caspase Induction and BCL2 Inhibition in Human Adipose Tissue

    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

  15. Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obesity and diabetes.

    Bleau, Christian; Karelis, Antony D; St-Pierre, David H; Lamontagne, Lucie

    2015-09-01

    Obesity is associated with a systemic chronic low-grade inflammation that contributes to the development of metabolic disorders such as cardiovascular diseases and type 2 diabetes. However, the etiology of this obesity-related pro-inflammatory process remains unclear. Most studies have focused on adipose tissue dysfunctions and/or insulin resistance in skeletal muscle cells as well as changes in adipokine profile and macrophage recruitment as potential sources of inflammation. However, low-grade systemic inflammation probably involves a complex network of signals interconnecting several organs. Recent evidences have suggested that disturbances in the composition of the gut microbial flora and alterations in levels of gut peptides following the ingestion of a high-fat diet may be a cause of low-grade systemic inflammation that may even precede and predispose to obesity, metabolic disorders or type 2 diabetes. This hypothesis is appealing because the gastrointestinal system is first exposed to nutrients and may thereby represent the first link in the chain of events leading to the development of obesity-associated systemic inflammation. Therefore, the present review will summarize the latest advances interconnecting intestinal mucosal bacteria-mediated inflammation, adipose tissue and skeletal muscle in a coordinated circuitry favouring the onset of a high-fat diet-related systemic low-grade inflammation preceding obesity and predisposing to metabolic disorders and/or type 2 diabetes. A particular emphasis will be given to high-fat diet-induced alterations of gut homeostasis as an early initiator event of mucosal inflammation and adverse consequences contributing to the promotion of extended systemic inflammation, especially in adipose and muscular tissues.

  16. Determinants of human adipose tissue gene expression

    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...... interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index...

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

    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...

  18. Brown adipose tissue in cetacean blubber.

    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

  19. Brown adipose tissue in cetacean blubber.

    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

  20. Metabolic inflammation in inflammatory bowel disease: crosstalk between adipose tissue and bowel.

    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.

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

    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.

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

    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.

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

    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

  4. Delivery of basic fibroblast growth factors from heparinized decellularized adipose tissue stimulates potent de novo adipogenesis.

    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.

  5. Effect of whole linseed and rumen-protected conjugated linoleic acid enriched diets on feedlot performance, carcass characteristics, and adipose tissue development in young Holstein bulls.

    Albertí, P; Gómez, I; Mendizabal, J A; Ripoll, G; Barahona, M; Sarriés, V; Insausti, K; Beriain, M J; Purroy, A; Realini, C

    2013-06-01

    Forty-eight young Holstein bulls (slaughtered at 458.6±9.79 kg body weight) were used to evaluate the effect of whole linseed and conjugated linoleic acid (CLA) supplementation on animal performance, adipose tissue development, and carcass characteristics. The animals were fed with one of four isoenergetic and isoproteic diets: control (0% linseed, 0% CLA), linseed (10% linseed, 0% CLA), CLA (0% linseed, 2% CLA), and linseed plus CLA (10% linseed, 2% CLA). Animal performance and carcass characteristics were unaffected by diet composition. Adding linseed or CLA to the concentrate diet did not result in significant differences in adipocyte size and number or lipogenic enzyme activity. However, while the frequency distribution of subcutaneous adipocyte diameters followed a normal distribution, the frequency distribution of intramuscular adipocyte diameters was not normal in any dietary group (skewness coefficients: 0.8, 1.2, 0.9, 0.8 for control, linseed, CLA, and linseed plus CLA, respectively; Padipose tissue.

  6. Depot-dependent effects of adipose tissue explants on co-cultured hepatocytes

    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...

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

    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.

  8. Automatic Segmentation of Abdominal Adipose Tissue in MRI

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

    2011-01-01

    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...

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

    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 ...

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

    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

  11. Altered autophagy in human adipose tissues in obesity

    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...

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

    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

  13. Involvement of mast cells in adipose tissue fibrosis.

    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.

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

    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.

  15. Preadipocyte and adipose tissue differentiation in meat animals: influence of species and anatomical location.

    Hausman, G J; Basu, U; Wei, S; Hausman, D B; Dodson, M V

    2014-02-01

    Early in porcine adipose tissue development, the stromal-vascular (SV) elements control and dictate the extent of adipogenesis in a depot-dependent manner. The vasculature and collagen matrix differentiate before overt adipocyte differentiation. In the fetal pig, subcutaneous (SQ) layer development is predictive of adipocyte development, as the outer, middle, and inner layers of dorsal SQ adipose tissue develop and maintain layered morphology throughout postnatal growth of SQ adipose tissue. Bovine and ovine fetuses contain brown adipose tissue but SQ white adipose tissue is poorly developed structurally. Fetal adipose tissue differentiation is associated with the precocious expression of several genes encoding secreted factors and key transcription factors like peroxisome proliferator activated receptor (PPAR)γ and CCAAT/-enhancer-binding protein. Identification of adipocyte-associated genes differentially expressed by age, depot, and species in vivo and in vitro has been achieved using single-gene analysis, microarrays, suppressive subtraction hybridization, and next-generation sequencing applications. Gene polymorphisms in PPARγ, cathepsins, and uncoupling protein 3 have been associated with back fat accumulation. Genome scans have mapped several quantitative trait loci (QTL) predictive of adipose tissue-deposition phenotypes in cattle and pigs.

  16. Comparative analysis of cardiovascular development related genes in stem cells isolated from deciduous pulp and adipose tissue.

    Loo, Zhang Xin; Kunasekaran, Wijenthiran; Govindasamy, Vijayendran; Musa, Sabri; Abu Kasim, Noor Hayaty

    2014-01-01

    Human exfoliated deciduous teeth (SHED) and adipose stem cells (ASC) were suggested as alternative cell choice for cardiac regeneration. However, the true functionability of these cells toward cardiac regeneration is yet to be discovered. Hence, this study was carried out to investigate the innate biological properties of these cell sources toward cardiac regeneration. Both cells exhibited indistinguishable MSCs characteristics. Human stem cell transcription factor arrays were used to screen expression levels in SHED and ASC. Upregulated expression of transcription factor (TF) genes was detected in both sources. An almost equal percentage of >2-fold changes were observed. These TF genes fall under several cardiovascular categories with higher expressions which were observed in growth and development of blood vessel, angiogenesis, and vasculogenesis categories. Further induction into cardiomyocyte revealed ASC to express more significantly cardiomyocyte specific markers compared to SHED during the differentiation course evidenced by morphology and gene expression profile. Despite this, spontaneous cellular beating was not detected in both cell lines. Taken together, our data suggest that despite being defined as MSCs, both ASC and SHED behave differently when they were cultured in a same cardiomyocytes culture condition. Hence, vigorous characterization is needed before introducing any cell for treating targeted diseases.

  17. Comparative Analysis of Cardiovascular Development Related Genes in Stem Cells Isolated from Deciduous Pulp and Adipose Tissue

    Zhang Xin Loo

    2014-01-01

    Full Text Available Human exfoliated deciduous teeth (SHED and adipose stem cells (ASC were suggested as alternative cell choice for cardiac regeneration. However, the true functionability of these cells toward cardiac regeneration is yet to be discovered. Hence, this study was carried out to investigate the innate biological properties of these cell sources toward cardiac regeneration. Both cells exhibited indistinguishable MSCs characteristics. Human stem cell transcription factor arrays were used to screen expression levels in SHED and ASC. Upregulated expression of transcription factor (TF genes was detected in both sources. An almost equal percentage of > 2-fold changes were observed. These TF genes fall under several cardiovascular categories with higher expressions which were observed in growth and development of blood vessel, angiogenesis, and vasculogenesis categories. Further induction into cardiomyocyte revealed ASC to express more significantly cardiomyocyte specific markers compared to SHED during the differentiation course evidenced by morphology and gene expression profile. Despite this, spontaneous cellular beating was not detected in both cell lines. Taken together, our data suggest that despite being defined as MSCs, both ASC and SHED behave differently when they were cultured in a same cardiomyocytes culture condition. Hence, vigorous characterization is needed before introducing any cell for treating targeted diseases.

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

    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.

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

    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.

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

    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.

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

    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.

    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

    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. Role of developmental transcription factors in white, brown and beige adipose tissues.

    Hilton, Catriona; Karpe, Fredrik; Pinnick, Katherine E

    2015-05-01

    In this review we discuss the role of developmental transcription factors in adipose tissue biology with a focus on how these developmental genes may contribute to regional variation in adipose tissue distribution and function. Regional, depot-specific, differences in lipid handling and signalling (lipolysis, lipid storage and adipokine/lipokine signalling) are important determinants of metabolic health. At a cellular level, preadipocytes removed from their original depot and cultured in vitro retain depot-specific functional properties, implying that these are intrinsic to the cells and not a function of their environment in situ. High throughput screening has identified a number of developmental transcription factors involved in embryological development, including members of the Homeobox and T-Box gene families, that are strongly differentially expressed between regional white adipose tissue depots and also between brown and white adipose tissue. However, the significance of depot-specific developmental signatures remains unclear. Developmental transcription factors determine body patterning during embryogenesis. The divergent developmental origins of regional adipose tissue depots may explain their differing functional characteristics. There is evidence from human genetics that developmental genes determine adipose tissue distribution: in GWAS studies a number of developmental genes have been identified as being correlated with anthropometric measures of adiposity and fat distribution. Additionally, compelling functional studies have recently implicated developmental genes in both white adipogenesis and the so-called 'browning' of white adipose tissue. Understanding the genetic and developmental pathways in adipose tissue may help uncover novel ways to intervene with the function of adipose tissue in order to promote health.

  5. Is Crohn’s creeping fat an adipose tissue?

    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...

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

    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...

  7. Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development.

    Migliaccio, Silvia; Greco, Emanuela A; Wannenes, Francesca; Donini, Lorenzo M; Lenzi, Andrea

    2014-01-01

    The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.

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

    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.

  9. Adipose tissue and vascular inflammation in coronary artery disease

    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.

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

    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.

  11. Resistin induces lipolysis and suppresses adiponectin secretion in cultured human visceral adipose tissue.

    Chen, Neng; Zhou, Lingmei; Zhang, Zixiang; Xu, Jiaying; Wan, Zhongxiao; Qin, Liqiang

    2014-11-01

    Resistin is an adipokine secreted from adipose tissue, which is likely involved in the development of obesity and insulin resistance via its interaction with other organs, as well as affecting adipose tissue function. The impact of resistin treatment on lipolysis and adiponectin secretion in human visceral adipose tissue is currently unknown. Mesenteric adipose tissue samples were obtained from 14 male subjects [age 54±6 yr, body mass index (BMI) 23.59±0.44 kg/m(2)] undergoing abdominal surgeries. Adipose tissues were cultured and treated with resistin (100 ng/mL, 24h) in the absence or presence of different signaling inhibitors: H89 (1 μM), PD98059 (25 μM) and SB201290 (20 μM) for glycerol and non-esterified fatty acid (NEFA) measurement. Adiponectin level from media at 24 h was also measured via ELISA. Adipose tissue minces after resistin incubation (100 ng/mL, 24 h) were also collected for further Western blotting analysis. Resistin resulted in significant induction of glycerol (3.62±0.57 vs. 5.30±1.11 mmol/L/g tissue, ptissue, ptissue, ptissues via its effect on adipose tissue function.

  12. Alcohol, Adipose Tissue and Lipid Dysregulation

    Jennifer L. Steiner

    2017-02-01

    Full Text Available Chronic alcohol consumption perturbs lipid metabolism as it increases adipose tissue lipolysis and leads to ectopic fat deposition within the liver and the development of alcoholic fatty liver disease. In addition to the recognition of the role of adipose tissue derived fatty acids in liver steatosis, alcohol also impacts other functions of adipose tissue and lipid metabolism. Lipid balance in response to long‐term alcohol intake favors adipose tissue loss and fatty acid efflux as lipolysis is upregulated and lipogenesis is either slightly decreased or unchanged. Study of the lipolytic and lipogenic pathways has identified several regulatory proteins modulated by alcohol that contribute to these effects. Glucose tolerance of adipose tissue is also impaired by chronic alcohol due to decreased glucose transporter‐4 availability at the membrane. As an endocrine organ, white adipose tissue (WAT releases several adipokines that are negatively modulated following chronic alcohol consumption including adiponectin, leptin, and resistin. When these effects are combined with the enhanced expression of inflammatory mediators that are induced by chronic alcohol, a proinflammatory state develops within WAT, contributing to the observed lipodystrophy. Lastly, while chronic alcohol intake may enhance thermogenesis of brown adipose tissue (BAT, definitive mechanistic evidence is currently lacking. Overall, both WAT and BAT depots are impacted by chronic alcohol intake and the resulting lipodystrophy contributes to fat accumulation in peripheral organs, thereby enhancing the pathological state accompanying chronic alcohol use disorder.

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

    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.

  14. Coordinated gene expression between skeletal muscle and intramuscular adipose tissue in growing beef cattle.

    Roberts, S L; Lancaster, P A; DeSilva, U; Horn, G W; Krehbiel, C R

    2015-09-01

    Previous research indicates that metabolism and fiber type of skeletal muscle is related to intramuscular lipid content. It is hypothesized that changes in skeletal muscle gene expression influence adipose tissue development. The objective of this study was to determine differences in the metabolism and intercellular signaling of skeletal muscle fibers within the same muscle group that could be responsible for the initiation of intramuscular adipose tissue development and differentiation. Longissimus dorsi muscle samples were collected from steers ( = 12; 385 d of age; 378 kg BW) grazing wheat pasture. Longissimus muscle samples were dissected under magnification and sorted into 3 categories based on visual stage of adipose tissue development: immature intramuscular adipose tissue (MM), intermediate intramuscular adipose tissue (ME), and mature intramuscular adipose tissue (MA). Additionally, muscle fibers lying adjacent to each intramuscular adipose tissue (IM) category and those not associated with IM tissue were collected and stored separately. Quantitative real-time PCR was used to determine relative fold change in genes involved in metabolism, angiogenesis, formation of extracellular matrix, and intercellular signaling pathways in both LM and IM samples. Gene expression data were analyzed using a GLM that included the fixed effect of tissue. Pearson correlation coefficients were also computed between gene expression in LM and IM tissue samples that were at the same stage of development. and γ mRNA expression were 3.56- and 1.97-fold greater ( development categories. Genes associated with metabolism and angiogenesis in LM tissue showed no differences among stages of development. Myostatin expression did not change in LM tissue; however, expression of and mRNA decreased ( tissue had a strong positive correlation ( ≥ 0.69) with angiogenic growth factors in LM associated with MM IM; however, no correlation was observed in ME or MA IM. These data indicate a

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

    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.

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

    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.

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

    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

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

    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

  19. Macronutrient composition determines accumulation of persistent organic pollutants from dietary exposure in adipose tissue of mice

    Myrmel, Lene Secher; Fjære, Even; Midtbø, Lisa Kolden;

    2016-01-01

    Accumulation of persistent organic pollutants (POPs) has been linked to adipose tissue expansion. As different nutrients modulate adipose tissue development, we investigated the influence of dietary composition on POP accumulation, obesity development and related disorders. Lifespan was determined...... or as mixtures in combination with different diets: one low fat diet and two high fat diets with different protein:sucrose ratios. We measured accumulation of POPs in adipose tissue and liver and determined obesity development, glucose tolerance, insulin sensitivity and hepatic expression of genes involved...... in metabolism of xenobiotics. Compared with mice fed diets with a low protein:sucrose ratio, mice fed diets with a high protein:sucrose ratio had significantly lower total burden of POPs in adipose tissue, were protected from obesity development and exhibited enhanced hepatic expression of genes involved...

  20. Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis.

    Lim, Sharon; Hosaka, Kayoko; Nakamura, Masaki; Cao, Yihai

    2016-06-21

    Many types of cancer develop in close association with highly vascularized adipose tissues. However, the role of adipose pre-existing vascular beds on tumor growth and angiogenesis is unknown. Here we report that pre-existing microvascular density in tissues where tumors originate is a crucial determinant for tumor growth and neovascularization. In three independent tumor types including breast cancer, melanoma, and fibrosarcoma, inoculation of tumor cells in the subcutaneous tissue, white adipose tissue (WAT), and brown adipose tissue (BAT) resulted in markedly differential tumor growth rates and angiogenesis, which were in concordance with the degree of pre-existing vascularization in these tissues. Relative to subcutaneous tumors, WAT and BAT tumors grew at accelerated rates along with improved neovascularization, blood perfusion, and decreased hypoxia. Tumor cells implanted in adipose tissues contained leaky microvessel with poor perivascular cell coverage. Thus, adipose vasculature predetermines the tumor microenvironment that eventually supports tumor growth.

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

    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...

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

    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.

  3. TAF7L modulates brown adipose tissue formation

    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...

  4. New concepts in white adipose tissue physiology

    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.

  5. Two types of brown adipose tissue in humans.

    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.

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

    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.

  7. Assessment of in situ adipose tissue inflammation by microdialysis

    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...

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

    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

  9. Adipose tissue trans fatty acids and changes in body weight and waist circumference

    Hansen, C.P.; Berentzen, T.L.; Østergaard, J.N.

    Previous studies have suggested that intake of trans fatty acids (TFA) may play a role in the development of obesity. For fatty acids not synthesized endogenously in humans, such as TFA, the proportions in adipose tissue tend to correlate well with the habitual dietary intake. Biomarkers may prov...... provide a more accurate measure of habitual TFA intake than dietary questionnaires. Our objective was to investigate the associations between specific TFA in adipose tissue and subsequent changes in body weight and waist circumference (WC)....

  10. Effects of glucose and insulin on secretion of amyloid‐β by human adipose tissue cells

    2016-01-01

    Objective Obesity and type 2 diabetes mellitus are risk factors for developing Alzheimer disease. Overlapping patterns of metabolic dysfunction may be common molecular links between these complex diseases. Amyloid‐β (Aβ) precursor protein and associated β‐ and γ‐secretases are expressed in adipose tissue. Aβ precursor protein is up‐regulated with obesity and correlated to insulin resistance. Aβ may be secreted by adipose tissue, its production may be regulated through metabolic pathways, and ...

  11. Biomimetic injectable HUVEC-adipocytes/collagen/alginate microsphere co-cultures for adipose tissue engineering.

    Yao, Rui; Zhang, Renji; Lin, Feng; Luan, Jie

    2013-05-01

    Engineering adipose tissue that has the ability to engraft and establish a vascular supply is a laudable goal that has broad clinical relevance, particularly for tissue reconstruction. In this article, we developed novel microtissues from surface-coated adipocyte/collagen/alginate microspheres and human umbilical vein endothelial cells (HUVECs) co-cultures that resembled the components and structure of natural adipose tissue. Firstly, collagen/alginate hydrogel microspheres embedded with viable adipocytes were obtained to mimic fat lobules. Secondly, collagen fibrils were allowed to self-assemble on the surface of the microspheres to mimic collagen fibrils surrounding the fat lobules in the natural adipose tissue and facilitate HUVEC attachment and co-cultures formation. Thirdly, the channels formed by the gap among the microspheres served as the room for in vitro prevascularization and in vivo blood vessel development. The endothelial cell layer outside the microspheres was a starting point of rapid vascular ingrowth. Adipose tissue formation was analyzed for 12 weeks at 4-week intervals by subcutaneous injection into the head of node mice. The vasculature in the regenerated tissue showed functional anastomosis with host blood vessels. Long-term stability of volume and weight of the injection was observed, indicating that the vasculature formed within the constructs benefited the formation, maturity, and maintenance of adipose tissue. This study provides a microsurgical method for adipose regeneration and construction of biomimetic model for drug screening studies.

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

    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.

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

    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.

  14. Long-term allergen exposure induces adipose tissue inflammation and circulatory system injury.

    Jung, Chien-Cheng; Su, Huey-Jen

    2016-05-01

    The purpose of this study was to study whether allergen exposure can induce inflammation and lower the anti-inflammation levels in serum and in adipose tissues, and further develop cardiovascular injury. Our data showed that heart rate was significantly higher in the OVA-challenged mice compared to control mice. Moreover, there were higher expressions of pro-inflammation genes in the OVA-challenged mice in adipose tissues, and the expressions of anti-inflammation genes were lower. The levels of inflammation mediators were associated in serum and adipose tissues. The level of circulatory injury lactate dehydrogenase was significantly associated with the levels of E-selectin, resistin and adiponectin in the serum. The hematoxylin and eosin and immunohistochemistry stains indicated the OVA-challenged mice had higher levels of inflammation. In summary, the current study demonstrated allergen exposure can cause cardiovascular injury, and inflammatory mediators in adipose tissues play an important role in the pathogenesis of cardiovascular injury.

  15. Brown adipose tissue and novel therapeutic approaches to treat metabolic disorders.

    Roman, Sabiniano; Agil, Ahmad; Peran, Macarena; Alvaro-Galue, Eduardo; Ruiz-Ojeda, Francisco J; Fernández-Vázquez, Gumersindo; Marchal, Juan A

    2015-04-01

    In humans, 2 functionally different types of adipose tissue coexist: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is involved in energy storage, whereas BAT is involved in energy expenditure. Increased amounts of WAT may contribute to the development of metabolic disorders, such as obesity-associated type 2 diabetes mellitus and cardiovascular diseases. In contrast, the thermogenic function of BAT allows high consumption of fatty acids because of the activity of uncoupling protein 1 in the internal mitochondrial membrane. Interestingly, obesity reduction and insulin sensitization have been achieved by BAT activation-regeneration in animal models. This review describes the origin, function, and differentiation mechanisms of BAT to identify new therapeutic strategies for the treatment of metabolic disorders related to obesity. On the basis of the animal studies, novel approaches for BAT regeneration combining stem cells from the adipose tissue with active components, such as melatonin, may have potential for the treatment of metabolic disorders in humans.

  16. Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

    Ahlqvist, Emma; Osmark, Peter; Kuulasmaa, Tiina

    2013-01-01

    Low-grade inflammation in obesity is associated with accumulation of the macrophage-derived cytokine osteopontin (OPN) in adipose tissue and induction of local as well as systemic insulin resistance. Since glucose-dependent insulinotropic polypeptide (GIP) is a strong stimulator of adipogenesis...... and may play a role in the development of obesity, we explored whether GIP directly would stimulate OPN expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher...... for transmembrane activity. Carriers of the A allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone but also as a trigger of inflammation and insulin resistance in adipose tissue...

  17. Adipose tissue, the skeleton and cardiovascular disease

    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. Increased asthma and adipose tissue inflammatory gene expression with obesity and Inuit migration to a western country

    Backer, Vibeke; Baines, Katherine J; Powell, Heather;

    2016-01-01

    BACKGROUND: An overlap between obesity and asthma exists, and inflammatory cells in adipose tissue could drive the development of asthma. Comparison of adipose tissue gene expression among Inuit living in Greenland to those in Denmark provides an opportunity to assess how changes in adipose tissue...... inflammation can be modified by migration and diet. OBJECTIVE: To examine mast cell and inflammatory markers in adipose tissue and the association with asthma. METHODS: Two Inuit populations were recruited, one living in Greenland and another in Denmark. All underwent adipose subcutaneous biopsy, followed...... by clinical assessment of asthma, and measurement of AHR. Adipose tissue biopsies were homogenised, RNA extracted, and PCR was performed to determine the relative gene expression of mast cell (tryptase, chymase, CPA3) and inflammatory markers (IL-6, IL-1β, and CD163). RESULTS: Of the 1059 Greenlandic Inuit...

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

    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.

  20. Cidea controls lipid droplet fusion and lipid storage in brown and white adipose tissue.

    Wu, Lizhen; Zhou, Linkang; Chen, Cheng; Gong, Jingyi; Xu, Li; Ye, Jing; Li, De; Li, Peng

    2014-01-01

    Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes, fatty liver and cardiovascular diseases. The lipid droplet (LD) is an important subcellular organelle responsible for lipid storage. We previously observed that Fsp27, a member of the CIDE family proteins, is localized to LD-contact sites and promotes atypical LD fusion and growth. Cidea, a close homolog of Fsp27, is expressed at high levels in brown adipose tissue. However, the exact role of Cidea in promoting LD fusion and lipid storage in adipose tissue remains unknown. Here, we expressed Cidea in Fsp27-knockdown adipocytes and observed that Cidea has similar activity to Fsp27 in promoting lipid storage and LD fusion and growth. Next, we generated Cidea and Fsp27 double-deficient mice and observed that these animals had drastically reduced adipose tissue mass and a strong lean phenotype. In addition, Cidea/Fsp27 double-deficient mice had improved insulin sensitivity and were intolerant to cold. Furthermore, we observed that the brown and white adipose tissues of Cidea/Fsp27 double-deficient mice had significantly reduced lipid storage and contained smaller LDs compared to those of Cidea or Fsp27 single deficient mice. Overall, these data reveal an important role of Cidea in controlling lipid droplet fusion, lipid storage in brown and white adipose tissue, and the development of obesity.

  1. The "Big Bang" in obese fat: Events initiating obesity-induced adipose tissue inflammation.

    Wensveen, Felix M; Valentić, Sonja; Šestan, Marko; Turk Wensveen, Tamara; Polić, Bojan

    2015-09-01

    Obesity is associated with the accumulation of pro-inflammatory cells in visceral adipose tissue (VAT), which is an important underlying cause of insulin resistance and progression to diabetes mellitus type 2 (DM2). Although the role of pro-inflammatory cytokines in disease development is established, the initiating events leading to immune cell activation remain elusive. Lean adipose tissue is predominantly populated with regulatory cells, such as eosinophils and type 2 innate lymphocytes. These cells maintain tissue homeostasis through the excretion of type 2 cytokines, such as IL-4, IL-5, and IL-13, which keep adipose tissue macrophages (ATMs) in an anti-inflammatory, M2-like state. Diet-induced obesity is associated with the loss of tissue homeostasis and development of type 1 inflammatory responses in VAT, characterized by IFN-γ. A key event is a shift of ATMs toward an M1 phenotype. Recent studies show that obesity-induced adipocyte hypertrophy results in upregulated surface expression of stress markers. Adipose stress is detected by local sentinels, such as NK cells and CD8(+) T cells, which produce IFN-γ, driving M1 ATM polarization. A rapid accumulation of pro-inflammatory cells in VAT follows, leading to inflammation. In this review, we provide an overview of events leading to adipose tissue inflammation, with a special focus on adipose homeostasis and the obesity-induced loss of homeostasis which marks the initiation of VAT inflammation.

  2. Exercise Regulation of Marrow Adipose Tissue

    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

  3. Exercise Regulation of Marrow Adipose Tissue

    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

  4. Organotypic culture of human bone marrow adipose tissue.

    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.

  5. Dietary Protein Source and Cyclooxygenase-Inhibition Influence Development of Diet-Induced Obesity, Glucose Homeostasis and Brown Adipose Tissue

    Aune, Ulrike Liisberg

    The prevalence of obesity and associated diseases, such as Type 2 diabetes, cardiovascular disease and non-alcoholic fatty liver disease, are accelerating worldwide and require urgent attention. Many of the obesity-related morbidities are likely to originate from a state of chronic low-grade infl......The prevalence of obesity and associated diseases, such as Type 2 diabetes, cardiovascular disease and non-alcoholic fatty liver disease, are accelerating worldwide and require urgent attention. Many of the obesity-related morbidities are likely to originate from a state of chronic low......-grade inflammation accompanying the increasing adipose mass. In order to investigate the relationship between obesity, inflammation and insulin resistance, we ran an experiment feeding mice a high fat/high sucrose diet supplemented with the antiinflammatory cyclooxygenase-inhibitor, indomethacin. We saw...... of endogenous n-3 PUFAs present in phospholipid fractions of the cod fillets was reflected in the red-blood cells and the livers of the mice. This subsequently caused an altered endocannabinoid tone in the mice. In addition to amino acids, changing protein sources also alters fat, which may affect the consumer...

  6. Identification of the avian RBP7 gene as a new adipose-specific gene and RBP7 promoter-driven GFP expression in adipose tissue of transgenic quail.

    Ahn, Jinsoo; Shin, Sangsu; Suh, Yeunsu; Park, Ju Yeon; Hwang, Seongsoo; Lee, Kichoon

    2015-01-01

    The discovery of an increasing number of new adipose-specific genes has significantly contributed to our understanding of adipose tissue biology and the etiology of obesity and its related diseases. In the present study, comparison of gene expression profiles among various tissues was performed by analysis of chicken microarray data, leading to identification of RBP7 as a novel adipose-specific gene in chicken. Adipose-specific expression of RBP7 in the avian species was further confirmed at the protein and mRNA levels. Examination of the transcription factor binding sites within the chicken RBP7 promoter by Matinspector software revealed potential binding sites for adipogenic transcription factors. This led to the hypothesis that the RBP7 promoter can be utilized to overexpress a transgene in adipose tissue in order to further investigate the function of a transgene in adipose tissue. Several lines of transgenic quail containing a green fluorescent protein (GFP) gene under the control of the RBP7 promoter were generated using lentivirus-mediated gene transfer. The GFP expression in transgenic quail was specific to adipose tissue and increased after adipocyte differentiation. This expression pattern was consistent with endogenous RBP7 expression, suggesting the RBP7 promoter is sufficient to overexpress a gene of interest in adipose tissue at later developmental stages. These findings will lead to the establishment of a novel RBP7 promoter cassette which can be utilized for overexpressing genes of interest in adipose tissue in vivo to study the function of genes in adipose tissue development and lipid metabolism.

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

    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.

  8. Controlled cellular energy conversion in brown adipose tissue thermogenesis

    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.

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

    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.

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

    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.

  11. Regulation of brown adipose tissue by stress and sex

    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

  12. Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

    2015-08-01

    oncogenes; inactivation of tumor suppression genes; and interaction between cancer cells and tumor-associated stroma and tumor- associated macrophages ...into inflamed tissue and dif- ferentiate into macrophages , which coordinate inflammatory re- sponses by producing chemokines and clearing debris by...AWARD NUMBER: W81XWH-10-1-0275 TITLE: Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions PRINCIPAL INVESTIGATOR

  13. Calorie Restriction Prevents Metabolic Aging Caused by Abnormal SIRT1 Function in Adipose Tissues.

    Xu, Cheng; Cai, Yu; Fan, Pengcheng; Bai, Bo; Chen, Jie; Deng, Han-Bing; Che, Chi-Ming; Xu, Aimin; Vanhoutte, Paul M; Wang, Yu

    2015-05-01

    Adipose tissue is a pivotal organ determining longevity, due largely to its role in maintaining whole-body energy homeostasis and insulin sensitivity. SIRT1 is a NAD-dependent protein deacetylase possessing antiaging activities in a wide range of organisms. The current study demonstrates that mice with adipose tissue-selective overexpression of hSIRT1(H363Y), a dominant-negative mutant that disrupts endogenous SIRT1 activity, show accelerated development of metabolic aging. These mice, referred to as Adipo-H363Y, exhibit hyperglycemia, dyslipidemia, ectopic lipid deposition, insulin resistance, and glucose intolerance at a much younger age than their wild-type littermates. The metabolic defects of Adipo-H363Y are associated with abnormal epigenetic modifications and chromatin remodeling in their adipose tissues, as a result of excess accumulation of biotin, which inhibits endogenous SIRT1 activity, leading to increased inflammation, cellularity, and collagen deposition. The enzyme acetyl-CoA carboxylase 2 plays an important role in biotin accumulation within adipose tissues of Adipo-H363Y. Calorie restriction prevents biotin accumulation, abolishes abnormal histone biotinylation, and completely restores the metabolic and adipose functions of Adipo-H363Y. The effects are mimicked by short-term restriction of biotin intake, an approach potentially translatable to humans for maintaining the epigenetic and chromatin remodeling capacity of adipose tissues and preventing aging-associated metabolic disorders.

  14. Adipogenesis: new insights into brown adipose tissue differentiation.

    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.

  15. Biomarkers of Habitual Fish Intake in Adipose-Tissue

    Marckmann, P.; Lassen, Anne Dahl; Haraldsdottir, H.;

    1995-01-01

    of the 8-mo study period. The adipose tissue fatty acid composition of each individual was determined by gas chromatography as the mean of two gluteal biopsies, obtained in the first and the last month of the study. The daily consumption of fish and of marine n-3 PUFAs in absolute terms (g......The association between habitual fish and marine n-3 polyunsaturated fatty acid (PUFA) intake, and the fatty acid composition of subcutaneous fat was studied in 24 healthy young volunteers. Habitual dietary intakes were estimated from three 7-d weighed food records made at months 0, 5, and 8....../d) was significantly associated with adipose tissue docosahexaenoic acid content (DHA; r = 0.55 and 0.58, respectively, P acid contents. Our study indicates that the adipose tissue DHA content is the biomarker of choice for the assessment of long...

  16. Bovine dedifferentiated adipose tissue (DFAT) cells

    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...

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

    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

  18. OXIDATIVE STRESS: ITS ROLE IN INSULIN SECRETION, HORMONE RECEPTION BY ADIPOCYTES AND LIPOLYSIS IN ADIPOSE TISSUE

    V. V. Ivanov

    2014-01-01

    Full Text Available Oxidative stress is one of the pathogenetic components of many diseases during which generation of reactive oxigen species increases and the capacity of the antioxidant protection system diminishes. In the research of the last decades special attention has been given to adipose tissue, production of adipokines by it and their role in development of immunoresistance associated with formation of the metabolic syndrome and diabetes.Search for methods of therapeutic correction of adipokine secretion disorders, their influence on metabolism of separate cells and the organism on the whole as well as development of new approaches to correction of disorders in cell sensitivity to insulin are extremely topical nowadays. Systematization and consolidation of accumulated data allow to determine the strategies of further research more accurately; as a result, we have attempted to summarize and analyze the accumulated data on the role of adipose tissue in oxidative stress development.On the basis of literature data and the results of the personal investigations, the role of adipose tissue in forming oxidative stress in diabetes has been analyzed in the article. Brief description of adipose tissue was given as a secretory organ regulating metabolic processes in adipocytes and influencing functions of various organs and systems of the body. Mechanisms of disorder in insulin secretion as well as development of insulin sesistance in type I diabetes were described along with the contribution of lipolysis in adipose tissue to these processes.

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

    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.

  20. Chagas disease, adipose tissue and the metabolic syndrome

    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.

  1. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

    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......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...

  2. Adipose tissue Fatty Acid patterns and changes in antrhropometry

    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...

  3. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

    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.

  4. Developmental regulation of adipose tissue growth through hyperplasia and hypertrophy in the embryonic Leghorn and broiler.

    Chen, Paula; Suh, Yeunsu; Choi, Young Min; Shin, Sangsu; Lee, Kichoon

    2014-07-01

    The United States is a world leader in poultry production, which is the reason why achieving better performance and muscle growth each year is a necessity. Reducing accretion of adipose tissue is another important factor for poultry producers because this allows more nutrients to be directed toward muscle growth, but the effect of embryonic adipose growth on posthatch development has not been fully understood. The purpose of this study was to investigate the total DNA mass, morphological characteristics, differentiation markers, and triglyceride breakdown factors of embryonic adipose tissue, and their relation to hyperplastic and hypertrophic growth within layers (Leghorn) and meat-type chickens (broilers). After embryonic day (E) 12, broiler weight was significantly higher than Leghorn, and this trend continued throughout the rest of incubation and posthatch (P hypertrophy. At embryonic stages and early posthatch, layer- and meat-type chicken adipose growth does not differ, which suggests breed differences occur posthatch.

  5. The effect of NALP3 inflammasome pathway in visceral adipose tissue on the development of insulin resistance in catch-up growth after food restriction in rats

    李燕

    2014-01-01

    Objective To investigate the effects of catch-up growth(CUG)on the natch domain,leucine-rich repeat and PVD-containing protein 3(NALP3)inflammasome pathway in visceral adipose tissue(VAT)and the mechanism of insulin resistance(IR)in CUG.Methods Sprague-Dawley rats were randomly divided into the normal chow(NC)and the catch-up growth group(CUG).General characteristics,glucose infusion rate60-120(GIR60-120)in hyperinsulinemic-euglycemic clamp and expression of NALP3 inflammasome,caspase1(p10)and

  6. Depot-dependent effects of adipose tissue explants on co-cultured hepatocytes.

    Zhen-Yu Du

    Full Text Available 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 adipose tissues. Expressions of inflammation related genes (IL-6, TNF-α, COX-2 were higher in the inguinal than the epididymal ATE. Similarly, expressions of marker genes of macrophage and monocyte (MPEG-1, CD68, F4/80, CD64 were higher in the stromal vascular fraction (SVF isolated from inguinal ATE than that from epididymal ATE. However, expressions of lipolysis related genes (ATGL, HSL, perilipin-1 were higher in the epididymal adipocytes than inguinal adipocytes. Moreover, secretion of IL-6 and PGE(2 was higher from inguinal ATEs than from epididymal ATEs. There was a trend that the total levels of IL-6, TNF-α 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 a stronger cytotoxic response and higher level of insulin resistance in the co-cultured hepatocytes. In conclusion, our results reveal depot-dependent effects of ATEs on co-cultured primary hepatocytes, which in part may be related to a more pronounced infiltration of stromal vascular cells (SVCs, particularly macrophages, in inguinal adipose tissue resulting in stronger responses in terms of hepatotoxicity and insulin-resistance.

  7. Vitamin D and adipose tissue - more than storage

    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.

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

    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. Metabolic characteristics and therapeutic potential of brown and ‘beige’ adipose tissues

    Ekaterina Olegovna Koksharova

    2014-10-01

    Full Text Available According to the International Diabetes Federation, 10.9 million people have diabetes mellitus (DM in Russia; however, only up to 4 million are registered. In addition, 11.9 million people have impaired glucose tolerance and impaired fasting glucose levels [1].One of the significant risk factors for type 2 DM (T2DM is obesity, which increases insulin resistance (IR. IR is the major pathogenetic link to T2DM.According to current concepts, there are three types of adipose tissue: white adipose tissue (WAT, brown adipose tissue (BAT and ‘beige’, of which the last two types have a thermogenic function. Some research results have revealed the main stages in the development of adipocytes; however, there is no general consensus regarding the development of ‘beige’ adipocytes. Furthermore, the biology of BAT and ‘beige’ adipose tissue is currently being intensively investigated, and some key transcription factors, signalling pathways and hormones that promote the development and activation of these tissues have been identified. The most discussed hormones are irisin and fibroblast growth factor 21, which have established positive effects on BAT and ‘beige’ adipose tissue with regard to carbohydrate, lipid and energy metabolism. The primary imaging techniques used to investigate BAT are PET-CT with 18F-fluorodeoxyglucose and magnetic resonance spectroscopy.With respect to the current obesity epidemic and associated diseases, including T2DM, there is a growing interest in investigating adipogenesis and the possibility of altering this process. BAT and ‘beige’ adipose tissue may be targets for developing drugs directed against obesity and T2DM.

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

    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.

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

    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....

  12. Effect of fetal undernutrition and postnatal overfeeding on rat adipose tissue and organ growth at early stages of postnatal development.

    Munoz-Valverde, D; Rodríguez-Rodríguez, P; Gutierrez-Arzapalo, P Y; López de Pablo, A L; Carmen González, M; López-Giménez, R; Somoza, B; Arribas, S M

    2015-01-01

    Intrauterine and perinatal life are critical periods for programming of cardiometabolic diseases. However, their relative role remains controversial. We aimed to assess, at weaning, sex-dependent alterations induced by fetal or postnatal nutritional interventions on key organs for metabolic and cardiovascular control. Fetal undernutrition was induced by dam food restriction (50 % from mid-gestation to delivery) returning to ad libitum throughout lactation (Maternal Undernutrition, MUN, 12 pups/litter). Postnatal overfeeding (POF) was induced by litter size reduction from normally fed dams (4 pups/litter). Compared to control, female and male MUN offspring exhibited: 1) low birth weight and accelerated growth, reaching similar weight and tibial length by weaning, 2) increased glycemia, liver and white fat weights; 3) increased ventricular weight and tendency to reduced kidney weight (males only). Female and male POF offspring showed: 1) accelerated growth; 2) increased glycemia, liver and white fat weights; 3) unchanged heart and kidney weights. In conclusion, postnatal accelerated growth, with or without fetal undernutrition, induces early alterations relevant for metabolic disease programming, while fetal undernutrition is required for heart abnormalities. The progression of cardiac alterations and their role on hypertension development needs to be evaluated. The similarities between sexes in pre-pubertal rats suggest a role of sex-hormones in female protection against programming.

  13. Adipose Tissue Dysfunction : Clinical Relevance and Diagnostic Possibilities

    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

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

    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.

  15. Spice Up Your Life: Adipose Tissue and Inflammation

    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.

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

    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

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

    Alexopoulos, Nikolaos; Katritsis, Demosthenes; Raggi, Paolo

    2014-03-01

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

  18. Adrenal gland volume, intra-abdominal and pericardial adipose tissue in major depressive disorder.

    Kahl, Kai G; Schweiger, Ulrich; Pars, Kaweh; Kunikowska, Alicja; Deuschle, Michael; Gutberlet, Marcel; Lichtinghagen, Ralf; Bleich, Stefan; Hüper, Katja; Hartung, Dagmar

    2015-08-01

    Major depressive disorder (MDD) is associated with an increased risk for the development of cardio-metabolic diseases. Increased intra-abdominal (IAT) and pericardial adipose tissue (PAT) have been found in depression, and are discussed as potential mediating factors. IAT and PAT are thought to be the result of a dysregulation of the hypothalamus-pituitary-adrenal axis (HPAA) with subsequent hypercortisolism. Therefore we examined adrenal gland volume as proxy marker for HPAA activation, and IAT and PAT in depressed patients. Twenty-seven depressed patients and 19 comparison subjects were included in this case-control study. Adrenal gland volume, pericardial, intraabdominal and subcutaneous adipose tissue were measured by magnetic resonance imaging. Further parameters included factors of the metabolic syndrome, fasting cortisol, fasting insulin, and proinflammatory cytokines. Adrenal gland and pericardial adipose tissue volumes, serum concentrations of cortisol and insulin, and serum concentrations tumor-necrosis factor-α were increased in depressed patients. Adrenal gland volume was positively correlated with intra-abdominal and pericardial adipose tissue, but not with subcutaneous adipose tissue. Our findings point to the role of HPAA dysregulation and hypercortisolism as potential mediators of IAT and PAT enlargement. Further studies are warranted to examine whether certain subtypes of depression are more prone to cardio-metabolic diseases.

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

    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...

  20. Alteration of local adipose tissue trace element homeostasis as a possible mechanism of obesity-related insulin resistance.

    Tinkov, Alexey A; Sinitskii, Anton I; Popova, Elizaveta V; Nemereshina, Olga N; Gatiatulina, Evgenia R; Skalnaya, Margarita G; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-09-01

    The mechanisms of association between obesity and the related metabolic disturbances in general and insulin resistance in particular are extensively studied. Taking into account a key role of adipose tissue insulin resistance in the development of systemic obesity-related insulin resistance, the estimation of mechanisms linking increased adiposity and impaired insulin signaling in adipocytes will allow to develop novel prophylactic and therapeutic approaches to treatment of these states. A number of trace elements like chromium, zinc, and vanadium have been shown to take part in insulin signaling via various mechanisms. Taking into account a key role of adipocyte in systemic carbohydrate homeostasis it can be asked if trace element homeostasis in adipose tissue may influence regulatory mechanisms of glucose metabolism. We hypothesize that caloric excess through currently unknown mechanisms results in decreased chromium, vanadium, and zinc content in adipocytes. Decreased content of trace elements in the adipose tissue causes impairment of intra-adipocyte insulin signaling subsequently leading to adipose tissue insulin resistance. The latter significantly contributes to systemic insulin resistance and further metabolic disruption in obesity. It is also possible that decreased adipose tissue trace element content is associated with dysregulation of insulin-sensitizing and proinflammatory adipokines also leading to insulin resistance. We hypothesize that insulin resistance and adipokine dysbalance increase the severity of obesity subsequently aggravating alteration of adipose tissue trace element balance. Single indications of high relative adipose tissue trace element content, decreased Cr, V, and Zn content in obese adipose tissue, and tight association between fat tissue chromium, vanadium, and zinc levels and metabolic parameters in obesity may be useful for hypothesis validation. If our hypothesis will be confirmed by later studies, adipose tissue chromium

  1. 兰州大尾羊尾部脂肪细胞发育性变化研究%Study on Development Changes of Tail Adipose Tissue in Lanzhou Fat-tailed Sheep

    何晓军; 臧荣鑫; 许小红; 马永华; 翟育忠

    2012-01-01

    为了研究兰州大尾羊尾部脂肪组织的发育变化,运用显微成像处理系统中的Measure distance功能,测定样品的脂肪细胞形态学参数.结果表明,兰州大尾羊尾部脂肪细胞大小随生长发育呈现持续增加的趋势.说明兰州大尾羊尾部脂肪的沉积以脂肪细胞增大为主要方式.%To investigate the development changes of tail adipose tissue in Lanzhou fat-tailed sheep,morphological parameters of adiposities were measured by using Measure distance function of the microscopic imaging processing system. The results showed that the size of tail adipose cells increased with the growth of the sheep. It was concluded that the size increase of the tail adiposities was the main way of fat deposition in Lanzhou fat-tailed sheep.

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

    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.

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

    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.

  4. The role of JAK-STAT signaling in adipose tissue function.

    Richard, Allison J; Stephens, Jacqueline M

    2014-03-01

    Adipocytes play important roles in lipid storage, energy homeostasis and whole body insulin sensitivity. The JAK-STAT (Janus Kinase-Signal Transducer and Activator of Transcription) pathway mediates a variety of physiological processes including development, hematopoiesis, and inflammation. Although the JAK-STAT signaling pathway occurs in all cells, this pathway can mediate cell specific responses. Studies in the last two decades have identified hormones and cytokines that activate the JAK-STAT signaling pathway. These cytokines and hormones have profound effects on adipocytes. The content of this review will introduce the types of adipocytes and immune cells that make up adipose tissue, the impact of obesity on adipose cellular composition and function, and the general constituents of the JAK-STAT pathway and how its activators regulate adipose tissue development and physiology. A summary of the identification of STAT target genes in adipocytes reveals how these transcription factors impact various areas of adipocyte metabolism including insulin action, modulation of lipid stores, and glucose homeostasis. Lastly, we will evaluate exciting new data linking the JAK-STAT pathway and brown adipose tissue and consider the future outlook in this area of investigation. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  5. File list: DNS.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available DNS.Adp.20.AllAg.Adipose_Tissue,_White hg19 DNase-seq Adipocyte Adipose Tissue, Whi...te http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Adp.20.AllAg.Adipose_Tissue,_White.bed ...

  6. File list: ALL.Adp.20.AllAg.Adipose_Tissue [Chip-atlas[Archive

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  7. File list: ALL.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  8. File list: His.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  9. File list: Pol.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  10. File list: NoD.Adp.10.AllAg.Adipose_Tissue [Chip-atlas[Archive

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  11. File list: NoD.Adp.20.AllAg.Adipose_Tissue [Chip-atlas[Archive

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  12. File list: NoD.Adp.05.AllAg.Adipose_Tissue [Chip-atlas[Archive

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  13. File list: Oth.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  14. File list: Pol.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  15. File list: ALL.Adp.10.AllAg.Adipose_Tissue [Chip-atlas[Archive

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  16. File list: ALL.Adp.05.AllAg.Adipose_Tissue [Chip-atlas[Archive

    Full Text Available ALL.Adp.05.AllAg.Adipose_Tissue hg19 All antigens Adipocyte Adipose Tissue SRX13473...2 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Adp.05.AllAg.Adipose_Tissue.bed ...

  17. File list: NoD.Adp.50.AllAg.Adipose_Tissue [Chip-atlas[Archive

    Full Text Available NoD.Adp.50.AllAg.Adipose_Tissue hg19 No description Adipocyte Adipose Tissue SRX134...732 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Adp.50.AllAg.Adipose_Tissue.bed ...

  18. File list: ALL.Adp.50.AllAg.Adipose_Tissue [Chip-atlas[Archive

    Full Text Available ALL.Adp.50.AllAg.Adipose_Tissue hg19 All antigens Adipocyte Adipose Tissue SRX13473...2 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Adp.50.AllAg.Adipose_Tissue.bed ...

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

    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

  20. File list: Oth.Adp.05.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  1. File list: DNS.Adp.05.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available DNS.Adp.05.AllAg.Adipose_Tissue,_White hg19 DNase-seq Adipocyte Adipose Tissue, White... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Adp.05.AllAg.Adipose_Tissue,_White.bed ...

  2. File list: His.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available His.Adp.10.AllAg.Adipose_Tissue,_White hg19 Histone Adipocyte Adipose Tissue, White... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Adp.10.AllAg.Adipose_Tissue,_White.bed ...

  3. File list: ALL.Adp.05.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  4. File list: DNS.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available DNS.Adp.50.AllAg.Adipose_Tissue,_White hg19 DNase-seq Adipocyte Adipose Tissue, White... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Adp.50.AllAg.Adipose_Tissue,_White.bed ...

  5. File list: Unc.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available Unc.Adp.50.AllAg.Adipose_Tissue,_White hg19 Unclassified Adipocyte Adipose Tissue, White... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Adp.50.AllAg.Adipose_Tissue,_White.bed ...

  6. File list: Unc.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available Unc.Adp.20.AllAg.Adipose_Tissue,_White hg19 Unclassified Adipocyte Adipose Tissue, White... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Adp.20.AllAg.Adipose_Tissue,_White.bed ...

  7. File list: ALL.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available ALL.Adp.10.AllAg.Adipose_Tissue,_White hg19 All antigens Adipocyte Adipose Tissue, White...X821821,SRX821815,SRX821811,SRX821817,SRX821809,SRX821810 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Adp.10.AllAg.Adipose_Tissue,_White.bed ...

  8. File list: Unc.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available Unc.Adp.10.AllAg.Adipose_Tissue,_White hg19 Unclassified Adipocyte Adipose Tissue, White... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Adp.10.AllAg.Adipose_Tissue,_White.bed ...

  9. File list: His.Adp.05.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available His.Adp.05.AllAg.Adipose_Tissue,_White hg19 Histone Adipocyte Adipose Tissue, White... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Adp.05.AllAg.Adipose_Tissue,_White.bed ...

  10. File list: ALL.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available ALL.Adp.20.AllAg.Adipose_Tissue,_White hg19 All antigens Adipocyte Adipose Tissue, ...X821817,SRX821821,SRX821815,SRX821811,SRX821810,SRX821809 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Adp.20.AllAg.Adipose_Tissue,_White.bed ...

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

    Full Text Available DNS.Adp.10.AllAg.Adipose_Tissue,_White hg19 DNase-seq Adipocyte Adipose Tissue, Whi...te http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Adp.10.AllAg.Adipose_Tissue,_White.bed ...

  12. File list: Oth.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available Oth.Adp.10.AllAg.Adipose_Tissue,_White hg19 TFs and others Adipocyte Adipose Tissue...SRX821821,SRX821815,SRX821811,SRX821817,SRX821809,SRX821810 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Adp.10.AllAg.Adipose_Tissue,_White.bed ...

  13. File list: Oth.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available Oth.Adp.50.AllAg.Adipose_Tissue,_White hg19 TFs and others Adipocyte Adipose Tissue...SRX821810,SRX821806,SRX821809,SRX821817,SRX821816,SRX821807 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Adp.50.AllAg.Adipose_Tissue,_White.bed ...

  14. File list: Pol.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available Pol.Adp.20.AllAg.Adipose_Tissue,_White hg19 RNA polymerase Adipocyte Adipose Tissue..., White http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Adp.20.AllAg.Adipose_Tissue,_White.bed ...

  15. File list: Unc.Adp.05.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available Unc.Adp.05.AllAg.Adipose_Tissue,_White hg19 Unclassified Adipocyte Adipose Tissue, ...White http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Adp.05.AllAg.Adipose_Tissue,_White.bed ...

  16. File list: Pol.Adp.05.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available Pol.Adp.05.AllAg.Adipose_Tissue,_White hg19 RNA polymerase Adipocyte Adipose Tissue..., White http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Adp.05.AllAg.Adipose_Tissue,_White.bed ...

  17. File list: His.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available His.Adp.50.AllAg.Adipose_Tissue,_White hg19 Histone Adipocyte Adipose Tissue, White http://dbarchi...ve.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Adp.50.AllAg.Adipose_Tissue,_White.bed ...

  18. in vitro development of bioimplants made up of elastomeric scaffolds with peptide gel filling seeded with human subcutaneous adipose tissue-derived progenitor cells.

    Castells-Sala, Cristina; Martínez-Ramos, Cristina; Vallés-Lluch, Ana; Monleón Pradas, Manuel; Semino, Carlos

    2015-11-01

    Myocardial tissue lacks the ability to regenerate itself significantly following a myocardial infarction. Thus, new strategies that could compensate this lack are of high interest. Cardiac tissue engineering (CTE) strategies are a relatively new approach that aims to compensate the tissue loss using combination of biomaterials, cells and bioactive molecules. The goal of the present study was to evaluate cell survival and growth, seeding capacity and cellular phenotype maintenance of subcutaneous adipose tissue-derived progenitor cells in a new synthetic biomaterial scaffold platform. Specifically, here we tested the effect of the RAD16-I peptide gel in microporous poly(ethyl acrylate) polymers using two-dimensional PEA films as controls. Results showed optimal cell adhesion efficiency and growth in the polymers coated with the self-assembling peptide RAD16-I. Importantly, subATDPCs seeded into microporous PEA scaffolds coated with RAD16-I maintained its phenotype and were able to migrate outwards the bioactive patch, hopefully toward the infarcted area once implanted. These data suggest that this bioimplant (scaffold/RAD16-I/cells) can be suitable for further in vivo implantation with the aim to improve the function of affected tissue after myocardial infarction.

  19. Theoretical model of ruminant adipose tissue metabolism in relation to the whole animal.

    Baldwin, R L; Yang, Y T; Crist, K; Grichting, G

    1976-09-01

    Based on theoretical considerations and experimental data, estimates of contributions of adipose tissue to energy expenditures in a lactating cow and a growing steer were developed. The estimates indicate that adipose energy expenditures range between 5 and 10% of total animal heat production dependent on productive function and diet. These energy expenditures can be partitioned among maintenance (3%), lipogenesis (1-5%) and lipolysis and triglyceride resynthesis (less thatn 1.0%). Specific sites at which acute and chronic effectors can act to produce changes in adipose function, and changes in adipose function produced by diet and during pregnancy, lactation and aging were discussed with emphasis being placed on the need for additional, definitive studies of specific interactions among pregnancy, diet, age, lactation and growth in producing ruminants.

  20. Clinical pilot study for the automatic segmentation and recognition of abdominal adipose tissue compartments from MRI data

    Noel, P.B.; Bauer, J.S.; Ganter, C.; Markus, C.; Rummeny, E.J.; Engels, H.P. [Klinikum rechts der Isar, Technische Univ. Muenchen (Germany). Inst. fuer Radiologie; Hauner, H. [Klinikum rechts der Isar, Technische Univ. Muenchen (Germany). Else Kroener-Fresenius-Center for Nutritional Medicine

    2012-06-15

    Purpose: In the diagnosis and risk assessment of obesity, both the amount and distribution of adipose tissue compartments are critical factors. We present a hybrid method for the quantitative measurement of human body fat compartments. Materials and Methods: MRI imaging was performed on a 1.5 T scanner. In a pre-processing step, the images were corrected for bias field inhomogeneity. For segmentation and recognition a hybrid algorithm was developed to automatically differentiate between different adipose tissue compartments. The presented algorithm is designed with a combination of shape and intensity-based techniques. To incorporate the presented algorithm into the clinical routine, we developed a graphical user interface. Results from our methods were compared with the known volume of an adipose tissue phantom. To evaluate our method, we analyzed 40 clinical MRI scans of the abdominal region. Results: Relatively low segmentation errors were found for subcutaneous adipose tissue (3.56 %) and visceral adipose tissue (0.29 %) in phantom studies. The clinical results indicated high correlations between the distribution of adipose tissue compartments and obesity. Conclusion: We present an approach that rapidly identifies and quantifies adipose tissue depots of interest. With this method examination and analysis can be performed in a clinically feasible timeframe. (orig.)

  1. Cardiac adipose tissue and its relationship to diabetes mellitus and cardiovascular disease

    Adam; M; Noyes; Kirandeep; Dua; Ramprakash; Devadoss; Lovely; Chhabra

    2014-01-01

    Type-2 diabetes mellitus(T2DM) plays a central role in the development of cardiovascular disease(CVD). However, its relationship to epicardial adipose tissue(EAT) and pericardial adipose tissue(PAT) in particular is important in the pathophysiology of coronary artery disease. Owing to its close proximity to the heart and coronary vasculature, EAT exerts a direct metabolic impact by secreting proinflammatory adipokines and free fatty acids, which promote CVD locally. In this review, we have discussed the relationship between T2 DM and cardiac fat deposits, particularly EAT and PAT, which together exert a big impact on the cardiovascular health.

  2. Disconnect Between Adipose Tissue Inflammation and Cardiometabolic Dysfunction in Ossabaw Pigs

    Vieira-Potter, Victoria J.; Lee, Sewon; Bayless, David S.; Scroggins, Rebecca J.; Welly, Rebecca J.; Fleming, Nicholas J.; Smith, Thomas N.; Meers, Grace M.; Hill, Michael A.; Rector, R. Scott; Padilla, Jaume

    2015-01-01

    Objective The Ossabaw pig is emerging as an attractive model of human cardiometabolic disease due to its size and susceptibility to atherosclerosis, among other characteristics. Here we investigated the relationship between adipose tissue inflammation and metabolic dysfunction in this model. Methods Young female Ossabaw pigs were fed a western-style high-fat diet (HFD) (n=4) or control low-fat diet (LFD) (n=4) for a period of 9 months and compared for cardiometabolic outcomes and adipose tissue inflammation. Results The HFD-fed “OBESE” pigs were 2.5 times heavier (p<0.001) than LFD-fed “LEAN” pigs and developed severe obesity. HFD-feeding caused pronounced dyslipidemia, hypertension, insulin resistance (systemic and adipose) as well as induction of inflammatory genes, impairments in vasomotor reactivity to insulin and atherosclerosis in the coronary arteries. Remarkably, visceral, subcutaneous and perivascular adipose tissue inflammation (via FACS analysis and RT-PCR) was not increased in OBESE pigs, nor were circulating inflammatory cytokines. Conclusions These findings reveal a disconnect between adipose tissue inflammation and cardiometabolic dysfunction induced by western diet feeding in the Ossabaw pig model. PMID:26524201

  3. Perivascular adipose tissue-secreted angiopoietin-like protein 2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury.

    Tian, Zhe; Miyata, Keishi; Tazume, Hirokazu; Sakaguchi, Hisashi; Kadomatsu, Tsuyoshi; Horio, Eiji; Takahashi, Otowa; Komohara, Yoshihiro; Araki, Kimi; Hirata, Yoichiro; Tabata, Minoru; Takanashi, Shuichiro; Takeya, Motohiro; Hao, Hiroyuki; Shimabukuro, Michio; Sata, Masataka; Kawasuji, Michio; Oike, Yuichi

    2013-04-01

    Much attention is currently focused on the role of perivascular adipose tissue in development of cardiovascular disease (CVD). Some researchers view it as promoting CVD through secretion of cytokines and growth factors called adipokines, while recent reports reveal that perivascular adipose tissue can exert a protective effect on CVD development. Furthermore, adiponectin, an anti-inflammatory adipokine, reportedly suppresses neointimal hyperplasia after endovascular injury, whereas such vascular remodeling is enhanced by pro-inflammatory adipokines secreted by perivascular adipose, such as tumor necrosis factor-α (TNF-α). These findings suggest that extent of vascular remodeling, a pathological process associated with CVD development, depends on the balance between pro- and anti-inflammatory adipokines secreted from perivascular adipose tissue. We previously demonstrated that angiopoietin-like protein 2 (Angptl2), a pro-inflammatory factor secreted by adipose tissue, promotes adipose tissue inflammation and subsequent systemic insulin resistance in obesity. Here, we examined whether Angptl2 secreted by perivascular adipose tissue contributes to vascular remodeling after endovascular injury in studies of transgenic mice expressing Angptl2 in adipose tissue (aP2-Angptl2 transgenic mice) and Angptl2 knockout mice (Angptl2(-/-) mice). To assess the role of Angptl2 secreted by perivascular adipose tissue on vascular remodeling after endovascular injury, we performed adipose tissue transplantation experiments using these mice. Wild-type mice with perivascular adipose tissue derived from aP2-Angptl2 mice exhibited accelerated neointimal hyperplasia after endovascular injury compared to wild-type mice transplanted with wild-type tissue. Conversely, vascular inflammation and neointimal hyperplasia after endovascular injury were significantly attenuated in wild-type mice transplanted with Angptl2(-/-) mouse-derived perivascular adipose tissue compared to wild-type mice

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

    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.

  5. Heterogeneous response of adipose tissue to cancer cachexia

    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.

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

    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.

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

    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.

  8. Overexpression of TNF-α converting enzyme promotes adipose tissue inflammation and fibrosis induced by high fat diet.

    Matsui, Yuki; Tomaru, Utano; Miyoshi, Arina; Ito, Tomoki; Fukaya, Shinji; Miyoshi, Hideaki; Atsumi, Tatsuya; Ishizu, Akihiro

    2014-12-01

    Obesity is a state in which chronic low-grade inflammation persists in adipose tissues. Pro-inflammatory cytokines, including TNF-α, produced by adipose tissues have been implicated as active participants in the development of obesity-related diseases. Since TNF-α converting enzyme (TACE) is the major factor that induces soluble TNF-α, TACE has been noted as a pivotal regulator in this field. To reveal the role of TACE in adipose tissue inflammation, TACE-transgenic (TACE-Tg) and wild type (WT) mice were fed with high fat diet (HFD) or control diet for 16 weeks. At 13 weeks after the beginning of the diet, serum TNF-α and macrophage-related cytokine/chemokine levels were elevated in TACE-Tg mice fed with HFD (Tg-HFD mice), and the number of the so-called crown-like adipocyte was significantly increased in adipose tissues of Tg-HFD mice at the end of the experiment. Although macrophage infiltration was not detected in the adipose tissues at this time, fibrosis was observed around the crown-like adipocytes. These findings suggested that TACE overexpression induced macrophage infiltration and subsequent fibrosis in adipose tissues under HFD regimen. The collective evidence suggested that TACE could be a therapeutic target of HFD-induced obesity-related adipose tissue inflammation.

  9. Content of Trans Fatty Acids in Human Cheek Epithelium: Comparison with Serum and Adipose Tissue

    Ransi A. Abraham

    2013-01-01

    Full Text Available Studies pertaining to trans fatty acids (TFA, which have been implicated in development of chronic diseases, are more relevant in developing countries where nutrition transition is changing traditional habits and practices. Measuring TFA is an arduous task because of the need for fat biopsies. This study identifies a tissue, which can be easily accessed for analytical measurement of trans fatty acid. In this cross-sectional study, fatty acid in adipose tissue, cheek epithelium, and blood samples were assessed by gas chromatography. Spearman correlation coefficient was computed to study the correlation of fatty acid distribution among the three tissues. The correlation coefficient of total trans fatty acid between cheek epithelium and serum was 0.30 ( and between cheek epithelium and adipose tissue was 0.33 (. This study is the first to report trans fatty acid profile in cheek epithelium giving scope for utilizing the cheek epithelium as a tissue for objective assessment of trans fatty acid intake.

  10. Molecular imaging of brown adipose tissue in health and disease

    Bauwens, Matthias [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Maastricht University, Research School NUTRIM, Maastricht (Netherlands); Wierts, Roel; Brans, Boudewijn [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Royen, Bart van; Backes, Walter [MUMC, Department of Medical Imaging, Division of Radiology, Maastricht (Netherlands); Bucerius, Jan [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany); Maastricht University, Research School CARIM, Maastricht (Netherlands); Mottaghy, Felix [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany)

    2014-04-15

    Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, {sup 18}F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to {sup 18}F-FDG, other radiopharmaceuticals such as {sup 99m}Tc-sestamibi, {sup 123}I-metaiodobenzylguanidine (MIBG), {sup 18}F-fluorodopa and {sup 18}F-14(R,S)-[{sup 18}F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity. (orig.)

  11. Retinoids and nuclear retinoid receptors in white and brown adipose tissues: physiopathologic aspects.

    Flajollet, Sébastien; Staels, Bart; Lefebvre, Philippe

    2013-08-01

    Vitamin A, ingested either as retinol or β-carotene from animal- or plant-derived foods respectively, is a nutrient essential for many biological functions such as embryonic development, vision, immune response, tissue remodeling, and metabolism. Its main active metabolite is all trans-retinoic acid (atRA), which regulates gene expression through the activation of α, β, and γ isotypes of the nuclear atRA receptor (RAR). More recently, retinol derivatives were also shown to control the RAR activity, enlightening the interplay between vitamin A metabolism and RAR-mediated transcriptional control. The white and brown adipose tissues regulate the energy homeostasis by providing dynamic fatty acid storing and oxidizing capacities to the organism, in connection with the other fatty acid-consuming tissues. This concerted interorgan response to fatty acid fluxes is orchestrated, in part, by the endocrine activity of the adipose tissue depots. The adipose tissues are also sites for synthesizing and storing vitamin A derivatives, which will act as hormonal cues or intracellularly to regulate essential aspects of adipocyte biology. As agents that prevent adipocyte differentiation hence, expected to decrease fat mass, and inducers of uncoupling protein expression, thus, favoring energy expenditure, retinoids have prompted many investigations to decipher their roles in adipose tissue pathophysiology, which are summarized in this review.

  12. Noninvasive metabolic imaging of engineered 3D human adipose tissue in a perfusion bioreactor.

    Andrew Ward

    Full Text Available The efficacy and economy of most in vitro human models used in research is limited by the lack of a physiologically-relevant three-dimensional perfused environment and the inability to noninvasively quantify the structural and biochemical characteristics of the tissue. The goal of this project was to develop a perfusion bioreactor system compatible with two-photon imaging to noninvasively assess tissue engineered human adipose tissue structure and function in vitro. Three-dimensional (3D vascularized human adipose tissues were engineered in vitro, before being introduced to a perfusion environment and tracked over time by automated quantification of endogenous markers of metabolism using two-photon excited fluorescence (TPEF. Depth-resolved image stacks were analyzed for redox ratio metabolic profiling and compared to prior analyses performed on 3D engineered adipose tissue in static culture. Traditional assessments with H&E staining were used to qualitatively measure extracellular matrix generation and cell density with respect to location within the tissue. The distribution of cells within the tissue and average cellular redox ratios were different between static and perfusion cultures, while the trends of decreased redox ratio and increased cellular proliferation with time in both static and perfusion cultures were similar. These results establish a basis for noninvasive optical tracking of tissue structure and function in vitro, which can be applied to future studies to assess tissue development or drug toxicity screening and disease progression.

  13. Noninvasive metabolic imaging of engineered 3D human adipose tissue in a perfusion bioreactor.

    Ward, Andrew; Quinn, Kyle P; Bellas, Evangelia; Georgakoudi, Irene; Kaplan, David L

    2013-01-01

    The efficacy and economy of most in vitro human models used in research is limited by the lack of a physiologically-relevant three-dimensional perfused environment and the inability to noninvasively quantify the structural and biochemical characteristics of the tissue. The goal of this project was to develop a perfusion bioreactor system compatible with two-photon imaging to noninvasively assess tissue engineered human adipose tissue structure and function in vitro. Three-dimensional (3D) vascularized human adipose tissues were engineered in vitro, before being introduced to a perfusion environment and tracked over time by automated quantification of endogenous markers of metabolism using two-photon excited fluorescence (TPEF). Depth-resolved image stacks were analyzed for redox ratio metabolic profiling and compared to prior analyses performed on 3D engineered adipose tissue in static culture. Traditional assessments with H&E staining were used to qualitatively measure extracellular matrix generation and cell density with respect to location within the tissue. The distribution of cells within the tissue and average cellular redox ratios were different between static and perfusion cultures, while the trends of decreased redox ratio and increased cellular proliferation with time in both static and perfusion cultures were similar. These results establish a basis for noninvasive optical tracking of tissue structure and function in vitro, which can be applied to future studies to assess tissue development or drug toxicity screening and disease progression.

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

    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.

  15. Browning of white adipose tissue uncouples glucose uptake from insulin signaling.

    Karin Mössenböck

    Full Text Available Presence of thermogenically active adipose tissue in adult humans has been inversely associated with obesity and type 2 diabetes. While it had been shown that insulin is crucial for the development of classical brown fat, its role in development and function of inducible brown-in-white (brite adipose tissue is less clear. Here we show that insulin deficiency impaired differentiation of brite adipocytes. However, adrenergic stimulation almost fully induced the thermogenic program under these settings. Although brite differentiation of adipocytes as well as browning of white adipose tissue entailed substantially elevated glucose uptake by adipose tissue, the capacity of insulin to stimulate glucose uptake surprisingly was not higher in the brite state. Notably, in line with the insulin-independent stimulation of glucose uptake, our data revealed that brite recruitment results in induction of solute carrier family 2 (GLUT-1 expression in adipocytes and inguinal WAT. These results for the first time demonstrate that insulin signaling is neither essential for brite recruitment, nor is it improved in cells or tissues upon browning.

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

    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.

  17. Browning of white adipose tissue uncouples glucose uptake from insulin signaling.

    Mössenböck, Karin; Vegiopoulos, Alexandros; Rose, Adam J; Sijmonsma, Tjeerd P; Herzig, Stephan; Schafmeier, Tobias

    2014-01-01

    Presence of thermogenically active adipose tissue in adult humans has been inversely associated with obesity and type 2 diabetes. While it had been shown that insulin is crucial for the development of classical brown fat, its role in development and function of inducible brown-in-white (brite) adipose tissue is less clear. Here we show that insulin deficiency impaired differentiation of brite adipocytes. However, adrenergic stimulation almost fully induced the thermogenic program under these settings. Although brite differentiation of adipocytes as well as browning of white adipose tissue entailed substantially elevated glucose uptake by adipose tissue, the capacity of insulin to stimulate glucose uptake surprisingly was not higher in the brite state. Notably, in line with the insulin-independent stimulation of glucose uptake, our data revealed that brite recruitment results in induction of solute carrier family 2 (GLUT-1) expression in adipocytes and inguinal WAT. These results for the first time demonstrate that insulin signaling is neither essential for brite recruitment, nor is it improved in cells or tissues upon browning.

  18. Bovine dedifferentiated adipose tissue (DFAT) cells

    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

  19. The role of mediastinal adipose tissue 11β-hydroxysteroid d ehydrogenase type 1 and glucocorticoid expression in the development of coronary atherosclerosis in obese patients with ischemic heart disease

    Atalar Fatmahan

    2012-09-01

    Full Text Available Abstract Background Visceral fat deposition and its associated atherogenic complications are mediated by glucocorticoids. Cardiac visceral fat comprises mediastinal adipose tissue (MAT and epicardial adipose tissue (EAT, and MAT is a potential biomarker of risk for obese patients. Aim Our objective was to evaluate the role of EAT and MAT 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD-1 and glucocorticoid receptor (GCR expression in comparison with subcutaneous adipose tissue (SAT in the development of coronary atherosclerosis in obese patients with coronary artery disease (CAD, and to assess their correlations with CD68 and fatty acids from these tissues. Methods and results Expression of 11β-HSD-1 and GCR was measured by qRT-PCR in EAT, MAT and SAT of thirty-one obese patients undergoing coronary artery bypass grafting due to CAD (obese CAD group and sixteen obese patients without CAD undergoing heart valve surgery (controls. 11β-HSD-1 and GCR expression in MAT were found to be significantly increased in the obese CAD group compared with controls (p  Conclusions We report for the first time the increased expression of 11β-HSD-1 and GCR in MAT compared with EAT and SAT, and also describe the interrelated effects of stearidonic acid, HOMA-IR, plasma cortisol and GCR mRNA levels, explaining 40.2% of the variance in 11β-HSD-1 mRNA levels in MAT of obese CAD patients. These findings support the hypothesis that MAT contributes locally to the development of coronary atherosclerosis via glucocorticoid action.

  20. CD40L Deficiency Ameliorates Adipose Tissue Inflammation and Metabolic Manifestations of Obesity in Mice

    M. Poggi; D. Engel; A. Christ; L. Beckers; E. Wijnands; L. Boon; A. Driessen; J. Cleutjens; C. Weber; N. Gerdes; E. Lutgens

    2011-01-01

    Obese adipose tissue shows hallmarks of chronic inflammation, which promotes the development of metabolic disorders. The mechanisms by which immune cells interact with each other or with metabolism-associated cell types, and the players involved, are still unclear. The CD40-CD40L costimulatory dyad

  1. Adipose tissue dysfunction and cardiometabolic risk. Ex vitro, in vivo and clinical studies

    Kranendonk, M.E.G.

    2014-01-01

    While the obesity epidemic develops at an alarming rate, scientifically we are still far behind with regard to diagnostic and therapeutic actions. In this thesis, we aimed to explore current and novel pathways in adipose tissue dysfunction, as a result of obesity, and investigated how they might con

  2. Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

    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.

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

    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.

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

    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.

  5. Mechanisms of perivascular adipose tissue dysfunction in obesity.

    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.

  6. Mechanisms of Perivascular Adipose Tissue Dysfunction in Obesity

    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.

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

    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.

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

    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.

  9. Sleep deprivation affects inflammatory marker expression in adipose tissue

    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.

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

    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.

  11. Adipose tissue-liver axis in alcoholic liver disease

    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.

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

    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.

  13. Adipose tissue-derived stromal cells express neuronal phenotypes

    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.

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

    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.

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

    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.

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

    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...

  17. Molecular clock integration of brown adipose tissue formation and function.

    Nam, Deokhwa; Yechoor, Vijay K; Ma, Ke

    2016-01-01

    The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation.

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

    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.

  19. Microbiota depletion promotes browning of white adipose tissue and reduces obesity.

    Suárez-Zamorano, Nicolas; Fabbiano, Salvatore; Chevalier, Claire; Stojanović, Ozren; Colin, Didier J; Stevanović, Ana; Veyrat-Durebex, Christelle; Tarallo, Valentina; Rigo, Dorothée; Germain, Stéphane; Ilievska, Miroslava; Montet, Xavier; Seimbille, Yann; Hapfelmeier, Siegfried; Trajkovski, Mirko

    2015-12-01

    Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue (ingSAT) and perigonadal visceral adipose tissue (pgVAT) is promoted by the depletion of microbiota either by means of antibiotic treatment or in germ-free mice. This leads to improved glucose tolerance and insulin sensitivity and decreased white fat and adipocyte size in lean mice, obese leptin-deficient (ob/ob) mice and high-fat diet (HFD)-fed mice. Such metabolic improvements are mediated by eosinophil infiltration, enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by the suppression of type 2 cytokine signaling, and they are reversed by recolonization of the antibiotic-treated or germ-free mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.

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

    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.

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

    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.

  2. Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues.

    Fukai, Nozomi; Yoshimoto, Takanobu; Sugiyama, Toru; Ozawa, Naoko; Sato, Ryuji; Shichiri, Masayoshi; Hirata, Yukio

    2005-01-01

    Adrenomedullin (AM) expressed by and secreted from a variety of cells plays pluripotent roles in an autocrine/paracrine fashion. The present study was undertaken to explore the expression of AM and its receptor genes in adipose tissues, their changes during the development of obesity, and the process of preadipocyte differentiation. Both mature adipocytes and stromal vascular cells constituting adipose tissue expressed AM transcript. AM and its receptor component [calcitonin receptor-like receptor and receptor activity-modifying protein-2 (CRLR/RAMP2)] mRNAs were expressed in a variety of rat adipose tissues, including epididymal, mesenteric, retroperitoneal, and subcutaneous adipose tissue. AM mRNA levels in rat and human epididymal adipose tissue were about one-tenth of those in the kidney. Steady-state mRNA levels of AM and CRLR/RAMP2 in epididymal, mesenteric, and retroperitoneal adipose tissues in rats fed a high-fat diet for 4 wk were far greater than those in rats with normal diet accompanied by increased plasma AM levels, whereas steady-state AM mRNA levels conversely decreased in other organs, such as kidney and liver. AM mRNA expressed in a mouse preadipocyte cell line (3T3-L1) transiently decreased by day 3, returned to basal level by day 6, and then increased by day 9 during preadipocyte differentiation, which paralleled AM secretion from the cells. However, the addition of either exogenous AM or AM receptor antagonist calcitonin gene-related peptide-(8-37), to block endogenous AM did not affect lipid droplet accumulation during preadipocyte differentiation. The present study demonstrates for the first time that AM and its receptor component (CRLR/RAMP2) mRNAs were concomitantly expressed in various adipose tissues, whose tissue-specific upregulation was induced during the development of obesity. These data suggest that AM may act as a new member of adipokines, although its functional role, as well as its pathophysiological significance in obesity

  3. Intrinsic regulation of blood flow in adipose tissue

    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...

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

    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. Phosphatase and Tension Homolog Overexpression in Insulin Resistant Diabetic Adipose Tissue

    Jing-bo Zeng; Yun Zhang; Qi Sun; and Yu-xiu Li

    2014-01-01

    Objective To investigate the expression of phosphatase and tension homolog (PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. Methods KKAy diabetic mice were fed with high fat diet for 4 weeks. After blood glucose met the criteria of diabetes (over 16.7 mmol/L), mice were randomly divided into 3 groups:a control group (without any treatment), a rosiglitazone group (treated with rosiglitazone 12.5 mg/kg·d once per day), and a metformin group (treated with metformin 3 g/kg·d twice daily). After 4 weeks, we then determined the expression of PTEN and phosphoserine 473-Akt (pS473-Akt) in the epididymal adipose tissue with Western blots. The mice in each group were further divided into the insulin (-) subgroup and insulin (+) subgroup, which were intraperitoneally injected with saline and insulin (5 mU/g body weight), respectively. Results The expression of PTEN was elevated in the epididymal adipose tissue obtained from KKAy diabetic mice compared with that from the C57BL/6J mice (P Conclusion PTEN may play an important role in the development of insulin resistance in adipose tissue of type 2 diabetes mice model.

  6. Perivascular adipose tissue: An unique fat compartment relevant for the cardiometabolic syndrome.

    Siegel-Axel, D I; Häring, H U

    2016-03-01

    Type 2 diabetes and its major risk factor, obesity, are an increasing worldwide health problem. The exact mechanisms that link obesity with insulin resistance, type 2 diabetes, hypertension, cardiovascular complications and renal diseases, are still not clarified sufficiently. Adipose tissue in general is an active endocrine and paracrine organ that may influence the development of these disorders. Excessive body fat in general obesity may also cause quantitative and functional alterations of specific adipose tissue compartments. Beside visceral and subcutaneous fat depots which exert systemic effects by the release of adipokines, cytokines and hormones, there are also locally acting fat depots such as peri- and epicardial fat, perivascular fat, and renal sinus fat. Perivascular adipose tissue is in close contact with the adventitia of large, medium and small diameter arteries, possesses unique features differing from other fat depots and may act also independently of general obesity. An increasing number of studies are dealing with the "good" or "bad" characteristics and functions of normally sized and dramatically increased perivascular fat mass in lean or heavily obese individuals. This review describes the origin of perivascular adipose tissue, its different locations, the dual role of a physiological and unphysiological fat mass and its impact on diabetes, cardiovascular and renal diseases. Clinical studies, new imaging methods, as well as basic research in cell culture experiments in the last decade helped to elucidate the various aspects of the unique fat compartment.

  7. The formation of brown adipose tissue induced by transgenic over-expression of PPARγ2.

    Zhou, Ying; Yang, Jinzeng; Huang, Jinliang; Li, Ting; Xu, Dequan; Zuo, Bo; Hou, Liming; Wu, Wangjun; Zhang, Lin; Xia, Xiaoliang; Ma, Zhiyuan; Ren, Zhuqing; Xiong, Yuanzhu

    2014-04-18

    Brown adipose tissue (BAT) is specialized to dissipate energy as heat, therefore reducing fat deposition and counteracting obesity. Brown adipocytes arise from myoblastic progenitors during embryonic development by the action of transcription regulator PRDM16 binding to PPARγ, which promotes BAT-like phenotype in white adipose tissue. To investigate the capability of converting white adipose tissue to BAT or browning by PPARγ in vivo, we generated transgenic mice with over-expressed PPARγ2. The transgenic mice showed strong brown fat features in subcutaneous fat in morphology and histology. To provide molecular evidences on browning characteristics of the adipose tissue, we employed quantitative real-time PCR to determine BAT-specific gene expressions. The transgenic mice had remarkably elevated mRNA level of UCP1, Elovl3, PGC1α and Cebpα in subcutaneous fat. Compared with wild-type mice, UCP1 protein levels were increased significantly in transgenic mice. ATP concentration was slightly decreased in the subcutaneous fat of transgenic mice. Western blotting analysis also confirmed that phosphorylated AMPK and ACC proteins were significantly (P<0.01) increased in the transgenic mice. Therefore, this study demonstrated that over-expression of PPARγ2 in skeletal muscle can promote conversion of subcutaneous fat to brown fat formation, which can have beneficial effects on increasing energy metabolisms and combating obesity.

  8. Diffuse Optical Spectroscopy and Imaging to Detect and Quantify Adipose Tissue Browning

    Dinish, U. S; Wong, Chi Lok; Sriram, Sandhya; Ong, Wee Kiat; Balasundaram, Ghayathri; Sugii, Shigeki; Olivo, Malini

    2017-01-01

    Adipose (fat) tissue is a complex metabolic organ that is highly active and essential. In contrast to white adipose tissue (WAT), brown adipose tissue (BAT) is deemed metabolically beneficial because of its ability to burn calories through heat production. The conversion of WAT-resident adipocytes to “beige” or “brown-like” adipocytes has recently attracted attention. However, it typically takes a few days to analyze and confirm this browning of WAT through conventional molecular, biochemical, or histological methods. Moreover, accurate quantification of the overall browning process is not possible by any of these methods. In this context, we report the novel application of diffuse reflectance spectroscopy (DRS) and multispectral imaging (MSI) to detect and quantify the browning process in mice. We successfully demonstrated the time-dependent increase in browning of WAT, following its induction through β-adrenergic agonist injections. The results from these optical techniques were confirmed with those of standard molecular and biochemical assays, which measure gene and protein expression levels of UCP1 and PGC-1α, as well as with histological examinations. We envision that the reported optical methods can be developed into a fast, real time, cost effective and easy to implement imaging approach for quantification of the browning process in adipose tissue. PMID:28145475

  9. Advances in Adipose-Derived Stem Cells Isolation, Characterization, and Application in Regenerative Tissue Engineering.

    Wankhade, Umesh D; Shen, Michael; Kolhe, Ravindra; Fulzele, Sadanand

    2016-01-01

    Obesity is a complex, multifactorial disease that has been extensively researched in recent times. Obesity is characterized by excess deposition of adipose tissue in response to surplus energy. Despite the negative connotations of adipose tissue (AT), it serves as a critical endocrine organ. Adipose tissue is a source of several adipokines and cytokines which have been deemed important for both normal metabolic function and disease formation. The discoveries of metabolically active brown AT in adult humans and adipose tissue derived stem cells (ADSC) have been key findings in the past decade with potential therapeutic implications. ADSCs represent an enticing pool of multipotent adult stem cells because of their noncontroversial nature, relative abundance, ease of isolation, and expandability. A decade and a half since the discovery of ADSCs, the scientific community is still working to uncover their therapeutic potential in a wide range of diseases. In this review, we provide an overview of the recent developments in the field of ADSCs and examine their potential use in transplantation and cell-based therapies for the regeneration of diseased organs and systems. We also hope to provide perspective on how to best utilize this readily available, powerful pool of stem cells in the future.

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

    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.

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

    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.

  12. The small leucine-rich proteoglycan, biglycan, is highly expressed in adipose tissue of Psammomys obesus and is associated with obesity and type 2 diabetes

    Bolton K

    2012-04-01

    Full Text Available Kristy Bolton1, David Segal1, Ken Walder1,21Metabolic Research Unit, School of Medicine, 2Institute for Technology, Research and Innovation, Deakin University, Waurn Ponds, Victoria, AustraliaAbstract: We have previously demonstrated that the small leucine-rich proteoglycan decorin may play a role in adipose tissue homeostasis and the pathophysiology of obesity. Biglycan is highly similar in structure to decorin, therefore we hypothesized it would have a similar expression profile and role to decorin in adipose tissue. Real time polymerase chain reaction was used to measure biglycan mRNA levels in adipose tissue from normal glucose tolerant and impaired glucose tolerant and type 2 diabetic (T2D Psammomys obesus. Biglycan mRNA was found to be highly expressed in adipose tissue, and gene expression was significantly higher in visceral compared to subcutaneous adipose tissue, with elevated levels in obese, T2D compared to lean normal glucose tolerant P. obesus (P < 0.04. Biglycan mRNA was predominantly expressed by stromal/vascular cells of fractionated adipose tissue (P = 0.023. Biglycan expression in adipose tissue, particularly in the obese state, was markedly upregulated. Collectively, our data suggest that the small leucine-rich proteoglycan family proteins biglycan and decorin may play a role in the development of obesity and T2D, possibly by facilitating expansion of adipose tissue mass.Keywords: biglycan, small leucine-rich proteoglycan, Psammomys obesus, adipose tissue, obesity, type 2 diabetes

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

    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.

  14. Adipose tissue engineering in three-dimensional levitation tissue culture system based on magnetic nanoparticles.

    Daquinag, Alexes C; Souza, Glauco R; Kolonin, Mikhail G

    2013-05-01

    White adipose tissue (WAT) is becoming widely used in regenerative medicine/cell therapy applications, and its physiological and pathological importance is increasingly appreciated. WAT is a complex organ composed of differentiated adipocytes, stromal mesenchymal progenitors known as adipose stromal cells (ASC), as well as endothelial vascular cells and infiltrating leukocytes. Two-dimensional (2D) culture that has been typically used for studying adipose cells does not adequately recapitulate WAT complexity. Improved methods for reconstruction of functional WAT ex vivo are instrumental for understanding of physiological interactions between the composing cell populations. Here, we used a three-dimensional (3D) levitation tissue culture system based on magnetic nanoparticle assembly to model WAT development and growth in organoids termed adipospheres. We show that 3T3-L1 preadipocytes remain viable in spheroids for a long period of time, while in 2D culture, they lose adherence and die after reaching confluence. Upon adipogenesis induction in 3T3-L1 adipospheres, cells efficiently formed large lipid droplets typical of white adipocytes in vivo, while only smaller lipid droplet formation is achievable in 2D. Adiposphere-based coculture of 3T3-L1 preadipocytes with murine endothelial bEND.3 cells led to a vascular-like network assembly concomitantly with lipogenesis in perivascular cells. Adipocyte-depleted stromal vascular fraction (SVF) of mouse WAT cultured in 3D underwent assembly into organoids with vascular-like structures containing luminal endothelial and perivascular stromal cell layers. Adipospheres made from primary WAT cells displayed robust proliferation and complex hierarchical organization reflected by a matricellular gradient incorporating ASC, endothelial cells, and leukocytes, while ASC quickly outgrew other cell types in adherent culture. Upon adipogenesis induction, adipospheres derived from the SVF displayed more efficient lipid droplet

  15. Investigations of the endocannabinoid system in adipose tissue: effects of obesity/ weight loss and treatment options.

    Bennetzen, Marianne Faurholt

    2011-04-01

    Obesity is a world wide epidemic; it is becoming more usual to be overweight or obese than to be normal weight. Obesity increases the risk of an extensive range of diseases such as cardiovascular disease, diabetes mellitus type 2, hypertension, depression and some types of cancer. Adipose tissue is more than a storage organ for surplus energy - it is also a setting for complex metabolic processes and adipose tissue releases substances that interact with other parts of the body to influence several systems including food intake and energy metabolism. The endocannabinoid system (ECS) is one of the signalling systems that control feeding behaviour. The ECS is implicated in many functions, such as pain, memory, addiction, inflammation, and feeding, and could be considered a stress recovery system. It also seems to integrate nutrient intake, metabolism and storage maintaining homeostatic balance. The ECS is a recently discovered system, and research indicates hyperactivity in obesity. The aim of this thesis is to elaborate on the relationships of this widespread system and its elements in adipose tissue in obesity. Study I is a 4 weeks rat intervention study to investigate whether weight independent effect of Rimonabant treatment exists. We found that food intake-tolerance development could be circumvented by cyclic administration of Rimonabant and implications of weight independent effects of treatment. Study II is a cross-sectional study to establish the expression of cannabinoid receptor 1 from various adipose tissue depots of lean and obese persons. In this study we conclude, that the subcutaneous adipose tissue express more CBR1 than the visceral depot in lean, but comparable levels in obese. Study III is a 10 weeks human intervention study to asses the effects on the ECS of 10% weight loss. We found reduction in the ECS in obesity that normalised with weight loss. Our results clearly show the presence of all the components of the ECS in human adipose tissue, and

  16. Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

    Kasten, Annika; Siegmund, Birte J.; Grüttner, Cordula; Kühn, Jens-Peter; Frerich, Bernhard

    2015-04-01

    Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time.

  17. Pattern specification and immune response transcriptional signatures of pericardial and subcutaneous adipose tissue.

    Frank H Lau

    Full Text Available Cardiovascular disease (CVD remains the leading cause of morbidity and mortality in the United States. Recent studies suggest that pericardial adipose tissue (PCAT secretes inflammatory factors that contribute to the development of CVD. To better characterize the role of PCAT in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between PCAT and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals. As it was unknown whether PCAT-secreted factors are produced by adipocytes or cells in the supporting stromal fraction, we also sought to identify differentially expressed genes in isolated pericardial adipocytes vs. isolated subcutaneous adipocytes. Using microarray analysis, we found that: 1 pericardial adipose tissue and isolated pericardial adipocytes both overexpress atherosclerosis-promoting chemokines and 2 pericardial and subcutaneous fat depots, as well as isolated pericardial adipocytes and subcutaneous adipocytes, express specific patterns of homeobox genes. In contrast, a core set of lipid processing genes showed no significant overlap with differentially expressed transcripts. These depot-specific homeobox signatures and transcriptional profiles strongly suggest different functional roles for the pericardial and subcutaneous adipose depots. Further characterization of these inter-depot differences should be a research priority.

  18. Pattern specification and immune response transcriptional signatures of pericardial and subcutaneous adipose tissue.

    Lau, Frank H; Deo, Rahul C; Mowrer, Gregory; Caplin, Joshua; Ahfeldt, Tim; Kaplan, Adam; Ptaszek, Leon; Walker, Jennifer D; Rosengard, Bruce R; Cowan, Chad A

    2011-01-01

    Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Recent studies suggest that pericardial adipose tissue (PCAT) secretes inflammatory factors that contribute to the development of CVD. To better characterize the role of PCAT in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between PCAT and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals. As it was unknown whether PCAT-secreted factors are produced by adipocytes or cells in the supporting stromal fraction, we also sought to identify differentially expressed genes in isolated pericardial adipocytes vs. isolated subcutaneous adipocytes. Using microarray analysis, we found that: 1) pericardial adipose tissue and isolated pericardial adipocytes both overexpress atherosclerosis-promoting chemokines and 2) pericardial and subcutaneous fat depots, as well as isolated pericardial adipocytes and subcutaneous adipocytes, express specific patterns of homeobox genes. In contrast, a core set of lipid processing genes showed no significant overlap with differentially expressed transcripts. These depot-specific homeobox signatures and transcriptional profiles strongly suggest different functional roles for the pericardial and subcutaneous adipose depots. Further characterization of these inter-depot differences should be a research priority.

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

    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.

  20. Decreased adipose tissue zinc content is associated with metabolic parameters in high fat fed Wistar rats

    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...

  1. Adipose Tissue-Derived Stem Cells for Myocardial Regeneration

    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.

  2. The fractionation of adipose tissue procedure to obtain stromal vascular fractions for regenerative purposes

    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

  3. The Fractionation of Adipose Tissue (FAT) procedure to obtain stromal vascular fractions for regenerative purposes

    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

  4. The Secretory Function of Adipocytes in the Physiology of White Adipose Tissue

    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

  5. TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling

    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.

  6. Modal response of a computational vocal fold model with a substrate layer of adipose tissue.

    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.

  7. Adrenergic regulation of cellular plasticity in brown, beige/brite and white adipose tissues.

    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.

  8. Prolactin suppresses malonyl-CoA concentration in human adipose tissue

    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...

  9. Sugar-sweetened and diet beverages in relation to visceral adipose tissue.

    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.

  10. Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

    Kasten, Annika; Siegmund, Birte J. [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35 D-18057 Rostock (Germany); Grüttner, Cordula [Micromod Partikeltechnologie GmbH, Warnemünde, D-18115 Rostock (Germany); Kühn, Jens-Peter [Department of Radiology and Neuroradiology, Greifswald University Medical Center, D-17475 Greifswald (Germany); Frerich, Bernhard, E-mail: bernhard.frerich@med.uni-rostock.de [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35 D-18057 Rostock (Germany)

    2015-04-15

    Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time. - Highlights: • Adipose tissue-derived stem cells (ASC) were labeled with magnetic iron oxide nanoparticles. • Nanoparticles influenced the adipogenic differentiation of ASC. • Labeled cells were seeded onto collagen scaffolds and implanted in SCID mice. • Nanoparticle-labeled cells were visualized in vivo using T2-weighted sequences. • Volume of collagen scaffolds was decreased over time after implantation.

  11. Characterization of mesenchymal stem cells derived from equine adipose tissue

    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.

  12. Adipose Tissue-Derived Stem Cells in Regenerative Medicine

    Frese, Laura; Dijkman, Petra E.; Hoerstrup, Simon P.

    2016-01-01

    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.

  13. Adipose Tissue-Derived Stem Cells in Regenerative Medicine.

    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.

  14. Endurance training changes in lipolytic responsiveness of obese adipose tissue.

    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.

  15. Hypothalamic regulation of brown adipose tissue thermogenesis and energy homeostasis

    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.

  16. Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

    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...

  17. [Epicardial adipose tissue and its role in cardiac physiology and disease].

    Toczyłowski, Kacper; Gruca, Michał; Baranowski, Marcin

    2013-06-20

    Adipose tissue secretes a number of cytokines, referred to as adipokines. Intensive studies conducted over the last two decades showed that adipokines exert broad effects on cardiac metabolism and function. In addition, the available data strongly suggests that these cytokines play an important role in development of cardiovascular diseases. Epicardial adipose tissue (EAT) has special properties that distinguish it from other deposits of visceral fat. Overall, there appears to be a close functional and anatomic relationship between the EAT and the cardiac muscle. They share the same coronary blood supply, and there is no structure separating the adipose tissue from the myocardium or coronary arteries. The role of EAT in osierdziocardiac physiology remains unclear. Its putative functions include buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, regulating fatty acid homeostasis in the coronary microcirculation, thermogenesis, and neuroprotection of the cardiac autonomic ganglia and nerves. Obesity (particularly the abdominal phenotype) leads to elevated EAT content, and the available data suggests that high amount of this fat depot is associated with increased risk of ischemic heart disease, cardiac hypertrophy and diastolic dysfunction. The mass of EAT is small compared to other fat deposits in the body. Nevertheless, its close anatomic relationship to the heart suggests that this organ is highly exposed to EAT-derived adipokines which makes this tissue a very promising area of research. In this paper we review the current knowledge on the role of EAT in cardiac physiology and development of heart disease.

  18. Intramuscular Adipose Tissue, Sarcopenia, and Mobility Function in Older Individuals

    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.

  19. Lipid Profiling of In Vitro Cell Models of Adipogenic Differentiation: Relationships With Mouse Adipose Tissues.

    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.

  20. Expression of circadian genes in subcutaneous adipose tissue of obese men with glucose intolerance and type 2 diabetes

    Dmytro O. Minchenko

    2015-03-01

    Results: The expression levels of circadian genes PER2, CLOCK, ARNTL/BMAL1 and CRY1 were decreased in subcutaneous adipose tissue of NGT obese men versus lean controls and these changes were negatively correlated with increased body mass index (BMI. At the same time, no significant changes were observed in PER1 gene expression in adipose tissue of this group of patients. In subcutaneous adipose tissue of IGT obese cases we found decreased levels of PER1, CLOCK and ARNTL/BMAL1 gene expressions compared to NGT obese individuals. Moreover, the expression levels of CLOCK, PER2 and CRY1 genes were down-regulated in subcutaneous adipose tissue of obese men with type 2 diabetes versus IGT obese patients; however, ARNTL/BMAL1 gene expression was up-regulated. Conclusions: Our data demonstrate that suppression of most circadian gene expressions in subcutaneous adipose tissue of obese men with NGT is negatively correlated with increased BMI and can contribute to the development of obesity. The decreased expression of PER1 gene as well as an additional suppression of ARNTL/BMAL1 and CLOCK gene expressions in subcutaneous adipose tissue of obese men with glucose intolerance is associated with insulin resistance and IGT. At the same time, development of type 2 diabetes in obese men correlates with suppression of CLOCK, PER2, and CRY1 gene expressions. These results demonstrate that obesity and its complications differentially suppress clock gene expressions in subcutaneous adipose tissue, rendering this pathway as a potential therapeutic target. [J Exp Integr Med 2015; 5(1.000: 23-29

  1. Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease

    Kamran Qureshi; Gary A Abrams

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality.It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR,metabolic syndrome and NAFLD.

  2. Weight Cycling Increases T-Cell Accumulation in Adipose Tissue and Impairs Systemic Glucose Tolerance

    Anderson, Emily K.; Gutierrez, Dario A.; Kennedy, Arion; Hasty, Alyssa H.

    2013-01-01

    Obesity is one of the leading causes of morbidity in the U.S. Accumulation of proinflammatory immune cells in adipose tissue (AT) contributes to the development of obesity-associated disorders. Weight loss is the ideal method to counteract the negative consequences of obesity; however, losses are rarely maintained, leading to bouts of weight cycling. Fluctuations in weight have been associated with worsened metabolic and cardiovascular outcomes; yet, the mechanisms explaining this potential c...

  3. Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue.

    Volden, Paul A; Wonder, Erin L; Skor, Maxwell N; Carmean, Christopher M; Patel, Feenalie N; Ye, Honggang; Kocherginsky, Masha; McClintock, Martha K; Brady, Matthew J; Conzen, Suzanne D

    2013-07-01

    Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen FVB/N (TAg) mouse model of "triple-negative" breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e., during the in situ carcinoma stage). To further understand the mechanisms underlying how accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2, and Acly was found in the adipocyte, rather than the epithelial fraction. Surprisingly, metabolic gene expression was not significantly increased in visceral adipose depots of socially isolated female mice. As expected, increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin secretion from this adipose depot. Furthermore, application of media that had been cultured with isolated mouse mammary adipose tissue (conditioned media) resulted in increased proliferation of mammary cancer cells relative to group-housed-conditioned media. These results suggest that exposure to a chronic stressor (social isolation) results in specific metabolic reprogramming in mammary gland adipocytes that in turn contributes to increased proliferation of adjacent preinvasive malignant epithelial cells. Metabolites and/or tumor growth-promoting proteins secreted from adipose tissue could identify biomarkers and/or targets for preventive intervention in breast cancer.

  4. Microarray Evidences the Role of Pathologic Adipose Tissue in Insulin Resistance and Their Clinical Implications

    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.

  5. Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues

    Harkema Jack R

    2011-07-01

    Full Text Available Abstract Background Prior studies have demonstrated a link between air pollution and metabolic diseases such as type II diabetes. Changes in adipose tissue and its mitochondrial content/function are closely associated with the development of insulin resistance and attendant metabolic complications. We investigated changes in adipose tissue structure and function in brown and white adipose depots in response to chronic ambient air pollutant exposure in a rodent model. Methods Male ApoE knockout (ApoE-/- mice inhaled concentrated fine ambient PM (PM 2.5 or filtered air (FA for 6 hours/day, 5 days/week, for 2 months. We examined superoxide production by dihydroethidium staining; inflammatory responses by immunohistochemistry; and changes in white and brown adipocyte-specific gene profiles by real-time PCR and mitochondria by transmission electron microscopy in response to PM2.5 exposure in different adipose depots of ApoE-/- mice to understand responses to chronic inhalational stimuli. Results Exposure to PM2.5 induced an increase in the production of reactive oxygen species (ROS in brown adipose depots. Additionally, exposure to PM2.5 decreased expression of uncoupling protein 1 in brown adipose tissue as measured by immunohistochemistry and Western blot. Mitochondrial number was significantly reduced in white (WAT and brown adipose tissues (BAT, while mitochondrial size was also reduced in BAT. In BAT, PM2.5 exposure down-regulated brown adipocyte-specific genes, while white adipocyte-specific genes were differentially up-regulated. Conclusions PM2.5 exposure triggers oxidative stress in BAT, and results in key alterations in mitochondrial gene expression and mitochondrial alterations that are pronounced in BAT. We postulate that exposure to PM2.5 may induce imbalance between white and brown adipose tissue functionality and thereby predispose to metabolic dysfunction.

  6. The contribution of different adipose tissue depots to plasma plasminogen activator inhibitor-1 (PAI-1) levels.

    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.

  7. 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

    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。

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

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

    2009-01-01

    but an unaffected amount of visceral adipose tissue. BMI changes during adolescence predict both visceral and subcutaneous adipose tissue of the abdomen, whereas BMI changes during late childhood predict only the subcutaneous adipose tissue. CONCLUSIONS: The amount of visceral adipose tissue in young adult men......OBJECTIVE: The amount of visceral adipose tissue is a risk factor for the metabolic syndrome. It is unclear how BMI changes during childhood and adolescence predict adult fat distribution. We hypothesized that there are critical periods during development for the prediction of adult subcutaneous...... and visceral fat mass by BMI changes during childhood and adolescence. RESEARCH DESIGN AND METHODS: Detailed growth charts were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study (n = 612). Body composition was analyzed using dual-energy X...

  9. Role of antigen presentation in the production of pro-inflammatory cytokines in obese adipose tissue.

    Majdoubi, Abdelilah; Kishta, Osama A; Thibodeau, Jacques

    2016-06-01

    Type II diabetes regroups different physiological anomalies that ultimately lead to low-grade chronic inflammation, insulin resistance and loss of pancreatic β-cells. Obesity is one of the best examples of such a condition that can develop into Metabolic Syndrome, causing serious health problems of great socio-economic consequences. The pathological outcome of obesity has a genetic basis and depends on the delicate balance between pro- and anti-inflammatory effectors of the immune system. The causal link between obesity and inflammation is well established. While innate immunity plays a key role in the development of a pro-inflammatory state in obese adipose tissues, it has now become clear that adaptive immune cells are also involved and participate in the cascade of events that lead to metabolic perturbations. The efficacy of some immunotherapeutic protocols in reducing the symptoms of obesity-driven metabolic syndrome in mice implicated all arms of the immune response. Recently, the production of pathogenic immunoglobulins and pro-inflammatory cytokines by B and T lymphocytes suggested an auto-immune basis for the establishment of a non-healthy obese state. Understanding the cellular landscape of obese adipose tissues and how immune cells sustain chronic inflammation holds the key to the development of targeted therapies. In this review, we emphasize the role of antigen-presenting cells and MHC molecules in obese adipose tissue and the general contribution of the adaptive arm of the immune system in inflammation-induced insulin resistance.

  10. Deleted in Breast Cancer 1 Limits Adipose Tissue Fat Accumulation and Plays a Key Role in the Development of Metabolic Syndrome Phenotype

    Escande, Carlos; Nin, Veronica; Pirtskhalava, Tamar; Chini, Claudia C. S.; Tchkonia, Tamar; Kirkland, James L.; Chini, Eduardo N.

    2015-01-01

    Obesity is often regarded as the primary cause of metabolic syndrome. However, many lines of evidence suggest that obesity may develop as a protective mechanism against tissue damage during caloric surplus and that it is only when the maximum fat accumulation capacity is reached and fatty acid spill

  11. Depot-dependent effects of adipose tissue explants on co-cultured hepatocytes

    Du, Zhen-Yu; Ma, Tao; Lock, Erik-Jan;

    2011-01-01

    a stronger cytotoxic response and higher level of insulin resistance in the co-cultured hepatocytes. In conclusion, our results reveal depot-dependent effects of ATEs on co-cultured primary hepatocytes, which in part may be related to a more pronounced infiltration of stromal vascular cells (SVCs......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...

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

    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.)

  13. Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo

    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...

  14. Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

    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.

  15. A pilot study of sampling subcutaneous adipose tissue to examine biomarkers of cancer risk

    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.

  16. Contact with existing adipose tissue is inductive for adipogenesis in matrigel.

    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.

  17. Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

    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.

  18. In vivo human lipolytic activity in preperitoneal and subdivisions of subcutaneous abdominal adipose tissue

    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...

  19. N-3 polyunsaturated fatty acids in adipose tissue and depression in different age groups from Crete

    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

  20. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

    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.

  1. Predictors of adipose tissue carotenoid and retinol levels in nine countries: The EURAMIC study

    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

  2. A biomimetic physiological model for human adipose tissue by adipocytes and endothelial cell cocultures with spatially controlled distribution.

    Yao, Rui; Du, Yanan; Zhang, Renji; Lin, Feng; Luan, Jie

    2013-08-01

    An in vitro model that recapitulates the characteristics of native human adipose tissue would largely benefit pathology studies and therapy development. In this paper, we fabricated a physiological model composed of both human adipocytes and endothelial cells with spatially controlled distribution that biomimics the structure and composition of human adipose tissue. Detailed studies into the cell-cell interactions between the adipocytes and endothelial cells revealed a mutual-enhanced effect which resembles the in vivo routine. Furthermore, comparisons between planar coculture and model coculture demonstrated improved adipocyte function as well as endothelial cell proliferation under the same conditions. This research provided a reliable model for human adipose tissue development studies and potential obesity-related therapy development.

  3. Metabolic inflexibility of white and brown adipose tissues in abnormal fatty acid partitioning of type 2 diabetes.

    Grenier-Larouche, T; Labbé, S M; Noll, C; Richard, D; Carpentier, A C

    2012-12-01

    Type 2 diabetes (T2D) is characterized by a general dysregulation of postprandial energy substrate partitioning. Although classically described in regard to glucose metabolism, it is now evident that metabolic inflexibility of plasma lipid fluxes is also present in T2D. The organ that is most importantly involved in the latter metabolic defect is the white adipose tissue (WAT). Both catecholamine-induced nonesterified fatty acid mobilization and insulin-stimulated storage of meal fatty acids are impaired in many WAT depots of insulin-resistant individuals. Novel molecular imaging techniques now demonstrate that these defects are linked to increased dietary fatty acid fluxes toward lean organs and myocardial dysfunction in humans. Recent findings also demonstrate functional abnormalities of brown adipose tissues in T2D, thus suggesting that a generalized adipose tissue dysregulation of energy storage and dissipation may be at play in the development of lean tissue energy overload and lipotoxicity.

  4. Adipokines and the role of visceral adipose tissue in inflammatory bowel disease

    Karrasch, Thomas; Schaeffler, Andreas

    2016-01-01

    Recently, adipocytes have been recognized as actively participating in local and systemic immune responses via the secretion of peptides detectable in relevant levels in the systemic circulation, the so-called “adipo(cyto)kines”. Multiple studies appearing within the last 10-15 years have focused on the possible impact of adipose tissue depots on inflammatory bowel disease (IBD). Consequently, various hypotheses regarding the role of different adipokines in inflammatory diseases in general and in intestinal inflammatory processes in particular have been developed and have been further refined in recent years. After a focused summary of the data reported concerning the impact of visceral adipose tissue on IBD, such as Crohn’s disease and ulcerative colitis, our review focuses on recent developments indicating that adipocytes as part of the innate immune system actively participate in antimicrobial host defenses in the context of intestinal bacterial translocation, which are of utmost importance for the homeostasis of the whole organism. Modulators of adipose tissue function and regulators of adipokine secretion, as well as modifiers of adipocytic pattern recognition molecules, might represent future potential drug targets in IBD. PMID:27708507

  5. Obesity and coronary microvascular disease - implications for adipose tissue-mediated remote inflammatory response.

    Bagi, Zsolt; Broskova, Zuzana; Feher, Attila

    2014-05-01

    It is believed that obesity has detrimental effects on the coronary circulation. These include immediate changes in coronary arterial vasomotor responsiveness and the development of occlusive large coronary artery disease. Despite its critical role in regulating myocardial perfusion, the altered behavior of coronary resistance arteries, which gives rise to coronary microvascular disease (CMD) is poorly understood in obesity. A chronic, low-grade vascular inflammation has been long considered as one of the main underlying pathology behind CMD. The expanded adipose tissue and the infiltrating macrophages are the major sources of pro-inflammatory mediators that have been implicated in causing inadequate myocardial perfusion and, in a long term, development of heart failure in obese patients. Much less is known the mechanisms regulating the release of these cytokines into the circulation that enable them to exert their remote effects in the coronary microcirculation. This mini review aims to examine recent studies describing alterations in the vasomotor function of coronary resistance arteries and the role of adipose tissue-derived pro-inflammatory cytokines and adipokines in contributing to CMD in obesity. We provide examples of regulatory mechanisms by which adipokines are released from adipose tissue to exert their remote inflammatory effects on coronary microvessels. We identify some of the important challenges and opportunities going forward.

  6. Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice.

    Nohara, Kazunari; Waraich, Rizwana S; Liu, Suhuan; Ferron, Mathieu; Waget, Aurélie; Meyers, Matthew S; Karsenty, Gérard; Burcelin, Rémy; Mauvais-Jarvis, Franck

    2013-06-15

    Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

  7. Identification of cyclopropaneoctanoic acid 2-hexyl in human adipose tissue and serum.

    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.

  8. Vascular and metabolic effects of adrenaline in adipose tissue in type 2 diabetes

    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...

  9. Adipose tissue lipolysis is increased during a repeated bout of aerobic exercise

    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...... leaving the adipose tissue. Seven male subjects performed two repeated bouts of 60-min exercise at 50% of their maximal aerobic power, separated by a 60-min recovery period. The exercise-induced increases in extracellular glycerol concentrations in adipose tissue and in plasma glycerol concentrations were...... levels were lower during the second exercise bout. The results suggest that adipose tissue lipolysis during aerobic exercise of moderate intensity is enhanced when an exercise bout is preceded by exercise of the same intensity and duration performed 1 h before. This response pattern is associated...

  10. Fatty acid binding protein 4 expression marks a population of adipocyte progenitors in white and brown adipose tissues.

    Shan, Tizhong; Liu, Weiyi; Kuang, Shihuan

    2013-01-01

    Adipose tissues regulate metabolism, reproduction, and life span. The development and growth of adipose tissue are due to increases of both adipocyte cell size and cell number; the latter is mediated by adipocyte progenitors. Various markers have been used to identify either adipocyte progenitors or mature adipocytes. The fatty acid binding protein 4 (FABP4), commonly known as adipocyte protein 2 (aP2), has been extensively used as a marker for differentiated adipocytes. However, whether aP2 is expressed in adipogenic progenitors is controversial. Using Cre/LoxP-based cell lineage tracing in mice, we have identified a population of aP2-expressing progenitors in the stromal vascular fraction (SVF) of both white and brown adipose tissues. The aP2-lineage progenitors reside in the adipose stem cell niche and express adipocyte progenitor markers, including CD34, Sca1, Dlk1, and PDGFRα. When isolated and grown in culture, the aP2-expressing SVF cells proliferate and differentiate into adipocytes upon induction. Conversely, ablation of the aP2 lineage greatly reduces the adipogenic potential of SVF cells. When grafted into wild-type mice, the aP2-lineage progenitors give rise to adipose depots in recipient mice. Therefore, the expression of aP2 is not limited to mature adipocytes, but also marks a pool of undifferentiated progenitors associated with the vasculature of adipose tissues. Our finding adds to the repertoire of adipose progenitor markers and points to a new regulator of adipose plasticity.

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

    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.

  12. The role of brown adipose tissue in temperature regulation. [of hibernating and hypothermic mammals

    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.

  13. Adipose tissue resistin gene expression in DIO and DR rats

    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.

  14. Protein turnover in adipose tissue from fasted or diabetic rats

    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.

  15. Negative regulators of brown adipose tissue (BAT)-mediated thermogenesis.

    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.

  16. Effect of diethylstilboestrol on adipose-tissue lipids.

    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.

  17. Evidence for two types of brown adipose tissue in humans.

    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.

  18. MAP3K8 (TPL2/COT affects obesity-induced adipose tissue inflammation without systemic effects in humans and in mice.

    Dov B Ballak

    Full Text Available Chronic low-grade inflammation in adipose tissue often accompanies obesity, leading to insulin resistance and increasing the risk for metabolic diseases. MAP3K8 (TPL2/COT is an important signal transductor and activator of pro-inflammatory pathways that has been linked to obesity-induced adipose tissue inflammation. We used human adipose tissue biopsies to study the relationship of MAP3K8 expression with markers of obesity and expression of pro-inflammatory cytokines (IL-1β, IL-6 and IL-8. Moreover, we evaluated obesity-induced adipose tissue inflammation and insulin resistance in mice lacking MAP3K8 and WT mice on a high-fat diet (HFD for 16 weeks. Individuals with a BMI >30 displayed a higher mRNA expression of MAP3K8 in adipose tissue compared to individuals with a normal BMI. Additionally, high mRNA expression levels of IL-1β, IL-6 and IL-8, but not TNF -α, in human adipose tissue were associated with higher expression of MAP3K8. Moreover, high plasma SAA and CRP did not associate with increased MAP3K8 expression in adipose tissue. Similarly, no association was found for MAP3K8 expression with plasma insulin or glucose levels. Mice lacking MAP3K8 had similar bodyweight gain as WT mice, yet displayed lower mRNA expression levels of IL-1β, IL-6 and CXCL1 in adipose tissue in response to the HFD as compared to WT animals. However, MAP3K8 deficient mice were not protected against HFD-induced adipose tissue macrophage infiltration or the development of insulin resistance. Together, the data in both human and mouse show that MAP3K8 is involved in local adipose tissue inflammation, specifically for IL-1β and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance.

  19. Comparison of fatty acid composition of subcutaneous, pericardial and epicardial adipose tissue and atrial tissue in patients with heart disease

    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...

  20. Comparison of fatty acid composition of subcutaneous, pericardial and epicardial adipose tissue and atrial tissue in patients with heart disease

    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...

  1. Comparison of different fabrication techniques for human adipose tissue engineering in severe combined immunodeficient mice.

    Frerich, Bernhard; Winter, Karsten; Scheller, Konstanze; Braumann, Ulf-Dietrich

    2012-03-01

    Adipose tissue engineering has been advocated for soft-tissue augmentation and for the treatment of soft tissue defects. The efficacy in terms of persistence of the engineered fat is, however, not yet understood and could depend on the nature of fabrication and application. The high metabolic demand of adipose tissue also points to the problem of vascularization. Endothelial cell (EC) cotransplantation could be a solution. Human adipose tissue-derived stromal cells were seeded on collagen microcarriers and submitted to adipogenic differentiation ("microparticles"). In a first run of experiments, these microparticles were implanted under the skin of severe combined immunodeficient (SCID) mice (n = 45) with and without the addition of human umbilical vein ECs (HUVECs). A group of carriers without any cells served as control. In a second run, adipose tissue constructs were fabricated by embedding microparticles in fibrin matrix with and without the addition of HUVEC, and were also implanted in SCID mice (n = 30). The mice were sacrificed after 12 days, 4 weeks, and 4 months. Mature adipose tissue, fibrous tissue, and acellular regions were quantified on whole-specimen histological sections. The implantation of microparticles showed a better sustainment of tissue volume and a higher degree of mature adipose tissue compared with adipose tissue constructs. Immunohistology proved obviously perfused human tissue-engineered vessels. There was a limited but not significant advantage in EC cotransplantation after 4 weeks in terms of tissue volume. In groups with EC cotransplantation, there were significantly fewer acellular/necrotic areas after 4 weeks and 4 months. In conclusion, the size of the implanted tissue equivalents is a crucial parameter, affecting volume maintenance and the gain of mature adipose tissue. EC cotransplantation leads to functional stable vascular networks connecting in part to the host vasculature and contributing to tissue perfusion; however

  2. [Effect of cytokines and stromal cells of adipose tissue on integration of a two-component composite net imlant into biological tissues].

    Dubinina, V G; Chetverikov, S G; Luk'ianchuk, O V; Rosha, L G; Sazhienko, V V; Lysenko, M A; Mikhaĭlov, A S; Chetverikov, M S

    2014-02-01

    Morphological changes in biological tissues, surrounding the composite net-like implant, owing large pores "Ultrapro", and also its combination with adipose transplant, fibrin, enriched with thrombocytes, were studied in experiment on 36 adult male rats of a Wistar line. While application of such construction the processes of creation and organization of connective tissue, neoangiogenesis as well as development of a new adipose tissue are improved. As a consequence of increase of concentration of highly active biological substances and regenerative cytokines in combination of the net implant with adipose transplant, containing multipotent stem cells, proliferative activity of all cellular elements, surrounding the net implant, is raising, what predispose its optimal integration into surrounding tissues.

  3. Microarray analysis of adipose tissue gene expression profiles between two chicken breeds

    Hongbao Wang; Hui Li; Qigui Wang; Yuxiang Wang; Huabin Han; Hui Shi

    2006-12-01

    The chicken is an important model organism that bridges the evolutionary gap between mammals and other vertebrates and provides a major protein source from meat and eggs throughout the world. Excessive accumulation of lipids in the adipose tissue is one of the main problems faced by the broiler industry nowadays. In order to visualize the mechanisms involved in the gene expression and regulation of lipid metabolism in adipose tissue, cDNA microarray containing 9 024 cDNA was used to construct gene expression profile and screen differentially expressed genes in adipose tissue between broilers and layers of 10 wk of age. Sixty-seven differentially expressed sequences were screened out, and 42 genes were found when blasted with the GenBank database. These genes are mainly related to lipid metabolism, energy metabolism, transcription and splicing factor, protein synthesis and degradation. The remained 25 sequences had no annotation available in the GenBank database. Furthermore, Northern blot and semi-quantitative RT-PCR were developed to confirm 4 differentially expressed genes screened by cDNA microarray, and it showed great consistency between the microarray data and Northern blot results or semi-quantitative RT-PCR results. The present study will be helpful for clarifying the molecular mechanism of obesity in chickens.

  4. Obesity and adipose tissue remodeling%肥胖与脂肪组织重构

    杨永玉; 胡长平

    2016-01-01

    Obesity is a major risk factor for the generation and development of diabetes, atherosclerosis, hyperlipidemia and cancer. Obesity is accompanied with remodeling of adipose tis-sue, such as changed cell component and function, angiogene-sis, extracellular matrix remodeling and infiltration of inflamma-tory cells. It is important for the prevention of obesity to study adipose tissue remodeling. This review summarizes recent ad-vances in adipose tissue remodeling.%肥胖是糖尿病、动脉粥样硬化、高脂血症和癌症发生发展的主要危险因素。肥胖发生时伴随着脂肪组织的重构,主要表现为各种细胞组成和功能的改变、血管新生、细胞外基质重构和炎症细胞浸润。深入研究脂肪组织重构对肥胖的防治具有重要意义。该文就肥胖发生时脂肪组织重构的最新研究进展进行综述。

  5. Insulin Resistance in Adipose Tissue but Not in Liver Is Associated with Aortic Valve Calcification

    Esteban Jorge-Galarza

    2016-01-01

    Full Text Available Background. Insulin resistance is involved in the pathogenesis of cardiovascular disease, but its relationship with cardiovascular calcification has yielded conflicting results. The purpose of the present study was to investigate the role of hepatic and adipose tissue insulin resistance on the presence of coronary artery (CAC > 0 and aortic valve calcification (AVC > 0. Methods. In 1201 subjects (52% women, 53.6±9.3 years old without familiar and personal history of coronary heart disease, CAC and AVC were assessed by multidetector-computed tomography. Cardiovascular risk factors were documented and lipid profile, inflammation markers, glucose, insulin, and free fatty acids were measured. Hepatic insulin resistance (HOMA-IR and adipose tissue insulin resistance (Adipo-IR indices were calculated. Results. There was a significant relationship between HOMA-IR and Adipo-IR indices (r=0.758, p 0 and AVC > 0. After full adjustment, subjects in the highest quartile of Adipo-IR index had higher odds of AVC > 0 (OR: 2.40; 95% CI: 1.30–4.43, as compared to those in the lowest quartile. Conclusions. Adipo-IR was independently associated with AVC > 0. This suggests that abnormal adipose tissue function favors insulin resistance that may promote the development and progression of AVC.

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

    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.

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

    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.

  8. Rorα deficiency and decreased adiposity are associated with induction of thermogenic gene expression in subcutaneous white adipose and brown adipose tissue.

    Lau, Patrick; Tuong, Zewen K; Wang, Shu-Ching; Fitzsimmons, Rebecca L; Goode, Joel M; Thomas, Gethin P; Cowin, Gary J; Pearen, Michael A; Mardon, Karine; Stow, Jennifer L; Muscat, George E O

    2015-01-15

    The Rar-related orphan receptor-α (Rorα) is a nuclear receptor that regulates adiposity and is a potential regulator of energy homeostasis. We have demonstrated that the Rorα-deficient staggerer (sg/sg) mice display a lean and obesity-resistant phenotype. Adaptive Ucp1-dependent thermogenesis in beige/brite and brown adipose tissue serves as a mechanism to increase energy expenditure and resist obesity. DEXA and MRI analysis demonstrated significantly decreased total fat mass and fat/lean mass tissue ratio in male chow-fed sg/sg mice relative to wt mice. In addition, we observed increased Ucp1 expression in brown adipose and subcutaneous white adipose tissue but not in visceral adipose tissue from Rorα-deficient mice. Moreover, this was associated with significant increases in the expression of the mRNAs encoding the thermogenic genes (i.e., markers of brown and beige adipose) Pparα, Errα, Dio2, Acot11/Bfit, Cpt1β, and Cidea in the subcutaneous adipose in the sg/sg relative to WT mice. These changes in thermogenic gene expression involved the significantly increased expression of the (cell-fate controlling) histone-lysine N-methyltransferase 1 (Ehmt1), which stabilizes the Prdm16 transcriptional complex. Moreover, primary brown adipocytes from sg/sg mice displayed a higher metabolic rate, and further analysis was consistent with increased uncoupling. Finally, core body temperature analysis and infrared thermography demonstrated that the sg/sg mice maintained greater thermal control and cold tolerance relative to the WT littermates. We suggest that enhanced Ucp1 and thermogenic gene expression/activity may be an important contributor to the lean, obesity-resistant phenotype in Rorα-deficient mice.

  9. Dynamic gene expression profiles during postnatal development of porcine subcutaneous adipose.

    Zhang, Jie; Ma, Jideng; Long, Keren; Jin, Long; Liu, Yihui; Zhou, Chaowei; Tian, Shilin; Chen, Lei; Luo, Zonggang; Tang, Qianzi; Jiang, An'an; Wang, Xun; Wang, Dawei; Jiang, Zhi; Wang, Jinyong; Li, Xuewei; Li, Mingzhou

    2016-01-01

    A better understanding of the control of lipogenesis is of critical importance for both human and animal physiology. This requires a better knowledge of the changes of gene expression during the process of adipose tissue development. Thus, the objective of the current study was to determine the effects of development on subcutaneous adipose tissue gene expression in growing and adult pigs. Here, we present a comprehensive investigation of mRNA transcriptomes in porcine subcutaneous adipose tissue across four developmental stages using digital gene expression profiling. We identified 3,274 differential expressed genes associated with oxidative stress, immune processes, apoptosis, energy metabolism, insulin stimulus, cell cycle, angiogenesis and translation. A set of universally abundant genes (ATP8, COX2, COX3, ND1, ND2, SCD and TUBA1B) was found across all four developmental stages. This set of genes may play important roles in lipogenesis and development. We also identified development-related gene expression patterns that are linked to the different adipose phenotypes. We showed that genes enriched in significantly up-regulated profiles were associated with phosphorylation and angiogenesis. In contrast, genes enriched in significantly down-regulated profiles were related to cell cycle and cytoskeleton organization, suggesting an important role for these biological processes in adipose growth and development. These results provide a resource for studying adipose development and promote the pig as a model organism for researching the development of human obesity, as well as being used in the pig industry.

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

    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.

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

    Ribeiro Ricardo

    2012-09-01

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

  12. The Use of Adipose Tissue-Derived Progenitors in Bone Tissue Engineering - a Review

    Bhattacharya, Indranil; Ghayor, Chafik; Weber, Franz E.

    2016-01-01

    2500 years ago, Hippocrates realized that bone can heal without scaring. The natural healing potential of bone is, however, restricted to small defects. Extended bone defects caused by trauma or during tumor resections still pose a huge problem in orthopedics and cranio-maxillofacial surgery. Bone tissue engineering strategies using stem cells, growth factors, and scaffolds could overcome the problems with the treatment of extended bone defects. In this review, we give a short overview on bone tissue engineering with emphasis on the use of adipose tissue-derived stem cells and small molecules.

  13. Improvement of Liquid Fructose-Induced Adipose Tissue Insulin Resistance by Ginger Treatment in Rats Is Associated with Suppression of Adipose Macrophage-Related Proinflammatory Cytokines

    Jianwei Wang

    2013-01-01

    Full Text Available Adipose tissue insulin resistance (Adipo-IR results in excessive release of free fatty acids from adipose tissue, which plays a key role in the development of “lipotoxicity.” Therefore, amelioration of Adipo-IR may benefit the treatment of other metabolic abnormalities. Here we found that treatment with the alcoholic extract of ginger (50 mg/kg/day, by oral gavage for five weeks attenuated liquid fructose-induced hyperinsulinemia and an increase in the homeostasis model assessment of insulin resistance (HOMA-IR index in rats. More importantly, ginger reversed the increases in the Adipo-IR index and plasma nonesterified fatty acid concentrations during the oral glucose tolerance test assessment. Adipose gene/protein expression profiles revealed that ginger treatment suppressed CD68 and F4/80, two important macrophage accumulation markers. Consistently, the macrophage-associated cytokines tissue necrosis factor alpha and interleukin-6 were also downregulated. In contrast, insulin receptor substrate (IRS-1, but not IRS-2, was upregulated. Moreover, monocyte chemotactic protein (MCP-1 and its receptor chemokine (C-C motif receptor-2 were also suppressed. Thus these results suggest that amelioration of fructose-induced Adipo-IR by ginger treatment in rats is associated with suppression of adipose macrophage-related proinflammatory cytokines.

  14. File list: InP.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  16. File list: InP.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  18. Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice

    Adipose tissue macrophages play an important role in the pathogenesis of obese type 2 diabetes. High-fat diet-induced obesity has been shown to lead to adipose tissue macrophages accumulation in rodents;however, the impact of hyperglycemia on adipose tissue macrophages dynamics in high-fat diet-fed ...

  19. File list: NoD.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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  1. File list: InP.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

    Full Text Available InP.Adp.20.AllAg.Adipose_Tissue,_White hg19 Input control Adipocyte Adipose Tissue,... White http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Adp.20.AllAg.Adipose_Tissue,_White.bed ...

  2. The effect of exercise on regional adipose tissue and splanchnic lipid metabolism in overweight type 2 diabetic subjects

    Simonsen, L; Henriksen, O; Enevoldsen, L H

    2004-01-01

    To test the hypothesis that adipose tissue lipolysis is enhanced in patients with Type 2 diabetes mellitus, we examined the effect of exercise on regional adipose tissue lipolysis and fatty acid mobilisation and measured the acute effects of exercise on the co-ordination of adipose tissue...

  3. Macrophages Undergo M1-to-M2 Transition in Adipose Tissue Regeneration in a Rat Tissue Engineering Model.

    Li, Zhijin; Xu, Fangfang; Wang, Zhifa; Dai, Taiqiang; Ma, Chao; Liu, Bin; Liu, Yanpu

    2016-10-01

    Macrophages are involved in the full processes of tissue healing or regeneration and play an important role in the regeneration of a variety of tissues. Although recent evidence suggests the role of different macrophage phenotypes in adipose tissue expansion, metabolism, and remodeling, the spectrum of macrophage phenotype in the adipose tissue engineering field remains unknown. The present study established a rat model of adipose tissue regeneration using a tissue engineering chamber. Macrophage phenotypes were assessed during the regenerative process in the model. Neo-adipose tissue was generated 6 weeks after implantation. Macrophages were obvious in the chamber constructs 3 days after implantation, peaked at day 7, and significantly decreased thereafter. At day 3, macrophages were predominantly M1 macrophages (CCR7+), and there were few M2 macrophages (CD206+). At day 7, the percentage of M2 macrophages significantly increased and remained stable at day 14. M2 macrophages became the predominant macrophage population at 42 days. Enzyme-linked immunosorbent assay demonstrated transition of cytokines from pro-inflammatory to anti-inflammatory, which was consistent with the transition of macrophage phenotype from M1 to M2. These results showed distinct transition of macrophage phenotypes from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 in adipose tissue regeneration in our tissue engineering model. This study provides new insight into macrophage phenotype transition in the regeneration of adipose tissue.

  4. 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.

    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

  5. Dedifferentiated fat cells: an alternative source of adult multipotent cells from the adipose tissues

    Shen, Jie-fei; Sugawara, Atsunori; Yamashita, Joe; Ogura, Hideo; Sato, Soh

    2011-01-01

    When adipose-derived stem cells (ASCs) are retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based on their buoyancy, mature adipocytes can be easily isolated from the adipose cell suspension and dedifferentiated into lipid-free fibroblast-like cells, named dedifferentiated fat (DFAT) cells. DFAT cells re-establish active proliferation ability and undertake multipotent capaciti...

  6. Sugar-sweetened and diet beverages in relation to visceral adipose tissue

    Odegaard, Andrew O.; Choh, Audrey C.; Czerwinski, Stefan A; TOWNE, BRADFORD; Demerath, Ellen W.

    2011-01-01

    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 associ...

  7. Increased lipolysis but diminished gene expression of lipases in subcutaneous adipose tissue of healthy young males with intrauterine growth retardation

    Højbjerre, Lise; Alibegovic, Amra C; Sonne, Mette P

    2011-01-01

    Intrauterine growth retardation (IUGR) is associated with a central fat distribution and risk of developing type 2 diabetes in adults when exposed to a sedentary Western lifestyle. Increased lipolysis is an early defect of metabolism in IUGR subjects, but the sites and molecular mechanisms involved......) and femoral (SCFAT) adipose tissue. Additionally, mRNA expression of lipases was evaluated in biopsies from SCAAT. Lipolysis in SCAAT was substantially higher in IUGR than in CON subjects despite markedly lower mRNA expression of lipases. Blood flow was higher in IUGR compared with CON in both SCAAT and SCFAT...... are characterized by increased in vivo adipose tissue lipolysis and blood flow with a paradoxically decreased expression of lipases compared with CON, and 10 days of physical inactivity underlined the baseline findings. Subjects with IUGR exhibit primary defects in adipose tissue metabolism....

  8. Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

    Basse, Astrid L.; Dixen, Karen; Yadav, Rachita;

    2015-01-01

    abundance and down-regulation of gene expression related to mitochondrial function and oxidative phosphorylation. Global gene expression profiling demonstrated that the time points grouped into three phases: a brown adipose phase, a transition phase and a white adipose phase. Between the brown adipose......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...... with a time course study of the perirenal adipose depot. We observed changes in tissue morphology, gene expression and metabolism within the first two weeks of postnatal life consistent with the expected transition from BAT to WAT. The transformation was characterized by massively decreased mitochondrial...

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

    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.

  10. Obtaining freshly isolated and cultured mesenchymal stem cells from human adipose tissue.

    Boquest, Andrew C; Collas, Philippe

    2012-01-01

    The stromal compartment of adipose tissue harbors mesenchymal stem cells (MSCs) (also called stromal stem cells) that display extensive proliferative capacity and multilineage differentiation potential. Such cells offer a practical avenue of generating patient-matched tissue for use in regenerative medicine. It is relatively easy to isolate these cells from adipose tissue in large enough quantities (tens of millions) to allow for their clinical use in a native, uncultured form. Alternatively, MSCs from adipose tissue can be expanded and differentiated into the desired tissue type in vitro using straightforward cell culture techniques. In this chapter, we outline procedures for isolating large numbers of highly purified MSCs from human adipose tissue in their native, uncultured form and methods for their subsequent expansion and differentiation in vitro.

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

    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....

  12. Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice.

    Rosell, Meritxell; Kaforou, Myrsini; Frontini, Andrea; Okolo, Anthony; Chan, Yi-Wah; Nikolopoulou, Evanthia; Millership, Steven; Fenech, Matthew E; MacIntyre, David; Turner, Jeremy O; Moore, Jonathan D; Blackburn, Edith; Gullick, William J; Cinti, Saverio; Montana, Giovanni; Parker, Malcolm G; Christian, Mark

    2014-04-15

    Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a "brite" transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with "browning," as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes.

  13. When fat becomes an ally of the enemy: adipose tissue as collaborator in human breast cancer.

    Lapeire, Lore; Denys, Hannelore; Cocquyt, Véronique; De Wever, Olivier

    2015-07-01

    Since the discovery of leptin in 1994, our vision of adipose tissue as a static organ regulating mainly lipid storage and release has been completely overthrown, and adipose tissue is now seen as an active and integral organ in human physiology. In the past years, extensive research has tremendously given us more insights in the mechanisms and pathways involved not only in normal but also in 'sick' adipose tissue, for example, in obesity and lipodystrophy. With growing evidence of a link between obesity and several types of cancer, research focusing on the interaction between adipose tissue and cancer has begun to unravel the interesting but complex multi-lateral communication between the different players. With breast cancer as one of the first cancer types where a positive correlation between obesity and breast cancer incidence and prognosis in post-menopausal women was found, we have focused this review on the paracrine and endocrine role of adipose tissue in breast cancer initiation and progression. As important inter-species differences in adipose tissue occur, we mainly selected human adipose tissue- and breast cancer-based studies with a short reflection on therapeutic possibilities. This review is part of the special issue on "Adiposopathy in Cancer and (Cardio)Metabolic Diseases".

  14. High-fat diet induces changes in adipose tissue trans-4-oxo-2-nonenal and trans-4-hydroxy-2-nonenal levels in a depot-specific manner.

    Long, Eric K; Olson, Dalay M; Bernlohr, David A

    2013-10-01

    Protein carbonylation is the covalent modification of proteins by α,β-unsaturated aldehydes produced by nonenzymatic lipid peroxidation of polyunsaturated fatty acids. The most widely studied aldehyde product of lipid peroxidation, trans-4-hydroxy-2-nonenal (4-HNE), is associated with obesity-induced metabolic dysfunction and has demonstrated reactivity toward key proteins involved in cellular function. However, 4-HNE is only one of many lipid peroxidation products and the lipid aldehyde profile in adipose tissue has not been characterized. To further understand the role of oxidative stress in obesity-induced metabolic dysfunction, a novel LC-MS/MS method was developed to evaluate aldehyde products of lipid peroxidation and applied to the analysis of adipose tissue. 4-HNE and trans-4-oxo-2-nonenal (4-ONE) were the most abundant aldehydes present in adipose tissue. In high fat-fed C57Bl/6J and ob/ob mice the levels of lipid peroxidation products were increased 5- to 11-fold in epididymal adipose, unchanged in brown adipose, but decreased in subcutaneous adipose tissue. Epididymal adipose tissue of high fat-fed mice also exhibited increased levels of proteins modified by 4-HNE and 4-ONE, whereas subcutaneous adipose tissue levels of these modifications were decreased. High fat feeding of C57Bl/6J mice resulted in decreased expression of a number of genes linked to antioxidant biology selectively in epididymal adipose tissue. Moreover, TNFα treatment of 3T3-L1 adipocytes resulted in decreased expression of GSTA4, GPx4, and Prdx3 while upregulating the expression of SOD2. These results suggest that inflammatory cytokines selectively downregulate antioxidant gene expression in visceral adipose tissue, resulting in elevated lipid aldehydes and increased protein carbonylation.

  15. Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels

    Tinahones Francisco

    2012-04-01

    Full Text Available Abstract Background The expansion of adipose tissue is linked to the development of its vasculature, which appears to have the potential to regulate the onset of obesity. However, at present, there are no studies highlighting the relationship between human adipose tissue angiogenesis and obesity-associated insulin resistance (IR. Results Our aim was to analyze and compare angiogenic factor expression levels in both subcutaneous (SC and omentum (OM adipose tissues from morbidly obese patients (n = 26 with low (OB/L-IR (healthy obese and high (OB/H-IR degrees of IR, and lean controls (n = 17. Another objective was to examine angiogenic factor correlations with obesity and IR. Here we found that VEGF-A was the isoform with higher expression in both OM and SC adipose tissues, and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans. This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in both SC and OM. Conclusion We hereby propose that the alteration in MMP15, VEGF-B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose tissue processes related to the development of IR, and the up-regulation of VEGF-A in adipose tissue could have a relationship with the prevention of this pathology.

  16. Prenatal low-protein and postnatal high-fat diets induce rapid adipose tissue growth by inducing Igf2 expression in Sprague Dawley rat offspring.

    Claycombe, Kate J; Uthus, Eric O; Roemmich, James N; Johnson, Luann K; Johnson, W Thomas

    2013-10-01

    Maternal low-protein diets result in lower birth weight followed by accelerated catch-up growth that is accompanied by the development of obesity and glucose intolerance in later life. Whether postnatal high-fat (HF) diets further contribute to the development of obesity and insulin resistance in offspring by affecting adipose tissue metabolism and DNA methylation is currently unknown. Obese-prone Sprague-Dawley rats were fed 8% low protein (LP) or 20% normal protein diets for 3 wk prior to conception and throughout pregnancy and lactation to investigate whether prenatal LP and postnatal HF diets affect the rate of adipose tissue growth, insulin-like growth factor 2 (Igf2) expression, and DNA methylation in male offspring. At weaning, the offspring were fed 10% normal fat or 45% HF diets for 12 wk. The adipose tissue growth rate was increased (up to 26-fold) by the LP prenatal and HF postnatal diets. Adipose tissue Igf2 mRNAs and DNA methylation were increased by the LP prenatal and HF postnatal diets. The LP prenatal and HF postnatal diet increased the number of small adipocytes in adipose tissue and decreased insulin sensitivity. These findings suggest that prenatal LP and postnatal HF intake result in adipose tissue catch-up growth through alterations in the expression of the Igf2 gene and DNA methylation within adipocytes. These alterations in adiposity are accompanied by an increased risk of development of type 2 diabetes.

  17. Loss of Oncostatin M Signaling in Adipocytes Induces Insulin Resistance and Adipose Tissue Inflammation in Vivo.

    Elks, Carrie M; Zhao, Peng; Grant, Ryan W; Hang, Hardy; Bailey, Jennifer L; Burk, David H; McNulty, Margaret A; Mynatt, Randall L; Stephens, Jacqueline M

    2016-08-12

    Oncostatin M (OSM) is a multifunctional gp130 cytokine. Although OSM is produced in adipose tissue, it is not produced by adipocytes. OSM expression is significantly induced in adipose tissue from obese mice and humans. The OSM-specific receptor, OSM receptor β (OSMR), is expressed in adipocytes, but its function remains largely unknown. To better understand the effects of OSM in adipose tissue, we knocked down Osmr expression in adipocytes in vitro using siRNA. In vivo, we generated a mouse line lacking Osmr in adiponectin-expressing cells (OSMR(FKO) mice). The effects of OSM on gene expression were also assessed in vitro and in vivo OSM exerts proinflammatory effects on cultured adipocytes that are partially rescued by Osmr knockdown. Osm expression is significantly increased in adipose tissue T cells of high fat-fed mice. In addition, adipocyte Osmr expression is increased following high fat feeding. OSMR(FKO) mice exhibit increased insulin resistance and adipose tissue inflammation and have increased lean mass, femoral length, and bone volume. Also, OSMR(FKO) mice exhibit increased expression of Osm, the T cell markers Cd4 and Cd8, and the macrophage markers F4/80 and Cd11c Interestingly, the same proinflammatory genes induced by OSM in adipocytes are induced in the adipose tissue of the OSMR(FKO) mouse, suggesting that increased expression of proinflammatory genes in adipose tissue arises both from adipocytes and other cell types. These findings suggest that adipocyte OSMR signaling is involved in the regulation of adipose tissue homeostasis and that, in obesity, OSMR ablation may exacerbate insulin resistance by promoting adipose tissue inflammation.

  18. Influence of age and position on the CT number of adipose tissues in pigs.

    McEvoy, Fintan J; Madsen, Mads T; Svalastoga, Eiliv L

    2008-10-01

    The location of adipose tissue depots is important in determining their significance. Research into the physical and chemical differences between these depots is therefore of interest. Using image analysis, this paper examines the influence of location on the linear attenuation coefficient of adipose tissue for X-rays, in computed tomography (as indicated by CT number) at three time points. Nine pigs were CT scanned on three separate occasions approximately 1 month apart. The mean CT number was -78, -100, and -104 for visceral adipose tissue (VAT) from the first to the final scan, respectively. The corresponding CT numbers for subcutaneous adipose tissue (SAT) were -80, -101, and -106. There was a significant difference between the CT numbers at each location at each scan (P values from 0.025 to <0.001) and between the CT numbers for each location at different times (P < 0.05). In a separate analysis of the final scan session, the mean CT number of adipose tissue at increasing distances from a mathematically defined center of the animal was determined. Regression analysis showed that the CT number of adipose tissue decreases with increasing distance from the animal's center (y = -102.7 - 0.04 x, P < 0.001, where y is the predicted CT number for adipose tissue, from the animal center (x = 0) to the skin (x = 100)). It can thus be expected that the overall mean CT number for adipose tissue can be used as an indicator of the relative quantities of adipose tissue at each location if the mean for each is known.

  19. Review article: Relationships between adipose tissue and psoriasis, with or without arthritis.

    ERIC eTOUSSIROT

    2014-08-01

    Full Text Available Psoriasis (Pso is a common chronic cutaneous inflammatory disease involving the skin that is associated with serious comorbidities. Comorbidities in Pso include psoriatic arthritis (PsA, reduced quality of life, malignancy, depression, but also a constellation of associated conditions that enhance the cardiovascular (CV risk. Indeed, obesity is common in patients with Pso or PsA and is considered to be a risk factor for the onset of these diseases. Patients with Pso and PsA share common obesity-related complications such as metabolic syndrome, dyslipidemia, diabetes or insulin resistance and CV diseases. Chronic inflammation in Pso and PsA partially explains the development of atherosclerosis and CV diseases. In parallel, body composition is disturbed in patients with Pso or PsA, as suggested by anthropometric measurements, while an excess of abdominal adiposity is observed in PsA, enhancing the risk of metabolic syndrome and CV diseases. Adipokines may link the adipose tissue to the obesity-related complications of Pso and PsA. Indeed, altered circulating levels of the adipokines leptin, adiponectin, visfatine, and resistin have been found in patients with Pso or PsA. In addition, an excess of adipose tissue may compromise the therapeutic response to traditional drugs or biological agents in Pso and PsA. This paper reviews the comorbidities that contribute to enhanced CV risk, the body composition results, and the potential role of adipokines in systemic inflammation and energetic balance in Pso and PsA.

  20. Polychlorinated biphenyls and polybrominated biphenyl ethers in adipose tissue and matched serum from an E-waste recycling area (Wenling, China).

    Lv, Quan-Xia; Wang, Wenyue; Li, Xing-Hong; Yu, Lianlian; Zhang, Yun; Tian, Yuan

    2015-04-01

    To Date, the knowledge on relationship between PCBs/PBDEs exposure and thyroid hormones (THs) levels during pregnancy still needs to be extended. Meanwhile, studies on congener-specific adipose-serum ratios for PCBs/PBDEs were limited. This study reports the levels of PCBs/PBDEs in serum-adipose tissue samples (n = 64) from expectant women living surrounding e-waste recycling sites in Wenling, China. Their concentrations varied from several to hundreds of ng g(-1) lipid. Maternal exposure to PCBs was associated with lower TSH during pregnancy, suggesting possible implication for maternal health and fetal development. The compound levels between the adipose tissue and matched serum samples were highly correlated (p < 0.001), generating a predicted adipose-serum partitioning relationship for individual PCB congener and PBDE congener. Molecular characteristics, such as Kow value, molecular weight and molecular volume, may play a key role in the variable partitioning of some compounds between serum and adipose tissue.

  1. Fatty acid composition of adipose tissue triglycerides after weight loss and weight maintenance: the DIOGENES study.

    Kunesova, M.; Hlavaty, P.; Tvrzicka, E.; Stankova, B.; Kalouskova, P.; Viguerie, N.; Larsen, T.M.; van Baak, M.A.; Jebb, S.A.; Martinez, J.A.; Pfeiffer, A.F.; Kafatos, A.; Handjieva Darlenska, T.; Hill, M.; Langin, D.; Zak, A.; Astrup, A.; Saris, W.H.

    2013-01-01

    Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. To assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants of the DIOGENES

  2. Diet and adipose tissue distributions: The Multi-Ethnic Study of Atherosclerosis

    Dietary quality affects cardiometabolic risk, yet its pathways of influence on regional adipose tissue depots involved in metabolic and diabetes risk are not well established. We aimed to investigate the relationship between dietary quality and regional adiposity. We investigated 5079 individuals in...

  3. Peroxisome Proliferator-activated Receptor - Activation Promotes Infiltration of Alternatively Activated Macrophages into Adipose Tissue

    Stienstra, R.; Duval, C.N.C.; Keshtkar Ghiasabadi, S.; Laak, van der J.; Kersten, A.H.; Müller, M.R.

    2008-01-01

    Obesity is associated with infiltration of macrophages into adipose tissue. Adipose macrophages may contribute to an elevated inflammatory status by secreting a variety of proinflammatory mediators, including tumor necrosis factor alpha and interleukin-6 (IL-6). Recent data suggest that during diet-

  4. Peroxisome proliferator-activated receptor gamma activation promotes infiltration of alternatively activated macrophages into adipose tissue.

    Stienstra, R.; Duval, C.; Keshtkar, S.; Laak, J. ter; Kersten, S.; Muller, M.

    2008-01-01

    Obesity is associated with infiltration of macrophages into adipose tissue. Adipose macrophages may contribute to an elevated inflammatory status by secreting a variety of proinflammatory mediators, including tumor necrosis factor alpha and interleukin-6 (IL-6). Recent data suggest that during diet-

  5. Computer tomographic investigation of subcutaneous adipose tissue as an indicator of body composition

    McEvoy, Fintan; Madsen, Mads T.; Nielsen, Mai B.;

    2009-01-01

    that CT can be used to measure subcutaneous adipose tissue thickness and identify novel measurement sites that can be used as predictors of general adiposity. Methods Growing pigs (N = 12), were each CT scanned on three occasions. From these data the total volume of adipose tissue was determined...... the limits of the relevant tissues and automated measurements were successfully generated. Two sites on the animal were identified where there was optimal correlation with fat-index. The first of these was located 4 intercostal spaces cranial to the caudal extremity of the last rib, the other, a further 5...

  6. Adipose tissue extracts plasma ammonia after sprint exercise in women and men

    Esbjörnsson, Mona; Bülow, Jens; Norman, Barbara;

    2006-01-01

    This study evaluates a possible contribution of adipose tissue to the elimination of plasma ammonia (NH(3)) after high-intensity sprint exercise. In 14 healthy men and women, repeated blood samples for plasma NH(3) analyses were obtained from brachial artery and from a subcutaneous abdominal vein...... before and after three repeated 30-s cycle sprints separated by 20 min of recovery. Biopsies from subcutaneous abdominal adipose tissue were obtained and analyzed for glutamine and glutamate content. After exercise, both arterial and abdominal venous plasma NH(3) concentrations were lower in women than...... in men (P adipose tissue. However, the fractional extraction (a...

  7. Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice.

    Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

    2015-01-01

    Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia - before severe fat loss - in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.

  8. White adipose tissue genome wide-expression profiling and adipocyte metabolic functions after soy protein consumption in rats.

    Frigolet, Maria E; Torres, Nimbe; Uribe-Figueroa, Laura; Rangel, Claudia; Jimenez-Sanchez, Gerardo; Tovar, Armando R

    2011-02-01

    Obesity is associated with an increase in adipose tissue mass due to an imbalance between high dietary energy intake and low physical activity; however, the type of dietary protein may contribute to its development. The aim of the present work was to study the effect of soy protein versus casein on white adipose tissue genome profiling, and the metabolic functions of adipocytes in rats with diet-induced obesity. The results showed that rats fed a Soy Protein High-Fat (Soy HF) diet gained less weight and had lower serum leptin concentration than rats fed a Casein High-Fat (Cas HF) diet, despite similar energy intake. Histological studies indicated that rats fed the Soy HF diet had significantly smaller adipocytes than those fed the Cas HF diet, and this was associated with a lower triglyceride/DNA content. Fatty acid synthesis in isolated adipocytes was reduced by the amount of fat consumed but not by the type of protein ingested. Expression of genes of fatty acid oxidation increased in adipose tissue of rats fed Soy diets; microarray analysis revealed that Soy protein consumption modified the expression of 90 genes involved in metabolic functions and inflammatory response in adipose tissue. Network analysis showed that the expression of leptin was regulated by the type of dietary protein and it was identified as a central regulator of the expression of lipid metabolism genes in adipose tissue. Thus, soy maintains the size and metabolic functions of adipose tissue through biochemical adaptations, adipokine secretion, and global changes in gene expression.

  9. Omentin-1 is decreased in maternal plasma, placenta and adipose tissue of women with pre-existing obesity.

    Gillian Barker

    Full Text Available OBJECTIVE: The aim of this study was to determine (i the effect of maternal obesity and gestational diabetes mellitus (GDM on (i the circulating levels of omentin-1 in cord and maternal plasma, and (ii gene expression and release of omentin-1 from human placenta and adipose tissue. The effect of pregnancy on circulating omentin-1 levels was also determined. DESIGN: Omentin-1 levels were measured in maternal and cord plasma from obese and non-obese normal glucose tolerant women (NGT; n = 44 and women with GDM (n = 39 at the time of term elective Caesarean section. Placenta and adipose tissue expression and release of omentin-1 was measured from 22 NGT and 22 GDM women collected at the time of term elective Caesarean section. Omentin-1 levels were also measured in maternal plasma from 13 NGT women at 11 and 28 weeks gestation and 7 weeks postpartum. RESULTS: Maternal obesity was associated with significantly lower omentin-1 levels in maternal plasma; however, there was no effect of maternal obesity on cord omentin levels. Omentin-1 gene expression was lower in placenta and adipose tissue obtained from women with pre-existing obesity. In addition to this, adipose tissue release of omentin-1 was significantly lower from obese pregnant women. Omentin-1 levels were significantly lower in non-obese GDM compared to non-obese NGT women. However, there was no difference in omentin-1 levels between obese NGT and obese GDM women. There was no effect of GDM on cord omentin levels, and placental and adipose tissue omentin-1 expression. Maternal omentin-1 levels were negatively correlated with fetal birthweight and fetal ponderal index. CONCLUSIONS: The data presented in this study demonstrate that pre-existing maternal obesity is associated with lower omentin-1 expression in placenta, adipose tissue and maternal plasma. Alteration in omentin-1 in pregnancy may influence the development of metabolic disorders in offspring later in life.

  10. Adipose tissue-targeted 11β-hydroxysteroid dehydrogenase type 1 inhibitor protects against diet-induced obesity.

    Liu, Juan; Wang, Long; Zhang, Aisen; Di, Wenjuan; Zhang, Xiao; Wu, Lin; Yu, Jing; Zha, Juanmin; Lv, Shan; Cheng, Peng; Hu, Miao; Li, Yujie; Qi, Hanmei; Ding, Guoxian; Zhong, Yi

    2011-01-01

    Current pharmacological treatments for obesity and metabolic syndrome have various limitations. Recently, adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of obesity and metabolic syndrome. Nevertheless, there is no adipose tissue-targeted 11β-HSD1 inhibitor available now. We sought to develop a new 11β-HSD1 pharmacological inhibitor that homes specifically to the white adipose tissue and aimed to investigate whether adipose tissue-targeted 11β-HSD1 inhibitor might decrease body weight gain and improve glucose tolerance in diet-induced obesity mice. BVT.2733, an 11β-HSD1 selective inhibitor was connected with a peptide CKGGRAKDC that homes to white fat vasculature. CKGGRAKDC-BVT.2733 (T-BVT) or an equimolar mixture of CKGGRAKDC and BVT.2733 (NT-BVT) was given to diet-induced obesity mice for two weeks through subcutaneous injection. T-BVT decreased body weight gain, improved glucose tolerance and decreased adipocyte size compared with vehicle treated mice. In adipose tissue T-BVT administration significantly increased adiponectin, vaspin mRNA levels; In liver T-BVT administration decreased the mRNA level of phosphoenolpyruvate carboxykinase (PEPCK), increased the mRNA levels of mitochondrial carnitine palmi-toyltransferase-I (mCPT-I) and peroxisome proliferator-activated receptorα(PPARα). No significant differences in adipocyte size and hepatic gene expression were observed after treatment with NT-BVT compared with vehicle treated mice, though NT-BVT also decreased body weight gain, improved glucose tolerance, and increased uncoupling protein-2 (UCP-2) mRNA levels in muscle. These results suggest that an adipose tissue-targeted pharmacological inhibitor of 11β-HSD1 may prove to be a new approach for the treatment of obesity and metabolic syndrome.

  11. Mice that are fed a high-fat diet display increased hepcidin expression in adipose tissue.

    Gotardo, Érica Martins Ferreira; dos Santos, Aline Noronha; Miyashiro, Renan Akira; Gambero, Sheley; Rocha, Thalita; Ribeiro, Marcelo Lima; Gambero, Alessandra

    2013-01-01

    Since the discovery that hepcidin is expressed in the adipose tissue of obese subjects, attention has been increasingly focused on alterations in iron homeostasis that are associated with adiposity. We examined the production of hepcidin, the expression of hepcidin-related genes and the iron content of the adipose tissue in obesity using Swiss mice fed a high-fat diet (HFD). The mice were maintained on a control diet or HFD for 12 or 24 wk, and body weight, adiposity and glucose homeostasis were evaluated. The expression of several genes (hepcidin, TfR1, TfR2, DMT1, FT-heavy, ferroportin, IRP-1, IRP-2 and HIF-1) and the protein expression of hepcidin and IL-6 were quantified. The iron level was assessed using a Prussian blue reaction in paraffin-embedded tissue. After 24 wk on the HFD, we observed increases in the levels of hepcidin in the serum and the visceral adipose tissue. The IL-6 levels also increased in the visceral adipose tissue. Adipocytes isolated from the visceral adipose tissues of lean and obese mice expressed hepcidin at comparable levels; however, isolated macrophages from the stromal vascular fraction expressed higher hepcidin levels. Adipose tissues from obese mice displayed increased tfR2 expression and the presence of iron. Our results indicate that IL-6 and iron may affect the signaling pathways governing hepcidin expression. Thus, the mice fed HFD for 24 wk represent a suitable model for the study of obesity-linked hepcidin alterations. In addition, hepcidin may play local roles in controlling iron availability and interfering with inflammation in adipose tissue.

  12. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue.

    Rönn, Tina; Volkov, Petr; Davegårdh, Cajsa; Dayeh, Tasnim; Hall, Elin; Olsson, Anders H; Nilsson, Emma; Tornberg, Asa; Dekker Nitert, Marloes; Eriksson, Karl-Fredrik; Jones, Helena A; Groop, Leif; Ling, Charlotte

    2013-06-01

    Epigenetic mechanisms are implicated in gene regulation and the development of different diseases. The epigenome differs between cell types and has until now only been characterized for a few human tissues. Environmental factors potentially alter the epigenome. Here we describe the genome-wide pattern of DNA methylation in human adipose tissue from 23 healthy men, with a previous low level of physical activity, before and after a six months exercise intervention. We also investigate the differences in adipose tissue DNA methylation between 31 individuals with or without a family history of type 2 diabetes. DNA methylation was analyzed using Infinium HumanMethylation450 BeadChip, an array containing 485,577 probes covering 99% RefSeq genes. Global DNA methylation changed and 17,975 individual CpG sites in 7,663 unique genes showed altered levels of DNA methylation after the exercise intervention (qtype 2 diabetes candidate genes had CpG sites with differences in adipose tissue DNA methylation in response to exercise (qadipose tissue in vivo affect adipocyte metabolism, we silenced Hdac4 and Ncor2 respectively in 3T3-L1 adipocytes, which resulted in increased lipogenesis both in the basal and insulin stimulated state. In conclusion, exercise induces genome-wide changes in DNA methylation in human adipose tissue, potentially affecting adipocyte metabolism.

  13. Assessing the effect of a high-fat diet on rodents' adipose tissue using Brillouin and Raman spectroscopy

    Troyanova-Wood, Maria; Gobbell, Cassidy; Meng, Zhaokai; Yakovlev, Vladislav V.

    2016-03-01

    The purpose of this study is to evaluate the effect of a high-lipid diet on elasticity of adipose tissue. We employed dual Raman/Brillouin microspectroscopy to analyze brown and white adipose tissues obtained from adult rats. The rats were divided into two groups, one of which received a high-fat feed, while the other served as a control. We hypothesized that the changes in the elasticity of adipose tissues between the two groups can be successfully assessed using Brillouin spectroscopy. We found that the brown adipose tissue possessed a lesser Brillouin shift than the white adipose within each group and that the elastic modulus of both adipose tissues increases in the high-fat diet group. The Raman spectra provided supplementary chemical information and indicated an increase in the lipid-to-protein ratio in the brown adipose, but not in the white adipose.

  14. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on a high-fat, high-sugar diet

    Jimenez-Gomez, Yolanda; Mattison, Julie A.; Pearson, Kevin J.; Martin-Montalvo, Alejandro; Palacios, Hector H; Sossong, Alex M.; Ward, Theresa M.; Younts, Caitlin M.; Lewis, Kaitlyn; Allard, Joanne S.; Longo, Dan L; Belman, Jonathan P.; Malagon, Maria M.; Navas, Placido; Sanghvi, Mitesh

    2013-01-01

    Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here we tested the effect of a 2-year resveratrol administration on pro-inflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT)...

  15. Epicardial adipose tissue and its role in cardiac physiology and disease 

    Kacper Toczyłowski

    2013-06-01

    Full Text Available Adipose tissue secretes a number of cytokines, referred to as adipokines. Intensive studies conducted over the last two decades showed that adipokines exert broad effects on cardiac metabolism and function. In addition, the available data strongly suggests that these cytokines play an important role in development of cardiovascular diseases. Epicardial adipose tissue (EAT has special properties that distinguish it from other deposits of visceral fat. Overall, there appears to be a close functional and anatomic relationship between the EAT and the cardiac muscle. They share the same coronary blood supply, and there is no structure separating the adipose tissue from the myocardium or coronary arteries. The role of EAT in osierdziocardiac physiology remains unclear. Its putative functions include buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, regulating fatty acid homeostasis in the coronary microcirculation, thermogenesis, and neuroprotection of the cardiac autonomic ganglia and nerves. Obesity (particularly the abdominal phenotype leads to elevated EAT content, and the available data suggests that high amount of this fat depot is associated with increased risk of ischemic heart disease, cardiac hypertrophy and diastolic dysfunction. The mass of EAT is small compared to other fat deposits in the body. Nevertheless, its close anatomic relationship to the heart suggests that this organ is highly exposed to EAT-derived adipokines which makes this tissue a very promising area of research. In this paper we review the current knowledge on the role of EAT in cardiac physiology and development of heart disease.

  16. Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells.

    Ritter, Andreas; Friemel, Alexandra; Fornoff, Friderike; Adjan, Mouhib; Solbach, Christine; Yuan, Juping; Louwen, Frank

    2015-10-27

    Adipose-derived stem cells are capable of differentiating into multiple cell types and thus considered useful for regenerative medicine. However, this differentiation feature seems to be associated with tumor initiation and metastasis raising safety concerns, which requires further investigation. In this study, we isolated adipose-derived stem cells from subcutaneous as well as from visceral adipose tissues of the same donor and systematically compared their features. Although being characteristic of mesenchymal stem cells, subcutaneous adipose-derived stem cells tend to be spindle form-like and are more able to home to cancer cells, whereas visceral adipose-derived stem cells incline to be "epithelial"-like and more competent to differentiate. Moreover, compared to subcutaneous adipose-derived stem cells, visceral adipose-derived stem cells are more capable of promoting proliferation, inducing the epithelial-to-mesenchymal transition, enhancing migration and invasion of breast cancer cells by cell-cell contact and by secreting interleukins such as IL-6 and IL-8. Importantly, ASCs affect the low malignant breast cancer cells MCF-7 more than the highly metastatic MDA-MB-231 cells. Induction of the epithelial-to-mesenchymal transition is mediated by the activation of multiple pathways especially the PI3K/AKT signaling in breast cancer cells. BCL6, an important player in B-cell lymphoma and breast cancer progression, is crucial for this transition. Finally, this transition fuels malignant properties of breast cancer cells and render them resistant to ATP competitive Polo-like kinase 1 inhibitors BI 2535 and BI 6727.

  17. Determination of time delay between blood and interstitial adipose tissue glucose concentration change by microdialysis in healthy volunteers

    Wientjes, KJC; Schoonen, AJM

    2001-01-01

    For the development and use of subcutaneous glucose sensors it is important to know the time lag between changes in blood glucose and subcutaneous interstitial glucose concentration. To determine the time lag we inserted a microdialysis probe into the abdominal subcutaneous adipose tissue of healthy

  18. Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women

    Menopausal women exhibit a loss of circadian coordination, a process that runs parallel with a redistribution of adipose tissue. However, the specific genetic mechanisms underlying these alterations have not been studied. Thus, the aim of the present study was to determine whether the development of...

  19. LSD1 promotes oxidative metabolism of white adipose tissue

    Duteil, Delphine; Metzger, Eric; Willmann, Dominica; Karagianni, Panagiota; Friedrichs, Nicolaus; Greschik, Holger; Günther, Thomas; Buettner, Reinhard; Talianidis, Iannis; Metzger, Daniel; Schüle, Roland

    2014-01-01

    Exposure to environmental cues such as cold or nutritional imbalance requires white adipose tissue (WAT) to adapt its metabolism to ensure survival. Metabolic plasticity is prominently exemplified by the enhancement of mitochondrial biogenesis in WAT in response to cold exposure or β3-adrenergic stimulation. Here we show that these stimuli increase the levels of lysine-specific demethylase 1 (LSD1) in WAT of mice and that elevated LSD1 levels induce mitochondrial activity. Genome-wide binding and transcriptome analyses demonstrate that LSD1 directly stimulates the expression of genes involved in oxidative phosphorylation (OXPHOS) in cooperation with nuclear respiratory factor 1 (Nrf1). In transgenic (Tg) mice, increased levels of LSD1 promote in a cell-autonomous manner the formation of islets of metabolically active brown-like adipocytes in WAT. Notably, Tg mice show limited weight gain when fed a high-fat diet. Taken together, our data establish LSD1 as a key regulator of OXPHOS and metabolic adaptation in WAT. PMID:24912735

  20. Adipose tissue-derived stem cells in neural regenerative medicine.

    Yeh, Da-Chuan; Chan, Tzu-Min; Harn, Horng-Jyh; Chiou, Tzyy-Wen; Chen, Hsin-Shui; Lin, Zung-Sheng; Lin, Shinn-Zong

    2015-01-01

    Adipose tissue-derived stem cells (ADSCs) have two essential characteristics with regard to regenerative medicine: the convenient and efficient generation of large numbers of multipotent cells and in vitro proliferation without a loss of stemness. The implementation of clinical trials has prompted widespread concern regarding safety issues and has shifted research toward the therapeutic efficacy of stem cells in dealing with neural degeneration in cases such as stroke, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, cavernous nerve injury, and traumatic brain injury. Most existing studies have reported that cell therapies may be able to replenish lost cells and promote neuronal regeneration, protect neuronal survival, and play a role in overcoming permanent paralysis and loss of sensation and the recovery of neurological function. The mechanisms involved in determining therapeutic capacity remain largely unknown; however, this concept can still be classified in a methodical manner by citing current evidence. Possible mechanisms include the following: 1) the promotion of angiogenesis, 2) the induction of neuronal differentiation and neurogenesis, 3) reductions in reactive gliosis, 4) the inhibition of apoptosis, 5) the expression of neurotrophic factors, 6) immunomodulatory function, and 7) facilitating neuronal integration. In this study, several human clinical trials using ADSCs for neuronal disorders were investigated. It is suggested that ADSCs are one of the choices among various stem cells for translating into clinical application in the near future.

  1. Measurement of subcutaneous adipose tissue thickness by near-infrared.

    Wang, Yu; Yang, Zeqiang; Hao, Dongmei; Zhang, Song; Yang, Yimin; Zeng, Yanjun

    2013-06-01

    Obesity is strongly associated with the risks of diabetes and cardiovascular disease, and there is a need to measure the subcutaneous adipose tissue (SAT) layer thickness and to understand the distribution of body fat. A device was designed to illuminate the body parts by near-infrared (NIR), measure the backscattered light, and predict the SAT layer thickness. The device was controlled by a single-chip microcontroller (SCM), and the thickness value was presented on a liquid crystal display (LCD). There were 30 subjects in this study, and the measurements were performed on 14 body parts for each subject. The paper investigated the impacts of pressure and skin colour on the measurement. Combining with principal component analysis (PCA) and support vector regression (SVR), the measurement accuracy of SAT layer thickness was 89.1 % with a mechanical caliper as reference. The measuring range was 5-11 mm. The study provides a non-invasive and low-cost technique to detect subcutaneous fat thickness, which is more accessible and affordable compared to other conventional techniques. The designed device can be used at home and in community.

  2. Postnatal changes in fatty acids composition of brown adipose tissue

    Ohno, T.; Ogawa, K.; Kuroshima, A.

    1992-03-01

    It has been demonstrated that thermogenic activity of brown adipose tissue (BAT) is higher during the early postnatal period, decreasing towards a low adult level. The present study examined postnatal changes in the lipid composition of BAT. BAT from pre-weaning rats at 4 and 14 days old showed the following differences in lipid composition compared to that from adults of 12 weeks old. (i) Relative weight of interscapular BAT to body weight was markedly greater. (ii) BAT-triglyceride (TG) level was lower, while BAT-phospholipid (PL)level was higher. (iii) In TG fatty acids (FA) polyunsaturated fatty acids (PU; mol %), arachidonate index (AI), unsaturation index (UI) and PU/saturated FA (SA) were higher; rare FA such as eicosadienoate, bishomo- γ-linolenic acid and lignoceric acid in mol % were also higher. (iv) In PL-FA monounsaturated FA (MU) in mol % was lower; PU mol %, AI and UI were higher. These features in BAT of pre-weaning rats resembled those in the cold-acclimated adults, suggesting a close relationship of the PL-FA profile to high activity of BAT.

  3. Progress toward automatic classification of human brown adipose tissue using biomedical imaging

    Gifford, Aliya; Towse, Theodore F.; Walker, Ronald C.; Avison, Malcom J.; Welch, E. B.

    2015-03-01

    Brown adipose tissue (BAT) is a small but significant tissue, which may play an important role in obesity and the pathogenesis of metabolic syndrome. Interest in studying BAT in adult humans is increasing, but in order to quantify BAT volume in a single measurement or to detect changes in BAT over the time course of a longitudinal experiment, BAT needs to first be reliably differentiated from surrounding tissue. Although the uptake of the radiotracer 18F-Fluorodeoxyglucose (18F-FDG) in adipose tissue on positron emission tomography (PET) scans following cold exposure is accepted as an indication of BAT, it is not a definitive indicator, and to date there exists no standardized method for segmenting BAT. Consequently, there is a strong need for robust automatic classification of BAT based on properties measured with biomedical imaging. In this study we begin the process of developing an automated segmentation method based on properties obtained from fat-water MRI and PET-CT scans acquired on ten healthy adult subjects.

  4. Multiaxial mechanical properties and constitutive modeling of human adipose tissue: a basis for preoperative simulations in plastic and reconstructive surgery.

    Sommer, Gerhard; Eder, Maximilian; Kovacs, Laszlo; Pathak, Heramb; Bonitz, Lars; Mueller, Christoph; Regitnig, Peter; Holzapfel, Gerhard A

    2013-11-01

    A preoperative simulation of soft tissue deformations during plastic and reconstructive surgery is desirable to support the surgeon's planning and to improve surgical outcomes. The current development of constitutive adipose tissue models, for the implementation in multilayer computational frameworks for the simulation of human soft tissue deformations, has proved difficult because knowledge of the required mechanical parameters of fat tissue is limited. Therefore, for the first time, human abdominal adipose tissues were mechanically investigated by biaxial tensile and triaxial shear tests. The results of this study suggest that human abdominal adipose tissues under quasi-static and dynamic multiaxial loadings can be characterized as a nonlinear, anisotropic and viscoelastic soft biological material. The nonlinear and anisotropic features are consequences of the material's collagenous microstructure. The aligned collagenous septa observed in histological investigations causes the anisotropy of the tissue. A hyperelastic model used in this study was appropriate to represent the quasi-static multiaxial mechanical behavior of fat tissue. The constitutive parameters are intended to serve as a basis for soft tissue simulations using the finite element method, which is an apparent method for obtaining promising results in the field of plastic and reconstructive surgery.

  5. Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

    Arner, Erik; Forrest, Alistair R R; Ehrlund, Anna; Mejhert, Niklas; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Laurencikiene, Jurga; Rydén, Mikael; Arner, Peter; Clevers, Hans

    2014-01-01

    Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone

  6. Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

    Basse, Astrid L.; Dixen, Karen; Yadav, Rachita;

    2015-01-01

    NR1H3, MYC, KLF4, ESR1, RELA and BCL6, which were linked to the overall changes in gene expression during the adipose tissue remodeling. Finally, the perirenal adipose tissue expressed both brown and brite/beige adipocyte marker genes at birth, the expression of which changed substantially over time...

  7. IL-6 regulates exercise and training-induced adaptations in subcutaneous adipose tissue in mice

    Brandt, Claus; Jakobsen, Anne Hviid; Hassing, Helle Adser

    2012-01-01

    Aim: The aim of this study was to test the hypothesis that IL-6 regulates exercise-induced gene responses in subcutaneous adipose tissue in mice. Methods: Four months old male IL-6 whole body knockout (KO) mice and C57B wild-type (WT) mice performed 1h of treadmill exercise, where subcutaneous...... adipose tissue (AT) was removed either immediately after, 4h or 10h after exercise as well as from mice not running acutely. Moreover, AT was sampled at resting conditions after 5 weeks of exercise training. Results: AT leptin mRNA decreased immediately after a single running exercise bout in both...... in regulating exercise and training-induced leptin and PPAR¿ expression in adipose tissue. In addition, while IL-6 is required for TNF-a mRNA reduction in response to acute exercise, IL-6 does not appear to be mandatory for anti-inflammatory effects of exercise training in adipose tissue....

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

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

    2000-01-01

    Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men...... [insulin infusion rates: 10,000 (step I), 20,000 (step II), and 150,000 (step III) microU x min(-1) x m(-2)]. Glucose and glycerol concentrations were measured in arterial blood and also by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose tissue and in quadriceps femoris muscle...... (glucose only). Adipose tissue blood flow was measured by (133)Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration...

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

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

    2006-01-01

    Visfatin [pre-beta-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression...... in abdominal subcutaneous adipose tissue and skeletal muscle biopsies obtained from healthy young men at time points 0, 3, 4.5, 6, 9, and 24 h in relation to either 3 h of ergometer cycle exercise at 60% of Vo(2 max) or rest. Adipose tissue visfatin mRNA expression increased threefold at the time points 3, 4.......5, and 6 h in response to exercise (n = 8) compared with preexercise samples and compared with the resting control group (n = 7, P = 0.001). Visfatin mRNA expression in skeletal muscle was not influenced by exercise. The exercise-induced increase in adipose tissue visfatin was, however, not accompanied...

  10. Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans

    Mulla, N A; Simonsen, L; Bülow, J

    2000-01-01

    , a subcutaneous abdominal vein and a femoral vein. Adipose tissue metabolism and skeletal muscle (leg) metabolism were measured using Fick's principle. The results show that the lipolytic rate in adipose tissue during exercise was the same in each experiment. Post-exercise, there was a very fast decrease......One purpose of the present experiments was to examine whether the relative workload or the absolute work performed is the major determinant of the lipid mobilization from adipose tissue during exercise. A second purpose was to determine the co-ordination of skeletal muscle and adipose tissue lipid...... in lipolysis, but it began to increase about 1 h post-exercise and remained elevated for the following 2 h. The increase in post-exercise non-esterified fatty acid (NEFA) mobilization was greater after 60% exercise than after 40 % exercise. It is concluded that the lipolytic rate in abdominal subcutaneous...

  11. The expression of testosterone converting enzymes in adipose tissue of polycystic ovary syndrome rat mode

    王丽华

    2013-01-01

    Objective To establish a polycystic ovary syndrome(PCOS) rat model and compare the expression of testosterone converting enzymes in adipose tissue of PCOS rat with that of controls.Methods 21-day-old female SD

  12. A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats

    Alexanderson, Camilla; Stener-Victorin, Elisabet; Kullberg, Joel;

    2010-01-01

    expression related to follicular development and adipose tissue metabolism, and developed a non-invasive volumetric estimation of parametrial adipose tissue by magnetic resonance imaging. Estradiol reduced ovarian weight, increased antral follicle size and number of atretic antral follicles, and decreased......Events during early life can affect reproductive and metabolic functions in adulthood. We evaluated the programming effects of a single early postnatal estradiol injection (within 3h after birth) in female rats. We assessed ovarian and parametrial adipose tissue morphology, evaluated gene...... theca interna thickness in atretic antral follicles. Adult estradiol-injected rats also had malformed vaginal openings and lacked corpora lutea, confirming anovulation. Estradiol markedly reduced parametrial adipose tissue mass. Adipocyte size was unchanged, suggesting reduced adipocyte number...

  13. CILAIR-Based Secretome Analysis of Obese Visceral and Subcutaneous Adipose Tissues Reveals Distinctive ECM Remodeling and Inflammation Mediators

    Roca-Rivada, Arturo; Belen Bravo, Susana; Pérez-Sotelo, Diego; Alonso, Jana; Isabel Castro, Ana; Baamonde, Iván; Baltar, Javier; Casanueva, Felipe F.; Pardo, María

    2015-01-01

    In the context of obesity, strong evidences support a distinctive pathological contribution of adipose tissue depending on its anatomical site of accumulation. Therefore, subcutaneous adipose tissue (SAT) has been lately considered metabolically benign compared to visceral fat (VAT), whose location is associated to the risk of developing cardiovascular disease, insulin resistance, and other associated comorbidities. Under the above situation, the chronic local inflammation that characterizes obese adipose tissue, has acquired a major role on the pathogenesis of obesity. In this work, we have analyzed for the first time human obese VAT and SAT secretomes using an improved quantitative proteomic approach for the study of tissue secretomes, Comparison of Isotope-Labeled Amino acid Incorporation Rates (CILAIR). The use of double isotope-labeling-CILAIR approach to analyze VAT and SAT secretomes allowed the identification of location-specific secreted proteins and its differential secretion. Additionally to the very high percentage of identified proteins previously implicated in obesity or in its comorbidities, this approach was revealed as a useful tool for the study of the obese adipose tissue microenvironment including extracellular matrix (ECM) remodeling and inflammatory status. The results herein presented reinforce the fact that VAT and SAT depots have distinct features and contribute differentially to metabolic disease. PMID:26198096

  14. Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue.

    Ruzickova, Jana; Rossmeisl, Martin; Prazak, Tomas; Flachs, Pavel; Sponarova, Jana; Veck, Marek; Tvrzicka, Eva; Bryhn, Morten; Kopecky, Jan

    2004-12-01

    Omega-3 PUFA of marine origin reduce adiposity in animals fed a high-fat diet. Our aim was to learn whether EPA and DHA could limit development of obesity and reduce cellularity of adipose tissue and whether other dietary FA could influence the effect of EPA/DHA. Weight gain induced by composite high-fat diet in C57BL/6J mice was limited when the content of EPA/DHA was increased from 1 to 12% (wt/wt) of dietary lipids. Accumulation of adipose tissue was reduced, especially of the epididymal fat. Low ratio of EPA to DHA promoted the effect. A higher dose of EPA/DHA was required to reduce adiposity when admixed to diets that did not promote obesity, the semisynthetic high-fat diets rich in EFA, either alpha-linolenic acid (ALA, 18:3 n-3, the precursor of EPA and DHA) or linoleic (18:2 n-6) acid. Quantification of adipose tissue DNA revealed that except for the diet rich in ALA the reduction of epididymal fat was associated with 34-50% depression of tissue cellularity, similar to the 30% caloric restriction in the case of the high-fat composite diet. Changes in plasma markers and adipose gene expression indicated improvement of lipid and glucose metabolism due to EPA/DHA even in the context of the diet rich in ALA. Our results document augmentation of the antiadipogenic effect of EPA/DHA during development of obesity and suggest that EPA/DHA could reduce accumulation of body fat by limiting both hypertrophy and hyperplasia of fat cells. Increased dietary intake of EPA/DHA may be beneficial regardless of the ALA intake.

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

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

    2013-01-01

    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 tissu...

  16. Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease

    Sun Zongquan

    2011-01-01

    Full Text Available Abstract Background Disorders of endocrine substances in epicardial adipose tissue are known causes of coronary artery disease (CAD. Adiponectin is associated with cardiovascular disease. However, expression of adiponectin in epicardial adipose tissue and its function in CAD pathogenesis is unclear. This study investigates adiponectin expression in epicardial adipose tissue in CAD patients. Methods Vessels or adipose tissue samples collected from CAD patients and non-CAD controls were examined after immunochemical staining. Adiponectin, cytokines of interleukin-6 (IL-6 and necrosis factor-α (TNF-α and toll-like receptor 4 (TLR4 expression level in adipose tissue were measured using real-time quantitative RT-PCR. Adiponectin concentrations in peripheral and coronary sinus vein plasma were measured with enzyme-linked immunosorbent assay. Peripheral vein plasma biochemistries were performed with routine laboratory techniques. Monocytes were collected from blood using lymphocyte separation medium. Expression level of cytokines and transcription factor NF-κB were measured to learn the effect of adiponectin on stearic acid-stimulated monocytes. Percentage of TLR4 positive monocytes was analyzed using flow cytometry. Results Histological examination revealed increased macrophage infiltration into epicardial adipose tissue of CAD patients. Decreased adiponectin displayed by real-time quantitative RT-PCR was associated with enhanced cytokines of IL-6 and TNF-α or TLR4 expression level in epicardial adipose tissue, suggesting decreased circulating adiponectin may be useful as a more sensitive predictor for coronary atherosclerosis than routine laboratory examinations. Adiponectin suppressed secretion of IL-6 and TNF-α in stimulated monocytes and TLR4 was expressed on cell surfaces. Conclusions Endocrine disorders in epicardial adipose tissue are strongly linked to CAD, and adiponectin has a protective effect by inhibiting macrophage

  17. Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue

    Simonsen, L; Bülow, J; Madsen, Jan Lysgård

    1992-01-01

    of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place...... in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis....

  18. Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control.

    Jones, B H; Standridge, M K; Taylor, J W; Moustaïd, N

    1997-07-01

    Synthesis of angiotensin II (ANG II) has recently been described in adipose cells and has been linked to regulation of adiposity. Angiotensinogen (AGT), the substrate from which ANG II is formed, was previously shown to be elevated in adipose tissue of obese (ob/ob and db/db) mice and regulated by nutritional manipulation. It is unknown, however, whether overexpression of adipose AGT can be extended to other models of obesity and whether hormonal and/or nutritional factors directly regulate AGT expression in adipocytes. We investigated these possibilities by analyzing AGT mRNA levels in adipose tissue of obese Zucker rats, viable yellow (Avy) mice, and humans and by treating 3T3-L1 adipocytes with insulin, glucose, and a beta-adrenergic agonist. We demonstrate that AGT mRNA is decreased by approximately 50 and 80%, respectively, in adipose tissue of obese vs. lean Zucker rats and Avy mice. We also report that AGT is expressed at variable levels in human adipose tissue. Finally, we show that AGT mRNA is upregulated by insulin and downregulated by beta-adrenergic stimulation in adipocytes.

  19. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue

    Yin, Jun; Gao, Zhanguo; He, Qing; Zhou, Dequan; Guo, ZengKui; Ye, Jianping

    2008-01-01

    Recent studies suggest that adipose tissue hypoxia (ATH) may contribute to endocrine dysfunction in adipose tissue of obese mice. In this study, we examined hypoxia's effects on metabolism in adipocytes. We determined the dynamic relationship of ATH and adiposity in ob/ob mice. The interstitial oxygen pressure (Po2) was monitored in the epididymal fat pads for ATH. During weight gain from 39.5 to 55.5 g, Po2 declined from 34.8 to 20.1 mmHg, which are 40–60% lower than those in the lean mice. ...

  20. Insulin action in muscle and adipose tissue in type 2diabetes: The significance of blood flow

    2015-01-01

    Under normal metabolic conditions insulin stimulatesmicrovascular perfusion (capillary recruitment) ofskeletal muscle and subcutaneous adipose tissue andthus increases blood flow mainly after meal ingestionor physical exercise. This helps the delivery of insulinitself but also that of substrates and of other signallingmolecules to multiple tissues beds and facilitatesglucose disposal and lipid kinetics. This effect is impairedin insulin resistance and type 2 diabetes early in thedevelopment of metabolic dysregulation and reflectsearly-onset endothelial dysfunction. Failure of insulinto increase muscle and adipose tissue blood flowresults in decreased glucose handling. In fat depots, ablunted postprandial blood flow response will result inan insufficient suppression of lipolysis and an increasedspill over of fatty acids in the circulation, leading toa more pronounced insulin resistant state in skeletalmuscle. This defect in blood flow response is apparenteven in the prediabetic state, implying that it is afacet of insulin resistance and exists long before overthyperglycaemia develops. The following review intendsto summarize the contribution of blood flow impairmentto the development of the atherogenic dysglycemia anddyslipidaemia.

  1. Monitoring of temperature-mediated adipose tissue phase transitions by refractive-index measurements

    Yanina, I. Yu.; Popov, A. P.; Bykov, A. V.; Tuchin, V. V.

    2014-10-01

    Monitoring of temperature-mediated adipose tissue phase transitions were studied in vitro using an Abbe refractometer. The 1-2-mm thick porcine fat tissues slices were used in the experiments. The observed change in the tissue was associated with several phase transitions of lipid components of the adipose tissue. It was found that overall heating of a sample from the room to higher temperature led to more pronounced and tissue changes in refractive index if other experimental conditions were kept constant. We observed an abrupt change in the refractive index in the temperature range of 37-60 °C.

  2. Immune-mediated activation of the endocannabinoid system in visceral adipose tissue in obesity.

    Kempf, K; Hector, J; Strate, T; Schwarzloh, B; Rose, B; Herder, C; Martin, S; Algenstaedt, P

    2007-08-01

    The aim of the study was to investigate if the endocannabinoid system (ECS) is activated in visceral adipose tissue and if adipose tissue inflammation affects the ECS activation state. Therefore, expression of fatty acid amide hydrolase (FAAH), cannabinoid receptor 1 (Cb1), adiponectin, and tumor necrosis factor (TNF)-alpha was compared in visceral adipose tissue from 10 normal-weight (BMI 24.4+/-1.1 kg/m2) and 11 obese subjects (BMI 37.6+/-13.6 kg/m2) using quantitative RT-PCR, and gene expression changes were analyzed after in vitro stimulation of visceral adipose tissue with TNF-alpha. The data demonstrate that the ECS is activated in obese visceral adipose tissue as shown by decreased FAAH, Cb1, and adiponectin expression. Obesity-related ECS activation is accompanied by elevated expression of the pro-inflammatory cytokine TNF-alpha, which in turn stimulates ECS activation in vitro. Our data show a strong association between adipose tissue inflammation and ECS activation in obesity, and indicate that a pro-inflammatory state may directly activate the ECS.

  3. Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue

    Remesar Xavier

    2007-08-01

    Full Text Available Abstract Background Short-term OE (oleoyl-estrone treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Results Gene expression in adipose tissue from female treated rats (48 hours was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL were decreased by 52%, those of Fatty Acid Synthase (FAS by 95%, those of Hormone Sensible Lipase (HSL by 32%, those of Acetyl CoA Carboxylase (ACC by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b by 45%, and those of Fatty Acid Transport Protein 1 (FATP1 and Adipocyte Fatty Acid Binding Protein (FABP4 by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFα values showed overexpression (198%. Conclusion Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism.

  4. Prolactin suppresses malonyl-CoA concentration in human adipose tissue.

    Nilsson, L A; Roepstorff, C; Kiens, B; Billig, H; Ling, C

    2009-10-01

    Prolactin is best known for its involvement in lactation, where it regulates mechanisms that supply nutrients for milk production. In individuals with pathological hyperprolactinemia, glucose and fat homeostasis have been reported to be negatively influenced. It is not previously known, however, whether prolactin regulates lipogenesis in human adipose tissue. The aim of this study was to investigate the effect of prolactin on lipogenesis in human adipose tissue in vitro. Prolactin decreased the concentration of malonyl-CoA, the product of the first committed step in lipogenesis, to 77+/-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 lipogenesis could contribute to an insulin resistant state with consequences for the health.

  5. HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

    Morse, Caryn G.; Voss, Joachim G.; Rakocevic, Goran; McLaughlin, Mary; Vinton, Carol L.; Huber, Charles; Hu, Xiaojun; Yang, Jun; Huang, Da Wei; Logun, Carolea; Danner, Robert L.; Rangel, Zoila G.; Munson, Peter J.; Orenstein, Jan M.; Rushing, Elisabeth J.; Lempicki, Richard A.; Dalakas, Marinos C.; Kovacs, Joseph A.

    2012-01-01

    Background. Although human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and function, comprehensive evaluations of their effects on mitochondria in muscle, adipose tissue, and blood cells are limited. Methods. Mitochondrial DNA quantification, mitochondrial genome sequencing, and gene expression analysis were performed on muscle, adipose tissue, and peripheral blood mononuclear cell (PBMC) samples from untreated HIV-positive patients, HIV-positive patients receiving nucleoside reverse transcriptase inhibitor (NRTI)–based ART, and HIV-negative controls. Results. The adipose tissue mtDNA/nuclear DNA (nDNA) ratio was increased in untreated HIV-infected patients (ratio, 353) and decreased in those receiving ART (ratio, 162) compared with controls (ratio, 255; P < .05 for both comparisons); the difference between the 2 HIV-infected groups was also significant (P = .002). In HIV-infected participants, mtDNA/nDNA in adipose tissue correlated with the level of activation (CD38+/HLA-DR+) for CD4+ and CD8+ lymphocytes. No significant differences in mtDNA content were noted in muscle or PMBCs among groups. Exploratory DNA microarray analysis identified differential gene expression between patient groups, including a subset of adipose tissue genes. Conclusions. HIV infection and ART have opposing effects on mtDNA content in adipose tissue; immune activation may mediate the effects of HIV, whereas NRTIs likely mediate the effects of ART. PMID:22476717

  6. Soya protein attenuates abnormalities of the renin-angiotensin system in adipose tissue from obese rats.

    Frigolet, María E; Torres, Nimbe; Tovar, Armando R

    2012-01-01

    Several metabolic disturbances during obesity are associated with adipose tissue-altered functions. Adipocytes contain the renin-angiotensin system (RAS), which regulates signalling pathways that control angiogenesis via Akt in an autocrine fashion. Soya protein (Soy) consumption modifies the gene expression pattern in adipose tissue, resulting in an improved adipocyte function. Therefore, the aim of the present work is to study whether dietary Soy regulates the expression of RAS and angiogenesis-related genes and its association with the phosphorylated state of Akt in the adipose tissue of obese rats. Animals were fed a 30 % Soy or casein (Cas) diet containing 5 or 25 % fat for 160 d. mRNA abundance was studied in the adipose tissue, and Akt phosphorylation and hormone release were measured in the primary adipocyte culture. The present results show that Soy treatment in comparison with Cas consumption induces lower angiotensin release and increased insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption varies the expression of RAS and angiogenesis-related genes, which maintain cell size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus, adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken together, these findings suggest that Soy can be used as a dietary strategy to preserve adipocyte functionality and to prevent obesity abnormalities.

  7. Adipose-derived stem cells and platelet-rich plasma: the keys to functional periodontal tissue engineering.

    Tobita, Morikuni; Mizuno, Hiroshi

    2013-09-01

    Numerous different types of periodontal tissue regeneration therapies have been developed clinically with variable outcomes and serious limitations. A key goal of periodontal therapy is to regenerate the destroyed periodontal tissues including alveolar bone, cementum and periodontal ligament. The critical factors in attaining successful periodontal tissue regeneration are the correct recruitment of cells to the site and the production of a suitable extra cellular matrix consistent with the periodontal tissues. Adipose tissue, from which mesenchymal stem cells can be harvested easily and safely, is an especially attractive stem cell source, because adipose-derived stem cells have a strong potential for cell differentiation and growth factor secretion. Meanwhile, the usefulness of platelet-rich plasma in the field of dental surgery has attracted attention. Therapeutic effects of platelet-rich plasma are believed to occur through the provision of concentrated levels of platelet-derived growth factors. Further, recent reports suggested the effect of platelet-rich plasma on mesenchymal stem cell proliferation, differentiation and survival rate. Therefore, the admixture of mesenchymal stem cells and platelet-rich plasma may indicate the great potential for tissue regenerations including periodontal tissue regeneration. In this review, the potential of adipose-derived stem cells and platelet-rich plasma is introduced. Of particular interest, the usefulness in periodontal tissue regeneration and future perspective is discussed.

  8. Updated survey of the steroid-converting enzymes in human adipose tissues.

    Tchernof, André; Mansour, Mohamed Fouad; Pelletier, Mélissa; Boulet, Marie-Michèle; Nadeau, Mélanie; Luu-The, Van

    2015-03-01

    Over the past decade, adipose tissues have been increasingly known for their endocrine properties, that is, their ability to secrete a number of adipocytokines that may exert local and/or systemic effects. In addition, adipose tissues have long been recognized as significant sites for steroid hormone transformation and action. We hereby provide an updated survey of the many steroid-converting enzymes that may be detected in human adipose tissues, their activities and potential roles. In addition to the now well-established role of aromatase and 11β-hydroxysteroid dehydrogenase (HSD) type 1, many enzymes have been reported in adipocyte cell lines, isolated mature cells and/or preadipocytes. These include 11β-HSD type 2, 17β-HSDs, 3β-HSD, 5α-reductases, sulfatases and glucuronosyltransferases. Some of these enzymes are postulated to bear relevance for adipose tissue physiology and perhaps for the pathophysiology of obesity. This elaborate set of steroid-converting enzymes in the cell types of adipose tissue deserves further scientific attention. Our work on 20α-HSD (AKR1C1), 3α-HSD type 3 (AKR1C2) and 17β-HSD type 5 (AKR1C3) allowed us to clarify the relevance of these enzymes for some aspects of adipose tissue function. For example, down-regulation of AKR1C2 expression in preadipocytes seems to potentiate the inhibitory action of dihydrotestosterone on adipogenesis in this model. Many additional studies are warranted to assess the impact of intra-adipose steroid hormone conversions on adipose tissue functions and chronic conditions such as obesity, diabetes and cancer.

  9. Altered lipid metabolism in residual white adipose tissues of Bscl2 deficient mice.

    Weiqin Chen

    Full Text Available Mutations in BSCL2 underlie human congenital generalized lipodystrophy type 2 disease. We previously reported that Bscl2 (-/- mice develop lipodystrophy of white adipose tissue (WAT due to unbridled lipolysis. The residual epididymal WAT (EWAT displays a browning phenotype with much smaller lipid droplets (LD and higher expression of brown adipose tissue marker proteins. Here we used targeted lipidomics and gene expression profiling to analyze lipid profiles as well as genes involved in lipid metabolism in WAT of wild-type and Bscl2(-/- mice. Analysis of total saponified fatty acids revealed that the residual EWAT of Bscl2(-/- mice contained a much higher proportion of oleic 18:1n9 acid concomitant with a lower proportion of palmitic 16:0 acid, as well as increased n3- polyunsaturated fatty acids (PUFA remodeling. The acyl chains in major species of triacylglyceride (TG and diacylglyceride (DG in the residual EWAT of Bscl2(-/- mice were also enriched with dietary fatty acids. These changes could be reflected by upregulation of several fatty acid elongases and desaturases. Meanwhile, Bscl2(-/- adipocytes from EWAT had increased gene expression in lipid uptake and TG synthesis but not de novo lipogenesis. Both mitochondria and peroxisomal β-oxidation genes were also markedly increased in Bscl2(-/- adipocytes, highlighting that these machineries were accelerated to shunt the lipolysis liberated fatty acids through uncoupling to dissipate energy. The residual subcutaneous white adipose tissue (ScWAT was not browning but displays similar changes in lipid metabolism. Overall, our data emphasize that, other than being essential for adipocyte differentiation, Bscl2 is also important in fatty acid remodeling and energy homeostasis.

  10. Effect of the anatomical site on telomere length and pref-1 gene expression in bovine adipose tissues

    Yamada, Tomoya, E-mail: toyamada@affrc.go.jp; Higuchi, Mikito; Nakanishi, Naoto

    2015-08-07

    Adipose tissue growth is associated with preadipocyte proliferation and differentiation. Telomere length is a biological marker for cell proliferation. Preadipocyte factor-1 (pref-1) is specifically expressed in preadipocytes and acts as a molecular gatekeeper of adipogenesis. In the present study, we investigated the fat depot-specific differences in telomere length and pref-1 gene expression in various anatomical sites (subcutaneous, intramuscular and visceral) of fattening Wagyu cattle. Visceral adipose tissue expressed higher pref-1 mRNA than did subcutaneous and intramuscular adipose tissues. The telomere length in visceral adipose tissue tended to be longer than that of subcutaneous and intramuscular adipose tissues. The telomere length of adipose tissue was not associated with adipocyte size from three anatomical sites. No significant correlation was found between the pref-1 mRNA level and the subcutaneous adipocyte size. In contrast, the pref-1 mRNA level was negatively correlated with the intramuscular and visceral adipocyte size. These results suggest that anatomical sites of adipose tissue affect the telomere length and expression pattern of the pref-1 gene in a fat depot-specific manner. - Highlights: • Visceral adipose tissue express higher pref-1 mRNA than other anatomical sites. • Telomere length in visceral adipose tissue is longer than other anatomical sites. • Telomere length of adipose tissue is not associated with adipocyte size. • Pref-1 mRNA is negatively correlated with intramuscular and visceral adipocyte size.

  11. Toxicity and oxidative stress of canine mesenchymal stromal cells from adipose tissue in different culture passages

    Arícia Gomes Sprada

    2015-12-01

    Full Text Available Abstract: Stem cells in regenerative therapy have received attention from researchers in recent decades. The culture of these cells allows studies about their behavior and metabolism. Thus, cell culture is the basis for cell therapy and tissue engineering researches. A major concern regarding the use of cultivated stem cell in human or veterinary clinical routine is the risk of carcinogenesis. Cellular activities require a balanced redox state. However, when there is an imbalance in this state, oxidative stress occurs. Oxidative stress contributes to cytotoxicity, which may result in cell death or genomic alterations, favoring the development of cancer cells. The aim of this study was to determine whether there are differences in the behavior of cultured mesenchymal stem cells from canine adipose tissue according to its site of collection (omentum and subcutaneous evaluating the rate of proliferation, viability, level of oxidative stress and cytotoxicity over six passages. For this experiment, two samples of adipose tissue from subcutaneous and omentum where taken from a female dog corpse, 13 years old, Pitbull. The results showed greater levels of oxidative stress in the first and last passages of both groups, favoring cytotoxicity and cell death.

  12. Early Overfeed-Induced Obesity Leads to Brown Adipose Tissue Hypoactivity in Rats

    Douglas L. de Almeida

    2013-12-01

    Full Text Available Background/Aims: Brown adipose tissue activation has been considered a potential anti-obesity mechanism because it is able to expend energy through thermogenesis. In contrast, white adipose tissue stores energy, contributing to obesity. We investigated whether the early programming of obesity by overfeeding during lactation changes structure of interscapular brown adipose tissue in adulthood and its effects on thermogenesis. Methods: Birth of litters was considered day 0. On day 2, litter size was adjusted to normal (9 pups and small (3 pups litters. On day 21, the litters were weaned. A temperature transponder was implanted underneath interscapular brown adipose tissue pads of 81-day-old animals; local temperature was measured during light and dark periods between days 87 and 90. The animals were euthanized, and tissue and blood samples were collected for further analysis. The vagus and retroperitoneal sympathetic nerve activity was recorded. Results: Small litter rats presented significant lower interscapular brown adipose tissue temperature during the light (NL 37.6°C vs. SL 37.2°C and dark (NL 38°C vs. SL 37.6°C periods compared to controls. Morphology of small litter brown adipose tissue showed fewer lipid droplets in the tissue center and more and larger in the periphery. The activity of vagus nerve was 19,9% greater in the small litter than in control (pConclusion: Early overfeeding programming of obesity changes the interscapular brown adipose tissue structure in adulthood, leading to local thermogenesis hypoactivity, which may contribute to obesity in adults.

  13. A metabolomic study of adipose tissue in mice with a disruption of the circadian system.

    Castro, C; Briggs, W; Paschos, G K; FitzGerald, G A; Griffin, J L

    2015-07-01

    Adipose tissue functions in terms of energy homeostasis as a rheostat for blood triglyceride, regulating its concentration, in response to external stimuli. In addition it acts as a barometer to inform the central nervous system of energy levels which can vary dramatically between meals and according to energy demand. Here a metabolomic approach, combining both Mass Spectrometry and Nuclear Magnetic Resonance spectroscopy, was used to analyse both white and brown adipose tissue in mice with adipocyte-specific deletion of Arntl (also known as Bmal1), a gene encoding a core molecular clock component. The results are consistent with a peripheral circadian clock playing a central role in metabolic regulation of both brown and white adipose tissue in rodents and show that Arntl induced global changes in both tissues which were distinct for the two types. In particular, anterior subcutaneous white adipose tissue (ASWAT) tissue was effected by a reduction in the degree of unsaturation of fatty acids, while brown adipose tissue (BAT) changes were associated with a reduction in chain length. In addition the aqueous fraction of metabolites in BAT were profoundly affected by Arntl disruption, consistent with the dynamic role of this tissue in maintaining body temperature across the day-night cycle and an upregulation in fatty acid oxidation and citric acid cycle activity to generate heat during the day when rats are inactive (increases in 3-hydroxybutyrate and glutamate), and increased synthesis and storage of lipids during the night when rats feed more (increased concentrations of glycerol, choline and glycerophosphocholine).

  14. Marrow Adipose Tissue Expansion Coincides with Insulin Resistance in MAGP1-Deficient Mice.

    Walji, Tezin A; Turecamo, Sarah E; Sanchez, Alejandro Coca; Anthony, Bryan A; Abou-Ezzi, Grazia; Scheller, Erica L; Link, Daniel C; Mecham, Robert P; Craft, Clarissa S

    2016-01-01

    Marrow adipose tissue (MAT) is an endocrine organ with the potential to influence skeletal remodeling and hematopoiesis. Pathologic MAT expansion has been studied in the context of severe metabolic challenge, including caloric restriction, high fat diet feeding, and leptin deficiency. However, the rapid change in peripheral fat and glucose metabolism associated with these models impedes our ability to examine which metabolic parameters precede or coincide with MAT expansion. Microfibril-associated glycoprotein-1 (MAGP1) is a matricellular protein that influences cellular processes by tethering signaling molecules to extracellular matrix structures. MAGP1-deficient (Mfap2 (-/-)) mice display a progressive excess adiposity phenotype, which precedes insulin resistance and occurs without changes in caloric intake or ambulation. Mfap2 (-/-) mice were, therefore, used as a model to associate parameters of metabolic disease, bone remodeling, and hematopoiesis with MAT expansion. Marrow adiposity was normal in Mfap2 (-/-) mice until 6 months of age; however, by 10 months, marrow fat volume had increased fivefold relative to wild-type control at the same age. Increased gonadal fat pad mass and hyperglycemia were detectable in Mfap2 (-/-) mice by 2 months, but peaked by 6 months. The development of insulin resistance coincided with MAT expansion. Longitudinal characterization of bone mass demonstrated a disconnection in MAT volume and bone volume. Specifically, Mfap2 (-/-) mice had reduced trabecular bone volume by 2 months, but this phenotype did not progress with age or MAT expansion. Interestingly, MAT expansion in the 10-month-old Mfap2 (-/-) mice was associated with modest alterations in basal hematopoiesis, including a shift from granulopoiesis to B lymphopoiesis. Together, these findings indicate MAT expansion is coincident with insulin resistance, but not excess peripheral adiposity or hyperglycemia in Mfap2 (-/-) mice; and substantial MAT accumulation does

  15. Differential Hematopoietic Activity in White Adipose Tissue Depending on its Localization.

    Luche, Elodie; Sengenès, Coralie; Arnaud, Emmanuelle; Laharrague, Patrick; Casteilla, Louis; Cousin, Beatrice

    2015-12-01

    White adipose tissue (WAT) can be found in different locations in the body, and these different adipose deposits exhibit specific physiopathological importance according to the subcutaneous or abdominal locations. We have shown previously the presence of functional hematopoietic stem/progenitor cells (HSPC) in subcutaneous adipose tissue (SCAT). These cells exhibit a specific hematopoietic activity that contributes to the renewal of the immune cell compartment within this adipose deposit. In this study, we investigated whether HSPC can be found in visceral adipose tissue (VAT) and whether a putative difference in in situ hematopoiesis may be related to anatomical location and to site-specific immune cell content in VAT compared to SCAT. Therein, we identified for the first time the presence of HSPC in VAT. Using both in vitro assays and in vivo competitive repopulation experiments with sorted HSPC from VAT or SCAT, we showed that the hematopoietic activity of HSPC was lower in VAT, compared to SCAT. In addition, this altered hematopoietic activity of HSPC in VAT was due to their microenvironment, and may be related to a specific combination of secreted factors and extracellular matrix molecules expressed by adipose derived stromal cells. Our results indicate that WAT specific hematopoietic activity may be generalized to all adipose deposits, although with specificity according to the fat pad location. Considering the abundance of WAT in the body, this emphasizes the potential importance of this hematopoietic activity in physiopathological situations.

  16. Adipose tissue deficiency results in severe hyperlipidemia and atherosclerosis in the low-density lipoprotein receptor knockout mice.

    Wang, Mengyu; Gao, Mingming; Liao, Jiawei; Qi, Yanfei; Du, Ximing; Wang, Yuhui; Li, Ling; Liu, George; Yang, Hongyuan

    2016-05-01

    Adipose tissue can store over 50% of whole-body cholesterol; however, the physiological role of adipose tissue in cholesterol metabolism and atherogenesis has not been directly assessed. Here, we examined lipoprotein metabolism and atherogenesis in a unique mouse model of severe lipodystrophy: the Seipin(-/-) mice, and also in mice deficient in both low-density lipoprotein receptor (Ldlr) and Seipin: the Ldlr(-/-)Seipin(-/-) mice. Plasma cholesterol was moderately increased in the Seipin(-/-) mice when fed an atherogenic diet. Strikingly, plasma cholesterol reached ~6000 mg/dl in the Seipin(-/-)Ldlr(-/-) mice on an atherogenic diet, as compared to ~1000 mg/dl in the Ldlr(-/-) mice on the same diet. The Seipin(-/-)Ldlr(-/-) mice also developed spontaneous atherosclerosis on chow diet and severe atherosclerosis on an atherogenic diet. Rosiglitazone treatment significantly reduced the hypercholesterolemia of the Seipin(-/-)Ldlr(-/-) mice, and also alleviated the severity of atherosclerosis. Our results provide direct evidence, for the first time, that the adipose tissue plays a critical role in the clearance of plasma cholesterol. Our results also reveal a previously unappreciated strong link between adipose tissue and LDLR in plasma cholesterol metabolism.