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1

Protein turnover in adipose tissue from fasted or diabetic rats  

NASA Technical Reports Server (NTRS)

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.

Tischler, Marc E.; Ost, Alan H.; Coffman, Julia

1986-01-01

2

Fatty acid-binding protein activities in bovine muscle, liver and adipose tissue  

SciTech Connect

Subcutaneous adipose tissue, sternomandibularis muscle and liver were obtained from steers immediately postmortem. Muscle strips and adipose tissue snips were incubated with 0.75 mM (1- UC)palmitate and 5 mM glucose. Muscle strips esterified palmitate at the rate of 2.5 nmol/min per gram tissue, which was 30% of the rate observed for adipose tissue. Fatty acid-binding protein activity was measured in 104,000 x g supernatant fractions of liver, muscle and adipose tissue homogenates. Muscle and adipose tissue fractions bound 840 and 140 pmol (1- UC)palmitoyl-CoA per gram tissue, respectively. Fatty acid-binding protein activity was greater in adipose tissue than in muscle when data were expressed per milligram protein. Fatty acid binding-protein activity was correlated with the rate of palmitate esterification within each tissue. Liver contained the highest fatty acid-binding protein activity.

Smith, S.B.; Ekeren, P.A.; Sanders, J.O.

1985-11-01

3

Surface protein expression between human adipose tissue-derived stromal cells and mature adipocytes  

Microsoft Academic Search

Adipose tissue contains a stroma that can be easily isolated. Thus, human adipose tissue presents an source of multipotent\\u000a stromal cells. In order to determine the implication of hematopoietic markers in adipocyte biology, we have defined part of\\u000a the phenotype of the human adipose tissue-derived stromal cells, and compared this to fully differentiated adipocytes. Flow\\u000a cytometry demonstrates that the protein

Franck Festy; Laurence Hoareau; Sandrine Bes-Houtmann; Anne-Marie Péquin; Marie-Paule Gonthier; Ashik Munstun; Jean Jacques Hoarau; Maya Césari; Régis Roche

2005-01-01

4

Leptin Modulated Changes in Adipose Tissue Protein Expression in ob\\/ob Mice  

Microsoft Academic Search

Comparative proteomic analyses were performed in adipose tissue of leptin-deficient ob\\/ob mice treated with leptin or control buffer in order to identify the protein expression changes as the potential targets of leptin. Mice were treated with either phosphate-buffered saline (control) or 10 µg\\/day leptin for 14 days via subcutaneous osmotic minipumps. Total protein from white adipose tissue was extracted and

Wei Zhang; Suresh Ambati; Mary Anne Della-Fera; Yang-Ho Choi; Clifton A. Baile; Tracy M. Andacht

2011-01-01

5

2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue.  

PubMed

Gestational diabetes mellitus (GDM) is a significant risk factor for the type 2 diabetes epidemic in many populations. Maternal adipose tissue plays a central role in the pathophysiology of GDM. Thus, the aim of this study was to determine the effect of GDM on the proteome of adipose tissue. Omental adipose tissue was obtained at the time of term Caesarean section from women with normal glucose tolerance (NGT) or GDM. 2D-difference gel electrophoresis (DIGE), followed by mass spectrometry, was used to identify protein spots (n = 6 patients per group). Western blotting was used for confirmation of six of the spot differences (n = 6 patients per group). We found 14 proteins that were differentially expressed between NGT and GDM adipose tissue (? 1.4-fold, P < 0.05). GDM was associated with an up-regulation of four proteins: collagen alpha-2(VI) chain (CO6A2 (COL6A2)), fibrinogen beta chain (FIBB (FGB)), lumican (LUM) and S100A9. On the other hand, a total of ten proteins were found to be down-regulated in adipose tissue from GDM women. These were alpha-1-antitrypsin (AIAT (SERPINA 1)), annexin A5 (ANXA5), fatty acid-binding protein, adipocyte (FABP4), glutathione S-transferase P (GSTP (GSTP1)), heat-shock protein beta-1 (HSP27 (HSPB1)), lactate dehydrogenase B chain (LDHB), perilipin-1 (PLIN1), peroxiredoxin-6 (PRX6 (PRDX6)), selenium-binding protein 1 (SBP1) and vinculin (VINC (VCL)). In conclusion, proteomic analysis of omental fat reveals differential expression of several proteins in GDM patients and NGT pregnant women. This study revealed differences in expression of proteins that are involved in inflammation, lipid and glucose metabolism and oxidative stress and added further evidence to support the role of visceral adiposity in the pathogenesis of GDM. PMID:23709000

Oliva, Karen; Barker, Gillian; Rice, Gregory E; Bailey, Mark J; Lappas, Martha

2013-01-01

6

Cellularity of bovine adipose tissue  

Microsoft Academic Search

Subcutaneous and perirenal adipose tissue from bo- vine animals that had different fat deposition patterns were characterized in terms of the weight of the adipose tissue organ and adipose cell number and mean cell size as determined by electronic counting of osmium-fixed adipose cells. Similar pa- rameters were also measured in the interfascicular adipose tissue dissected from four muscles. Adipose

R. L. Hood; C. E. Allen

2009-01-01

7

Defining dermal adipose tissue.  

PubMed

Here, we explore the evolution and development of skin-associated adipose tissue with the goal of establishing nomenclature for this tissue. Underlying the reticular dermis, a thick layer of adipocytes exists that encases mature hair follicles in rodents and humans. The association of lipid-filled cells with the skin is found in many invertebrate and vertebrate species. Historically, this layer of adipocytes has been termed subcutaneous adipose, hypodermis and subcutis. Recent data have revealed a common precursor for dermal fibroblasts and intradermal adipocytes during development. Furthermore, the development of adipocytes in the skin is independent from that of subcutaneous adipose tissue development. Finally, the role of adipocytes has been shown to be relevant for epidermal homoeostasis during hair follicle regeneration and wound healing. Thus, we propose a refined nomenclature for the cells and adipose tissue underlying the reticular dermis as intradermal adipocytes and dermal white adipose tissue, respectively. PMID:24841073

Driskell, Ryan R; Jahoda, Colin A B; Chuong, Cheng-Ming; Watt, Fiona M; Horsley, Valerie

2014-09-01

8

Aging-associated reductions in lipolytic and mitochondrial proteins in mouse adipose tissue are not rescued by metformin treatment.  

PubMed

Mitochondrial enzyme expression is reduced in adipose tissue from old mice, yet little is known regarding mechanisms that could be mediating, or interventions that could be used, to reverse these changes. The purpose of this study was to examine the relationship between lipolytic and fatty acid reesterification enzymes, 5' adenosine monophosphate-activated protein kinase and mitochondrial proteins in adipose tissue from young versus old mice. A second aim was to determine whether metformin treatment could rescue the age-associated decline in adipose tissue mitochondrial proteins. Approximately 22-month-old male C57BL/6 mice were fed a diet with or without 0.5% metformin for 8 weeks. Compared with young mice (~11 wk of age), the protein content/phosphorylation of hormone-sensitive lipase, adipose tissue triglyceride lipase, and phosphoenolpyruvate carboxykinase were reduced in old mice. This was paralleled by increases in the plasma nonesterified fatty acid:glycerol ratio and reductions in adipose tissue 5' adenosine monophosphate-activated protein kinase activity and select mitochondrial proteins in old mice. There were no differences in these variables when comparing adipose tissue from young and 6-month-old mice. While metformin improved glucose homeostasis, it did not increase 5' adenosine monophosphate-activated protein kinase phosphorylation or mitochondrial enzymes. Our findings demonstrate a co-ordinated down regulation of lipolytic, reesterification, and mitochondrial enzymes in adipose tissue with aging that is unresponsive to metformin treatment. PMID:24127429

Mennes, Elise; Dungan, Cory M; Frendo-Cumbo, Scott; Williamson, David L; Wright, David C

2014-09-01

9

A Dangerous Duo in Adipose Tissue: High-Mobility Group Box 1 Protein and Macrophages  

PubMed Central

High-mobility group box 1 (HMGB1) protein first made headlines 40 years ago as a non-histone nuclear protein that regulates gene expression. Not so long ago, it was also shown that HMGB1 has an additional surprising function. When released into the extracellular milieu, HMGB1 triggers an inflammatory response by serving as an endogenous danger signal. The pro-inflammatory role of HMGB1 is now well-established and has been associated with several diseases, including sepsis, rheumatoid arthritis, and atherosclerosis. Yet very little is known about its role in obesity, wherein adipose tissue is typified by a persistent, smoldering inflammatory response instigated by high macrophage infiltrate that potentiates the risk of obesity-associated comorbidities. This mini-review focuses on the putative causal relationship between HMGB1 and macrophage pro-inflammatory activation in pathologically altered adipose tissue associated with obesity. PMID:24910558

Wagner, Marek

2014-01-01

10

Divergent effects of rosiglitazone on protein-mediated fatty acid uptake in adipose and in muscle tissues of Zucker rats  

Microsoft Academic Search

Thiazolidinediones (TZDs) increase tissue insulin sensitivity in diabetes. Here, we hypothesize that, in adipose tissue, skeletal muscle, and heart, alterations in protein- mediated FA uptake are involved in the effect of TZDs. As a model, we used obese Zucker rats, orally treated for 16 days with 5 mg rosiglitazone (Rgz)\\/kg body mass\\/day. In adipose tissue from Rgz-treated rats, FA uptake

S. L. M. Coort; W. A. Coumans; A. Bonen; G. J. van der Vusse; J. F. C. Glatz; J. J. F. P. Luiken

2005-01-01

11

Effect of running training on uncoupling protein mRNA expression in rat brown adipose tissue  

NASA Astrophysics Data System (ADS)

The effect was investigated of endurance training on the expression of uncoupling protein (UCP) mRNA in brown adipose tissue (BAT) of rats. The exercised rats were trained on a rodent treadmill for 5 days per week and a total of 9 weeks. After the training programme, a marked decrease in BAT mass was found in terms of weight or weight per unit body weight; there was a corresponding decrease in DNA content and a downward trend in RNA and glycogen levels. The UCP mRNA was present at a markedly decreased level in BAT of trained animals. In consideration of the reduced levels of mRNAs for hormone-sensitive lipase and acylCoA synthetase, the brown adipose tissue investigated appeared to be in a relatively atrophied and thermogenically quiescent state.

Yamashita, Hitoshi; Yamamoto, Mikio; Sato, Yuzo; Izawa, Tetsuya; Komabayashi, Takao; Saito, Daizo; Ohno, Hideki

1993-03-01

12

Impact of dietary protein on lipid metabolism-related gene expression in porcine adipose tissue  

PubMed Central

Background High dietary protein can reduce fat deposition in animal subcutaneous adipose tissue, but little is known about the mechanism. Methods Sixty Wujin pigs of about 15 kg weight were fed either high protein (HP: 18%) or low protein (LP: 14%) diets, and slaughtered at body weights of 30, 60 or 100 kg. Bloods were collected to measure serum parameters. Subcutaneous adipose tissues were sampled for determination of adipocyte size, protein content, lipid metabolism-related gene expression, and enzyme activities. Results HP significantly reduced adipocyte size, fat meat percentage and backfat thickness, but significantly increased daily gain, lean meat percentage and loin eye area at 60 and 100 kg. Serum free fatty acid and triglyceride concentrations in the HP group were significantly higher than in the LP group. Serum glucose and insulin concentrations were not significantly affected by dietary protein at any body weight. HP significantly reduced gene expression of acetyl CoA carboxylase (ACC), fatty acid synthase (FAS) and sterol regulatory element binding protein 1c (SREBP-1c) at 60 kg and 100 kg; however, the mRNA level and enzyme activity of FAS were increased at 30 kg. HP promoted gene and protein expression and enzyme activities of lipoprotein lipase (LPL), carmitine palmtoyltransferase-1B (CPT-1B), peroxisome proliferator-activated receptor ? (PPAR?) and adipocyte-fatty acid binding proteins (A-FABP) at 60 kg, but reduced their expression at 100 kg. Gene expression and enzyme activity of hormone sensitive lipase (HSL) was reduced markedly at 60 kg but increased at 100 kg by the high dietary protein. Levels of mRNA, enzyme activities and protein expression of ACC, FAS, SREBP-1c and PPAR? in both LP and HP groups increased with increasing body weight. However, gene and protein expression levels/enzyme activities of LPL, CPT-1B, A-FABP and HSL in both groups were higher at 60 kg than at 30 and 100 kg. Conclusion Fat deposition in Wujin pigs fed high dietary protein for 25 weeks was reduced mainly by depression of lipogenic gene expression. The mechanism of lipid transport, lipolysis and oxidation in adipose tissue regulated by dietary protein appeared to be different at 60 kg and 100 kg body weights. PMID:20205889

2010-01-01

13

Decreased RB1 mRNA, Protein, and Activity Reflect Obesity-Induced Altered Adipogenic Capacity in Human Adipose Tissue  

PubMed Central

Retinoblastoma (Rb1) has been described as an essential player in white adipocyte differentiation in mice. No studies have been reported thus far in human adipose tissue or human adipocytes. We aimed to investigate the possible role and regulation of RB1 in adipose tissue in obesity using human samples and animal and cell models. Adipose RB1 (mRNA, protein, and activity) was negatively associated with BMI and insulin resistance (HOMA-IR) while positively associated with the expression of adipogenic genes (PPAR? and IRS1) in both visceral and subcutaneous human adipose tissue. BMI increase was the main contributor to adipose RB1 downregulation. In rats, adipose Rb1 gene expression and activity decreased in parallel to dietary-induced weight gain and returned to baseline with weight loss. RB1 gene and protein expression and activity increased significantly during human adipocyte differentiation. In fully differentiated adipocytes, transient knockdown of Rb1 led to loss of the adipogenic phenotype. In conclusion, Rb1 seems to play a permissive role for human adipose tissue function, being downregulated in obesity and increased during differentiation of human adipocytes. Rb1 knockdown findings further implicate Rb1 as necessary for maintenance of adipogenic characteristics in fully differentiated adipocytes. PMID:23315497

Moreno-Navarrete, Jose Maria; Petrov, Petar; Serrano, Marta; Ortega, Francisco; Garcia-Ruiz, Estefania; Oliver, Paula; Ribot, Joan; Ricart, Wifredo; Palou, Andreu; Bonet, M? Luisa; Fernandez-Real, Jose Manuel

2013-01-01

14

Targeting adipose tissue.  

PubMed

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 ? (PPAR?) 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. PMID:23102228

Haas, Bodo; Schlinkert, Paul; Mayer, Peter; Eckstein, Niels

2012-01-01

15

Cellularity of porcine adipose tissue: effects of growth and adiposity  

Microsoft Academic Search

Adipose tissue, from two depots in pigs of three breeding groups with different propensities to fatten, was characterized in terms of weight of the adipose tissue organ, adipose cell number, and mean cell volume as determined by electronic counting of adipose cells fixed with osmium tetroxide. Perirenal and extramuscular adipose tissue growth was accompanied by progressive adipose cell en- largement

R. L. Hood; C. E. Allen

2009-01-01

16

Adipose tissue proteomes of intrauterine growth-restricted piglets artificially reared on a high-protein neonatal formula.  

PubMed

The eventuality that adipose tissues adapt to neonatal nutrition in a way that may program later adiposity or obesity in adulthood is receiving increasing attention in neonatology. This study assessed the immediate effects of a high-protein neonatal formula on proteome profiles of adipose tissues in newborn piglets with intrauterine growth restriction. Piglets (10th percentile) were fed milk replacers formulated to provide an adequate (AP) or a high (HP) protein supply from day 2 to the day prior weaning (day 28, n=5 per group). Adipocytes with small diameters were present in greater proportions in subcutaneous and perirenal adipose tissues from HP piglets compared with AP ones at this age. Two-dimensional gel electrophoresis analysis of adipose tissue depots revealed a total of 32 protein spots being up- or down-regulated (P<.10) for HP piglets compared with AP piglets; 18 of them were unambiguously identified by mass spectrometry. These proteins were notably related to signal transduction (annexin 2), redox status (peroxiredoxin 6, glutathione S-transferase omega 1, cyclophilin-A), carbohydrate metabolism (ribose-5-phosphate dehydrogenase, lactate dehydrogenase), amino acid metabolism (glutamate dehydrogenase 1) and cell cytoskeleton dynamics (dynactin and cofilin-1). Proteomic changes occurred mainly in dorsal subcutaneous adipose tissue, with the notable exception of annexin 1 involved in lipid metabolic process having a lower abundance in HP piglets for perirenal adipose tissue only. Together, modulation in those proteins could represent a novel starting point for elucidating catch-up fat growth observed in later life in growing animals having been fed HP formula. PMID:22221677

Sarr, Ousseynou; Louveau, Isabelle; Le Huërou-Luron, Isabelle; Gondret, Florence

2012-11-01

17

Renaissance of Brown Adipose Tissue  

Microsoft Academic Search

The recent discovery of functional brown adipose tissue in human adults raised this tissue again into the focus of current investigations concerning human energy homeostasis. Brown fat is a key thermogenic tissue and is essential for non-shivering thermogenesis in the human newborn and hibernating mammals. This review highlights the biological and molecular aspects of brown adipose tissue development and function

D. Tews; M. Wabitsch

2011-01-01

18

Influence of Dietary Fat and Protein on Metabolic and Enzymatic Activities in Adipose Tissue of Meal-Fed Rats.  

National Technical Information Service (NTIS)

The influence of dietary protein and fat on the response of adipose tissue to meal-feeding (a single daily 2-hour meal) has been investigated in the rat. Meal-feeding stimulated the incorporation of pyruvate carbon into fatty acids and the oxidation of py...

G. A. Leveille

1966-01-01

19

A Ketogenic Diet Increases Brown Adipose Tissue Mitochondrial Proteins and UCP1 Levels in Mice  

PubMed Central

We evaluated the effects of feeding a ketogenic diet (KD) for a month on general physiology with emphasis on brown adipose tissue (BAT) in mice. KD did not reduce the caloric intake, or weight or lipid content of BAT. Relative epididymal fat pads were 40% greater in the mice fed the KD (P = 0.06) while leptin was lower (P < 0.05). Blood glucose levels were 30% lower while D-?-hydroxybutyrate levels were about 3.5-fold higher in the KD group. Plasma insulin and leptin levels in the KD group were about half of that of the mice fed NIH-31 pellets (chow group). Median mitochondrial size in the inter-scapular BAT (IBAT) of the KD group was about 60% greater, whereas the median lipid droplet size was about half of that in the chow group. Mitochondrial oxidative phosphorylation proteins were increased (1.5–3-fold) and the uncoupling protein 1 levels were increased by threefold in mice fed the KD. The levels of PPAR?, PGC-1?, and Sirt1 in KD group were 1.5–3-fold while level of Sirt3 was about half of that in the chow-fed group. IBAT cyclic AMP levels were 60% higher in the KD group and cAMP response element binding protein was 2.5-fold higher, suggesting increased sympathetic system activity. These results demonstrate that a KD can also increase BAT mitochondrial size and protein levels. PMID:23233333

Srivastava, Shireesh; Baxa, Ulrich; Niu, Gang; Chen, Xiaoyuan; Veech, Richard L.

2013-01-01

20

A Comparative Approach to Understanding Tissue-Specific Expression of Uncoupling Protein 1 Expression in Adipose Tissue  

PubMed Central

The thermoregulatory function of brown adipose tissue (BAT) is due to the tissue-specific expression of uncoupling protein 1 (UCP1) which is thought to have evolved in early mammals. We report that a CpG island close to the UCP1 transcription start site is highly conserved in all 29 vertebrates examined apart from the mouse and xenopus. Using methylation sensitive restriction digest and bisulfite mapping we show that the CpG island in both the bovine and human is largely un-methylated and is not related to differences in UCP1 expression between white and BAT. Tissue-specific expression of UCP1 has been proposed to be regulated by a conserved 5? distal enhancer which has been reported to be absent in marsupials. We demonstrate that the enhancer, is also absent in five eutherians as well as marsupials, monotremes, amphibians, and fish, is present in pigs despite UCP1 having become a pseudogene, and that absence of the enhancer element does not relate to BAT-specific UCP1 expression. We identify an additional putative 5? regulatory unit which is conserved in 14 eutherian species but absent in other eutherians and vertebrates, but again unrelated to UCP1 expression. We conclude that despite clear evidence of conservation of regulatory elements in the UCP1 5? untranslated region, this does not appear to be related to species or tissues-specific expression of UCP1. PMID:23293654

Shore, Andrew; Emes, Richard D.; Wessely, Frank; Kemp, Paul; Cillo, Clemente; D'Armiento, Maria; Hoggard, Nigel; Lomax, Michael A.

2012-01-01

21

Orexin modulation of adipose tissue.  

PubMed

The orexins are neuropeptides with critical functions in the central nervous system. These neuropeptides have important roles in energy balance and obesity, and therefore on the accumulation of adipose tissue. Rodents lacking orexins, typically through genetic knockouts, experience increased weight gain and accumulation of adipose tissue. Evidence indicates that the lack of the orexins increase adiposity as a result of decreased energy expenditure, principally through a reduction of physical activity. Different lines of evidence suggest that other mechanisms are likely also in play, and neural influences on both white and brown adipose tissues remain to be fully and functionally defined. In addition, the orexin peptides and their receptors are expressed in adipose tissue, with little available information as to their significance. This review summarizes our current understanding of how the orexin peptides affect adipose tissue. We provide a brief introduction to the physiology of orexins and their effects on white and brown adipose tissues in the context of energy balance. We conclude this review by integrating this information in the context of the known physiology of the orexins. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. PMID:23791983

Perez-Leighton, Claudio E; Billington, Charles J; Kotz, Catherine M

2014-03-01

22

Advances in adipose tissue metabolism  

Microsoft Academic Search

This review will focus on the recent findings in adipose tissue metabolism with special attention to human adipocyte biology and physiology. There are major advances stemming from the concomitant results obtained from studies on mature human adipocytes, human preadipocytes differentiated in vitro and murine adipose cell lines. Physiological developments have been based on the expanded utilization of various kinds of

M Lafontan

2008-01-01

23

5-Lipoxygenase-activating protein: a potential link between innate and adaptive immunity in atherosclerosis and adipose tissue inflammation.  

PubMed

Transforming growth factor-beta (TGF-beta) is a major antiinflammatory mediator in atherosclerosis. Transgenic ApoE(-/-) mice with a dominant-negative TGFbeta type II receptor (dnTGFbetaRII) on CD4(+) and CD8(+) T cells display aggravated atherosclerosis. The aim of the present study was to elucidate the mechanisms involved in this enhanced inflammatory response. Gene array analyses identified the 5-lipoxygenase-activating protein (FLAP) among the most upregulated genes in both the aorta and adipose tissue of dnTGFbetaRII transgenic ApoE(-/-) mice compared with their ApoE(-/-) littermates, a finding that was confirmed by real-time quantitative RT-PCR. Aortas from the former mice in addition produced increased amounts of the lipoxygenase product leukotriene B(4) after ex vivo stimulation. FLAP protein expression in both the aorta and adipose tissue was detected in macrophages, but not in T cells. Four weeks of treatment with the FLAP inhibitor MK-886 (10 mg/kg in 1% tylose delivered by osmotic pumps) significantly reduced atherosclerotic lesion size and T-cell content. Finally, FLAP mRNA levels were upregulated approximately 8-fold in adipose tissue derived from obese ob/ob mice. In conclusion, the results of the present study suggest a key role for mediators of the 5-lipoxygenase pathway in inflammatory reactions of atherosclerosis and metabolic disease. PMID:17379835

Bäck, Magnus; Sultan, Ariane; Ovchinnikova, Olga; Hansson, Göran K

2007-04-13

24

Differential modulation of the functionality of white adipose tissue of obese Zucker (fa/fa) rats by the type of protein and the amount and type of fat.  

PubMed

Recent evidence indicates that several metabolic abnormalities developed during obesity are associated with the presence of dysfunctional adipose tissue. Diet is a key factor that modulates several functions of adipose tissue; however, each nutrient in the diet produces specific changes. Thus, the aim of this work was to study the effect of the interaction of the type (coconut or soybean oil) and amount (5% or 10%) of fat with the type of dietary protein (casein or soy protein) on the functionality of white adipose tissue of Zucker (fa/fa) rats. The results showed that soybean oil reduced adipocyte size and decreased esterified saturated fatty acids in white adipose tissue. Excess dietary fat also modified the composition of esterified fatty acids in white adipose tissue, increased the secretion of saturated fatty acids to serum from white adipose tissue and reduced the process of fatty acids re-esterification. On the other hand, soy protein sensitized the activation of the hormone-sensitive lipase by increasing the phosphorylation of this enzyme (Ser 563) despite rats fed soy protein were normoglucagonemic, in contrast with rats fed casein that showed hyperglucagonemia but reduced hormone-sensitive lipase phosphorylation. Finally, in white adipose tissue, the interaction between the tested dietary components modulated the transcription/translation process of lipid and carbohydrate metabolism genes via the activity of the PERK-endoplasmic reticulum stress response. Therefore, our results showed that the type of protein and the type and amount of dietary fat selectively modify the activity of white adipose tissue, even in a genetic model of obesity. PMID:23773624

Díaz-Villaseñor, Andrea; Granados, Omar; González-Palacios, Berenice; Tovar-Palacio, Claudia; Torre-Villalvazo, Ivan; Olivares-García, Verónica; Torres, Nimbe; Tovar, Armando R

2013-11-01

25

Absence of humoral mediated 5'AMP-activated protein kinase activation in human skeletal muscle and adipose tissue during exercise.  

PubMed

5'AMP-activated protein kinase (AMPK) exists as a heterotrimer comprising a catalytic alpha subunit and regulatory beta and gamma subunits. The AMPK system is activated under conditions of cellular stress, indicated by an increase in the AMP/ATP ratio, as observed, e.g. in muscles during contractile activity. AMPK was originally thought to be activated only by local intracellular mechanisms. However, recently it has become apparent that AMPK in mammals is also regulated by humoral substances, e.g. catecholamines. We studied whether humoral factors released during exercise regulate AMPK activity in contracting and resting muscles as well as in abdominal subcutaneous adipose tissue in humans. In resting leg muscle and adipose tissue the AMPK activity was not up-regulated by humoral factors during one-legged knee extensor exercise even when arm cranking exercise, inducing a approximately 20-fold increase in plasma catecholamine level, was added simultaneously. In exercising leg muscle the AMPK activity was increased by one-legged knee extensor exercise eliciting a whole body respiratory load of only 30% .VO(2,peak) but was not further increased by adding arm cranking exercise. In conclusion, during exercise with combined leg kicking and arm cranking, the AMPK activity in human skeletal muscle is restricted to contracting muscle without influence of marked increased catecholamine levels. Also, with this type of exercise the catecholamines or other humoral factors do not seem to be physiological regulators of AMPK in the subcutaneous adipose tissue. PMID:17962330

Kristensen, Jonas Møller; Johnsen, Anders Bo; Birk, Jesper B; Nielsen, Jakob Nis; Jensen, Bente Rona; Hellsten, Ylva; Richter, Erik A; Wojtaszewski, Jørgen F P

2007-12-15

26

Absence of humoral mediated 5?AMP-activated protein kinase activation in human skeletal muscle and adipose tissue during exercise  

PubMed Central

5?AMP-activated protein kinase (AMPK) exists as a heterotrimer comprising a catalytic ? subunit and regulatory ? and ? subunits. The AMPK system is activated under conditions of cellular stress, indicated by an increase in the AMP/ATP ratio, as observed, e.g. in muscles during contractile activity. AMPK was originally thought to be activated only by local intracellular mechanisms. However, recently it has become apparent that AMPK in mammals is also regulated by humoral substances, e.g. catecholamines. We studied whether humoral factors released during exercise regulate AMPK activity in contracting and resting muscles as well as in abdominal subcutaneous adipose tissue in humans. In resting leg muscle and adipose tissue the AMPK activity was not up-regulated by humoral factors during one-legged knee extensor exercise even when arm cranking exercise, inducing a ?20-fold increase in plasma catecholamine level, was added simultaneously. In exercising leg muscle the AMPK activity was increased by one-legged knee extensor exercise eliciting a whole body respiratory load of only 30% but was not further increased by adding arm cranking exercise. In conclusion, during exercise with combined leg kicking and arm cranking, the AMPK activity in human skeletal muscle is restricted to contracting muscle without influence of marked increased catecholamine levels. Also, with this type of exercise the catecholamines or other humoral factors do not seem to be physiological regulators of AMPK in the subcutaneous adipose tissue. PMID:17962330

Kristensen, Jonas M?ller; Johnsen, Anders Bo; Birk, Jesper B; Nielsen, Jakob Nis; Jensen, Bente Rona; Hellsten, Ylva; Richter, Erik A; Wojtaszewski, J?rgen F P

2007-01-01

27

The interaction of hydrocortisone and thyroxine during fetal adipose tissue differentiation: CCAAT enhancing binding protein expression and capillary cytodifferentiation.  

PubMed

Late-term fetal pigs from genetically obese dams have elevated levels of thyroid hormones and glucocorticoids, depressed levels of GH, larger fat cells and elevated lipogenesis than do fetal pigs from lean dams. We investigated the influence of elevated levels of thyroid hormones and glucocorticoids per se on adipose tissue traits by chronically treating hypophysectomized (hypox; d 70) fetal pigs between d 90 and 105 of gestation with either thyroxine (T4), hydrocortisone (HC), or the combination of T4 + HC. Treatment with T4 and T4 + HC increased serum T4 and IGF-I levels and enhanced skin and hair development. Treatment with HC and T4 + HC increased serum HC levels, fat cell size, and inner subcutaneous adipose tissue thickness. Quantitative analysis of stained adipose tissue sections indicated that T4 + HC treatment increased lipid accretion and fat cell cluster development more than did either hormone alone. The T4 + HC markedly increased apparent fat cell number, because there was only a 19% increase in fat cell size. A hypox-induced deficit in cytodifferentiation of capillaries associated with adipocytes was not influenced by T4, but was partially normalized by treatment with HC and T4 + HC. Immunocytochemical and Western blot analyses showed no influence of hormonal treatment on expression of three CCAAT enhancing binding protein (C/EBP) isoforms. However, expression of C/EBPdelta in adipose tissue was markedly reduced in control fetal pigs compared with hypox fetal pigs. These studies indicate that concurrent action of glucocorticoids and thyroid hormones may be the critical aspect of endocrine regulation of fetal adipogenesis. PMID:10461986

Hausman, G J

1999-08-01

28

Adipose tissue macrophages: Amicus adipem?  

PubMed

Chronic overnutrition drives complex adaptations within both professional metabolic and bystander tissues that, despite intense investigation, are still poorly understood. Xu et al. (2013) now describe the unexpected ability of adipose tissue macrophages to buffer lipids released from obese adipocytes in a manner independent of inflammatory macrophage activation. PMID:24315364

Odegaard, Justin I; Ganeshan, Kirthana; Chawla, Ajay

2013-12-01

29

Triacylglycerol metabolism in adipose tissue  

PubMed Central

Triacylglycerol (TAG) in adipose tissue serves as the major energy storage form in higher eukaryotes. Obesity, resulting from excess white adipose tissue, has increased dramatically in recent years resulting in a serious public health problem. Understanding of adipocyte-specific TAG synthesis and hydrolysis is critical to the development of strategies to treat and prevent obesity and its closely associated diseases, for example, Type 2 diabetes, hypertension and atherosclerosis. In this review, we present an overview of the major enzymes in TAG synthesis and lipolysis, including the recent discovery of a novel adipocyte TAG hydrolase. PMID:19194515

Ahmadian, Maryam; Duncan, Robin E; Jaworski, Kathy; Sarkadi-Nagy, Eszter; Sul, Hei Sook

2009-01-01

30

The developmental origins of adipose tissue  

PubMed Central

Adipose tissue is formed at stereotypic times and locations in a diverse array of organisms. Once formed, the tissue is dynamic, responding to homeostatic and external cues and capable of a 15-fold expansion. The formation and maintenance of adipose tissue is essential to many biological processes and when perturbed leads to significant diseases. Despite this basic and clinical significance, understanding of the developmental biology of adipose tissue has languished. In this Review, we highlight recent efforts to unveil adipose developmental cues, adipose stem cell biology and the regulators of adipose tissue homeostasis and dynamism. PMID:24046315

Berry, Daniel C.; Stenesen, Drew; Zeve, Daniel; Graff, Jonathan M.

2013-01-01

31

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

PubMed

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. PMID:24559078

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

2014-11-01

32

In a Model of Batten Disease, Palmitoyl Protein Thioesterase-1 Deficiency Is Associated with Brown Adipose Tissue and Thermoregulation Abnormalities  

PubMed Central

Infantile neuronal ceroid lipofuscinosis (INCL) is a fatal neurodegenerative disorder caused by a deficiency of palmitoyl-protein thioesterase-1 (PPT1). We have previously shown that children with INCL have increased risk of hypothermia during anesthesia and that PPT1-deficiency in mice is associated with disruption of adaptive energy metabolism, downregulation of peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?), and mitochondrial dysfunction. Here we hypothesized that Ppt1-knockout mice, a well-studied model of INCL that shows many of the neurologic manifestations of the disease, would recapitulate the thermoregulation impairment observed in children with INCL. We also hypothesized that when exposed to cold, Ppt1-knockout mice would be unable to maintain body temperature as in mice thermogenesis requires upregulation of Pgc-1? and uncoupling protein 1 (Ucp-1) in brown adipose tissue. We found that the Ppt1-KO mice had lower basal body temperature as they aged and developed hypothermia during cold exposure. Surprisingly, this inability to maintain body temperature during cold exposure in Ppt1-KO mice was associated with an adequate upregulation of Pgc-1? and Ucp-1 but with lower levels of sympathetic neurotransmitters in brown adipose tissue. In addition, during baseline conditions, brown adipose tissue of Ppt1-KO mice had less vacuolization (lipid droplets) compared to wild-type animals. After cold stress, wild-type animals had significant decreases whereas Ppt1-KO had insignificant changes in lipid droplets compared with baseline measurements, thus suggesting that Ppt1-KO had less lipolysis in response to cold stress. These results uncover a previously unknown phenotype associated with PPT1 deficiency, that of altered thermoregulation, which is associated with impaired lipolysis and neurotransmitter release to brown adipose tissue during cold exposure. These findings suggest that INCL should be added to the list of neurodegenerative diseases that are linked to alterations in peripheral metabolic processes. In addition, extrapolating these findings clinically, impaired thermoregulation and hypothermia are potential risks in patients with INCL. PMID:23139814

Khaibullina, Alfia; Kenyon, Nicholas; Guptill, Virginia; Quezado, Martha M.; Wang, Li; Koziol, Deloris; Wesley, Robert; Moya, Pablo R.; Zhang, Zhongjian; Saha, Arjun; Mukherjee, Anil B.; Quezado, Zenaide M.N.

2012-01-01

33

Hypothalamic control of adipose tissue.  

PubMed

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. PMID:25256764

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

2014-10-01

34

Quantification of Adipose Tissue Leukocytosis in Obesity  

PubMed Central

Summary The infiltration of immune cell subsets in adipose tissue termed ‘adipose tissue leukocytosis’ is a critical event in the development of chronic inflammation and obesity-associated comorbidities. Given that a significant proportion of cells in adipose tissue of obese patients are of hematopoietic lineage, the distinct adipose depots represent an uncharacterized immunological organ that can impact metabolic functions. Here, we describe approaches to characterize and isolate leukocytes from the complex adipose tissue microenvironment to aid mechanistic studies to understand the role of specific pattern recognition receptors (PRRs) such as inflammasomes in adipose-immune crosstalk. PMID:23852606

Grant, Ryan; Youm, Yun-Hee; Ravussin, Anthony; Dixit, Vishwa Deep

2014-01-01

35

Sustainable Three-Dimensional Tissue Model of Human Adipose Tissue  

PubMed Central

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 PPAR?) 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. PMID:23373822

Bellas, Evangelia; Marra, Kacey G.

2013-01-01

36

Adipose Stem Cells: From Liposuction to Adipose Tissue Engineering  

Microsoft Academic Search

\\u000a A large volume of adipose tissue can be easily harvested through a well-established cosmetic surgical procedure, liposuction.\\u000a Mesenchymal adherent stem\\/progenitor cells, similar to those from bone marrow, can be extracted from liposuction aspirates\\u000a with a high efficiency and thus adipose tissue is now regarded as a potential source of adult stem\\/progenitor cells for regenerative\\u000a medicine. Many features of adipose stem\\/progenitor

Kotaro Yoshimura; Hitomi Eto; Harunosuke Kato; Kentaro Doi; Hirotaka Suga

37

Adipose tissue immunity and cancer  

PubMed Central

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 pro-inflammatory adipokines and cytokines providing a microenvironment favorable for tumor growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching toward M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumor 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 tumor cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumor microenvironment with more sophisticated and selective anti-tumoral drugs. PMID:24106481

Catalan, Victoria; Gomez-Ambrosi, Javier; Rodriguez, Amaia; Fruhbeck, Gema

2013-01-01

38

Chronic Alcohol Exposure Stimulates Adipose Tissue Lipolysis in Mice  

PubMed Central

Alcohol consumption induces liver steatosis; therefore, this study investigated the possible role of adipose tissue dysfunction in the pathogenesis of alcoholic steatosis. Mice were pair-fed an alcohol or control liquid diet for 8 weeks to evaluate the alcohol effects on lipid metabolism at the adipose tissue–liver axis. Chronic alcohol exposure reduced adipose tissue mass and adipocyte size. Fatty acid release from adipose tissue explants was significantly increased in alcohol-fed mice in association with the activation of adipose triglyceride lipase and hormone-sensitive lipase. Alcohol exposure induced insulin intolerance and inactivated adipose protein phosphatase 1 in association with the up-regulation of phosphatase and tensin homolog (PTEN) and suppressor of cytokine signaling 3 (SOCS3). Alcohol exposure up-regulated fatty acid transport proteins and caused lipid accumulation in the liver. To define the mechanistic link between adipose triglyceride loss and hepatic triglyceride gain, mice were first administered heavy water for 5 weeks to label adipose triglycerides with deuterium, and then pair-fed alcohol or control diet for 2 weeks. Deposition of deuterium-labeled adipose triglycerides in the liver was analyzed using Fourier transform ion cyclotron mass spectrometry. Alcohol exposure increased more than a dozen deuterium-labeled triglyceride molecules in the liver by up to 6.3-fold. These data demonstrate for the first time that adipose triglycerides due to alcohol-induced hyperlipolysis are reverse transported and deposited in the liver. PMID:22234172

Zhong, Wei; Zhao, Yantao; Tang, Yunan; Wei, Xiaoli; Shi, Xue; Sun, Wenlong; Sun, Xiuhua; Yin, Xinmin; Sun, Xinguo; Kim, Seongho; McClain, Craig J.; Zhang, Xiang; Zhou, Zhanxiang

2012-01-01

39

Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity  

PubMed Central

Background Middle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. Methodology/Principal Findings To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. Conclusions/Significance Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-? and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokine secretion with no obvious effects on adipocyte culture phenotype. These data support the hypothesis that high fat diet-dependent obesity results in concomitant pro-inflammatory changes in brain and adipose tissue that is characterized, in part, by increased levels of APP that may be contributing specifically to inflammatory changes that occur. PMID:22276186

Puig, Kendra L.; Floden, Angela M.; Adhikari, Ramchandra; Golovko, Mikhail Y.; Combs, Colin K.

2012-01-01

40

Increased glyceroneogenesis in adipose tissue from rats adapted to a high-protein, carbohydrate-free diet: role of dietary fatty acids  

Microsoft Academic Search

We have previously shown in in vivo experiments that adipose tissue glyceroneogenesis is increased in rats adapted to a high-protein, carbohydrate-free (HP) diet. The objectives of the present study were (1) to verify if the increased glyceroneogenic activity is also observed in isolated adipocytes and (2) to investigate the role of preformed fatty acids in the production of the increased

Salete Cipriano Brito; William Lara Festuccia; Nair Honda Kawashita; Maria Ferreira Moura; Analúcia Rampazzo Xavier; Maria Antonieta Garófalo; Isis Carmo Kettelhut; Renato Hélios Migliorini

2006-01-01

41

Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet.  

PubMed

We measured the effects of a diet in which D-?-hydroxybutyrate-(R)-1,3 butanediol monoester [ketone ester (KE)] replaced equicaloric amounts of carbohydrate on 8-wk-old male C57BL/6J mice. Diets contained equal amounts of fat, protein, and micronutrients. The KE group was fed ad libitum, whereas the control (Ctrl) mice were pair-fed to the KE group. Blood d-?-hydroxybutyrate levels in the KE group were 3-5 times those reported with high-fat ketogenic diets. Voluntary food intake was reduced dose dependently with the KE diet. Feeding the KE diet for up to 1 mo increased the number of mitochondria and doubled the electron transport chain proteins, uncoupling protein 1, and mitochondrial biogenesis-regulating proteins in the interscapular brown adipose tissue (IBAT). [(18)F]-Fluorodeoxyglucose uptake in IBAT of the KE group was twice that in IBAT of the Ctrl group. Plasma leptin levels of the KE group were more than 2-fold those of the Ctrl group and were associated with increased sympathetic nervous system activity to IBAT. The KE group exhibited 14% greater resting energy expenditure, but the total energy expenditure measured over a 24-h period or body weights was not different. The quantitative insulin-sensitivity check index was 73% higher in the KE group. These results identify KE as a potential antiobesity supplement. PMID:22362892

Srivastava, Shireesh; Kashiwaya, Yoshihiro; King, M Todd; Baxa, Ulrich; Tam, Joseph; Niu, Gang; Chen, Xiaoyuan; Clarke, Kieran; Veech, Richard L

2012-06-01

42

Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton's jelly  

PubMed Central

Introduction Different mesenchymal stromal cells (MSC) have been successfully isolated and expanded in vitro and nowadays they are tested in clinical trials for a wide variety of diseases. Whether all MSC express the same cell surface markers or have a similar secretion profile is still controversial, making it difficult to decide which stromal cell may be better for a particular application. Methods We isolated human mesenchymal stromal cells from bone marrow (BM), adipose tissue (AT) and Wharton’s jelly (WJ) and cultured them in fetal bovine serum supplemented media. We evaluated proliferation, in vitro differentiation (osteogenic, adipogenic and chondrogenic potential), expression of cell surface markers and protein secretion using Luminex and ELISA assays. Results Cell proliferation was higher for WJ-MSC, followed by AT-MSC. Differences in surface expression markers were observed only for CD54 and CD146. WJ-MSC secreted higher concentrations of chemokines, pro-inflammatory proteins and growth factors. AT-MSC showed a better pro-angiogenic profile and secreted higher amounts of extracellular matrix components and metalloproteinases. Conclusions Mesenchymal stromal cells purified from different tissues have different angiogenic, inflammatory and matrix remodeling potential properties. These abilities should be further characterized in order to choose the best protocols for their therapeutic use. PMID:24739658

2014-01-01

43

Whey protein isolate counteracts the effects of a high-fat diet on energy intake and hypothalamic and adipose tissue expression of energy balance-related genes.  

PubMed

The intake of whey protein isolate (WPI) is known to reduce high-fat diet (HFD)-induced body-weight gain and adiposity. However, the molecular mechanisms are not fully understood. To this end, we fed C57BL/6J mice for 8 weeks with diets containing 10 % energy as fat (low-fat diet, LFD) or 45 % energy as fat (HFD) enriched with either 20 % energy as casein (LFD and HFD) or WPI (high-fat WPI). Metabolic parameters and the hypothalamic and epididymal adipose tissue expression of energy balance-related genes were investigated. The HFD increased fat mass and plasma leptin levels and decreased the dark-phase energy intake, meal number, RER, and metabolic (VO? and heat) and locomotor activities compared with the LFD. The HFD increased the hypothalamic tissue mRNA expression of the leptin receptor, insulin receptor (INSR) and carnitine palmitoyltransferase 1b (CPT1b). The HFD also reduced the adipose tissue mRNA expression of GLUT4 and INSR. In contrast, WPI reduced fat mass, normalised dark-phase energy intake and increased meal size in HFD-fed mice. The dietary protein did not have an impact on plasma leptin, insulin, glucose or glucagon-like peptide 1 levels, but increased plasma TAG levels in HFD-fed mice. At a cellular level, WPI significantly reduced the HFD-associated increase in the hypothalamic tissue mRNA expression of the leptin receptor, INSR and CPT1b. Also, WPI prevented the HFD-induced reduction in the adipose tissue mRNA expression of INSR and GLUT4. In comparison with casein, the effects of WPI on energy intake and hypothalamic and adipose tissue gene expression may thus represent a state of reduced susceptibility to weight gain on a HFD. PMID:23731955

McAllan, Liam; Keane, Deirdre; Schellekens, Harriët; Roche, Helen M; Korpela, Riitta; Cryan, John F; Nilaweera, Kanishka N

2013-12-14

44

Adipose and mammary epithelial tissue engineering  

PubMed Central

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. PMID:23628872

Zhu, Wenting; Nelson, Celeste M.

2013-01-01

45

Adaptations of Maternal Adipose Tissue to Lactation  

Microsoft Academic Search

The ability to store substantial amounts of energy as lipid in adipose tissue has allowed development of a variety of strategies in wild animals to meet the considerable metabolic challenge of lactation. The ability to use adipose tissue energy has also been critical for development of the exceptional rates of milk production achieved in the dairy cow. Lactation thus results

Richard G. Vernon; Caroline M. Pond

1997-01-01

46

Imaging White Adipose Tissue With Confocal Microscopy  

PubMed Central

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. PMID:24480339

Martinez-Santibanez, Gabriel; Cho, Kae Won; Lumeng, Carey N.

2014-01-01

47

Identification and functional characterization of lipid binding proteins in liver and adipose tissues of Gallus domesticus  

E-print Network

characterize the two chicken liver proteins; and 4) to prepare and validate polyclonal antisera against A-FABP and the two lipid binding proteins in liver. CHAPTER II LITERATURE REVIEW Much scientific as well as popular attention has focused... characterize the two chicken liver proteins; and 4) to prepare and validate polyclonal antisera against A-FABP and the two lipid binding proteins in liver. CHAPTER II LITERATURE REVIEW Much scientific as well as popular attention has focused...

Sams, Gretchen Hubler

2012-06-07

48

Adipose Tissue Sensitivity to Radiation Exposure  

PubMed Central

Treatment of cancer using radiation can be significantly compromised by the development of severe acute and late damage to normal tissue. Treatments that either reduce the risk and severity of damage or that facilitate the healing of radiation injuries are being developed, including autologous adipose tissue grafts to repair tissue defects or involutional disorders that result from tumor resection. Adipose tissue is specialized in energy storage and contains different cell types, including preadipocytes, which could be used for autologous transplantation. It has long been considered a poorly proliferative connective tissue; however, the acute effects of ionizing radiation on adipose tissue have not been investigated. Therefore, the aim of this study was to characterize the alterations induced in adipose tissue by total body irradiation. A severe decrease in proliferating cells, as well as a significant increase in apoptotic cells, was observed in vivo in inguinal fat pads following irradiation. Additionally, irradiation altered the hematopoietic population. Decreases in the proliferation and differentiation capacities of non-hematopoietic progenitors were also observed following irradiation. Together, these data demonstrate that subcutaneous adipose tissue is very sensitive to irradiation, leading to a profound alteration of its developmental potential. This damage could also alter the reconstructive properties of adipose tissue and, therefore, calls into question its use in autologous fat transfer following radiotherapy. PMID:19095959

Poglio, Sandrine; Galvani, Sylvain; Bour, Sandy; Andre, Mireille; Prunet-Marcassus, Benedicte; Penicaud, Luc; Casteilla, Louis; Cousin, Beatrice

2009-01-01

49

Circadian rhythms in white adipose tissue.  

PubMed

Adipose tissue is an important endocrine organ. It is involved in the regulation of energy metabolism by secreting factors (adipokines) that regulate appetite, food intake, glucose disposal, and energy expenditure. Many of these adipokines display profound day/night rhythms, and accumulating evidence links disruption of these rhythms to metabolic diseases such as obesity and type 2 diabetes. Here, we briefly present the circadian system, describe the development of white adipose tissue (WAT) and its depot-specific characteristics and innervation, we discuss energy storage in WAT and, lastly, review recent findings that link circadian rhythmicity to adipose tissue biology and obesity. PMID:22877666

van der Spek, Rianne; Kreier, Felix; Fliers, Eric; Kalsbeek, Andries

2012-01-01

50

Adipose tissue engineering by human adipose-derived stromal cells.  

PubMed

Tissue engineering has emerged as a promising alternative approach to current clinical treatments for restoration of soft tissue defects. The purpose of this study was to investigate adipose tissue formation in vitro and in vivo by using human adipose-derived stromal cells (ADSCs) utilizing a gelatin sponge (Gelform) as a scaffold. Adipogenic potentials of human ADSCs were demonstrated by Oil-O-red staining and cellular morphology. After seeding human ADSCs in a density of 3 x 10(6) cells/ml on three-dimensional gelatin sponges, tissue-engineered constructs were exposed to adipogenic differentiation medium for in vitro studies and implanted in the backs of severe combined immunodeficient (SCID) mice for in vivo adipose regeneration. Adipogenesis of ADSC-seeded gelatin sponges was confirmed by Oil-O-red staining after 4 weeks of in vitro incubation. The optical density of the elution from Oil-O-red staining of adipogenic constructs is significantly higher than that of the control group (p < 0.05, n = 4). With short-term in vitro differentiation, adipogenic constructs turned into fat tissue 4 weeks after in vivo implantation, confirmed by biochemical and immunohistochemical examination. No adipogenic-morphological change or fat formation was observed in in vitro or in vivo studies when ADSCs were exposed to a control medium without adipogenic stimulation. These results indicate that engineered adipose tissue can be achieved using human ADSCs and biocompatible and degradable gelatin sponges. PMID:17108684

Hong, Liu; Peptan, Ioana A; Colpan, Aylin; Daw, Joseph L

2006-01-01

51

Flow Cytometry Analyses of Adipose Tissue Macrophages  

PubMed Central

Within adipose tissue, multiple leukocyte interactions contribute to metabolic homeostasis in health as well as to the pathogenesis of insulin resistance with obesity. Adipose tissue macrophages (ATMs) are the predominant leukocyte population in fat and contribute to obesity-induced inflammation. Characterization of ATMs and other leukocytes in the stromal vascular fraction from fat has benefited from the use of flow cytometry and flow-assisted cell sorting techniques. These methods permit the immunophenotyping, quantification, and purification of these unique cell populations from multiple adipose tissue depots in rodents and humans. Proper isolation, quantification, and characterization of ATM phenotypes are critical for understanding their role in adipose tissue function and obesity-induced metabolic diseases. Here, we present the flow cytometry protocols for phenotyping ATMs in lean and obese mice employed by our laboratory. PMID:24480353

Cho, Kae Won; Morris, David L.; Lumeng, Carey N.

2014-01-01

52

Adipose Tissue Quantification by Imaging Methods: A Proposed Classification  

Microsoft Academic Search

Recent advances in imaging techniques and understanding of differences in the molecular biology of adipose tissue has rendered classical anatomy obsolete, requiring a new classification of the topography of adipose tissue. Adipose tissue is one of the largest body compartments, yet a classification that defines specific adipose tissue depots based on their anatomic location and related functions is lacking. The

Wei Shen; ZiMian Wang; Mark Punyanita; Jianbo Lei; Ahmet Sinav; John G. Kral; Celina Imielinska; Robert Ross; Steven B. Heymsfield

2003-01-01

53

Expression of proteins associated with adipocyte lipolysis was significantly changed in the adipose tissues of the obese spontaneously hypertensive/NDmcr-cp rat  

PubMed Central

Background The etiology of the metabolic syndrome is complex, and is determined by the interplay of both genetic and environmental factors. The present study was designed to identify genes and proteins in the adipose tissues with altered expression in the spontaneously hypertensive/NIH –corpulent rat, SHR/NDmcr-cp (CP) and to find possible molecular targets associated with the pathogenesis or progression of obesity related to the metabolic syndrome. Methods We extracted RNAs and proteins from the epididymal adipose tissues in CP, SHR/Lean (Lean), and Wistar Kyoto (WKY) rats and performed microarray analysis and two-dimensional difference in gel electrophoresis (2D-DIGE) linked to a matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS). Results The results showed different mRNA and protein expression levels in the adipose tissue: oligo DNA microarray identified 33 genes that were significantly (P?proteins were associated with lipolytic enzymes stimulated by peroxisome proliferator-activated receptor (PPAR) signaling. Further analysis using the 2D-DIGE connected with MALDI-TOF/TOF analysis, the expression of monoglyceride lipase (MGLL) was significantly up-regulated and that of carboxylesterase 3 (CES3) was significantly down-regulated in 6- and 25-week-old CP compared with age-matched control (WKY and Lean rats). Conclusions Our results suggest the possible involvement of proteins associated with adipocyte lipolysis in obesity related to the metabolic syndrome. PMID:24468282

2014-01-01

54

Reduced Adipose Tissue Oxygenation in Human Obesity  

PubMed Central

OBJECTIVE— Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation. RESEARCH DESIGN AND METHODS— Oxygen partial pressure (AT pO2) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay. RESULTS— AT pO2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO2 was negatively correlated with percent body fat (R = ?0.50, P < 0.05). Compared with lean subjects, overweight/obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator–activated receptor ?1 and higher collagen VI mRNA expression, which correlated with AT pO2 (P < 0.05). Of clinical importance, AT pO2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1? secretion (R = ?0.58, R = ?0.79, P < 0.05), suggesting that lower AT pO2 could drive AT inflammation in obesity. CONCLUSIONS— Adipose tissue rarefaction might lie upstream of both low AT pO2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity. PMID:19074987

Pasarica, Magdalena; Sereda, Olga R.; Redman, Leanne M.; Albarado, Diana C.; Hymel, David T.; Roan, Laura E.; Rood, Jennifer C.; Burk, David H.; Smith, Steven R.

2009-01-01

55

Adipose tissue insulin sensitivity and macrophage recruitment  

PubMed Central

In the United States, obesity is a burgeoning health crisis, with over 30% of adults and nearly 20% of children classified as obese. Insulin resistance, a common metabolic complication associated with obesity, significantly increases the risk of developing metabolic diseases such as hypertension, coronary heart disease, stroke, type 2 diabetes, and certain cancers. With the seminal finding that obese adipose tissue harbors cytokine secreting immune cells, obesity-related research over the past decade has focused on understanding adipocyte–macrophage crosstalk and its impact on systemic insulin sensitivity. Indeed, adipose tissue has emerged as a central mediator of obesity- and diet-induced insulin resistance. In this mini-review, we focus on a potential role of adipose tissue phosphoinositide 3-kinase (PI3K) as a point of convergence of cellular signaling pathways that integrates nutrient sensing and inflammatory signaling to regulate tissue insulin sensitivity. PMID:23991359

McCurdy, Carrie E; Klemm, Dwight J

2013-01-01

56

Reassessing triglyceride synthesis in adipose tissue  

Microsoft Academic Search

The synthesis and breakdown of triglycerides in adipose tissue and muscle is a crucial element of energy metab- olism because it ensures that adequate fuel is available during starvation. Triglyceride turnover determines the availability of fatty acids for utilization by mammalian tissues, and any dysfunction in this process can lead to alterationsinglucosemetabolism,insulinresistanceand type 2 diabetes. Our understanding of the reactions

Colleen Nye; Jaeyeon Kim; Satish C. Kalhan; Richard W. Hanson

2008-01-01

57

Adipose Triglyceride Lipase (ATGL) and Hormone-Sensitive Lipase (HSL) Deficiencies Affect Expression of Lipolytic Activities in Mouse Adipose Tissues*  

PubMed Central

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 patters 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. PMID:22984285

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

2012-01-01

58

A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation  

PubMed Central

Background There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis factor alpha (hTNF?). Methods hTNF? mice (C57BL/6 hTNF?) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma. Results The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of ?6 and ?9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-? level was observed. Plasma carnitine and the carnitine precursor ?-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal ?-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice. Conclusions The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin. PMID:24098955

2013-01-01

59

CCAAT/enhancer-binding protein ? (C/EBP?) expression regulates dietary-induced inflammation in macrophages and adipose tissue in mice.  

PubMed

Strong evidence exists for a link between chronic low level inflammation and dietary-induced insulin resistance; however, little is known about the transcriptional networks involved. Here we show that high fat diet (HFD) or saturated fatty acid exposure directly activates CCAAT/enhancer-binding protein ? (C/EBP?) protein expression in liver, adipocytes, and macrophages. Global C/EBP? deletion prevented HFD-induced inflammation and surprisingly increased mitochondrial gene expression in white adipose tissue along with brown adipose tissue markers PRDM16, CIDEa, and UCP1, consistent with a resistance to HFD-induced obesity. In isolated peritoneal macrophages from C/EBP?(-/-) mice, the anti-inflammatory gene LXR? and its targets SCD1 and DGAT2 were strikingly up-regulated along with IL-10, while NLRP3, a gene important for activating the inflammasome, was suppressed in response to palmitate. Using RAW 264.7 macrophage cells or 3T3-L1 adipocytes, C/EBP? knockdown prevented palmitate-induced inflammation and p65-NF?B DNA binding activity, while C/EBP? overexpression induced NF?B binding, JNK activation, and pro-inflammatory cytokine gene expression directly. Finally, chimeric bone marrow mice transplanted with bone marrow lacking C/EBP?(-/-) demonstrated reduced systemic and adipose tissue inflammatory markers, macrophage content, and maintained insulin sensitivity on HFD. Taken together, these results demonstrate that HFD or palmitate exposure triggers C/EBP? expression that controls expression of distinct aspects of alternative macrophage activation. Reducing C/EBP? in macrophages confers protection from HFD-induced systemic inflammation and insulin resistance, suggesting it may be an attractive therapeutic target for ameliorating obesity-induced inflammatory responses. PMID:22902781

Rahman, Shaikh M; Janssen, Rachel C; Choudhury, Mahua; Baquero, Karalee C; Aikens, Rebecca M; de la Houssaye, Becky A; Friedman, Jacob E

2012-10-01

60

Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages  

Microsoft Academic Search

Adipokines are involved in the obesity-induced chronic inflammatory response that plays a crucial role in the development of obesity-related pathologies such as type II diabetes and atherosclerosis. We here demonstrate that capsaicin, a naturally occurring phytochemical, can suppress obesity-induced inflammation by modulating adipokine release from and macrophage behavior in obese mice adipose tissues. Capsaicin inhibited the expressions of IL-6 and

Ji-Hye Kang; Chu-Sook Kim; In-Seob Han; Teruo Kawada; Rina Yu

2007-01-01

61

Mechanisms of Disease: adipocytokines and visceral adipose tissue—emerging role in nonalcoholic fatty liver disease  

Microsoft Academic Search

There is increasing evidence that visceral adipose tissue is a causative risk factor for fatty liver and nonalcoholic steatohepatitis. Adipose tissue-derived secretory proteins are collectively named adipocytokines. Obesity and mainly visceral fat accumulation impair adipocyte function and adipocytokine secretion and the altered release of these proteins contributes to hypertension, impaired fibrinolysis and insulin resistance. This review summarizes recent findings on

Andreas Schäffler; Jürgen Schölmerich; Christa Büchler

2005-01-01

62

Understanding androgen action in adipose tissue.  

PubMed

Androgens play an important role in regulation of body fat distribution in humans. They exert direct effects on adipocyte differentiation in a depot-specific manner, via the androgen receptor (AR), leading to modulation of adipocyte size and fat compartment expansion. Androgens also impact directly on key adipocyte functions including insulin signalling, lipid metabolism, fatty acid uptake and adipokine production. Androgen excess and deficiency have implications for metabolic health in both males and females, and these metabolic effects may be mediated through adipose tissue via effects on fat distribution, adipocyte function and lipolysis. Research into the field of androgen metabolism in human and animal adipose tissue has produced inconsistent results; it is important to take into account the sex-, depot- and organism-specific effects of androgens in fat. In general, studies point towards a stimulatory effect on lipolysis, with impairment of adipocyte differentiation, insulin signalling and adipokine generation. Observed effects are frequently gender-specific. Adipose tissue is an important organ of pre-receptor androgen metabolism, through which local androgen availability is rigorously controlled. Adipose androgen exposure is tightly controlled by isoenzymes of AKR1C, 5?-reductase and others, but regulation of the balance between generation and irreversible inactivation remains poorly understood. In particular, AKR1C2 and AKR1C3 are crucial in the regulation of local androgen bioavailability within adipose tissue. These isoforms control the balance between activation of androstenedione (A) to testosterone (T) by the 17?-hydroxysteroid dehydrogenase activity (17?-HSD) of AKR1C3, or inactivation of 5?-dihydrotestosterone (DHT) to 5?-androstane-3?,17?-diol by the 3?-hydroxysteroid dehydrogenase (3?-HSD) activity of AKR1C2. Most studies suggest that androgen inactivation is the predominant reaction in fat, particularly in the abdominal subcutaneous (SC) depot. Modulation of local adipose androgen availability may afford future therapeutic options to improve metabolic phenotype in disorders of androgen excess and deficiency. PMID:24787657

O'Reilly, Michael W; House, Philip J; Tomlinson, Jeremy W

2014-09-01

63

Immunohistochemical profiling of the heat shock response in obese non-diabetic subjects revealed impaired expression of heat shock proteins in the adipose tissue  

PubMed Central

Background Obesity is characterized by a chronic low-grade inflammation and altered stress responses in key metabolic tissues. Impairment of heat shock response (HSR) has been already linked to diabetes and insulin resistance as reflected by decrease in heat shock proteins (HSPs) expression. However, the status of HSR in non-diabetic human obese has not yet been elucidated. The aim of the current study was to investigate whether obesity triggers a change in the HSR pattern and the impact of physical exercise on this pattern at protein and mRNA levels. Methods Two groups of adult non-diabetic human subjects consisting of lean and obese (n?=?47 for each group) were enrolled in this study. The expression pattern of HSP-27, DNAJB3/HSP-40, HSP-60, HSC-70, HSP72, HSP-90 and GRP-94 in the adipose tissue was primarily investigated by immunohistochemistry and then complemented by western blot and qRT-PCR in Peripheral blood mononuclear cells (PBMCs). HSPs expression levels were correlated with various physical, clinical and biochemical parameters. We have also explored the effect of a 3-month moderate physical exercise on the HSPs expression pattern in obese subjects. Results Obese subjects displayed increased expression of HSP-60, HSC-70, HSP-72, HSP-90 and GRP-94 and lower expression of DNAJB3/HSP-40 (P?proteins correlated positively with the indices of obesity (body mass index and percent body fat) and circulating levels of IFN-gamma-inducible protein 10 (IP-10) and RANTES chemokines. This expression pattern was concomitant with increased inflammatory response in the adipose tissue as monitored by increased levels of Interleukin-6 (IL-6), Tumor necrosis factor-? (TNF-?), and RANTES (P?adipose tissue with concomitant attenuation in the inflammatory response. PMID:24986468

2014-01-01

64

Insulin effects in muscle and adipose tissue  

Microsoft Academic Search

The major effects of insulin on muscle and adipose tissue are: (1) Carbohydrate metabolism: (a) it increases the rate of glucose transport across the cell membrane, (b) it increases the rate of glycolysis by increasing hexokinase and 6-phosphofructokinase activity, (c) it stimulates the rate of glycogen synthesis and decreases the rate of glycogen breakdown. (2) Lipid metabolism: (a) it decreases

George Dimitriadis; Panayota Mitron; Vaia Lambadiari; Eirini Maratou; Sotirios A. Raptis

2011-01-01

65

Vitamin D and adipose tissue-more than storage.  

PubMed

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(OH)D), no evidence was obtained for a BMI lowering effect by higher 25(OH)D. Some of the physiological functions of 1,25(OH)2D3 (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(OH)2D3, vitamin D binding proteins (VDBPs) and nuclear vitamin D receptor (VDR) after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH)2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH)2D3 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(OH)2D3. Experimental studies demonstrate that 1,25(OH)2D3 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. PMID:25009502

Mutt, Shivaprakash J; Hyppönen, Elina; Saarnio, Juha; Järvelin, Marjo-Riitta; Herzig, Karl-Heinz

2014-01-01

66

Intermuscular adipose tissue rivals visceral adipose tissue in independent associations with cardiovascular risk  

Microsoft Academic Search

Background:The metabolic implications of intermuscular adipose tissue (IMAT) are poorly understood compared to those of visceral adipose tissue (VAT) even though the absolute quantities of both depots are similar in many individuals.Objective:The aim was to determine the independent relationship between whole-body IMAT and cardiovascular risk factor parameters.Design:Whole body magnetic resonance imaging (MRI) was used to quantify total skeletal muscle (SM),

J-E Yim; S Heshka; J Albu; S Heymsfield; P Kuznia; T Harris; D Gallagher

2007-01-01

67

Rhein Protects against Obesity and Related Metabolic Disorders through Liver X Receptor-Mediated Uncoupling Protein 1 Upregulation in Brown Adipose Tissue  

PubMed Central

Liver X receptors (LXRs) play important roles in regulating cholesterol homeostasis, and lipid and energy metabolism. Therefore, LXR ligands could be used for the management of metabolic disorders. We evaluated rhein, a natural compound from Rheum palmatum L., as an antagonist for LXRs and investigated its anti-obesity mechanism in high-fat diet-fed mice. Surface plasmon resonance assays were performed to examine the direct binding of rhein to LXRs. LXR target gene expression was assessed in 3T3-L1 adipocytes and HepG2 hepatic cells in vitro. C57BL/6J mice fed a high-fat diet were orally administered with rhein for 4 weeks, and then the expression levels of LXR-related genes were analyzed. Rhein bound directly to LXRs. The expression levels of LXR target genes were suppressed by rhein in 3T3-L1 and HepG2 cells. In white adipose tissue, muscle and liver, rhein reprogrammed the expression of LXR target genes related to adipogenesis and cholesterol metabolism. Rhein activated uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) in wild-type mice, but did not affect UCP1 expression in LXR knockout mice. In HIB-1B brown adipocytes, rhein activated the UCP1 gene by antagonizing the repressive effect of LXR on UCP1 expression. This study suggests that rhein may protect against obesity and related metabolic disorders through LXR antagonism and regulation of UCP1 expression in BAT. PMID:23139635

Sheng, Xiaoyan; Zhu, Xuehua; Zhang, Yuebo; Cui, Guoliang; Peng, Linling; Lu, Xiong; Zang, Ying Qin

2012-01-01

68

Measurement of the Increase in Endoplasmic Reticulum Stress-Related Proteins and Genes in Adipose Tissue of Obese, Insulin-Resistant Individuals  

PubMed Central

Here, we provide a detailed description of proteomic, Western blot and RT-PCR analyses performed to examine fat biopsy samples from lean insulin-sensitive and obese insulin-resistant nondiabetic individuals for evidence of endoplasmic reticulum (ER) stress. Subcutaneous fat biopsies were obtained from the upper thighs of six lean and six obese nondiabetic subjects. Fat homogenates were used for proteomic (two-dimensional gel (2DE) and MALDI-TOF/TOF), Western blot, and RT-PCR analysis. Proteomic analysis revealed 19 differentially upregulated proteins in fat of obese subjects. Three of these proteins were the ER stress-related unfolded protein response (UPR) proteins calreticulin, protein disulfide-isomerase A3, and glutathione-S-transferase P; Western blotting revealed upregulation of several other UPR stress-related proteins, including calnexin, a membrane-bound chaperone, and phospho c-jun NH2-terminal kinase (JNK)-1, a downstream effector protein of ER stress; RT-PCR analysis revealed upregulation of the spliced form of X-box-binding protein-1s, a potent transcription factor and part of the proximal ER stress sensor inositol-requiring enzyme-1 pathway. These findings demonstrate of UPR activation in subcutaneous adipose tissue of obese human subjects. As JNK can inhibit insulin action and activate proinflammatory pathways, ER stress activation of JNK may be a link between obesity, insulin resistance, and inflammation. PMID:21266224

Boden, Guenther; Merali, Salim

2011-01-01

69

Laminin ?4 Deficient Mice Exhibit Decreased Capacity for Adipose Tissue Expansion and Weight Gain  

PubMed Central

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 ?4, 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 ?4 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 ?4 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. PMID:25310607

Moverare-Skrtic, Sofia; Kortesmaa, Jarkko; Soininen, Raija; Bergstrom, Goran; Ohlsson, Claes; Chong, Li Yen; Rozell, Bjorn; Emont, Margo; Cohen, Ronald N.; Brey, Eric M.; Tryggvason, Karl

2014-01-01

70

Laminin ?4 Deficient Mice Exhibit Decreased Capacity for Adipose Tissue Expansion and Weight Gain.  

PubMed

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 ?4, 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 ?4 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 ?4 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. PMID:25310607

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

71

Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase  

Microsoft Academic Search

Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial

Robert Zimmermann; Juliane G. Strauss; Guenter Haemmerle; Gabriele Schoiswohl; Ruth Birner-Gruenberger; Monika Riederer; Achim Lass; Georg Neuberger; Frank Eisenhaber; Albin Hermetter; Rudolf Zechner

2004-01-01

72

IL-6 Is Not Necessary for the Regulation of Adipose Tissue Mitochondrial Content  

PubMed Central

Background Adipose tissue mitochondria have been implicated as key mediators of systemic metabolism. We have shown that IL-6 activates AMPK, a mediator of mitochondrial biogenesis, in adipose tissue; however, IL-6?/? mice fed a high fat diet have been reported to develop insulin resistance. These findings suggest that IL-6 may control adipose tissue mitochondrial content in vivo, and that reductions in adipose tissue mitochondria may be causally linked to the development of insulin resistance in IL-6?/? mice fed a high fat diet. On the other hand, IL-6 has been implicated as a negative regulator of insulin action. Given these discrepancies the purpose of the present investigation was to further evaluate the relationship between IL-6, adipose tissue mitochondrial content and whole body insulin action. Methodology and Principal Findings In cultured epididymal mouse adipose tissue IL-6 (75 ng/ml) induced the expression of the transcriptional co-activators PGC-1? and PRC, reputed mediators of mitochondrial biogenesis. Similarly, IL-6 increased the expression of COXIV and CPT-1. These effects were absent in cultured subcutaneous adipose tissue and were associated with lower levels of GP130 and IL-6 receptor alpha protein content. Markers of mitochondrial content were intact in adipose tissue from chow fed IL-6?/? mice. When fed a high fat diet IL-6?/? mice were more glucose and insulin intolerant than controls fed the same diet; however this was not explained by decreases in adipose tissue mitochondrial content or respiration. Conclusions and Significance Our findings demonstrate depot-specific differences in the ability of IL-6 to induce PGC-1? and mitochondrial enzymes and demonstrate that IL-6 is not necessary for the maintenance of adipose tissue mitochondrial content in vivo. Moreover, reductions in adipose tissue mitochondria do not explain the greater insulin resistance in IL-6?/? mice fed a high fat diet. These results question the role of adipose tissue mitochondrial dysfunction in the etiology of insulin resistance. PMID:23240005

Wan, Zhongxiao; Perry, Christopher G. R.; Macdonald, Tara; Chan, Catherine B.; Holloway, Graham P.; Wright, David C.

2012-01-01

73

Vasodilator signals from perivascular adipose tissue  

PubMed Central

Visceral fat has been linked to metabolic disturbances and increased risk for cardiovascular disease and type 2 diabetes. Recent studies propose a paracrine role for periadventitial adipose tissue in the control of arterial vascular tone. This regulation depends on the anatomical integrity of the vessels and involves a transferable mediator(s) (adipokine) released from either periadventitial adipocytes or perivascular adipose tissue. Although a number of adipokines with vasoactive properties have been identified, a still unidentified adipocyte-derived relaxing factor (ADRF) plays a major role in the periadventitial vasoregulation of visceral arteries, such as the aorta and mesenteric arteries. ADRF is released by visceral periadventitial adipocytes and primarily produces endothelium-independent vasorelaxation by opening voltage-dependent (Kv) K+ channels in the plasma membrane of smooth muscle cells. At least in part, KCNQ (Kv7) channels could represent the subtype of Kv channels involved. Glibenclamide-sensitive KATP channels are not involved or play a minor role. The ‘third gas’, namely H2S, could represent ADRF. Alterations in the paracrine control of arterial tone by visceral periadventitial adipose tissue have been found in animal models of hypertension and metabolic disease. ADRF, or perhaps its putative targets, might represent exciting new targets for the development of drugs for treatment of cardiovascular and metabolic disorders. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21486288

Gollasch, Maik

2012-01-01

74

The Role of GH in Adipose Tissue: Lessons from Adipose-Specific GH Receptor Gene-Disrupted Mice  

PubMed Central

GH receptor (GHR) gene-disrupted mice (GHR?/?) have provided countless discoveries as to the numerous actions of GH. Many of these discoveries highlight the importance of GH in adipose tissue. For example GHR?/? mice are insulin sensitive yet obese with preferential enlargement of the sc adipose depot. GHR?/? mice also have elevated levels of leptin, resistin, and adiponectin, compared with controls leading some to suggest that GH may negatively regulate certain adipokines. To help clarify the role that GH exerts specifically on adipose tissue in vivo, we selectively disrupted GHR in adipose tissue to produce Fat GHR Knockout (FaGHRKO) mice. Surprisingly, FaGHRKOs shared only a few characteristics with global GHR?/? mice. Like the GHR?/? mice, FaGHRKO mice are obese with increased total body fat and increased adipocyte size. However, FaGHRKO mice have increases in all adipose depots with no improvements in measures of glucose homeostasis. Furthermore, resistin and adiponectin levels in FaGHRKO mice are similar to controls (or slightly decreased) unlike the increased levels found in GHR?/? mice, suggesting that GH does not regulate these adipokines directly in adipose tissue in vivo. Other features of FaGHRKO mice include decreased levels of adipsin, a near-normal GH/IGF-1 axis, and minimal changes to a large assortment of circulating factors that were measured such as IGF-binding proteins. In conclusion, specific removal of GHR in adipose tissue is sufficient to increase adipose tissue and decrease circulating adipsin. However, removal of GHR in adipose tissue alone is not sufficient to increase levels of resistin or adiponectin and does not alter glucose metabolism. PMID:23349524

List, Edward O.; Berryman, Darlene E.; Funk, Kevin; Gosney, Elahu S.; Jara, Adam; Kelder, Bruce; Wang, Xinyue; Kutz, Laura; Troike, Katie; Lozier, Nicholas; Mikula, Vincent; Lubbers, Ellen R.; Zhang, Han; Vesel, Clare; Junnila, Riia K.; Frank, Stuart J.; Masternak, Michal M.; Bartke, Andrzej

2013-01-01

75

Adipose tissue remodeling in lipedema: adipocyte death and concurrent regeneration  

Microsoft Academic Search

Lipedema is a disease with unknown etiology presenting as bilateral and symmetric enlargement of the lower extremities due to subcutaneous deposition of the adipose tissue. Here we describe the histopathological features of the lipedema tissue and nonaffected adipose tissue obtained from a typical patient with severe lipedema. Immunohistochemical analyses indicated degenerative and regenerative changes of the lipedema tissue, characterized by

Hirotaka Suga; Jun Araki; Noriyuki Aoi; Harunosuke Kato; Takuya Higashino; Kotaro Yoshimura

2009-01-01

76

Maternal nutritional programming of fetal adipose tissue development: differential effects on messenger ribonucleic acid abundance for uncoupling proteins and peroxisome proliferator-activated and prolactin receptors.  

PubMed

Maternal nutrient restriction at specific stages of gestation has differential effects on fetal development such that the offspring are programmed to be at increased risk of a range of adult diseases, including obesity. We investigated the effect of maternal nutritional manipulation through gestation on fetal adipose tissue deposition in conjunction with mRNA abundance for uncoupling protein (UCP)1 and 2, peroxisome proliferator-activated receptors (PPAR)alpha and gamma, together with long and short forms of the prolactin receptor (PRLR). Singleton-bearing ewes were either nutrient restricted (3.2-3.8 MJ day(-1) metabolizable energy) or fed to appetite (8.7-9.9 MJ day(-1)) over the period of maximal placental growth, i.e. between 28 and 80 d gestation. After 80 d gestation, ewes were either fed to calculated requirements, (6.7-7.5 MJ day(-1)), or to appetite (8.0-10.9 MJ day(-1)). At term, offspring of nutrient-restricted ewes possessed more adipose tissue, an adaptation that was greatest in those born to mothers that fed to requirements in late gestation. This was accompanied by an increased mRNA abundance for UCP2 and PPARalpha, an adaptation not seen in mothers re-fed to appetite. Maternal nutrition had no effect on mRNA abundance for UCP1, PPARgamma, or PRLR. Irrespective of maternal nutrition, mRNA abundance for UCP1 was positively correlated with PPARgamma and the long and short forms of PRLR, indicating that these factors may act together to ensure that UCP1 abundance is maximized in the newborn. In conclusion, we have shown, for the first time, differential effects of maternal nutrition on key regulatory components of fetal fat metabolism. PMID:15961559

Bispham, J; Gardner, D S; Gnanalingham, M G; Stephenson, T; Symonds, M E; Budge, H

2005-09-01

77

Metabolic remodeling of white adipose tissue in obesity.  

PubMed

Adipose tissue metabolism is a critical regulator of adiposity and whole body energy expenditure; however, metabolic changes that occur in white adipose tissue (WAT) with obesity remain unclear. The purpose of this study was to understand the metabolic and bioenergetic changes occurring in WAT with obesity. Wild-type (C57BL/6J) mice fed a high-fat diet (HFD) showed significant increases in whole body adiposity, had significantly lower V?(O?), V?(CO?), and respiratory exchange ratios, and demonstrated worsened glucose and insulin tolerance compared with low-fat-fed mice. Metabolomic analysis of WAT showed marked changes in lipid, amino acid, carbohydrate, nucleotide, and energy metabolism. Tissue levels of succinate and malate were elevated, and metabolites that could enter the Krebs cycle via anaplerosis were mostly diminished in high-fat-fed mice, suggesting altered mitochondrial metabolism. Despite no change in basal oxygen consumption or mitochondrial DNA abundance, citrate synthase activity was decreased by more than 50%, and responses to FCCP were increased in WAT from mice fed a high-fat diet. Moreover, Pgc1a was downregulated and Cox7a1 upregulated after 6 wk of HFD. After 12 wk of high-fat diet, the abundance of several proteins in the mitochondrial respiratory chain or matrix was diminished. These changes were accompanied by increased Parkin and Pink1, decreased p62 and LC3-I, and ultrastructural changes suggestive of autophagy and mitochondrial remodeling. These studies demonstrate coordinated restructuring of metabolism and autophagy that could contribute to the hypertrophy and whitening of adipose tissue in obesity. PMID:24918202

Cummins, Timothy D; Holden, Candice R; Sansbury, Brian E; Gibb, Andrew A; Shah, Jasmit; Zafar, Nagma; Tang, Yunan; Hellmann, Jason; Rai, Shesh N; Spite, Matthew; Bhatnagar, Aruni; Hill, Bradford G

2014-08-01

78

Fabrication of porous extracellular matrix scaffolds from human adipose tissue.  

PubMed

Adipose tissue is found over the whole body and easily obtained in large quantities with minimal risk by a common surgical operation, liposuction. Although liposuction was originally intended for the removal of undesired adipose tissue, it may provide an ideal material for tissue engineering scaffolds. Here we present novel, porous scaffolds prepared from human adipose tissues. The scaffolds were fabricated in a variety of macroscopic shapes such as round dishes, squares, hollow tubes, and beads. The microscopic inner porous structure was controlled by the freezing temperature, with a decrease in pore size as the freezing temperature decreased. The scaffold prepared from human adipose tissue contains extracellular matrix components including collagen. Preliminary in vitro studies showed that human adipose-derived stem cells attached to a human extracellular matrix scaffold and proliferated. This scaffold based on human adipose tissue holds great promise for many clinical applications in regenerative medicine, particularly in patients requiring soft-tissue regeneration. PMID:19601696

Choi, Ji Suk; Yang, Hyun-Jin; Kim, Beob Soo; Kim, Jae Dong; Lee, Sang Hoon; Lee, Eun Kyu; Park, Kinam; Cho, Yong Woo; Lee, Hee Young

2010-06-01

79

Brown adipose tissue--a new role in humans?  

PubMed

New targets for pharmacological interventions are of great importance to combat the epidemic of obesity. Brown adipose tissue could potentially represent one such target. Unlike white adipose tissue, brown adipose tissue has the ability to dissipate energy by producing heat rather than storing it as triglycerides. In small mammals, the presence of active brown adipose tissue is pivotal for the maintenance of body temperature and possibly to protect against the detrimental effects of surplus energy intake. Animal studies have shown that expansion and/or activation of brown adipose tissue counteracts diet-induced weight gain and related disorders such as type 2 diabetes mellitus. Several independent studies have now confirmed the presence of functional brown adipose tissue in adult humans, for whom this tissue is probably metabolically beneficial given its association with both low BMI and low total adipose tissue content. Over the past few years, knowledge of the transcriptional control and development of brown adipose tissue has increased substantially. Thus, several possible targets that may be useful for the expansion and/or activation of this tissue by pharmacological means have been identified. Whether or not brown adipose tissue will be useful in the battle against obesity remains to be seen. However, this possibility is certainly well worth exploring. PMID:20386559

Lidell, Martin E; Enerbäck, Sven

2010-06-01

80

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

PubMed

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 PPAR? 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 PPAR? 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 PPAR? in accumulated visceral adipose tissues. PMID:25324014

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

2015-01-01

81

The browning of white adipose tissue: some burning issues.  

PubMed

Igniting thermogenesis within white adipose tissue (i.e., promoting expression and activity of the uncoupling protein UCP1) has attracted much interest. Numerous "browning agents" have now been described (gene ablations, transgenes, food components, drugs, environments, etc.). The implied action of browning agents is that they increase UCP1 through this heat production, leading to slimming. Here, we particularly point to the possibility that cause and effect may on occasion be the reverse: browning agents may disrupt, for example, the fur, leading to increased heat loss, increased thermogenic demand to counteract this heat loss, and thus, through sympathetic nervous system activation, to enhanced UCP1 expression in white (and brown) adipose tissues. PMID:25127354

Nedergaard, Jan; Cannon, Barbara

2014-09-01

82

Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity  

Microsoft Academic Search

BackgroundMiddle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the

Kendra L. Puig; Angela M. Floden; Ramchandra Adhikari; Mikhail Y. Golovko; Colin K. Combs

2012-01-01

83

Decellularized extracellular matrix derived from porcine adipose tissue as a xenogeneic biomaterial for tissue engineering.  

PubMed

Cells in tissues are surrounded by the extracellular matrix (ECM), a gel-like material of proteins and polysaccharides that are synthesized and secreted by cells. Here we propose that the ECM can be isolated from porcine adipose tissue and holds great promise as a xenogeneic biomaterial for tissue engineering and regenerative medicine. Porcine adipose tissue is easily obtained in large quantities from commonly discarded food waste. Decellularization protocols have been developed for extracting an intact ECM while effectively eliminating xenogeneic epitopes and minimally disrupting the ECM composition. Porcine adipose tissue was defatted by homogenization and centrifugation. It was then decellularized via chemical (1.5?M sodium chloride and 0.5% sodium dodecyl sulfate) and enzymatic treatments (DNase and RNase) with temperature control. After decellularization, immunogenic components such as nucleic acids and ?-Gal were significantly reduced. However, abundant ECM components, such as collagen (332.9±12.1??g/mg ECM dry weight), sulfated glycosaminoglycan (GAG, 85±0.7??g/mg ECM dry weight), and elastin (152.6±4.5 ?g/mg ECM dry weight), were well preserved in the decellularized material. The biochemical and mechanical features of a decellularized ECM supported the adhesion and growth of human cells in vitro. Moreover, the decellularized ECM exhibited biocompatibility, long-term stability, and bioinductivity in vivo. The overall results suggest that the decellularized ECM derived from porcine adipose tissue could be useful as an alternative biomaterial for xenograft tissue engineering. PMID:22559904

Choi, Young Chan; Choi, Ji Suk; Kim, Beob Soo; Kim, Jae Dong; Yoon, Hwa In; Cho, Yong Woo

2012-11-01

84

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

SciTech Connect

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.

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)] [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)] [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

2011-03-04

85

Brown adipose tissue: development, metabolism and beyond.  

PubMed

Obesity represents a major risk factor for the development of several of our most common medical conditions, including Type 2 diabetes, dyslipidaemia, non-alcoholic fatty liver, cardiovascular disease and even some cancers. Although increased fat mass is the main feature of obesity, not all fat depots are created equal. Adipocytes found in white adipose tissue contain a single large lipid droplet and play well-known roles in energy storage. By contrast, brown adipose tissue is specialized for thermogenic energy expenditure. Owing to its significant capacity to dissipate energy and regulate triacylglycerol (triglyceride) and glucose metabolism, and its demonstrated presence in adult humans, brown fat could be a potential target for the treatment of obesity and metabolic syndrome. Undoubtedly, fundamental knowledge about the formation of brown fat and regulation of its activity is imperatively needed to make such therapeutics possible. In the present review, we integrate the recent advancements on the regulation of brown fat formation and activity by developmental and hormonal signals in relation to its metabolic function. PMID:23805974

Schulz, Tim J; Tseng, Yu-Hua

2013-07-15

86

Brain-Adipose Tissue Neural Crosstalk1  

PubMed Central

The preponderance of basic research on obesity focuses on its development as affected by diet and other environmental factors, genetics and their interactions. By contrast, we have been studying the reversal of a naturally-occurring seasonal obesity in Siberian hamsters. In the course of this work, we determined that the sympathetic innervation of white adipose tissue (WAT) is the principal initiator of lipid mobilization not only in these animals, but in all mammals including humans. We present irrefutable evidence for the sympathetic nervous system (SNS) innervation of WAT with respect to neuroanatomy (including it central origins as revealed by transneuronal viral tract tracers), neurochemistry (norepinephrine turnover studies) and function (surgical and chemical denervation). A relatively unappreciated role of WAT SNS innervation also is reviewed - the control of fat cell proliferation as shown by selective chemical denervation that triggers adipocyte proliferation, although the precise mechanism by which this occurs presently is unknown. There is not, however, equally strong evidence for the parasympathetic innervation of this tissue; indeed, the data largely are negative severely questioning its existence and importance. Convincing evidence also is given for the sensory innervation of WAT (as shown by tract tracing and by markers for sensory nerves in WAT), with suggestive data supporting a possible role in conveying information on the degree of adiposity to the brain. Collectively, these data offer an additional view to the predominate one of the control of body fat stores via circulating factors that serve as efferent and afferent communicators. PMID:17521684

Bartness, Timothy J.; Song, C. Kay

2007-01-01

87

SirT1 Regulates Adipose Tissue Inflammation  

PubMed Central

OBJECTIVE Macrophage recruitment to adipose tissue is a reproducible feature of obesity. However, the events that result in chemokine production and macrophage recruitment to adipose tissue during states of energetic excess are not clear. Sirtuin 1 (SirT1) is an essential nutrient-sensing histone deacetylase, which is increased by caloric restriction and reduced by overfeeding. We discovered that SirT1 depletion causes anorexia by stimulating production of inflammatory factors in white adipose tissue and thus posit that decreases in SirT1 link overnutrition and adipose tissue inflammation. RESEARCH DESIGN AND METHODS We used antisense oligonucleotides to reduce SirT1 to levels similar to those seen during overnutrition and studied SirT1-overexpressing transgenic mice and fat-specific SirT1 knockout animals. Finally, we analyzed subcutaneous adipose tissue biopsies from two independent cohorts of human subjects. RESULTS We found that inducible or genetic reduction of SirT1 in vivo causes macrophage recruitment to adipose tissue, whereas overexpression of SirT1 prevents adipose tissue macrophage accumulation caused by chronic high-fat feeding. We also found that SirT1 expression in human subcutaneous fat is inversely related to adipose tissue macrophage infiltration. CONCLUSIONS Reduction of adipose tissue SirT1 expression, which leads to histone hyperacetylation and ectopic inflammatory gene expression, is identified as a key regulatory component of macrophage influx into adipose tissue during overnutrition in rodents and humans. Our results suggest that SirT1 regulates adipose tissue inflammation by controlling the gain of proinflammatory transcription in response to inducers such as fatty acids, hypoxia, and endoplasmic reticulum stress. PMID:22110092

Gillum, Matthew P.; Kotas, Maya E.; Erion, Derek M.; Kursawe, Romy; Chatterjee, Paula; Nead, Kevin T.; Muise, Eric S.; Hsiao, Jennifer J.; Frederick, David W.; Yonemitsu, Shin; Banks, Alexander S.; Qiang, Li; Bhanot, Sanjay; Olefsky, Jerrold M.; Sears, Dorothy D.; Caprio, Sonia; Shulman, Gerald I.

2011-01-01

88

LIPOGENESIS IN OVINE ADIPOSE TISSUE IN TISSUE CULTURE R.G. VERNON  

E-print Network

responsi- ble for the low rate of glucose utilization for fatty acid synthesis in ovine adipose tissue-antagonists in ovine adipose tissue. The very low rate of utilization of glucose carbon for fatty acid synthesis in ruminant adipose tissue is thought to be due to the low activity of ATP-citrate lyase (Ballard et a/., 1969

Paris-Sud XI, Université de

89

Adipose tissue as a buffer for daily lipid flux  

Microsoft Academic Search

Insulin resistance occurs in obesity and Type II (non-insulin-dependent) diabetes mellitus, but it is also a prominent feature of lipodystrophy. Adipose tissue could play a crucial part in buffering the flux of fatty acids in the circulation in the postprandial period, analogous to the roles of the liver and skeletal muscle in buffering postprandial glucose fluxes. Adipose tissue provides its

K. N. Frayn

2002-01-01

90

Prospective influences of circadian clocks in adipose tissue and metabolism  

Microsoft Academic Search

Circadian rhythms make a critical contribution to endocrine functions that involve adipose tissue. These contributions are made at the systemic, organ and stem cell levels. The transcription factors and enzymes responsible for the maintenance of circadian rhythms in adipose depots and other peripheral tissues that are metabolically active have now been identified. Furthermore, the circadian regulation of glucose and lipid

Gregory M. Sutton; Bruce A. Bunnell; Andrey A. Ptitsyn; Z. Elizabeth Floyd; Jeffrey M. Gimble

2010-01-01

91

Activation of brown adipose tissue mitochondrial GDP binding sites  

SciTech Connect

The primary function of brown adipose tissue (BAT) is heat production. This ability is attributed to the existence of a unique inner mitochondrial membrane protein termed the uncoupling protein or thermogenin. This protein is permeable to H+ and thus allows respiration (and therefore thermogenesis) to proceed at a rapid rate, independent of ADP phosphorylation. Proton conductance can be inhibited by the binding of purine nucleotides to the uncoupling protein. The binding of (/sup 3/H)-GDP to BAT mitochondria is frequently used as a measure of BAT thermogenic activity. Rats fed a diet that was low but adequate in protein exhibited a decrease in feed efficiency. In addition, BAT thermogenesis was activated as indicated by an elevation in the level of GDP binding to BAT mitochondria. This phenomena occurred in older rats and persisted over time.

Swick, A.G.

1987-01-01

92

The effect of maternal prolactin infusion during pregnancy on fetal adipose tissue development  

Microsoft Academic Search

The present study determines whether maternal administration of prolactin (PRL) to dams promotes the abundance of the brown adipose tissue-specific uncoupling protein-1 (UCP1) in fetal and neonatal rat pups. Recombinant PRL (24 µg\\/kg per day), or an equivalent volume of saline, were infused into dams (n=19 per group) throughout pregnancy from 12 h after mating. Interscapular brown adipose tissue was

H Budge; A Mostyn; V Wilson; A Khong; A M Walker; M E Symonds; T Stephenson

2002-01-01

93

Adipose tissue as regulator of vascular tone.  

PubMed

Adipokines secreted by visceral, subcutaneous, and perivascular adipocytes are involved in the regulation of vascular tone by acting as circulatory hormones (leptin, adiponectin, omentin, visfatin, angiotensin II, resistin, tumor necrosis factor-?, interleukin-6, apelin) and/or via local paracrine factors (perivascular adipocyte-derived relaxing and contractile factors). Vascular tone regulation by adipokines is compromised in obesitas and obesity-related disorders. Hypoxia created in growing adipose tissue dysregulates synthesis of vasoactive adipokines in favor of harmful proinflammatory adipokines, while the levels of the cardioprotective adipokines adiponectin and omentin decrease. Considering the potential of the role of adipokines in obesity-related vascular diseases, strategies to counter these diseases by targeting the adipokines are discussed. PMID:22415539

Boydens, Charlotte; Maenhaut, Nele; Pauwels, Bart; Decaluwé, Kelly; Van de Voorde, Johan

2012-06-01

94

Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia  

Microsoft Academic Search

OBJECTIVES: To investigate the relationships of fat cell weight (FCW) as well as of estimated total adipose cell number to fasting plasma leptin concentration.DESIGN: Cross-sectional correlational study.SUBJECTS: A sample of 63 men (mean age±s.d.: 36±4 y) and 42 premenopausal women (35±5 y).MEASUREMENTS: Adipose tissue (AT) biopsies were obtained in order to determine FCW as well as estimated adipose cell number.

C Couillard; P Mauriège; P Imbeault; D Prud’homme; A Nadeau; A Tremblay; C Bouchard; J-P Després

2000-01-01

95

Scaffold preferences of mesenchymal stromal cells and adipose-derived stem cells from green fluorescent protein transgenic mice influence the tissue engineering of bone.  

PubMed

We have analysed the growth and differentiation of mesenchymal stromal cells (MSC) from bone marrow, and of adipose derived stem cells (ASC) from murine abdominal fat tissue, of green fluorescent protein (GFP) transgenic animals grown directly on two types of hydroxyapatite ceramic bone substitutes. BONITmatrix® and NanoBone® have specific mechanical and physiochemical properties such as porosity and an inner surface that influence cellular growth. Both MSC and ASC were separately seeded on 200mg of each biomaterial and cultured for 3 weeks under osteogenic differentiation conditions. The degree of mineralisation was assessed by alizarin red dye and the specific alkaline phosphatase activity of the differentiated cells. The morphology of the cells was examined by scanning electron microscopy and confocal microscopy. The osteoblastic phenotype of the cells was confirmed by analysing the expression of bone-specific genes (Runx2, osteocalcin, osteopontin, and osteonectin) by semiquantitative reverse transcriptase polymerase chain reaction (PCR). Comparison of BONITmatrix® and NanoBone® showed cell type-specific preferences in terms of osteogenic differentiation. MSC-derived osteoblast-like cells spread optimally on the surface of NanoBone® but not BONITmatrix® granules. In contrast BONITmatrix® granules conditioned the growth of osteoblast-like cells derived from ASC. The osteoblastic phenotype of the cultured cells on all matrices was confirmed by specific gene expression. Our results show that the in vitro growth and osteogenic differentiation of murine MSC or ASC of GFP transgenic mice are distinctly influenced by the ceramic substratum. While NanoBone® granules support the proliferation and differentiation of murine MSC isolated from bone marrow, the growth of murine ASC is supported by BONITmatrix® granules. NanoBone® is therefore recommended for use as scaffold in tissue engineering that requires MSC, whereas ASC can be combined with BONITmatrix® for in vitro bone engineering. PMID:24685477

Wittenburg, Gretel; Flade, Viktoria; Garbe, Annette I; Lauer, Günter; Labudde, Dirk

2014-05-01

96

The radioprotective 105/MD-1 complex contributes to diet-induced obesity and adipose tissue inflammation.  

PubMed

Recent accumulating evidence suggests that innate immunity is associated with obesity-induced chronic inflammation and metabolic disorders. Here, we show that a Toll-like receptor (TLR) protein, radioprotective 105 (RP105)/myeloid differentiation protein (MD)-1 complex, contributes to high-fat diet (HFD)-induced obesity, adipose tissue inflammation, and insulin resistance. An HFD dramatically increased RP105 mRNA and protein expression in stromal vascular fraction of epididymal white adipose tissue (eWAT) in wild-type (WT) mice. RP105 mRNA expression also was significantly increased in the visceral adipose tissue of obese human subjects relative to nonobese subjects. The RP105/MD-1 complex was expressed by most adipose tissue macrophages (ATMs). An HFD increased RP105/MD-1 expression on the M1 subset of ATMs that accumulate in eWAT. Macrophages also acquired this characteristic in coculture with 3T3-L1 adipocytes. RP105 knockout (KO) and MD-1 KO mice had less HFD-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance compared with wild-type (WT) and TLR4 KO mice. Finally, the saturated fatty acids, palmitic and stearic acids, are endogenous ligands for TLR4, but they did not activate RP105/MD-1. Thus, the RP105/MD-1 complex is a major mediator of adipose tissue inflammation independent of TLR4 signaling and may represent a novel therapeutic target for obesity-associated metabolic disorders. PMID:22396206

Watanabe, Yasuharu; Nakamura, Tomoya; Ishikawa, Sho; Fujisaka, Shiho; Usui, Isao; Tsuneyama, Koichi; Ichihara, Yoshinori; Wada, Tsutomu; Hirata, Yoichiro; Suganami, Takayoshi; Izaki, Hirofumi; Akira, Shizuo; Miyake, Kensuke; Kanayama, Hiro-omi; Shimabukuro, Michio; Sata, Masataka; Sasaoka, Toshiyasu; Ogawa, Yoshihiro; Tobe, Kazuyuki; Takatsu, Kiyoshi; Nagai, Yoshinori

2012-05-01

97

Adipose-derived stem/progenitor cells: roles in adipose tissue remodeling and potential use for soft tissue augmentation.  

PubMed

Many features of adipose tissue-specific stem/progenitor cells, such as physiological function and localization, have recently been examined. Adipose-tissue turnover is very slow and its perivascular progenitor cells differentiate into adipocytes in the next generation. The progenitor cells play important roles in physiological turnover, hyperplasia and atrophy of adipose tissue, as well as in incidental remodeling, such as postinjury repair. Adipose tissue has been used as an autologous filler for soft tissue defects, despite unpredictable clinical results and a low rate of graft survival, which may be due to the relative deficiency of progenitor cells in graft materials. A novel transplantation strategy, termed cell-assisted lipotransfer, involves the enrichment of adipose progenitor cells in grafts; preliminary results suggest this approach to be safe and effective. PMID:19317645

Yoshimura, Kotaro; Suga, Hirotaka; Eto, Hitomi

2009-03-01

98

Adipose-derived stem cells: Implications in tissue regeneration  

PubMed Central

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 differentiate 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 damaged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration. PMID:25126381

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

2014-01-01

99

GADD45? regulates the thermogenic capacity of brown adipose tissue.  

PubMed

The coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 ? (PGC-1?) is widely considered a central transcriptional regulator of adaptive thermogenesis in brown adipose tissue (BAT). However, mice lacking PGC-1? specifically in adipose tissue have only mild thermogenic defects, suggesting the presence of additional regulators. Using the activity of estrogen-related receptors (ERRs), downstream effectors of PGC-1?, as read-out in a high-throughput genome-wide cDNA screen, we identify here growth arrest and DNA-damage-inducible protein 45 ? (GADD45?) as a cold-induced activator of uncoupling protein 1 (UCP1) and oxidative capacity in BAT. Mice lacking Gadd45? have defects in Ucp1 induction and the thermogenic response to cold. GADD45? works by activating MAPK p38, which is a potent activator of ERR? and ERR? transcriptional function. GADD45? activates ERR? independently of PGC-1 coactivators, yet synergizes with PGC-1? to induce the thermogenic program. Our findings elucidate a previously unidentified GADD45?/p38/ERR? pathway that regulates BAT thermogenesis and may enable new approaches for the stimulation of energy expenditure. Our study also implicates GADD45 proteins as general metabolic regulators. PMID:25071184

Gantner, Marin L; Hazen, Bethany C; Conkright, Juliana; Kralli, Anastasia

2014-08-12

100

Adipocyte differentiation of multipotent cells established from human adipose tissue  

Microsoft Academic Search

In this study multipotent adipose-derived stem cells isolated from human adipose tissue (hMADS cells) were shown to differentiate into adipose cells in serum-free, chemically defined medium. During the differentiation process, hMADS cells exhibited a gene expression pattern similar to that described for rodent clonal preadipocytes and human primary preadipocytes. Differentiated cells displayed the key features of human adipocytes, i.e., expression

Anne-Marie Rodriguez; Christian Elabd; Frédéric Delteil; Julien Astier; Cécile Vernochet; Perla Saint-Marc; Joëlle Guesnet; Anne Guezennec; Ez-Zoubir Amri; Christian Dani; Gérard Ailhaud

2004-01-01

101

Optical model of thermo-sensitive heterophase medium (adipose tissue)  

NASA Astrophysics Data System (ADS)

The study of thermoinduced changes of optical properties of adipose tissue is very actual problem. We made the optical model of thermo-sensitive heterophase medium (adipose tissue). Here the elementary adipose cell will consist of a cube which basic volume will contain a adipose ball, everything else- water. The adipose ball will contain liquid and crystal phases. Has been created the experimental scheme for research of angular distribution of the light passed through the adipose tissue sample. The same model has been created in program Tracepro - General Raytracing. It is presented the good coordination of calculated and experimental curves for temperatures 5, 26 and 40 °C. We have made a calculated curve of dependence of intensity transmitted through the multyphase medium (adipose tissue) from a ratio of volume of liquid phase to total volume. Experimentally knowing also, that intensity of transmitted light depends on temperature, we have made the dependence of a ratio of volume of a liquid phase to total volume of a cell from temperature. Also we have put the experiment. We have keep the sample of adipose tissue at temperature 20, 30 and 39 °C in drying box. And we have received a ratio of hard and liquid phases in the sample. Thus the dependence of observed in experiment intensity on temperature can be caused by dependence of a ratio of volume of liquid and hard phases in the medium on temperature.

Belikov, A. V.; Smolyanskaya, O. A.

2007-05-01

102

Molecular Approach to Thermogenesis in Brown Adipose Tissue: cDNA Cloning of the Mitochondrial Uncoupling Protein  

Microsoft Academic Search

The uncoupling protein (UCP) of mammalian brown fat is a specialized and unique component responsible for energy dissipation as heat. Translation and immunoprecipitation from sucrose-fractionated mRNA indicated that the mRNA of UCP sedimented at 14-16 S. A recombinant cDNA library prepared from mRNA of thermoactive brown fat enriched for UCP mRNA has been constructed and cloned in Escherichia coli. Recombinant

Frederic Bouillaud; Daniel Ricquier; Jean Thibault; Jean Weissenbach

1985-01-01

103

Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells  

Microsoft Academic Search

Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. As adipose tissues were recently demonstrated to contain pluripotent stem cells, the emergence of cardiomyocyte phenotype from adipose-derived cells was investigated. We demonstrated that rare beating

V. Planat-Bénard; C. Menard; M. André; M. Puceat; A. Perez; J.-M. Garcia-Verdugo; L. Pénicaud; L. Casteilla

2007-01-01

104

AN INJECTABLE ADIPOSE MATRIX FOR SOFT TISSUE RECONSTRUCTION  

PubMed Central

Background Soft tissue repair is currently limited by the availability of autologous tissue sources and the absence of an ideal soft tissue replacement comparable to native adipose tissue. Extracellular matrix (ECM)-based biomaterials have demonstrated great potential as instructive scaffolds for regenerative medicine, mechanically and biochemically defined by the tissue of origin. As such, the distinctive high lipid content of adipose tissue requires unique processing conditions to generate a biocompatible scaffold for soft tissue repair. Methods Human adipose tissue was decellularized to obtain a matrix devoid of lipids and cells, while preserving ECM architecture and bioactivity. To control degradation and volume persistence, the scaffold was crosslinked using hexamethylene diisocyanate and 1-Ethyl-3-(-3-dimethylaminopropyl) carbodiimide. In vitro studies with human adipose-derived stem cells were used to assess cell viability and adipogenic differentiation on the biomaterial. In vivo biocompatibility and volume persistence were evaluated by subcutaneous implantation over 12 weeks in a small animal model. Results The scaffold provided a biocompatible matrix supporting the growth and differentiation of adipose-derived stem cells in vitro. Crosslinking the matrix increased its resistance to enzymatic degradation. Subcutaneous implantation of the acellular adipose matrix in Sprague-Dawley rats showed minimal inflammatory reaction. Adipose tissue development and vascularization was observed in the implant, with host cells migrating into the matrix indicating the instructive potential of the matrix for guiding tissue remodeling and regeneration. Conclusions With its unique biological and mechanical properties, decellularized adipose ECM is a promising biomaterial scaffold that can potentially be used allogenically for the correction of soft tissue defects. PMID:22327888

Wu, Iwen; Nahas, Zayna; Kimmerling, Kelly A.; Rosson, Gedge D.; Elisseeff, Jennifer H.

2012-01-01

105

Adipose Tissue and Immune Function: A Review of Evidence Relevant to HIV Infection  

PubMed Central

Human immunodeficiency virus type 1 (HIV) infection and antiretroviral therapy (ART) have long been associated with abnormalities in adipose tissue distribution and metabolism. More-recent evidence demonstrates that adipocytes and adipose-resident immune cells have a role in the response to HIV. Clinical and laboratory studies indicate that viral proteins and antiretroviral medications alter adipocyte biology to enhance the persistent, systemic inflammatory state characteristic of untreated and treated HIV infection. Relationships between body composition and lymphocyte populations, cellular immune activation, and immune reconstitution in HIV-infected individuals receiving ART suggest that adipose tissue may also affect cellular immune function. This is further supported by in vitro studies demonstrating the effect of adipocytes and adipokines on lymphocyte proliferation, differentiation, and activation. Synthesis of the literature on adipose tissue biology and immune function in uninfected individuals may shed light on major outstanding research questions in the HIV field. PMID:23878320

Koethe, John R.; Hulgan, Todd; Niswender, Kevin

2013-01-01

106

Central Control of Brown Adipose Tissue Thermogenesis  

PubMed Central

Thermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. Mitochondrial oxidation in brown adipose tissue (BAT) is a significant source of neurally regulated metabolic heat production in many species from mouse to man. BAT thermogenesis is regulated by neural networks in the central nervous system which responds to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate BAT sympathetic nerve activity. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates BAT thermogenesis and includes the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E2, to increase body temperature during fever. The cold thermal afferent circuit from cutaneous thermal receptors, through second-order thermosensory neurons in the dorsal horn of the spinal cord ascends to activate neurons in the lateral parabrachial nucleus which drive GABAergic interneurons in the preoptic area (POA) to inhibit warm-sensitive, inhibitory output neurons of the POA. The resulting disinhibition of BAT thermogenesis-promoting neurons in the dorsomedial hypothalamus activates BAT sympathetic premotor neurons in the rostral ventromedial medulla, including the rostral raphe pallidus, which provide excitatory, and possibly disinhibitory, inputs to spinal sympathetic circuits to drive BAT thermogenesis. Other recently recognized central sites influencing BAT thermogenesis and energy expenditure are also described. PMID:22389645

Morrison, Shaun F.; Madden, Christopher J.; Tupone, Domenico

2011-01-01

107

New concepts in white adipose tissue physiology  

PubMed Central

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. PMID:24676492

Proenca, A.R.G.; Sertie, R.A.L.; Oliveira, A.C.; Campaaa, A.B.; Caminhotto, R.O.; Chimin, P.; Lima, F.B.

2014-01-01

108

Adipose tissue inflammation in glucose metabolism.  

PubMed

Obesity is now recognised as a low grade, chronic inflammatory disease that is linked to a myriad of disorders including cancer, cardiovascular disease and type 2 diabetes (T2D). With respect to T2D, work in the last decade has revealed that cells of the immune system are recruited to white adipose tissue beds (WAT), where they can secrete cytokines to modulate metabolism within WAT. As many of these cytokines are known to impair insulin action, blocking the recruitment of immune cells has been purported to have therapeutic utility for the treatment of obesity-induced T2D. As inflammation is critical for host defence, and energy consuming in nature, the blockade of inflammatory processes may, however, result in unwanted complications. In this review, we outline the immunological changes that occur within the WAT with respect to systemic glucose homeostasis. In particular, we focus on the role of major immune cell types in regulating nutrient homeostasis and potential initiating stimuli for WAT inflammation. PMID:24048715

Kammoun, H L; Kraakman, M J; Febbraio, M A

2014-03-01

109

Recent progress in the study of brown adipose tissue.  

PubMed

Brown adipose tissue in mammals plays a critical role in maintaining energy balance by thermogenesis, which means dissipating energy in the form of heat. It is held that in mammals, long-term surplus food intake results in energy storage in the form of triglyceride and may eventually lead to obesity. Stimulating energy-dissipating function of brown adipose tissue in human body may counteract fat accumulation. In order to utilize brown adipose tissue as a therapeutic target, the mechanisms underlying brown adipocyte differentiation and function should be better elucidated. Here we review the molecular mechanisms involved in brown adipose tissue development and thermogenesis, and share our thoughts on current challenges and possible future therapeutic approaches. PMID:22035495

Yao, Xuan; Shan, Shifang; Zhang, Ying; Ying, Hao

2011-01-01

110

Is Adipose Tissue a Place for Mycobacterium tuberculosis Persistence?  

E-print Network

Is Adipose Tissue a Place for Mycobacterium tuberculosis Persistence? Olivier Neyrolles1 of Electron Microscopy, Institut Pasteur, Paris, France Background. Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), has the ability to persist in its human host for exceptionally long

Paris-Sud XI, Université de

111

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications.  

PubMed

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75-81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications.-Vernochet, C., Damilano, F., Mourier, A., Bezy, O., Mori, M. A., Smyth, G., Rosenzweig, A., Larsson, N.-G., Kahn, C. R. Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications. PMID:25005176

Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C Ronald

2014-10-01

112

Link between GIP and osteopontin in adipose tissue and insulin resistance.  

PubMed

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 in adipose tissue of obese individuals (0.13 ± 0.04 vs. 0.04 ± 0.01, P < 0.05) and correlated inversely with measures of insulin sensitivity (r = -0.24, P = 0.001). A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with a lower amount of the exon 9-containing isoform required 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. Carriers of the GIPR rs10423928 A allele showed protective properties via reduced GIP effects. Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions. PMID:23349498

Ahlqvist, Emma; Osmark, Peter; Kuulasmaa, Tiina; Pilgaard, Kasper; Omar, Bilal; Brøns, Charlotte; Kotova, Olga; Zetterqvist, Anna V; Stancáková, Alena; Jonsson, Anna; Hansson, Ola; Kuusisto, Johanna; Kieffer, Timothy J; Tuomi, Tiinamaija; Isomaa, Bo; Madsbad, Sten; Gomez, Maria F; Poulsen, Pernille; Laakso, Markku; Degerman, Eva; Pihlajamäki, Jussi; Wierup, Nils; Vaag, Allan; Groop, Leif; Lyssenko, Valeriya

2013-06-01

113

Regional Adipose Tissue Associations With Calcified Atherosclerotic Plaque: African American–Diabetes Heart Study  

Microsoft Academic Search

Coronary artery calcified atherosclerotic plaque (CP) is strongly associated with nonsubcutaneous adipose tissue, particularly pericardial adipose tissue (PAT), in community-based studies. We tested for relationships between regional adipose tissue depots and CP in African Americans with longstanding type 2 diabetes. Infrarenal aorta, coronary, and carotid artery CP and pericardial, visceral, intermuscular, and subcutaneous organ-specific adipose tissue volumes were measured using

Jasmin Divers; Lynne E. Wagenknecht; Donald W. Bowden; J. Jeffrey Carr; R. Caresse Hightower; Jingzhong Ding; Jianzhao Xu; Carl D. Langefeld; Barry I. Freedman

2010-01-01

114

Human extracellular matrix (ECM) powders for injectable cell delivery and adipose tissue engineering  

Microsoft Academic Search

Here, we present extracellular matrix (ECM) powders derived from human adipose tissue as injectable cell delivery carriers for adipose tissue engineering. We postulate that human adipose tissue may provide an ideal biomaterial because it contains large amounts of ECM components including collagen. Fresh human adipose tissue was obtained by a simple surgical operation (liposuction). After removing blood and oil components,

Ji Suk Choi; Hyun-Jin Yang; Beob Soo Kim; Jae Dong Kim; Jun Young Kim; Bongyoung Yoo; Hee Young Lee; Yong Woo Cho

2009-01-01

115

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

Microsoft Academic Search

This review focuses on adipose tissue biology and introduces the concept of adipose tissue plasticity and expandability as key determinants of obesity-associated meta- bolic dysregulation. This concept is fundamental to our under- standing of adipose tissue as a dynamic organ at the center of nutritional adaptation. Here, we summarize the current knowledge of the mechanisms by which adipose tissue can

Jaswinder K. Sethi; Antonio J. Vidal-Puig

2007-01-01

116

Long-acting glucose-dependent insulinotropic polypeptide ameliorates obesity-induced adipose tissue inflammation.  

PubMed

Obesity induces low-grade chronic inflammation, manifested by proinflammatory polarization of adipose tissue innate and adaptive resident and recruited immune cells that contribute to insulin resistance (IR). The glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that mediates postprandial insulin secretion and has anabolic effects on the adipose tissue. Importantly, recent evidence suggested that GIP is a potential suppressor of inflammation in several metabolic models. In this study, we aimed to investigate the immunoregulatory role of GIP in a murine model of diet-induced obesity (DIO) using the long-acting GIP analog [d-Ala(2)]GIP. Administration of [d-Ala(2)]GIP resulted in adipocytes of increased size, increased levels of adipose tissue lipid droplet proteins, indicating better lipid storage capacity, and reduced adipose tissue inflammation. Flow cytometry analysis revealed reduced numbers of inflammatory Ly6C(hi) monocytes and F4/80(hi)CD11c(+) macrophages, associated with IR. In addition, [d-Ala(2)]GIP reduced adipose tissue infiltration of IFN-?-producing CD8(+) and CD4(+) T cells. Furthermore, [d-Ala(2)]GIP treatment induced a favorable adipose tissue adipokine profile, manifested by a prominent reduction in key inflammatory cytokines (TNF-?, IL-1?, IFN-?) and chemokines (CCL2, CCL8, and CCL5) and an increase in adiponectin. Notably, [d-Ala(2)]GIP also reduced the numbers of circulating neutrophils and proinflammatory Ly6C(hi) monocytes in mice fed regular chow or a high-fat diet. Finally, the beneficial immune-associated effects were accompanied by amelioration of IR and improved insulin signaling in liver and adipose tissue. Collectively, our results describe key beneficial immunoregulatory properties for GIP in DIO and reveal that its augmentation ameliorates adipose tissue inflammation and improves IR. PMID:25217161

Varol, Chen; Zvibel, Isabel; Spektor, Lior; Mantelmacher, Fernanda Dana; Vugman, Milena; Thurm, Tamar; Khatib, Marian; Elmaliah, Elinor; Halpern, Zamir; Fishman, Sigal

2014-10-15

117

Resistin in Dairy Cows: Plasma Concentrations during Early Lactation, Expression and Potential Role in Adipose Tissue  

PubMed Central

Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA) levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IR?, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6) in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase) in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro. PMID:24675707

Reverchon, Maxime; Rame, Christelle; Cognie, Juliette; Briant, Eric; Elis, Sebastien; Guillaume, Daniel; Dupont, Joelle

2014-01-01

118

Cardiac adipose tissue: a new frontier for cardiac regeneration?  

PubMed

The human heart has limited regenerative capacity. We focused on cardiac adipose tissue as a source of progenitor cells and biological matrix material for salvaging injured myocardium. First, a population of human adult mesenchymal-like progenitors derived from cardiac adipose tissue, with inherent cardiac and endothelial cell potential, was identified and characterized. Next, a salvage strategy was tested, where a pericardial-derived, vascularized, adipose flap was used to cover oxygen-deprived myocardium in a porcine model. The fat flap reduced the myocardial scar size, in both acute and chronic infarcts. A human clinical trial to examine this novel intervention is currently underway. PMID:22709728

Bayes-Genis, Antoni; Gálvez-Montón, Carolina; Prat-Vidal, Cristina; Soler-Botija, Carolina

2013-07-15

119

Pomegranate vinegar attenuates adiposity in obese rats through coordinated control of AMPK signaling in the liver and adipose tissue  

PubMed Central

Background The effect of pomegranate vinegar (PV) on adiposity was investigated in high-fat diet (HF)-induced obese rats. Methods The rats were divided into 5 groups and treated with HF with PV or acetic acid (0, 6.5 or 13% w/w) for 16 weeks. Statistical analyses were performed by the Statistical Analysis Systems package, version 9.2. Results Compared to control, PV supplementation increased phosphorylation of AMP-activated protein kinase (AMPK), leading to changes in mRNA expressions: increases for hormone sensitive lipase and mitochondrial uncoupling protein 2 and decreases for sterol regulatory element binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor? (PPAR?) in adipose tissue; increases for PPAR? and carnitinepalmitoyltransferase-1a (CPT-1a) and decrease for SREBP-1c in the liver. Concomitantly, PV reduced increases of body weight (p?=?0.048), fat mass (p?=?0.033), hepatic triglycerides (p?=?0.005), and plasma triglycerides (p?=?0.001). Conclusions These results suggest that PV attenuates adiposity through the coordinated control of AMPK, which leads to promotion of lipolysis in adipose tissue and stimulation of fatty acid oxidation in the liver. PMID:24180378

2013-01-01

120

Brown adipose tissue: a promising target to combat obesity.  

PubMed

Obesity has now reached pandemic proportions leading to a collection of morbidities referred to as metabolic syndrome including insulin resistance, type 2 diabetes and cardiovascular disease. The expansion of adipose tissue is a direct cause of these comorbidities due to excessive accumulation of triglycerides within adipocytes, causing disruption of normal adipose function. There are two major types of adipose tissue, white and brown. The former stores energy as triglycerides within large droplets, whereas the latter catabolizes lipids to produce heat. A strategy to combat obesity-associated disorders, therefore, includes enhancement of brown adipose tissue activity by targeting the recently identified regulators of brown adipocyte development and function, including its master regulator, PRDM16. PMID:20862392

Vernochet, Cecile; McDonald, Meghan E; Farmer, Stephen R

2010-09-01

121

Cold-Induced Changes in Gene Expression in Brown Adipose Tissue, White Adipose Tissue and Liver  

PubMed Central

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 HNF4? and PPAR? 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. PMID:23894377

Shore, Andrew M.; Karamitri, Angeliki; Kemp, Paul; Speakman, John R.; Graham, Neil S.; Lomax, Michael A.

2013-01-01

122

Adipose Tissue Invariant NKT Cells Protect against Diet-Induced Obesity and Metabolic  

E-print Network

Immunity Article Adipose Tissue Invariant NKT Cells Protect against Diet-Induced Obesity in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were-inflammatory cytokine production by adipose- derived iNKT cells. This finding highlights the poten- tial of iNKT cell

O'Mahony, Donal E.

123

Peripheral blood leucocyte subclasses as potential biomarkers of adipose tissue inflammation and obesity subphenotypes in humans.  

PubMed

While obesity is clearly accepted as a major risk factor for cardio-metabolic morbidity, it is also apparent that some obese patients largely escape this association, forming a unique obese subphenotype(s). Current approaches to define such subphenotypes include clinical biomarkers that largely reflect already manifested comorbidities, such as markers of dyslipidaemia, hyperglycaemia and impaired regulation of vascular tone, and anthropometric or imaging-based assessment of adipose tissue distribution. Low-grade inflammation, evident both systemically and within adipose tissue (particularly intra-abdominal fat depots), seems to characterize the more cardio-metabolically morbid forms of obesity. Indeed, several systemic inflammatory markers (C-reactive protein), adipokines (retinol-binding protein 4, adiponectin) and cytokines have been shown to correlate in humans with adipose tissue inflammation and with obesity-associated health risks. Circulating leucocytes constitute a diverse group of cells that form a major arm of the immune system. They are both major sources of cytokines and likely also of infiltrating adipose tissue immune cells in obesity. In the present review, we summarize currently available literature on 'classical' blood white cell classes and on more specific leucocyte subclasses present in the circulation in human obesity. We critically raise the possibility that leucocytes may constitute clinically available markers for the more morbidity-associated obesity subphenotype(s), and when available, for intra-abdominal adipose tissue inflammation. PMID:24251825

Pecht, T; Gutman-Tirosh, A; Bashan, N; Rudich, A

2014-04-01

124

Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK.  

PubMed

Estrogens play a major role in the modulation of energy balance through central and peripheral actions. Here, we demonstrate that central action of estradiol (E2) inhibits AMP-activated protein kinase (AMPK) through estrogen receptor alpha (ER?) selectively in the ventromedial nucleus of the hypothalamus (VMH), leading to activation of thermogenesis in brown adipose tissue (BAT) through the sympathetic nervous system (SNS) in a feeding-independent manner. Genetic activation of AMPK in the VMH prevented E2-induced increase in BAT-mediated thermogenesis and weight loss. Notably, fluctuations in E2 levels during estrous cycle also modulate this integrated physiological network. Together, these findings demonstrate that E2 regulation of the VMH AMPK-SNS-BAT axis is an important determinant of energy balance and suggest that dysregulation in this axis may account for the common changes in energy homeostasis and obesity linked to dysfunction of the female gonadal axis. PMID:24856932

Martínez de Morentin, Pablo B; González-García, Ismael; Martins, Luís; Lage, Ricardo; Fernández-Mallo, Diana; Martínez-Sánchez, Noelia; Ruíz-Pino, Francisco; Liu, Ji; Morgan, Donald A; Pinilla, Leonor; Gallego, Rosalía; Saha, Asish K; Kalsbeek, Andries; Fliers, Eric; Bisschop, Peter H; Diéguez, Carlos; Nogueiras, Rubén; Rahmouni, Kamal; Tena-Sempere, Manuel; López, Miguel

2014-07-01

125

Estradiol Regulates Brown Adipose Tissue Thermogenesis via Hypothalamic AMPK  

PubMed Central

Summary Estrogens play a major role in the modulation of energy balance through central and peripheral actions. Here, we demonstrate that central action of estradiol (E2) inhibits AMP-activated protein kinase (AMPK) through estrogen receptor alpha (ER?) selectively in the ventromedial nucleus of the hypothalamus (VMH), leading to activation of thermogenesis in brown adipose tissue (BAT) through the sympathetic nervous system (SNS) in a feeding-independent manner. Genetic activation of AMPK in the VMH prevented E2-induced increase in BAT-mediated thermogenesis and weight loss. Notably, fluctuations in E2 levels during estrous cycle also modulate this integrated physiological network. Together, these findings demonstrate that E2 regulation of the VMH AMPK-SNS-BAT axis is an important determinant of energy balance and suggest that dysregulation in this axis may account for the common changes in energy homeostasis and obesity linked to dysfunction of the female gonadal axis. PMID:24856932

Martinez de Morentin, Pablo B.; Gonzalez-Garcia, Ismael; Martins, Luis; Lage, Ricardo; Fernandez-Mallo, Diana; Martinez-Sanchez, Noelia; Ruiz-Pino, Francisco; Liu, Ji; Morgan, Donald A.; Pinilla, Leonor; Gallego, Rosalia; Saha, Asish K.; Kalsbeek, Andries; Fliers, Eric; Bisschop, Peter H.; Dieguez, Carlos; Nogueiras, Ruben; Rahmouni, Kamal; Tena-Sempere, Manuel; Lopez, Miguel

2014-01-01

126

Germline ablation of VGF increases lipolysis in white adipose tissue.  

PubMed

Targeted deletion of VGF, a neuronal and endocrine secreted protein and neuropeptide precursor, produces a lean, hypermetabolic mouse that is resistant to diet-, lesion-, and genetically induced obesity and diabetes. We hypothesized that increased sympathetic nervous system activity in Vgf-/Vgf- knockout mice is responsible for increased energy expenditure and decreased fat storage and that increased ?-adrenergic receptor stimulation induces lipolysis in white adipose tissue (WAT) of Vgf-/Vgf- mice. We found that fat mass was markedly reduced in Vgf-/Vgf- mice. Within knockout WAT, phosphorylation of protein kinase A substrate increased in males and females, phosphorylation of hormone-sensitive lipase (HSL) (ser563) increased in females, and levels of adipose triglyceride lipase, comparative gene identification-58, and phospho-perilipin were higher in male Vgf-/Vgf- WAT compared with wild-type, consistent with increased lipolysis. The phosphorylation of AMP-activated protein kinase (AMPK) (Thr172) and levels of the AMPK kinase, transforming growth factor ?-activated kinase 1, were decreased. This was associated with a decrease in HSL ser565 phosphorylation, the site phosphorylated by AMPK, in both male and female Vgf-/Vgf- WAT. No significant differences in phosphorylation of CREB or the p42/44 MAPK were noted. Despite this evidence supporting increased cAMP signaling and lipolysis, lipogenesis as assessed by fatty acid synthase protein expression and phosphorylated acetyl-CoA carboxylase was not decreased. Our data suggest that the VGF precursor or selected VGF-derived peptides dampen sympathetic outflow pathway activity to WAT to regulate fat storage and lipolysis. PMID:22942234

Fargali, Samira; Scherer, Thomas; Shin, Andrew C; Sadahiro, Masato; Buettner, Christoph; Salton, Stephen R

2012-11-01

127

Subcutaneous adipose tissue thickness alters cooling time during cryotherapy  

Microsoft Academic Search

Otte JW, Merrick MA, Ingersoll CD, Cordova ML. Subcutaneous adipose tissue thickness alters cooling time during cryotherapy. Arch Phys Med Rehabil 2002;83:1501-5. Objective: To determine if differing subcutaneous adipose thickness alters the treatment duration required to produce a standard cooling effect during cryotherapy. Design: A 4-group, between-groups comparison in which the independent variable was skinfold thickness (0[ndash ]10mm, 11[ndash ]20mm,

Jeffrey W. Otte; Mark A. Merrick; Christopher D. Ingersoll; Mitchell L. Cordova

2002-01-01

128

Brown Adipose Tissue in Morbidly Obese Subjects  

PubMed Central

Background Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI) and body fat percentage (BF%), suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT) after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure. Methods and Findings After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT). Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n?=?39) from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001), respectively explaining 64% and 60% of the variance in BMI (r?=?0.8; P<0.001) and BF% (r?=?0.75; P<0.001). Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n?=?26) mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P?=?0.001), and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P?=?0.001), indicating a role for BAT in CIT in humans. Conclusions This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid) obesity. PMID:21390318

Vijgen, Guy H. E. J.; Bouvy, Nicole D.; Teule, G. J. Jaap; Brans, Boudewijn; Schrauwen, Patrick; van Marken Lichtenbelt, Wouter D.

2011-01-01

129

Characteristic Expression of Extracellular Matrix in Subcutaneous Adipose Tissue Development and Adipogenesis; Comparison with Visceral Adipose Tissue  

PubMed Central

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. PMID:25076859

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

2014-01-01

130

Circulatory and Metabolic Processes in Adipose Tissue in vivo  

Microsoft Academic Search

To permit the study in vivo of circulatory and metabolic processes in adipose tissue, a part of the dog's subcutaneous tissue was prepared with intact circulation and innervation. The preparation was found to be suitable for quantitative investigations on the nervous control of the blood flow and of the release of free fatty acids. We considered it to be of

Lars Oro; Lars Wallenberg; Sune Rosell

1965-01-01

131

Enhanced glycogen metabolism in adipose tissue decreases triglyceride mobilization.  

PubMed

Adipose tissue is a primary site for lipid storage containing trace amounts of glycogen. However, refeeding after a prolonged partial fast produces a marked transient spike in adipose glycogen, which dissipates in coordination with the initiation of lipid resynthesis. To further study the potential interplay between glycogen and lipid metabolism in adipose tissue, the aP2-PTG transgenic mouse line was utilized since it contains a 100- to 400-fold elevation of adipocyte glycogen levels that are mobilized upon fasting. To determine the fate of the released glucose 1-phosphate, a series of metabolic measurements were made. Basal and isoproterenol-stimulated lactate production in vitro was significantly increased in adipose tissue from transgenic animals. In parallel, basal and isoproterenol-induced release of nonesterified fatty acids (NEFAs) was significantly reduced in transgenic adipose tissue vs. control. Interestingly, glycerol release was unchanged between the genotypes, suggesting that enhanced triglyceride resynthesis was occurring in the transgenic tissue. Qualitatively similar results for NEFA and glycerol levels between wild-type and transgenic animals were obtained in vivo during fasting. Additionally, the physiological upregulation of the phosphoenolpyruvate carboxykinase cytosolic isoform (PEPCK-C) expression in adipose upon fasting was significantly blunted in transgenic mice. No changes in whole body metabolism were detected through indirect calorimetry. Yet weight loss following a weight gain/loss protocol was significantly impeded in the transgenic animals, indicating a further impairment in triglyceride mobilization. Cumulatively, these results support the notion that the adipocyte possesses a set point for glycogen, which is altered in response to nutritional cues, enabling the coordination of adipose glycogen turnover with lipid metabolism. PMID:20424138

Markan, Kathleen R; Jurczak, Michael J; Allison, Margaret B; Ye, Honggang; Sutanto, Maria M; Cohen, Ronald N; Brady, Matthew J

2010-07-01

132

Allele Compensation in Tip60+/? Mice Rescues White Adipose Tissue Function In Vivo  

PubMed Central

Adipose tissue is a key regulator of energy homestasis. The amount of adipose tissue is largely determined by adipocyte differentiation (adipogenesis), a process that is regulated by the concerted actions of multiple transcription factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes and human primary preadipocytes, the transcriptional cofactor and acetyltransferase Tip60 was recently identified as an essential adipogenic factor. We therefore investigated the role of Tip60 on adipocyte differentiation and function, and possible consequences on energy homeostasis, in vivo. Because homozygous inactivation results in early embryonic lethality, Tip60+/? mice were used. Heterozygous inactivation of Tip60 had no effect on body weight, despite slightly higher food intake by Tip60+/? mice. No major effects of heterozygous inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/? displayed normal glucose tolerance, both on a low fat and a high fat diet. While Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were unaltered, suggesting compensation by the intact allele. These findings indicate that the in vivo role of Tip60 in adipocyte differentiation and function cannot be properly addressed in Tip60+/? mice, but requires the generation of adipose tissue-specific knock out animals or specific knock-in mice. PMID:24870614

Gao, Yuan; Hamers, Nicole; Rakhshandehroo, Maryam; Berger, Ruud; Lough, John; Kalkhoven, Eric

2014-01-01

133

Markers of oxidative stress in adipose tissue during Trypanosoma cruzi infection.  

PubMed

The protozoan parasite Trypanosoma cruzi causes Chagas disease. Cardiac and adipose tissues are among the early targets of infection and are sites of persistent infection. In the heart and adipose tissue, T. cruzi infection results in an upregulation of pro-inflammatory mediators. In the heart, infection is associated with an increase in the markers of oxidative stress. To date, markers of oxidative stress have not been evaluated in adipose tissue in this infection. Brown and white adipose tissues were obtained from CD-1 mice infected with the Brazil strain of T. cruzi for 15, 30, and 130 days post infection. Protein carbonylation and lipid peroxidation assays were performed on these samples. There was an upregulation of these markers of oxidative stress at all time-points in both white and brown adipose tissue. Determinants of anti-oxidative stress were downregulated at similar time-points. This increase in oxidative stress during T. cruzi infection most likely has a deleterious effect on host metabolism and on the heart. PMID:24948102

Wen, Jian-Jun; Nagajyothi, Fnu; Machado, Fabiana S; Weiss, Louis M; Scherer, Philipp E; Tanowitz, Herbert B; Garg, Nisha Jain

2014-09-01

134

Allele compensation in tip60+/- mice rescues white adipose tissue function in vivo.  

PubMed

Adipose tissue is a key regulator of energy homestasis. The amount of adipose tissue is largely determined by adipocyte differentiation (adipogenesis), a process that is regulated by the concerted actions of multiple transcription factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes and human primary preadipocytes, the transcriptional cofactor and acetyltransferase Tip60 was recently identified as an essential adipogenic factor. We therefore investigated the role of Tip60 on adipocyte differentiation and function, and possible consequences on energy homeostasis, in vivo. Because homozygous inactivation results in early embryonic lethality, Tip60+/- mice were used. Heterozygous inactivation of Tip60 had no effect on body weight, despite slightly higher food intake by Tip60+/- mice. No major effects of heterozygous inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/- displayed normal glucose tolerance, both on a low fat and a high fat diet. While Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were unaltered, suggesting compensation by the intact allele. These findings indicate that the in vivo role of Tip60 in adipocyte differentiation and function cannot be properly addressed in Tip60+/- mice, but requires the generation of adipose tissue-specific knock out animals or specific knock-in mice. PMID:24870614

Gao, Yuan; Hamers, Nicole; Rakhshandehroo, Maryam; Berger, Ruud; Lough, John; Kalkhoven, Eric

2014-01-01

135

Modulation of angiogenesis during adipose tissue development in murine models of obesity.  

PubMed

Development of vasculature and mRNA expression of 17 pro- or antiangiogenic factors were studied during adipose tissue development in nutritionally induced or genetically determined murine obesity models. Subcutaneous (SC) and gonadal (GON) fat pads were harvested from male C57Bl/6 mice kept on standard chow [standard fat diet (SFD)] or on high-fat diet for 0-15 wk and from male ob/ob mice kept on SFD. Ob/ob mice and C57Bl/6 mice on high-fat diet had significantly larger SC and GON fat pads, accompanied by significantly higher blood content, increased total blood vessel volume, and higher number of proliferating cells. mRNA and protein levels of angiopoietin (Ang)-1 were down-regulated, whereas those of thrombospondin-1 were up-regulated in developing adipose tissue in both obesity models. Ang-1 mRNA levels correlated negatively with adipose tissue weight in the early phase of nutritionally induced obesity as well as in genetically determined obesity. Placental growth factor and Ang-2 expression were increased in SC adipose tissue of ob/ob mice, and thrombospondin-2 was increased in both their SC and GON fat pads. mRNA levels of vascular endothelial growth factor (VEGF)-A isoforms VEGF-B, VEGF-C, VEGF receptor-1, -2, and -3, and neuropilin-1 were not markedly modulated by obesity. This modulation of angiogenic factors during development of adipose tissue supports their important functional role in obesity. PMID:16020476

Voros, Gabor; Maquoi, Erik; Demeulemeester, Diego; Clerx, Natalie; Collen, Désiré; Lijnen, H Roger

2005-10-01

136

Adipose Tissue Macrophages Function As Antigen-Presenting Cells and Regulate Adipose Tissue CD4+ T Cells in Mice  

PubMed Central

The proinflammatory activation of leukocytes in adipose tissue contributes to metabolic disease. How crosstalk between immune cells initiates and sustains adipose tissue inflammation remains an unresolved question. We have examined the hypothesis that adipose tissue macrophages (ATMs) interact with and regulate the function of T cells. Dietary obesity was shown to activate the proliferation of effector memory CD4+ T cells in adipose tissue. Our studies further demonstrate that ATMs are functional antigen-presenting cells that promote the proliferation of interferon-?–producing CD4+ T cells in adipose tissue. ATMs from lean and obese visceral fat process and present major histocompatibility complex (MHC) class II–restricted antigens. ATMs were sufficient to promote proliferation and interferon-? production from antigen-specific CD4+ T cells in vitro and in vivo. Diet-induced obesity increased the expression of MHC II and T-cell costimulatory molecules on ATMs in visceral fat, which correlated with an induction of T-cell proliferation in that depot. Collectively, these data indicate that ATMs provide a functional link between the innate and adaptive immune systems within visceral fat in mice. PMID:23493569

Morris, David L.; Cho, Kae Won; DelProposto, Jennifer L.; Oatmen, Kelsie E.; Geletka, Lynn M.; Martinez-Santibanez, Gabriel; Singer, Kanakadurga; Lumeng, Carey N.

2013-01-01

137

Natural Killer T Cells in Adipose Tissue Are Activated in Lean Mice  

PubMed Central

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-?, whereas the V? 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 V? 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-? raises the possibility that NKT cells in adipose tissue may be stimulated by some physiological mechanism. PMID:24172196

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

2013-01-01

138

Benefits of healthy adipose tissue in the treatment of diabetes  

PubMed Central

The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin. Insulin deficiency is either absolute due to destruction or failure of pancreatic ? cells, or relative due to decreased sensitivity of peripheral tissues to insulin. The primary lesion being related to insulin, treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin. These therapies have their own limitations and complications, some of which can be life-threatening. For example, exogenous insulin administration can lead to fatal hypoglycemic episodes; islet/pancreas transplantation requires life-long immunosuppressive therapy; and anti-diabetic drugs have dangerous side effects including edema, heart failure and lactic acidosis. Thus the need remains for better safer long term treatments for diabetes. The ultimate goal in treating diabetes is to re-establish glucose homeostasis, preferably through endogenously generated hormones. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism. While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines, healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties, which can complement and/or compensate for the function of insulin. Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes, and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin. Although specific adipokines may correct diabetes, administration of individual adipokines still carries risks similar to those of insulin monotherapy. Thus a better approach is to achieve glucose homeostasis with endogenously-generated adipokines through transplantation or regeneration of healthy adipose tissue. Our recent studies on mouse models show that type 1 diabetes can be reversed without insulin through subcutaneous transplantation of embryonic brown adipose tissue, which leads to replenishment of recipients’ white adipose tissue; increase of a number of beneficial adipokines; and fast and long-lasting euglycemia. Insulin-independent glucose homeostasis is established through a combination of endogenously generated hormones arising from the transplant and/or newly-replenished white adipose tissue. Transplantation of healthy white adipose tissue is reported to alleviate type 2 diabetes in rodent models on several occasions, and increasing the content of endogenous brown adipose tissue is known to combat obesity and type 2 diabetes in both humans and animal models. While the underlying mechanisms are not fully documented, the beneficial effects of healthy adipose tissue in improving metabolism are increasingly reported, and are worthy of attention as a powerful tool in combating metabolic disease. PMID:25126390

Gunawardana, Subhadra C

2014-01-01

139

Hypothalamic inflammation and thermogenesis: the brown adipose tissue connection.  

PubMed

Hypothalamic inflammation and dysfunction are common features of experimental obesity. An imbalance between caloric intake and energy expenditure is generated as a consequence of this inflammation, leading to the progressive increase of body adiposity. Thermogenesis, is one of the main functions affected by obesity-linked hypothalamic dysfunction and the complete characterization of the mechanisms involved in this process may offer new therapeutic perspectives for obesity. The brown adipose tissue is an important target for hypothalamic action in thermogenesis. This tissue has been thoroughly studied in rodents and hibernating mammals; however, until recently, its advocated role in human thermogenesis was neglected due to the lack of substantial evidence of its presence in adult humans. The recent demonstration of the presence of functional brown adipose tissue in adult humans has renovated the interest in this tissue. Here, we review some of the work that shows how inflammation and dysfunction of the hypothalamus can control brown adipose tissue activity and how this can impact on whole body thermogenesis and energy expenditure. PMID:21271281

Arruda, Ana Paula; Milanski, Marciane; Velloso, Licio A

2011-02-01

140

Browning of white adipose tissue: role of hypothalamic signaling.  

PubMed

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. PMID:23980536

Bi, Sheng; Li, Lin

2013-10-01

141

"Browning" of adipose tissue--regulation and therapeutic perspectives.  

PubMed

Obesity is considered a worldwide health concern. Most of obesity therapies are aimed at decreasing energy intake. However, recent data suggest that increasing cellular energy expenditure could be a useful approach to reduce adiposity. Adaptive thermogenesis, a biological process within the brown fat by which energy is dissipated in mitochondria, is a great tool to increase energy expenditure. Several studies have confirmed the presence of brown adipose tissue in adult humans, whose activity may make it a target for the treatment of obesity. Differentiation of brown adipocytes could be a potent tool to promote weight loss by increasing energy expenditure. Here we review the mechanisms potentially associated with expansion and activation of brown adipose tissue, and modulation of adaptive thermogenesis. Controlling one or more of these pathways could induce a positive regulation of brown adipogenesis. A better understanding of these molecular pathways could potentially result in novel anti-obesity therapies. PMID:23721302

Peschechera, Alessandro; Eckel, Juergen

2013-10-01

142

Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes  

E-print Network

Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging resembles both, white and brown adipose tissue (WAT and BAT, respectively). Marrow adipocytes express gene TZD rosiglitazone, which sensitizes cells to insulin and increases adipocyte metabolic functions

Toledo, University of

143

Prolactin and Insulin Ultradian Secretion and Adipose Tissue Lipoprotein lipase Expression in Severely Obese Women After Bariatric Surgery  

Microsoft Academic Search

Background:Hyperprolactinemia is associated with obesity. Furthermore, in human adipose tissue cultured in vitro, prolactin (PRL) inhibited lipoprotein lipase (LPL) activity via functional PRL receptors.Objective:Tostudy PRL and insulin ultradian rhythm and subcutaneous adipose tissue LPL mRNA and protein expressions in severely obese women before and after malabsorptive bariatric surgery.Methods and Procedures:Seven severely obese, fertile women were studied twice, once before and

Geltrude Mingrone; Melania Manco; Amerigo Iaconelli; Donatella Gniuli; Roberto Bracaglia; Laura Leccesi; Menotti Calvani; Giuseppe Nolfe; Subhabrata Basu; Rachele Berria

2008-01-01

144

Continuous low-dose infusion of tumor necrosis factor alpha in adipose tissue elevates adipose tissue interleukin 10 abundance and fails to alter metabolism in lactating dairy cows.  

PubMed

Repeated bolus doses of tumor necrosis factor-? (TNF?) alters systemic metabolism in lactating cows, but whether chronic release of inflammatory cytokines from adipose tissue has similar effects is unclear. Late-lactation Holstein cows (n=9-10/treatment) were used to evaluate the effects of continuous adipose tissue TNF? administration on glucose and fatty acid (FA) metabolism. Cows were blocked by feed intake and milk yield and randomly assigned within block to control or TNF? treatments. Treatments (4mL of saline or 14µg/kg of TNF? in 4mL of saline) were infused continuously over 7d via 2 osmotic pumps implanted in a subcutaneous adipose depot. Plasma, milk samples, milk yield, and feed intake data were collected daily, and plasma glucose turnover rate was measured on d 7. At the end of d 7, pumps were removed and liver and contralateral tail-head adipose biopsies were collected. Results were modeled with the fixed effect of treatment and the random effect of block. Treatment with TNF? increased plasma concentrations of the acute phase protein haptoglobin, but did not alter plasma TNF?, IL-4, IL-6, or IFN-? concentrations, feed intake, or rectal temperature. Milk yield and composition were unchanged, and treatments did not alter the proportion of short- versus long-chain FA in milk on d 7. Treatments did not alter plasma free FA concentration, liver triglyceride content, or plasma glucose turnover rate. Surprisingly, TNF? infusion tended to decrease liver TNF? and IL-1 receptor 1 mRNA abundance and significantly increased adipose tissue IL-10 protein concentration. Continuous infusion of TNF? did not induce the metabolic responses previously observed following bolus doses delivered at the same rate per day. Metabolic homeostasis may have been protected by an adaptive anti-inflammatory response to control systemic inflammation. PMID:24881787

Martel, Cynthia A; Mamedova, Laman K; Minton, J Ernest; Jones, Meredyth L; Carroll, Jeff A; Bradford, Barry J

2014-08-01

145

FACTORS INFLUENCING THE LIPOGENIC RATE IN SWINE ADIPOSE TISSUE  

Microsoft Academic Search

Summary Measurements of the lipogenic rate in adipose tissue samples obtained sequentially by biopsy from the same pig may be useful for many nutritional experiments. The average lipogenic rate over a short period (several days to 2 weeks) appears to be relatively stable if the pigs weigh about 20 kg initially and if approximately 10 animals are allotted to each

H. J. Mersmann; C. D. Allen; E. Y. Chai; L. J. Brown; T. J. Fogg

2010-01-01

146

Sleep deprivation affects inflammatory marker expression in adipose tissue  

Microsoft Academic Search

: 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

José C Rosa Neto; Fábio S Lira; Daniel P Venancio; Cláudio A Cunha; Lila M Oyama; Gustavo D Pimentel; Sérgio Tufik; Cláudia M Oller do Nascimento; Ronaldo VT Santos; Marco T de Mello

2010-01-01

147

Clinical Note Unequivocal Identification of Brown Adipose Tissue  

E-print Network

demonstrated. In the present work, large bilateral supra- clavicular BAT depots were clearly visualized of weight gain and the development of obesity. Current findings suggest that BAT is present in significant potential to counteract weight gain and development of obesity (1­3). In con- trast to white adipose tissue

Southern California, University of

148

GOAT ADIPOSE TISSUE MOBILIZATION AND MILK PRODUCTION LEVEL  

E-print Network

GOAT ADIPOSE TISSUE MOBILIZATION AND MILK PRODUCTION LEVEL D. SAUVANT Y. CHILLIARD, P. BAS P weight that high levels of milk production are closely associated with an intense mobili- zation of body work was conducted to study the relationships which associate milk yield and lipomobilization levels

Paris-Sud XI, Université de

149

Spice Up Your Life: Adipose Tissue and Inflammation  

PubMed Central

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. PMID:24701352

Agarwal, Anil K.

2014-01-01

150

Larger Amounts of Visceral Adipose Tissue in Asian Americans  

Microsoft Academic Search

Objective: Excess visceral adipose tissue (VAT) is recognized as an important risk factor for the development of coronary heart disease and type 2 diabetes. Several studies have reported less VAT in African Americans compared with whites. As little is known about the levels of VAT in Asians, we compared whole-body VAT in Asian Americans with European Americans.Research Methods and Procedures:

Yong-Woo Park; David B. Allison; Steven B. Heymsfield; Dympna Gallagher

2001-01-01

151

12- and 15-Lipoxygenases in Adipose Tissue Inflammation  

PubMed Central

The lipoxygenases (LOs) are principal enzymes involved in the oxidative metabolism of polyunsaturated fatty acids, including arachidonic acid. 12- and 15-LO and their lipid metabolites have been implicated in the development of insulin resistance and diabetes. Adipose tissue, and in particular visceral adipose tissue, plays a primary role in the development of the inflammation seen in these conditions. 12- and 15-LO and their lipid metabolites act as upstream regulators of many of the cytokines involved in the inflammatory response in adipose tissue. While the role that 12- and 15-LO play in chronically inflamed adipose tissue is becoming clearer, there are still many questions that remain unanswered regarding their activation, signaling pathways, and roles in healthy fat. 12- and 15-LO also generate products with anti-inflammatory properties that are under investigation. Therefore, 12- and 15-LO have the potential to be very important targets for therapeutics aimed at reducing insulin resistance and the comorbid conditions associated with obesity. PMID:22951339

Cole, Banumathi K.; Lieb, David C.; Dobrian, Anca D.; Nadler, Jerry L.

2012-01-01

152

Obesity and polymorphisms in genes regulating human adipose tissue  

Microsoft Academic Search

Obesity is the result of an imbalance between food intake and energy expenditure resulting in the storing of energy as fat. Adipose tissue contains the largest store of energy in the body and plays important roles in regulating energy partitioning. Developments in genomics, in particular microarray-based expression profiling, have provided scientists with a number of new candidate genes whose expression

I Dahlman; P Arner

2007-01-01

153

Retinoids and adipose tissues: metabolism, cell differentiation and gene expression  

Microsoft Academic Search

Vitamin A derivatives (retinoids) play a key role in mammalian development and cell differentiation. Isomers of retinoic acid, the main active metabolite of vitamin A, activate retinoid receptors that act as ligand-dependent transcription factors and affect gene expression. White and brown adipose tissues are major sites of storage of vitamin A derivatives and they play an active role in whole

F Villarroya; M Giralt; R Iglesias

1999-01-01

154

Activation of Natural Killer T Cells Promotes M2 Macrophage Polarization in Adipose Tissue and Improves Systemic Glucose Tolerance via Interleukin-4 (IL-4)/STAT6 Protein Signaling Axis in Obesity*  

PubMed Central

Natural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type 1 NKT cells, whose abundance decreases with increased adiposity and insulin resistance. Although loss-of-function of NKT cells had no effect on glucose tolerance in animals with prolonged high fat diet feeding, activation of NKT cells by lipid agonist ?-galactosylceramide enhances alternative macrophage polarization in adipose tissue and improves glucose homeostasis in animals at different stages of obesity. Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6 signaling axis in obese adipose tissue. Thus, our data identify a novel therapeutic target for the treatment of obesity-associated inflammation and type 2 diabetes. PMID:22396530

Ji, Yewei; Sun, Shengyi; Xu, Aimin; Bhargava, Prerna; Yang, Liu; Lam, Karen S. L.; Gao, Bin; Lee, Chih-Hao; Kersten, Sander; Qi, Ling

2012-01-01

155

An accelerated mouse model for atherosclerosis and adipose tissue inflammation  

PubMed Central

Background Obesity and particularly the metabolic syndrome, which is often associated with obesity, combine a major risk for type 2 diabetes and cardiovascular disease. Emerging evidence indicate obesity-associated subclinical inflammation primarily originating from adipose tissue as a common cause for type 2 diabetes and cardiovascular disease. However, a suitable and well-characterized mouse model to simultaneously study obesity-associated metabolic disorders and atherosclerosis is not available yet. Here we established and characterized a murine model combining diet-induced obesity and associated adipose tissue inflammation and metabolic deteriorations as well as atherosclerosis, hence reflecting the human situation of cardio-metabolic disease. Methods We compared a common high-fat diet with 0.15% cholesterol (HFC), and a high-fat, high-sucrose diet with 0.15% cholesterol (HFSC) fed to LDL receptor-deficient (LDLR-/-) mice. Insulin resistance, glucose tolerance, atherosclerotic lesion formation, hepatic lipid accumulation, and inflammatory gene expression in adipose tissue and liver were assessed. Results After 12–16 weeks, LDLR-/- mice fed HFSC or HFC developed significant diet-induced obesity, adipose tissue inflammation, insulin resistance, and impaired glucose tolerance compared to lean controls. Notably, HFSC-fed mice developed significantly higher adipose tissue inflammation in parallel with significantly elevated atherosclerotic lesion area compared to those on HFC. Moreover, LDLR-/- mice on HFSC showed increased insulin resistance and impaired glucose tolerance relative to those on HFC. After prolonged feeding (20 weeks), however, no significant differences in inflammatory and metabolic parameters as well as atherosclerotic lesion formation were detectable any more between LDLR-/- mice fed HFSC or HFC. Conclusion The use of high sucrose rather than more complex carbohydrates in high-fat diets significantly accelerates development of obesity-driven metabolic complications and atherosclerotic plaque formation parallel to obesity-induced adipose tissue inflammation in LDLR-/- mice. Hence LDLR-/- mice fed high-fat high-sucrose cholesterol-enriched diet appear to be a suitable and time-saving animal model for cardio-metabolic disease. Moreover our results support the suggested interrelation between adipose tissue inflammation and atherosclerotic plaque formation. PMID:24438079

2014-01-01

156

Thermogenic and metabolic consequences of thyroid hormone treatment in brown and white adipose tissue  

Microsoft Academic Search

Male rats were treated with triiodothyronine in the drinking water for 12 days. In vitro rates of isoprenaline stimulated lipolysis were significantly greater in brown but not white adipose tissue. Rates of [14C]glucose incorporation into triacylglycerols were significantly reduced in BAT (brown adipose tissue) and WAT (white adipose tissue) under basal and isoprenaline stimulated conditions, in a second experiment, hyperthyroid

Christine M. Williams; Rodney Ellis

1985-01-01

157

Blood flow in different adipose tissue depots during prolonged exercise in dogs  

Microsoft Academic Search

Adipose tissue blood flow was measured by the microsphere technique in all major adipose tissue depots in dogs during exercise. The measurements were done during rest, after 1 and 2 h of exercise and after a postexercise rest period. It was found that the blood flow to the inguinal, subcutaneous adipose tissue increased from about 6 ml\\/(100g·min) during rest to

Jens Biilow; Erik Tøndevold

1982-01-01

158

Fabrication of Adipose-Derived Mesenchymal Stem Cell Aggregates using Biodegradable Porous Microspheres for Injectable Adipose Tissue Regeneration  

Microsoft Academic Search

Injectable mesenchymal stem cell aggregates were formed using hyaluronic acid (HA)-immobilized porous biodegradable microspheres for adipose tissue regeneration. Adipose tissue-derived mesenchymal stem cells (AMSCs) were aggregated in a controlled manner and differentiated into adipocytes by cultivating in a stirred suspension bioreactor. The resultant cellular aggregates were approx. 1700 ?m in diameter and exhibited fully differentiated adipocytes, as shown by immunocytochemistry

Hyun Jung Chung; Jin Sup Jung; Tae Gwan Park

2011-01-01

159

Brown adipose tissue thermogenesis is `suppressed' during lactation in mice  

Microsoft Academic Search

Brown adipose tissue is considered to be the main site of thermoregulatory non-shivering thermogenesis in the newborn of many mammalian species, in arousing hibernators, and in adult cold-adapted rats and mice1-4. Several recent studies have now suggested that the tissue may also be important in the regulation of energy balance. Evidence has been obtained indicating that the ability of genetically

Paul Trayhurn; Jenny B. Douglas; Martina M. McGuckin

1982-01-01

160

Plasma and white adipose tissue lipid composition in marmots.  

PubMed

White adipose tissue biopsies and plasma samples were obtained from hibernating yellow-bellied marmots (Marmota flaviventris) maintained in the laboratory. In addition, biopsies and plasma samples were obtained from normothermic animals in the field and laboratory. Measurement of plasma free fatty acid (FA) levels indicated that winter laboratory animals exhibited increased lipolysis. Additionally, analysis of white adipose tissue triacylglycerol revealed that the FA composition of the storage fat in animals maintained on the standard laboratory diet is remarkably simple and uniform between different adipose depots in the same animal. Three FAs (palmitic, oleic, and linoleic acids) made up greater than 95% of the total. Triene (alpha-linolenate) was found in newly captured animals, but the percentage of this FA decreased rapidly when the animals were maintained on the standard laboratory diet. Throughout the hibernation season (October to April), white adipose tissue-saturated FA percentage decreased, monoene percentage remained constant, and diene percentage increased. Analysis of plasma FA composition suggested that these animals tended to metabolize saturated FAs from stored lipid during hibernation and that dienes were mobilized briefly after the last arousal from hibernation in spring. From these observations, we hypothesize that marmots preferentially metabolize saturated fats during the hibernation period and that essential FAs of the omega 6 series tend to be metabolized more slowly than other FAs. These characteristics suggest that marmots are a valuable animal model in which to study lipid metabolism. PMID:2337195

Florant, G L; Nuttle, L C; Mullinex, D E; Rintoul, D A

1990-05-01

161

Hyperglycemic Challenge and Distribution of Adipose Tissue in Obese Baboons  

PubMed Central

Background Blood glucose levels regulate the rate of insulin secretion, which is the body’s mechanism for preventing excessive elevation in blood glucose. Impaired glucose metabolism and insulin resistance have been linked to excess body fat composition. Here, we quantify abdominal muscle and abdominal adipose tissue compartments in a large nonhuman primate, the baboon, and investigate their relationship with serum glucose response to a hyperglycemic challenge. Methods Five female baboons were fasted for 16 hours prior to 90 minute body imaging experiment that consisted of a 20-min baseline, followed by a bolus infusion of glucose (500mg/kg). The blood glucose was sampled at regular intervals. The total volumes of the muscle, visceral and subcutaneous adipose tissue were measured. Results and discussion We found that adipose tissue composition predicted fluctuations in glucose responses to a hyperglycemic challenge of a non-human primate. Animals with higher visceral adiposity showed significantly reduced glucose elimination. The glucose responses were positively correlated with body weight, visceral and muscle fat (p < 0.005). Polynomial regression analysis showed that body weight, visceral and muscle were significant Conclusions These results reveal the similarity between humans and baboons with respect to glucose metabolism and strengthen the utility of baboon for biomedical research.

Kulkarni, Tanmay; Slaughter, Gymama; Ego-Osuala, Chimdi; Kochunov, Peter; Bastarrachea, Raul A.; Mattern, Vicki; Andrade, Marcia; Higgins, Paul B.; Comuzzie, Anthony G.; Voruganti, V. Saroja

2014-01-01

162

Interplay between the immune system and adipose tissue in obesity.  

PubMed

Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. Alongside its major role in energy storage, WAT is an important endocrine organ, producing many bioactive molecules, termed adipokines, which not only serve as regulators of systemic metabolism, but also possess immunoregulatory properties. Furthermore, WAT contains a unique immune cell repertoire, including an accumulation of leukocytes that are rare in other locations. These include alternatively activated macrophages, invariant natural killer T cells, and regulatory T cells. Disruption of resident adipose leukocyte homeostasis contributes to obesity-associated inflammation and consequent metabolic disorder. Despite many recent advances in this new field of immuno-metabolism, fundamental questions of why and how inflammation arises as obesity develops are not yet fully understood. Exploring the distinct immune system of adipose tissue is fundamental to our understanding of the endocrine as well as immune systems. In this review, we discuss the roles of adipose tissue leukocytes in the transition to obesity and progression of inflammation and highlight potential anti-inflammatory therapies for combating obesity-related pathology. PMID:25228503

Exley, Mark A; Hand, Laura; O'Shea, Donal; Lynch, Lydia

2014-11-01

163

Hyperhomocysteinemia Promotes Insulin Resistance by Inducing Endoplasmic Reticulum Stress in Adipose Tissue*  

PubMed Central

Type 2 diabetes is a chronic inflammatory metabolic disease, the key point being insulin resistance. Endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of type 2 diabetes. Previously, we found that hyperhomocysteinemia (HHcy) induced insulin resistance in adipose tissue. Here, we hypothesized that HHcy induces ER stress, which in turn promotes insulin resistance. In the present study, the direct effect of Hcy on adipose ER stress was investigated by the use of primary rat adipocytes in vitro and mice with HHcy in vivo. The mechanism and the effect of G protein-coupled receptor 120 (GPR120) were also investigated. We found that phosphorylation or expression of variant ER stress markers was elevated in adipose tissue of HHcy mice. HHcy activated c-Jun N-terminal kinase (JNK), the downstream signal of ER stress in adipose tissue, and activated JNK participated in insulin resistance by inhibiting Akt activation. Furthermore, JNK activated c-Jun and p65, which in turn triggered the transcription of proinflammatory cytokines. Both in vivo and in vitro assays revealed that Hcy-promoted macrophage infiltration aggravated ER stress in adipose tissue. Chemical chaperones PBA and TUDCA could reverse Hcy-induced inflammation and restore insulin-stimulated glucose uptake and Akt activation. Activation of GPR120 reversed Hcy-induced JNK activation and prevented inflammation but not ER stress. Therefore, HHcy inhibited insulin sensitivity in adipose tissue by inducing ER stress, activating JNK to promote proinflammatory cytokine production and facilitating macrophage infiltration. These findings reveal a new mechanism of HHcy in the pathogenesis of insulin resistance. PMID:23417716

Li, Yang; Zhang, Heng; Jiang, Changtao; Xu, Mingjiang; Pang, Yanli; Feng, Juan; Xiang, Xinxin; Kong, Wei; Xu, Guoheng; Li, Yin; Wang, Xian

2013-01-01

164

Adipose Tissue Biology and Cardiomyopathy-Translational Implications  

PubMed Central

It is epidemiologically established that obesity is frequently associated with the metabolic syndrome and poses an increased risk for the development of type 2 diabetes and cardiovascular disease. The molecular links that connect the phenomenon of obesity per se with insulin resistance and cardiovascular disease are still not fully elucidated. It is increasingly apparent that fully functional adipose tissue can be cardioprotective by reducing lipotoxic effects in other peripheral tissues and by maintaining a healthy balance of critical adipokines, thereby allowing the heart to maintain its full metabolic flexibility. The present review highlights both basic as well as clinical findings that emphasize the complex interplay of adipose tissue physiology, adipokine-mediated effects on the heart exerted by either direct effects on cardiac myocytes or indirect actions via central mechanisms through sympathetic outflow to the heart. PMID:23223931

Turer, Aslan T.; Hill, Joseph A.; Elmquist, Joel K.; Scherer, Philipp E.

2012-01-01

165

Adipose tissue attracts and protects acute lymphoblastic leukemia cells from chemotherapy.  

PubMed

Obesity is associated with an increased risk of acute lymphoblastic leukemia (ALL) relapse. Using mouse and cell co-culture models, we investigated whether adipose tissue attracts ALL to a protective microenvironment. Syngeneically implanted ALL cells migrated into adipose tissue within ten days. In vitro, murine ALL cells migrated towards adipose tissue explants and 3T3-L1 adipocytes. Human and mouse ALL cells migrated toward adipocyte conditioned media, which was mediated by SDF-1?. In addition, adipose tissue explants protected ALL cells against daunorubicin and vincristine. Our findings suggest that ALL migration into adipose tissue could contribute to drug resistance and potentially relapse. PMID:23332453

Pramanik, Rocky; Sheng, Xia; Ichihara, Brian; Heisterkamp, Nora; Mittelman, Steven D

2013-05-01

166

Suppression of the C/EBP family of transcription factors in adipose tissue causes lipodystrophy.  

PubMed

Adipose-specific inactivation of both AP-1 and CCAAT-enhancer-binding protein (C/EBP) families of B-ZIP transcription factors in transgenic mice causes severe lipoatrophy. To evaluate whether inactivation of only C/EBP members was critical for lipoatrophy, A-C/EBP, a dominant-negative protein that specifically inhibits the DNA binding of the C/EBP members, was expressed in adipose tissue. For the first 2 weeks after birth, aP2-A-C/EBP mice had no white adipose tissue (WAT), drastically reduced brown adipose tissue (BAT), and exhibited marked hepatic steatosis, hyperinsulinemia, and hyperlipidemia. However, WAT appeared during the third week, coinciding with significantly improved metabolic functioning. In adults, BAT remained reduced, causing cold intolerance. At 30 weeks, the aP2-A-C/EBP mice had only 35% reduced WAT, with clear morphological signs of lipodystrophy in subcutaneous fat. Circulating leptin and adiponectin levels were less than the wild-type levels, and these mice exhibited impaired triglyceride clearance. Insulin resistance, glucose intolerance, and reduced free fatty acid release in response to ?3-adrenergic agonist suggest improper functioning of the residual WAT. Gene expression analysis of inguinal WAT identified reduced mRNA levels of several enzymes involved in fatty acid synthesis and glucose metabolism that are known C/EBP? transcriptional targets. There were increased levels for genes involved in inflammation and muscle differentiation. However, when dermal fibroblasts from aP2-A-C/EBP mice were differentiated into adipocytes in tissue culture, muscle markers were elevated more than the inflammatory markers. These results demonstrate that the C/EBP family is essential for adipose tissue development during the early postnatal period, the regulation of glucose and lipid homeostasis in adults, and the suppression of the muscle lineage. PMID:21321096

Chatterjee, Raghunath; Bhattacharya, Paramita; Gavrilova, Oksana; Glass, Kimberly; Moitra, Jaideep; Myakishev, Max; Pack, Stephanie; Jou, William; Feigenbaum, Lionel; Eckhaus, Michael; Vinson, Charles

2011-06-01

167

Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia.  

PubMed

Cancer cachexia induces loss of fat mass that accounts for a large part of the dramatic weight loss observed both in humans and in animal models; however, the literature does not provide consistent information regarding the set point of weight loss and how the different visceral adipose tissue depots contribute to this symptom. To evaluate that, 8-week-old male Wistar rats were subcutaneously inoculated with 1?ml (2×10(7)) of tumour cells (Walker 256). Samples of different visceral white adipose tissue (WAT) depots were collected at days 0, 4, 7 and 14 and stored at -80?°C (seven to ten animals/each day per group). Mesenteric and retroperitoneal depot mass was decreased to the greatest extent on day 14 compared with day 0. Gene and protein expression of PPAR?2 (PPARG) fell significantly following tumour implantation in all three adipose tissue depots while C/EBP? (CEBPA) and SREBP-1c (SREBF1) expression decreased over time only in epididymal and retroperitoneal depots. Decreased adipogenic gene expression and morphological disruption of visceral WAT are further supported by the dramatic reduction in mRNA and protein levels of perilipin. Classical markers of inflammation and macrophage infiltration (f4/80, CD68 and MIF-1?) in WAT were significantly increased in the later stage of cachexia (although showing a incremental pattern along the course of cachexia) and presented a depot-specific regulation. These results indicate that impairment in the lipid-storing function of adipose tissue occurs at different times and that the mesenteric adipose tissue is more resistant to the 'fat-reducing effect' than the other visceral depots during cancer cachexia progression. PMID:23033362

Batista, M L; Neves, R X; Peres, S B; Yamashita, A S; Shida, C S; Farmer, S R; Seelaender, M

2012-12-01

168

Effects of sucrose, caffeine, and cola beverages on obesity, cold resistance, and adipose tissue cellularity.  

PubMed

Rats consuming Coca-Cola and Purina chow ad libitum increased their total energy intake by 50% without excess weight gain. Their resistance to cold was markedly improved. These phenomena were characterized by significant increases in interscapular brown adipose tissue weight (IBAT) (91%), cellularity (59%), triglyceride content (52%), protein content (94%), and cytochrome oxidase activity (167%). In contrast, Coca-Cola consumption did not significantly affect the cellularity or triglyceride content of parametrial white adipose tissue (PWAT), although it slightly augmented PWAT weight. The effects of Coca-Cola on cold resistance, IBAT cellularity, and composition were entirely reproduced by sucrose, but not caffeine, consumption. Although caffeine also increased IBAT cellularity and composition, it significantly decreased the rate of body weight gain, PWAT weight, and adipocyte size. Moreover, it markedly inhibited adipocyte proliferation in PWAT thereby mimicking the effects of exercise training and food restriction (Bukowiecki et al., Am. J. Physiol. 239 (Endocrinol. Metab. 2): E422-E429, 1980). It is concluded a) that sucrose and Coca-Cola consumption improve the resistance of rats to cold, most probably by increasing brown adipose tissue cellularity, and b) that moderate caffeine intake might be useful for inhibiting proliferative activity in white adipose tissue, thereby preventing obesity. PMID:6837766

Bukowiecki, L J; Lupien, J; Folléa, N; Jahjah, L

1983-04-01

169

Culture of isolated human adipocytes and isolated adipose tissue.  

PubMed

Adipose tissue (AT) is no longer considered merely as insulation or padding for human organs. It is an endocrine organ in its own right, which includes composite cells with the ability to differentiate into multiple cell lines. In fact, there is increasing evidence to support the theory that the causation of obesity and its associated metabolic disorders originate at the cellular or tissue level. Adipocyte dysfunction and chronic inflammatory states are able to modulate triglyceride storage and mobilization directly through cytokine and adipokine release. Significant variability exists between adipocyte isolation and culture techniques which subsequently can impact experimental results. We aim to explain the importance of controlling these variables, to assist tailoring methodological choice towards the investigational outcomes, and modifications of the techniques used accordingly. The techniques described in this chapter yield cell and adipose tissue which can be utilised in many different ways, including adipose tissue stem cells for differentiation, DNA analysis, RT-PCR, immunohistochemistry, lipolysis, glucose uptake, and LPL activity. PMID:22057454

Carswell, Kirstin A; Lee, Mi-Jeong; Fried, Susan K

2012-01-01

170

Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice  

PubMed Central

Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27?/? mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs) from wildtype and Fsp27?/? mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT) and white adipose tissue (WAT) and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27?/? mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27?/? and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27?/? mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1? were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27?/? mice. Remarkably, Fsp27?/? MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3). Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity. PMID:18682832

Li, John Zhong; Yang, Shuqun; Ye, Jing; Yao, Huilan; Zhang, Yinxin; Xue, Bofu; Li, Qing; Yang, Hongyuan; Wen, Zilong; Li, Peng

2008-01-01

171

Obesity is defined as an excess accumulation of adipose tissue. It occurs in mammalian  

E-print Network

is a heterogeneous organ consisting of multiple cell types. Classically, adipose tissue is subdivided into white and other immune cells (FIG. 1). Cell types in both fractions of adipose tissue can change the metabolic biology or in the non-adipose cells in the stromal-vascular fraction. The relative contribution of cells

Cai, Long

172

Effect of diet and ovariectomy on adipose tissue cellularity E. PALLIER Roberte AUBERT, D. LEMONNIER  

E-print Network

and abdominal subcu- taneous adipose tissue) and the length of the femur. Total fat cell number and size were measured at those sites as described previously by Lemonnier (1972) : the adipose cells on portionsEffect of diet and ovariectomy on adipose tissue cellularity in mice E. PALLIER Roberte AUBERT, D

Paris-Sud XI, Université de

173

Peanut sprouts extract (Arachis hypogaea L.) has anti-obesity effects by controlling the protein expressions of PPAR? and adiponectin of adipose tissue in rats fed high-fat diet  

PubMed Central

BACKGROUD/OBEJECTIVES This study aims to find out the effects of peanut sprout extracts on weight controls and protein expressions of transcription factors related to adipocyte differentiation and adipocytokine in rats under high-fat diets. MATERIALS/METHODS Four week-old Sparague-Dawley (SD) were assigned to 4 groups; normal-fat (NF) diets (7% fat diet), high-fat (HF) diets (20% fat diet), high fat diets with low peanut sprout extract (HF + PSEL) diet (20% fat and 0.025% peanut sprout extract), and high fat diets with high peanut sprout extract (HF + PSEH) diet (20% fat and 0.05% peanut sprout extract). Body weight changes, lipid profiles in adipose tissue, and the mRNA protein expressions, such as peroxisome proliferator-activated receptor ? (PPAR?), CCAAT element binding protein ? (C/EBP ?), leptin, and adiponectin, were determined. RESULTS After 9 weeks of feeding, the HF + PSEH group had significantly less weight gains than the HF group (P < 0.05). However, the total dietary intakes or food efficiency ratios among groups were not significantly different. The weight of epididymal fat in HF + PSEH group, 3.61 ± 0.5 g, or HF + PSEL group, 3.80 ± 0.7 g, was significantly lower than the HF group, 4.39 ± 0.4g, (P < 0.05). Total lipids and total cholesterol in adipose tissue were significantly decreased in HF + PSEH group compared to those in the HF group, respectively (P < 0.05). PSEH supplementation caused AST and ALT levels to decrease when it compared to HF group, but it was not statistically significant. The protein expression of PPAR? in HF + PSEH group was significantly lower than the HF group (P < 0.05). Comparing with the HF group, the protein expression of adiponectin in HF + PSEH group was significantly increased (P < 0.05). The protein expressions of C/EBP ? and leptin in HF + PSEH group were lower than the HF group, but it was not statistical significant. CONCLUSIONS In conclusion, peanut sprout extract has anti-obesity effect by lowering the expressions of PPAR? which regulates the expression of adiponectin. PMID:24741399

Kang, Nam E; Ha, Ae Wha; Woo, Hye Won

2014-01-01

174

Mechanisms of Perivascular Adipose Tissue Dysfunction in Obesity  

PubMed Central

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. PMID:24307898

Fernandez-Alfonso, Maria S.; Garcia-Prieto, Concha F.; Aranguez, Isabel; Ruiz-Gayo, Mariano; Somoza, Beatriz

2013-01-01

175

Levels of chlordane, oxychlordane, and nonachlor in human adipose tissues  

SciTech Connect

Chlordane was used as a termiticide for more than twenty years in Japan. Chlordane is stable in the environment such as sediment and its bioaccumulation in some species of bacteria, freshwater invertebrates, and marine fish is large. Many researches were done to elucidate the levels of chlordane and/or its metabolite oxychlordane in human adipose tissues. A comprehensive review concerning chlordane was recently provided by USEPA. On the other hand, Japan authorities banned the use of chlordane in September 1986. In the last paper, the authors reported that both water and sediment of the rivers around Saga city were slightly contaminated with chlordane. In the present study, they investigated the levels of chlordane, oxychlordane and nonachlor in human adipose tissues.

Hirai, Yukio; Tomokuni, Katsumaro (Saga Medical School (Japan))

1991-08-01

176

Fully automated adipose tissue measurement on abdominal CT  

NASA Astrophysics Data System (ADS)

Obesity has become widespread in America and has been associated as a risk factor for many illnesses. Adipose tissue (AT) content, especially visceral AT (VAT), is an important indicator for risks of many disorders, including heart disease and diabetes. Measuring adipose tissue (AT) with traditional means is often unreliable and inaccurate. CT provides a means to measure AT accurately and consistently. We present a fully automated method to segment and measure abdominal AT in CT. Our method integrates image preprocessing which attempts to correct for image artifacts and inhomogeneities. We use fuzzy cmeans to cluster AT regions and active contour models to separate subcutaneous and visceral AT. We tested our method on 50 abdominal CT scans and evaluated the correlations between several measurements.

Yao, Jianhua; Sussman, Daniel L.; Summers, Ronald M.

2011-03-01

177

Coming home at last: dermal white adipose tissue.  

PubMed

The upper part of subcutaneous white adipose tissue (SWAT) is closely associated with the reticular dermis, surrounds hair follicles and is of great importance for a range of skin functions. In this issue of Experimental Dermatology, Driskell and colleagues propose a nomenclature in which the upper SWAT layer is renamed dermal WAT (DWAT), and its cells intradermal adipocytes. Some pros and cons are discussed below. PMID:24815604

Schneider, Marlon R

2014-09-01

178

Residue Analysis of Chlorinated Pesticides in Jordanian Human Adipose Tissues  

Microsoft Academic Search

To study the long-term environmental pollution in Jordan, thirty two adipose tissue samples were analysed for 15 Organochlorine Compounds using the capillary GC-ECD.The results were discussed in terms of clinical aspects and in terms of environmental and hygienic effects.To explain the sources of pollution, the major fat-containing food stuffs usually used in Jordan were analysed. It has been found that

M. A. Alawi; M. Ababneh

1991-01-01

179

Technical note: Alternatives to reduce adipose tissue sampling bias.  

PubMed

Understanding the mechanisms by which nutritional and pharmaceutical factors can manipulate adipose tissue growth and development in production animals has direct and indirect effects in the profitability of an enterprise. Adipocyte cellularity (number and size) is a key biological response that is commonly measured in animal science research. The variability and sampling of adipocyte cellularity within a muscle has been addressed in previous studies, but no attempt to critically investigate these issues has been proposed in the literature. The present study evaluated 2 sampling techniques (random and systematic) in an attempt to minimize sampling bias and to determine the minimum number of samples from 1 to 15 needed to represent the overall adipose tissue in the muscle. Both sampling procedures were applied on adipose tissue samples dissected from 30 longissimus muscles from cattle finished either on grass or grain. Briefly, adipose tissue samples were fixed with osmium tetroxide, and size and number of adipocytes were determined by a Coulter Counter. These results were then fit in a finite mixture model to obtain distribution parameters of each sample. To evaluate the benefits of increasing number of samples and the advantage of the new sampling technique, the concept of acceptance ratio was used; simply stated, the higher the acceptance ratio, the better the representation of the overall population. As expected, a great improvement on the estimation of the overall adipocyte cellularity parameters was observed using both sampling techniques when sample size number increased from 1 to 15 samples, considering both techniques' acceptance ratio increased from approximately 3 to 25%. When comparing sampling techniques, the systematic procedure slightly improved parameters estimation. The results suggest that more detailed research using other sampling techniques may provide better estimates for minimum sampling. PMID:25184847

Cruz, G D; Wang, Y; Fadel, J G

2014-10-01

180

Glucocorticoids and 11beta-Hydroxysteroid Dehydrogenase in Adipose Tissue  

Microsoft Academic Search

The highly prevalent metabolic syndrome (insulin resistance, type 2 diabetes, dyslipidemia, hypertension, along with abdominal obesity) resembles Cushing's syndrome. However, in simple obesity, plasma cortisol levels are not elevated. 11beta-hydroxysteroid dehydrogenase type 1 (11-HSD1), at least in mature adipocytes and hepatocytes, converts inactive circulating 11-keto steroids into active glucocorticoids, amplifying local glucocorticoid action. 11-HSD1 is elevated in adipose tissue in

JONATHAN R. SECKL; IK M. MORTON; K AREN E. CHAPMAN; BRIAN R. WALKER

2010-01-01

181

Studies on triacylglycerol ester hydrolase from bat adipose tissue  

Microsoft Academic Search

Triacylglycerol ester hydrolase was isolated from bat adipose tissue and characterized. The partially purified enzyme had\\u000a pH optimum of 8.6 and a Km value of 0.6 mM. The enzyme was denaturated upon freezing and thawing, which was prevented by 25% glycerol. The enzyme was\\u000a activated by EDTA and NaCl, while it was inhibited by serum and bovine serum albumin. Heparin,

Subhash S. Patil; Chanda K. Bhandari; Vijay A. Sawant

1983-01-01

182

Release of Inflammatory Mediators by Human Adipose Tissue Is Enhanced in Obesity and Primarily by the Nonfat Cells: A Review  

PubMed Central

This paper considers the role of putative adipokines that might be involved in the enhanced inflammatory response of human adipose tissue seen in obesity. Inflammatory adipokines [IL-6, IL-10, ACE, TGF?1, TNF?, IL-1?, PAI-1, and IL-8] plus one anti-inflammatory [IL-10] adipokine were identified whose circulating levels as well as in vitro release by fat are enhanced in obesity and are primarily released by the nonfat cells of human adipose tissue. In contrast, the circulating levels of leptin and FABP-4 are also enhanced in obesity and they are primarily released by fat cells of human adipose tissue. The relative expression of adipokines and other proteins in human omental as compared to subcutaneous adipose tissue as well as their expression in the nonfat as compared to the fat cells of human omental adipose tissue is also reviewed. The conclusion is that the release of many inflammatory adipokines by adipose tissue is enhanced in obese humans. PMID:20508843

Fain, John N.

2010-01-01

183

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues.  

PubMed

It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein ?, peroxisome proliferator-activated receptor ?, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent. PMID:23872146

Fujii, Masakazu; Inoguchi, Toyoshi; Batchuluun, Battsetseg; Sugiyama, Naonobu; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi

2013-08-16

184

Adipose tissue and adipocytes supports tumorigenesis and metastasis#  

PubMed Central

Adipose tissue influences tumor development in two major ways. First, obese individuals have a higher risk of developing certain cancers (endometrial, esophageal, and renal cell cancer). However, the risk of developing other cancers (melanoma, rectal, and ovarian) is not altered by body mass. In obesity, hypertrophied adipose tissue depots are characterized by a state of low grade inflammation. In this activated state, adipocytes and inflammatory cells secrete adipokines and cytokines which are known to promote tumor development. In addition, the adipocyte mediated conversion of androgens to estrogen specifically contributes to the development of endometrial cancer, which shows the greatest relative risk (6.3-fold) increase between lean and obese individuals. Second, many tumor types (gastric, breast, colon, renal, and ovarian) grow in the anatomical vicinity of adipose tissue. During their interaction with cancer cells, adipocytes dedifferentiate into pre-adipocytes or are reprogrammed into cancer-associated adipocytes (CAA). CAA secrete adipokines which stimulate the adhesion, migration, and invasion of tumor cells. Cancer cells and CAA also undergo a dynamic exchange of metabolites. Specifically, CAA release fatty acids through lipolysis which are then transferred to cancer cells and used for energy production through ?-oxidation. The abundant availability of lipids from adipocytes in the tumor microenvironment supports tumor progression and uncontrolled growth. Given that adipocytes are a major source of adipokines and energy for the cancer cell, understanding the mechanisms of metabolic symbiosis between cancer cells and adipocytes should reveal new therapeutic possibilities. PMID:23500888

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

2013-01-01

185

Deep Sequencing of the Transcriptome Reveals Inflammatory Features of Porcine Visceral Adipose Tissue  

PubMed Central

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. PMID:23781149

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

2013-01-01

186

Adipose tissue immune response: novel triggers and consequences for chronic inflammatory conditions.  

PubMed

Adipose tissue inflammation mediates the association between excessive body fat accumulation and several chronic inflammatory diseases. A high prevalence of obesity-associated adipose tissue inflammation was observed not only in patients with cardiovascular conditions but also in patients with inflammatory bowel diseases, abdominal aortic aneurysm, or cardiorenal syndrome. In addition to excessive caloric intake, other triggers promote visceral adipose tissue inflammation followed by chronic, low-grade systemic inflammation. The infiltration and accumulation of immune cells in the inflamed and hypertrophied adipose tissue promote the production of inflammatory cytokines, contributing to target organ damages. This comorbidity seems to delimit subgroups of individuals with systemic adipose tissue inflammation and more severe chronic inflammatory diseases that are refractory to conventional treatment. This review highlights the association between adipose tissue immune response and the pathophysiology of visceral adiposity-related chronic inflammatory diseases, while suggesting several new therapeutic strategies. PMID:24823865

Ghigliotti, Giorgio; Barisione, Chiara; Garibaldi, Silvano; Fabbi, Patrizia; Brunelli, Claudio; Spallarossa, Paolo; Altieri, Paola; Rosa, Gianmarco; Spinella, Giovanni; Palombo, Domenico; Arsenescu, Razvan; Arsenescu, Violeta

2014-08-01

187

Regulation of S100B in white adipose tissue by obesity in mice  

PubMed Central

S100B is a calcium binding protein found in adipose tissue; however, relatively little is known about the physiologic regulation or distribution of the protein within this organ. We examined plasma S100B concentration and white adipose tissue (WAT) s100b mRNA levels in lean and diet-induced obese (DIO) mice. Plasma S100B levels were increased by obesity. In WAT, s100b gene expression was also significantly increased by obesity and this increase was reversed following weight-loss. s100b gene expression was detected in both the adipocyte-enriched and stromal-vascular fractions of WAT; however, the increase in s100b gene expression in obese animals was only detected in the adipocyte-enriched fraction. Our results support published in vitro data indicating that WAT S100B may contribute to obesity-associated inflammation. PMID:25068089

Buckman, Laura B; Anderson-Baucum, Emily K; Hasty, Alyssa H; Ellacott, Kate LJ

2014-01-01

188

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

PubMed Central

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. PMID:24959194

2014-01-01

189

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

PubMed

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. PMID:24959194

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

2014-01-01

190

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

NASA Astrophysics Data System (ADS)

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.

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

2006-01-01

191

A new thiazolidinedione, NC-2100, which is a weak PPAR-gamma activator, exhibits potent antidiabetic effects and induces uncoupling protein 1 in white adipose tissue of KKAy obese mice.  

PubMed

Thiazolidinediones (TZDs) reduce insulin resistance in type 2 diabetes by increasing peripheral uptake of glucose, and they bind to and activate the transcriptional factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Studies have suggested that TZD-induced activation of PPAR-gamma correlates with antidiabetic action, but the mechanism by which the activated PPAR-gamma is involved in reducing insulin resistance is not known. To examine whether activation of PPAR-gamma directly correlates with antidiabetic activities, we compared the effects of 4 TZDs (troglitazone, pioglitazone, BRL-49653, and a new derivative, NC-2100) on the activation of PPAR-gamma in a reporter assay, transcription of the target genes, adipogenesis, plasma glucose and triglyceride levels, and body weight using obese KKAy mice. There were 10- to 30-fold higher concentrations of NC-2100 required for maximal activation of PPAR-gamma in a reporter assay system, and only high concentrations of NC-2100 weakly induced transcription of the PPAR-gamma but not PPAR-alpha target genes in a whole mouse and adipogenesis of cultured 3T3L1 cells, which indicates that NC-2100 is a weak PPAR-gamma activator. However, low concentrations of NC-2100 efficiently lowered plasma glucose levels in KKAy obese mice. These results strongly suggest that TZD-induced activation of PPAR-gamma does not directly correlate with antidiabetic (glucose-lowering) action. Furthermore, NC-2100 caused the smallest body weight increase of the 4 TZDs, which may be partly explained by the finding that NC-2100 efficiently induces uncoupling protein (UCP)-2 mRNA and significantly induces UCP1 mRNA in white adipose tissue (WAT). NC-2100 induced UCP1 efficiently in mesenteric WAT and less efficiently in subcutaneous WAT, although pioglitazone and troglitazone also slightly induced UCP1 only in mesenteric WAT. These characteristics of NC-2100 should be beneficial for humans with limited amounts of brown adipose tissue. PMID:10905484

Fukui, Y; Masui, S; Osada, S; Umesono, K; Motojima, K

2000-05-01

192

Thyroid hormone upregulates zinc-?2-glycoprotein production in the liver but not in adipose tissue.  

PubMed

Overproduction of zinc-?2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-?2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-?2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-?2-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-?2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-?2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-?2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-?2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-?2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-?2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-?2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-?2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-?2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-?2-glycoprotein expression in adipose tissue could be the reason why zinc-?2-glycoprotein is not related to weight loss in hyperthyroidism. PMID:24465683

Simó, Rafael; Hernández, Cristina; Sáez-López, Cristina; Soldevila, Berta; Puig-Domingo, Manel; Selva, David M

2014-01-01

193

Adiponutrin gene is regulated by insulin and glucose in human adipose tissue  

Microsoft Academic Search

Objective: Adiponutrin is a new transmembrane protein specifically expressed in adipose tissue. In obese subjects, short- or long-term calorie restriction diets were associated with a reduction in adiponutrin gene expression. Adiponut.rin mRNA level was previously shown to be negatively correlated with fasting glucose plasma levels and associated with insulin sensitivity of non-diabetic obese and non- obese subjects. The purpose of

Marthe Moldes; Genevieve Beauregard; Noel Peretti; Pierre-Henri Ducluzeau; Hubert Vidal; Karine Clement; R. Laennec; Marie Curie-Paris

2006-01-01

194

Effect of exercise training and dietary fat on rat adipose tissue lipolysis and morphology  

E-print Network

, 26) did not support the hypothesis that adipocyte proliferation can only be induced early in life. For instance, it has been Epinephrine Norepinephnne ACTH TSH Glucagon Insulin Nicotinic acid Receptors Adenylate Cyclase Complex... theophylline Triglycerides Protein Kinase HSL Glycerol Free-tattY acid Fig. 1 Representation of metabolic steps involved in the control of lipolysis in adipose tissue in rats. ACTH (adrenocorticotropic), TSH (thyroid stimulated hormone), PGE 1...

Neale, Sonia Barstad

2012-06-07

195

Adipose tissue in muscle: a novel depot similar in size to visceral adipose tissue1-3  

Microsoft Academic Search

Background: The manner in which fat depot volumes and distri- butions, particularly the adipose tissue (AT) between the muscles, vary by race is unknown. Objective:Theobjectivewastoquantifyapreviouslyunstudiedand novel intermuscular AT (IMAT) depot and subcutaneous AT, vis- ceral AT (VAT), and total-body skeletal muscle mass in healthy sedentary African American (AA), Asian, and white adults by whole-body magnetic resonance imaging. IMAT is the

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

196

Regulation of glucose homoeostasis by brown adipose tissue.  

PubMed

Brown adipose tissue (BAT) has emerged as a therapeutic target for the treatment of obesity. Activation of BAT in human beings could also have beneficial metabolic effects that might resolve common complications of obesity, such as type 2 diabetes, by ameliorating the glucolipotoxic pathological changes that underlie the development of peripheral insulin resistance and impaired insulin secretion due to pancreatic ?-cell failure. Evidence from rodent models suggests that BAT activation improves glucose homoeostasis through several mechanisms, which could point to new strategies to optimise stimulation of BAT in human beings and reverse insulin resistance in peripheral tissues. PMID:24622420

Peirce, Vivian; Vidal-Puig, Antonio

2013-12-01

197

Cellular mechanisms regulating fuel metabolism in mammals: role of adipose tissue and lipids during prolonged food deprivation  

PubMed Central

Food deprivation in mammals results in profound changes in fuel metabolism and substrate regulation. Among these changes are decreased reliance on the counter-regulatory dynamics by insulin-glucagon due to reduced glucose utilization, and increased concentrations of lipid substrates in plasma to meet the energetic demands of peripheral tissues. As the primary storage site of lipid substrates, adipose tissue must then be a primary contributor to the regulation of metabolism in food deprived states. Through its regulation of lipolysis, adipose tissue influences the availability of carbohydrate, lipid, and protein substrates. Additionally, lipid substrates can act as ligands to various nuclear receptors (retinoid x receptor (RXR), liver x receptor (LXR), and peroxisome proliferator-activated receptor (PPAR)) and exhibit prominent regulatory capabilities over the expression of genes involved in substrate metabolism within various tissues. Therefore, through its control of lipolysis, adipose tissue also indirectly regulates the utilization of metabolic substrates within peripheral tissues. In this review, these processes are described in greater detail and the extent to which adipose tissue and lipid substrates regulate metabolism in food deprived mammals is explored with comments on future directions to better assess the contribution of adipose tissue to metabolism. PMID:23357530

Viscarra, Jose Abraham; Ortiz, Rudy Martin

2013-01-01

198

The adipose tissue production of adiponectin is increased in end-stage renal disease.  

PubMed

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6?mg/ml in cases compared with 8.4?mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis factor ?, interleukin 6, and high-sensitivity C-reactive protein were significantly higher in cases compared with controls. Adiponectin mRNA and protein expression in visceral and subcutaneous fat were significantly higher in cases than controls, while adiponectin receptor-1 mRNA expression was significantly increased in peripheral blood cells, muscle, and adipose tissue in cases compared with controls. Thus, our study suggests that adipose tissue production of adiponectin contributes to the high plasma levels seen in end-stage renal disease. PMID:23283133

Martinez Cantarin, Maria P; Waldman, Scott A; Doria, Cataldo; Frank, Adam M; Maley, Warren R; Ramirez, Carlo B; Keith, Scott W; Falkner, Bonita

2013-03-01

199

The adipose tissue production of adiponectin is increased in end stage renal disease  

PubMed Central

Adiponectin has anti-diabetic properties and patients with obesity, diabetes and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end stage renal disease. Here we determine if adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared to 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis factor ?, interleukin 6 and high sensitivity C-reactive protein were significantly higher in cases compared to controls. Adiponectin mRNA and protein expression in visceral and subcutaneous fat was significantly higher in cases than controls while adiponectin receptor 1 mRNA expression was significantly increased in peripheral blood cells, muscle and adipose tissue in cases compared to controls. Thus, our study suggests that adipose tissue production of adiponectin contributes to the high plasma levels seen in end stage renal disease. PMID:23283133

Cantarin, Maria P Martinez; Waldman, Scott; Doria, Cataldo; Frank, Adam M.; Maley, Warren R.; Ramirez, Carlo B.; Keith, Scott W.; Falkner, Bonita

2012-01-01

200

Adjustment of directly measured adipose tissue volume in infants  

PubMed Central

Background: Direct measurement of adipose tissue (AT) using magnetic resonance imaging is increasingly used to characterise infant body composition. Optimal techniques for adjusting direct measures of infant AT remain to be determined. Objectives: To explore the relationships between body size and direct measures of total and regional AT, the relationship between AT depots representing the metabolic load of adiposity and to determine optimal methods of adjusting adiposity in early life. Design: Analysis of regional AT volume (ATV) measured using magnetic resonance imaging in longitudinal and cross-sectional studies. Subjects: Healthy term infants; 244 in the first month (1–31 days), 72 in early infancy (42–91 days). Methods: The statistical validity of commonly used indices adjusting adiposity for body size was examined. Valid indices, defined as mathematical independence of the index from its denominator, to adjust ATV for body size and metabolic load of adiposity were determined using log-log regression analysis. Results: Indices commonly used to adjust ATV are significantly correlated with body size. Most regional AT depots are optimally adjusted using the index ATV/(height)3 in the first month and ATV/(height)2 in early infancy. Using these indices, height accounts for<2% of the variation in the index for almost all AT depots. Internal abdominal (IA) ATV was optimally adjusted for subcutaneous abdominal (SCA) ATV by calculating IA/SCA0.6. Conclusions: Statistically optimal indices for adjusting directly measured ATV for body size are ATV/height3 in the neonatal period and ATV/height2 in early infancy. The ratio IA/SCA ATV remains significantly correlated with SCA in both the neonatal period and early infancy; the index IA/SCA0.6 is statistically optimal at both of these ages. PMID:24662695

Gale, C; Santhakumaran, S; Wells, J C K; Modi, N

2014-01-01

201

Treatment with a SOD mimetic reduces visceral adiposity, adipocyte death and adipose tissue inflammation in high fat fed mice  

PubMed Central

Objective Obesity is associated with enhanced reactive oxygen species (ROS) accumulation in adipose tissue. However, a causal role for ROS in adipose tissue expansion after high fat feeding is not established. The aim of this study is to investigate the effect of the cell permeable superoxide dismutase mimetic and peroxynitrite scavenger Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) on adipose tissue expansion and remodeling in response to high fat diet (HFD) in mice. Design and Methods Male C57BL/6j mice were fed normal chow or high fat diet (HFD) and treated with saline or MnTBAP for 5 weeks. The effects of MnTBAP on body weights, whole body energy expenditure, adipose tissue morphology and gene expression were determined. Results MnTBAP attenuated weight gain and adiposity through a reduction in adipocyte hypertrophy, adipogenesis and fatty acid uptake in epididymal (eWAT) but not in inguinal (iWAT) white adipose tissue. Furthermore, MnTBAP reduced adipocyte death and inflammation in eWAT and diminished circulating levels of free fatty acids and leptin. Despite these improvements, the development of systemic insulin resistance and diabetes after HFD was not prevented with MnTBAP treatment. Conclusions Taken together, these data suggest a causal role for ROS in the development of diet-induced visceral adiposity but not in the development of insulin resistance and type 2 diabetes. PMID:23526686

Pires, Karla M.; Ilkun, Olesya; Valente, Marina; Boudina, Sihem

2013-01-01

202

Limitations of Ractopamine to Affect Adipose Tissue Metabolism in Swine  

Microsoft Academic Search

ABSTRACT: To determine,the temporal,effect of ractopamine (Rac), a phenethanolamine, on adipose lipogenic enzyme activity and gene expression, 20 crossbred barrows,were fed Rac (20 mgkg,of diet) for 0, 1, 8, or 24 d before slaughter (105 & 1 kg). Ractopamine,had no effect , Rac, and,P-adrenoceptor down-regulation. Key Words: Ractopamine, Lipogenesis, Acetyl-coA Carboxylase, Pigs, Glucose Transport Proteins

C. Y. Liu; A. L. Grant; K. H. Kim; S. Q. Ji; D. L. Hancock; D. B. Anderson; S. E. Mills

203

Adipose tissue and vascular inflammation in coronary artery disease  

PubMed Central

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. PMID:25068015

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

2014-01-01

204

Levels of Persistent Organic Pollutant Residues in Human Adipose and Muscle Tissues in Singapore  

Microsoft Academic Search

Persistent organic pollutants (POPs), due to their persistence and bioconcentration in lipid-rich tissue, bioaccumulate in food chains, resulting in elevated concentrations in humans. This study was performed to determine and compare levels of POPs in human adipose and muscle tissues in the female population of Singapore. In total, 36 human adipose tissues and 8 human muscle tissues were collected from

Qing Qing Li; Annamalai Loganath; Yap Seng Chong; Jing Tan; Jeffrey Philip Obbard

2006-01-01

205

Identification of Macrophage Migration Inhibitory Factor in Adipose Tissue and Its Induction by Tumor Necrosis Factor-?  

Microsoft Academic Search

Macrophage migration inhibitory factor (MIF) has been rediscovered as a proinflammatory cytokine, pituitary hormone, and glucocorticoid-induced immunoregulator. A survey of tissue distribution revealed that MIF expression is not limited to T lymphocytes, but exists in several other tissues; however, its presence in adipose tissue has never been investigated. In this study, we examined the expression of MIF in adipose tissue

Junichi Hirokawa; Shinji Sakaue; Seiichi Tagami; Yoshikazu Kawakami; Masaharu Sakai; Shinzo Nishi; Jun Nishihira

1997-01-01

206

Unequivocal Identification of Brown Adipose Tissue in a Human Infant  

PubMed Central

We report the unique depiction of brown adipose tissue (BAT) by MRI and computed tomography (CT) in a human three month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and X-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and non-shivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties. PMID:22180228

Hu, Houchun H.; Tovar, Jason; Pavlova, Zdena; Smith, Michelle L.; Gilsanz, Vicente

2011-01-01

207

?1B adaptin regulates adipogenesis by mediating the sorting of sortilin in adipose tissue.  

PubMed

Here, we describe altered sorting of sortilin in adipocytes deficient for the ?1B-containing AP-1 complex, leading to the inhibition of adipogenesis. The AP-1 complex mediates protein sorting between the trans-Golgi network and endosomes. Vertebrates express three AP1 ?1 subunit isoforms - ?1A, ?1B and ?1C (also known as AP1S1, AP1S2 and AP1S3, respectively). ?1B-deficient mice display impaired recycling of synaptic vesicles and lipodystrophy. Here, we show that sortilin is overexpressed in adipose tissue from ?1B(-/-) mice, and that its overexpression in wild-type cells is sufficient to suppress adipogenesis. ?1B-specific binding of sortilin requires the sortilin DxxD-x12-DSxxxL motif. ?1B deficiency does not lead to a block of sortilin transport out of a specific organelle, but the fraction that reaches lysosomes is reduced. Sortilin binds to the receptor DLK1, an inhibitor of adipocyte differentiation, and the overexpression of sortilin prevents DLK1 downregulation, leading to enhanced inhibition of adipogenesis. DLK1 and sortilin expression are not increased in the brain tissue of ?1B(-/-) mice, although this is the tissue with the highest expression of ?1B and sortilin. Thus, adipose-tissue-specific and ?1B-dependent routes for the transport of sortilin exist and are involved in the regulation of adipogenesis and adipose-tissue mass. PMID:24928897

Baltes, Jennifer; Larsen, Jakob Vejby; Radhakrishnan, Karthikeyan; Geumann, Constanze; Kratzke, Manuel; Petersen, Claus Munck; Schu, Peter

2014-08-15

208

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  

PubMed Central

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. PMID:24871103

Lancha, Andoni; Rodriguez, Amaia; Catalan, Victoria; Becerril, Sara; Sainz, Neira; Ramirez, Beatriz; Burrell, Maria A.; Salvador, Javier; Fruhbeck, Gema; Gomez-Ambrosi, Javier

2014-01-01

209

Weight Cycling Enhances Adipose Tissue Inflammatory Responses in Male Mice  

PubMed Central

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. PMID:22848362

Barbosa-da-Silva, Sandra; Fraulob-Aquino, Julio C.; Lopes, Jessica R.; Mandarim-de-Lacerda, Carlos A.; Aguila, Marcia B.

2012-01-01

210

Evaluation of macrophage plasticity in brown and white adipose tissue.  

PubMed

There are still questions about whether macrophage differentiation is predetermined or is induced in response to tissue microenvironments. C2D macrophage cells reside early in the macrophage lineage in vitro, but differentiate to a more mature phenotype after adoptive transfer to the peritoneal cavity (PEC-C2D). Since C2D macrophage cells also traffic to adipose tissue after adoptive transfer, we explored the impact of white adipose tissue (WAT), brown adipose tissue (BAT) and in vitro cultured adipocytes on C2D macrophage cells. When PEC-C2D macrophage cells were cultured with preadipocytes the cells stretched out and CD11b and Mac-2 expression was lower compared to PEC-C2D macrophage cells placed in vitro alone. In contrast, PEC-C2D cells co-cultured with adipocytes maintained smaller, round morphology and more cells expressed Mac-2 compared to PEC-C2D co-cultured with preadipocytes. After intraperitoneal injection, C2D macrophage cells migrated into both WAT and BAT. A higher percentage of C2D macrophage cells isolated from WAT (WAT-C2D) expressed Ly-6C (33%), CD11b (11%), Mac-2 (11%) and F4/80 (29%) compared to C2D macrophage cells isolated from BAT (BAT-C2D). Overall, BAT-C2D macrophage cells had reduced expression of many cytokine, chemokine and receptor gene transcripts when compared to in vitro grown C2D macrophages, while WAT-C2D macrophage cells and PEC-C2D up-regulated many of these gene transcripts. These data suggest that the C2D macrophage phenotype can change rapidly and distinct phenotypes are induced by different microenvironments. PMID:21757190

Ortega, M Teresa; Xie, Linglin; Mora, Silvia; Chapes, Stephen K

2011-01-01

211

Diversity of lipid mediators in human adipose tissue depots  

PubMed Central

Adipose tissue is a heterogeneous organ with remarkable variations in fat cell metabolism depending on the anatomical location. However, the pattern and distribution of bioactive lipid mediators between different fat depots and their relationships in complex diseases have not been investigated. Using LC-MS/MS-based metabolo-lipidomics, here we report that human subcutaneous (SC) adipose tissues possess a range of specialized proresolving mediators (SPM) including resolvin (Rv) D1, RvD2, protectin (PD) 1, lipoxin (LX) A4, and the monohydroxy biosynthetic pathway markers of RvD1 and PD1 (17-HDHA), RvE1 (18-HEPE), and maresin 1 (14-HDHA). The “classic” eicosanoids prostaglandin (PG) E2, PGD2, PGF2?, leukotriene (LT) B4, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE were also identified in SC fat. SC fat from patients with peripheral vascular disease (PVD) exhibited a marked deficit in PD1 and 17-HDHA levels. Compared with SC, perivascular adipose tissue displayed higher SPM levels, suggesting an enhanced resolution capacity in this fat depot. In addition, augmented levels of eicosanoids and SPM were observed in SC fat surrounding foot wounds. Notably, the profile of SC PGF2? differed significantly when patients were grouped by body mass index (BMI). In the case of peri-wound SC fat, BMI negatively correlated with PGE2. In this tissue, proresolving mediators RvD2 and LXA4 were identified in lower levels than the proinflammatory LTB4. Collectively, these findings demonstrate a diverse distribution of bioactive lipid mediators depending on the localization of human fat depots and uncover a specific SPM pattern closely associated with PVD. PMID:23364264

Clària, Joan; Nguyen, Binh T.; Madenci, Arin L.; Ozaki, C. Keith

2013-01-01

212

Diversity of lipid mediators in human adipose tissue depots.  

PubMed

Adipose tissue is a heterogeneous organ with remarkable variations in fat cell metabolism depending on the anatomical location. However, the pattern and distribution of bioactive lipid mediators between different fat depots and their relationships in complex diseases have not been investigated. Using LC-MS/MS-based metabolo-lipidomics, here we report that human subcutaneous (SC) adipose tissues possess a range of specialized proresolving mediators (SPM) including resolvin (Rv) D1, RvD2, protectin (PD) 1, lipoxin (LX) A4, and the monohydroxy biosynthetic pathway markers of RvD1 and PD1 (17-HDHA), RvE1 (18-HEPE), and maresin 1 (14-HDHA). The "classic" eicosanoids prostaglandin (PG) E?, PGD?, PGF2?, leukotriene (LT) B?, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE were also identified in SC fat. SC fat from patients with peripheral vascular disease (PVD) exhibited a marked deficit in PD1 and 17-HDHA levels. Compared with SC, perivascular adipose tissue displayed higher SPM levels, suggesting an enhanced resolution capacity in this fat depot. In addition, augmented levels of eicosanoids and SPM were observed in SC fat surrounding foot wounds. Notably, the profile of SC PGF2? differed significantly when patients were grouped by body mass index (BMI). In the case of peri-wound SC fat, BMI negatively correlated with PGE?. In this tissue, proresolving mediators RvD2 and LXA? were identified in lower levels than the proinflammatory LTB?. Collectively, these findings demonstrate a diverse distribution of bioactive lipid mediators depending on the localization of human fat depots and uncover a specific SPM pattern closely associated with PVD. PMID:23364264

Clària, Joan; Nguyen, Binh T; Madenci, Arin L; Ozaki, C Keith; Serhan, Charles N

2013-06-15

213

Two types of brown adipose tissue in humans.  

PubMed

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. PMID:24575372

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

2014-01-01

214

Quantifying size and number of adipocytes in adipose tissue.  

PubMed

White adipose tissue (WAT) is a dynamic and modifiable tissue that develops late during gestation in humans and through early postnatal development in rodents. WAT is unique in that it can account for as little as 3% of total body weight in elite athletes or as much as 70% in the morbidly obese. With the development of obesity, WAT undergoes a process of tissue remodeling in which adipocytes increase in both number (hyperplasia) and size (hypertrophy). Metabolic derangements associated with obesity, including type 2 diabetes, occur when WAT growth through hyperplasia and hypertrophy cannot keep pace with the energy storage needs associated with chronic energy excess. Accordingly, hypertrophic adipocytes become overburdened with lipids, resulting in changes in the secreted hormonal milieu. Lipids that cannot be stored in the engorged adipocytes become ectopically deposited in organs such as the liver, muscle, and pancreas. WAT remodeling therefore coincides with obesity and secondary metabolic diseases. Obesity, however, is not unique in causing WAT remodeling: changes in adiposity also occur with aging, calorie restriction, cancers, and diseases such as HIV infection. In this chapter, we describe a semiautomated method of quantitatively analyzing the histomorphometry of WAT using common laboratory equipment. With this technique, the frequency distribution of adipocyte sizes across the tissue depot and the number of total adipocytes per depot can be estimated by counting as few as 100 adipocytes per animal. In doing so, the method described herein is a useful tool for accurately quantifying WAT development, growth, and remodeling. PMID:24480343

Parlee, Sebastian D; Lentz, Stephen I; Mori, Hiroyuki; MacDougald, Ormond A

2014-01-01

215

Two types of brown adipose tissue in humans  

PubMed Central

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. PMID:24575372

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

2014-01-01

216

Ceruloplasmin Is a Novel Adipokine Which Is Overexpressed in Adipose Tissue of Obese Subjects and in Obesity-Associated Cancer Cells  

PubMed Central

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 to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity. For this purpose expression data from human adipose tissue of obese and non-obese as well as from a large panel of human cancer cell lines and corresponding primary cells and tissues were explored. We found expression of ceruloplasmin to be the most enriched in obesity-associated cancer cells. This gene was also significantly up-regulated in adipose tissue of obese subjects. Ceruloplasmin is the body's main copper carrier and is involved in angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is produced and secreted at increased rates in obesity. In the obese state, adipose tissue contributed markedly (up to 22%) to the total circulating protein level. In summary, we have through bioinformatic screening identified ceruloplasmin as a novel adipokine with increased expression in adipose tissue of obese subjects as well as in cells from obesity-associated cancers. Whether there is a causal relationship between adipose overexpression of ceruloplasmin and cancer development in obesity cannot be answered by these cross-sectional comparisons. PMID:24676332

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

2014-01-01

217

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

PubMed

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 to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity. For this purpose expression data from human adipose tissue of obese and non-obese as well as from a large panel of human cancer cell lines and corresponding primary cells and tissues were explored. We found expression of ceruloplasmin to be the most enriched in obesity-associated cancer cells. This gene was also significantly up-regulated in adipose tissue of obese subjects. Ceruloplasmin is the body's main copper carrier and is involved in angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is produced and secreted at increased rates in obesity. In the obese state, adipose tissue contributed markedly (up to 22%) to the total circulating protein level. In summary, we have through bioinformatic screening identified ceruloplasmin as a novel adipokine with increased expression in adipose tissue of obese subjects as well as in cells from obesity-associated cancers. Whether there is a causal relationship between adipose overexpression of ceruloplasmin and cancer development in obesity cannot be answered by these cross-sectional comparisons. PMID:24676332

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

2014-01-01

218

Up-regulation of the Sirtuin 1 (Sirt1) and Peroxisome Proliferator-activated Receptor ? Coactivator-1? (PGC-1?) Genes in White Adipose Tissue of Id1 Protein-deficient Mice: IMPLICATIONS IN THE PROTECTION AGAINST DIET AND AGE-INDUCED GLUCOSE INTOLERANCE.  

PubMed

Id1, a helix-loop-helix (HLH) protein that inhibits the function of basic HLH E protein transcription factors in lymphoid cells, has been implicated in diet- and age-induced obesity by unknown mechanisms. Here we show that Id1-deficient mice are resistant to a high fat diet- and age-induced obesity, as revealed by reduced weight gain and body fat, increased lipid oxidation, attenuated hepatosteatosis, lower levels of lipid droplets in brown adipose tissue, and smaller white adipocytes after a high fat diet feeding or in aged animals. Id1 deficiency improves glucose tolerance, lowers serum insulin levels, and reduces TNF? gene expression in white adipose tissue. Id1 deficiency also increased expression of Sirtuin 1 and peroxisome proliferator-activated receptor ? coactivator 1?, regulators of mitochondrial biogenesis and energy expenditure, in the white adipose tissue. This effect was accompanied by the elevation of several genes encoding proteins involved in oxidative phosphorylation and fatty acid oxidation, such as cytochrome c, medium-chain acyl-CoA dehydrogenase, and adipocyte protein 2. Moreover, the phenotype for Id1 deficiency was similar to that of mice expressing an E protein dominant-positive construct, ET2, suggesting that the balance between Id and E proteins plays a role in regulating lipid metabolism and insulin sensitivity. PMID:25190816

Zhao, Ying; Ling, Flora; Griffin, Timothy M; He, Ting; Towner, Rheal; Ruan, Hong; Sun, Xiao-Hong

2014-10-17

219

Expression and functional analysis of Krüppel-like factor 2 in chicken adipose tissue.  

PubMed

Studies in mammalian species showed that Krüppel-like factor 2 (KLF2) regulates adipogenesis. However, its role in birds is unclear. The objective of the current study was to explore the expression and function of KLF2 in chicken adipogenesis. Results showed that chicken KLF2 (Gallus gallus KLF2 [gKLF2]) was greatly expressed in abdominal adipose tissue, and its transcripts fluctuated during adipose tissue development. In addition, gKLF2 transcripts in abdominal adipose tissue of lean broilers were greater at 1 wk of age but lower at 3, 5, and 8 wk of age than those in fat broilers (P < 0.05). The gKLF2 was more greatly expressed in preadipocytes than in mature adipocytes (P < 0.05), and its expression level decreased during the preadipocyte differentiation in vitro (P < 0.05). The functional analysis showed that gKLF2 overexpression inhibited chicken preadipocyte differentiation (P < 0.05), accompanied by the reduced expression of CCAAT/enhancer binding protein ? (C/EBP?) and peroxisome proliferator-activated receptor ? (PPAR?) and the elevated expression of GATA binding protein 2 (GATA2). Additionally, the luciferase reporter assays showed that gKLF2 overexpression suppressed the promoter activities of chicken C/EBP? and PPAR? (P < 0.05). In conclusion, our results indicated that gKLF2 inhibits chicken adipogenesis, at least in part, through inhibition of PPAR? and C/EBP? expression. PMID:25349335

Zhang, Z W; Rong, E G; Shi, M X; Wu, C Y; Sun, B; Wang, Y X; Wang, N; Li, H

2014-11-01

220

Profilin-1 haploinsufficiency protects against obesity-associated glucose intolerance and preserves adipose tissue immune homeostasis.  

PubMed

Metabolic inflammation may contribute to the pathogenesis of obesity and its comorbidities, including type 2 diabetes and cardiovascular disease. Previously, we showed that the actin-binding protein profilin-1 (pfn) plays a role in atherogenesis because pfn heterozygote mice (PfnHet) exhibited a significant reduction in atherosclerotic lesion burden and vascular inflammation. In the current study, we tested whether pfn haploinsufficiency would also limit diet-induced adipose tissue inflammation and insulin resistance (IR). First, we found that a high-fat diet (HFD) upregulated pfn expression in epididymal and subcutaneous white adipose tissue (WAT) but not in the liver or muscle of C57BL/6 mice compared with normal chow. Pfn expression in WAT correlated with F4/80, an established marker for mature macrophages. Of note, HFD elevated pfn protein levels in both stromal vascular cells and adipocytes of WAT. We also found that PfnHet were significantly protected from HFD-induced glucose intolerance observed in pfn wild-type mice. With HFD, PfnHet displayed blunted expression of systemic and WAT proinflammatory cytokines and decreased accumulation of adipose tissue macrophages, which were also preferentially biased toward an M2-like phenotype; this correlated with preserved frequency of regulatory T cells. Taken together, the findings indicate that pfn haploinsufficiency protects against diet-induced IR and inflammation by modulating WAT immune homeostasis. PMID:23884883

Romeo, Giulio R; Pae, Munkyong; Eberlé, Delphine; Lee, Jongsoon; Shoelson, Steven E

2013-11-01

221

Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats  

Microsoft Academic Search

Background  Menopause is associated with increased adiposity, especially increased deposition of intra-abdominal (IA) adipose tissue (AT).\\u000a This differs from common or 'dietary' obesity, i.e., obesity apparently due to environmentally stimulated overeating, in which\\u000a IAAT and subcutaneous (S) AT increase in similar proportions. The effect of menopause on adiposity is thought to be due to\\u000a the decreased secretion of ovarian estrogens. Ovariectomy

Viktoria Gloy; Wolfgang Langhans; Jacquelien JG Hillebrand; Nori Geary; Lori Asarian

2011-01-01

222

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

PubMed

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. PMID:23780289

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

223

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

PubMed Central

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 pre-invasive 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. PMID:23780289

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.

2013-01-01

224

Is adipose tissue oversold as a health risk?  

PubMed

A high percentage of body fat is considered to be the primary cause of risks associated with high body weight. Yet body fat content per se may not cause the risks. The contribution of obesity to risks may be because overfilled adipose tissue cannot remove offending substances from circulation. The ability to remove excess glucose, lipids, and offending materials from circulation, not the amount of body fat, may be the important factor. People with large, partially filled adipose depots may have less risk than people with small, but filled adipose depots. This concept is supported by many studies. Energy restriction in genetically obese animals greatly increases longevity and slows signs of aging even while the animals remain obese. Weight reduction often corrects weight-associated medical problems in obese persons without returning body-fat levels to normal. Statistically generated desirable body-fat contents or desirable height-weight tables may have little meaning for individuals and may cause more harm than good. Because these standards are not appropriate for some people, they should be discarded as a guide for all. More emphasis should be placed on healthy lifestyles and less on body-fat percentages. PMID:8195553

Abernathy, R P; Black, D R

1994-06-01

225

Regulatory sequence elements of mouse GLUT4 gene expression in adipose tissues  

Microsoft Academic Search

Ablation of GLUT4 in adipose tissues results in whole body insulin resistance and high-fat feeding down-regulates GLUT4 mRNA in white adipose tissues. Previous studies demonstrated that adipose tissue specific element(s) (ASE) of the murine GLUT4 gene is located between ?551 and ?442 relative to transcription start site and that high-fat responsive element(s) (HFRE) for down-regulation of the GLUT4 gene is

Shinji Miura; Nobuyo Tsunoda; Shinobu Ikeda; Yuko Kai; Misaki Ono; Kayo Maruyama; Mayumi Takahashi; Keiji Mochida; Junichiro Matsuda; Osamu Ezaki

2003-01-01

226

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

PubMed Central

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 ?m in aerodynamic diameter; PM2.5) 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. PMID:21745393

2011-01-01

227

Brown Adipose Tissue in the Buccal Fat Pad during Infancy  

PubMed Central

Background The buccal fat pad (BFP) is an encapsulated mass of adipose tissue thought to enhance the sucking capabilities of the masticatory muscles during infancy. To date, no conclusive evidence has been provided as to the composition of the BFP in early postnatal life. Objective The purpose of this study was to examine whether the BFP of neonates and infants is primarily composed of white adipose tissue (WAT) or brown adipose tissue (BAT). Materials and Methods The percentage of fat in the BFP in 32 full-term infants (16 boys and 16 girls), aged one day to 10.6 months, was measured using magnetic resonance imaging (MRI) determinations of fat fraction. Results BFP fat fraction increased with age (r?=?0.67; P<.0001) and neonates had significantly lower values when compared to older infants; 72.6±9.6 vs. 91.8±2.4, P<.0001. Multiple regression analysis indicated that the age-dependent relationship persisted after accounting for gender, gestational age, and weight percentile (P?=?.001). Two subjects (aged one and six days) depicted a change in the MRI characteristics of the BFP from primarily BAT to WAT at follow-up examinations two to six weeks later, respectively. Histological post-mortem studies of a 3 day and 1.1 month old revealed predominantly BAT and WAT in the BFP, respectively. Conclusion The BFP is primarily composed of BAT during the first weeks of life, but of WAT thereafter. Studies are needed to investigate the contributions of BAT in the BFP to infant feeding and how it is altered by postnatal nutrition. PMID:24586852

Ponrartana, Skorn; Patil, Shilpa; Aggabao, Patricia C.; Pavlova, Zdena; Devaskar, Sherin U.; Gilsanz, Vicente

2014-01-01

228

Adipose tissue distribution in relation to insulin sensitivity and inflammation in Pakistani and Norwegian subjects with type 2 diabetes.  

PubMed

Abstract Immigrants from South Asia to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM) associated with obesity. We investigated the relationship between diabetes and adipose tissue distribution in a group of younger T2DM subjects from Norway and Pakistan. Eighteen immigrant Pakistani and 21 Norwegian T2DM subjects (age 29-45, 49% men) were included. They underwent anthropometrical measurements including bioelectrical impedance analysis, CT scans measuring fatty infiltration in liver and adipose and muscle tissue compartments in mid-abdomen and thigh, a euglycemic clamp, and blood samples for serum insulin and plasma glucose, adipokines and inflammation markers. Adipose tissue distribution was similar in Norwegians and Pakistanis. Pakistanis, but not Norwegians, showed a negative correlation between insulin sensitivity and visceral adipose tissue (VAT, rs = - 0.704, p = 0.003). Subcutaneous adipose tissue (SAT) correlated to leptin in both Pakistanis and Norwegians (rs = 0.88, p < 0.001 and 0.67, p = 0.001). SAT also correlated to C-reactive protein (CRP) in the Pakistanis only (rs = 0.55, p = 0.03), and superficial SAT to Interleukin-1 receptor antagonist (IL-1RA) in Norwegians only (rs = 0.47, p = 0.04). In conclusion, despite similar adipose tissue distribution in the two groups Pakistanis were more insulin resistant, with a negative correlation of VAT to insulin sensitivity, not present in Norwegians. The correlation of adipose tissue to Leptin, CRP and IL-1RA showed ethnic differences. PMID:25223599

Wium, Cecilie; Eggesbø, Heidi B; Ueland, Thor; Michelsen, Annika E; Torjesen, Peter A; Aukrust, Pål; Birkeland, Kåre

2014-11-01

229

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

PubMed

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. PMID:21901024

Odegaard, Andrew O; Choh, Audrey C; Czerwinski, Stefan A; Towne, Bradford; Demerath, Ellen W

2012-03-01

230

Adipose tissue lipogenic gene networks due to lipid feeding and milk fat depression in lactating cows.  

PubMed

Dietary lipid supplements have been extensively evaluated for their effects on mammary tissue mRNA abundance, including the classical lipogenic genes ACACA, SCD, FASN, and the transcription regulators SREBF1, THRSP, and PPARG. Novel gene isoforms with key regulatory roles in triacylglycerol synthesis have been recently identified including LPIN1 and AGPAT6. Transcriptional networks (i.e., genes whose mRNA expression is regulated by a transcription factor or nuclear receptor) coordinate adipogenesis and lipid filling in nonruminant adipose tissue. To investigate whether long-term milk fat depression affects adipogenic networks in subcutaneous adipose tissue, we characterized mRNA expression via quantitative PCR of 20 genes in cows fed saturated and polyunsaturated lipid for 3 wk. Adipose tissue from cows fed a control diet, control with fish (10 g/kg of dry matter) and soybean oil (25 g/kg of dry matter) (FSO), or control with saturated lipid (35 g/kg, EB100; Energy Booster 100, Milk Specialties, Dundee, IL) was biopsied after 21 d of feeding. Milk production did not differ across treatments (averaged 32 kg +/- 2.8 kg/d during the 21 d) but dry matter intake (DMI) decreased in cows fed FSO versus controls (averaged 18 vs. 22 kg/d during the 21 d). Despite the decrease in DMI, FSO resulted in similar energy intake as EB100 during the last 2 wk of the study. Cows fed FSO had a gradual decline in milk fat and energy yield leading to an overall 25% decrease in milk fat yield during the study (averaged 0.90 vs. 1.2 kg/d) compared with control or EB100. Thus, during the 21-d study, FSO led to a gradual increase in intake energy available for adipose tissue deposition. Relative mRNA expression of LPL and SCD as well as ADFP (coding for a protein involved in lipid droplet formation) and LPIN1 (coding for a protein involved in diacylglycerol synthesis/transcriptional regulation) was upregulated with FSO relative to other diets. Expression of the transcription regulator THRSP tended to be greater in cows fed FSO. Overall, results suggest that long-term milk fat depression caused by feeding FSO provided additional energy as well as long-chain fatty acids that, coupled with upregulation of a subset of adipogenic genes in subcutaneous adipose tissue, might have resulted in greater tissue lipid deposition. PMID:19700689

Thering, B J; Graugnard, D E; Piantoni, P; Loor, J J

2009-09-01

231

Netrin-1 promotes adipose tissue macrophage accumulation and insulin resistance in obesity  

PubMed Central

During obesity, macrophage accumulation in adipose tissue propagates the chronic inflammation and insulin resistance associated with type 2 diabetes. The factors that regulate the accrual of macrophages in adipose are not well understood. Here we show that the neuroimmune guidance cue netrin-1 is highly expressed in obese, but not lean adipose tissue of humans and mice, where it directs the retention of macrophages. Expression of netrin-1 is induced in macrophages by the saturated fatty acid palmitate, and acts via its receptor Unc5b to block macrophage migration. In a mouse model of diet-induced obesity, we show that adipose tissue macrophages exhibit reduced migratory capacity, which can be restored by blocking netrin-1. Furthermore, hematopoietic deletion of Ntn1 facilitates adipose tissue macrophage emigration, reduces inflammation, and improves insulin sensitivity. Collectively, these findings identify netrin-1 as a macrophage retention signal in adipose tissue during obesity, which promotes chronic inflammation and insulin resistance. PMID:24584118

Ramkhelawon, Bhama; Hennessy, Elizabeth J; Menager, Mickael; Ray, Tathagat Dutta; Sheedy, Frederick J; Hutchison, Susan; Wanschel, Amarylis; Oldebeken, Scott; Geoffrion, Michele; Spiro, Westley; Miller, George; McPherson, Ruth; Rayner, Katey J; Moore, Kathryn J

2014-01-01

232

Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis  

PubMed Central

Background Growing evidence suggests that epicardial adipose tissue (EAT) may play a key role in the pathogenesis and development of coronary artery disease (CAD) by producing several inflammatory adipokines. Chemerin, a novel adipokine, has been reported to be involved in regulating immune responses and glucolipid metabolism. Given these properties, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis. In this study, we sought to determine the relationship of chemerin expression in EAT and the severity of coronary atherosclerosis in Han Chinese patients. Methods Serums and adipose tissue biopsies (epicardial and thoracic subcutaneous) were obtained from CAD (n = 37) and NCAD (n = 16) patients undergoing elective cardiac surgery. Gensini score was used to assess the severity of CAD. Serum levels of chemerin, adiponectin and insulin were measured by ELISA. Chemerin protein expression in adipose tissue was detected by immunohistochemistry. The mRNA levels of chemerin, chemR23, adiponectin and TNF-alpha in adipose tissue were detected by RT-PCR. Results We found that EAT of CAD group showed significantly higher levels of chemerin and TNF-alpha mRNA, and significantly lower level of adiponectin mRNA than that of NCAD patients. In CAD group, significantly higher levels of chemerin mRNA and protein were observed in EAT than in paired subcutaneous adipose tissue (SAT), whereas such significant difference was not found in NCAD group. Chemerin mRNA expression in EAT was positively correlated with Gensini score (r = 0.365, P < 0.05), moreover, this correlation remained statistically significant (r = 0.357, P < 0.05) after adjusting for age, gender, BMI and waist circumference. Chemerin mRNA expression in EAT was also positively correlated with BMI (r = 0.305, P < 0.05), waist circumference (r = 0.384, P < 0.01), fasting blood glucose (r = 0.334, P < 0.05) and negatively correlated with adiponectin mRNA expression in EAT (r = -0.322, P < 0.05). However, there were no significant differences in the serum levels of chemerin or adiponectin between the two groups. Likewise, neither serum chemerin nor serum adiponectin was associated with Gensini score (P > 0.05). Conclusions The expressions of chemerin mRNA and protein are significantly higher in EAT from patients with CAD in Han Chinese patients. Furthermore, the severity of coronary atherosclerosis is positive correlated with the level of chemerin mRNA in EAT rather than its circulating level. PMID:21981776

2011-01-01

233

A decade of progress in adipose tissue macrophage biology.  

PubMed

One decade has passed since seminal publications described macrophage infiltration into adipose tissue (AT) as a key contributor to inflammation and obesity-related insulin resistance. Currently, a PubMed search for 'adipose tissue inflammation' reveals over 3500 entries since these original reports. We now know that resident macrophages in lean AT are alternatively activated, M2-like, and play a role in AT homeostasis. In contrast, the macrophages in obese AT are dramatically increased in number and are predominantly classically activated, M1-like, and promote inflammation and insulin resistance. Mediators of AT macrophage (ATM) phenotype include adipokines and fatty acids secreted from adipocytes as well as cytokines secreted from other immune cells in AT. There are several mechanisms that could explain the large increase in ATMs in obesity. These include recruitment-dependent mechanisms such as adipocyte death, chemokine release, and lipolysis of fatty acids. Newer evidence also points to recruitment-independent mechanisms such as impaired apoptosis, increased proliferation, and decreased egress. Although less is known about the homeostatic function of M2-like resident ATMs, recent evidence suggests roles in AT expansion, thermoregulation, antigen presentation, and iron homeostasis. The field of immunometabolism has come a long way in the past decade, and many exciting new discoveries are bound to be made in the coming years that will expand our understanding of how AT stands at the junction of immune and metabolic co-regulation. PMID:25319332

Hill, Andrea A; Reid Bolus, W; Hasty, Alyssa H

2014-11-01

234

Pref-1 marks very early mesenchymal precursors required for adipose tissue development and expansion.  

PubMed

Pref-1 is an EGF-repeat-containing protein that inhibits adipocyte differentiation. To better understand the origin and development of white adipose tissue (WAT), we generated transgenic mouse models for transient or permanent fluorescent labeling of cells using the Pref-1 promoter, facilitating inducible ablation. We show that Pref-1-marked cells retain proliferative capacity and are very early adipose precursors, prior to expression of Zfp423 or PPAR?. In addition, the Pref-1-marked cells establish that adipose precursors are mesenchymal, but not endothelial or pericytal, in origin. During embryogenesis, Pref-1-marked cells first appear in the dorsal mesenteric region as early as embryonic day 10.5 (E10.5). These cells become lipid-laden adipocytes at E17.5 in the subcutaneous region, whereas visceral WAT develops after birth. Finally, ablation of Pref-1-marked cells prevents not only embryonic WAT development but also later adult adipose expansion upon high-fat feeding, demonstrating the requirement of Pref-1 cells for adipogenesis. PMID:25088414

Hudak, Carolyn S; Gulyaeva, Olga; Wang, Yuhui; Park, Seung-Min; Lee, Luke; Kang, Chulho; Sul, Hei Sook

2014-08-01

235

Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Conjugated linoleic acid supplementation suppresses perilipin1 in epididymal fat. Black-Right-Pointing-Pointer Conjugated linoleic acid inhibits promoter activity of perilipin1 in 3T3-L1 cells. Black-Right-Pointing-Pointer Conjugated linoleic acids elevate basal but blunt hormone-stimulated lipolysis. -- Abstract: Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte lipolysis and fat formation of adipose tissues. However, it is not clear how the expression of perilipin1 is affected in the decreased white adipose tissues (WAT) of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here we obtained lipodystrophic mice by dietary administration of CLA which exhibited reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of leptin in this tissue. We found both transcription and translation of perilipin1 was suppressed significantly in EPI WAT of CLA-treated mice compared to that of control mice. The gene expression of negative regulator tumor necrosis factor {alpha} (TNF{alpha}) and the positive regulator Peroxisome Proliferator-Activated Receptor-{gamma} (PPAR{gamma}) of perilipin1 was up-regulated and down-regulated, respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was dramatically inhibited in the presence of CLA. Using ex vivo experiment we found that the basal lipolysis was elevated but the hormone-stimulated lipolysis blunted in adipose explants of CLA-treated mice compared to that of control mice, suggesting that the reduction of perilipin1 in white adipose tissues may at least in part contribute to CLA-mediated alternation of lipolysis of WAT.

Cai, Demin [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China)] [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China); Li, Hongji [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China)] [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China); Zhou, Bo [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China)] [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China); Han, Liqiang [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China)] [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China); Zhang, Xiaomei [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China)] [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China); Yang, Guoyu, E-mail: haubiochem@163.com [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China)] [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China); Yang, Guoqing, E-mail: gqyang@yeah.net [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China)] [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People's Republic of China (China)

2012-06-15

236

Differentiation ability of adipose-derived stem cells separated from adipose tissue by a membrane filtration method  

Microsoft Academic Search

Adipose-derived stem cells (ADSCs) were purified from mice adipose-tissue cell solutions by the conventional culture method and the membrane filtration (i.e., batch-type filtration and perfusion-type filtration) method. The ADSCs expressing the mesenchymal stem cell marker CD73 were concentrated in a recovery solution through one sheet of polyurethane (PU) foaming membranes with a pore size of 11?m, and in a permeate

Akon Higuchi; Chung-Wei Chuang; Qing-Dong Ling; See-Chang Huang; Ling-Mei Wang; Hui Chen; Yung Chang; Han-Chow Wang; Jun-Tang Bing; Yu Chang; Shih-Tien Hsu

2011-01-01

237

Seasonal acclimation of bank voles and wood mice: nonshivering thermogenesis and thermogenic properties of brown adipose tissue mitochondria  

Microsoft Academic Search

Summary Seasonal acclimation of nonshivering thermogenesis and brown adipose tissue was studied in wild bank voles (Clethrionomys glareolus), yellow necked field mice and wood mice (Apodemus flavicollis, A. sylvaticus). Both, voles and mice increased their capacity for nonshivering thermogenesis during winter. Thermogenic properties of brown fat (cytochrome c oxidase activity, mitochondrial protein content, GDP-binding of brown fat mitochondria) showed similar

Susanne Klaus; Gerhard Heldmaier; Daniel Ricquier

1988-01-01

238

Fusion of the Endoplasmic Reticulum and Mitochondrial Outer Membrane in Rats Brown Adipose Tissue: Activation of Thermogenesis by Ca2+  

Microsoft Academic Search

Brown adipose tissue (BAT) mitochondria thermogenesis is regulated by uncoupling protein 1 (UCP 1), GDP and fatty acids. In this report, we observed fusion of the endoplasmic reticulum (ER) membrane with the mitochondrial outer membrane of rats BAT. Ca2+-ATPase (SERCA 1) was identified by immunoelectron microscopy in both ER and mitochondria. This finding led us to test the Ca2+ effect

Leopoldo de Meis; Luisa A. Ketzer; Rodrigo Madeiro da Costa; Ivone Rosa de Andrade; Marlene Benchimol; Stefan Wölfl

2010-01-01

239

Controlled cellular energy conversion in brown adipose tissue thermogenesis  

NASA Technical Reports Server (NTRS)

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.

Horowitz, J. M.; Plant, R. E.

1978-01-01

240

Stranger in a Strange Land: Roles of Glycogen Turnover in Adipose Tissue Metabolism  

PubMed Central

Summary Triglyceride storage in adipose tissue comprises the principal energy reserve in mammals. Additionally glucose can be stored as glycogen in the fed state, primarily in liver and skeletal muscle, for mobilization during times of energy deficit. Adipose tissue also contains glycogen stores albeit at very low levels. The physiological role of glycogen metabolism in adipocytes remains unclear. However, both classical literature and more recent work demonstrate that the dynamic regulation of adipose glycogen may serve as an energy sensing modality in the coordination of glucose and lipid metabolism in adipose tissue, especially during the fasted to fed transition. PMID:19703517

Markan, Kathleen R.; Jurczak, Michael J.; Brady, Matthew J.

2009-01-01

241

Defective Apoptosis in Intestinal and Mesenteric Adipose Tissue of Crohn's Disease Patients  

PubMed Central

Background Crohn’s disease (CD) is associated with complex pathogenic pathways involving defects in apoptosis mechanisms. Recently, mesenteric adipose tissue (MAT) has been associated with CD ethiopathology, since adipose thickening is detected close to the affected intestinal area. However, the potential role of altered apoptosis in MAT of CD has not been addressed. Aims To evaluate apoptosis in the intestinal mucosa and MAT of patients with CD. Methods Samples of intestinal mucosa and MAT from patients with ileocecal CD and from non-inflammatory bowel diseases patients (controls) were studied. Apoptosis was assessed by TUNEL assay and correlated with the adipocytes histological morphometric analysis. The transcriptional and protein analysis of selected genes and proteins related to apoptosis were determined. Results TUNEL assay showed fewer apoptotic cells in CD, when compared to the control groups, both in the intestinal mucosa and in MAT. In addition, the number of apoptotic cells (TUNEL) correlated significantly with the area and perimeter of the adipose cells in MAT. Transcriptomic and proteomic analysis reveal a significantly lower transcript and protein levels of Bax in the intestinal mucosa of CD, compared to the controls; low protein levels of Bax were found localized in the lamina propria and not in the epithelium of this tissue. Furthermore, higher level of Bcl-2 and low level of Caspase 3 were seen in the MAT of CD patients. Conclusion The defective apoptosis in MAT may explain the singular morphological characteristics of this tissue in CD, which may be implicated in the pathophysiology of the disease. PMID:24887376

Dias, Cilene Bicca; Milanski, Marciane; Portovedo, Mariana; Horita, Vivian; Ayrizono, Maria de Lourdes Setsuko; Planell, Nuria; Coy, Claudio Saddy Rodrigues; Velloso, Licio Augusto; Meirelles, Luciana Rodrigues; Leal, Raquel Franco

2014-01-01

242

Cardiac Adiposity and Cardiovascular Risk: Potential Role of Epicardial Adipose Tissue  

Microsoft Academic Search

Emerging evidence suggests that cardiac adiposity may play an important role in the development of an unfa- vorable cardiovascular risk profile. The concept of adiposity of the heart, as new cardiovascular risk factor and marker, is rapidly emerging. Recent papers suggest that epicardial fat, an index of cardiac visceral adiposity could locally modulate the morphology and function of the heart.

Gianluca Iacobellis; Navneet Singh; Arya M. Sharma

2007-01-01

243

Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss.  

PubMed

The aim of this study was to investigate the potential role of adipose cytokines in the obesity-associated insulin resistance. To that end, we compared: 1) serum concentrations of interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), and leptin in eight healthy lean control females and in android obese female without (n = 14) and with (n = 7) type 2 diabetes; and 2) the levels of these cytokines both in serum and in sc adipose tissue in the 14 obese nondiabetic women before and after 3 weeks of a very low-calorie diet (VLCD). As compared with lean controls, obese nondiabetic and diabetic patients were more insulin resistant and presented increased values for leptin, IL-6, TNFalpha, and C-reactive protein. In the whole group, IL-6 values were more closely related to the parameters evaluating insulin resistance than leptin or TNFalpha values. VLCD resulted in weight loss and decreased body fat mass (approximately 3 kg). Insulin sensitivity was improved with no significant change in both serum and adipose tissue TNFalpha levels. In contrast, VLCD induced significant decreases in IL-6 and leptin levels in both adipose tissue and serum. These results suggest that, as for leptin, circulating IL-6 concentrations reflect, at least in part, adipose tissue production. The reduced production and serum concentrations after weight loss could play a role in the improved sensitivity to insulin observed in these patients. PMID:10999830

Bastard, J P; Jardel, C; Bruckert, E; Blondy, P; Capeau, J; Laville, M; Vidal, H; Hainque, B

2000-09-01

244

Obesity and Weight Loss Result in Increased Adipose Tissue ABCG1 Expression in db/db Mice  

PubMed Central

The prevalence of obesity has reached epidemic proportions and is associated with several co-morbid conditions including diabetes, dyslipidemia, cancer, atherosclerosis and gallstones. Obesity is associated with low systemic inflammation and an accumulation of adipose tissue macrophages (ATMs) that are thought to modulate insulin resistance. ATMs may also modulate adipocyte metabolism and take up lipids released during adipocyte lipolysis and cell death. We suggest that high levels of free cholesterol residing in adipocytes are released during these processes and contribute to ATM activation and accumulation during obesity and caloric restriction. Db/db mice were studied for extent of adipose tissue inflammation under feeding conditions of ad libitum (AL) and caloric restriction (CR). The major finding was a marked elevation in epididymal adipose ABCG1 mRNA levels with obesity and CR (6-fold and 16-fold, respectively) over that seen for lean wild-type mice. ABCG1 protein was also elevated for CR as compared to AL adipose tissue. ABCG1 is likely produced by cholesterol loaded ATMs since this gene is not highly expressed in adipocytes and ABCG1 expression is sterol mediated. Our data supports the concept that metabolic changes in adipocytes due to demand lipolysis and cell death lead to cholesterol loading of ATMs. Based on finding cholesterol-loaded peritoneal leukocytes with elevated levels of ABCG1 in CR as compared to AL mice, we suggest that pathways for cholesterol trafficking out of adipose tissue involve ATM egress as well as ABCG1 mediated cholesterol efflux. PMID:22179025

Edgel, Kimberly A.; McMillen, Timothy S.; Wei, Hao; Pamir, Nathalie; Houston, Barbara A.; Caldwell, Mark T.; Mai, Phuong-Oanh T.; Oram, John F.; Tang, Chongren; LeBoeuf, Renee C.

2012-01-01

245

Adipose Tissue Fatty Acids in Breast Cancer Patients versus Healthy Control Women from Crete  

Microsoft Academic Search

Background: Few studies have implemented biomarkers of fatty acid intake in relation to breast cancer. Aims: To examine possible differences in adipose tissue fatty acid composition between breast cancer patients and healthy control women. The relationship between tumor promotion and adipose tissue fatty acid synthesis was also investigated. Methods: The study was conducted at the University of Crete. Subjects included

G. Mamalakis; C. Hatzis; E. de Bree; E. Sanidas; D. D. Tsiftsis; J. Askoxylakis; M. Daskalakis; G. Tsibinos; A. Kafatos

2009-01-01

246

Role of NKG2D in Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance  

PubMed Central

The early events that initiate inflammation in the adipose tissue during obesity are not well defined. It is unclear whether the recruitment of CD8 T cells to the adipose tissue during onset of obesity occurs through antigen-dependent or -independent processes. We have previously shown that interaction between NKG2D (natural-killer group 2, member D) and its ligand Rae-1? is sufficient to recruit cytotoxic T lymphocytes to the pancreas and induce insulitis. Here, we tested whether NKG2D–NKG2D ligand interaction is also involved in obesity-induced adipose tissue inflammation and insulin resistance. We observed a significant induction of NKG2D ligand expression in the adipose tissue of obese mice, especially during the early stages of obesity. However, mice lacking NKG2D developed similar levels of insulin resistance and adipose tissue inflammation compared to control mice when placed on a high-fat diet. Moreover, overexpression of Rae-1? in the adipose tissue did not increase immune cell infiltration to the adipose tissue either in the setting of a normal or high-fat diet. These results indicate that, unlike in the pancreas, NKG2D–NKG2D ligand interaction does not play a critical role in obesity-induced inflammation in the adipose tissue. PMID:25333972

Chung, Jun-Jae; Markiewicz, Mary A.; Polic, Bojan; Shaw, Andrey S.

2014-01-01

247

Novel findings regarding Glut4 expression in adipose tissue and muscle in horses – A preliminary report  

Microsoft Academic Search

One of the hallmarks of insulin resistance is a reduction in glucose transporter-4 (Glut-4) expression in adipose tissue but not in skeletal muscle. However, while Glut-4 has been demonstrated in skeletal and cardiac muscles in horses it has not been demonstrated in adipose tissue. The initial objectives of the present study were: (1) to test the hypothesis that Glut-4 expression

Helio C. Manso Filho; Kenneth H. McKeever; Mary E. Gordon; Helena Emilia C. Costa; Malcolm Watford

2007-01-01

248

Developmental changes in lipogenic enzyme activities in liver and adipose tissue of post-weaning rats.  

E-print Network

Developmental changes in lipogenic enzyme activities in liver and adipose tissue of post and castration had a weak effect on the activity pattern of the 3 enzymes studied in the adipose tissue and Kauffman, 1973) at different developmental sta- ges. These enzyme activities have also been studied

Paris-Sud XI, Université de

249

Epigenetic regulation of depot-specific gene expression in adipose tissue.  

PubMed

In humans, adipose tissue is distributed in subcutaneous abdominal and subcutaneous gluteal depots that comprise a variety of functional differences. Whereas energy storage in gluteal adipose tissue has been shown to mediate a protective effect, an increase of abdominal adipose tissue is associated with metabolic disorders. However, the molecular basis of depot-specific characteristics is not completely understood yet. Using array-based analyses of transcription profiles, we identified a specific set of genes that was differentially expressed between subcutaneous abdominal and gluteal adipose tissue. To investigate the role of epigenetic regulation in depot-specific gene expression, we additionally analyzed genome-wide DNA methylation patterns in abdominal and gluteal depots. By combining both data sets, we identified a highly significant set of depot-specifically expressed genes that appear to be epigenetically regulated. Interestingly, the majority of these genes form part of the homeobox gene family. Moreover, genes involved in fatty acid metabolism were also differentially expressed. Therefore we suppose that changes in gene expression profiles might account for depot-specific differences in lipid composition. Indeed, triglycerides and fatty acids of abdominal adipose tissue were more saturated compared to triglycerides and fatty acids in gluteal adipose tissue. Taken together, our results uncover clear differences between abdominal and gluteal adipose tissue on the gene expression and DNA methylation level as well as in fatty acid composition. Therefore, a detailed molecular characterization of adipose tissue depots will be essential to develop new treatment strategies for metabolic syndrome associated complications. PMID:24340035

Gehrke, Sandra; Brueckner, Bodo; Schepky, Andreas; Klein, Johannes; Iwen, Alexander; Bosch, Thomas C G; Wenck, Horst; Winnefeld, Marc; Hagemann, Sabine

2013-01-01

250

Seasonal, sexual and anatomical variability in the adipose tissue of polar bears (Ursus maritimus)  

Microsoft Academic Search

We collected 245 adipose tissue biopsies from adult polar bears Ursus maritimus in north-eastern Manitoba during the course of long-term population studies between fall 2001 and spring 2004. In summer, the sea ice of Hudson Bay melts completely and the entire polar bear population is forced to fast on land for c. 4 months. During this period, the adipose tissue

G. W. Thiemann; S. J. Iverson; I. Stirling

2006-01-01

251

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

Microsoft Academic Search

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

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

2011-01-01

252

Subcutaneous adipose tissue blood flow and triacylglycerol-mobilization during prolonged exercise in dogs  

Microsoft Academic Search

In 6 dogs concentration differences for glycerol and FFA were measured between the aorta and the external pudendal vein, a vein which mainly drains subcutaneous adipose tissue in dogs, during prolonged exercise. It was found that the a-v differences increased about 2-fold for both glycerol and FFA, however great interindividual differences were found. In 4 dogs adipose tissue blood flow,

Jens Billow

1982-01-01

253

Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity.  

PubMed

Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in adipose tissues are involved in obesity-mediated metabolic complications, including insulin resistance. Here, we summarize recent findings on the key roles of innate (neutrophils, macrophages, mast cells, eosinophils) and adaptive (regulatory T cells, type 1 helper T cells, CD8 T cells, B cells) immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. In particular, the roles of natural killer T cells, one type of innate lymphocyte, in adipose tissue inflammation will be discussed. Finally, a new role of adipocytes as antigen presenting cells to modulate T cell activity and subsequent adipose tissue inflammation will be proposed. PMID:24781408

Huh, Jin Young; Park, Yoon Jeong; Ham, Mira; Kim, Jae Bum

2014-05-01

254

Spontaneous secretion of lipoprotein lipase by bovine and ovine adipose tissue incubated for 7 days  

E-print Network

Spontaneous secretion of lipoprotein lipase by bovine and ovine adipose tissue incubated for 7 days such as insulin, serum, heparin (Garfinkel et al, 1976, Bioch Biophys Acta, 424, 147-156 ; Pradines- Figu6res et was to measure the secretion of LPL activity by bovine and ovine adipose tissue (AT) explants incubated for 7

Boyer, Edmond

255

Diet-induced obese rats exhibit impaired LKB1-AMPK signaling in hypothalamus and adipose tissue.  

PubMed

AMPK not only acts as a sensor of cellular energy status but also plays a critical role in the energy balance of the body. In this study, LKB1-AMPK signaling was investigated in diet-induced obese (DIO) and diet resistant (DR) rats. In hypothalamus, DIO rats had lower level of LKB1, AMPK? and pAMPK? than chow-fed or DR rats. Both orexigenic peptide NPY and anorexigenic peptide POMC expression were reduced in hypothalamus of DIO rats. i.c.v. injection of AICAR, an activator of AMPK, increased NPY expression but did not alter POMC expression in DIO rats. In periphery, LKB1 protein content and pAMPK? level were lower in the adipose tissue of DIO rats compared to chow-fed and DR rats. Moreover, pAMPK? and LKB1 protein levels obtained from epididymal fat pad were inversely correlated with epididymal fat mass. LKB1 protein content and pAMPK? in skeletal muscle of DIO rats were not different from those in the muscles of chow-fed and DR rats. In summary, DIO rats, but not DR rats, have impaired LKB1-AMPK signaling in hypothalamus and adipose tissue, suggesting the disturbed energy balance observed in DIO rats is related with abnormalities of AMPK signaling in a tissue specific manner. PMID:22465622

Fei-Wang; Tian, De-Run; Tso, Patrick; Han, Ji-Sheng

2012-05-01

256

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues  

SciTech Connect

Highlights: •CTLA-4Ig completely alleviates HFD-induced insulin resistance. •CTLA-4Ig reduces epididymal and subcutaneous fat tissue weight and adipocyte size. •CTLA-4Ig alters ATM polarization from inflammatory M1 to anti-inflammatory M2. •CTLA-4Ig may lead to a novel anti-obesity/inflammation/insulin resistance agent. •We identified the mechanism of the novel favorable effects of CTLA-4lg. -- Abstract: It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein ?, peroxisome proliferator-activated receptor ?, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent.

Fujii, Masakazu, E-mail: masakazu731079@yahoo.co.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)] [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Inoguchi, Toyoshi, E-mail: toyoshi@intmed3.med.kyushu-u.ac.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan) [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Batchuluun, Battsetseg, E-mail: battsetseg.batchuluun@gmail.com [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)] [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sugiyama, Naonobu, E-mail: nao1@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)] [Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Kobayashi, Kunihisa, E-mail: nihisak@fukuoka-u.ac.jp [Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, 1-1-1 Zokumyoin, Chikushino, Fukuoka 818-8502 (Japan)] [Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, 1-1-1 Zokumyoin, Chikushino, Fukuoka 818-8502 (Japan); Sonoda, Noriyuki, E-mail: noriyuki@intmed3.med.kyushu-u.ac.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan) [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Takayanagi, Ryoichi, E-mail: takayana@intmed3.med.kyushu-u.ac.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)] [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

2013-08-16

257

Calcium Sensing Receptor (CaSR) activation elevates proinflammatory factor expression in human adipose cells and adipose tissue  

PubMed Central

We have previously established that human adipose cells and the human adipose cell line LS14 express the calcium sensing receptor (CaSR) and that its expression is elevated upon exposure to inflammatory cytokines that are typically elevated in obese humans. Research in recent years has established that an important part of the adverse metabolic and cardiovascular consequences of obesity derive from a dysfunction of the tissue, one of the mechanisms being a disordered secretion pattern leading to an excess of proinflammatory cytokines and chemokines. Given the reported association of the CaSR to inflammatory processes in other tissues, we sought to evaluate its role elevating the adipose expression of inflammatory factors. We exposed adipose tissue and in-vitro cultured LS14 preadipocytes and differentiated adipocytes to the calcimimetic cinacalcet and evaluated the expression or production of the proinflammatory cytokines IL6, IL1? and TNF? as well as the chemoattractant factor CCL2. CaSR activation elicited an elevation in the expression of the inflammatory factors, which was in part reverted by SN50, an inhibitor of the inflammatory mediator NF?B. Our observations suggest that CaSR activation elevates cytokine and chemokine production through a signaling pathway involving activation of NF?B nuclear translocation. These findings confirm the relevance of the CaSR in the pathophysiology of obesity-induced adipose tissue dysfunction, with an interesting potential for pharmacological manipulation in the fight against obesity- associated diseases. PMID:22449852

Cifuentes, Mariana; Fuentes, Cecilia; Acevedo, Ingrid; Villalobos, Elisa; Hugo, Eric; Ben Jonathan, Nira; Reyes, Marcela

2013-01-01

258

Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis.  

PubMed

Triiodothyroacetic acid (TRIAC) is a physiological product of triiodothyronine (T(3)) metabolism, with high affinity for T(3) nuclear receptors. Its interest stems from its potential thermogenic effects. Thus this work aimed 1) to clarify these thermogenic effects mediated by TRIAC vs. T(3) in vivo and 2) to determine whether they occurred predominantly in adipose tissues. To examine this, control rats were infused with equimolar T(3) or TRIAC doses (0.8 or 4 nmolx100 g body wt(-1) x day(-1)) or exposed for 48 h to cold. Both T(3) doses and only the highest TRIAC dose inhibited plasma and pituitary thyroid-stimulating hormone (TSH) and thyroxine (T(4)) in plasma and tissues. Interestingly, the lower TRIAC dose marginally inhibited plasma T(4). T(3) infusion increased plasma and tissue T(3) in a tissue-specific manner. The highest TRIAC dose increased TRIAC concentrations in plasma and tissues, decreasing plasma T(3). TRIAC concentrations in tissues were <10% those of T(3). Under cold exposure or high T(3) doses, TRIAC increased only in white adipose tissue (WAT). Remarkably, only the lower TRIAC dose activated thermogenesis, inducing ectopic uncoupling protein (UCP)-1 expression in WAT and maximal increases in UCP-1, UCP-2, and lipoprotein lipase (LPL) expression in brown adipose tissue (BAT), inhibiting UCP-2 in muscle and LPL in WAT. TRIAC, T(3), and cold exposure inhibited leptin secretion and mRNA in WAT. In summary, TRIAC, at low doses, induces thermogenic effects in adipose tissues without concomitant inhibition of TSH or hypothyroxinemia, suggesting a specific role regulating energy balance. This selective effect of TRIAC in adipose tissues might be considered a potential tool to increase energy metabolism. PMID:18285526

Medina-Gomez, G; Calvo, R M; Obregon, M-J

2008-04-01

259

Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype  

PubMed Central

Adipose tissue plays an essential role in metabolic homeostasis, and holds promise as an alternative depot organ in gene therapy. However, efficient methods of gene transfer into adipose tissue in vivo have yet to be established. Here we assessed the transduction efficiency to fat depots by a family of novel engineered hybrid capsid serotypes (Rec1~4) recombinant AAV vectors in comparison with natural serotypes AAV1, AAV8, and AAV9. Rec2 serotype led to widespread transduction in both brown fat and white fat with the highest efficiency among the seven serotypes tested. As a proof-of-efficacy, Rec2 serotype was used to deliver Cre recombinase to adipose tissues of insulin receptor floxed animals. Insulin receptor knockdown led to decreased fat pad mass, morphological and molecular changes in the targeted depot. These novel hybrid AAV vectors can serve as powerful tools to genetically manipulate adipose tissue and provide valuable vehicles to gene therapy targeting adipose tissue.

Liu, Xianglan; Magee, Daniel; Wang, Chuansong; McMurphy, Travis; Slater, Andrew; During, Matthew; Cao, Lei

2014-01-01

260

Human extracellular matrix (ECM) powders for injectable cell delivery and adipose tissue engineering.  

PubMed

Here, we present extracellular matrix (ECM) powders derived from human adipose tissue as injectable cell delivery carriers for adipose tissue engineering. We postulate that human adipose tissue may provide an ideal biomaterial because it contains large amounts of ECM components including collagen. Fresh human adipose tissue was obtained by a simple surgical operation (liposuction). After removing blood and oil components, the tissue was homogenized, centrifuged, freeze-dried, and ground to powders by milling. In an in vitro study, the human ECM powders were highly effective for promotion of cell attachment and proliferation for three-dimensional (3D) cell culture. In in vivo studies, suspensions of human ECM powders containing human adipose-derived stem cells (hASCs) were subcutaneously injected into nude mice. At eight weeks post-injection, numerous blood vessels were observed and the newly formed tissue exhibited adipogenesis with accumulated intracellular small lipid droplets. Overall, the grafts showed well-organized adipose tissue constructs without any signs of tissue necrosis, cystic spaces, or fibrosis. We believe that human ECM powders could act as efficient injectable biomaterials for tissue engineering and have great potential for meeting clinical challenges in regenerative medicine, particularly in relation to adipose tissue engineering. PMID:19481576

Choi, Ji Suk; Yang, Hyun-Jin; Kim, Beob Soo; Kim, Jae Dong; Kim, Jun Young; Yoo, Bongyoung; Park, Kinam; Lee, Hee Young; Cho, Yong Woo

2009-10-01

261

Evidence for posttranscriptional regulation of GLUT4 expression in muscle and adipose tissue from streptozotocin-induced diabetic and benfluorex-treated rats  

Microsoft Academic Search

In this study we explored the expression of GLUT4 glucose carriers in muscle and adipose tissues from streptozotocin-induced diabetic and benfluorex-treated rats. In nondiabetic rats, benfluorex treatment decreased GLUT4 protein content in muscle and brown adipose tissue, with no change in GLUT4 mRNA. This effect occurred in the presence of normal circulating levels of insulin and glucose. Seventeen days after

Purificación Muñoz; Josep Chillarón; Marta Camps; Anna Castelló; Marc Furriols; Xavier Testar; Manuel Palacín; Antonio Zorzano

1996-01-01

262

Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone.  

PubMed

Brown adipose tissue (BAT) and brown-like cells in white adipose tissue (WAT) can dissipate energy through thermogenesis, a process mediated by uncoupling protein 1 (UCP1). We investigated whether stress hormones ACTH and corticosterone contribute to BAT activation and browning of WAT. ACTH and corticosterone were studied in male mice exposed to 4 or 23°C for 24 h. Direct effects were studied in T37i mouse brown adipocytes and primary cultured murine BAT and inguinal WAT (iWAT) cells. In vivo effects were studied using (18)F-deoxyglucose positron emission tomography. Cold exposure doubled serum ACTH concentrations (P=0.03) and fecal corticosterone excretion (P=0.008). In T37i cells, ACTH dose-dependently increased Ucp1 mRNA (EC50=1.8 nM) but also induced Ucp1 protein content 88% (P=0.02), glycerol release 32% (P=0.03) and uncoupled respiration 40% (P=0.003). In cultured BAT and iWAT, ACTH elevated Ucp1 mRNA by 3-fold (P=0.03) and 3.7-fold (P=0.01), respectively. In T37i cells, corticosterone prevented induction of Ucp1 mRNA and Ucp1 protein by both ACTH and norepinephrine in a glucocorticoid receptor (GR)-dependent fashion. ACTH and GR antagonist RU486 independently doubled BAT (18)F-deoxyglucose uptake (P=0.0003 and P=0.004, respectively) in vivo. Our results show that ACTH activates BAT and browning of WAT while corticosterone counteracts this.-Van den Beukel, J. C., Grefhorst, A., Quarta, C., Steenbergen, J., Mastroberardino, P. G., Lombès, M., Delhanty, P. J., Mazza, R., Pagotto, U., van der Lely, A. J., Themmen, A. P. N. Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone. PMID:25085924

van den Beukel, Johanna C; Grefhorst, Aldo; Quarta, Carmelo; Steenbergen, Jacobie; Mastroberardino, Pier G; Lombès, Marc; Delhanty, Patric J; Mazza, Roberta; Pagotto, Uberto; van der Lely, Aart Jan; Themmen, Axel P N

2014-11-01

263

Human adipose tissue-resident monocytes exhibit an endothelial-like phenotype and display angiogenic properties  

PubMed Central

Introduction Adipose tissue has the unique property of expanding throughout adult life, and angiogenesis is required for its growth. However, endothelial progenitor cells contribute minimally to neovascularization. Because myeloid cells have proven to be angiogenic, and monocytes accumulate in expanding adipose tissue, they might contribute to vascularization. Methods The stromal vascular fraction (SVF) cells from human adipose tissue were magnetically separated according to CD45 or CD14 expression. Adipose-derived mesenchymal stromal cells (MSCs) were obtained from SVF CD45- cells. CD14+ monocytes were isolated from peripheral blood (PB) mononuclear cells and then cultured with SVF-derived MSCs. Freshly isolated or cultured cells were characterized with flow cytometry; the conditioned media were analyzed for the angiogenic growth factors, angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) with Luminex Technology; their angiogenic capacity was determined in an in vivo gelatinous protein mixture (Matrigel) plug angiogenesis assay. Results CD45+ hematopoietic cells within the SVF contain CD14+ cells that co-express the CD34 progenitor marker and the endothelial cell antigens VEGF receptor 2 (VEGFR2/KDR), VEGFR1/Flt1, and Tie2. Co-culture experiments showed that SVF-derived MSCs promoted the acquisition of KDR and Tie-2 in PB monocytes. MSCs secreted significant amounts of Ang-2 and HGF, but minimal amounts of bFGF, G-CSF, or GM-CSF, whereas the opposite was observed for SVF CD14+ cells. Additionally, SVF CD14+ cells secreted significantly higher levels of VEGF and bFGF than did MSCs. Culture supernatants of PB monocytes cultured with MSCs contained significantly higher concentrations of VEGF, HGF, G-CSF, and GM-CSF than did the supernatants from cultures without MSCs. Quantitative analysis of angiogenesis at 14 days after implantation demonstrated that neovascularization of the implants containing SVF CD14+ cells or PB monocytes previously co-cultured with MSCs was 3.5 or 2 times higher than that observed in the implants with SVF-derived MSCs. Moreover, immunofluorescence of Matrigel sections revealed that SVF CD14+ cells differentiated into endothelial cells and contributed to vascular endothelium. Conclusions The results from this study suggest that adipose tissue-resident monocytes should contribute to tissue vascularization. Because SVF CD14+ cells were more efficient in inducing angiogenesis than SVF-derived MSCs, and differentiated into vascular endothelial cells, they may constitute a new cell source for cell-based therapeutic angiogenesis. PMID:24731246

2014-01-01

264

Mitochondrial function/dysfunction in white adipose tissue.  

PubMed

The role of mitochondria in white adipocytes has long been neglected due in part to their lower abundance in these cells. However, accumulating evidence suggests that mitochondria are vital for maintaining metabolic homeostasis in white adipocytes because of their involvement in adipogenesis, fatty acid synthesis and esterification, branched-chain amino acid catabolism and lipolysis. It is therefore not surprising that white adipose tissue function can be perturbed by altering mitochondrial components or oxidative capacity. Moreover, studies in humans and animals with significantly altered fat mass, such as in obesity or lipoatrophy, indicate that impaired mitochondrial function in adipocytes may be linked directly to the development of metabolic diseases such as diabetes and insulin resistance. However, recent studies that specifically targeted mitochondrial function in adipocytes indicated dissociation between impaired mitochondrial oxidative capacity and systemic insulin sensitivity. PMID:25128326

Boudina, Sihem; Graham, Timothy E

2014-09-01

265

Brown adipose tissue in humans: therapeutic potential to combat obesity.  

PubMed

Harnessing the considerable capacity of brown adipose tissue (BAT) to consume energy was first proposed as a potential target to control obesity nearly 40years ago. The plausibility of this approach was, however, questioned due to the prevailing view that BAT was either not present or not functional in adult humans. Recent definitive identification of functional BAT in adult humans as well as a number of important advances in the understanding of BAT biology has reignited interest in BAT as an anti-obesity target. Proof-of-concept evidence demonstrating drug-induced BAT activation provides an important foundation for development of targeted pharmacological approaches with clinical application. This review considers evidence from both human and relevant animal studies to determine whether harnessing BAT for the treatment of obesity via pharmacological intervention is a realistic goal. PMID:23718981

Carey, Andrew L; Kingwell, Bronwyn A

2013-10-01

266

Brown adipose tissue as a therapeutic target for human obesity.  

PubMed

Brown adipose tissue (BAT) is the major site of sympathetically activated adaptive thermogenesis during cold exposure and after spontaneous hyperphagia, thereby controlling whole-body energy expenditure and body fat. Recent radionuclide studies have demonstrated the existence of metabolically active BAT in healthy adult humans. Human BAT is activated by acute cold exposure, being positively correlated to cold-induced increases in energy expenditure. The metabolic activity of BAT is lower in older and obese individuals. The inverse relationship between the BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. In fact, either repeated cold exposure or daily ingestion of some food ingredients acting on transient receptor potential channels recruited BAT in association with increased energy expenditure and decreased body fat even in individuals with low BAT activities before the treatment. Thus, BAT is a promising therapeutic target for combating human obesity and related metabolic disorders. PMID:24459687

Saito, Masayuki

2013-12-01

267

Human brown adipose tissue: regulation and anti-obesity potential.  

PubMed

Brown adipose tissue (BAT) is the site of sympathetically activated adaptive thermognenesis during cold exposure and after hyperphagia, thereby controlling whole-body energy expenditure (EE) and body fat. Radionuclide imaging studies have demonstrated that adult humans have metabolically active BAT composed of mainly beige/brite adipocytes, recently identified brown-like adipocytes. The inverse relationship between the BAT activity and body fatness suggests that BAT is, because of its energy dissipating activity, protective against body fat accumulation in humans as it is in small rodents. In fact, either repeated cold exposure or daily ingestion of some food ingredients acting on transient receptor potential channels recruits BAT in parallel with increased EE and decreased body fat. In addition to the sympathetic nervous system, several endocrine factors are also shown to recruit BAT. Thus, BAT is a promising therapeutic target for combating human obesity and related metabolic disorders. PMID:24401694

Saito, Masayuki

2014-01-01

268

Fabrication of Adipose-Derived Mesenchymal Stem Cell Aggregates using Biodegradable Porous Microspheres for Injectable Adipose Tissue Regeneration.  

PubMed

Injectable mesenchymal stem cell aggregates were formed using hyaluronic acid (HA)-immobilized porous biodegradable microspheres for adipose tissue regeneration. Adipose tissue-derived mesenchymal stem cells (AMSCs) were aggregated in a controlled manner and differentiated into adipocytes by cultivating in a stirred suspension bioreactor. The resultant cellular aggregates were approx. 1700 mum in diameter and exhibited fully differentiated adipocytes, as shown by immunocytochemistry and RT-PCR. The cultured aggregates could be smoothly injected into the subcutaneous region of mice through a syringe needle due to their soft elasticity and deformability. The in vivo regenerated adipose tissue maintained a proper dimension and shape, showing natural adipose tissue characteristics, as demonstrated by various histological staining procedures. HA-immobilized microspheres significantly enhanced cell differentiation during 3D cultivation, and tissue regeneration when implanted in vivo, compared to unmodified porous microspheres. This study showed that AMSC cellular aggregates prepared by using porous microspheres could be delivered in an injectable manner into the body and could have great therapeutic potential for soft tissue augmentation and reconstruction. PMID:20546678

Chung, Hyun Jung; Jung, Jin Sup; Park, Tae Gwan

2010-06-11

269

Sucrose Counteracts the Anti-Inflammatory Effect of Fish Oil in Adipose Tissue and Increases Obesity Development in Mice  

PubMed Central

Background 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. Methodology/Principal Findings We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein?sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state. Conclusions/Significance The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice. PMID:21738749

Ma, Tao; Liaset, Bjørn; Hao, Qin; Petersen, Rasmus Koefoed; Fjære, Even; Ngo, Ha Thi; Lillefosse, Haldis Haukås; Ringholm, Stine; Sonne, Si Brask; Treebak, Jonas Thue; Pilegaard, Henriette; Frøyland, Livar; Kristiansen, Karsten; Madsen, Lise

2011-01-01

270

Rosiglitazone-Induced Mitochondrial Biogenesis in White Adipose Tissue Is Independent of Peroxisome Proliferator-Activated Receptor ? Coactivator-1?  

PubMed Central

Background Thiazolidinediones, a family of insulin-sensitizing drugs commonly used to treat type 2 diabetes, are thought to exert their effects in part by promoting mitochondrial biogenesis in white adipose tissue through the transcriptional coactivator PGC-1? (Peroxisome Proliferator-Activated Receptor ? Coactivator-1?). Methodology/Principal Findings To assess the role of PGC-1? in the control of rosiglitazone-induced mitochondrial biogenesis, we have generated a mouse model that lacks expression of PGC-1? specifically in adipose tissues (PGC-1?-FAT-KO mice). We found that expression of genes encoding for mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle or fatty acid oxidation, was similar in white adipose tissue of wild type and PGC-1?-FAT-KO mice. Furthermore, the absence of PGC-1? did not prevent the positive effect of rosiglitazone on mitochondrial gene expression or biogenesis, but it precluded the induction by rosiglitazone of UCP1 and other brown fat-specific genes in white adipose tissue. Consistent with the in vivo findings, basal and rosiglitazone-induced mitochondrial gene expression in 3T3-L1 adipocytes was unaffected by the knockdown of PGC-1? but it was impaired when PGC-1? expression was knockdown by the use of specific siRNA. Conclusions/Significance These results indicate that in white adipose tissue PGC-1? is dispensable for basal and rosiglitazone-induced mitochondrial biogenesis but required for the rosiglitazone-induced expression of UCP1 and other brown adipocyte-specific markers. Our study suggests that PGC-1? is important for the appearance of brown adipocytes in white adipose tissue. Our findings also provide evidence that PGC-1? and not PGC-1? regulates basal and rosiglitazone-induced mitochondrial gene expression in white adipocytes. PMID:22087241

Pardo, Rosario; Enguix, Natàlia; Lasheras, Jaime; Feliu, Juan E.; Kralli, Anastasia; Villena, Josep A.

2011-01-01

271

Establishment of a preadipocyte cell line derived from mature adipocytes of GFP transgenic mice and formation of adipose tissue  

Microsoft Academic Search

We established a preadipocyte cell line from mature adipocytes obtained from subcutaneous fat tissue of green fluorescent\\u000a protein (GFP) transgenic mice. The floating top layer, containing mature adipocytes, was isolated from subcutaneous fat tissue\\u000a by collagenase digestion and filtration. Fluorescence-activated cell sorting and microscopic analysis revealed that the floating\\u000a cell fraction comprised a highly homogeneous adipocyte population with no adipose

Hiroyuki Nobusue; Tsuyoshi Endo; Koichiro Kano

2008-01-01

272

Exploratory Studies on Biomarkers: An Example Study on Brown Adipose Tissue  

NASA Astrophysics Data System (ADS)

In mammals, two kinds of adipose tissue are known to exist, i.e., white (WAT) and brown (BAT) adipose tissue. The physiological role of WAT is storage of excess energy as fat, whereas that of BAT is the expenditure of excess energy as heat. The uncoupling protein UCP1, which is specifically expressed in brown fat mitochondria, dissipates the proton electrochemical potential across the inner mitochondrial membrane, known as a driving force of ATP synthesis, and thus it dissipates excess energy in a form of heat. Because deficiency in effective expenditure of excess energy causes accumulation of this energy in the form of fat (i.e., obesity), it is very important to understand the energy metabolism in this tissue for the development of anti-obesity drugs. In this article, in addition to providing a brief introduction to the functional properties of BAT and UCP1, the results of our exploratory studies on protein components involved in the energy-dissipating function in BAT.

Watanabe, Masahiro; Yamazaki, Naoshi; Kataoka, Masatoshi; Shinohara, Yasuo

273

Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone  

PubMed Central

Adipose tissue plays a central role in the control of energy homeostasis through the storage and turnover of triglycerides and through the secretion of factors that affect satiety and fuel utilization. Agents that enhance insulin sensitivity, such as rosiglitazone, appear to exert their therapeutic effect through adipose tissue, but the precise mechanisms of their actions are unclear. Rosiglitazone changes the morphological features and protein profiles of mitochondria in 3T3-L1 adipocytes. To examine the relevance of these effects in vivo, we studied white adipocytes from ob/ob mice during the development of obesity and after treatment with rosiglitazone. The levels of approximately 50% of gene transcripts encoding mitochondrial proteins were decreased with the onset of obesity. About half of those genes were upregulated after treatment with rosiglitazone, and this was accompanied by an increase in mitochondrial mass and changes in mitochondrial structure. Functionally, adipocytes from rosiglitazone-treated mice displayed markedly enhanced oxygen consumption and significantly increased palmitate oxidation. These data reveal mitochondrial remodeling and increased energy expenditure in white fat in response to rosiglitazone treatment in vivo and suggest that enhanced lipid utilization in this tissue may affect whole-body energy homeostasis and insulin sensitivity. PMID:15520860

Wilson-Fritch, Leanne; Nicoloro, Sarah; Chouinard, My; Lazar, Mitchell A.; Chui, Patricia C.; Leszyk, John; Straubhaar, Juerg; Czech, Michael P.; Corvera, Silvia

2004-01-01

274

Human adipose tissue-derived mesenchymal stem cells acquire muscle identity only after spontaneous fusion with myoblasts  

E-print Network

1 Human adipose tissue-derived mesenchymal stem cells acquire muscle identity only after transplantation. Previously, mesenchymal stem cells derived from human adipose tissue (hMADS cells) have been, and skeletal muscle (1-5). From a cell therapy perspective adipose tissue presents several advantages

Paris-Sud XI, Université de

275

Adult Stromal Cells Derived from Human Adipose Tissue Provoke Pancreatic Cancer Cell Death both In Vitro and  

E-print Network

Adult Stromal Cells Derived from Human Adipose Tissue Provoke Pancreatic Cancer Cell Death both adipose tissue (ADSC) on pancreatic tumor cell proliferation. Principal Findings: Co-culturing pancreatic from Human Adipose Tissue Provoke Pancreatic Cancer Cell Death both In Vitro and In Vivo. PLoS ONE 4

Paris-Sud XI, Université de

276

Metabolic signatures of human adipose tissue hypoxia in obesity.  

PubMed

Adipose tissue (AT) hypoxia has been proposed as the cause of obesity-related AT dysfunction, moving the tissue toward a proinflammatory phenotype. In humans, AT oxygenation has been assessed by expression of hypoxia-sensitive genes or direct assessment of O? tension; the obvious read out of hypoxia, effects on intermediary metabolism, has not been investigated. We used tissue-specific venous catheterization of subcutaneous abdominal AT in humans to investigate oxygen-related metabolic processes, searching for metabolic signatures relating to hypoxia in obesity. O? delivery to AT was reduced in obesity (P < 0.05). However, O? consumption was low (<30% of resting forearm skeletal muscle [SM], P < 0.001); this was not related to obesity. AT primarily oxidized glucose, as demonstrated by a respiratory quotient close to 1.0 (higher than SM, P < 0.05). AT was a net producer of lactate, but there was an inverse relationship in venous outflow between lactate-to-pyruvate ratio (a marker of cytosolic redox state) and BMI, suggesting that AT is glycolytic but obese AT is not hypoxic. Although delivery of O? to the obese AT is reduced, O? consumption is low, and metabolic signatures of human AT do not support the notion of a hypoxic state in obesity. PMID:23274888

Hodson, Leanne; Humphreys, Sandy M; Karpe, Fredrik; Frayn, Keith N

2013-05-01

277

Synthetic Adipose Tissue Models for Studying Mammary Gland Development and Breast Tissue Engineering  

Microsoft Academic Search

The mammary gland is a dynamic organ that continually changes its architecture and function. Reciprocal interactions between\\u000a epithelium and adipocyte-containing stroma exert profound effects on all stages of its development, even though the details\\u000a of these events are not fully understood. To address this issue, enormous potential exists in the utilization of synthetic\\u000a adipose tissue model systems to uncover the

Xiuli Wang; Michaela R. Reagan; David L. Kaplan

2010-01-01

278

Interleukin-15 contributes to the regulation of murine adipose tissue and human adipocytes.  

PubMed

An alarming global rise in the prevalence of obesity and its contribution to the development of chronic diseases is a serious health concern. Recently, obesity has been described as a chronic low-grade inflammatory condition, influenced by both adipose tissue and immune cells suggesting proinflammatory cytokines may play a role in its etiology. Here we examined the effects of interleukin-15 (IL-15) on adipose tissue and its association with obesity. Over expression of IL-15 (IL-15tg) was associated with lean body condition whereas lack of IL-15 (IL-15(-/-)) results in significant increase in weight gain without altering appetite. Interestingly, there were no differences in proinflammatory cytokines such as IL-6 and tumor necrosis factor-alpha (TNF-alpha) in serum between the three strains of mice. In addition, there were significant numbers of natural killer (NK) cells in fat tissues from IL-15tg and B6 compared to IL-15(-/-) mice. IL-15 treatment results in significant weight loss in IL-15(-/-) knockout and diet-induced obese mice independent of food intake. Fat pad cross-sections show decreased pad size with over expression of IL-15 is due to adipocyte shrinkage. IL-15 induces weight loss without altering food consumption by affecting lipid deposition in adipocytes. Treatment of differentiated human adipocytes with recombinant human IL-15 protein resulted in decreased lipid deposition. In addition, obese patients had significantly lower serum IL-15 levels when compared to normal weight individuals. These results clearly suggest that IL-15 may be involved in adipose tissue regulation and linked to obesity. PMID:20019685

Barra, Nicole G; Reid, Sarah; MacKenzie, Randy; Werstuck, Geoff; Trigatti, Bernardo L; Richards, Carl; Holloway, Alison C; Ashkar, Ali A

2010-08-01

279

Global DNA modifications suppress transcription in brown adipose tissue during hibernation.  

PubMed

Hibernation is crucial to winter survival for many small mammals and is characterized by prolonged periods of torpor during which strong global controls are applied to suppress energy-expensive cellular processes. We hypothesized that one strategy of energy conservation is a global reduction in gene transcription imparted by reversible modifications to DNA and to proteins involved in chromatin packing. Transcriptional regulation during hibernation was examined over euthermic control groups and five stages of the torpor/arousal cycle in brown adipose tissue of thirteen-lined ground squirrels (Ictidomys tridecemlineatus). Brown adipose is crucial to hibernation success because it is responsible for the non-shivering thermogenesis that rewarms animals during arousal. A direct modification of DNA during torpor was revealed by a 1.7-fold increase in global DNA methylation during long term torpor as compared with euthermic controls. Acetylation of histone H3 (on Lys23) was reduced by about 50% when squirrels entered torpor, which would result in increased chromatin packing (and transcriptional repression). This was accompanied by strong increases in histone deacetylase protein levels during torpor; e.g. HDAC1 and HDAC4 levels rose by 1.5- and 6-fold, respectively. Protein levels of two co-repressors of transcription, MBD1 and HP1, also increased by 1.9- and 1.5-fold, respectively, in long-term torpor and remained high during early arousal. MBD1, HP1 and HDACs all returned to near control values during interbout indicating a reversal of their inhibitory actions. Overall, the data presents strong evidence for a global suppression of transcription during torpor via the action of epigenetic regulatory mechanisms in brown adipose tissue of hibernating thirteen-lined ground squirrels. PMID:25192827

Biggar, Yulia; Storey, Kenneth B

2014-10-01

280

Molecular Characterization of Adipose Tissue in the African Elephant (Loxodonta africana)  

PubMed Central

Adipose tissue (AT) is a dynamic and flexible organ with regulatory roles in physiological functions including metabolism, reproduction and inflammation; secreted adipokines, including leptin, and fatty acids facilitate many of these roles. The African elephant (Loxodonta africana) is experiencing serious challenges to optimal reproduction in captivity. The physiological and molecular basis of this impaired fertility remains unknown. AT production of leptin is a crucial molecular link between nutritional status, adiposity and fertility in many species. We propose that leptin has a similar function in the African elephant. African elephant visceral and subcutaneous adipose tissue (AT) was obtained from both sexes and a range of ages including females with known pregnancy status. RNA was extracted and histological sections created and analyzed by microarray, PCR and immunohistochemistry respectively. Gas-chromatography was used to determine the fatty acid composition of AT. Microarray expression profiling was used to compare gene expression profiles of AT from pre-pubertal versus reproductively competent adult African elephants. This study demonstrates, for the first time, leptin mRNA and protein expression in African elephant AT. The derived protein sequence of the elephant leptin protein was exploited to determine its relationship within the class I helical cytokine superfamily, which indicates that elephant leptin is most closely related to the leptin orthologs of Oryctolagus cuniculus (European rabbit), Lepus oiostolus (woolly hare), and members of the Ochotonidae (Pika). Immunohistological analysis identified considerable leptin staining within the cytoplasm of adipocytes. Significant differences in fatty acid profiles between pregnant and non-pregnant animals were revealed, most notably a reduction in both linoleic and ? linoleic acid in pregnant animals. This report forms the basis for future studies to address the effect of nutrient composition and body condition on reproduction in captive and wild elephants. PMID:24633017

Choong, Siew S.; Giles, Thomas C.; Sells, James; May, Sean; Stansfield, Fiona J.; Allen, William R.; Emes, Richard D.; Mostyn, Alison; Mongan, Nigel P.; Yon, Lisa

2014-01-01

281

Molecular characterization of adipose tissue in the African elephant (Loxodonta africana).  

PubMed

Adipose tissue (AT) is a dynamic and flexible organ with regulatory roles in physiological functions including metabolism, reproduction and inflammation; secreted adipokines, including leptin, and fatty acids facilitate many of these roles. The African elephant (Loxodonta africana) is experiencing serious challenges to optimal reproduction in captivity. The physiological and molecular basis of this impaired fertility remains unknown. AT production of leptin is a crucial molecular link between nutritional status, adiposity and fertility in many species. We propose that leptin has a similar function in the African elephant. African elephant visceral and subcutaneous adipose tissue (AT) was obtained from both sexes and a range of ages including females with known pregnancy status. RNA was extracted and histological sections created and analyzed by microarray, PCR and immunohistochemistry respectively. Gas-chromatography was used to determine the fatty acid composition of AT. Microarray expression profiling was used to compare gene expression profiles of AT from pre-pubertal versus reproductively competent adult African elephants. This study demonstrates, for the first time, leptin mRNA and protein expression in African elephant AT. The derived protein sequence of the elephant leptin protein was exploited to determine its relationship within the class I helical cytokine superfamily, which indicates that elephant leptin is most closely related to the leptin orthologs of Oryctolagus cuniculus (European rabbit), Lepus oiostolus (woolly hare), and members of the Ochotonidae (Pika). Immunohistological analysis identified considerable leptin staining within the cytoplasm of adipocytes. Significant differences in fatty acid profiles between pregnant and non-pregnant animals were revealed, most notably a reduction in both linoleic and ? linoleic acid in pregnant animals. This report forms the basis for future studies to address the effect of nutrient composition and body condition on reproduction in captive and wild elephants. PMID:24633017

Nilsson, Emeli M; Fainberg, Hernan P; Choong, Siew S; Giles, Thomas C; Sells, James; May, Sean; Stansfield, Fiona J; Allen, William R; Emes, Richard D; Mostyn, Alison; Mongan, Nigel P; Yon, Lisa

2014-01-01

282

Levels of persistent organic pollutant residues in human adipose and muscle tissues in Singapore.  

PubMed

Persistent organic pollutants (POPs), due to their persistence and bioconcentration in lipid-rich tissue, bioaccumulate in food chains, resulting in elevated concentrations in humans. This study was performed to determine and compare levels of POPs in human adipose and muscle tissues in the female population of Singapore. In total, 36 human adipose tissues and 8 human muscle tissues were collected from volunteer expectant mothers admitted to the National University Hospital Singapore for cesarean section delivery between August 2003 and January 2005. Samples were analyzed using a validated and quality-assured gas chromatography-mass spectroscopy (GC-MS) method in conjunction with microwave-assisted extraction (MAE). Analytes recoveries from certified reference materials, that is, IRMM-446 (polychlorinated biphenyls [PCBs] in pork fat) and BCR-430 (organochlorine pesticides in pork fat), were between 70 and 130%, indicating reliable analytical precision for this methodology. MAE efficiency for polybrominated diphenyl ethers (PBDEs) was compared to Soxhlet extraction (SE) efficiency and yielded comparable results (variation < 13%). Analytical results indicate that p,p'-DDE of the dichlorodiphenyltrichloroethane (DDT) residues group is the predominant compound in adipose tissue, followed by beta-hexachlorocyclohexane (beta-HCH) among HCH isomers, then hexachlorobenzene (HCB) compound and specific PCB and PBDE congeners. Among the 36 adipose tissues, the lipid contents in adipose tissue were in the range of 60% to 95%, while in the 8 muscle tissues, lipids were undetectable. However, the profile of PCBs and pesticide residues present in muscle tissues were similar to those in adipose tissues. PMID:16982531

Li, Qing Qing; Loganath, Annamalai; Chong, Yap Seng; Tan, Jing; Obbard, Jeffrey Philip

2006-11-01

283

An early inflammatory gene profile in visceral adipose tissue in children.  

PubMed

The aim of this study was to characterize expression profiles of visceral and subcutaneous adipose tissue in children. Adipose tissue samples were collected from children having elective surgery (n = 71, [54 boys], 6.0 ± 4.3 years). Affymetrix microarrays (n = 20) were performed to characterize the functional profile and identify genes of interest in adipose tissue. Visceral adipose tissue had an overrepresentation of Gene Ontology themes related to immune and inflammatory responses and subcutaneous adipose tissue had an overrepresentation of themes related to adipocyte growth and development. Likewise, qPCR performed in the whole cohort showed a 30-fold increase in haptoglobin (P = 0.005), 7-fold increase in IL-10 (P < 0.001), 8-fold decrease in VEGF (P = 0.01) and a 28-fold decrease in TBOX15 (P < 0.001) in visceral compared to subcutaneous adipose tissue. The inflammatory pattern in visceral adipose tissue may represent an early stage of the adverse effects of this depot, and combined with chronic obesity, may contribute to increased metabolic and cardiovascular risk. PMID:21609243

Tam, Charmaine S; Heilbronn, Leonie K; Henegar, Corneliu; Wong, Melanie; Cowell, Christopher T; Cowley, Mark J; Kaplan, Warren; Clément, Karine; Baur, Louise A

2011-06-01

284

Stimulation of adipogenesis of adult adipose-derived stem cells using substrates that mimic the stiffness of adipose tissue  

PubMed Central

Biochemical and biomechanical extracellular matrix (ECM) cues have recently been shown to play a role in stimulating stem cell differentiation towards several lineages, though how they combine to induce adipogenesis has been less well studied. The objective of this study was to recapitulate both the ECM composition and mechanical properties of adipose tissue in vitro to stimulate adipogenesis of human adipose-derived stem cells (ASCs) in the absence of exogenous adipogenic growth factors and small molecules. Adipose specific ECM biochemical cues have been previously shown to influence adipogenic differentiation; however, the ability of biomechanical cues to promote adipogenesis has been less defined. Decellularized human lipoaspirate was used to functionalize polyacrylamide gels of varying stiffness to allow the cells to interact with adipose-specific ECM components. Culturing ASCs on gels that mimicked the native stiffness of adipose tissue (2 kPa) significantly upregulated adipogenic markers, in the absence of exogenous adipogenic growth factors and small molecules. As substrate stiffness increased, the cells became more spread, lost their rounded morphology, and failed to upregulate adipogenic markers. Together these data imply that as with other lineages, mechanical cues are capable of regulating adipogenesis in ASCs. PMID:23953825

Young, D. Adam; Choi, Yu Suk; Engler, Adam J.; Christman, Karen L.

2013-01-01

285

Cerenkov luminescence imaging of interscapular brown adipose tissue.  

PubMed

Brown adipose tissue (BAT), widely known as a "good fat" plays pivotal roles for thermogenesis in mammals. This special tissue is closely related to metabolism and energy expenditure, and its dysfunction is one important contributor for obesity and diabetes. Contrary to previous belief, recent PET/CT imaging studies indicated the BAT depots are still present in human adults. PET imaging clearly shows that BAT has considerably high uptake of (18)F-FDG under certain conditions. In this video report, we demonstrate that Cerenkov luminescence imaging (CLI) with (18)F-FDG can be used to optically image BAT in small animals. BAT activation is observed after intraperitoneal injection of norepinephrine (NE) and cold treatment, and depression of BAT is induced by long anesthesia. Using multiple-filter Cerenkov luminescence imaging, spectral unmixing and 3D imaging reconstruction are demonstrated. Our results suggest that CLI with (18)F-FDG is a practical technique for imaging BAT in small animals, and this technique can be used as a cheap, fast, and alternative imaging tool for BAT research. PMID:25349986

Zhang, Xueli; Kuo, Chaincy; Moore, Anna; Ran, Chongzhao

2014-01-01

286

Toxicological Function of Adipose Tissue: Focus on Persistent Organic Pollutants  

PubMed Central

Background: Adipose tissue (AT) is involved in several physiological functions, including metabolic regulation, energy storage, and endocrine functions. Objectives: In this review we examined the evidence that an additional function of AT is to modulate persistent organic pollutant (POP) toxicity through several mechanisms. Methods: We reviewed the literature on the interaction of AT with POPs to provide a comprehensive model for this additional function of AT. Discussion: As a storage compartment for lipophilic POPs, AT plays a critical role in the toxicokinetics of a variety of drugs and pollutants, in particular, POPs. By sequestering POPs, AT can protect other organs and tissues from POPs overload. However, this protective function could prove to be a threat in the long run. The accumulation of lipophilic POPs will increase total body burden. These accumulated POPs are slowly released into the bloodstream, and more so during weight loss. Thus, AT constitutes a continual source of internal exposure to POPs. In addition to its buffering function, AT is also a target of POPs and may mediate part of their metabolic effects. This is particularly relevant because many POPs induce obesogenic effects that may lead to quantitative and qualitative alterations of AT. Some POPs also induce a proinflammatory state in AT, which may lead to detrimental metabolic effects. Conclusion: AT appears to play diverse functions both as a modulator and as a target of POPs toxicity. PMID:23221922

La Merrill, Michele; Emond, Claude; Kim, Min Ji; Antignac, Jean-Philippe; Le Bizec, Bruno; Clement, Karine; Birnbaum, Linda S.

2012-01-01

287

5. cap alpha. -reductase activity in rat adipose tissue  

SciTech Connect

We measured the 5 ..cap alpha..-reductase activity in isolated cell preparations of rat adipose tissue using the formation of (/sup 3/H) dihydrotestosterone from (/sup 3/H) testosterone as an endpoint. Stromal cells were prepared from the epididymal fat pad, perinephric fat, and subcutaneous fat of male rats and from perinephric fat of female rats. Adipocytes were prepared from the epididymal fat pad and perinephric fat of male rats. Stromal cells from the epididymal fat pad and perinephric fat contained greater 5..cap alpha..-reductase activity than did the adipocytes from these depots. Stromal cells from the epididymal fat pad contained greater activity than those from perinephric and subcutaneous depots. Perinephric stromal cells from female rats were slightly more active than those from male rats. Estradiol (10/sup -8/ M), when added to the medium, caused a 90% decrease in 5..cap alpha..-reductase activity. Aromatase activity was minimal, several orders of magnitude less than 5..cap alpha..-reductase activity in each tissue studied.

Zyirek, M.; Flood, C.; Longcope, C.

1987-11-01

288

Selective overexpression of human SIRT1 in adipose tissue enhances energy homeostasis and prevents the deterioration of insulin sensitivity with ageing in mice  

PubMed Central

SIRT1, a longevity regulator and NAD+-dependent deacetylase, plays a critical role in promoting metabolic fitness associated with calorie restriction and healthy ageing. Using a tissue-specific transgenic approach, the present study demonstrates that over-expression of human SIRT1 selectively in adipose tissue of mice prevents ageing-induced deterioration of insulin sensitivity and ectopic lipid distribution, reduces whole body fat mass and enhances locomotor activity. During ageing, the water-soluble vitamin biotin is progressively accumulated in adipose tissue. Over-expression of SIRT1 alleviates ageing-associated biotin accumulation and reduces the amount of biotinylated proteins, including acetyl CoA carboxylase, a major reservoir of biotin in adipose tissues. Chronic biotin supplementation increases adipose biotin contents and abolishes adipose SIRT1-mediated beneficial effects on insulin sensitivity, lipid metabolism and locomotor activity. Biochemical, spectrometric and chromatographic analysis revealed that biotin and its metabolites act as competitive inhibitors of SIRT1-mediated deacetylation. In summary, these results demonstrate that adipose SIRT1 is a key player in maintaining systemic energy homeostasis and insulin sensitivity; enhancing its activity solely in adipose tissue can prevent ageing-associated metabolic disorders. PMID:23724165

Xu, Cheng; Bai, Bo; Fan, Pengcheng; Cai, Yu; Huang, Bosheng; Law, Ivy KM; Liu, Ling; Xu, Aimin; Tung, Chunling; Li, Xuechen; Siu, Fung-Ming; Che, Chi-Ming; Vanhoutte, Paul M; Wang, Yu

2013-01-01

289

Determination of inflammatory and prominent proteomic changes in plasma and adipose tissue after high-intensity intermittent training in overweight and obese males  

PubMed Central

This study aimed to determine whether 2 wk of high-intensity intermittent training (HIIT) altered inflammatory status in plasma and adipose tissue in overweight and obese males. Twelve participants [mean (SD): age 23.7 (5.2) yr, body mass 91.0 (8.0) kg, body mass index 29.1 (3.1) kg/m2] undertook six HIIT sessions over 2 wk. Resting blood and subcutaneous abdominal adipose tissue samples were collected and insulin sensitivity determined, pre- and posttraining. Inflammatory proteins were quantified in plasma and adipose tissue. There was a significant decrease in soluble interleukin-6 receptor (sIL-6R; P = 0.050), monocyte chemotactic protein-1 (MCP-1, P = 0.047), and adiponectin (P = 0.041) in plasma posttraining. Plasma IL-6, intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-? (TNF-?), IL-10, and insulin sensitivity did not change. In adipose tissue, IL-6 significantly decreased (P = 0.036) and IL-6R increased (P = 0.037), while adiponectin tended to decrease (P = 0.056), with no change in ICAM-1 posttraining. TNF-?, MCP-1, and IL-10 were not detectable in adipose tissue. Adipose tissue homogenates were then resolved using one-dimensional gel electrophoresis, and major changes in the adipose tissue proteome, as a consequence of HIIT, were evaluated. This proteomic approach identified significant reductions in annexin A2 (P = 0.046) and fatty acid synthase (P = 0.016) as a response to HIIT. The present investigation suggests 2 wk of HIIT is sufficient to induce beneficial alterations in the resting inflammatory profile and adipose tissue proteome of an overweight and obese male cohort. PMID:22267387

Leggate, Melanie; Carter, Wayne G.; Evans, Matthew J. C.; Vennard, Rebecca A.; Sribala-Sundaram, Sarah

2012-01-01

290

Determination of inflammatory and prominent proteomic changes in plasma and adipose tissue after high-intensity intermittent training in overweight and obese males.  

PubMed

This study aimed to determine whether 2 wk of high-intensity intermittent training (HIIT) altered inflammatory status in plasma and adipose tissue in overweight and obese males. Twelve participants [mean (SD): age 23.7 (5.2) yr, body mass 91.0 (8.0) kg, body mass index 29.1 (3.1) kg/m(2)] undertook six HIIT sessions over 2 wk. Resting blood and subcutaneous abdominal adipose tissue samples were collected and insulin sensitivity determined, pre- and posttraining. Inflammatory proteins were quantified in plasma and adipose tissue. There was a significant decrease in soluble interleukin-6 receptor (sIL-6R; P = 0.050), monocyte chemotactic protein-1 (MCP-1, P = 0.047), and adiponectin (P = 0.041) in plasma posttraining. Plasma IL-6, intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-? (TNF-?), IL-10, and insulin sensitivity did not change. In adipose tissue, IL-6 significantly decreased (P = 0.036) and IL-6R increased (P = 0.037), while adiponectin tended to decrease (P = 0.056), with no change in ICAM-1 posttraining. TNF-?, MCP-1, and IL-10 were not detectable in adipose tissue. Adipose tissue homogenates were then resolved using one-dimensional gel electrophoresis, and major changes in the adipose tissue proteome, as a consequence of HIIT, were evaluated. This proteomic approach identified significant reductions in annexin A2 (P = 0.046) and fatty acid synthase (P = 0.016) as a response to HIIT. The present investigation suggests 2 wk of HIIT is sufficient to induce beneficial alterations in the resting inflammatory profile and adipose tissue proteome of an overweight and obese male cohort. PMID:22267387

Leggate, Melanie; Carter, Wayne G; Evans, Matthew J C; Vennard, Rebecca A; Sribala-Sundaram, Sarah; Nimmo, Myra A

2012-04-01

291

Functional Brown Adipose Tissue is Related to Muscle Volume in Children and Adolescents  

E-print Network

Functional Brown Adipose Tissue is Related to Muscle Volume in Children and Adolescents Vicente/ computed tomography (PET/CT) in pediatric patients is associated with anthropometric meaures. Study design We determined measures of body mass, adiposity, and musculature in 71 children and adolescents who

Southern California, University of

292

Adipose tissue-derived stem cells: the friendly side of a classic cardiovascular foe.  

PubMed

Recently, the existence of a population of stem cells located in the adipose tissue has been observed. Adipose-derived stem cells are able to differentiate into multiple cell lineages including cardiac myocytes. Hence, adipose-derived cells are emerging as a new source of adult stem cells for cardiovascular repair. In this review, we discuss the basic principles of adipose-derived stem cells (types and characteristics, obtention processes, immunophenotypic characterization, and cell potency), the initial experimental studies, and the currently ongoing clinical trials. PMID:20559958

Sanz-Ruiz, Ricardo; Santos, María Eugenia Fernández; Muñoa, Marta Domínguez; Martín, Ingrid Ludwig; Parma, Radoslaw; Fernández, Pedro L Sánchez; Fernández-Avilés, Francisco

2008-03-01

293

Transcriptomic analysis of brown adipose tissue across the physiological extremes of natural hibernation.  

PubMed

We used RNAseq to generate a comprehensive transcriptome of Brown Adipose Tissue (BAT) over the course of a year in the naturally hibernating thirteen-lined ground squirrel, Ictidomys tridecemlineatus. During hibernation ground squirrels do not feed and use fat stored in White Adipose Tissue (WAT) as their primary source of fuel. Stored lipid is consumed at high rates by BAT to generate heat at specific points during the hibernation season. The highest rate of BAT activity occurs during periodic arousals from hypothermic torpor bouts, referred to as Interbout Arousals (IBAs). IBAs are characterized by whole body re-warming (from 5 to 37 °C) in 2-3 hours, and provide a unique opportunity to determine the genes responsible for the highly efficient lipid oxidation and heat generation that drives the arousal process. Illumina HighSeq sequencing identified 14,573 distinct BAT mRNAs and quantified their levels at four points: active ground squirrels in April and October, and hibernating animals during both torpor and IBA. Based on significant changes in mRNA levels across the four collection points, 2,083 genes were shown to be differentially expressed. In addition to providing detail on the expression of nuclear genes encoding mitochondrial proteins, and genes involved in beta-adrenergic and lipolytic pathways, we identified differentially expressed genes encoding various transcription factors and other regulatory proteins which may play critical roles in high efficiency fat catabolism, non-shivering thermogenesis, and transitions into and out of the torpid state. PMID:24386461

Hampton, Marshall; Melvin, Richard G; Andrews, Matthew T

2013-01-01

294

Adipose tissue as a stem cell source for musculo-skeletal regeneration  

PubMed Central

Adipose tissue is an abundant, easily accessible, and reproducible cell source for musculo-skeletal regenerative medicine applications. Initial derivation steps yield a heterogeneous population of cells collectively termed the stromal vascular fraction (SVF), which consist of endothelial cells, immune cells, pericytes, and pre-adipocytes. Subsequent selection of an adherent cell subset from the SVF results in a relatively homogeneous population of adipose-derived stromal/stem cells (ASCs). Mammalian ASCs exhibit the ability to selectively differentiate into chondrogenic, myogenic, and osteogenic lineages in response to inductive stimuli in vitro (when cultured on scaffolds in bioreactors) and in vivo (when implanted in pre-clinical animal models). Unlike hematopoietic cells, ASCs do not elicit a robust lymphocyte reaction and instead generate and release immunosuppressive factors, such as prostaglandin E2. These unique immunomodulatory features suggest that both allogeneic and autologous ASCs will engraft successfully following application for tissue regeneration purposes. The differentiation and expansion potential of ASCs can be modified by growth factors like bone morphogenetic protein 6, bio-inductive scaffolds, and bioreactors providing environmental control and biophysical stimulation. Gene therapy approaches using lentiviral transduction can also be used to direct differentiation of ASCs along particular lineage pathways. We discuss here the utility of ASCs for musculo-skeletal tissue repair and some of the technologies that can be implemented to unlock the full regenerative potential of these highly valuable cells. PMID:21196358

Gimble, Jeffrey M.; Grayson, Warren; Guilak, Farshid; Lopez, Mandi J.; Vunjak-Novakovic, Gordana

2013-01-01

295

Defining the human adipose tissue proteome to reveal metabolic alterations in obesity.  

PubMed

White adipose tissue (WAT) has a major role in the progression of obesity. Here, we combined data from RNA-Seq and antibody-based immunohistochemistry to describe the normal physiology of human WAT obtained from three female subjects and explored WAT-specific genes by comparing WAT to 26 other major human tissues. Using the protein evidence in WAT, we validated the content of a genome-scale metabolic model for adipocytes. We employed this high-quality model for the analysis of subcutaneous adipose tissue (SAT) gene expression data obtained from subjects included in the Swedish Obese Subjects Sib Pair study to reveal molecular differences between lean and obese individuals. We integrated SAT gene expression and plasma metabolomics data, investigated the contribution of the metabolic differences in the mitochondria of SAT to the occurrence of obesity, and eventually identified cytosolic branched-chain amino acid (BCAA) transaminase 1 as a potential target that can be used for drug development. We observed decreased glutaminolysis and alterations in the BCAAs metabolism in SAT of obese subjects compared to lean subjects. We also provided mechanistic explanations for the changes in the plasma level of BCAAs, glutamate, pyruvate, and ?-ketoglutarate in obese subjects. Finally, we validated a subset of our model-based predictions in 20 SAT samples obtained from 10 lean and 10 obese male and female subjects. PMID:25219818

Mardinoglu, Adil; Kampf, Caroline; Asplund, Anna; Fagerberg, Linn; Hallström, Björn M; Edlund, Karolina; Blüher, Matthias; Pontén, Fredrik; Uhlen, Mathias; Nielsen, Jens

2014-11-01

296

Modulation of Adipogenic Conditions for Prospective Use of hADSCs in Adipose Tissue Engineering  

PubMed Central

Modern strategies in adipose tissue engineering (ATE) take advantage of the easy harvest, abundance and differentiation potential towards mesenchymal lineages of hADSCs. The controlled conversion of hADSCs to committed adipogenic precursors and further mature adipocytes formation is important for good long-term results in soft tissue regeneration. Thus, in this study, we report: (i) the isolation of the processed lipoaspirate (PLA) cells from adipose tissue and sanguine fractions; (ii) the phenotypic characterization of the PLA descendants; (iii) the design of a novel protocol for the modulation of adipogenic conditions in the perspectives of ATE applications. To modulate the differentiation rate through our protocol, we propose to selectively modify the formulation of the adipogenic media in accordance with the evolution of the process. Therefore, we aimed to ensure the long-term proliferation of the precursor cells and to delay the late adipogenic events. The status of differentiation was characterized in terms of intracellular lipid accumulation and reorganization of the cytoskeleton simultaneously with perilipin protein expression. Moreover, we studied the sequential activation of PPAR?2, FAS, aP2 and perilipin genes which influence the kinetics of the adipogenic process. The strategies developed in this work are the prerequisites for prospective 3D regenerative systems. PMID:23443100

Galateanu, Bianca; Dinescu, Sorina; Cimpean, Anisoara; Dinischiotu, Anca; Costache, Marieta

2012-01-01

297

Physical Exercise Reduces the Expression of RANTES and Its CCR5 Receptor in the Adipose Tissue of Obese Humans  

PubMed Central

RANTES and its CCR5 receptor trigger inflammation and its progression to insulin resistance in obese. In the present study, we investigated for the first time the effect of physical exercise on the expression of RANTES and CCR5 in obese humans. Fifty-seven adult nondiabetic subjects (17 lean and 40 obese) were enrolled in a 3-month supervised physical exercise. RANTES and CCR5 expressions were measured in PBMCs and subcutaneous adipose tissue before and after exercise. Circulating plasma levels of RANTES were also investigated. There was a significant increase in RANTES and CCR5 expression in the subcutaneous adipose tissue of obese compared to lean. In PBMCs, however, while the levels of RANTES mRNA and protein were comparable between both groups, CCR5 mRNA was downregulated in obese subjects (P < 0.05). Physical exercise significantly reduced the expression of both RANTES and CCR5 (P < 0.05) in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNF-?, IL-6, and P-JNK. Circulating RANTES correlated negatively with anti-inflammatory IL-1ra (P = 0.001) and positively with proinflammatory IP-10 and TBARS levels (P < 0.05). Therefore, physical exercise may provide an effective approach for combating the deleterious effects associated with obesity through RANTES signaling in the adipose tissue. PMID:24895488

Baturcam, Engin; Tiss, Ali; Khadir, Abdelkrim; Al-Ghimlas, Fahad; Al-Khairi, Irina; Cherian, Preethi; Elkum, Naser; John, Jeena; Kavalakatt, Sina; Lehe, Cynthia; Warsame, Samia; Behbehani, Kazem; Dermime, Said

2014-01-01

298

UCP1 is present in porcine adipose tissue and is responsive to postnatal leptin.  

PubMed

Intrauterine growth restriction (IUGR) may be accompanied by inadequate thermoregulation, especially in piglets that are not considered to possess any brown adipose tissue (BAT) and are thus entirely dependent on shivering thermogenesis in order to maintain body temperature after birth. Leptin can stimulate heat production by promoting non-shivering thermogenesis in BAT, but whether this response occurs in piglets is unknown. Newborn female piglets that were characterised as showing IUGR (mean birth weight of approximately 0.98?kg) were therefore administered injections of either saline or leptin once a day for the first 5 days of neonatal life. The dose of leptin was 0.5?mg/kg, which is sufficient to increase plasma leptin by approximately tenfold and on the day of birth induced a rapid increase in body temperature to values similar to those of normal-sized 'control' piglets (mean birth weight of ?1.47?kg). Perirenal adipose tissue was then sampled from all offspring at 21 days of age and the presence of the BAT-specific uncoupling protein 1 (UCP1) was determined by immunohistochemistry and immunoblotting. UCP1 was clearly detectable in all samples analysed and its abundance was significantly reduced in the IUGR piglets that had received saline compared with controls, but was raised to the same amount as in controls in those IUGR females given leptin. There were no differences in gene expression between primary markers of brown and white adipose tissues between groups. In conclusion, piglets possess BAT that when stimulated exogenously by leptin can promote increased body temperature. PMID:25122002

Mostyn, Alison; Attig, Linda; Larcher, Thibaut; Dou, Samir; Chavatte-Palmer, Pascale; Boukthir, Monia; Gertler, Arieh; Djiane, Jean; E Symonds, Michael; Abdennebi-Najar, Latifa

2014-10-01

299

Altered Lipid Metabolism in Residual White Adipose Tissues of Bscl2 Deficient Mice  

PubMed Central

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 oleic18:1n9 acid concomitant with a lower proportion of palmitic16:0 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 ?-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. PMID:24358199

Chen, Weiqin; Zhou, Hongyi; Liu, Siyang; Fhaner, Cassie J.; Gross, Bethany C.; Lydic, Todd A.; Reid, Gavin E.

2013-01-01

300

Weight Reduction Increases Plasma Levels of an Adipose-Derived Anti-Inflammatory Protein, Adiponectin  

Microsoft Academic Search

Adiponectin, an adipose tissue-specific plasma protein, was recently revealed to have anti-inflammatory effects on the cellular components of vascular wall. Its plasma levels were significantly lower in men than in women and lower in human subjects with obesity, type 2 diabetes mellitus, or coronary artery disease. Therefore, it may provide a biological link between obesity and obesity-related disorders such as

WEI-SHIUNG YANG; WEI-JEI LEE; TOHRU FUNAHASHI; SACHIYO TANAKA; YUJI MATSUZAWA; CHIA-LING CHAO; CHI-LING CHEN; TONG-YUAN TAI; LEE-MING CHUANG

2010-01-01

301

Early postnatal maternal separation causes alterations in the expression of ?3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity  

SciTech Connect

Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of ?3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), ?3-adrenergic receptor (?3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through ?3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the ?3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan)] [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan)] [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan)] [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan)] [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan)] [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan)] [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

2013-12-06

302

Thymidine Kinase 2 Deficiency-Induced Mitochondrial DNA Depletion Causes Abnormal Development of Adipose Tissues and Adipokine Levels in Mice  

PubMed Central

Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues. PMID:22216345

Villarroya, Joan; Dorado, Beatriz; Vila, Maya R.; Garcia-Arumi, Elena; Domingo, Pere; Giralt, Marta; Hirano, Michio; Villarroya, Francesc

2011-01-01

303

Evidence of in Situ Proliferation of Adult Adipose Tissue-Derived Progenitor Cells: Influence of Fat Mass  

E-print Network

Evidence of in Situ Proliferation of Adult Adipose Tissue-Derived Progenitor Cells: Influence by the degree of adiposity. Changes in the progenitor cell microenvironment involving adipokines, hypoxia cells. (J Clin Endocrinol Metab 93: 4098­4106, 2008) The excessive development of human adipose tissue

Paris-Sud XI, Université de

304

Reprogramming human adipose tissue stem cells using epidermal keratinocyte extracts  

PubMed Central

Human adipose tissue stem cells (ATSCs) can differentiate into various types of cell in response to lineage-specific induction factors. Reprogramming cells using nuclear and cytoplasmic extracts derived from another type of somatic cell is an effective method of producing specific types of differentiated cell. In the present study, the ability of reprogrammed ATSCs to acquire epidermal keratinocyte properties following transient exposure to epidermal keratinocyte extracts was demonstrated. Reversibly permeabilized ATSCs were incubated for 1 h in nuclear and cytoplasmic extracts from epidermal keratinocytes, resealed with CaCl2 and cultured. ATSC reprogramming is demonstrated by nuclear uptake of epidermal keratinocyte extracts. After one week of exposure to extracts, ATSCs underwent changes in cell morphology, cell-specific genes were activated, and epidermal keratinocyte markers including K19 and K1/K10 (markers of stem cells and terminally differentiated keratinocytes, respectively) were expressed. This study indicates that the reprogramming of ATSCs using nuclear and cytoplasmic extracts from epidermal keratinocytes is a viable option for the production of specific types of cell. PMID:25333210

XIE, FENG; TANG, XINJIE; ZHANG, QUN; DENG, CHENLIANG

2015-01-01

305

Adipose Tissue Distribution Predicts Survival in Amyotrophic Lateral Sclerosis  

PubMed Central

Background amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to death within a few years after diagnosis. Malnutrition and weight loss are frequent and are indexes of poor prognosis. Total body fat and fat distribution have not been studied in ALS patients. Objectives Our aim was to describe adipose tissue content and distribution in ALS patients. Design We performed a cross-sectional study in a group of ALS patients (n?=?62, mean disease duration 22 months) along with age and gender matched healthy controls (n?=?62) using a MRI-based method to study quantitatively the fat distribution. Results Total body fat of ALS patients was not changed as compared with controls. However, ALS patients displayed increased visceral fat and an increased ratio of visceral to subcutaneous fat. Visceral fat was not correlated with clinical severity as judged using the ALS functional rating scale (ALS-FRS-R), while subcutaneous fat in ALS patients correlated positively with ALS-FRS-R and disease progression. Multiple regression analysis showed that gender and ALS-FRS-R, but not site of onset, were significant predictors of total and subcutaneous fat. Increased subcutaneous fat predicted survival in male patients but not in female patients (p<0.05). Conclusions Fat distribution is altered in ALS patients, with increased visceral fat as compared with healthy controls. Subcutaneous fat content is a predictor of survival of ALS patients. PMID:23826340

Lindauer, Eva; Dupuis, Luc; Müller, Hans-Peter; Neumann, Heiko; Ludolph, Albert C.; Kassubek, Jan

2013-01-01

306

Reprogramming human adipose tissue stem cells using epidermal keratinocyte extracts.  

PubMed

Human adipose tissue stem cells (ATSCs) can differentiate into various types of cell in response to lineage?specific induction factors. Reprogramming cells using nuclear and cytoplasmic extracts derived from another type of somatic cell is an effective method of producing specific types of differentiated cell. In the present study, the ability of reprogrammed ATSCs to acquire epidermal keratinocyte properties following transient exposure to epidermal keratinocyte extracts was demonstrated. Reversibly permeabilized ATSCs were incubated for 1 h in nuclear and cytoplasmic extracts from epidermal keratinocytes, resealed with CaCl2 and cultured. ATSC reprogramming is demonstrated by nuclear uptake of epidermal keratinocyte extracts. After one week of exposure to extracts, ATSCs underwent changes in cell morphology, cell?specific genes were activated, and epidermal keratinocyte markers including K19 and K1/K10 (markers of stem cells and terminally differentiated keratinocytes, respectively) were expressed. This study indicates that the reprogramming of ATSCs using nuclear and cytoplasmic extracts from epidermal keratinocytes is a viable option for the production of specific types of cell. PMID:25333210

Xie, Feng; Tang, Xinjie; Zhang, Qun; Deng, Chenliang

2015-01-01

307

The influence of perivascular adipose tissue on vascular homeostasis  

PubMed Central

The perivascular adipose tissue (PVAT) is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT. PMID:23576873

Szasz, Theodora; Bomfim, Gisele Facholi; Webb, R Clinton

2013-01-01

308

Central sympathetic innervations to visceral and subcutaneous white adipose tissue.  

PubMed

There is a link between visceral white adipose tissue (WAT) and the metabolic syndrome in humans, with health improvements produced with small visceral WAT reduction. By contrast, subcutaneous WAT provides a site for lipid storage that is rather innocuous relative to ectopic lipid storage in muscle or liver. The sympathetic nervous system (SNS) is the principal initiator for lipolysis in WAT by mammals. Nothing is known, however, about the central origins of the SNS circuitry innervating the only true visceral WAT in rodents, mesenteric WAT (MWAT), which drains into the hepatic portal vein. We tested whether the central sympathetic circuits to subcutaneous [inguinal WAT (IWAT)] and visceral WAT (MWAT) are separate or shared and whether they possess differential sympathetic drives with food deprivation in Siberian hamsters. Using two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer within the same hamsters, we found some overlap (?20-55% doubly infected neurons) between the two circuitries across the neural axis with lesser overlap proximal to the depots (spinal cord and sympathetic chain) and with more neurons involved in the innervation of IWAT than MWAT in some brain regions. Food deprivation triggered a greater sympathetic drive to subcutaneous (IWAT) than visceral (MWAT) depots. Collectively, we demonstrated both shared and separate populations of brain, spinal cord, and sympathetic chain neurons ultimately project to a subcutaneous WAT depot (IWAT) and the only visceral WAT depot in rodents (MWAT). In addition, the lipolytic stimulus of food deprivation only increased SNS drive to subcutaneous fat (IWAT). PMID:24452544

Nguyen, Ngoc Ly T; Randall, Jessica; Banfield, Bruce W; Bartness, Timothy J

2014-03-15

309

Adipose tissue stem cells meet preadipocyte commitment: going back to the future[S  

PubMed Central

White adipose tissue (WAT) is perhaps the most plastic organ in the body, capable of regeneration following surgical removal and massive expansion or contraction in response to altered energy balance. Research conducted for over 70 years has investigated adipose tissue plasticity on a cellular level, spurred on by the increasing burden that obesity and associated diseases are placing on public health globally. This work has identified committed preadipocytes in the stromal vascular fraction of adipose tissue and led to our current understanding that adipogenesis is important not only for WAT expansion, but also for maintenance of adipocyte numbers under normal metabolic states. At the turn of the millenium, studies investigating preadipocyte differentiation collided with developments in stem cell research, leading to the discovery of multipotent stem cells within WAT. Such adipose tissue-derived stem cells (ASCs) are capable of differentiating into numerous cell types of both mesodermal and nonmesodermal origin, leading to their extensive investigation from a therapeutic and tissue engineering perspective. However, the insights gained through studying ASCs have also contributed to more-recent progress in attempts to better characterize committed preadipocytes in adipose tissue. Thus, ASC research has gone back to its roots, thereby expanding our knowledge of preadipocyte commitment and adipose tissue biology. PMID:22140268

Cawthorn, William P.; Scheller, Erica L.; MacDougald, Ormond A.

2012-01-01

310

Lipogenesis in liver, lung and adipose tissue of rats fed with oleoylanilide.  

PubMed Central

Oleoylanilide was administered orally to groups of rats according to different patterns. Subcellular fractionation of liver, lung and adipose tissue was then carried out in order to study the main enzyme activities involved in the lipogenesis. The observed findings indicate that adipose tissue and lung are the main target organs for the anilide, adipose tissue being involved in a general decrease of the enzyme activities, whereas transacylation reaction exhibits the most marked depletion of all the enzyme activities in the lung. The enzyme activities in liver were not markedly affected by this oral administration, although some data support the existence of a latent liver toxicity. These data suggest that oleoylanilide has the capacity to alter lipid metabolism of lung and adipose tissue to a considerable extent, whereas no major effect was produced in the liver. This different organ response could be related to the lymphatic gland via absorption of the substance. PMID:6882376

Casals, C; Garcia-Barreno, P; Municio, A M

1983-01-01

311

ER? upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue  

PubMed Central

Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor ? (ER?) have the opposite effect. Here we identify an Estrogen Response Element (ERE) in the promoter of Phd3, which is a negative regulatory enzyme of HIF-1, and we demonstrate HIF-1? is ubiquitinated following 17-? estradiol (E2)/ER? mediated Phd3 transcription. Manipulating ER? in vivo increases Phd3 transcription and reduces HIF-1 activity, while addition of PHD3 ameliorates adipose tissue fibrosis and inflammation. Our findings outline a novel regulatory relationship between E2/ER?, PHD3 and HIF-1 in adipose tissues, providing a mechanistic explanation for the protective effect of E2/ER? in adipose tissue. PMID:25161887

Kim, Min; Neinast, Michael D.; Frank, Aaron P.; Sun, Kai; Park, Jiyoung; Zehr, Jordan A.; Vishvanath, Lavanya; Morselli, Eugenia; Amelotte, Mason; Palmer, Biff F.; Gupta, Rana K.; Scherer, Philipp E.; Clegg, Deborah J.

2014-01-01

312

Lipid Metabolism in Bovine Subcutaneous Adipose Tissue of Steers Fed Supplementary Palm Oil or Soybean Oil  

E-print Network

We hypothesized that supplementing finishing diets with palm oil would elevate Stearoyl-CoA desaturase (SCD) activity in muscle and subcutaneous (s.c.) adipose tissue, promoting adipocyte differentiation and increase monounsaturated fatty acids...

Gang, Gyoung Ok

2012-10-19

313

ER? upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue.  

PubMed

Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor ? (ER?) have the opposite effect. Here we identify an Estrogen Response Element (ERE) in the promoter of Phd3, which is a negative regulatory enzyme of HIF-1, and we demonstrate HIF-1? is ubiquitinated following 17-? estradiol (E2)/ER? mediated Phd3 transcription. Manipulating ER? in vivo increases Phd3 transcription and reduces HIF-1 activity, while addition of PHD3 ameliorates adipose tissue fibrosis and inflammation. Our findings outline a novel regulatory relationship between E2/ER?, PHD3 and HIF-1 in adipose tissues, providing a mechanistic explanation for the protective effect of E2/ER? in adipose tissue. PMID:25161887

Kim, Min; Neinast, Michael D; Frank, Aaron P; Sun, Kai; Park, Jiyoung; Zehr, Jordan A; Vishvanath, Lavanya; Morselli, Eugenia; Amelotte, Mason; Palmer, Biff F; Gupta, Rana K; Scherer, Philipp E; Clegg, Deborah J

2014-09-01

314

Physiologically Based Pharmacokinetic Models for the Transport of Trichloroethylene in Adipose Tissue.  

National Technical Information Service (NTIS)

In this paper we present three physiologically based pharmacokinetic (PBPK) models for the systemic transport of trichloroethylene (TCE), with a focus on the adipose, or fat tissue. TCE is a widespread environmental contaminant, and has been shown to prod...

R. A. Albanese, H. T. Banks, M. V. Evans, L. K. Potter

2001-01-01

315

Investigation of the mechanisms that influence the accretion of bovine intramuscular and subcutaneous adipose tissue  

SciTech Connect

The understanding of the mechanisms that differ between breeds of cattle and their ability to deposit intramuscular adipose tissue is imperative to profitable beef production. Thus, the interactions among breeds, metabolic substrates and specific hormones in bovine intramuscular and subcutaneous adipose tissue were investigated. Subcutaneous and intramuscular adipose tissues were obtained from 10 Angus and 9 Santa Gertrudis steers immediately postmortem. The adipose tissues were incubated for 2 h and 48 h with and without 1 mU/ml insulin and 30 mg/ml bovine serum albumin (BSA) to measure the incorporation of /sup 14/C-labeled acetate and glucose into lipid fractions. At the same chronological age, Angus steers had a more youthful lean maturity score, higher USDA marbling scores and higher USDA quality grades than carcasses from Santa Gertrudis steers.

Miller, M.F.

1987-01-01

316

Retinyl Ester Homeostasis in the Adipose Differentiation-related Protein-deficient Retina*S  

E-print Network

droplets (4). Although perilipin expression is more limited to adipose and steroidogenic cells (5, 6), AdfpRetinyl Ester Homeostasis in the Adipose Differentiation-related Protein-deficient Retina of the gene encoding adipose differentiation-related protein (Adfp), a structural component of RESTs. We found

Palczewski, Krzysztof

317

Abundance of leptin mRNA in fetal adipose tissue is related to fetal body weight  

Microsoft Academic Search

Leptin mRNA was measured in adipose tissue of fetal sheep by reverse transcription polymerase chain reaction (RTPCR). Abundance of leptin mRNA relative to ?-actin mRNA in fetal perirenal adipose tissue increased ( P<0.02) with gestation, being higher at 144 d (0.73 ± 0.10, n=5) than at 90-91 d (0.40 ± 0.08, n=6) or 125 d (0.40 ± 0.04, n=5) gestation

S J Bernard; I Yuen; C McMillen; M E Symonds; P C Owens

1999-01-01

318

Tocotrienol levels in adipose tissue of benign and malignant breast lumps in patients in Malaysia.  

PubMed

Data on dietary exposure to vitamin E by plasma or adipose tissue concentrations of alpha-tocopherol (alpha-T) in observational studies have failed to provide consistent support for the idea that alpha-T provides women with any protection from breast cancer. In contrast, studies indicate that alpha, gamma, and delta-tocotrienols but not alpha-T have potent anti-proliferative effects in human breast cancer cells. Our aim was to investigate whether there was a difference in tocopherol and tocotrienol concentrations in malignant and benign adipose tissue, in a Malaysian population consuming predominantly a palm oil diet. The study was undertaken using fatty acid levels in breast adipose tissue as a biomarker of qualitative dietary intake of fatty acids. The major fatty acids in breast adipose tissue of patients (benign and malignant) were oleic acid (45-46%), palmitic (28-29%) and linoleic (11-12%). No differences were evident in the fatty acid composition of the two groups. There was a significant difference (p=0.006) in the total tocotrienol levels between malignant (13.7 +/- 6.0 microg/g) and benign (20+/-6.0 microg/g) adipose tissue samples. However, no significant differences were seen in the total tocopherol levels (p=0.42) in the two groups. The study reveals that dietary intake influences adipose tissue fatty acid levels and that adipose tissue is a dynamic reservoir of fat soluble nutrients. The higher adipose tissue concentrations of tocotrienols in benign patients provide support for the idea that tocotrienols may provide protection against breast cancer. PMID:17704032

Nesaretnam, Kalanithi; Gomez, Patricia Alison; Selvaduray, Kanga Rani; Razak, Ghazali Abdul

2007-01-01

319

Adenosine A 1 receptors regulate lipolysis and lipogenesis in mouse adipose tissue — Interactions with insulin  

Microsoft Academic Search

Adenosine acting at adenosine A1 receptors is considered to be one major regulator of adipose tissue physiology. We have examined the role of adenosine and its interactions with insulin in adipose tissue by using A1R knock out (?\\/?) mice. Removal of endogenous adenosine with adenosine deaminase caused lipolysis in A1R (+\\/+), but not A1R (?\\/?) adipocytes. The adenosine analogue, 2-chloroadenosine,

Stina M. Johansson; Eva Lindgren; Jiang-Ning Yang; Andreas W. Herling; Bertil B. Fredholm

2008-01-01

320

The Role of Adipose Tissue and Lipotoxicity in the Pathogenesis of Type 2 Diabetes  

Microsoft Academic Search

The widespread epidemics of obesity and type 2 diabetes mellitus (T2DM) suggest that both conditions are closely linked. An\\u000a increasing body of evidence has shifted our view of adipose tissue from a passive energy depot to a dynamic “endocrine organ”\\u000a that tightly regulates nutritional balance by means of a complex crosstalk of adipocytes with their microenvironment. Dysfunctional\\u000a adipose tissue, particularly

Kenneth Cusi

2010-01-01

321

Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue.  

PubMed

Adipose tissue plays a central role in maintaining metabolic homeostasis under normal conditions. Metabolic diseases such as obesity and type 2 diabetes are often accompanied by chronic inflammation and adipose tissue dysfunction. In this study, we observed that endoplasmic reticulum (ER) stress and the inflammatory response occurred in adipose tissue of mice fed a high-fat diet for a period of 16 weeks. After 16 weeks of feeding, ER stress markers increased and chronic inflammation occurred in adipose tissue. We found that ER stress is induced by free fatty acid (FFA)-mediated reactive oxygen species (ROS) generation and up-regulated gene expression of inflammatory cytokines in 3T3-L1 adipocytes. Oral administration to obese mice of chemical chaperons, which alleviate ER stress, improved chronic inflammation in adipose tissue, followed by the suppression of increased body weight and improved insulin signaling. These results indicate that ER stress plays important pathophysiological roles in obesity-induced adipose tissue dysfunction. PMID:23150771

Kawasaki, Noritaka; Asada, Rie; Saito, Atsushi; Kanemoto, Soshi; Imaizumi, Kazunori

2012-01-01

322

Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue  

PubMed Central

Adipose tissue plays a central role in maintaining metabolic homeostasis under normal conditions. Metabolic diseases such as obesity and type 2 diabetes are often accompanied by chronic inflammation and adipose tissue dysfunction. In this study, we observed that endoplasmic reticulum (ER) stress and the inflammatory response occurred in adipose tissue of mice fed a high-fat diet for a period of 16 weeks. After 16 weeks of feeding, ER stress markers increased and chronic inflammation occurred in adipose tissue. We found that ER stress is induced by free fatty acid (FFA)-mediated reactive oxygen species (ROS) generation and up-regulated gene expression of inflammatory cytokines in 3T3-L1 adipocytes. Oral administration to obese mice of chemical chaperons, which alleviate ER stress, improved chronic inflammation in adipose tissue, followed by the suppression of increased body weight and improved insulin signaling. These results indicate that ER stress plays important pathophysiological roles in obesity-induced adipose tissue dysfunction. PMID:23150771

Kawasaki, Noritaka; Asada, Rie; Saito, Atsushi; Kanemoto, Soshi; Imaizumi, Kazunori

2012-01-01

323

Enhanced Polyamine Catabolism Alters Homeostatic Control of White Adipose Tissue Mass, Energy Expenditure, and Glucose Metabolism?  

PubMed Central

Peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?) is an attractive candidate gene for type 2 diabetes, as genes of the oxidative phosphorylation (OXPHOS) pathway are coordinatively downregulated by reduced expression of PGC-1? in skeletal muscle and adipose tissue of patients with type 2 diabetes. Here we demonstrate that transgenic mice with activated polyamine catabolism due to overexpression of spermidine/spermine N1-acetyltransferase (SSAT) had reduced white adipose tissue (WAT) mass, high basal metabolic rate, improved glucose tolerance, high insulin sensitivity, and enhanced expression of the OXPHOS genes, coordinated by increased levels of PGC-1? and 5?-AMP-activated protein kinase (AMPK) in WAT. As accelerated polyamine flux caused by SSAT overexpression depleted the ATP pool in adipocytes of SSAT mice and N1,N11-diethylnorspermine-treated wild-type fetal fibroblasts, we propose that low ATP levels lead to the induction of AMPK, which in turn activates PGC-1? in WAT of SSAT mice. Our hypothesis is supported by the finding that the phenotype of SSAT mice was reversed when the accelerated polyamine flux was reduced by the inhibition of polyamine biosynthesis in WAT. The involvement of polyamine catabolism in the regulation of energy and glucose metabolism may offer a novel target for drug development for obesity and type 2 diabetes. PMID:17485446

Pirinen, Eija; Kuulasmaa, Teemu; Pietila, Marko; Heikkinen, Sami; Tusa, Maija; Itkonen, Paula; Boman, Susanna; Skommer, Joanna; Virkamaki, Antti; Hohtola, Esa; Kettunen, Mikko; Fatrai, Szabolcs; Kansanen, Emilia; Koota, Suvi; Niiranen, Kirsi; Parkkinen, Jyrki; Levonen, Anna-Liisa; Yla-Herttuala, Seppo; Hiltunen, J. Kalervo; Alhonen, Leena; Smith, Ulf; Janne, Juhani; Laakso, Markku

2007-01-01

324

White adipose tissue overproduces the lipid-mobilizing factor zinc alpha2-glycoprotein in chronic kidney disease  

PubMed Central

Chronic kidney disease (CKD) is frequently associated with protein energy wasting which has been recognized as a strong predictive factor of mortality. Zinc ?2-glycoprotein (ZAG) has been proposed as a new adipokine involved in body weight control through its lipid mobilizing activity. We hypothesized that the uremic environment in CKD could alter ZAG production by white adipose tissue and contribute to CKD-associated metabolic disturbances. ZAG protein was quantified in 3T3-L1 adipocytes after incubation with plasma from healthy volunteers and CKD patients (20%, v/v). ZAG was also measured in white adipose tissue (WAT) from 5/6 nephrectomized rodents (Nx5/6) and subcutaneous adipose tissue biopsies from end-stage renal disease patients. Uremic plasma induced a significant increase in ZAG synthesis in 3T3-L1 adipocytes (+124%, p<0.001), associated with an increased basal lipolysis (+31%, p<0.01) and a blunted lipogenesis (?53%, p<0.05). In vivo, Nx5/6 rats and mice exhibited a significant decrease in WAT accretion (?44%, p<0.01 and ?43%, p<0.005, respectively) and a higher content of ZAG protein in WAT than control (+498%, p<0.05 and +106%, p<0.01 respectively). Human WAT biopsies from CKD patients exhibited a higher content of ZAG (+573%, p<0.05) than age matched control. This study demonstrated for the first time that ZAG protein content is increased in white adipose tissue from CKD patients or animal models. Overproduction of ZAG in CKD could be a major contributor to dysmetabolism associated with CKD. PMID:23423258

Pelletier, Caroline C.; Koppe, Laetitia; Croze, Marine L.; Kalbacher, Emilie; Vella, Roxane E.; Guebre-Egziabher, Fitsum; Geloen, Alain; Badet, Lionel; Fouque, Denis; Soulage, Christophe O.

2013-01-01

325

Visceral adipose tissue and inflammation correlate with elevated liver tests in a cohort of overweight and obese patients  

Microsoft Academic Search

Objective:To study the relationship between elevated liver tests and high sensitive C-reactive protein (hs-CRP), as potential markers of liver inflammation and non-alcoholic steatohepatitis (NASH), with anthropometric and laboratory parameters in overweight patients, especially the relationship with visceral adipose tissue (VAT).Methods:Patients presenting to the obesity clinic were prospectively included. Detailed anthropometry, computed tomography (CT)-measured VAT, liver tests (aspartate transaminase (AST), alanine

A Verrijken; S Francque; I Mertens; M Talloen; F Peiffer; L Van Gaal

2010-01-01

326

Downstream Signaling Pathways in Mouse Adipose Tissues Following Acute In Vivo Administration of Fibroblast Growth Factor 21  

PubMed Central

FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic profiling of adipocytes, following FGF21 treatment revealed several specific changes in gene expression and post-translational modifications, specifically phosphorylation, in several relevant proteins. Affymetrix microarray analysis of white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD) and db/db mice identified over 150 robust potential RNA transcripts and over 50 potential secreted proteins that were changed greater than 1.5 fold by FGF21 acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic analysis of the combined gene and phosphoprotein profiling data identified a number of known metabolic pathways such as glucose uptake, insulin receptor signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number of novel events with hitherto unknown links to FGF21 signaling were observed at both the transcription and protein phosphorylation levels following treatment. We conclude that such a combined "omics" approach can be used not only to identify robust biomarkers for novel therapeutics but can also enhance our understanding of downstream signaling pathways; in the example presented here, novel FGF21-mediated signaling events in adipose tissue have been revealed that warrant further investigation. PMID:24039848

Chi, An; Tan, Yejun; Zhao, Xuemei; Liu, Franklin; Dallas-yang, Qing; Wu, Margaret; Sarr, Tim; Zhu, Lan; Guo, Hongbo; Li, Zhihua; Li, Wenyu; Hu, Weiwen; Jiang, Guoqiang; Paweletz, Cloud P.; Hendrickson, Ronald C.; Thompson, John R.; Mu, James; Berger, Joel P.; Mehmet, Huseyin

2013-01-01

327

Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity.  

PubMed

The chemokine receptor CXCR4 is expressed on adipocytes and macrophages in adipose tissue, but its role in this tissue remains unknown. We evaluated whether deficiency in either adipocyte or myeloid leukocyte CXCR4 affects body weight (BW) and adiposity in a mouse model of high-fat-diet (HFD)-induced obesity. We found that ablation of adipocyte, but not myeloid leukocyte, CXCR4 exacerbated obesity. The HFD-fed adipocyte-specific CXCR4-knockout (AdCXCR4ko) mice, compared to wild-type C57BL/6 control mice, had increased BW (average: 52.0 g vs. 35.5 g), adiposity (average: 49.3 vs. 21.0% of total BW), and inflammatory leukocyte content in white adipose tissue (WAT), despite comparable food intake. As previously reported, HFD feeding increased uncoupling protein 1 (UCP1) expression (fold increase: 3.5) in brown adipose tissue (BAT) of the C57BL/6 control mice. However, no HFD-induced increase in UCP1 expression was observed in the AdCXCR4ko mice, which were cold sensitive. Thus, our study suggests that adipocyte CXCR4 limits development of obesity by preventing excessive inflammatory cell recruitment into WAT and by supporting thermogenic activity of BAT. Since CXCR4 is conserved between mouse and human, the newfound role of CXCR4 in mouse adipose tissue may parallel the role of this chemokine receptor in human adipose tissue.-Yao, L., Heuser-Baker, J., Herlea-Pana, O., Zhang, N., Szweda, L. I., Griffin, T. M., Barlic-Dicen, J. Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity. PMID:25016030

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Zhang, Nan; Szweda, Luke I; Griffin, Timothy M; Barlic-Dicen, Jana

2014-10-01

328

ENPP2 Contributes to Adipose Tissue Expansion and Insulin Resistance in Diet-Induced Obesity.  

PubMed

Body weight is tightly regulated by food intake and energy dissipation, and obesity is related to decreased energy expenditure (EE). Herein, we show that nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2, autotaxin) is an adipose-derived, secreted enzyme that controls adipose expansion, brown adipose tissue (BAT) function, and EE. In mice, Enpp2 was highly expressed in visceral white adipose tissue and BAT and is downregulated in hypertrophied adipocytes/adipose tissue. Enpp2(+/-) mice and adipocyte-specific Enpp2 knockout mice fed a high-fat diet showed smaller body weight gains and less insulin resistance than control mice fed the same diet. BAT was functionally more active and EE was increased in Enpp2-deficient mice. In humans, ENPP2 expression in subcutaneous fat and ENPP2 levels in serum were reduced in obese subjects. Taken together, our results establish ENPP2 as an adipose-derived, secreted enzyme that regulates adipose obesity and systemic metabolism. They also suggest ENPP2 could be a useful therapeutic target for the treatment of metabolic disease. PMID:24969110

Nishimura, Satoshi; Nagasaki, Mika; Okudaira, Shinichi; Aoki, Junken; Ohmori, Tsukasa; Ohkawa, Ryunosuke; Nakamura, Kazuhiro; Igarashi, Koji; Yamashita, Hiroshi; Eto, Koji; Uno, Kansei; Hayashi, Naoto; Kadowaki, Takashi; Komuro, Issei; Yatomi, Yutaka; Nagai, Ryozo

2014-12-01

329

Adipose tissue-derived stem cells show considerable promise for regenerative medicine applications.  

PubMed

The stromal-vascular cell fraction (SVF) of adipose tissue can be an abundant source of both multipotent and pluripotent stem cells, known as adipose-derived stem cells or adipose tissue-derived stromal cells (ADSCs). The SVF also contains vascular cells, targeted progenitor cells, and preadipocytes. Stromal cells isolated from adipose tissue express common surface antigens, show the ability to adhere to plastic, and produce forms that resemble fibroblasts. They are characterized by a high proliferation potential and the ability to differentiate into cells of meso-, ecto- and endodermal origin. Although stem cells obtained from an adult organism have smaller capabilities for differentiation in comparison to embryonic and induced pluripotent stem cells (iPSs), the cost of obtaining them is significantly lower. The 40 years of research that mainly focused on the potential of bone marrow stem cells (BMSCs) revealed a number of negative factors: the painful sampling procedure, frequent complications, and small cell yield. The number of stem cells in adipose tissue is relatively large, and obtaining them is less invasive. Sampling through simple procedures such as liposuction performed under local anesthesia is less painful, ensuring patient comfort. The isolated cells are easily grown in culture, and they retain their properties over many passages. That is why adipose tissue has recently been treated as an attractive alternative source of stem cells. Essential aspects of ADSC biology and their use in regenerative medicine will be analyzed in this article. PMID:23949841

Harasymiak-Krzy?anowska, Izabela; Niedojad?o, Alicja; Karwat, Jolanta; Kotu?a, Lidia; Gil-Kulik, Paulina; Sawiuk, Magdalena; Kocki, Janusz

2013-12-01

330

Epicardial Adipose Tissue in Patients with Chronic Obstructive Pulmonary Disease  

PubMed Central

Rationale Epicardial Adipose Tissue (EAT) volume as determined by chest computed tomography (CT) is an independent marker of cardiovascular events in the general population. COPD patients have an increased risk of cardiovascular disease, however nothing is known about the EAT volume in this population. Objectives To assess EAT volume in COPD and explore its association with clinical and physiological variables of disease severity. Methods We measured EAT using low-dose CT in 171 stable COPD patients and 70 controls matched by age, smoking history and BMI. We determined blood pressure, cholesterol, glucose and HbA1c levels, microalbuminuria, lung function, BODE index, co-morbidity index and coronary artery calcium score (CAC). EAT volume were compared between groups. Uni and multivariate analyses explored the relationship between EAT volume and the COPD related variables. Results COPD patients had a higher EAT volume [143.7 (P25–75, 108.3–196.6) vs 129.1 (P25–75, 91.3–170.8) cm3, p?=?0.02)] and the EAT volume was significantly associated with CAC (r?=?0.38, p<0.001) and CRP (r?=?0.32, p<0.001) but not with microalbuminuria (r?=?0.12, p?=?0.13). In COPD patients, EAT volume was associated with: age, pack-years, BMI, gender, FEV1%, 6 MWD, MMRC and HTN. Multivariate analysis showed that only pack-years (B?=?0.6, 95% CI: 0.5–1.3), BMI (B?=?7.8, 95% CI: 5.7–9.9) and 6 MWD (B?=??0.2, 95% CI: ?0.3–?0.1), predicted EAT volume. Conclusions EAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity, all modifiable risk factors of future cardiovascular events. EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular events. PMID:23762399

Zagaceta, Jorge; Zulueta, Javier J.; Bastarrika, Gorka; Colina, Inmaculada; Alcaide, Ana B.; Campo, Arantza; Celli, Bartolome R.; de Torres, Juan P.

2013-01-01

331

Epicardial Adipose Tissue Thickness and Ablation Outcome of Atrial Fibrillation  

PubMed Central

Objectives Epicardial fat was closely related to atrial fibrillation (AF). Transthoracic echocardiography (TTE) has been proposed to be a convenient imaging tool in assessing epicardial adipose tissue (EAT). The goal of the present study was to investigate whether the EAT thickness measured on TTE was a useful parameter in predicting procedural outcomes of AF ablations. Methods and Results A total of 227 paroxysmal AF (PAF) and 56 non-paroxysmal AF (non-PAF) patients receiving catheter ablations from 2008-2010 were enrolled. Echocardiography-derived regional EAT thickness from parasternal long-axis view was quantified for each patient. Free of recurrence was defined as the absence of atrial arrhythmias without using antiarrhythmic agents after ablations. The mean EAT thickness of the study population was 6.1 ± 0.8 mm. Non-PAF patients had a thicker EAT than that of PAF patients (7.0 ± 0.7 mm versus 5.9 ± 0.7 mm, p value <0.001). During the follow-up of 16 ± 9 months, there were 95 patients (33.6%) suffering from recurrences of atrial arrhythmias. Non-PAF, chads2 score, left atrial diameter and EAT thickness were independent predictors of recurrence after catheter ablations. At a cutoff value of 6 mm for PAF and 6.9 mm for non-PAF, the measurement of EAT thickness could help us to identify patients at risk of recurrences. Conclusions EAT thickness may serve as a useful parameter in predicting recurrences after AF ablations. Compared to other imaging modalities, TTE can be an alternative choice with less cost and time in assessing the effects of EAT on ablation outcomes. PMID:24066158

Tsao, Hsuan-Ming; Lin, Yenn-Jiang; Yun, Chun-Ho; Lai, Yau-Huei; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Chang, Hung-Yu; Kuo, Jen-Yuan; Yeh, Hung-I; Wu, Tsu-Juey; Hsieh, Ming-Hsiung; Yu, Wen-Chung; Chen, Shih-Ann

2013-01-01

332

Obesity and weight loss result in increased adipose tissue ABCG1 expression in db/db mice.  

PubMed

The prevalence of obesity has reached epidemic proportions and is associated with several co-morbid conditions including diabetes, dyslipidemia, cancer, atherosclerosis and gallstones. Obesity is associated with low systemic inflammation and an accumulation of adipose tissue macrophages (ATMs) that are thought to modulate insulin resistance. ATMs may also modulate adipocyte metabolism and take up lipids released during adipocyte lipolysis and cell death. We suggest that high levels of free cholesterol residing in adipocytes are released during these processes and contribute to ATM activation and accumulation during obesity and caloric restriction. Db/db mice were studied for extent of adipose tissue inflammation under feeding conditions of ad libitum (AL) and caloric restriction (CR). The major finding was a marked elevation in epididymal adipose ABCG1 mRNA levels with obesity and CR (6-fold and 16-fold, respectively) over that seen for lean wild-type mice. ABCG1 protein was also elevated for CR as compared to AL adipose tissue. ABCG1 is likely produced by cholesterol loaded ATMs since this gene is not highly expressed in adipocytes and ABCG1 expression is sterol mediated. Our data supports the concept that metabolic changes in adipocytes due to demand lipolysis and cell death lead to cholesterol loading of ATMs. Based on finding cholesterol-loaded peritoneal leukocytes with elevated levels of ABCG1 in CR as compared to AL mice, we suggest that pathways for cholesterol trafficking out of adipose tissue involve ATM egress as well as ABCG1 mediated cholesterol efflux. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010). PMID:22179025

Edgel, Kimberly A; McMillen, Timothy S; Wei, Hao; Pamir, Nathalie; Houston, Barbara A; Caldwell, Mark T; Mai, Phuong-Oanh T; Oram, John F; Tang, Chongren; Leboeuf, Renée C

2012-03-01

333

Epicardial adipose tissue thickness and NGAL levels in women with polycystic ovary syndrome  

PubMed Central

Background Polycystic ovary syndrome (PCOS) is associated with an increased cardiovascular disease (CVD) risk and early atherosclerosis. Epicardial adipose tissue thickness (EATT) is clinically related to subclinical atherosclerosis. In the present study, considering the major role of neutrophil gelatinase-associated lipocalin (NGAL) which is an acute phase protein rapidly releasing upon inflammation and tissue injury, we aimed to evaluate NGAL levels and EATT in PCOS patients and assess their relationship with cardiometabolic factors. Methods 64 patients with PCOS and 50 age- and body mass index-matched healthy controls were included in the study. We evaluated anthropometric, hormonal and metabolic parameters. EATT was measured by echocardiography above the free wall of the right ventricle. Serum NGAL and high-sensitive C- reactive protein (hsCRP) levels were measured by ELISA. Results Mean EATT was 0,38 +/-0,16 mm in the PCOS group and 0,34 +/-0,36 mm in the control group (p?=?0,144). In the obese PCOS group (n?=?44) EAT was thicker compared to the obese control group (n?=?41) (p?=?0.026). Mean NGAL levels of the patients with PCOS were 101,98 +/-21,53 pg/ml, while mean NGAL levels were 107,40 +/-26,44 pg/ml in the control group (p?=?0,228). We found a significant positive correlation between EATT and age, BMI, waist circumference, fasting insulin, HOMA-IR, triglyceride and hsCRP levels in PCOS group. Conclusions Thickness of the epicardial adipose tissue can be used to follow the risk of CVD development in obese PCOS cases. However serum NGAL levels do not differ in patients with PCOS and control group. PMID:24528623

2014-01-01

334

Human adipose-derived stem cells: definition, isolation, tissue-engineering applications.  

PubMed

Recent researches have demonstrated that the most effective repair system of the body is represented by stem cells - unspecialized cells, capable of self-renewal through successive mitoses, which have also the ability to transform into different cell types through differentiation. The discovery of adult stem cells represented an important step in regenerative medicine because they no longer raises ethical or legal issues and are more accessible. Only in 2002, stem cells isolated from adipose tissue were described as multipotent stem cells. Adipose tissue stem cells benefits in tissue engineering and regenerative medicine are numerous. Development of adipose tissue engineering techniques offers a great potential in surpassing the existing limits faced by the classical approaches used in plastic and reconstructive surgery. Adipose tissue engineering clinical applications are wide and varied, including reconstructive, corrective and cosmetic procedures. Nowadays, adipose tissue engineering is a fast developing field, both in terms of fundamental researches and medical applications, addressing issues related to current clinical pathology or trauma management of soft tissue injuries in different body locations. PMID:24398986

Nae, S; Bordeianu, I; St?ncioiu, A T; Antohi, N

2013-01-01

335

Sexual dimorphism in white and brown adipose tissue with obesity and inflammation.  

PubMed

This article is part of a Special Issue "Energy Balance". Obesity and its associated comorbidities remain at epidemic levels globally and show no signs of abatement in either adult or child populations. White adipose tissue has long been established as an endocrine signalling organ possessing both metabolic and immune functions. This role can become dysregulated following excess adiposity caused by adipocyte hypertrophy and hyperplasia. In contrast, brown adipose tissue (BAT) is only present in comparatively small amounts in the body but can significantly impact on heat production, and thus could prevent excess white adiposity. Obesity and associated risk factors for adverse metabolic health are not only linked with enlarged fat mass but also are dependent on its anatomical deposition. In addition, numerous studies have revealed a disparity in white adipose tissue deposition prior to and during the development of obesity between the sexes. Females therefore tend to develop a greater abundance of femoral and gluteal subcutaneous fat whereas males exhibit more central adiposity. In females, lower body subcutaneous adipose tissue depots appear to possess a greater capacity for lipid storage, enhanced lipolytic flux and hyperplastic tissue remodelling compared to visceral adipocytes. These differences are acknowledged to contribute to the poorer metabolic and inflammatory profiles observed in males. Importantly, the converse outcomes between sexes disappear after the menopause, suggesting a role for sex hormones within the onset of metabolic complications with obesity. This review further considers how BAT impacts upon on the relationship between excess adiposity, gender, inflammation and endocrine signalling and could thus ultimately be a target to prevent obesity. PMID:24589990

Bloor, Ian D; Symonds, Michael E

2014-06-01

336

Characterization of Cre recombinase models for the study of adipose tissue  

PubMed Central

The study of adipose tissue in vivo has been significantly advanced through the use of genetic mouse models. While the aP2-CreBI and aP2-CreSalk lines have been widely used to target adipose tissue, the specificity of these lines for adipocytes has recently been questioned. Here we characterize Cre recombinase activity in multiple cell populations of the major adipose tissue depots of these and other Cre lines using the membrane-Tomato/membrane-GFP (mT/mG) dual fluorescent reporter. We find that the aP2-CreBI and aP2-CreSalk lines lack specificity for adipocytes within adipose tissue, and that the aP2-CreBI line does not efficiently target adipocytes in white adipose depots. Alternatively, the Adiponectin-CreERT line shows high efficiency and specificity for adipocytes, while the PdgfR?-CreERUCL and PdgfR?-CreERJHU lines do not efficiently target adipocyte precursor cells in the major adipose depots. Instead, we show that the PdgfR?-Cre line is preferable for studies targeting adipocyte precursor cells in vivo. PMID:25068087

Jeffery, Elise; Berry, Ryan; Church, Christopher D; Yu, Songtao; Shook, Brett A; Horsley, Valerie; Rosen, Evan D; Rodeheffer, Matthew S

2014-01-01

337

Hypoxia enhances the relaxing influence of perivascular adipose tissue in isolated mice aorta.  

PubMed

Adipose tissue releases an "adipocyte-derived relaxing factor" (ADRF) lowering tone of isolated arteries. The potential influence of hypoxia on the vasorelaxing properties of adipose tissue was investigated. Aortas from male Swiss mice with or without adherent adipose tissue were mounted in a wire myograph for isometric tension recording. Hypoxia (bubbling with 95% N(2), 5% CO(2)) relaxed precontracted (norephinephrine, 5 microM) aorta with adipose tissue while only a minimal vasorelaxing effect was observed in arteries without adipose tissue. This effect was also seen after precontraction with prostaglandin F(2alpha) (30 microM) or U-46619 (10 nM). Precontraction with 60 or 120 mM K(+), incubation with tetraethylammoniumchloride (3 mM) or glibenclamide (30 microM) significantly impaired the hypoxic response. Glibenclamide (30 microM) enhanced the vasorelaxing effect of NaHS (except at high concentrations of NaHS). Lactate (10 nM to 1 mM) had no effect on preparations with or without adipose tissue. 8-(p-sulfophenyl)theophylline (0.1 mM), zinc protoporphyrin IX (10 microM), 1 H-[1, 2, 4]oxadiazolo[4,3-A]quinoxalin-1-one (10 microM) and removal of the endothelium did not influence the hypoxic relaxation. Our findings indicate that hypoxia has a relaxing influence on mice aorta that is dependent on the presence of adherent adipose tissue. This relaxation is partly mediated by opening K(ATP) channels and independent of the endothelium and soluble guanylyl cyclase. Neither lactate, adenosine, CO nor H(2)S seems to be involved in this hypoxic response. However, the involvement of the as yet unidentified "adipocyte-derived relaxing factor" (ADRF) cannot be excluded. PMID:20553914

Maenhaut, Nele; Boydens, Charlotte; Van de Voorde, Johan

2010-09-01

338

ABCD2 is abundant in adipose tissue and opposes the accumulation of dietary erucic acid (C22:1) in fat[S  

PubMed Central

The ATP binding cassette transporter, ABCD2 (D2), is a peroxisomal protein whose mRNA has been detected in the adrenal, brain, liver, and fat. Although the role of this transporter in neural tissues has been studied, its function in adipose tissue remains unexplored. The level of immunoreactive D2 in epididymal fat is >50-fold of that found in brain or adrenal. D2 is highly enriched in adipocytes and is upregulated during adipogenesis but is not essential for adipocyte differentiation or lipid accumulation in day 13.5 mouse embryonic fibroblasts isolated from D2-deficient (D2?/?) mice. Although no differences were appreciated in differentiation percentage, total lipid accumulation was greater in D2?/? adipocytes compared with the wild type. These results were consistent with in vivo observations in which no significant differences in adiposity or adipocyte diameter between wild-type and D2?/? mice were observed. D2?/? adipose tissue showed an increase in the abundance of 20:1 and 22:1 fatty acids. When mice were challenged with a diet enriched in erucic acid (22:1), this lipid accumulated in the adipose tissue in a gene-dosage-dependent manner. In conclusion, D2 is a sterol regulatory element binding protein target gene that is highly abundant in fat and opposes the accumulation of dietary lipids generally absent from the triglyceride storage pool within adipose tissue. PMID:19556607

Liu, Jingjing; Sabeva, Nadezhda S.; Bhatnagar, Saloni; Li, Xiang-An; Pujol, Aurora; Graf, Gregory A.

2010-01-01

339

Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells  

PubMed Central

Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models. This body of work has provided evidence supporting clinical translational applications of adipose-derived cells in safety and efficacy trials. The present article reviews the case reports and phase I-III clinical evidence using autologous adipose-derived cells that have been published, to date, in the fields of gastroenterology, neurology, orthopedics, reconstructive surgery, and related clinical disciplines. Future directions and challenges facing the field are discussed and evaluated. PMID:20587076

2010-01-01

340

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

PubMed

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 accumulation than 2D cultures. This indicates that 3D intercellular signaling better recapitulates WAT organogenesis. Combined, our studies show that adipospheres are appropriate for WAT modeling ex vivo and provide a new platform for functional screens to identify molecules bioactive toward individual adipose cell populations. This 3D methodology could be adopted for WAT transplantation applications and aid approaches to WAT-based cell therapy. PMID:23017116

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

2013-05-01

341

Tyk2 and Stat3 Regulate Brown Adipose Tissue Differentiation and Obesity  

PubMed Central

Mice lacking the Jak tyrosine kinase member Tyk2 become progressively obese due to aberrant development of Myf5+ brown adipose tissue (BAT). Tyk2 RNA levels in BAT and skeletal muscle, which shares a common progenitor with BAT, are dramatically decreased in mice placed on a high fat diet and in obese humans. Expression of Tyk2 or the constitutively active form of the transcription factor Stat3 (CAStat3) restores differentiation in Tyk2?/? brown preadipocytes. Furthermore, Tyk2?/? mice expressing CAStat3 transgene in BAT also show improved BAT development, normal levels of insulin and significantly lower body weights. Stat3 binds to PRDM16, a master regulator of BAT differentiation, and enhances the stability of PRDM16 protein. These results define Tyk2 and Stat3 as critical determinants of brown fat-lineage and suggest that altered levels of Tyk2 are associated with obesity in both rodents and humans. PMID:23217260

Derecka, Marta; Gornicka, Agnieszka; Koralov, Sergei B.; Szczepanek, Karol; Morgan, Magdalena; Raje, Vidisha; Sisler, Jennifer; Zhang, Qifang; Otero, Dennis; Cichy, Joanna; Rajewsky, Klaus; Shimoda, Kazuya; Poli, Valeria; Strobl, Birgit; Pellegrini, Sandra; Harris, Thurl E.; Seale, Patrick; Russell, Aaron P.; McAinch, Andrew J.; O'Brien, Paul E.; Keller, Susanna R.; Croniger, Colleen M.; Kordula, Tomasz; Larner, Andrew C.

2012-01-01

342

Peripheral effects of the endocannabinoid system in energy homeostasis: adipose tissue, liver and skeletal muscle.  

PubMed

The endocannabinoid system (ECS) is composed of lipid signalling ligands, their G-protein coupled receptors and the enzymes involved in ligand generation and metabolism. Increasingly, the ECS is emerging as a critical agent of energy metabolism regulation through its ability to modulate caloric intake centrally as well as nutrient transport, cellular metabolism and energy storage peripherally. Visceral obesity has been associated with an upregulation of ECS activity in several systems and inhibition of the ECS, either pharmacologically or genetically, results in decreased energy intake and increased metabolic output. This review aims to summarize the recent advances that have been made regarding our understanding of the role the ECS plays in crucial peripheral systems pertaining to energy homeostasis: adipose tissues, the liver and skeletal muscle. PMID:21336842

Silvestri, Cristoforo; Ligresti, Alessia; Di Marzo, Vincenzo

2011-09-01

343

Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages.  

PubMed

Adipose tissue macrophage (ATM)-driven inflammation plays a key role in insulin resistance; however, factors activating ATMs are poorly understood. Using a proteomics approach, we show that markers of classical activation are absent on ATMs from obese humans but are readily detectable on airway macrophages of patients with cystic fibrosis, a disease associated with chronic bacterial infection. Moreover, treating macrophages with glucose, insulin, and palmitate-conditions characteristic of the metabolic syndrome-produces a "metabolically activated" phenotype distinct from classical activation. Markers of metabolic activation are expressed by proinflammatory ATMs in obese humans/mice and are positively correlated with adiposity. Metabolic activation is driven by independent proinflammatory and anti-inflammatory pathways, which regulate balance between cytokine production and lipid metabolism. We identify PPAR? and p62/SQSTM1 as two key proteins that promote lipid metabolism and limit inflammation in metabolically activated macrophages. Collectively, our data provide important mechanistic insights into pathways that drive the metabolic-disease-specific phenotype of macrophages. PMID:25242226

Kratz, Mario; Coats, Brittney R; Hisert, Katherine B; Hagman, Derek; Mutskov, Vesco; Peris, Eduard; Schoenfelt, Kelly Q; Kuzma, Jessica N; Larson, Ilona; Billing, Peter S; Landerholm, Robert W; Crouthamel, Matthew; Gozal, David; Hwang, Seungmin; Singh, Pradeep K; Becker, Lev

2014-10-01

344

Inhibition of the central melanocortin system decreases brown adipose tissue activity.  

PubMed

The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose tissue (BAT) activity. Therefore, female APOE*3-Leiden.CETP transgenic mice were fed a Western-type diet for 4 weeks and infused intracerebroventricularly with the melanocortin 3/4 receptor (MC3/4R) antagonist SHU9119 or vehicle for 2 weeks. SHU9119 increased food intake (+30%) and body fat (+50%) and decreased EE by reduction in fat oxidation (-42%). In addition, SHU9119 impaired the uptake of VLDL-TG by BAT. In line with this, SHU9119 decreased uncoupling protein-1 levels in BAT (-60%) and induced large intracellular lipid droplets, indicative of severely disturbed BAT activity. Finally, SHU9119-treated mice pair-fed to the vehicle-treated group still exhibited these effects, indicating that MC4R inhibition impairs BAT activity independent of food intake. These effects were not specific to the APOE*3-Leiden.CETP background as SHU9119 also inhibited BAT activity in wild-type mice. We conclude that inhibition of central MC3/4R signaling impairs BAT function, which is accompanied by reduced EE, thereby promoting adiposity. We anticipate that activation of MC4R is a promising strategy to combat obesity by increasing BAT activity. PMID:25016380

Kooijman, Sander; Boon, Mariëtte R; Parlevliet, Edwin T; Geerling, Janine J; van de Pol, Vera; Romijn, Johannes A; Havekes, Louis M; Meurs, Illiana; Rensen, Patrick C N

2014-10-01

345

Genetically selected stem cells from human adipose tissue express cardiac markers  

Microsoft Academic Search

In the present study, the potential of human adipose-derived stem cells to differentiate into cells with characteristics of cardiomyocytes was investigated. Adipose tissue-derived stem cells (ADSCs) were transduced with two different lentiviral vectors simultaneously: (1) a lentiviral vector expressing eGFP controlled by the Nkx2.5 promoter and (2) a lentiviral vector expressing DsRed2 controlled by the myosin light chain-2v promoter (MLC-2v).

Xiaowen Bai; Kai Pinkernell; Yao-Hua Song; Christoph Nabzdyk; Jakob Reiser; Eckhard Alt

2007-01-01

346

Epicardial adipose tissue in patients with heart failure  

PubMed Central

Purpose The aim of this study was to evaluate the extent of epicardial adipose tissue (EAT) and its relationship with left ventricular (LV) parameters assessed by cardiovascular magnetic resonance (CMR) in patients with congestive heart failure (CHF) and healthy controls. Background EAT is the true visceral fat deposited around the heart which generates various bioactive molecules. Previous studies found that EAT is related to left ventricular mass (LVM) in healthy subjects. Further studies showed a constant EAT to myocardial mass ratio in normal, ischemic and hypertrophied hearts. Methods CMR was performed in 66 patients with CHF due to ischemic cardiomyopathy (ICM), or dilated cardiomyopathy (DCM) and 32 healthy controls. Ventricular volumes, dimensions and LV function were assessed. The amount of EAT was determined volumetrically and expressed as mass indexed to body surface area. Additionally, the EAT/LVM and the EAT/left ventricular remodelling index (LVRI) ratios were calculated. Results Patients with CHF had less indexed EAT mass than controls (22 ± 5 g/m2 versus 34 ± 4 g/m2, p < 0.0001). In the subgroup analysis there were no significant differences in indexed EAT mass between patients with ICM and DCM (21 ± 4 g/m2 versus 23 ± 6 g/m2, p = 0.14). Linear regression analysis showed that with increasing LV end-diastolic diameter (LV-EDD) (r = 0.42, p = 0.0004) and LV end-diastolic mass (LV-EDM) (r = 0.59, p < 0.0001), there was a significantly increased amount of EAT in patients with CHF. However, the ratio of EAT mass/LV-EDM was significantly reduced in patients with CHF compared to healthy controls (0.54 ± 0.1 versus 0.21 ± 0.1, p < 0.0001). In CHF patients higher indexed EAT/LVRI-ratios in CHF patients correlated best with a reduced LV-EF (r = 0.49, p < 0.0001). Conclusion Patients with CHF revealed significantly reduced amounts of EAT. An increase in LVM is significantly related to an increase in EAT in both patients with CHF and controls. However, different from previous reports the EAT/LVEDM-ratio in patients with CHF was significantly reduced compared to healthy controls. Furthermore, the LV function correlated best with the indexed EAT/LVRI ratio in CHF patients. Metabolic abnormalities and/or anatomic alterations due to disturbed cardiac function and geometry seem to play a key role and are a possible explanation for these findings. PMID:20624277

2010-01-01

347

Regulation of leptin synthesis in white adipose tissue of the female fruit bat, Cynopterus sphinx: role of melatonin with or without insulin.  

PubMed

Factors regulating leptin synthesis during adipogenesis in wild species are not well known. Studies in the female Cynopterus sphinx bat have shown that it undergoes seasonal changes in its fat deposition and serum leptin and melatonin levels. The aim of the present study was to investigate the hormonal regulation of leptin synthesis by the white adipose tissue during the period of fat deposition in female C. sphinx. This study showed a significant correlation between the seasonal changes in serum melatonin level with the circulating leptin level (r = 0.78; P < 0.05) and with the changes in body fat mass (r = 0.88; P < 0.05) in C. sphinx. A significant correlation between circulating insulin and leptin levels (r = 0.65; P < 0.05) was also found in this species. This in vivo finding suggests that melatonin together with insulin may enhance leptin synthesis by increasing adipose tissue accumulation. The in vitro study showed that melatonin interacts synergistically with insulin in stimulating leptin synthesis by adipose tissue in C. sphinx. The study showed MT(2) receptors in adipose tissue and a stimulatory effect of melatonin on leptin synthesis, which was blocked by treatment with an MT(2) receptor antagonist, suggesting that the effect of melatonin on leptin synthesis by adipose tissue is mediated through the MT(2) receptor in C. sphinx. The in vitro study showed that the synthesis of leptin is directly proportional to the amount of glucose uptake by the adipose tissue. It further showed that melatonin together with insulin synergistically enhanced the leptin synthesis by adipose tissue through phosphorylation of mitogen-activated protein kinase in C. sphinx. PMID:20971799

Banerjee, A; Udin, S; Krishna, A

2011-02-01

348

Differences in the Inflammatory Response Induced by Acute Pancreatitis in Different White Adipose Tissue Sites in the Rat  

PubMed Central

Background There is increasing evidence of the role of adipose tissue on the systemic effects of acute pancreatitis. Patients with higher body mass index have increased risk of local and systemic complications and patients with android fat distribution and higher waist circumference are at greater risk for developing the severe form of the disease. Here we evaluated the changes on different areas of adipose tissue and its involvement on the inflammatory response in an experimental model of acute pancreatitis. Methods Pancreatitis was induced in male Wistar rats by intraductal administration of sodium taurocholate. Orlistat was administered to inhibit lipase activity. Activation of peritoneal macrophages was evaluated by measuring IL1? and TNF? expression. Inflammation was evaluated by measuring myeloperoxidase activity in mesenteric, epididymal and retroperitoneal areas of adipose tissue. Changes in the expression of inflammatory mediator in these areas of adipose tissue were also evaluated by RT-PCR. Results Pancreatitis induces the activation of peritoneal macrophages and a strong inflammatory response in mesenteric and epididymal sites of adipose tissue. By contrast, no changes were found in retroperitoneal adipose tissue. Inhibition of lipase prevented the activation of macrophages and the local inflammation in adipose tissue. Conclusions Our results confirm the involvement of adipose tissue on the progression of systemic inflammatory response during acute pancreatitis. However, there is a considerable diversity in different adipose tissue sites. These differences need to be taken into account in order to understand the progression from local pancreatic damage to systemic inflammation during acute pancreatitis. PMID:22870264

Gea-Sorli, Sabrina; Bonjoch, Laia; Closa, Daniel

2012-01-01

349

Dioxins and dibenzofurans in adipose tissue of the general US population and selected subpopulations.  

PubMed Central

OBJECTIVES. The Environmental Protection Agency's National Human Adipose Tissue Survey (NHATS) was conducted in fiscal year (FY) 1987 to (1) estimate average concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in the adipose tissue of humans in the US population, (2) identify differences in average concentrations among subpopulations, and (3) compare average concentrations with those from the FY 1982 NHATS. METHODS. Population estimates of the average levels of PCDDs and PCDFs were established on the basis of 865 human adipose tissue specimens collected in FY 1987. Average levels among subpopulations were compared. RESULTS. The average concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the adipose tissue of the US population was 5.38 pg/g, increasing from 1.98 pg/g in children under 14 years of age to 9.40 pg/g in adults over 45. The effect of age was significant for nine compounds. Regional differences in the levels of 2,3,4,7,8-pentachlorinated dibenzofurans were statistically significant, but there were no significant differences associated with sex or race. CONCLUSIONS. The survey provides a baseline of average levels of PCDDs and PCDFs in the adipose tissue of humans in the US population. PMID:8129062

Orban, J E; Stanley, J S; Schwemberger, J G; Remmers, J C

1994-01-01

350

RNA-seq analysis of bovine intramuscular, subcutaneous and perirenal adipose tissues.  

PubMed

The deposition of intramuscular fat is an important factor affecting the beef quality, such as flavour and palatability. In this study, for further identifying the differential molecular mechanisms regulating the deposition of fat between intramuscular and external adipose tissues, particularly subcutaneous and perirenal adipose tissues, it was designed to obtain transcript sequence data and compare the transcriptomes among intramuscular, subcutaneous, and perirenal adipose tissues by RNA-Seq. A total of 66,206,912, 55,114,070 and 67,320,426 fragments were sequenced for the intramuscular (IAT), subcutaneous (SAT), and perirenal adipose tissue (PAT) respectively. Among them, total 953, 1,534, 2,026 genes showing differential expression between IAT and SAT, IAT and PAT, SAT and PAT, were identified respectively (FDR < 0.05). When these data had been mixed and analyzed together, 110 genes were differentially expressed among these three adipose tissues. Using GO enrichment analysis, multiple biological pathways were found to be significantly enriched for differentially expressed genes (FDR < 0.01), including cellular process, biological regulation, and metabolic process. In addition, total 4,625, 4,775 and 4,147 alternative splicing events occurred in IAT, SAT, and PAT, had also been detected respectively. Thus, our results logically provide the evidence for further understanding the bovine fat deposition, especially intramuscular fat, at a fine scale. PMID:24398553

Sheng, Xihui; Ni, Hemin; Liu, Yunhai; Li, Junya; Zhang, Lupei; Guo, Yong

2014-03-01

351

Association of Scavenger Receptors in Adipose Tissue With Insulin Resistance in Nondiabetic Humans  

PubMed Central

Objective Scavenger receptors play crucial roles in the pathogenesis of atherosclerosis, but their role in insulin resistance has not been explored. We hypothesized that scavenger receptors are present in human adipose tissue resident macrophages, and their gene expression is regulated by adiponectin and thaizolidinediones. Methods and Results The gene expression of scavenger receptors including scavenger receptor-A (SRA), CD36, and lectin-like oxidized LDL receptor-1 (LOX-1) were studied in subcutaneous adipose tissue of nondiabetic subjects and in vitro. Adipose tissue SRA expression was independently associated with insulin resistance. Pioglitazone downregulated SRA gene expression in adipose tissue of subjects with impaired glucose tolerance and decreased LOX-1 mRNA in vitro. Macrophage LOX-1 expression was decreased when macrophages were cocultured with adipocytes or when exposed to adipocyte conditioned medium. Adding adiponectin neutralizing antibody resulted in a 2-fold increase in LOX-1 gene expression demonstrating that adiponectin regulates LOX-1 expression. Conclusion Adipose tissue scavenger receptors are strongly associated with insulin resistance. Pioglitazone and adiponectin regulate gene expression of SRA and LOX-1, and this may have clinical implications in arresting the untoward sequalae of insulin resistance and diabetes, including accelerated atherosclerosis. PMID:19667111

Rasouli, Neda; Yao-Borengasser, Aiwei; Varma, Vijayalakshmi; Spencer, Horace J.; McGehee, Robert E.; Peterson, Charlotte A.; Mehta, Jawahar L.; Kern, Philip A.

2009-01-01

352

Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.  

PubMed

Impaired adipogenesis renders an adipose tissue unable to expand, leading to lipotoxicity and conditions such as diabetes and cardiovascular disease. While factors important for adipogenesis have been studied extensively, those that set the limits of adipose tissue expansion remain undetermined. Feeding a Western-type diet to apolipoprotein E2 knock-in mice, a model of metabolic syndrome, produced 3 groups of equally obese mice: mice with normal glucose tolerance, hyperinsulinemic yet glucose-tolerant mice, and prediabetic mice with impaired glucose tolerance and reduced circulating insulin. Using proteomics, we compared subcutaneous adipose tissues from mice in these groups and found that the expression of PTRF (polymerase I and transcript release factor) associated selectively with their glucose tolerance status. Lentiviral and pharmacologically overexpressed PTRF, whose function is critical for caveola formation, compromised adipocyte differentiation of cultured 3T3-L1cells. In human adipose tissue, PTRF mRNA levels positively correlated with markers of lipolysis and cellular senescence. Furthermore, a negative relationship between telomere length and PTRF mRNA levels was observed in human subcutaneous fat. PTRF is associated with limited adipose tissue expansion underpinning the key role of caveolae in adipocyte regulation. Furthermore, PTRF may be a suitable adipocyte marker for predicting pathological obesity and inform clinical management. PMID:24812087

Perez-Diaz, Sergio; Johnson, Lance A; DeKroon, Robert M; Moreno-Navarrete, Jose M; Alzate, Oscar; Fernandez-Real, Jose M; Maeda, Nobuyo; Arbones-Mainar, Jose M

2014-08-01

353

Omega-3-derived mediators counteract obesity-induced adipose tissue inflammation.  

PubMed

Chronic low-grade inflammation in adipose tissue has been recognized as a key step in the development of obesity-associated complications. In obesity, the accumulation of infiltrating macrophages in adipose tissue and their phenotypic switch to M1-type dysregulate inflammatory adipokine production leading to obesity-linked insulin resistance. Resolvins are potent anti-inflammatory and pro-resolving mediators endogenously generated from omega-3 fatty acids that act as "stop-signals" of the inflammatory response promoting the resolution of inflammation. Recently, a deficit in the production of these endogenous anti-inflammatory signals has been demonstrated in obese adipose tissue. The restoration of their levels by either exogenous administration of these mediators or feeding omega-3-enriched diets, improves the inflammatory status of adipose tissue and ameliorates metabolic dysfunction. Here, we review the current knowledge on the role of these endogenous autacoids in the resolution of adipose tissue inflammation with special emphasis on their functional actions on macrophages. PMID:23707933

Titos, Esther; Clària, Joan

2013-12-01

354

Adipose-Tissue and Intestinal Inflammation - Visceral Obesity and Creeping Fat  

PubMed Central

Obesity has become one of the main threats to health worldwide and therefore gained increasing clinical and economic significance as well as scientific attention. General adipose-tissue accumulation in obesity is associated with systemically increased pro-inflammatory mediators and humoral and cellular changes within this compartment. These adipose-tissue changes and their systemic consequences led to the concept of obesity as a chronic inflammatory state. A pathognomonic feature of Crohn’s disease (CD) is creeping fat (CF), a locally restricted hyperplasia of the mesenteric fat adjacent to the inflamed segments of the intestine. The precise role of this adipose-tissue and its mediators remains controversial, and ongoing work will have to define whether this compartment is protecting from or contributing to disease activity. This review aims to outline specific cellular changes within the adipose-tissue, occurring in either obesity or CF. Hence the potential impact of adipocytes and resident immune cells from the innate and adaptive immune system will be discussed for both diseases. The second part focuses on the impact of generalized adipose-tissue accumulation in obesity, respectively on the locally restricted form in CD, on intestinal inflammation and on the closely related integrity of the mucosal barrier. PMID:25309544

Kredel, Lea I.; Siegmund, Britta

2014-01-01

355

IDENTIFICATION OF POLYBROMINATED BIPHENYLS IN THE ADIPOSE TISSUES OF THE GENERAL POPULATION OF THE UNITED STATES  

EPA Science Inventory

Hexabromobiphenyl has been identified by gas chromatography/mass spectrometry (GC/MS) in pooled extracts of adipose tissue samples collected from the general population of the conterminous United States. Mass spectra derived from tissue extracts subjected to gel permeation chroma...

356

Enzyme Activities in Liver, Muscle, and Adipose Tissue of Calves and Steers1  

Microsoft Academic Search

Enzyme a~laptations associated with the development of a functional rumen were investigated in liver, skeletal muscle, and abdominal adipose tissue. The activities of several enzymes representative of pathways of carbohydrate metabolism were deter- mined in tissues from milk-fed calves, early weaned calves, and finished steers. Associ- ated with a functional rumen there was, in liver, a reduced capacity for glucose

R. E. Howarth; R. L. Baldwin; M. Ronning

1968-01-01

357

2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN LEVELS IN ADIPOSE TISSUE OF VIETNAM VETERANS  

EPA Science Inventory

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been detected at levels ranging from 20 to 173 parts per trillion in adipose tissue from three Vietnam veterans who were 'heavily exposed' to Herbicide Orange. Some tissue samples from other Vietnam veterans and from controls also co...

358

Obesity modifies expression profiles of metabolic markers in superficial and deep subcutaneous abdominal adipose tissue depots.  

PubMed

While visceral adipose tissue (VAT) associates to obesity, there is debate for subcutaneous adipose tissue (SAT). One explanation may be SAT subcompartments, superficial-SAT (sSAT) and deep-SAT (dSAT), recently recognized as independent depots. Our aim was to establish roles for sSAT/dSAT with obesity by examining the expression of proteins key to adipocyte metabolism. Paired biopsies from sSAT and dSAT of 10 normal-weight (BMI 21.8 ± 0.8 kg/m(2)) and 11 obese subjects (BMI 44 ± 2.1 kg/m(2)) were analyzed for differences in insulin sensitivity using adiponectin, GLUT4 and resistin, glucocorticoid metabolism by 11?HSD1 and alterations of the adipokines leptin and TNF?. Between lean and obese subjects, sSAT and dSAT changes for GLUT4, resistin and TNF? were equivalent. Resistin and TNF? increased in both obese SAT sub-compartments; 33-fold (sSAT; P < 0.006) and 18.5-fold (dSAT; P < 0.003) higher resistin, with undetectable in leans to significant TNF? levels in obese. In contrast, GLUT4 showed 5.5-fold (sSAT; P < 0.03) and 7-fold (dSAT; P < 0.03) lower levels in obese, correlating to BMI (r = -0.6423, P = 0.007) and HOMA-IR (r = -0.5882, P = 0.017). Exclusive sSAT-specific differences were observed for adiponectin, leptin, and 11?HSD1. Both sSAT 11?HSD1 and leptin increased in obese, with 11?HSD1 2.5-fold (P = 0.052) and leptin 3.3-fold (P < 0.008) higher, with 11?HSD1 correlating to HOMA-IR (r = 0.5203, P = 0.0323) and leptin to BMI (r = 0.5810, P = 0.01). In contrast, obese had 7-fold (P < 0.02) lower sSAT adiponectin, correlating to BMI (r = -0.5178, P = 0.027) and HOMA-IR (r = -0.4570, P = 0.049). Overall, sSAT and dSAT are distinct abdominal adipose tissue depots with independent metabolic functions. Between the two, sSAT shows clear independent effects that associate to obesity and its metabolic complications. PMID:24030694

Walker, Gillian E; Marzullo, Paolo; Prodam, Flavia; Bona, Gianni; Di Blasio, Anna Maria

2014-05-01

359

Visceral adipose tissue mass in nonlactating dairy cows fed diets differing in energy density(1).  

PubMed

Our objective was to determine dietary energy effects on feed intake, internal fat deposition, body condition score (BCS), visceral organ mass, and blood analytes in Holstein cows. Eighteen nonpregnant, nonlactating cows (BCS = 3.04 ± 0.25) were blocked based on initial BCS and were randomly assigned within each block to 2 treatments. Treatments were either high energy [HE; net energy for lactation (NEL)=1.62 Mcal/kg] or low energy (LE; NEL = 1.35 Mcal/kg) diets fed as total mixed rations for 8 wk. The LE diet consisted of 81.7% forage, including 40.5% wheat straw and 28.3% corn silage, whereas the HE diet contained 73.8% forage with no straw and 49.9% corn silage (dry matter basis). Cows were fed for ad libitum intake once daily at 0800 h. Feed intake was recorded daily, blood was sampled at wk 1, 4, and 7, and BCS was assigned at wk 1, 4, and 7. Cows were killed following the 8-wk period, and visceral organs, mammary gland, and internal adipose tissues were weighed and sampled. The HE group had greater dry matter intake (15.9 vs. 11.2 ± 0.5 kg/d) and energy intakes than cows fed LE, but neutral detergent fiber intake did not differ (5.8 vs. 5.6 ± 0.25 kg/d for HE and LE). Final body weight was greater for cows fed HE (807 vs. 750 kg), but BCS did not differ between groups (3.52 vs. 3.47 for HE and LE). Omental (26.8 vs. 15.2 ± 1.6 kg/d), mesenteric (21.5 vs. 11.2 ± 1.9 kg), and perirenal (8.9 vs. 5.4 ± 0.9 kg) adipose tissue masses were larger in HE cows than in LE cows. Although subcutaneous adipose mass was not measured, carcass weight (including hide and subcutaneous fat) did not differ between HE (511 kg) and LE (496 kg). Liver weight tended to be greater for cows fed HE, but weights of gastrointestinal tract, heart, and kidney did not differ. Serum insulin tended to be greater and the glucose to insulin ratio was lower for cows fed HE. Serum concentrations of ?-hydroxybutyrate and cholesterol were greater for HE cows than for LE cows but concentrations of glucose, nonesterified fatty acids, total protein, and albumin did not differ. Final BCS was correlated with masses of omental (r = 0.57), mesenteric (r = 0.59), and perirenal (r = 0.72) adipose tissue, but mesenteric adipose mass increased more as BCS increased for cows fed HE. The similar final BCS between HE and LE cows demonstrates that BCS may lack sensitivity to detect differences in visceral fat deposition that might increase risk for peripartal diseases and disorders. PMID:24704224

Drackley, J K; Wallace, R L; Graugnard, D; Vasquez, J; Richards, B F; Loor, J J

2014-06-01

360

Mechanical Tissue Optical Clearing Devices: Enhancement of Light Penetration in Ex-Vivo Porcine Skin and Adipose Tissue  

PubMed Central

Background and Objective The complex morphological structure of tissue and associated variations in the indices of refraction of components therein, provides a highly scattering medium for visible and near-infrared wavelengths of light. Tissue optical clearing permits delivery of light deeper into tissue, potentially improving the capabilities of various light-based therapeutic techniques, such as adipose tissue removal or reshaping. Study Design/ Materials and Methods We report results of a study to evaluate effectiveness of novel mechanical tissue optical clearing devices (TOCD) using white light photography and infrared imaging radiometry (IIR). The TOCD consists of a pin array and vacuum pressure source applied directly to the skin surface. IIR images recorded light absorption and temperature increase of ex vivo porcine skin and adipose during laser irradiation (980 and 1210 nm) before and after TOCD application. Results White light photographic images of in vivo human skin demonstrated localized compression and altered visual appearance, indicative of water and blood movement in skin. White light photographic images also showed increased visible light transport through regions of ex vivo porcine skin compressed by TOCD pins. Rate of heating in sub-dermal adipose regions beneath TOCD pins was two-fold higher following TOCD application. Conclusions Results of our study suggest that mechanical optical clearing may provide a means to deliver increased light fluence to dermal and adipose tissues. PMID:19065559

Milner, Thomas E.; Baranov, Stepan; Nelson, J. Stuart

2008-01-01

361

Role of renin-angiotensin-aldosterone system in adipose tissue dysfunction.  

PubMed

The renin-angiotensin-aldosterone system (RAAS) is known to be closely linked to the pathogenesis of insulin resistance. The angiotensin (Ang) II type 1 (AT?) receptor mediates the major effects of Ang II in adipose tissue, and blockade of the AT? receptor improves insulin sensitivity, with enhanced adipocyte differentiation. In contrast, the role of angiotensin type 2 (AT?) receptor activation in insulin sensitivity is still controversial, although AT? receptor functions are thought to be mutually antagonistic against those of the AT? receptor in the cardiovascular system. Aldosterone exerts its biological roles via the mineralocorticoid receptor (MR), and inhibition of MR signaling in adipose tissue ameliorates inflammation, with upregulation of insulin-mediated glucose transport and adipocyte differentiation. Clinical studies indicate that blockade of RAAS prevents the new onset of type 2 diabetes and improves the metabolic syndrome in diabetic patients. We here review the recent concepts of the roles of RAAS in adipose tissue. PMID:22465098

Jing, Fei; Mogi, Masaki; Horiuchi, Masatsugu

2013-09-25

362

What's the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health  

PubMed Central

Marrow adipose tissue (MAT) is functionally distinct from both white and brown adipose tissue and can contribute to systemic and skeletal metabolism. MAT formation is a spatially and temporally defined developmental event, suggesting that MAT is an organ that serves important functions and, like other organs, can undergo pathologic change. The well-documented inverse relationship between MAT and bone mineral density has been interpreted to mean that MAT removal is a possible therapeutic target for osteoporosis. However, the bone and metabolic phenotypes of patients with lipodystrophy argues that retention of MAT may actually be beneficial in some circumstances. Furthermore, MAT may exist in two forms, regulated and constitutive, with divergent responses to hematopoietic and nutritional demands. In this review, we discuss the role of MAT in lipodystrophy, bone loss, and metabolism, and highlight our current understanding of this unique adipose tissue depot. PMID:24650218

Scheller, Erica L; Rosen, Clifford J

2014-01-01

363

Adipose Tissue and Adipokines: The Association with and Application of Adipokines in Obesity  

PubMed Central

2014 marks the 20th anniversary of adipokines. Through the identification of leptin, our perceived understanding of adipose tissue was changed instantaneously. From a simple dormant site of energy storage, adipose tissue is now recognized as an integral hub of various hormones known as adipokines. Although great strides have been made in characterizing these hormones in health, research also shows they are significantly implicated in a series of pathologies. One such condition is obesity. Defined as an excess of adipose tissue, obesity remains one of the greatest healthcare epidemics of the 21st century. With no definitive treatment, attention has shifted to understanding the role of adipokines in obesity. This review provides an introduction to the salient obesity-related adipokines and their possible application as a treatment for obesity. PMID:25309775

Khan, Muhammad; Joseph, Frank

2014-01-01

364

Interactions among bone, liver, and adipose tissue predisposing to diabesity and fatty liver.  

PubMed

Growing epidemiological evidence connects obesity and its complications, including metabolic syndrome, diabetes, and nonalcoholic fatty liver disease (NAFLD) to reduced bone health and osteoporosis. Parallel to human studies, experimental data disclosed a complex network of interaction among adipose tissue, the liver, and the bone, which reciprocally modulate the function of each other. The main mediators of such crosstalk include hormonal/cytokine signals from the bone (osteopontin, osteocalcin, and osteoprotegerin), the liver (fetuin-A), and adipose tissue [leptin, tumor necrosis factor-? (TNF-?), and adiponectin]. Dysregulation of this network promotes the development of diabesity, NAFLD, and osteoporosis. We will review recent advances in understanding the mechanisms of bone-liver-adipose tissue interaction predisposing to obesity, diabetes, NAFLD, and osteoporosis and their potential clinical implications. PMID:23816817

Musso, Giovanni; Paschetta, Elena; Gambino, Roberto; Cassader, Maurizio; Molinaro, Federica

2013-09-01

365

What's the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health.  

PubMed

Marrow adipose tissue (MAT) is functionally distinct from both white and brown adipose tissue and can contribute to systemic and skeletal metabolism. MAT formation is a spatially and temporally defined developmental event, suggesting that MAT is an organ that serves important functions and, like other organs, can undergo pathologic change. The well-documented inverse relationship between MAT and bone mineral density has been interpreted to mean that MAT removal is a possible therapeutic target for osteoporosis. However, the bone and metabolic phenotypes of patients with lipodystrophy argues that retention of MAT may actually be beneficial in some circumstances. Furthermore, MAT may exist in two forms, regulated and constitutive, with divergent responses to hematopoietic and nutritional demands. In this review, we discuss the role of MAT in lipodystrophy, bone loss, and metabolism, and highlight our current understanding of this unique adipose tissue depot. PMID:24650218

Scheller, Erica L; Rosen, Clifford J

2014-04-01

366

Adipose tissue transplantation may be a potential treatment for diabetes, atherosclerosis and nonalcoholic steatohepatitis.  

PubMed

Adipose tissue is critical in energy homeostasis. Adipose tissue 'buffers' the lipids and energy rich compounds which are pumped into the blood stream soon after meals. It senses, signals other organs like liver and brain about the energy reserves via adipokines. Adiponectin, the most abundant adipokine has insulin sensitizing, anti-inflammatory antiatherogenic and antisteatotic effects. Adipose tissue dysfunction is accompanied by abnormal lipid distribution and storage which contributes to diseases like diabetes, nonalcoholic fatty liver disease and atherosclerosis. Obesity and lipodystrophy are associated with dysfunctional adipocytes. Pre-adipocytes are easy to isolate and culture. A personalized depot specific liposuction to remove the inactive adipocytes followed by adipocyte repopulation could be useful in the treatment of these diseases. PMID:19046821

Sanal, Madhusudana Girija

2009-03-01

367

Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells  

SciTech Connect

Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal model. MSC from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes. Adipose tissue is abundant and easily accessible and could thus also harbor cells with the potential to differentiate in insulin producing cells. We isolated human adipose tissue-derived MSC from four healthy donors. During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. The cells were induced to differentiate into a pancreatic endocrine phenotype by defined culture conditions within 3 days. Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin.

Timper, Katharina [Department of Research, University Hospital, Basel (Switzerland); Seboek, Dalma [Department of Research, University Hospital, Basel (Switzerland); Eberhardt, Michael [Department of Research, University Hospital, Basel (Switzerland); Linscheid, Philippe [Department of Research, University Hospital, Basel (Switzerland); Christ-Crain, Mirjam [Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital, Basel (Switzerland); Keller, Ulrich [Department of Research, University Hospital, Basel (Switzerland); Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital, Basel (Switzerland); Mueller, Beat [Department of Research, University Hospital, Basel (Switzerland); Division of Endocrinology, Diabetes and Clinical Nutri