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Sample records for adipose tissue specific

  1. The role of GH in adipose tissue: lessons from adipose-specific GH receptor gene-disrupted mice.

    PubMed

    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; Kopchick, John J

    2013-03-01

    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

  2. The Adipose Tissue Microenvironment Regulates Depot-Specific Adipogenesis in Obesity.

    PubMed

    Jeffery, Elise; Wing, Allison; Holtrup, Brandon; Sebo, Zachary; Kaplan, Jennifer L; Saavedra-Peña, Rocio; Church, Christopher D; Colman, Laura; Berry, Ryan; Rodeheffer, Matthew S

    2016-07-12

    The sexually dimorphic distribution of adipose tissue influences the development of obesity-associated pathologies. The accumulation of visceral white adipose tissue (VWAT) that occurs in males is detrimental to metabolic health, while accumulation of subcutaneous adipose tissue (SWAT) seen in females may be protective. Here, we show that adipocyte hyperplasia contributes directly to the differential fat distribution between the sexes. In male mice, high-fat diet (HFD) induces adipogenesis specifically in VWAT, while in females HFD induces adipogenesis in both VWAT and SWAT in a sex hormone-dependent manner. We also show that the activation of adipocyte precursors (APs), which drives adipocyte hyperplasia in obesity, is regulated by the adipose depot microenvironment and not by cell-intrinsic mechanisms. These findings indicate that APs are plastic cells, which respond to both local and systemic signals that influence their differentiation potential independent of depot origin. Therefore, depot-specific AP niches coordinate adipose tissue growth and distribution. PMID:27320063

  3. Differential Patterns of Serum Concentration and Adipose Tissue Expression of Chemerin in Obesity: Adipose Depot Specificity and Gender Dimorphism

    PubMed Central

    Alfadda, Assim A; Sallam, Reem M; Chishti, Muhammad Azhar; Moustafa, Amr S; Fatma, Sumbul; Alomaim, Waleed S; Al-Naami, Mohammed Y; Bassas, Abdulelah F; Chrousos, George P; Jo, Hyunsun

    2012-01-01

    Chemerin, a recognized chemoattractant, is expressed in adipose tissue and plays a role in adipocytes differentiation and metabolism. Gender- and adipose tissue-specific differences in human chemerin expression have not been well characterized. Therefore, these differences were assessed in the present study. The body mass index (BMI) and the circulating levels of chemerin and other inflammatory, adiposity and insulin resistance markers were assessed in female and male adults of varying degree of obesity. Chemerin mRNA expression was also measured in paired subcutaneous and visceral adipose tissue samples obtained from a subset of the study subjects. Serum chemerin concentrations correlated positively with BMI and serum leptin levels and negatively with high density lipoprotein (HDL)-cholesterol levels. No correlation was found between serum chemerin concentrations and fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, C-reactive protein or adiponectin. Similarly, no relation was observed with the homeostasis model assessment for insulin resistance (HOMA-IR) values. Gender- and adipose tissue-specific differences were observed in chemerin mRNA expression levels, with expression significantly higher in women than men and in subcutaneous than visceral adipose tissue. Interestingly, we found a significant negative correlation between circulating chemerin levels and chemerin mRNA expression in subcutaneous fat. Among the subjects studied, circulating chemerin levels were associated with obesity markers but not with markers of insulin resistance. At the tissue level, fat depot-specific differential regulation of chemerin mRNA expression might contribute to the distinctive roles of subcutaneous vs. visceral adipose tissue in human obesity. PMID:22544171

  4. Adipose tissue depot specific differences of PLIN protein content in endurance trained rats.

    PubMed

    Ramos, Sofhia V; Turnbull, Patrick C; MacPherson, Rebecca E K

    2016-01-01

    Adipose tissue is classified as either white (WAT) or brown (BAT) and differs not only by anatomical location but also in function. WAT is the main source of stored energy and releases fatty acids in times of energy demand, whereas BAT plays a role in regulating non-shivering thermogenesis and oxidizes fatty acids released from the lipid droplet. The PLIN family of proteins has recently emerged as being integral in the regulation of fatty acid storage and release in adipose tissue. Previous work has demonstrated that PLIN protein content varies among adipose tissue depots, however an examination of endurance training-induced depot specific changes in PLIN protein expression has yet to be done. Male Sprague-dawley rats (n = 10) underwent 8-weeks of progressive treadmill training (18-25 m/min for 30-60 min at 10% incline) or remained sedentary as control. Following training, under isoflurane induced anesthesia epidydmal (eWAT), inguinal subcutaneous (iWAT) and intrascapular brown adipose tissue (BAT) was excised, and plasma was collected. Endurance training resulted in an increase in BAT PLIN5 and iWAT PLIN3 content, while there was no difference in PLIN protein content in endurance trained eWAT. Interestingly, endurance training resulted in a robust increase in ATGL and CGI-58 in eWAT alone. Together these results suggest the potential of a depot specific function of PLIN3 and PLIN5 in adipose tissue in response to endurance training. PMID:27386161

  5. Adipose tissue fibrosis

    PubMed Central

    Buechler, Christa; Krautbauer, Sabrina; Eisinger, Kristina

    2015-01-01

    The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. Thereby adipose tissue growth is limited and excess triglycerides are stored in ectopic tissues. Stressed adipocytes and hypoxia contribute to immune cell immigration and activation which further aggravates adipose tissue fibrosis. There is substantial evidence that adipose tissue fibrosis is linked to metabolic dysfunction, both in rodent models and in the clinical setting. Peroxisome proliferator activated receptor gamma agonists and adiponectin both reduce adipose tissue fibrosis, inflammation and insulin resistance. Current knowledge suggests that antifibrotic drugs, increasing adipose tissue oxygen supply or HIF-1 antagonists will improve adipose tissue function and thereby ameliorate metabolic diseases. PMID:25987952

  6. Depot- and sex-specific effects of maternal obesity in offspring's adipose tissue.

    PubMed

    Lecoutre, Simon; Deracinois, Barbara; Laborie, Christine; Eberlé, Delphine; Guinez, Céline; Panchenko, Polina E; Lesage, Jean; Vieau, Didier; Junien, Claudine; Gabory, Anne; Breton, Christophe

    2016-07-01

    According to the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term programming of individual body weight (BW) setpoint. In particular, maternal obesity, excessive nutrition, and accelerated growth in neonates have been shown to sensitize offspring to obesity. The white adipose tissue may represent a prime target of metabolic programming induced by maternal obesity. In order to unravel the underlying mechanisms, we have developed a rat model of maternal obesity using a high-fat (HF) diet (containing 60% lipids) before and during gestation and lactation. At birth, newborns from obese dams (called HF) were normotrophs. However, HF neonates exhibited a rapid weight gain during lactation, a key period of adipose tissue development in rodents. In males, increased BW at weaning (+30%) persists until 3months of age. Nine-month-old HF male offspring was normoglycemic but showed mild glucose intolerance, hyperinsulinemia, and hypercorticosteronemia. Despite no difference in BW and energy intake, HF adult male offspring was predisposed to fat accumulation showing increased visceral (gonadal and perirenal) depots weights and hyperleptinemia. However, only perirenal adipose tissue depot exhibited marked adipocyte hypertrophy and hyperplasia with elevated lipogenic (i.e. sterol-regulated element binding protein 1 (Srebp1), fatty acid synthase (Fas), and leptin) and diminished adipogenic (i.e. peroxisome proliferator-activated receptor gamma (Pparγ), 11β-hydroxysteroid dehydrogenase type 1 (11β-Hds1)) mRNA levels. By contrast, very few metabolic variations were observed in HF female offspring. Thus, maternal obesity and accelerated growth during lactation program offspring for higher adiposity via transcriptional alterations of visceral adipose tissue in a depot- and sex-specific manner. PMID:27122310

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

    PubMed Central

    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

    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

  8. The lipid profile of brown adipose tissue is sex-specific in mice.

    PubMed

    Hoene, Miriam; Li, Jia; Häring, Hans-Ulrich; Weigert, Cora; Xu, Guowang; Lehmann, Rainer

    2014-10-01

    Brown adipose tissue (BAT) is a thermogenic organ with a vital function in small mammals and potential as metabolic drug target in humans. By using high-resolution LC-tandem-mass spectrometry, we quantified 329 lipid species from 17 (sub)classes and identified the fatty acid composition of all phospholipids from BAT and subcutaneous and gonadal white adipose tissue (WAT) from female and male mice. Phospholipids and free fatty acids were higher in BAT, while DAG and TAG levels were higher in WAT. A set of phospholipids dominated by the residue docosahexaenoic acid, which influences membrane fluidity, showed the highest specificity for BAT. We additionally detected major sex-specific differences between the BAT lipid profiles, while samples from the different WAT depots were comparatively similar. Female BAT contained less triacylglycerol and more phospholipids rich in arachidonic and stearic acid whereas another set of fatty acid residues that included linoleic and palmitic acid prevailed in males. These differences in phospholipid fatty acid composition could greatly affect mitochondrial membranes and other cellular organelles and thereby regulate the function of BAT in a sex-specific manner. PMID:25128765

  9. Gender and Obesity Specific MicroRNA Expression in Adipose Tissue from Lean and Obese Pigs.

    PubMed

    Mentzel, Caroline M Junker; Anthon, Christian; Jacobsen, Mette J; Karlskov-Mortensen, Peter; Bruun, Camilla S; Jørgensen, Claus B; Gorodkin, Jan; Cirera, Susanna; Fredholm, Merete

    2015-01-01

    Obesity is a complex condition that increases the risk of life threatening diseases such as cardiovascular disease and diabetes. Studying the gene regulation of obesity is important for understanding the molecular mechanisms behind the obesity derived diseases and may lead to better intervention and treatment plans. MicroRNAs (miRNAs) are short non-coding RNAs regulating target mRNA by binding to their 3'UTR. They are involved in numerous biological processes and diseases, including obesity. In this study we use a mixed breed pig model designed for obesity studies to investigate differentially expressed miRNAs in subcutaneous adipose tissue by RNA sequencing (RNAseq). Both male and female pigs are included to explore gender differences. The RNAseq study shows that the most highly expressed miRNAs are in accordance with comparable studies in pigs and humans. A total of six miRNAs are differentially expressed in subcutaneous adipose tissue between the lean and obese group of pigs, and in addition gender specific significant differential expression is observed for a number of miRNAs. The differentially expressed miRNAs have been verified using qPCR. The results of these studies in general confirm the trends found by RNAseq. Mir-9 and mir-124a are significantly differentially expressed with large fold changes in subcutaneous adipose tissue between lean and obese pigs. Mir-9 is more highly expressed in the obese pigs with a fold change of 10 and a p-value < 0.001. Mir-124a is more highly expressed in the obese pigs with a fold change of 114 and a p-value < 0.001. In addition, mir-124a is significantly higher expressed in abdominal adipose tissue in male pigs with a fold change of 119 and a p-value < 0.05. Both miRNAs are also significantly higher expressed in the liver of obese male pigs where mir-124a has a fold change of 12 and mir-9 has a fold change of 1.6, both with p-values < 0.05. PMID:26222688

  10. Adiposity is associated with DNA methylation profile in adipose tissue

    PubMed Central

    Agha, Golareh; Houseman, E Andres; Kelsey, Karl T; Eaton, Charles B; Buka, Stephen L; Loucks, Eric B

    2015-01-01

    Background: Adiposity is a risk factor for type 2 diabetes and cardiovascular disease, suggesting an important role for adipose tissue in the development of these conditions. The epigenetic underpinnings of adiposity are not well understood, and studies of DNA methylation in relation to adiposity have rarely focused on target adipose tissue. Objectives were to evaluate whether genome-wide DNA methylation profiles in subcutaneous adipose tissue and peripheral blood leukocytes are associated with measures of adiposity, including central fat mass, body fat distribution and body mass index. Methods: Participants were 106 men and women (mean age 47 years) from the New England Family Study. DNA methylation was evaluated using the Infinium HumanMethylation450K BeadChip. Adiposity phenotypes included dual-energy X-ray absorptiometry-assessed android fat mass, android:gynoid fat ratio and trunk:limb fat ratio, as well as body mass index. Results: Adipose tissue genome-wide DNA methylation profiles were associated with all four adiposity phenotypes, after adjusting for race, sex and current smoking (omnibus p-values <0.001). After further adjustment for adipose cell-mixture effects, associations with android fat mass, android:gynoid fat ratio, and trunk:limb fat ratio remained. In gene-specific analyses, adiposity phenotypes were associated with adipose tissue DNA methylation in several genes that are biologically relevant to the development of adiposity, such as AOC3, LIPE, SOD3, AQP7 and CETP. Blood DNA methylation profiles were not associated with adiposity, before or after adjustment for blood leukocyte cell mixture effects. Conclusion: Findings show that DNA methylation patterns in adipose tissue are associated with adiposity. PMID:25541553

  11. Adipose tissues and thyroid hormones

    PubMed Central

    Obregon, Maria-Jesus

    2014-01-01

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

  12. Lysine-specific demethylase 1 promotes brown adipose tissue thermogenesis via repressing glucocorticoid activation.

    PubMed

    Zeng, Xing; Jedrychowski, Mark P; Chen, Yi; Serag, Sara; Lavery, Gareth G; Gygi, Steve P; Spiegelman, Bruce M

    2016-08-15

    Brown adipocytes display phenotypic plasticity, as they can switch between the active states of fatty acid oxidation and energy dissipation versus a more dormant state. Cold exposure or β-adrenergic stimulation favors the active thermogenic state, whereas sympathetic denervation or glucocorticoid administration promotes more lipid accumulation. Our understanding of the molecular mechanisms underlying these switches is incomplete. Here we found that LSD1 (lysine-specific demethylase 1), a histone demethylase, regulates brown adipocyte metabolism in two ways. On the one hand, LSD1 associates with PRDM16 to repress expression of white fat-selective genes. On the other hand, LSD1 represses HSD11B1 (hydroxysteroid 11-β-dehydrogenase isozyme 1), a key glucocorticoid-activating enzyme, independently from PRDM16. Adipose-specific ablation of LSD1 impaired mitochondrial fatty acid oxidation capacity of the brown adipose tissue, reduced whole-body energy expenditure, and increased fat deposition, which can be significantly alleviated by simultaneously deleting HSD11B1. These findings establish a novel regulatory pathway connecting histone modification and hormone activation with mitochondrial oxidative capacity and whole-body energy homeostasis. PMID:27566776

  13. A comparative approach to understanding tissue-specific expression of uncoupling protein 1 expression in adipose tissue.

    PubMed

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

    2012-01-01

    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

  14. Triacylglycerol metabolism in adipose tissue

    PubMed Central

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

    2009-01-01

    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

  15. Site-specific circadian expression of leptin and its receptor in human adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian variability of circulating leptin levels has been well established over the last decade. However, the circadian behavior of leptin in human adipose tissue remains unknown. This also applies to the soluble leptin receptor. We investigated the ex vivo circadian behavior of leptin and its rec...

  16. Post-mortem stability of RNA in skeletal muscle and adipose tissue and the tissue-specific expression of myostatin, perilipin and associated factors in the horse.

    PubMed

    Morrison, Philippa K; Bing, Chen; Harris, Patricia A; Maltin, Charlotte A; Grove-White, Dai; Argo, Caroline McG

    2014-01-01

    Obesity, a major concern for equine welfare, is highly prevalent in the leisure horse population. Skeletal-muscle and adipose tissues are important determinants of maintenance energy requirements. The myostatin and perilipin pathways play key roles in the regulation of muscle mass and lipolysis respectively and have both been associated with obesity predisposition in other mammalian species. High quality samples, suitable for molecular biology, are an essential prerequisite for detailed investigations of gene and protein expression. Hence, this study has evaluated a) the post-mortem stability of RNA extracted from skeletal-muscle and adipose-tissues collected under commercial conditions and b) the tissue-specific presence of myostatin, the moystatin receptor (activin receptor IIB, ActRIIB), follistatin and perilipin, genes and proteins across a range of equine tissues. Objectives were addressed using tissues from 7 Thoroughbred horses presented for slaughter at a commercial abattoir; a) samples were collected at 7 time-points from Masseter muscle and perirenal adipose from 5 minutes to 6 hours post-mortem. Extracted RN was appraised by Optical Density analysis and agarose-gel electrophoresis. b) Quantitative real time PCR and Western Blotting were used to evaluate gene and protein expression in anatomically-defined samples collected from 17 tissues (6 organs, 4 skeletal muscles and 7 discrete adipose depots). The results indicate that, under the present collection conditions, intact, good quality RNA could be extracted from skeletal-muscle for up to 2 hours post-mortem. However, RNA from adipose tissue may be more susceptible to degradation/contamination and samples should be collected no later than 30 minutes post-mortem. The data also show that myostatin and ActRIIB genes and proteins were almost exclusively expressed in skeletal muscle. The follistatin gene showed a more diverse gene expression profile, with expression evident in several organs, adipose tissue

  17. Post-Mortem Stability of RNA in Skeletal Muscle and Adipose Tissue and the Tissue-Specific Expression of Myostatin, Perilipin and Associated Factors in the Horse

    PubMed Central

    Morrison, Philippa K.; Bing, Chen; Harris, Patricia A.; Maltin, Charlotte A.; Grove-White, Dai; Argo, Caroline McG.

    2014-01-01

    Obesity, a major concern for equine welfare, is highly prevalent in the leisure horse population. Skeletal-muscle and adipose tissues are important determinants of maintenance energy requirements. The myostatin and perilipin pathways play key roles in the regulation of muscle mass and lipolysis respectively and have both been associated with obesity predisposition in other mammalian species. High quality samples, suitable for molecular biology, are an essential prerequisite for detailed investigations of gene and protein expression. Hence, this study has evaluated a) the post-mortem stability of RNA extracted from skeletal-muscle and adipose-tissues collected under commercial conditions and b) the tissue-specific presence of myostatin, the moystatin receptor (activin receptor IIB, ActRIIB), follistatin and perilipin, genes and proteins across a range of equine tissues. Objectives were addressed using tissues from 7 Thoroughbred horses presented for slaughter at a commercial abattoir; a) samples were collected at 7 time-points from Masseter muscle and perirenal adipose from 5 minutes to 6 hours post-mortem. Extracted RN was appraised by Optical Density analysis and agarose-gel electrophoresis. b) Quantitative real time PCR and Western Blotting were used to evaluate gene and protein expression in anatomically-defined samples collected from 17 tissues (6 organs, 4 skeletal muscles and 7 discrete adipose depots). The results indicate that, under the present collection conditions, intact, good quality RNA could be extracted from skeletal-muscle for up to 2 hours post-mortem. However, RNA from adipose tissue may be more susceptible to degradation/contamination and samples should be collected no later than 30 minutes post-mortem. The data also show that myostatin and ActRIIB genes and proteins were almost exclusively expressed in skeletal muscle. The follistatin gene showed a more diverse gene expression profile, with expression evident in several organs, adipose tissue

  18. Perivascular Adipose Tissue

    PubMed Central

    Maille, Nicole; Clas, Darren; Osol, George

    2015-01-01

    Perivascular adipose tissue (PVAT) contributes to vasoregulation. The role of this adipose tissue bed in pregnancy has not been examined. Here, we tested the hypothesis that PVAT in pregnant rats decreases resistance artery tone. Mesenteric arteries from nonpregnant (NP) and late pregnant (LP) rats were exposed to phenylephrine (PHE) or KCl in the presence (+) versus absence (−) of PVAT. The LP PVAT(+) vessels showed a 44% decrease in sensitivity to PHE in the presence of PVAT. There was no attenuation of the contractile response to KCl when PVAT was present. The LP arteries perfused with LP or NP PVAT underwent vasodilation; unexpectedly, NP vessels in the presence of PVAT from LP rats sustained a 48% vasoconstriction. The PVAT attenuates vasoconstriction by a mechanism that involves hyperpolarization. The vasoconstriction observed when nonpregnant vessels were exposed to pregnant PVAT suggests pregnant vessels adapt to the vasoconstricting influence of pregnant PVAT. PMID:25527422

  19. Adipose tissue-specific inactivation of the retinoblastoma protein protects against diabesity because of increased energy expenditure

    PubMed Central

    Dali-Youcef, Nassim; Mataki, Chikage; Coste, Agnès; Messaddeq, Nadia; Giroud, Sylvain; Blanc, Stéphane; Koehl, Christian; Champy, Marie-France; Chambon, Pierre; Fajas, Lluis; Metzger, Daniel; Schoonjans, Kristina; Auwerx, Johan

    2007-01-01

    The role of the tumor suppressor retinoblastoma protein (pRb) has been firmly established in the control of cell cycle, apoptosis, and differentiation. Recently, it was demonstrated that lack of pRb promotes a switch from white to brown adipocyte differentiation in vitro. We used the Cre-Lox system to specifically inactivate pRb in adult adipose tissue. Under a high-fat diet, pRb-deficient (pRbad−/−) mice failed to gain weight because of increased energy expenditure. This protection against weight gain was caused by the activation of mitochondrial activity in white and brown fat as evidenced by histologic, electron microscopic, and gene expression studies. Moreover, pRb−/− mouse embryonic fibroblasts displayed higher proliferation and apoptosis rates than pRb+/+ mouse embryonic fibroblasts, which could contribute to the altered white adipose tissue morphology. Taken together, our data support a direct role of pRb in adipocyte cell fate determination in vivo and suggest that pRb could serve as a potential therapeutic target to trigger mitochondrial activation in white adipose tissue and brown adipose tissue, favoring an increase in energy expenditure and subsequent weight loss. PMID:17556545

  20. Depot-specific effects of treadmill running and rutin on white adipose tissue function in diet-induced obese mice.

    PubMed

    Chen, Neng; Lei, Ting; Xin, Lili; Zhou, Lingmei; Cheng, Jinbo; Qin, Liqiang; Han, Shufen; Wan, Zhongxiao

    2016-09-01

    White adipose tissue (WAT) is a critical organ involved in regulating metabolic homeostasis under obese condition. Strategies that could positively affect WAT function would hold promise for fighting against obesity and its complications. The aim of the present study is to explore the effects of treadmill exercise training and rutin intervention on adipose tissue function from diet-induced obese (DIO) mice and whether fat depot-specific effects existed. In epididymal adipose tissue, high-fat diet (HFD) resulted in reduction in adiponectin mRNA expression, peroxisome proliferator-activated receptors (PPAR)-γ and DsbA-L protein expression, elevation in endoplasmic reticulum (ER) stress markers including 78 kDa glucose-regulated protein (GRP-78), C/EBP homologous protein (CHOP) and p-c-Jun N-terminal kinase (JNK). Isoproterenol-stimulated lipolysis and insulin stimulated Akt phosphorylation ex vivo were blunted from HFD group. The combination of rutin with exercise (HRE) completely restored GRP78 and p-JNK protein expression to normal levels, as well as blunted signaling ex vivo. In inguinal adipose tissue, HFD led to increased adiponectin mRNA expression, PPAR-γ, GRP78, and p-JNK protein expression, and reduction in DsbA-L. HRE is effective for restoring p-JNK, PPAR-γ, and DsbA-L. In conclusion, depot-specific effects may exist in regard to the effects of rutin and exercise on key molecules involved in regulating adipose tissue function (i.e., ER stress markers, PPAR-γ and DsbA-L, adiponectin expression, and secretion, ex vivo catecholamine stimulated lipolysis and insulin stimulated Akt phosphorylation) from DIO mice. PMID:27192989

  1. Fibrosis and Adipose Tissue Dysfunction

    PubMed Central

    Sun, Kai; Tordjman, Joan; Clément, Karine; Scherer, Philipp E.

    2013-01-01

    Fibrosis is increasingly appreciated as a major player in adipose tissue dysfunction. In rapidly expanding adipose tissue, pervasive hypoxia leads to an induction of HIF1α that in turn leads to a potent pro-fibrotic transcriptional program. The pathophysiological impact of adipose tissue fibrosis is likely to play an equally important role on systemic metabolic alterations as fibrotic conditions play in the liver, heart and kidney. Here, we discuss recent advances in our understanding of the genesis, modulation and systemic impact of excessive extracellular matrix (ECM) accumulation in adipose tissue of both rodents and humans and the ensuing impact on metabolic dysfunction. PMID:23954640

  2. Bioengineering Beige Adipose Tissue Therapeutics.

    PubMed

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

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

  3. Bioengineering Beige Adipose Tissue Therapeutics

    PubMed Central

    Tharp, Kevin M.; Stahl, Andreas

    2015-01-01

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

  4. Heat stress in pigs is accompanied by adipose tissue-specific responses that favor increased triglyceride storage.

    PubMed

    Qu, H; Yan, H; Lu, H; Donkin, S S; Ajuwon, K M

    2016-05-01

    Heat stress (HS) negatively affects all aspects of performance in pigs. Although certain tissue-specific responses in the liver, skeletal muscle, and intestine are known, there is paucity of information on responses within the adipose tissue. Therefore, the objective of this study was to delineate adipose tissue responses during HS in pigs. Thirty crossbred (Ossabaw × Duroc × Landrace) pigs were assigned to 3 treatments for 7 d. Treatments were 1) control and libitum fed (CON) with room temperature set at 20°C ± 1°C, 2) pair fed (PF) with room temperature as the CON treatment but pair fed to HS pigs, and 3) HS with room temperature 35°C ± 1°C and ad libitum access to feed. Compared with CON pigs, HS pigs had decreased feed intake and elevated skin temperature and respiration rate ( < 0.01). Blood urea nitrogen was higher ( = 0.01) in HS pigs compared with CON pigs only in males. In both subcutaneous and mesenteric adipose tissue, mRNA abundance of phosphoenolpyruvate carboxykinase (PCK1) was more elevated ( < 0.01) in HS groups compared with the CON and PF groups. Heat stress also caused increased heat shock protein 70 (HSP70; = 0.067) and CCAT/enhancer-binding homologous protein (CHOP) content ( < 0.05) in the mesenteric fat compared with the CON treatment. In conclusion, induction of PCK1 expression in adipose tissue by HS suggests elevated glyceroneogenesis might be involved in the increased fat storage in pigs under HS. PMID:27285686

  5. Site-specific concentrations of carotenoids in adipose tissue: relations with dietary and serum carotenoid concentrations in healthy adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary carotenoids are related to decreased risk of certain diseases. Serum and adipose tissue carotenoid concentrations are used as biomarkers of intake. This study examined relationships among concentrations of carotenoids in diet, serum and adipose tissue. Twelve women and thirteen healthy men p...

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

    PubMed

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

    2016-05-01

    An adipose tissue engineering chamber model of spontaneous adipose tissue generation from an existing fat flap has been described. However, the chamber does not completely fill with adipose tissue in this model. Here, the effect of adipose tissue extract (ATE) on adipose tissue regeneration was investigated. In vitro, the adipogenic and angiogenic capacities of ATE were evaluated using Oil Red O and tube formation assays on adipose-derived stem cells (ASCs) and rat aortic endothelial cells (RAECs), respectively. In vivo, saline or ATE was injected into the adipose tissue engineering chamber 1 week after its implantation. At different time points post-injection, the contents were morphometrically, histologically, and immunohistochemically evaluated, and the expression of growth factors and adipogenic genes was analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. With the exception of the baseline control group, in which fat flaps were not inserted into a chamber, the total volume of fat flap tissue increased significantly in all groups, especially in the ATE group. Better morphology and structure, a thinner capsule, and more vessels were observed in the ATE group than in the control group. Expression of angiogenic growth factors and adipogenic markers were significantly higher in the ATE group. ATE therefore significantly promoted adipose tissue regeneration and reduced capsule formation in an adipose tissue engineering chamber model. These data suggest that ATE provides a more angiogenic and adipogenic microenvironment for adipose tissue formation by releasing various cytokines and growth factors that also inhibit capsule formation. PMID:26678825

  7. Age-related and depot-specific changes in white adipose tissue of growth hormone receptor-null mice.

    PubMed

    Sackmann-Sala, Lucila; Berryman, Darlene E; Lubbers, Ellen R; Zhang, Han; Vesel, Clare B; Troike, Katie M; Gosney, Elahu S; List, Edward O; Kopchick, John J

    2014-01-01

    Growth hormone receptor-null (GHR(-/-)) mice are dwarf, insulin sensitive, and long-lived in spite of increased adiposity. However, their adiposity is not uniform, with select white adipose tissue (WAT) depots enlarged. To study WAT depot-specific effects on insulin sensitivity and life span, we analyzed individual WAT depots of 12- and 24-month-old GHR(-) (/-) and wild-type (WT) mice, as well as their plasma levels of selected hormones. Adipocyte sizes and plasma insulin, leptin, and adiponectin levels decreased with age in both GHR(-) (/-) and WT mice. Two-dimensional gel electrophoresis proteomes of WAT depots were similar among groups, but several proteins involved in endocytosis and/or cytoskeletal organization (Ehd2, S100A10, actin), anticoagulation (S100A10, annexin A5), and age-related conditions (alpha2-macroglobulin, apolipoprotein A-I, transthyretin) showed significant differences between genotypes. Because Ehd2 may regulate endocytosis of Glut4, we measured Glut4 levels in the WAT depots of GHR(-) (/-) and WT mice. Inguinal WAT of 12-month-old GHR(-) (/-) mice displayed lower levels of Glut4 than WT. Overall, the protein changes detected in this study offer new insights into possible mechanisms contributing to enhanced insulin sensitivity and extended life span in GHR(-) (/-) mice. PMID:23873966

  8. Age-Related and Depot-Specific Changes in White Adipose Tissue of Growth Hormone Receptor-Null Mice

    PubMed Central

    2014-01-01

    Growth hormone receptor-null (GHR−/−) mice are dwarf, insulin sensitive, and long-lived in spite of increased adiposity. However, their adiposity is not uniform, with select white adipose tissue (WAT) depots enlarged. To study WAT depot–specific effects on insulin sensitivity and life span, we analyzed individual WAT depots of 12- and 24-month-old GHR− /− and wild-type (WT) mice, as well as their plasma levels of selected hormones. Adipocyte sizes and plasma insulin, leptin, and adiponectin levels decreased with age in both GHR− /− and WT mice. Two-dimensional gel electrophoresis proteomes of WAT depots were similar among groups, but several proteins involved in endocytosis and/or cytoskeletal organization (Ehd2, S100A10, actin), anticoagulation (S100A10, annexin A5), and age-related conditions (alpha2-macroglobulin, apolipoprotein A-I, transthyretin) showed significant differences between genotypes. Because Ehd2 may regulate endocytosis of Glut4, we measured Glut4 levels in the WAT depots of GHR− /− and WT mice. Inguinal WAT of 12-month-old GHR− /− mice displayed lower levels of Glut4 than WT. Overall, the protein changes detected in this study offer new insights into possible mechanisms contributing to enhanced insulin sensitivity and extended life span in GHR− /− mice. PMID:23873966

  9. Cell type-specific modulation of lipid mediator's formation in murine adipose tissue by omega-3 fatty acids.

    PubMed

    Kuda, Ondrej; Rombaldova, Martina; Janovska, Petra; Flachs, Pavel; Kopecky, Jan

    2016-01-15

    Mutual interactions between adipocytes and immune cells in white adipose tissue (WAT) are involved in modulation of lipid metabolism in the tissue and also in response to omega-3 polyunsaturated fatty acids (PUFA), which counteract adverse effects of obesity. This complex interplay depends in part on in situ formed anti- as well as pro-inflammatory lipid mediators, but cell types engaged in the synthesis of the specific mediators need to be better characterized. We used tissue fractionation and metabolipidomic analysis to identify cells producing lipid mediators in epididymal WAT of mice fed for 5 weeks obesogenic high-fat diet (lipid content 35% wt/wt), which was supplemented or not by omega-3 PUFA (4.3 mg eicosapentaenoic acid and 14.7 mg docosahexaenoic acid per g of diet). Our results demonstrate selective increase in levels of anti-inflammatory lipid mediators in WAT in response to omega-3, reflecting either their association with adipocytes (endocannabinoid-related N-docosahexaenoylethanolamine) or with stromal vascular cells (pro-resolving lipid mediator protectin D1). In parallel, tissue levels of obesity-associated pro-inflammatory endocannabinoids were suppressed. Moreover, we show that adipose tissue macrophages (ATMs), which could be isolated using magnetic force from the stromal vascular fraction, are not the major producers of protectin D1 and that omega-3 PUFA lowered lipid load in ATMs while promoting their less-inflammatory phenotype. Taken together, these results further document specific roles of various cell types in WAT in control of WAT inflammation and metabolism and they suggest that also other cells but ATMs are engaged in production of pro-resolving lipid mediators in response to omega-3 PUFA. PMID:26707880

  10. Specific collagen XVIII isoforms promote adipose tissue accrual via mechanisms determining adipocyte number and affect fat deposition.

    PubMed

    Aikio, Mari; Elamaa, Harri; Vicente, David; Izzi, Valerio; Kaur, Inderjeet; Seppinen, Lotta; Speedy, Helen E; Kaminska, Dorota; Kuusisto, Sanna; Sormunen, Raija; Heljasvaara, Ritva; Jones, Emma L; Muilu, Mikko; Jauhiainen, Matti; Pihlajamäki, Jussi; Savolainen, Markku J; Shoulders, Carol C; Pihlajaniemi, Taina

    2014-07-29

    Collagen XVIII is an evolutionary conserved ubiquitously expressed basement membrane proteoglycan produced in three isoforms via two promoters (P). Here, we assess the function of the N-terminal, domain of unknown function/frizzled-like sequences unique to medium/long collagen XVIII by creating P-specific null mice. P2-null mice, which only produce short collagen XVIII, developed reduced bulk-adiposity, hepatic steatosis, and hypertriglyceridemia. These abnormalities did not develop in P1-null mice, which produce medium/long collagen XVIII. White adipose tissue samples from P2-null mice contain larger reserves of a cell population enriched in early adipocyte progenitors; however, their embryonic fibroblasts had ∼ 50% lower adipocyte differentiation potential. Differentiating 3T3-L1 fibroblasts into mature adipocytes produced striking increases in P2 gene-products and dramatic falls in P1-transcribed mRNA, whereas Wnt3a-induced dedifferentiation of mature adipocytes produced reciprocal changes in P1 and P2 transcript levels. P2-derived gene-products containing frizzled-like sequences bound the potent adipogenic inhibitor, Wnt10b, in vitro. Previously, we have shown that these same sequences bind Wnt3a, inhibiting Wnt3a-mediated signaling. P2-transcript levels in visceral fat were positively correlated with serum free fatty acid levels, suggesting that collagen α1 (XVIII) expression contributes to regulation of adipose tissue metabolism in visceral obesity. Medium/long collagen XVIII is deposited in the Space of Disse, and interaction between hepatic apolipoprotein E and this proteoglycan is lost in P2-null mice. These results describe a previously unidentified extracellular matrix-directed mechanism contributing to the control of the multistep adipogenic program that determines the number of precursors committing to adipocyte differentiation, the maintenance of the differentiated state, and the physiological consequences of its impairment on ectopic fat

  11. Proteome-wide alterations on adipose tissue from obese patients as age-, diabetes- and gender-specific hallmarks

    PubMed Central

    Gómez-Serrano, María; Camafeita, Emilio; García-Santos, Eva; López, Juan A.; Rubio, Miguel A.; Sánchez-Pernaute, Andrés; Torres, Antonio; Vázquez, Jesús; Peral, Belén

    2016-01-01

    Obesity is a main global health issue and an outstanding cause of morbidity and mortality predisposing to type 2 diabetes (T2DM) and cardiovascular diseases. Huge research efforts focused on gene expression, cellular signalling and metabolism in obesity have improved our understanding of these disorders; nevertheless, to bridge the gap between the regulation of gene expression and changes in signalling/metabolism, protein levels must be assessed. We have extensively analysed visceral adipose tissue from age-, T2DM- and gender-matched obese patients using high-throughput proteomics and systems biology methods to identify new biomarkers for the onset of T2DM in obesity, as well as to gain insight into the influence of aging and gender in these disorders. About 250 proteins showed significant abundance differences in the age, T2DM and gender comparisons. In diabetic patients, remarkable gender-specific hallmarks were discovered regarding redox status, immune response and adipose tissue accumulation. Both aging and T2DM processes were associated with mitochondrial remodelling, albeit through well-differentiated proteome changes. Systems biology analysis highlighted mitochondrial proteins that could play a key role in the age-dependent pathophysiology of T2DM. Our findings could serve as a framework for future research in Translational Medicine directed at improving the quality of life of obese patients. PMID:27160966

  12. Proteome-wide alterations on adipose tissue from obese patients as age-, diabetes- and gender-specific hallmarks.

    PubMed

    Gómez-Serrano, María; Camafeita, Emilio; García-Santos, Eva; López, Juan A; Rubio, Miguel A; Sánchez-Pernaute, Andrés; Torres, Antonio; Vázquez, Jesús; Peral, Belén

    2016-01-01

    Obesity is a main global health issue and an outstanding cause of morbidity and mortality predisposing to type 2 diabetes (T2DM) and cardiovascular diseases. Huge research efforts focused on gene expression, cellular signalling and metabolism in obesity have improved our understanding of these disorders; nevertheless, to bridge the gap between the regulation of gene expression and changes in signalling/metabolism, protein levels must be assessed. We have extensively analysed visceral adipose tissue from age-, T2DM- and gender-matched obese patients using high-throughput proteomics and systems biology methods to identify new biomarkers for the onset of T2DM in obesity, as well as to gain insight into the influence of aging and gender in these disorders. About 250 proteins showed significant abundance differences in the age, T2DM and gender comparisons. In diabetic patients, remarkable gender-specific hallmarks were discovered regarding redox status, immune response and adipose tissue accumulation. Both aging and T2DM processes were associated with mitochondrial remodelling, albeit through well-differentiated proteome changes. Systems biology analysis highlighted mitochondrial proteins that could play a key role in the age-dependent pathophysiology of T2DM. Our findings could serve as a framework for future research in Translational Medicine directed at improving the quality of life of obese patients. PMID:27160966

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

    PubMed

    Lee, Hyun-Jeong; Jang, Mi; Kim, Hyeongmin; Kwak, Woori; Park, Woncheoul; Hwang, Jae Yeon; Lee, Chang-Kyu; Jang, Gul Won; Park, Mi Na; Kim, Hyeong-Cheol; Jeong, Jin Young; Seo, Kang Seok; Kim, Heebal; Cho, Seoae; Lee, Bo-Young

    2013-01-01

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

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

    PubMed Central

    Lee, Hyun-Jeong; Jang, Mi; Kim, Hyeongmin; Kwak, Woori; Park, WonCheoul; Hwang, Jae Yeon; Lee, Chang-Kyu; Jang, Gul Won; Park, Mi Na; Kim, Hyeong-Cheol; Jeong, Jin Young; Seo, Kang Seok; Kim, Heebal; Cho, Seoae; Lee, Bo-Young

    2013-01-01

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

  15. Secretory function of adipose tissue.

    PubMed

    Kuryszko, J; Sławuta, P; Sapikowski, G

    2016-01-01

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

  16. Site-Specific Reduction of Oxidative and Lipid Metabolism in Adipose Tissue of 3′-Azido-3′-Deoxythymidine-Treated Rats▿

    PubMed Central

    Deveaud, Catherine; Beauvoit, Bertrand; Reynaud, Annabel; Bonnet, Jacques

    2007-01-01

    Although it is well accepted that treatment with some nucleoside reverse transcriptase inhibitors modifies both fat metabolism and fat distribution in humans, the mechanisms underlying these modifications are not yet known. The present investigation examined whether a decrease in oxidative capacity, induced by a chronic oral administration of 3′-azido-3′-deoxythymidine (AZT) in rats, could be associated with an alteration of the lipogenic capacity of white adipose tissues. The impact of obesity as a factor was then evaluated. Results showed that AZT treatment induced differential effects depending on anatomical localization. Indeed, in the inguinal adipose tissue, the specific activities of cytochrome c oxidase and fatty acid synthase, two rate-controlling enzymes in energy and lipogenic metabolisms, respectively, both decreased under AZT treatment, thus leading to a lowered cell lipid accumulation. Moreover, the AMP-activated protein kinase phosphorylation level tended to increase, thus implying that AZT causes an energy imbalance. Furthermore, the inguinal tissue of obese rats presented a sensitivity to AZT treatment that was higher than that of lean rats. In contrast, for epididymal tissue, no significant change in all these parameters could be detected under AZT treatment, regardless of the nutritional status of the animals. Taken together, these data demonstrate differential effects of AZT on subcutaneous adipose tissue and visceral white adipose tissue. It could be considered that the chronic decreases in energy and lipogenic metabolism of inguinal adipocyte, consecutive to AZT treatment, may lead, in the long term, to adipose tissue atrophy. PMID:17158934

  17. Carotenoids in Adipose Tissue Biology and Obesity.

    PubMed

    Bonet, M Luisa; Canas, Jose A; Ribot, Joan; Palou, Andreu

    2016-01-01

    Cell, animal and human studies dealing with carotenoids and carotenoid derivatives as nutritional regulators of adipose tissue biology with implications for the etiology and management of obesity and obesity-related metabolic diseases are reviewed. Most studied carotenoids in this context are β-carotene, cryptoxanthin, astaxanthin and fucoxanthin, together with β-carotene-derived retinoids and some other apocarotenoids. Studies indicate an impact of these compounds on essential aspects of adipose tissue biology including the control of adipocyte differentiation (adipogenesis), adipocyte metabolism, oxidative stress and the production of adipose tissue-derived regulatory signals and inflammatory mediators. Specific carotenoids and carotenoid derivatives restrain adipogenesis and adipocyte hypertrophy while enhancing fat oxidation and energy dissipation in brown and white adipocytes, and counteract obesity in animal models. Intake, blood levels and adipocyte content of carotenoids are reduced in human obesity. Specifically designed human intervention studies in the field, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. In summary, studies support a role of specific carotenoids and carotenoid derivatives in the prevention of excess adiposity, and suggest that carotenoid requirements may be dependent on body composition. PMID:27485231

  18. Exercise regulation of adipose tissue.

    PubMed

    Stanford, Kristin I; Goodyear, Laurie J

    2016-01-01

    Exercise training results in adaptations to numerous organ systems and offers protection against metabolic disorders including obesity and type 2 diabetes, and recent reports suggest that adipose tissue may play a role in these beneficial effects of exercise on overall health. Multiple studies have investigated the effects of exercise training on both white adipose tissue (WAT) and brown adipose tissue (BAT), as well as the induction of beige adipocytes. Studies from both rodents and humans show that there are exercise training-induced changes in WAT including decreased cell size and lipid content, and increased mitochondrial activity. In rodents, exercise training causes an increased beiging of WAT. Whether exercise training causes a beiging of human scWAT, as well as which factors contribute to the exercise-induced beiging of WAT are areas of current investigation. Studies investigating the effects of exercise training on BAT mass and function have yielded conflicting data, and hence, is another area of intensive investigation. This review will focus on studies aimed at elucidating the mechanisms regulating exercise training induced-adaptations to adipose tissue. PMID:27386159

  19. Tissue Engineering Chamber Promotes Adipose Tissue Regeneration in Adipose Tissue Engineering Models Through Induced Aseptic Inflammation

    PubMed Central

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

    2014-01-01

    Tissue engineering chamber (TEC) makes it possible to generate significant amounts of mature, vascularized, stable, and transferable adipose tissue. However, little is known about the role of the chamber in tissue engineering. Therefore, to investigate the role of inflammatory response and the change in mechanotransduction started by TEC after implantation, we placed a unique TEC model on the surface of the groin fat pads in rats to study the expression of cytokines and tissue development in the TEC. The number of infiltrating cells was counted, and vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) expression levels in the chamber at multiple time points postimplantation were analyzed by enzyme-linked immunosorbent assay. Tissue samples were collected at various time points and labeled for specific cell populations. The result showed that new adipose tissue formed in the chamber at day 60. Also, the expression of MCP-1 and VEGF in the chamber decreased slightly from an early stage as well as the number of the infiltrating cells. A large number of CD34+/perilipin− perivascular cells could be detected at day 30. Also, the CD34+/perilipin+ adipose precursor cell numbers increased sharply by day 45 and then decreased by day 60. CD34−/perilipin+ mature adipocytes were hard to detect in the chamber content at day 30, but their number increased and then peaked at day 60. Ki67-positive cells could be found near blood vessels and their number decreased sharply over time. Masson's trichrome showed that collagen was the dominant component of the chamber content at early stage and was replaced by newly formed small adipocytes over time. Our findings suggested that the TEC implantation could promote the proliferation of adipose precursor cells derived from local adipose tissue, increase angiogenesis, and finally lead to spontaneous adipogenesis by inducing aseptic inflammation and changing local mechanotransduction. PMID:24559078

  20. Quantification of adipose tissue insulin sensitivity.

    PubMed

    Søndergaard, Esben; Jensen, Michael D

    2016-06-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses. PMID:27073214

  1. Assessment of brown adipose tissue function

    PubMed Central

    Virtue, Sam; Vidal-Puig, Antonio

    2013-01-01

    In this review we discuss practical considerations for the assessment of brown adipose tissue in rodent models, focusing on mice. The central aim of the review is to provide a critical appraisal of the utility of specialized techniques for assessing brown adipose tissue function in vivo. We cover several of the most common specialized methods for analysing brown adipose tissue function in vivo, including assessment of maximal thermogenic capacity by indirect calorimetry and the measurement of sympathetic tone to brown adipose tissue. While these techniques are powerful, they are not readily available to all laboratories; therefore we also cover several simple measurements that, particularly in combination, can be used to determine if a mouse model is likely to have alterations in brown adipose tissue function. Such techniques include: pair feeding, analysis of brown adipose tissue lipid content and mRNA and protein markers of brown adipose tissue activation. PMID:23760815

  2. Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues

    PubMed Central

    Scheller, Erica L.; Doucette, Casey R.; Learman, Brian S.; Cawthorn, William P.; Khandaker, Shaima; Schell, Benjamin; Wu, Brent; Ding, Shi-Ying; Bredella, Miriam A.; Fazeli, Pouneh K.; Khoury, Basma; Jepsen, Karl J.; Pilch, Paul F.; Klibanski, Anne; Rosen, Clifford J.; MacDougald, Ormond A.

    2015-01-01

    Marrow adipose tissue (MAT) accumulates in diverse clinical conditions but remains poorly understood. Here we show region-specific variation in MAT adipocyte development, regulation, size, lipid composition, gene expression, and genetic determinants. Early MAT formation in mice is conserved, while later development is strain dependent. Proximal, but not distal, MAT is lost with 21-day cold exposure. Rat MAT adipocytes from distal sites have an increased proportion of monounsaturated fatty acids and expression of Scd1/Scd2, Cebpa and Cebpb. Humans also have increased distal marrow fat unsaturation. We define proximal ‘regulated’ MAT (rMAT) as single adipocytes interspersed with active hematopoiesis, whereas distal ‘constitutive’ MAT (cMAT) has low hematopoiesis, contains larger adipocytes, develops earlier, and remains preserved upon systemic challenges. Loss of rMAT occurs in mice with congenital generalized lipodystrophy type 4, whereas both rMAT and cMAT are preserved in mice with congenital generalized lipodystrophy type 3. Consideration of these MAT subpopulations may be important for future studies linking MAT to bone biology, hematopoiesis and whole-body metabolism. PMID:26245716

  3. Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation.

    PubMed

    Ramage, Lynne E; Akyol, Murat; Fletcher, Alison M; Forsythe, John; Nixon, Mark; Carter, Roderick N; van Beek, Edwin J R; Morton, Nicholas M; Walker, Brian R; Stimson, Roland H

    2016-07-12

    The discovery of brown adipose tissue (BAT) in adult humans presents a new therapeutic target for metabolic disease; however, little is known about the regulation of human BAT. Chronic glucocorticoid excess causes obesity in humans, and glucocorticoids suppress BAT activation in rodents. We tested whether glucocorticoids regulate BAT activity in humans. In vivo, the glucocorticoid prednisolone acutely increased (18)fluorodeoxyglucose uptake by BAT (measured using PET/CT) in lean healthy men during mild cold exposure (16°C-17°C). In addition, prednisolone increased supraclavicular skin temperature (measured using infrared thermography) and energy expenditure during cold, but not warm, exposure in lean subjects. In vitro, glucocorticoids increased isoprenaline-stimulated respiration and UCP-1 in human primary brown adipocytes, but substantially decreased isoprenaline-stimulated respiration and UCP-1 in primary murine brown and beige adipocytes. The highly species-specific regulation of BAT function by glucocorticoids may have important implications for the translation of novel treatments to activate BAT to improve metabolic health. PMID:27411014

  4. Does bariatric surgery improve adipose tissue function?

    PubMed

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

    2016-09-01

    Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. © 2016 World Obesity. PMID:27272117

  5. Adipose tissue immunity and cancer

    PubMed Central

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema

    2013-01-01

    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

  6. Site-specific differences of insulin action in adipose tissue derived from normal prepubertal children

    SciTech Connect

    Grohmann, Malcolm; Stewart, Claire; Welsh, Gavin; Hunt, Linda; Tavare, Jeremy; Holly, Jeff; Shield, Julian; Sabin, Matt; Crowne, Elizabeth . E-mail: Liz.Crowne@ubht.swest.nhs.uk

    2005-08-15

    Body fat distribution determines obesity-related morbidity in adults but little is known of the aetiology or pathophysiology in children. This study investigates differences in insulin-mediated metabolism in primary cell cultures of subcutaneous and visceral preadipocytes derived from prepubertal children. The impact of differentiation and responses to TNF{alpha} exposure was also investigated. Proliferation rates were greater in subcutaneous versus visceral preadipocytes (41 h(3) versus 69 h(4); P = 0.008). Insulin caused a dose-dependent increase in GSK-3 phosphorylation and an increase in MAPK phosphorylation over time, with increased sensitivity in subcutaneous preadipocytes. Post-differentiation, dose-dependent increases in GSK-3 phosphorylation were maintained, while MAPK phosphorylation was identical in both subtypes. No changes were observed in insulin receptor abundance pre-/post-differentiation. GLUT4 abundance was significantly increased in visceral versus subcutaneous adipocytes by 76(4)%; P = 0.03), coincidental with increased insulin-stimulated 2-deoxy-glucose transport (+150(26)% versus +79(10)%; P = 0.014) and further elevated by acute exposure to TNF{alpha} (+230(52)%; P = 0.019 versus +123(24)%; P = 0.025, respectively). TNF{alpha} also significantly increased basal glucose transport rates (+44(14)%; P = 0.006 versus +34(11)%; P = 0.007) and GLUT1 localisation to the plasma membrane. These data establish site-specific differences in subcutaneous and visceral fat cells from children. Responses to insulin varied with differentiation and TNF{alpha} exposure in the two depots, consistent with parallel changes in GLUT1/4 abundance and localisation.

  7. Lipodystrophy Due to Adipose Tissue-Specific Insulin Receptor Knockout Results in Progressive NAFLD.

    PubMed

    Softic, Samir; Boucher, Jeremie; Solheim, Marie H; Fujisaka, Shiho; Haering, Max-Felix; Homan, Erica P; Winnay, Jonathon; Perez-Atayde, Antonio R; Kahn, C Ronald

    2016-08-01

    Ectopic lipid accumulation in the liver is an almost universal feature of human and rodent models of generalized lipodystrophy and is also a common feature of type 2 diabetes, obesity, and metabolic syndrome. Here we explore the progression of fatty liver disease using a mouse model of lipodystrophy created by a fat-specific knockout of the insulin receptor (F-IRKO) or both IR and insulin-like growth factor 1 receptor (F-IR/IGFRKO). These mice develop severe lipodystrophy, diabetes, hyperlipidemia, and fatty liver disease within the first weeks of life. By 12 weeks of age, liver demonstrated increased reactive oxygen species, lipid peroxidation, histological evidence of balloon degeneration, and elevated serum alanine aminotransferase and aspartate aminotransferase levels. In these lipodystrophic mice, stored liver lipids can be used for energy production, as indicated by a marked decrease in liver weight with fasting and increased liver fibroblast growth factor 21 expression and intact ketogenesis. By 52 weeks of age, liver accounted for 25% of body weight and showed continued balloon degeneration in addition to inflammation, fibrosis, and highly dysplastic liver nodules. Progression of liver disease was associated with improvement in blood glucose levels, with evidence of altered expression of gluconeogenic and glycolytic enzymes. However, these mice were able to mobilize stored glycogen in response to glucagon. Feeding F-IRKO and F-IR/IGFRKO mice a high-fat diet for 12 weeks accelerated the liver injury and normalization of blood glucose levels. Thus, severe fatty liver disease develops early in lipodystrophic mice and progresses to advanced nonalcoholic steatohepatitis with highly dysplastic liver nodules. The liver injury is propagated by lipotoxicity and is associated with improved blood glucose levels. PMID:27207510

  8. Characterization of Visceral and Subcutaneous Adipose Tissue Transcriptome and Biological Pathways in Pregnant and Non-Pregnant Women: Evidence for Pregnancy-Related Regional-Specific Differences in Adipose Tissue

    PubMed Central

    Mazaki-Tovi, Shali; Vaisbuch, Edi; Tarca, Adi L.; Kusanovic, Juan Pedro; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Dong, Zhong; Hassan, Sonia S.; Romero, Roberto

    2015-01-01

    Objective The purpose of this study was to compare the transcriptome of visceral and subcutaneous adipose tissues between pregnant and non-pregnant women. Study Design The transcriptome of paired visceral and abdominal subcutaneous adipose tissues from pregnant women at term and matched non-pregnant women (n = 11) was profiled with the Affymetrix Human Exon 1.0 ST array. Differential expression of selected genes was validated with the use of quantitative reverse transcription–polymerase chain reaction. Results Six hundred forty-four transcripts from 633 known genes were differentially expressed (false discovery rate (FDR) <0.1; fold-change >1.5), while 42 exons from 36 genes showed differential usage (difference in FIRMA scores >2 and FDR<0.1) between the visceral and subcutaneous fat of pregnant women. Fifty-six known genes were differentially expressed between pregnant and non-pregnant subcutaneous fat and three genes in the visceral fat. Enriched biological processes in the subcutaneous adipose tissue of pregnant women were mostly related to inflammation. Conclusion The transcriptome of visceral and subcutaneous fat depots reveals pregnancy-related gene expression and splicing differences in both visceral and subcutaneous adipose tissue. Furthermore, for the first time, alternative splicing in adipose tissue has been associated with regional differences and human parturition. PMID:26636677

  9. Age and gender specific estimation of visceral adipose tissue amounts from radiological images in morbidly obese patients

    PubMed Central

    Linder, Nicolas; Schaudinn, Alexander; Garnov, Nikita; Blüher, Matthias; Dietrich, Arne; Schütz, Tatjana; Lehmann, Stefanie; Retschlag, Ulf; Karlas, Thomas; Kahn, Thomas; Busse, Harald

    2016-01-01

    Image-based quantifications of visceral adipose tissue (VAT) volumes from segmented VAT areas are increasingly considered for risk assessment in obese patients. The goal of this study was to determine the power of partial VAT areas to predict total VAT volume in morbidly obese patients (BMI > 40 kg/m2) as a function of gender, age and anatomical landmarks. 130 morbidly obese patients (mean BMI 46.5 kg/m2; 94 females) underwent IRB-approved MRI. Total VAT volumes were predicted from segmented VAT areas (of single or five adjacent slices) at common axial landmark levels and compared with the measured ones (VVAT-T, about 40 slices between diaphragm and pelvic floor). Standard deviations σ1 and σ5 of the respective VAT volume differences served as measures of agreement. Mean VVAT-T was 4.9 L for females and 8.1 L for males. Best predictions were found at intervertebral spaces L3-L4 for females (σ5 = 688 ml, σ1 = 832 ml) and L1-L2 for males (σ5 = 846 ml, σ1 = 992 ml), irrespective of age. In conclusion, VAT volumes in morbidly obese patients can be reliably predicted by multiplying the segmented VAT area at a gender-specific lumbar reference level with a fixed scaling factor and effective slice thickness. PMID:27009353

  10. Sex differences in adipose tissue

    PubMed Central

    Fuente-Martín, Esther; Argente-Arizón, Pilar; Ros, Purificación; Argente, Jesús; Chowen, Julie A

    2013-01-01

    Obesity and its associated secondary complications are active areas of investigation in search of effective treatments. As a result of this intensified research numerous differences between males and females at all levels of metabolic control have come to the forefront. These differences include not only the amount and distribution of adipose tissue, but also differences in its metabolic capacity and functions between the sexes. Here, we review some of the recent advances in our understanding of these dimorphisms and emphasize the fact that these differences between males and females must be taken into consideration in hopes of obtaining successful treatments for both sexes. PMID:23991358

  11. Depot- and gender-specific expression of NLRP3 inflammasome and toll-like receptors in adipose tissue of cancer patients.

    PubMed

    Shimabukuro, Michio; Sato, Hiromi; Izaki, Hirofumi; Fukuda, Daiju; Uematsu, Etsuko; Hirata, Yoichiro; Yagi, Shusuke; Soeki, Takeshi; Sakaue, Hiroshi; Kanayama, Hiro-Omi; Masuzaki, Hiroaki; Sata, Masataka

    2016-07-01

    Gender difference in obesity-associated cardiovascular complication could be derived from divergent chronic inflammation. We evaluated depot- and gender-specific regulation of the innate immune system in human adipose tissues. Pair samples were obtained from subcutaneous (SAT) and visceral adipose tissue (VAT) during elective surgery (Male: 35; Female: 27). Expressions of pro- and anti-inflammatory adipocytokines were evaluated by semi-quantitative qPCR. Adipose cell-size distribution was obtained from tissue samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. Levels of adiponectin were higher in SAT and VAT of female than those of male (P < 0.001 and P = 0.011, respectively). NLRP3, IL1β-IL18, TLR2 were comparable in SAT and VAT between genders. However, TLR4 and TLR9 were increased in female SAT and VAT and HMGB1 in female VAT. Levels of adiponectin were not correlated with mean diameter of adipocyte (φ, μm) in SAT and VAT of male, but negatively well correlated in those of female (r = -0.392 and r = -0.616). Such negative correlations were also observed between levels of TLR2, TLR4, and HMGB1 and φ in female. Levels of NLRP3 and IL1β were positively correlated with φ in male, but not in female. In conclusion, Innate signals were differentially expressed in male and female adipose tissues, suggesting that the depot- and gender-specific signals could be related to gender difference in chronic inflammation. © 2016 BioFactors, 42(4):397-406, 2016. PMID:27086574

  12. Brown adipose tissue and bone

    PubMed Central

    Lidell, M E; Enerbäck, S

    2015-01-01

    Brown adipose tissue (BAT) is capable of transforming chemically stored energy, in the form of triglycerides, into heat. Recent studies have shown that metabolically active BAT is present in a large proportion of adult humans, where its activity correlates with a favorable metabolic status. Hence, the tissue is now regarded as an interesting target for therapies against obesity and associated diseases such as type 2 diabetes, the hypothesis being that an induction of BAT would be beneficial for these disease states. Apart from the association between BAT activity and a healthier metabolic status, later studies have also shown a positive correlation between BAT volume and both bone cross-sectional area and bone mineral density, suggesting that BAT might stimulate bone anabolism. The aim of this review is to give the reader a brief overview of the BAT research field and to summarize and discuss recent findings regarding BAT being a potential player in bone metabolism. PMID:27152171

  13. Adipose tissue: cell heterogeneity and functional diversity.

    PubMed

    Esteve Ràfols, Montserrat

    2014-02-01

    There are two types of adipose tissue in the body whose function appears to be clearly differentiated. White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat. A good balance between them is important to maintain energy homeostasis. The concept of white adipose tissue has radically changed in the past decades, and is now considered as an endocrine organ that secretes many factors with autocrine, paracrine, and endocrine functions. In addition, we can no longer consider white adipose tissue as a single tissue, because it shows different metabolic profiles in its different locations, with also different implications. Although the characteristic cell of adipose tissue is the adipocyte, this is not the only cell type present in adipose tissue, neither the most abundant. Other cell types in adipose tissue described include stem cells, preadipocytes, macrophages, neutrophils, lymphocytes, and endothelial cells. The balance between these different cell types and their expression profile is closely related to maintenance of energy homeostasis. Increases in adipocyte size, number and type of lymphocytes, and infiltrated macrophages are closely related to the metabolic syndrome diseases. The study of regulation of proliferation and differentiation of preadipocytes and stem cells, and understanding of the interrelationship between the different cell types will provide new targets for action against these diseases. PMID:23834768

  14. The adipose organ: morphological perspectives of adipose tissues.

    PubMed

    Cinti, S

    2001-08-01

    Anatomically, an organ is defined as a series of tissues which jointly perform one or more interconnected functions. The adipose organ qualifies for this definition as it is made up of two tissue types, the white and brown adipose tissues, which collaborate in partitioning the energy contained in lipids between thermogenesis and the other metabolic functions. In rats and mice the adipose organ consists of several subcutaneous and visceral depots. Some areas of these depots are brown and correspond to brown adipose tissue, while many are white and correspond to white adipose tissue. The number of brown adipocytes found in white areas varies with age, strain of animal and environmental conditions. Brown and white adipocyte precursors are morphologically dissimilar. Together with a rich vascular supply, brown areas receive abundant noradrenergic parenchymal innervation. The gross anatomy and histology of the organ vary considerably in different physiological (cold acclimation, warm acclimation, fasting) and pathological conditions such as obesity; many important genes, such as leptin and uncoupling protein-1, are also expressed very differently in the two cell types. These basic mechanisms should be taken into account when addressing the physiopathology of obesity and its treatment. PMID:11681806

  15. Biochemistry of adipose tissue: an endocrine organ

    PubMed Central

    Coelho, Marisa; Oliveira, Teresa

    2013-01-01

    Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example). This paper reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance. PMID:23671428

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

    PubMed

    Kim, Bong-Sung; Rongisch, Robert; Hager, Stephan; Grieb, Gerrit; Nourbakhsh, Mahtab; Rennekampff, Hans-Oliver; Bucala, Richard; Bernhagen, Juergen; Pallua, Norbert

    2015-01-01

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

  17. Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation

    PubMed Central

    Kim, Bong-Sung; Rongisch, Robert; Hager, Stephan; Grieb, Gerrit; Nourbakhsh, Mahtab; Rennekampff, Hans-Oliver; Bucala, Richard; Bernhagen, Juergen; Pallua, Norbert

    2015-01-01

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

  18. Animal Models for Adipose Tissue Engineering

    PubMed Central

    Uthamanthil, Rajesh; Beahm, Elisabeth; Frye, Cindy

    2008-01-01

    Abstract There is a critical need for adequate reconstruction of soft tissue defects resulting from tumor resection, trauma, and congenital abnormalities. To be sure, adipose tissue engineering strategies offer promising solutions. However, before clinical translation can occur, efficacy must be proven in animal studies. The aim of this review is to provide an overview of animal models currently employed for adipose tissue engineering. PMID:18544014

  19. Gene Expression Signature in Adipose Tissue of Acromegaly Patients

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

    Human studies of the influence of aging and other factors on intermuscular fat (INTMF) were reviewed. Intermuscular fat increased with weight loss, weight gain, or with no weight change with age in humans. An increase in INTMF represents a similar threat to type 2 diabetes and insulin resistance as does visceral adipose tissue (VAT). Studies of INTMF in animals covered topics such as quantitative deposition and genetic relationships with other fat depots. The relationship between leanness and higher proportions of INTMF fat in pigs was not observed in human studies and was not corroborated by other pig studies. In humans, changes in muscle mass, strength and quality are associated with INTMF accretion with aging. Gene expression profiling and intrinsic methylation differences in pigs demonstrated that INTMF and VAT are primarily associated with inflammatory and immune processes. It seems that in the pig and humans, INTMF and VAT share a similar pattern of distribution and a similar association of components dictating insulin sensitivity. Studies on intramuscular (IM) adipocyte development in meat animals were reviewed. Gene expression analysis and genetic analysis have identified candidate genes involved in IM adipocyte development. Intramuscular (IM) adipocyte development in human muscle is only seen during aging and some pathological circumstance. Several genetic links between human and meat animal adipogenesis have been identified. In pigs, the Lipin1 and Lipin 2 gene have strong genetic effects on IM accumulation. Lipin1 deficiency results in immature adipocyte development in human lipodystrophy. In humans, overexpression of Perilipin 2 (PLIN2) facilitates intramyocellular lipid accretion whereas in pigs PLIN2 gene expression is associated with IM deposition. Lipins and perilipins may influence intramuscular lipid regardless of species. PMID:26317048

  1. Brown Adipose Tissue in Cetacean Blubber

    PubMed Central

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

    2015-01-01

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

  2. Influencing Factors of Thermogenic Adipose Tissue Activity

    PubMed Central

    Zhang, Guoqing; Sun, Qinghua; Liu, Cuiqing

    2016-01-01

    Obesity is an escalating public health challenge and contributes tremendously to the disease burden globally. New therapeutic strategies are required to alleviate the health impact of obesity-related metabolic dysfunction. Brown adipose tissue (BAT) is specialized for dissipating chemical energy for thermogenesis as a defense against cold environment. Intriguingly, the brown-fat like adipocytes that dispersed throughout white adipose tissue (WAT) in rodents and humans, called “brite” or “beige” adipocytes, share similar thermogenic characteristics to brown adipocytes. Recently, researchers have focused on cognition of these thermogenic adipose tissues. Some factors have been identified to regulate the development and function of thermogenic adipose tissues. Cold exposure, pharmacological conditions, and lifestyle can enhance non-shivering thermogenesis and metabolism via some mechanisms. However, environmental pollutants, such as ambient fine particulates and ozone, may impair the function of these thermogenic adipose tissues and thereby induce metabolic dysfunction. In this review, the origin, function and influencing factors of thermogenic adipose tissues were summarized and it will provide insights into identifying new therapeutic strategies for the treatment of obesity and obesity-related diseases. PMID:26903879

  3. Influencing Factors of Thermogenic Adipose Tissue Activity.

    PubMed

    Zhang, Guoqing; Sun, Qinghua; Liu, Cuiqing

    2016-01-01

    Obesity is an escalating public health challenge and contributes tremendously to the disease burden globally. New therapeutic strategies are required to alleviate the health impact of obesity-related metabolic dysfunction. Brown adipose tissue (BAT) is specialized for dissipating chemical energy for thermogenesis as a defense against cold environment. Intriguingly, the brown-fat like adipocytes that dispersed throughout white adipose tissue (WAT) in rodents and humans, called "brite" or "beige" adipocytes, share similar thermogenic characteristics to brown adipocytes. Recently, researchers have focused on cognition of these thermogenic adipose tissues. Some factors have been identified to regulate the development and function of thermogenic adipose tissues. Cold exposure, pharmacological conditions, and lifestyle can enhance non-shivering thermogenesis and metabolism via some mechanisms. However, environmental pollutants, such as ambient fine particulates and ozone, may impair the function of these thermogenic adipose tissues and thereby induce metabolic dysfunction. In this review, the origin, function and influencing factors of thermogenic adipose tissues were summarized and it will provide insights into identifying new therapeutic strategies for the treatment of obesity and obesity-related diseases. PMID:26903879

  4. n-3 PUFA: bioavailability and modulation of adipose tissue function.

    PubMed

    Kopecky, Jan; Rossmeisl, Martin; Flachs, Pavel; Kuda, Ondrej; Brauner, Petr; Jilkova, Zuzana; Stankova, Barbora; Tvrzicka, Eva; Bryhn, Morten

    2009-11-01

    Adipose tissue has a key role in the development of metabolic syndrome (MS), which includes obesity, type 2 diabetes, dyslipidaemia, hypertension and other disorders. Systemic insulin resistance represents a major factor contributing to the development of MS in obesity. The resistance is precipitated by impaired adipose tissue glucose and lipid metabolism, linked to a low-grade inflammation of adipose tissue and secretion of pro-inflammatory adipokines. Development of MS could be delayed by lifestyle modifications, while both dietary and pharmacological interventions are required for the successful therapy of MS. The n-3 long-chain (LC) PUFA, EPA and DHA, which are abundant in marine fish, act as hypolipidaemic factors, reduce cardiac events and decrease the progression of atherosclerosis. Thus, n-3 LC PUFA represent healthy constituents of diets for patients with MS. In rodents n-3 LC PUFA prevent the development of obesity and impaired glucose tolerance. The effects of n-3 LC PUFA are mediated transcriptionally by AMP-activated protein kinase and by other mechanisms. n-3 LC PUFA activate a metabolic switch toward lipid catabolism and suppression of lipogenesis, i.e. in the liver, adipose tissue and small intestine. This metabolic switch improves dyslipidaemia and reduces ectopic deposition of lipids, resulting in improved insulin signalling. Despite a relatively low accumulation of n-3 LC PUFA in adipose tissue lipids, adipose tissue is specifically linked to the beneficial effects of n-3 LC PUFA, as indicated by (1) the prevention of adipose tissue hyperplasia and hypertrophy, (2) the induction of mitochondrial biogenesis in adipocytes, (3) the induction of adiponectin and (4) the amelioration of adipose tissue inflammation by n-3 LC PUFA. PMID:19698199

  5. Myogenic potential of adipose-tissue-derived cells.

    PubMed

    Di Rocco, Giuliana; Iachininoto, Maria Grazia; Tritarelli, Alessandra; Straino, Stefania; Zacheo, Antonella; Germani, Antonia; Crea, Filippo; Capogrossi, Maurizio C

    2006-07-15

    Adipose-tissue-derived mesenchymal stem cells can be directed towards a myogenic phenotype in vitro by the addition of specific inductive media. However, the ability of these or other adipose-tissue-associated cells to respond to ;natural' myogenic cues such as a myogenic environment has never been investigated in detail. Here, we provide evidence that a restricted subpopulation of freshly harvested adipose-tissue-derived cells possesses an intrinsic myogenic potential and can spontaneously differentiate into skeletal muscle. Conversion of adipose-tissue-derived cells to a myogenic phenotype is enhanced by co-culture with primary myoblasts in the absence of cell contact and is maximal when the two cell types are co-cultured in the same plate. Conversely, in vitro expanded adipose-tissue-derived mesenchymal stem cells require direct contact with muscle cells to generate skeletal myotubes. Finally, we show that uncultured adipose-tissue-associated cells have a high regenerative capacity in vivo since they can be incorporated into muscle fibers following ischemia and can restore significantly dystrophin expression in mdx mice. PMID:16825428

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

    PubMed

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

    2016-01-01

    Obesity is a major public health problem in the twenty-first century. Mutations in genes that regulate substrate metabolism, subsequent dysfunction in their protein products, and other factors, such as increased adipose tissue inflammation, are some underlying etiologies of this disease. Increased inflammation in the adipose tissue microenvironment is partly mediated by the presence of cells from the innate and adaptive immune system. A subset of the innate immune population in adipose tissue include macrophages, termed adipose tissue macrophages (ATMs), which are central players in adipose tissue inflammation. Being extremely plastic, their responses to diverse molecular signals in the microenvironment dictate their identity and functional properties, where they become either pro-inflammatory (M1) or anti-inflammatory (M2). Endurance exercise training exerts global anti-inflammatory responses in multiple organs, including skeletal muscle, liver, and adipose tissue. The purpose of this review is to discuss the different mechanisms that drive ATM-mediated inflammation in obesity and present current evidence of how exercise training, specifically endurance exercise training, modulates the polarization of ATMs from an M1 to an M2 anti-inflammatory phenotype. PMID:27379017

  7. Brown Adipose Tissue Growth and Development

    PubMed Central

    Symonds, Michael E.

    2013-01-01

    Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle. PMID:24278771

  8. Maintenance of white adipose tissue in man.

    PubMed

    Hyvönen, Mervi T; Spalding, Kirsty L

    2014-11-01

    Obesity is increasing in an epidemic manner in most countries and constitutes a public health problem by enhancing the risk for diseases such as diabetes, fatty liver disease and atherosclerosis. Together these diseases form a cluster referred to as the metabolic syndrome. Despite the negative health consequences associated with excess adipose tissue, very little is known about the origin and maintenance of white adipose tissue in man. In this review we discuss what is known about the turnover of adult human adipocytes and their precursors, as well as adipose tissue heterogeneity, plasticity and developmental origins. The focus of this review is human tissue, however in many cases human data are missing and are inferred from animal studies. As such, reference to animal studies are made where human data is not available. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. PMID:25240584

  9. Adipose Tissue Residing Progenitors (Adipocyte Lineage Progenitors and Adipose Derived Stem Cells (ADSC)

    PubMed Central

    Berry, Ryan; Rodeheffer, Matthew S.; Rosen, Clifford J.; Horowitz, Mark C.

    2015-01-01

    The formation of brown, white and beige adipocytes have been a subject of intense scientific interest in recent years due to the growing obesity epidemic in the United States and around the world. This interest has led to the identification and characterization of specific tissue resident progenitor cells that give rise to each adipocyte population in vivo. However, much still remains to be discovered about each progenitor population in terms of their “niche” within each tissue and how they are regulated at the cellular and molecular level during healthy and diseased states. While our knowledge of brown, white and beige adipose tissue is rapidly increasing, little is still known about marrow adipose tissue and its progenitor despite recent studies demonstrating possible roles for marrow adipose tissue in regulating the hematopoietic space and systemic metabolism at large. This chapter focuses on our current knowledge of brown, white, beige and marrow adipose tissue with a specific focus on the formation of each tissue from tissue resident progenitor cells. PMID:26526875

  10. Adipose Tissue - Adequate, Accessible Regenerative Material.

    PubMed

    Kolaparthy, Lakshmi Kanth; Sanivarapu, Sahitya; Moogla, Srinivas; Kutcham, Rupa Sruthi

    2015-11-01

    The potential use of stem cell based therapies for the repair and regeneration of various tissues offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in genetic manipulation of human ESCs, even though these cells are highly beneficial. Mesenchymal stem cells seen to be an ideal population of stem cells in particular, Adipose derived stem cells (ASCs) which can be obtained in large number and easily harvested from adipose tissue. It is ubiquitously available and has several advantages compared to other sources as easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose derived mesenchymal stem cells yield a high amount of stem cells which is essential for stem cell based therapies and tissue engineering. Recently, periodontal tissue regeneration using ASCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because various secreted growth factors from ASCs might not only promote the regeneration of periodontal tissues but also encourage neovascularization of the damaged tissues. This review summarizes the sources, isolation and characteristics of adipose derived stem cells and its potential role in periodontal regeneration is discussed. PMID:26634060

  11. Adipose Tissue - Adequate, Accessible Regenerative Material

    PubMed Central

    Kolaparthy, Lakshmi Kanth.; Sanivarapu, Sahitya; Moogla, Srinivas; Kutcham, Rupa Sruthi

    2015-01-01

    The potential use of stem cell based therapies for the repair and regeneration of various tissues offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in genetic manipulation of human ESCs, even though these cells are highly beneficial. Mesenchymal stem cells seen to be an ideal population of stem cells in particular, Adipose derived stem cells (ASCs) which can be obtained in large number and easily harvested from adipose tissue. It is ubiquitously available and has several advantages compared to other sources as easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose derived mesenchymal stem cells yield a high amount of stem cells which is essential for stem cell based therapies and tissue engineering. Recently, periodontal tissue regeneration using ASCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because various secreted growth factors from ASCs might not only promote the regeneration of periodontal tissues but also encourage neovascularization of the damaged tissues. This review summarizes the sources, isolation and characteristics of adipose derived stem cells and its potential role in periodontal regeneration is discussed. PMID:26634060

  12. Control of adipose tissue lipolysis in ectotherm vertebrates.

    PubMed

    Migliorini, R H; Lima-Verde, J S; Machado, C R; Cardona, G M; Garofalo, M A; Kettelhut, I C

    1992-10-01

    Lipolytic activity of fish (Hoplias malabaricus), toad (Bufo paracnemis), and snake (Philodryas patagoniensis) adipose tissue was investigated in vivo and in vitro. Catecholamines or glucagon did not affect the release of free fatty acids (FFA) by incubated fish and toad adipose tissue. Catecholamines also failed to activate snake adipose tissue lipolysis, which even decreased in the presence of epinephrine. However, glucagon stimulated both the lipolytic activity of reptilian tissue in vitro and the mobilization of FFA to plasma when administered to snakes in vivo. The release of FFA from incubated fish, amphibian, and reptilian adipose tissue increased markedly in the presence of cAMP or xanthine derivatives, inhibitors of phosphodiesterase. Forskolin or fluoride, activators of specific components of the adenylate cyclase system, strongly stimulated toad adipose tissue lipolysis. The data suggest that adipocyte triacylglycerol lipase of ectotherm vertebrates is activated by a cAMP-mediated phosphorylation and that the organization of the membrane-bound adenylate cyclase system is similar to that of mammals. PMID:1329567

  13. Regulation of cholesteryl ester transfer activity in adipose tissue: comparison between hamster and rat species.

    PubMed

    Shen, G X; Angel, A

    1995-07-01

    The present study demonstrates cholesteryl ester transfer activity (CETA) in cultured hamster and rat adipose tissue. Cultured hamster and rat adipose tissue fragments released CETA into the conditioned medium, and this was associated with a reciprocal decrease in adipose tissue CETA. Regional variations in adipose CETA were observed. The levels of CETA released from cultured hamster and rat adipocytes were higher than those from adipose tissue fragments. In hamsters but not in rats, the secretion of CETA from cultured adipose tissue was increased by insulin and inhibited by EDTA in a dose-dependent fashion. Monoclonal antibodies against human cholesteryl ester transfer protein inhibited the CETA secreted from hamster adipose tissue but not that from rat adipose tissue. Fasting for 24 h and a high-cholesterol saturated fat-rich diet increased adipose CETA in hamsters and rats, and this was associated with an elevation of plasma CETA only in hamsters. This supports the view that, in hamsters, adipose CETA has in situ and intravascular functions, whereas in rats the role of adipose CETA is restricted to tissue-specific functions. Hamster cholesteryl ester transfer protein may differ from rat adipose-associated CETA in the structure of the active site and the regulatory mechanism for its secretion. PMID:7631784

  14. The development and endocrine functions of adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    White adipose tissue is a mesenchymal tissue that begins developing in the fetus. Classically known for storing the body’s fuel reserves, adipose tissue is now recognized as an endocrine organ. As such, the secretions from adipose tissue are known to affect several systems such as the vascular and...

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

    PubMed

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

    2016-08-01

    Type 2 diabetes follows a well-defined progressive pathogenesis, beginning with insulin resistance in metabolic tissues such as the adipose. Intracellular signaling downstream of insulin receptor activation regulates critical metabolic functions of adipose tissue, including glucose uptake, lipogenesis, lipolysis and adipokine secretion. Previous studies have used the aP2 promoter to drive Cre recombinase expression in adipose tissue. Insulin receptor (IR) knockout mice created using this aP2-Cre strategy (FIRKO mice) were protected from obesity and glucose intolerance. Later studies demonstrated the promiscuity of the aP2 promoter, casting doubts upon the tissue specificity of aP2-Cre models. It is our goal to use the increased precision of the Adipoq promoter to investigate adipocyte-specific IR function. Towards this end we generated an adipocyte-specific IR knockout (AIRKO) mouse using an Adipoq-driven Cre recombinase. Here we report AIRKO mice are less insulin sensitive throughout life, and less glucose tolerant than wild-type (WT) littermates at the age of 16 weeks. In contrast to WT littermates, the insulin sensitivity of AIRKO mice is unaffected by age or dietary regimen. At any age, AIRKO mice are comparably insulin resistant to old or obese WT mice and have a significantly reduced lifespan. Similar results were obtained when these phenotypes were re-examined in FIRKO mice. We also found that the AIRKO mouse is protected from high-fat diet-induced weight gain, corresponding with a 90% reduction in tissue weight of major adipose depots compared to WT littermates. Adipose tissue mass reduction is accompanied by hepatomegaly and increased hepatic steatosis. These data indicate that adipocyte IR function is crucial to systemic energy metabolism and has profound effects on adiposity, hepatic homeostasis and lifespan. PMID:27246738

  16. Injectable Biomaterials for Adipose Tissue Engineering

    PubMed Central

    Young, D. Adam; Christman, Karen L.

    2012-01-01

    Adipose tissue engineering has recently gained significant attention from materials scientists as a result of the exponential growth of soft tissue filler procedures being performed within the clinic. While several injectable materials are currently being marketed for filling subcutaneous voids, they often face limited longevity due to rapid resorption. Their inability to encourage natural adipose formation or ingrowth necessitates repeated injections for a prolonged effect, and thus classifies them as temporary fillers. As a result, a significant need for injectable materials that not only act as fillers, but also promote in vivo adipogenesis is beginning to be realized. This review will discuss the advantages and disadvantages of commercially available soft tissue fillers. It will then summarize the current state of research using injectable synthetic materials, biopolymers, and extracellular matrix-derived materials for adipose tissue engineering. Furthermore, the successful attributes observed across each of these materials will be outlined along with a discussion of the current difficulties and future directions for adipose tissue engineering. PMID:22456805

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

    PubMed

    Lewandowska, Ewa; Zieliński, Andrzej

    2016-05-01

    Obesity is a disease with continuingly increasing prevalence. It occurs worldwide independently of age group, material status or country of origin. At these times the most common reasons for obesity are bad eating habits and dramatic reduction of physical activity, which cause the energy imbalance of organism. Fundamental alteration observed in obese subjects is white adipose tissue overgrowth, which is linked to increased incidence of obesity-related comorbidities, such as: cardiovascular diseases, type 2 diabetes or digestive tract diseases. What is more, obesity is also a risk factor for some cancers. Special risk for diseases linked to excessive weight is associated with overgrowth of visceral type of adipose tissue. Adipose tissue, which is the main energy storehouse in body and acts also as an endocrine organ, undergoes both the morphological and the functional changes in obesity, having a negative impact on whole body function. In this article we summarize the most important alterations in morphology and function of white adipose tissue, observed in obese subjects. PMID:27234867

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

    PubMed Central

    2014-01-01

    The Visceral Adiposity Index (VAI) has recently proven to be an indicator of adipose distribution and function that indirectly expresses cardiometabolic risk. In addition, VAI has been proposed as a useful tool for early detection of a condition of cardiometabolic risk before it develops into an overt metabolic syndrome. The application of the VAI in particular populations of patients (women with polycystic ovary syndrome, patients with acromegaly, patients with NAFLD/NASH, patients with HCV hepatitis, patients with type 2 diabetes, and general population) has produced interesting results, which have led to the hypothesis that the VAI could be considered a marker of adipose tissue dysfunction. Unfortunately, in some cases, on the same patient population, there is conflicting evidence. We think that this could be mainly due to a lack of knowledge of the application limits of the index, on the part of various authors, and to having applied the VAI in non-Caucasian populations. Future prospective studies could certainly better define the possible usefulness of the VAI as a predictor of cardiometabolic risk. PMID:24829577

  19. The relation of location-specific epicardial adipose tissue thickness and obstructive coronary artery disease: systemic review and meta-analysis of observational studies

    PubMed Central

    2014-01-01

    Background There is growing evidence about the importance of epicardial adiposity on cardiometabolic risk. However, the relation of location-specific epicardial adipose tissue (EAT) thickness to coronary atherosclerotic burden is still unclear. Methods This meta-analysis was used to study the relations between location-specific EAT thickness and obstructive coronary artery disease (CAD). A systemic literature search to identify eligible studies that met the inclusion criteria from the beginning until January 2014 was made. We conducted the meta-analysis of all included 10 published studies. Pre-specified subgroup analyses were performed according to ethnicity, body mass index, diagnostic tools for CAD, and measurement tool if presence of high heterogeneity between studies. Potential publication bias was also assessed. Results We identified ten observed studies with a total of 1625 subjects for planned comparison. With regard to the association between obstructive CAD and location-specific EAT thickness at the right ventricular free wall, caution is warranted. The pooled estimate showed that location-specific EAT thickness at the right ventricular free wall was significantly higher in the CAD group than non-CAD group (standardized mean difference (SMD): 0.70 mm, 95% CI: 0.26-1.13, P = 0.002), although heterogeneity was high (I2 = 93%). It should be clear that only the result of echocardiography-based studies showed a significant association (SMD: 0.98 mm, 95% CI: 0.43-1.53, P = 0.0005), and the result of all included CT-based studies showed a non-significant association (SMD: 0.06 mm, 95% CI: -0.12-0.25, P = 0.50). In the subgroup analysis, the “diagnostic tools for CAD” or “measurement tool of EAT thickness” are potential major sources of heterogeneity between studies. With regard to location-specific EAT thickness at the left atrioventricular (AV) groove, it was significantly higher in the CAD group than non-CAD group (SMD: 0.74 mm, 95

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

    PubMed

    Lecoutre, Simon; Breton, Christophe

    2015-01-01

    Based on the concept of Developmental Origin of Health and Disease, both human and animal studies have demonstrated a close link between nutrient supply perturbations in the fetus or neonate (i.e., maternal undernutrition, obesity, gestational diabetes and/or rapid catch-up growth) and increased risk of adult-onset obesity. Indeed, the adipose tissue has been recognized as a key target of developmental programming in a sex-and depot-specific manner. Despite different developmental time windows, similar mechanisms of adipose tissue programming have been described in rodents and in bigger mammals (sheep, primates). Maternal nutritional manipulations reprogram offspring's adipose tissue resulting in series of alterations: enhanced adipogenesis and lipogenesis, impaired sympathetic activity with reduced noradrenergic innervations and thermogenesis as well as low-grade inflammation. These changes affect adipose tissue development, distribution and composition predisposing offspring to fat accumulation. Modifications of hormonal tissue sensitivity (i.e., leptin, insulin, glucocorticoids) and/or epigenetic mechanisms leading to persistent changes in gene expression may account for long-lasting programming across generations. PMID:26029119

  1. [Cancer cachexia and white adipose tissue browning].

    PubMed

    Zhang, S T; Yang, H M

    2016-08-01

    Cancer cachexia occurs in a majority of advanced cancer patients. These patients with impaired physical function are unable to tolerance cancer treatment well and have a significantly reduced survival rate. Currently, there is no effective clinical treatment available for cancer cachexia, therefore, it is necessary to clarify the molecular mechanisms of cancer cachexia, moreover, new therapeutic targets for cancer cachexia treatment are urgently needed. Very recent studies suggest that, during cancer cachexia, white adipose tissue undergo a 'browning' process, resulting in increased lipid mobilization and energy expenditure, which may be necessary for the occurrence of cancer cachexia. In this article, we summarize the definition and characteristics of cancer cachexia and adipose tissue 'browning', then, we discuss the new study directions presented in latest research. PMID:27531474

  2. Adipocyte-Specific Hypoxia-Inducible Factor 2α Deficiency Exacerbates Obesity-Induced Brown Adipose Tissue Dysfunction and Metabolic Dysregulation

    PubMed Central

    Alexaki, Vasileia I.; Qin, Nan; Rubín de Celis, María F.; Economopoulou, Matina; Ziogas, Athanasios; Gercken, Bettina; Kotlabova, Klara; Phieler, Julia; Ehrhart-Bornstein, Monika; Bornstein, Stefan R.; Eisenhofer, Graeme; Breier, Georg; Blüher, Matthias; Hampe, Jochen; El-Armouche, Ali; Chatzigeorgiou, Antonios; Chung, Kyoung-Jin

    2015-01-01

    Angiogenesis is a central regulator for white (WAT) and brown (BAT) adipose tissue adaptation in the course of obesity. Here we show that deletion of hypoxia-inducible factor 2α (HIF2α) in adipocytes (by using Fabp4-Cre transgenic mice) but not in myeloid or endothelial cells negatively impacted WAT angiogenesis and promoted WAT inflammation, WAT dysfunction, hepatosteatosis, and systemic insulin resistance in obesity. Importantly, adipocyte HIF2α regulated vascular endothelial growth factor (VEGF) expression and angiogenesis of obese BAT as well as its thermogenic function. Consistently, obese adipocyte-specific HIF2α-deficient mice displayed BAT dysregulation, associated with reduced levels of uncoupling protein 1 (UCP1) and a dysfunctional thermogenic response to cold exposure. VEGF administration reversed WAT and BAT inflammation and BAT dysfunction in adipocyte HIF2α-deficient mice. Together, our findings show that adipocyte HIF2α is protective against maladaptation to obesity and metabolic dysregulation by promoting angiogenesis in both WAT and BAT and by counteracting obesity-mediated BAT dysfunction. PMID:26572826

  3. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

    PubMed Central

    Sun, Kai; Park, Jiyoung; Gupta, Olga T.; Holland, William L.; Auerbach, Pernille; Zhang, Ningyan; Marangoni, Roberta Goncalves; Nicoloro, Sarah M.; Czech, Michael P.; Varga, John; Ploug, Thorkil; An, Zhiqiang; Scherer, Philipp E.

    2014-01-01

    We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonstrate that endotrophin plays a pivotal role in shaping a metabolically unfavourable microenvironment in adipose tissue during consumption of a high-fat diet (HFD). Endotrophin serves as a powerful co-stimulator of pathologically relevant pathways within the ‘unhealthy’ adipose tissue milieu, triggering fibrosis and inflammation and ultimately leading to enhanced insulin resistance. We further demonstrate that blocking endotrophin with a neutralizing antibody ameliorates metabolically adverse effects and effectively reverses metabolic dysfunction induced during HFD exposure. Collectively, our findings demonstrate that endotrophin exerts a major influence in adipose tissue, eventually resulting in systemic elevation of pro-inflammatory cytokines and insulin resistance, and the results establish endotrophin as a potential target in the context of metabolism and cancer. PMID:24647224

  4. Epicardial adipose tissue and atrial fibrillation.

    PubMed

    Hatem, Stéphane N; Sanders, Prashanthan

    2014-05-01

    Atrial fibrillation (AF) is the most frequent cardiac arrhythmia in clinical practice. AF is often associated with profound functional and structural alterations of the atrial myocardium that compose its substrate. Recently, a relationship between the thickness of epicardial adipose tissue (EAT) and the incidence and severity of AF has been reported. Adipose tissue is a biologically active organ regulating the metabolism of neighbouring organs. It is also a major source of cytokines. In the heart, EAT is contiguous with the myocardium without fascia boundaries resulting in paracrine effects through the release of adipokines. Indeed, Activin A, which is produced in abundance by EAT during heart failure or diabetes, shows a marked fibrotic effect on the atrial myocardium. The infiltration of adipocytes into the atrial myocardium could also disorganize the depolarization wave front favouring micro re-entry circuits and local conduction block. Finally, EAT contains progenitor cells in abundance and therefore could be a source of myofibroblasts producing extracellular matrix. The study on the role played by adipose tissue in the pathogenesis of AF is just starting and is highly likely to uncover new biomarkers and therapeutic targets for AF. PMID:24648445

  5. Peptides from adipose tissue in mental disorders

    PubMed Central

    Wędrychowicz, Andrzej; Zając, Andrzej; Pilecki, Maciej; Kościelniak, Barbara; Tomasik, Przemysław J

    2014-01-01

    Adipose tissue is a dynamic endocrine organ that is essential to regulation of metabolism in humans. A new approach to mental disorders led to research on involvement of adipokines in the etiology of mental disorders and mood states and their impact on the health status of psychiatric patients, as well as the effects of treatment for mental health disorders on plasma levels of adipokines. There is evidence that disturbances in adipokine secretion are important in the pathogenesis, clinical presentation and outcome of mental disorders. Admittedly leptin and adiponectin are involved in pathophysiology of depression. A lot of disturbances in secretion and plasma levels of adipokines are observed in eating disorders with a significant impact on the symptoms and course of a disease. It is still a question whether observed dysregulation of adipokines secretion are primary or secondary. Moreover findings in this area are somewhat inconsistent, owing to differences in patient age, sex, socioeconomic status, smoking habits, level of physical activity, eating pathology, general health or medication. This was the rationale for our detailed investigation into the role of the endocrine functions of adipose tissue in mental disorders. It seems that we are continually at the beginning of understanding of the relation between adipose tissue and mental disorders. PMID:25540725

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

    PubMed

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

    2015-12-01

    Decellularized adipose tissue (DAT) has shown promise as an adipogenic bioscaffold for soft tissue augmentation and reconstruction. The objective of the current study was to investigate the effects of allogeneic adipose-derived stem/stromal cells (ASCs) on in vivo fat regeneration in DAT bioscaffolds using an immunocompetent rat model. ASC seeding significantly enhanced angiogenesis and adipogenesis, with cell tracking studies indicating that the newly-forming tissues were host-derived. Incorporating ASCs also mediated the inflammatory response and promoted a more constructive macrophage phenotype. A fraction of the CD163(+) macrophages in the implants expressed adipogenic markers, with higher levels of this "adipocyte-like" phenotype in proximity to the developing adipose tissues. Our results indicate that the combination of ASCs and adipose extracellular matrix (ECM) provides an inductive microenvironment for adipose regeneration mediated by infiltrating host cell populations. The DAT scaffolds are a useful tissue-specific model system for investigating the mechanisms of in vivo adipogenesis that may help to develop a better understanding of this complex process in the context of both regeneration and disease. Overall, combining adipose-derived matrices with ASCs is a highly promising approach for the in situ regeneration of host-derived adipose tissue. PMID:26360790

  7. Pulsed electric breakdown in adipose tissue

    NASA Astrophysics Data System (ADS)

    Kolb, Juergen F.; Scully, Noah; Paithankar, Dilip

    2011-08-01

    High voltage pulses of sub-microsecond duration can instigate electrical breakdown in adipose tissue, which is followed by a spark discharge. Breakdown voltages are generally lower than observed for purified lipids but higher than for air. Development of breakdown for the repetitive application of pulses resembles a gradual and stochastic process as reported for partial discharges in solid dielectrics. The inflicted tissue damage itself is confined to the gap between electrodes, providing a method to use spark discharges as a precise surgical technique.

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

    PubMed Central

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

    2016-01-01

    Adipose tissue is a highly heterogeneous endocrine organ. The heterogeneity among different anatomical depots stems from their intrinsic differences in cellular and physiological properties, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, insulin sensitivity, hormonal control, thermogenic ability and vascularization. Additional factors that influence adipose tissue heterogeneity are genetic predisposition, environment, gender and age. Under obese condition, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. For instance, individuals with central obesity are more susceptible to developing diabetes and cardiovascular complications, whereas those with peripheral obesity are more metabolically healthy. This review summarizes the clinical and mechanistic evidence for the depot-specific differences that give rise to different metabolic consequences, and provides therapeutic insights for targeted treatment of obesity. PMID:26964831

  9. Methods in Enzymology (MIE): Methods of Adipose Tissue Biology-

    PubMed Central

    Berry, Ryan; Church, Christopher; Gericke, Martin T.; Jeffery, Elise; Colman, Laura; Rodeheffer, Matthew S.

    2014-01-01

    Adipose tissue is an endocrine organ that specializes in lipid metabolism and is distributed throughout the body in distinct white adipose tissue (WAT) and brown adipose tissue (BAT) depots. These tissues have opposing roles in lipid metabolism with WAT storing excessive caloric intake in the form of lipid, and BAT burning lipid through non-shivering thermogenesis. As accumulation of lipid in mature adipocytes of WAT leads to obesity and increased risk of comorbidity (Pi-Sunyer et al., 1998), detailed understanding of the mechanisms of BAT activation and WAT accumulation could produce therapeutic strategies for combatting metabolic pathologies. As morphological changes accompany alterations in adipose function, imaging of adipose tissue is one of the most important tools for understanding how adipose tissue mass fluctuates in response to various physiological contexts. Therefore, this chapter details several methods of processing and imaging adipose tissue, including brightfield colorimetric imaging of paraffin sectioned adipose tissue with a detailed protocol for automated adipocyte size analysis; fluorescent imaging of paraffin and frozen sectioned adipose tissue; and confocal fluorescent microscopy of whole mounted adipose tissue. We have also provided many example images showing results produced using each protocol, as well as commentary on the strengths and limitations of each approach. PMID:24480341

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

    PubMed Central

    Stanford, Kristin I.; Middelbeek, Roeland J.W.

    2015-01-01

    Regular physical activity and exercise training have long been known to cause adaptations to white adipose tissue (WAT), including decreases in cell size and lipid content and increases in mitochondrial proteins. In this article, we discuss recent studies that have investigated the effects of exercise training on mitochondrial function, the “beiging” of WAT, regulation of adipokines, metabolic effects of trained adipose tissue on systemic metabolism, and depot-specific responses to exercise training. The major WAT depots in the body are found in the visceral cavity (vWAT) and subcutaneously (scWAT). In rodent models, exercise training increases mitochondrial biogenesis and activity in both these adipose tissue depots. Exercise training also increases expression of the brown adipocyte marker uncoupling protein 1 (UCP1) in both adipose tissue depots, although these effects are much more pronounced in scWAT. Consistent with the increase in UCP1, exercise training increases the presence of brown-like adipocytes in scWAT, also known as browning or beiging. Training results in changes in the gene expression of thousands of scWAT genes and an altered adipokine profile in both scWAT and vWAT. Transplantation of trained scWAT in sedentary recipient mice results in striking improvements in skeletal muscle glucose uptake and whole-body metabolic homeostasis. Human and rodent exercise studies have indicated that exercise training can alter circulating adipokine concentration as well as adipokine expression in adipose tissue. Thus, the profound changes to WAT in response to exercise training may be part of the mechanism by which exercise improves whole-body metabolic health. PMID:26050668

  11. Marrow Adipose Tissue: Trimming the Fat.

    PubMed

    Scheller, Erica L; Cawthorn, William P; Burr, Aaron A; Horowitz, Mark C; MacDougald, Ormond A

    2016-06-01

    Marrow adipose tissue (MAT) is a unique fat depot, located in the skeleton, that has the potential to contribute to both local and systemic metabolic processes. In this review we highlight several recent conceptual developments pertaining to the origin and function of MAT adipocytes; consider the relationship of MAT to beige, brown, and white adipose depots; explore MAT expansion and turnover in humans and rodents; and discuss future directions for MAT research in the context of endocrine function and metabolic disease. MAT has the potential to exert both local and systemic effects on metabolic homeostasis, skeletal remodeling, hematopoiesis, and the development of bone metastases. The diversity of these functions highlights the breadth of the potential impact of MAT on health and disease. PMID:27094502

  12. Stearic acid content of abdominal adipose tissues in obese women

    PubMed Central

    Caron-Jobin, M; Mauvoisin, D; Michaud, A; Veilleux, A; Noël, S; Fortier, M P; Julien, P; Tchernof, A; Mounier, C

    2012-01-01

    Objective: Subcutaneous (SC) adipose tissue stearic acid (18:0) content and stearoyl-CoA desaturase-1 (SCD1)-mediated production of oleic acid (18:1) have been suggested to be altered in obesity. The objective of our study was to examine abdominal adipose tissue fatty acid content and SCD1 mRNA/protein level in women. Subjects and methods: Fatty acid content was determined by capillary gas chromatography in SC and omental (OM) fat tissues from two subgroups of 10 women with either small or large OM adipocytes. Samples from 10 additional women were used to measure SCD1 mRNA and protein expression, total extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 protein as well as insulin receptor (IR) expression levels. Results: OM fat 18:0 content was significantly lower in women with large OM adipocytes compared with women who had similar adiposity, but small OM adipocytes (2.37±0.45 vs 2.75±0.30 mg per 100 g adipose tissue, respectively, P⩽0.05). OM fat 18:0 content was negatively related to the visceral adipose tissue area (r=−0.44, P=0.05) and serum triglyceride levels (r=−0.56, P<0.05), while SC fat 18:0 content was negatively correlated with total body fat mass (BFM) (r=−0.48, P<0.05) and fasting insulin concentration (r=−0.73, P<0.005). SC adipose tissue desaturation index (18:1/18:0), SCD1 expression and protein levels were positively correlated with BFM. Moreover, obese women were characterized by a reduced OM/SC ratio of SCD1 mRNA and protein levels. A similar pattern was observed for ERK1/2 and IR expression. Conclusion: The presence of large adipocytes and increased adipose mass in a given fat compartment is related to reduced 18:0 content and increased desaturation index in women, independently of dietary fat intake. The depot-specific difference in ERK1/2 expression and activation, as well as in SCD1 and IR expression in obese women is consistent with the hypothesis that they may predominantly develop SC fat, which

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

    PubMed

    Liaw, Lucy; Prudovsky, Igor; Koza, Robert A; Anunciado-Koza, Rea V; Siviski, Matthew E; Lindner, Volkhard; Friesel, Robert E; Rosen, Clifford J; Baker, Paul R S; Simons, Brigitte; Vary, Calvin P H

    2016-09-01

    Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MS(ALL) . Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-derived BAT-C1 cells were also characterized. Over 3000 unique lipid species were quantified. Principal component analysis showed that perirenal versus inguinal white adipose tissues varied in lipid composition of triacyl- and diacylglycerols, sphingomyelins, glycerophospholipids and, notably, cardiolipin CL 72:3. In contrast, hexosylceramides and sphingomyelins distinguished brown from white adipose. Adipocyte differentiation models showed broad differences in lipid composition among themselves, upon adipogenic differentiation, and with adipose tissues. Palmitoyl triacylglycerides predominate in 3T3-L1 differentiation models, whereas cardiolipin CL 72:1 and SM 45:4 were abundant in brown adipose-derived cell differentiation models, respectively. MS/MS(ALL) data suggest new lipid biomarkers for tissue-specific lipid contributions to adipogenesis, thus providing a foundation for using in vitro models of adipogenesis to reflect potential changes in adipose tissues in vivo. J. Cell. Biochem. 117: 2182-2193, 2016. © 2016 Wiley Periodicals, Inc. PMID:26910604

  14. Differential response of human adipose tissue-derived mesenchymal stem cells, dermal fibroblasts, and keratinocytes to burn wound exudates: potential role of skin-specific chemokine CCL27.

    PubMed

    van den Broek, Lenie J; Kroeze, Kim L; Waaijman, Taco; Breetveld, Melanie; Sampat-Sardjoepersad, Shakun C; Niessen, Frank B; Middelkoop, Esther; Scheper, Rik J; Gibbs, Susan

    2014-01-01

    Many cell-based regenerative medicine strategies toward tissue-engineered constructs are currently being explored. Cell-cell interactions and interactions with different biomaterials are extensively investigated, whereas very few studies address how cultured cells will interact with soluble wound-healing mediators that are present within the wound bed after transplantation. The aim of this study was to determine how adipose tissue-derived mesenchymal stem cells (ASC), dermal fibroblasts, and keratinocytes will react when they come in contact with the deep cutaneous burn wound bed. Burn wound exudates isolated from deep burn wounds were found to contain many cytokines, including chemokines and growth factors related to inflammation and wound healing. Seventeen mediators were identified by ELISA (concentration range 0.0006-9 ng/mg total protein), including the skin-specific chemokine CCL27. Burn wound exudates activated both ASC and dermal fibroblasts, but not keratinocytes, to increase secretion of CXCL1, CXCL8, CCL2, and CCL20. Notably, ASC but not fibroblasts or keratinocytes showed significant increased secretion of vascular endothelial growth factor (5-fold) and interleukin-6 (253-fold), although when the cells were incorporated in bi-layered skin substitute (SS) these differences were less pronounced. A similar discrepancy between ASC and dermal fibroblast mono-cultures was observed when recombinant human-CCL27 was used instead of burn wound exudates. Although CCL27 did not stimulate the secretion of any of the wound-healing mediators by keratinocytes, these cells, in contrast to ASC or dermal fibroblasts, showed increased proliferation and migration. Taken together, these results indicate that on transplantation, keratinocytes are primarily activated to promote wound closure. In contrast, dermal fibroblasts and, in particular, ASC respond vigorously to factors present in the wound bed, leading to increased secretion of angiogenesis/granulation tissue formation

  15. Brominated dioxins and dibenzofurans in human adipose tissue. Final report

    SciTech Connect

    Cramer, P.H.; Stanley, J.S.; Bauer, K.; Ayling, R.E.; Thornburg, K.R.

    1990-04-11

    The report describes the analytical efforts for the determination of polybrominated dioxins (PBDDs) and furans (PBDFs) in human adipose tissues. Data on the precision and accuracy of the method for three tetra- through hexabrominated dioxins and three tetra- through hexabrominated furans (specific 2,3,7,8-substituted isomers) were generated from the analysis of 5 unspiked and 10 spiked (5 replicates at 2 spike levels) adipose tissue samples that were included with the analysis of the FY 1987 samples. In addition, data are presented on the results of the analysis of 48 composite samples for the six specific PBDD and PBDF compounds. The targeted 2,3,7,8-substituted PBDDs and PBDFs were not detected in any of the samples except those prepared as spiked QC materials. The detection limits calculated for the tetrabromo congeners in the samples ranged from 0.46 to 8.9 pg/g (lipid basis). The detection limits for the higher brominated congeners were typically greater than that observed for the tetrabrominated compounds. There is some evidence for the presence of other brominated compounds in the adipose tissue samples. Specifically, responses were noted that correspond to the qualitative criteria for polybrominated diphenyl ethers (hexa through octabromo).

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

    PubMed Central

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

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

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

    PubMed

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

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

  18. Differential responses of white adipose tissue and brown adipose tissue to caloric restriction in rats.

    PubMed

    Okita, Naoyuki; Hayashida, Yusuke; Kojima, Yumiko; Fukushima, Mayumi; Yuguchi, Keiko; Mikami, Kentaro; Yamauchi, Akiko; Watanabe, Kyoko; Noguchi, Mituru; Nakamura, Megumi; Toda, Toshifusa; Higami, Yoshikazu

    2012-05-01

    Caloric restriction (CR) slows the aging process and extends longevity, but the exact underlying mechanisms remain debatable. It has recently been suggested that the beneficial action of CR may be mediated in part by adipose tissue remodeling. Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). In this study, proteome analysis using two-dimensional gel electrophoresis combined with MALDI-TOF MS, and subsequent analyses were performed on both WAT and BAT from 9-month-old male rats fed ad libitum or subjected to CR for 6 months. Our findings suggest that CR activates mitochondrial energy metabolism and fatty acid biosynthesis in WAT. It is likely that in CR animals WAT functions as an energy transducer from glucose to energy-dense lipid. In contrast, in BAT CR either had no effect on, or down-regulated, the mitochondrial electron transport chain, but enhanced fatty acid biosynthesis. This suggests that in CR animals BAT may change its function from an energy consuming system to an energy reservoir system. Based on our findings, we conclude that WAT and BAT cooperate to use energy effectively via a differential response of mitochondrial function to CR. PMID:22414572

  19. Adiposity-Dependent Regulatory Effects on Multi-tissue Transcriptomes.

    PubMed

    Glastonbury, Craig A; Viñuela, Ana; Buil, Alfonso; Halldorsson, Gisli H; Thorleifsson, Gudmar; Helgason, Hannes; Thorsteinsdottir, Unnur; Stefansson, Kari; Dermitzakis, Emmanouil T; Spector, Tim D; Small, Kerrin S

    2016-09-01

    Obesity is a global epidemic that is causally associated with a range of diseases, including type 2 diabetes and cardiovascular disease, at the population-level. However, there is marked heterogeneity in obesity-related outcomes among individuals. This might reflect genotype-dependent responses to adiposity. Given that adiposity, measured by BMI, is associated with widespread changes in gene expression and regulatory variants mediate the majority of known complex trait loci, we sought to identify gene-by-BMI (G × BMI) interactions on the regulation of gene expression in a multi-tissue RNA-sequencing (RNA-seq) dataset from the TwinsUK cohort (n = 856). At a false discovery rate of 5%, we identified 16 cis G × BMI interactions (top cis interaction: CHURC1, rs7143432, p = 2.0 × 10(-12)) and one variant regulating 53 genes in trans (top trans interaction: ZNF423, rs3851570, p = 8.2 × 10(-13)), all in adipose tissue. The interactions were adipose-specific and enriched for variants overlapping adipocyte enhancers, and regulated genes were enriched for metabolic and inflammatory processes. We replicated a subset of the interactions in an independent adipose RNA-seq dataset (deCODE genetics, n = 754). We also confirmed the interactions with an alternate measure of obesity, dual-energy X-ray absorptiometry (DXA)-derived visceral-fat-volume measurements, in a subset of TwinsUK individuals (n = 682). The identified G × BMI regulatory effects demonstrate the dynamic nature of gene regulation and reveal a functional mechanism underlying the heterogeneous response to obesity. Additionally, we have provided a web browser allowing interactive exploration of the dataset, including of association between expression, BMI, and G × BMI regulatory effects in four tissues. PMID:27588447

  20. Adipose tissue as a medium for epidemiologic exposure assessment.

    PubMed Central

    Kohlmeier, L; Kohlmeier, M

    1995-01-01

    In the United States, adipose tissue is rarely used as a medium for assessment of prior exposures in epidemiologic studies. Adipose tissue aspirations are in general less invasive and carry less risk than phlebotomy. Tissue samples can be analyzed for a wide number of epidemiologically important exposures. Beyond reflecting long-term energy balance, this tissue offers a relatively stable depot of triglyceride and fat-soluble substances, such as fat-soluble vitamins, and pesticides. As a tissue it represents the greatest reservoir of carotenoids in the body. Halogenated hydrocarbons may be measured in concentrations of hundreds-fold greater than those in blood of the same individuals. The composition of adipose tissue also reflects the long-term dietary intakes of a number of essential fatty acids. The turnover times of all of these substances in adipose tissue remain under-researched. Sampling and storage of adipose tissue, homogeneity of sampling sites, turnover times, and the effects of diet, age, gender, race, hormones, and disease on adipose tissue composition are discussed in this review of current knowledge about adipose tissue stability. Experience in the use of adipose tissue sampling in epidemiologic studies in various countries has shown that it is simple to conduct, requires little training, carries little risk, and does not result in excessive participant refusal. PMID:7635122

  1. Id transcriptional regulators in adipogenesis and adipose tissue metabolism

    PubMed Central

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

    2014-01-01

    Id proteins (Id1-Id4) are helix-loop-helix (HLH) transcriptional regulators that lack a basic DNA binding domain. They act as negative regulators of basic helixloop-helix (bHLH) transcription factors by forming heterodimers and inhibit their DNA binding and transcriptional activity. Id proteins are implicated in the regulation of various cellular mechanisms such as cell proliferation, cellular differentiation, cell fate determination, angiogenesis and tumorigenesis. A handful of recent studies also disclosed that Id proteins have critical functions in adipocyte differentiation and adipose tissue metabolism. Here, we reviewed the progress made thus far in understanding the specific functions of Id proteins in adipose tissue differentiation and metabolism. In addition to reviewing the known mechanisms of action, we also discuss possible additional mechanisms in which Id proteins might participate in regulating adipogenic and metabolic pathways. PMID:24896358

  2. Comparison of human adipose-derived stem cells isolated from subcutaneous, omental, and intrathoracic adipose tissue depots for regenerative applications.

    PubMed

    Russo, Valerio; Yu, Claire; Belliveau, Paul; Hamilton, Andrew; Flynn, Lauren E

    2014-02-01

    Adipose tissue is an abundant source of multipotent progenitor cells that have shown promise in regenerative medicine. In humans, fat is primarily distributed in the subcutaneous and visceral depots, which have varying biochemical and functional properties. In most studies to date, subcutaneous adipose tissue has been investigated as the adipose-derived stem cell (ASC) source. In this study, we sought to develop a broader understanding of the influence of specific adipose tissue depots on the isolated ASC populations through a systematic comparison of donor-matched abdominal subcutaneous fat and omentum, and donor-matched pericardial adipose tissue and thymic remnant samples. We found depot-dependent and donor-dependent variability in the yield, viability, immunophenotype, clonogenic potential, doubling time, and adipogenic and osteogenic differentiation capacities of the ASC populations. More specifically, ASCs isolated from both intrathoracic depots had a longer average doubling time and a significantly higher proportion of CD34(+) cells at passage 2, as compared with cells isolated from subcutaneous fat or the omentum. Furthermore, ASCs from subcutaneous and pericardial adipose tissue demonstrated enhanced adipogenic differentiation capacity, whereas ASCs isolated from the omentum displayed the highest levels of osteogenic markers in culture. Through cell culture analysis under hypoxic (5% O(2)) conditions, oxygen tension was shown to be a key mediator of colony-forming unit-fibroblast number and osteogenesis for all depots. Overall, our results suggest that depot selection is an important factor to consider when applying ASCs in tissue-specific cell-based regenerative therapies, and also highlight pericardial adipose tissue as a potential new ASC source. PMID:24361924

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

    SciTech Connect

    Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo; Horiuchi, Masatsugu

    2011-03-04

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

  4. Macrophage Elastase Suppresses White Adipose Tissue Expansion with Cigarette Smoking

    PubMed Central

    Tsuji, Takao; Kelly, Neil J.; Takahashi, Saeko; Leme, Adriana S.; McGarry Houghton, A.

    2014-01-01

    Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced emphysema, yet its role in other smoking related pathologies remains unclear. The weight suppressing effects of smoking are a major hindrance to cessation efforts, and MMP12 is known to suppress the vascularization on which adipose tissue growth depends by catalyzing the formation of antiangiogenic peptides endostatin and angiostatin. The goal of this study was to determine the role of MMP12 in adipose tissue growth and smoking-related suppression of weight gain. Whole body weights and white adipose depots from wild-type and Mmp12-deficient mice were collected during early postnatal development and after chronic CS exposure. Adipose tissue specimens were analyzed for angiogenic and adipocytic markers and for content of the antiangiogenic peptides endostatin and angiostatin. Cultured 3T3-L1 adipocytes were treated with adipose tissue homogenate to examine its effects on vascular endothelial growth factor (VEGF) expression and secretion. MMP12 content and activity were increased in the adipose tissue of wild-type mice at 2 weeks of age, leading to elevated endostatin production, inhibition of VEGF secretion, and decreased adipose tissue vascularity. By 8 weeks of age, adipose MMP12 levels subsided, and the protein was no longer detectable. However, chronic CS exposure led to macrophage accumulation and restored adipose MMP12 activity, thereby suppressing adipose tissue mass and vascularity. Our results reveal a novel systemic role for MMP12 in postnatal adipose tissue expansion and smoking-associated weight loss by suppressing vascularity within the white adipose tissue depots. PMID:24914890

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

    SciTech Connect

    Yamada, Tomoya Higuchi, Mikito; Nakanishi, Naoto

    2015-08-07

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

  6. Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis

    PubMed Central

    Garcia, Briana; Francois-Vaughan, Heather; Onikoyi, Omobola; Kostadinov, Stefan; De Paepe, Monique E.; Gruppuso, Philip A.; Sanders, Jennifer A.

    2014-01-01

    Obesity during childhood and beyond may have its origins during fetal or early postnatal life. At present, there are no suitable in vivo experimental models to study factors that modulate or perturb human fetal white adipose tissue (WAT) expansion, remodeling, development, adipogenesis, angiogenesis, or epigenetics. We have developed such a model. It involves the xenotransplantation of midgestation human WAT into the renal subcapsular space of immunocompromised SCID-beige mice. After an initial latency period of approximately 2 weeks, the tissue begins expanding. The xenografts are healthy and show robust expansion and angiogenesis for at least 2 months following transplantation. Data and cell size and gene expression are consistent with active angiogenesis. The xenografts maintain the expression of genes associated with differentiated adipocyte function. In contrast to the fetal tissue, adult human WAT does not engraft. The long-term viability and phenotypic maintenance of fetal adipose tissue following xenotransplantation may be a function of its autonomous high rates of adipogenesis and angiogenesis. Through the manipulation of the host mice, this model system offers the opportunity to study the mechanisms by which nutrients and other environmental factors affect human adipose tissue development and biology. PMID:25193996

  7. Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis.

    PubMed

    Garcia, Briana; Francois-Vaughan, Heather; Onikoyi, Omobola; Kostadinov, Stefan; De Paepe, Monique E; Gruppuso, Philip A; Sanders, Jennifer A

    2014-12-01

    Obesity during childhood and beyond may have its origins during fetal or early postnatal life. At present, there are no suitable in vivo experimental models to study factors that modulate or perturb human fetal white adipose tissue (WAT) expansion, remodeling, development, adipogenesis, angiogenesis, or epigenetics. We have developed such a model. It involves the xenotransplantation of midgestation human WAT into the renal subcapsular space of immunocompromised SCID-beige mice. After an initial latency period of approximately 2 weeks, the tissue begins expanding. The xenografts are healthy and show robust expansion and angiogenesis for at least 2 months following transplantation. Data and cell size and gene expression are consistent with active angiogenesis. The xenografts maintain the expression of genes associated with differentiated adipocyte function. In contrast to the fetal tissue, adult human WAT does not engraft. The long-term viability and phenotypic maintenance of fetal adipose tissue following xenotransplantation may be a function of its autonomous high rates of adipogenesis and angiogenesis. Through the manipulation of the host mice, this model system offers the opportunity to study the mechanisms by which nutrients and other environmental factors affect human adipose tissue development and biology. PMID:25193996

  8. Altered autophagy in human adipose tissues in obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  9. Adipose tissue and the reproductive axis: biological aspects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The discovery of leptin clearly demonstrated a relationship between body fat and the neuroendocrine axis since leptin influences appetite and the reproductive axis. Since adipose tissue is a primary source of leptin, adipose tissue is no longer considered as simply a depot to store fat. Recent find...

  10. Ontogeny of adipokine expression in neonatal pig adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined ontogeny of development for a range of adipokines in neonatal adipose tissue. Pigs were selected across six litters for sampling at d1, d4, d7 or d21 of age. Subcutaneous (SQ) and perirenal (PR) adipose tissue were collected and extracted for total RNA. SQ was also collected f...

  11. Albumin induced cytokine expression in porcine adipose tissue explants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Albumin has historically been included in medium designed for use with adipose tissue when evaluating metabolism, gene expression or protein secretion. However, recent studies with mouse adipocytes (Ruan et al., J. Biol. Chem. 278:47585-47593, 2003) and human adipose tissue (Schlesinger et al., Ame...

  12. Identification of progesterone receptor in human subcutaneous adipose tissue.

    PubMed

    O'Brien, S N; Welter, B H; Mantzke, K A; Price, T M

    1998-02-01

    Sex steroids are postulated to play a role in adipose tissue regulation and distribution, because the amount and location of adipose tissue changes during puberty and menopause. Because of the nature of adipose tissue, receptors for the female sex steroids have been difficult to demonstrate. To date, estrogen receptor messenger RNA and protein have been identified in human subcutaneous adipose tissue, but the presence of progesterone receptor (PR) has not been reported. In this study, we demonstrate PR message by Northern blot analysis in RNA isolated from the abdominal subcutaneous adipose tissue of premenopausal women. These preliminary studies revealed that PR messenger RNA levels are higher in the stromal-vascular fraction as opposed to the adipocyte fraction. Western blot analysis demonstrates both PR protein isoforms (human PR-A and human PR-B) in human subcutaneous adipose tissue. Using an enzyme-linked immunosorbent assay, total PR could be quantitated. These studies substantiate that sex steroid receptors are present in human adipose tissue, thereby providing a direct route for regulation of adipose tissue by female sex steroids. PMID:9467566

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2015-01-01

    Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis. PMID:25864946

  15. Surgical injury induces local and distant adipose tissue browning.

    PubMed

    Longchamp, Alban; Tao, Ming; Bartelt, Alexander; Ding, Kui; Lynch, Lydia; Hine, Christopher; Corpataux, Jean-Marc; Kristal, Bruce S; Mitchell, James R; Ozaki, C Keith

    2016-01-01

    The adipose organ, which comprises brown, white and beige adipocytes, possesses remarkable plasticity in response to feeding and cold exposure. The development of beige adipocytes in white adipose tissue (WAT), a process called browning, represents a promising route to treat metabolic disorders. While surgical procedures constantly traumatize adipose tissue, its impact on adipocyte phenotype remains to be established. Herein, we studied the effect of trauma on adipocyte phenotype one day after sham, incision control, or surgical injury to the left inguinal adipose compartment. Caloric restriction was used to control for surgery-associated body temperature changes and weight loss. We characterized the trauma-induced cellular and molecular changes in subcutaneous, visceral, interscapular, and perivascular adipose tissue using histology, immunohistochemistry, gene expression, and flow cytometry analysis. After one day, surgical trauma stimulated adipose tissue browning at the site of injury and, importantly, in the contralateral inguinal depot. Browning was not present after incision only, and was largely independent of surgery-associated body temperature and weight loss. Adipose trauma rapidly recruited monocytes to the injured site and promoted alternatively activated macrophages. Conversely, PDGF receptor-positive beige progenitors were reduced. In this study, we identify adipose trauma as an unexpected driver of selected local and remote adipose tissue browning, holding important implications for the biologic response to surgical injury. PMID:27386152

  16. Immunomagnetic Separation of Fat Depot-Specific Sca1high Adipose-Derived Stem Cells (Ascs)

    PubMed Central

    Barnes, Richard H; Chun, Tae-Hwa

    2016-01-01

    The isolation of adipose-derived stem cells (ASCs) is an important method in the field of adipose tissue biology, adipogenesis, and extracellular matrix (ECM) remodeling. In vivo, ECM-rich environment consisting of fibrillar collagens provides a structural support to adipose tissues during the progression and regression of obesity. Physiological ECM remodeling mediated by matrix metalloproteinases (MMPs) plays a major role in regulating adipose tissue size and function1, 2. The loss of physiological collagenolytic ECM remodeling may lead to excessive collagen accumulation (tissue fibrosis), macrophage infiltration, and ultimately, a loss of metabolic homeostasis including insulin resistance3, 4. When a phenotypic change of the adipose tissue is observed in gene-targeted mouse models, isolating primary ASCs from fat depots for in vitro studies is an effective approach to define the role of the specific gene in regulating the function of ASCs. In the following, we define an immunomagnetic separation of Sca1high ASCs. PMID:27583550

  17. Immunomagnetic Separation of Fat Depot-specific Sca1high Adipose-derived Stem Cells (ASCs).

    PubMed

    Barnes, Richard H; Chun, Tae-Hwa

    2016-01-01

    The isolation of adipose-derived stem cells (ASCs) is an important method in the field of adipose tissue biology, adipogenesis, and extracellular matrix (ECM) remodeling. In vivo, ECM-rich environment consisting of fibrillar collagens provides a structural support to adipose tissues during the progression and regression of obesity. Physiological ECM remodeling mediated by matrix metalloproteinases (MMPs) plays a major role in regulating adipose tissue size and function(1,2). The loss of physiological collagenolytic ECM remodeling may lead to excessive collagen accumulation (tissue fibrosis), macrophage infiltration, and ultimately, a loss of metabolic homeostasis including insulin resistance(3,4). When a phenotypic change of the adipose tissue is observed in gene-targeted mouse models, isolating primary ASCs from fat depots for in vitro studies is an effective approach to define the role of the specific gene in regulating the function of ASCs. In the following, we define an immunomagnetic separation of Sca1(high) ASCs. PMID:27583550

  18. The Ontogeny of Brown Adipose Tissue.

    PubMed

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

    2015-01-01

    There are three different types of adipose tissue (AT)-brown, white, and beige-that differ with stage of development, species, and anatomical location. Of these, brown AT (BAT) is the least abundant but has the greatest potential impact on energy balance. BAT is capable of rapidly producing large amounts of heat through activation of the unique uncoupling protein 1 (UCP1) located within the inner mitochondrial membrane. White AT is an endocrine organ and site of lipid storage, whereas beige AT is primarily white but contains some cells that possess UCP1. BAT first appears in the fetus around mid-gestation and is then gradually lost through childhood, adolescence, and adulthood. We focus on the interrelationships between adipocyte classification, anatomical location, and impact of diet in early life together with the extent to which fat development differs between the major species examined. Ultimately, novel dietary interventions designed to reactivate BAT could be possible. PMID:26076904

  19. Perivascular adipose tissue, vascular reactivity and hypertension.

    PubMed

    Oriowo, Mabayoje A

    2015-01-01

    Most blood vessels are surrounded by a variable amount of adventitial adipose tissue, perivascular adipose tissue (PVAT), which was originally thought to provide mechanical support for the vessel. It is now known that PVAT secretes a number of bioactive substances including vascular endothelial growth factor, tumor necrosis factor-alpha (TNF-α), leptin, adiponectin, insulin-like growth factor, interleukin-6, plasminogen activator substance, resistin and angiotensinogen. Several studies have shown that PVAT significantly modulated vascular smooth muscle contractions induced by a variety of agonists and electrical stimulation by releasing adipocyte-derived relaxing (ADRF) and contracting factors. The identity of ADRF is not yet known. However, several vasodilators have been suggested including adiponectin, angiotensin 1-7, hydrogen sulfide and methyl palmitate. The anticontractile effect of PVAT is mediated through the activation of potassium channels since it is abrogated by inhibiting potassium channels. Hypertension is characterized by a reduction in the size and amount of PVAT and this is associated with the attenuated anticontractile effect of PVAT in hypertension. However, since a reduction in size and amount of PVAT and the attenuated anticontractile effect of PVAT were already evident in prehypertensive rats with no evidence of impaired release of ADRF, there is the possibility that the anticontractile effect of PVAT was not directly related to an altered function of the adipocytes per se. Hypertension is characterized by low-grade inflammation and infiltration of macrophages. One of the adipokines secreted by macrophages is TNF-α. It has been shown that exogenously administered TNF-α enhanced agonist-induced contraction of a variety of vascular smooth muscle preparations and reduced endothelium-dependent relaxation. Other procontractile factors released by the PVAT include angiotensin II and superoxide. It is therefore possible that the loss could be due

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

    PubMed

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

    2015-01-01

    Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value. PMID:26124828

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

    PubMed Central

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

    2015-01-01

    Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value. PMID:26124828

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

    PubMed

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

    2011-01-01

    Although obesity is a complex metabolic disorder often associated with insulin resistance, hyperinsulinemia and Type 2 diabetes, as well as with accelerated atherosclerosis, the molecular changes in obesity that promote these disorders are not completely understood. Several mechanisms have been proposed to explain how increased adipose tissue mass affects whole body insulin resistance and cardiovascular risk. One theory is that increased adipose derived inflammatory cytokines induces a chronic inflammatory state that not only increases cardiovascular risk, but also antagonizes insulin signaling and mitochondrial function and thereby impair glucose hemostasis. Another suggests that lipid accumulation in nonadipose tissues not suited for fat storage leads to the buildup of bioactive lipids that inhibit insulin signaling and metabolism. Recent evidence demonstrates that sphingolipid metabolism is dysregulated in obesity and specific sphingolipids may provide a common pathway that link excess nutrients and inflammation to increased metabolic and cardiovascular risk. This chapter will focus primarily on the expression and regulation of adipose and plasma ceramide biosynthesis in obesity and, its potential contribution to the pathogenesis of obesity and the metabolic syndrome. PMID:21910083

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

    PubMed Central

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

    2014-01-01

    Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to 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

  4. Proline oxidase–adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation

    PubMed Central

    Lettieri Barbato, D; Aquilano, K; Baldelli, S; Cannata, S M; Bernardini, S; Rotilio, G; Ciriolo, M R

    2014-01-01

    The nutrient-sensing lipolytic enzyme adipose triglyceride lipase (ATGL) has a key role in adipose tissue function, and alterations in its activity have been implicated in many age-related metabolic disorders. In adipose tissue reduced blood vessel density is related to hypoxia state, cell death and inflammation. Here we demonstrate that adipocytes of poorly vascularized enlarged visceral adipose tissue (i.e. adipose tissue of old mice) suffer from limited nutrient delivery. In particular, nutrient starvation elicits increased activity of mitochondrial proline oxidase/dehydrogenase (POX/PRODH) that is causal in triggering a ROS-dependent induction of ATGL. We demonstrate that ATGL promotes the expression of genes related to mitochondrial oxidative metabolism (peroxisome proliferator-activated receptor-α, peroxisome proliferator-activated receptor-γ coactivator-1α), thus setting a metabolic switch towards fat utilization that supplies energy to starved adipocytes and prevents cell death, as well as adipose tissue inflammation. Taken together, these results identify ATGL as a stress resistance mediator in adipocytes, restraining visceral adipose tissue dysfunction typical of age-related metabolic disorders. PMID:24096872

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

    SciTech Connect

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

    1989-01-01

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

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

    PubMed Central

    Porter, Craig; Børsheim, Elisabet; Sidossis, Labros S.

    2013-01-01

    The function ascribed to brown adipose tissue in humans has long been confined to thermoregulation in neonates, where this thermogenic capacity was thought lost with maturation. Recently, brown adipose tissue depots have been identified in adult humans. The significant oxidative capacity of brown adipocytes and the ability of their mitochondria to respire independently of ATP production, has led to renewed interest in the role that these adipocytes play in human energy metabolism. In our view, there is a need for robust physiological studies determining the relationship between molecular signatures of brown adipose tissue, adipose tissue mitochondrial function, and whole body energy metabolism, in order to elucidate the significance of thermogenic adipose tissue in humans. Until such information is available, the role of thermogenic adipose tissue in human metabolism and the potential that these adipocytes may prevent or treat obesity and metabolic diseases in humans will remain unknown. In this article, we summarize the recent literature pertaining to brown adipose tissue function with the aims of drawing the readers' attention to the lack of data concerning the role of brown adipocytes in human physiology, and to the potential limitations of current research strategies. PMID:23691283

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

    PubMed

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

    2016-08-12

    Oncostatin M (OSM) is a multifunctional gp130 cytokine. Although OSM is produced in adipose tissue, it is not produced by adipocytes. OSM expression is significantly induced in adipose tissue from obese mice and humans. The OSM-specific receptor, OSM receptor β (OSMR), is expressed in adipocytes, but its function remains largely unknown. To better understand the effects of OSM in adipose tissue, we knocked down Osmr expression in adipocytes in vitro using siRNA. In vivo, we generated a mouse line lacking Osmr in adiponectin-expressing cells (OSMR(FKO) mice). The effects of OSM on gene expression were also assessed in vitro and in vivo OSM exerts proinflammatory effects on cultured adipocytes that are partially rescued by Osmr knockdown. Osm expression is significantly increased in adipose tissue T cells of high fat-fed mice. In addition, adipocyte Osmr expression is increased following high fat feeding. OSMR(FKO) mice exhibit increased insulin resistance and adipose tissue inflammation and have increased lean mass, femoral length, and bone volume. Also, OSMR(FKO) mice exhibit increased expression of Osm, the T cell markers Cd4 and Cd8, and the macrophage markers F4/80 and Cd11c Interestingly, the same proinflammatory genes induced by OSM in adipocytes are induced in the adipose tissue of the OSMR(FKO) mouse, suggesting that increased expression of proinflammatory genes in adipose tissue arises both from adipocytes and other cell types. These findings suggest that adipocyte OSMR signaling is involved in the regulation of adipose tissue homeostasis and that, in obesity, OSMR ablation may exacerbate insulin resistance by promoting adipose tissue inflammation. PMID:27325693

  8. Total DDT and dieldrin content of human adipose tissue

    SciTech Connect

    Ahmad, N.; Harsas, W.; Marolt, R.S.; Morton, M.; Pollack, J.K.

    1988-12-01

    As far as the authors could ascertain only 4 well-documented analytical studies have been carried out in Australia determining the total DDT and dieldrin content of human adipose tissue. The latest of these studies was published over 16 years ago. Therefore it is timely and important to re-examine the total DDT and dieldrin concentration within the adipose tissue of the Australian population. The present investigation has analyzed 290 samples of human adipose tissue obtained from Westmead Hospital situated in an outer suburb of Sydney, New South Wales for their content of total DDT and dieldrin.

  9. IMMUNOLOGICAL GOINGS-ON IN VISCERAL ADIPOSE TISSUE

    PubMed Central

    Mathis, Diane

    2014-01-01

    Chronic, low-grade inflammation of visceral adipose tissue, and systemically, is a critical link between recent strikingly parallel rises in the incidence of obesity and type-2 diabetes. Macrophages have been recognized for some time to be critical participants in obesity-induced inflammation of adipose-tissue. Of late, a score of other cell-types of the innate and adaptive arms of the immune system have been suggested to play a positive or negative role in adipose-tissue infiltrates. This piece reviews the existing data on these new participants; discusses experimental uncertainties, inconsistencies and complexities; and puts forward a minimalist synthetic scheme. PMID:23747244

  10. Isoliquiritigenin Attenuates Adipose Tissue Inflammation in vitro and Adipose Tissue Fibrosis through Inhibition of Innate Immune Responses in Mice

    PubMed Central

    Watanabe, Yasuharu; Nagai, Yoshinori; Honda, Hiroe; Okamoto, Naoki; Yamamoto, Seiji; Hamashima, Takeru; Ishii, Yoko; Tanaka, Miyako; Suganami, Takayoshi; Sasahara, Masakiyo; Miyake, Kensuke; Takatsu, Kiyoshi

    2016-01-01

    Isoliquiritigenin (ILG) is a flavonoid derived from Glycyrrhiza uralensis and potently suppresses NLRP3 inflammasome activation resulting in the improvement of diet-induced adipose tissue inflammation. However, whether ILG affects other pathways besides the inflammasome in adipose tissue inflammation is unknown. We here show that ILG suppresses adipose tissue inflammation by affecting the paracrine loop containing saturated fatty acids and TNF-α by using a co-culture composed of adipocytes and macrophages. ILG suppressed inflammatory changes induced by the co-culture through inhibition of NF-κB activation. This effect was independent of either inhibition of inflammasome activation or activation of peroxisome proliferator-activated receptor-γ. Moreover, ILG suppressed TNF-α-induced activation of adipocytes, coincident with inhibition of IκBα phosphorylation. Additionally, TNF-α-mediated inhibition of Akt phosphorylation under insulin signaling was alleviated by ILG in adipocytes. ILG suppressed palmitic acid-induced activation of macrophages, with decreasing the level of phosphorylated Jnk expression. Intriguingly, ILG improved high fat diet-induced fibrosis in adipose tissue in vivo. Finally, ILG inhibited TLR4- or Mincle-stimulated expression of fibrosis-related genes in stromal vascular fraction from obese adipose tissue and macrophages in vitro. Thus, ILG can suppress adipose tissue inflammation by both inflammasome-dependent and -independent manners and attenuate adipose tissue fibrosis by targeting innate immune sensors. PMID:26975571

  11. Role of adipose tissue in haemostasis, coagulation and fibrinolysis.

    PubMed

    Faber, D R; de Groot, Ph G; Visseren, F L J

    2009-09-01

    Obesity is associated with an increased incidence of insulin resistance (IR), type 2 diabetes mellitus and cardiovascular diseases. The increased risk for cardiovascular diseases could partly be caused by a prothrombotic state that exists because of abdominal obesity. Adipose tissue induces thrombocyte activation by the production of adipose tissue-derived hormones, often called adipokines, of which some such as leptin and adiponectin have been shown to directly interfere with platelet function. Increased adipose tissue mass induces IR and systemic low-grade inflammation, also affecting platelet function. It has been demonstrated that adipose tissue directly impairs fibrinolysis by the production of plasminogen activator inhibitor-1 and possibly thrombin-activatable fibrinolysis inhibitor. Adipose tissue may contribute to enhanced coagulation by direct tissue factor production, but hypercoagulability is likely to be primarily caused by affecting hepatic synthesis of the coagulation factors fibrinogen, factor VII, factor VIII and tissue factor, by releasing free fatty acids and pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-1beta and interleukin-6) into the portal circulation and by inducing hepatic IR. Adipose tissue dysfunction could thus play a causal role in the prothrombotic state observed in obesity, by directly and indirectly affecting haemostasis, coagulation and fibrinolysis. PMID:19460118

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

    SciTech Connect

    Miller, M.F.

    1987-01-01

    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.

  13. Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling.

    PubMed

    Wernstedt Asterholm, Ingrid; Tao, Caroline; Morley, Thomas S; Wang, Qiong A; Delgado-Lopez, Fernando; Wang, Zhao V; Scherer, Philipp E

    2014-07-01

    Chronic inflammation constitutes an important link between obesity and its pathophysiological sequelae. In contrast to the belief that inflammatory signals exert a fundamentally negative impact on metabolism, we show that proinflammatory signaling in the adipocyte is in fact required for proper adipose tissue remodeling and expansion. Three mouse models with an adipose tissue-specific reduction in proinflammatory potential were generated that display a reduced capacity for adipogenesis in vivo, while the differentiation potential is unaltered in vitro. Upon high-fat-diet exposure, the expansion of visceral adipose tissue is prominently affected. This is associated with decreased intestinal barrier function, increased hepatic steatosis, and metabolic dysfunction. An impaired local proinflammatory response in the adipocyte leads to increased ectopic lipid accumulation, glucose intolerance, and systemic inflammation. Adipose tissue inflammation is therefore an adaptive response that enables safe storage of excess nutrients and contributes to a visceral depot barrier that effectively filters gut-derived endotoxin. PMID:24930973

  14. Characterization of microRNA expression in bovine adipose tissues: a potential regulatory mechanism of subcutaneous adipose tissue development

    PubMed Central

    2010-01-01

    Background MicroRNAs (miRNAs), a family of small non-coding RNA molecules, appear to regulate animal lipid metabolism and preadipocyte conversion to form lipid-assimilating adipocytes (i.e. adipogenesis). However, no miRNA to date has been reported to modulate adipogenesis and lipid deposition in beef cattle. Results The expression patterns of 89 miRNAs including four bovine specific miRNAs in subcutaneous adipose tissues from three groups of crossbred steers differing in backfat thickness were compared using qRT-PCR analysis. Eighty-six miRNAs were detectable in all samples, with 42 miRNAs differing among crossbreds (P < 0.05) and 15 miRNAs differentially expressed between tissues with high and low backfat thickness (P < 0.05). The expression levels of 18 miRNAs were correlated with backfat thickness (P < 0.05). The miRNA most differentially expressed and the most strongly associated with backfat thickness was miR-378, with a 1.99-fold increase in high backfat thickness tissues (r = 0.72). Conclusions MiRNA expression patterns differed significantly in response to host genetic components. Approximately 20% of the miRNAs in this study were identified as being correlated with backfat thickness. This result suggests that miRNAs may play a regulatory role in white adipose tissue development in beef animals. PMID:20423511

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

    PubMed Central

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

    2016-01-01

    Obesity is an unconstrained worldwide epidemic. Unraveling molecular controls in adipose tissue development holds promise to treat obesity or diabetes. Although numerous immortalized adipogenic cell lines have been established, adipose-derived stem cells from the stromal vascular fraction of subcutaneous white adipose tissues provide a reliable cellular system ex vivo much closer to adipose development in vivo. Pig adipose-derived stem cells (pADSC) are isolated from 7- to 9-day old piglets. The dorsal white fat depot of porcine subcutaneous adipose tissues is sliced, minced and collagenase digested. These pADSC exhibit strong potential to differentiate into adipocytes. Moreover, the pADSC also possess multipotency, assessed by selective stem cell markers, to differentiate into various mesenchymal cell types including adipocytes, osteocytes, and chondrocytes. These pADSC can be used for clarification of molecular switches in regulating classical adipocyte differentiation or in direction to other mesenchymal cell types of mesodermal origin. Furthermore, extended lineages into cells of ectodermal and endodermal origin have recently been achieved. Therefore, pADSC derived in this protocol provide an abundant and assessable source of adult mesenchymal stem cells with full multipotency for studying adipose development and application to tissue engineering of regenerative medicine. PMID:27077225

  16. Hypothalamic control of brown adipose tissue thermogenesis

    PubMed Central

    Labbé, Sebastien M.; Caron, Alexandre; Lanfray, Damien; Monge-Rofarello, Boris; Bartness, Timothy J.; Richard, Denis

    2015-01-01

    It has long been known, in large part from animal studies, that the control of brown adipose tissue (BAT) thermogenesis is insured by the central nervous system (CNS), which integrates several stimuli in order to control BAT activation through the sympathetic nervous system (SNS). SNS-mediated BAT activity is governed by diverse neurons found in brain structures involved in homeostatic regulations and whose activity is modulated by various factors including oscillations of energy fluxes. The characterization of these neurons has always represented a challenging issue. The available literature suggests that the neuronal circuits controlling BAT thermogenesis are largely part of an autonomic circuitry involving the hypothalamus, brainstem and the SNS efferent neurons. In the present review, we recapitulate the latest progresses in regards to the hypothalamic regulation of BAT metabolism. We briefly addressed the role of the thermoregulatory pathway and its interactions with the energy balance systems in the control of thermogenesis. We also reviewed the involvement of the brain melanocortin and endocannabinoid systems as well as the emerging role of steroidogenic factor 1 (SF1) neurons in BAT thermogenesis. Finally, we examined the link existing between these systems and the homeostatic factors that modulate their activities. PMID:26578907

  17. Salsalate activates brown adipose tissue in mice.

    PubMed

    van Dam, Andrea D; Nahon, Kimberly J; Kooijman, Sander; van den Berg, Susan M; Kanhai, Anish A; Kikuchi, Takuya; Heemskerk, Mattijs M; van Harmelen, Vanessa; Lombès, Marc; van den Hoek, Anita M; de Winther, Menno P J; Lutgens, Esther; Guigas, Bruno; Rensen, Patrick C N; Boon, Mariëtte R

    2015-05-01

    Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the current study was to unravel the molecular mechanisms involved in these beneficial metabolic effects of salsalate by treating mice with salsalate during and after development of high-fat diet-induced obesity. We found that salsalate attenuated and reversed high-fat diet-induced weight gain, in particular fat mass accumulation, improved glucose tolerance, and lowered plasma triglyceride levels. Mechanistically, salsalate selectively promoted the uptake of fatty acids from glycerol tri[(3)H]oleate-labeled lipoprotein-like emulsion particles by brown adipose tissue (BAT), decreased the intracellular lipid content in BAT, and increased rectal temperature, all pointing to more active BAT. The treatment of differentiated T37i brown adipocytes with salsalate increased uncoupled respiration. Moreover, salsalate upregulated Ucp1 expression and enhanced glycerol release, a dual effect that was abolished by the inhibition of cAMP-dependent protein kinase (PKA). In conclusion, salsalate activates BAT, presumably by directly activating brown adipocytes via the PKA pathway, suggesting a novel mechanism that may explain its beneficial metabolic effects in type 2 diabetes patients. PMID:25475439

  18. Deep subcutaneous adipose tissue is more saturated than superficial subcutaneous adipose tissue.

    PubMed

    Lundbom, J; Hakkarainen, A; Lundbom, N; Taskinen, M-R

    2013-04-01

    Upper body abdominal subcutaneous adipose tissue (SAT) can be divided into deep SAT (DSAT) and superficial SAT (SSAT) depots. Studies on adipose tissue fatty acid (FA) composition have made no distinction between these two depots. The aim of this study is to determine whether DSAT and SSAT differ in FA composition. We studied the FA composition of DSAT and SSAT in 17 male and 13 female volunteers using non-invasive proton magnetic resonance spectroscopy in vivo. Magnetic resonance imaging was used to differentiate between DSAT and SSAT. Adipose tissue spectra were analysed for lipid unsaturation, or double bond (DB) content, and polyunsaturation (PU), according to previously validated methods. The DSAT depot was more saturated than the SSAT depot, in both men (0.833 ± 0.012 vs 0.846 ± 0.009 DB, P<0.002) and women (0.826 ± 0.018 vs 0.850 ± 0.018 DB, P<0.002). In contrast, PU did not differ between DSAT and SSAT in either men (0.449 ± 0.043 vs 0.461 ± 0.044 PU, P=0.125) or women (0.411 ± 0.070 vs 0.442 ± 0.062 PU, P=0.234) and displayed a close correlation between the depots (R=0.908, P<0.001, n=30). The higher saturation in DSAT compared with SSAT can be attributed to a higher ratio of saturated to monounsaturated FAs. These results should be taken into account when determining the FA composition of SAT. PMID:22641063

  19. Delivery of human mesenchymal adipose-derived stem cells restores multiple urological dysfunctions in a rat model mimicking radical prostatectomy damages through tissue-specific paracrine mechanisms.

    PubMed

    Yiou, René; Mahrouf-Yorgov, Meriem; Trébeau, Céline; Zanaty, Marc; Lecointe, Cécile; Souktani, Richard; Zadigue, Patricia; Figeac, Florence; Rodriguez, Anne-Marie

    2016-02-01

    Urinary incontinence (UI) and erectile dysfunction (ED) are the most common functional urological disorders and the main sequels of radical prostatectomy (RP) for prostate cancer. Mesenchymal stem cell (MSC) therapy holds promise for repairing tissue damage due to RP. Because animal studies accurately replicating post-RP clinical UI and ED are lacking, little is known about the mechanisms underlying the urological benefits of MSC in this setting. To determine whether and by which mechanisms MSC can repair damages to both striated urethral sphincter (SUS) and penis in the same animal, we delivered human multipotent adipose stem cells, used as MSC model, in an immunocompetent rat model replicating post-RP UI and ED. In this model, we demonstrated by using noninvasive methods in the same animal from day 7 to day 90 post-RP injury that MSC administration into both the SUS and the penis significantly improved urinary continence and erectile function. The regenerative effects of MSC therapy were not due to transdifferentiation and robust engraftment at injection sites. Rather, our results suggest that MSC benefits in both target organs may involve a paracrine process with not only soluble factor release by the MSC but also activation of the recipient's secretome. These two effects of MSC varied across target tissues and damaged-cell types. In conclusion, our work provides new insights into the regenerative properties of MSC and supports the ability of MSC from a single source to repair multiple types of damage, such as those seen after RP, in the same individual. Stem Cells 2016;34:392-404. PMID:26439006

  20. Segmentation and quantification of adipose tissue by magnetic resonance imaging.

    PubMed

    Hu, Houchun Harry; Chen, Jun; Shen, Wei

    2016-04-01

    In this brief review, introductory concepts in animal and human adipose tissue segmentation using proton magnetic resonance imaging (MRI) and computed tomography are summarized in the context of obesity research. Adipose tissue segmentation and quantification using spin relaxation-based (e.g., T1-weighted, T2-weighted), relaxometry-based (e.g., T1-, T2-, T2*-mapping), chemical-shift selective, and chemical-shift encoded water-fat MRI pulse sequences are briefly discussed. The continuing interest to classify subcutaneous and visceral adipose tissue depots into smaller sub-depot compartments is mentioned. The use of a single slice, a stack of slices across a limited anatomical region, or a whole body protocol is considered. Common image post-processing steps and emerging atlas-based automated segmentation techniques are noted. Finally, the article identifies some directions of future research, including a discussion on the growing topic of brown adipose tissue and related segmentation considerations. PMID:26336839

  1. More insights into a human adipose tissue GPAT activity assay

    PubMed Central

    Morgan-Bathke, Maria; Chen, Liang; Oberschneider, Elisabeth; Harteneck, Debra; Jensen, Michael D

    2016-01-01

    ABSTRACT Adipose tissue fatty acid storage varies according to sex, adipose tissue depot and degree of fat gain. However, the mechanism(s) for these variations is not completely understood. We recently published findings based on the glycerol 3-phosphate acyltransferase (GPAT) enzyme activity assay we optimized for use with human adipose tissue. These findings include a decrease in total GPAT and GPAT1 as a function of adipocyte size in both omental and subcutaneous adipose tissue and a strong, positive correlations between ACS, GPAT, and DGAT activities for both sexes and depots and between these storage factors and palmitate storage rates into TAG. The aim of this commentary is to expand upon the data from our recent publication. We describe here additional details on the optimization of the GPAT enzyme activity assay, a correlation between DGAT and percentage palmitate in the diacylglycerol fraction, and sex differences in fatty acid storage factors and storage rates into TAG at high palmitate concentrations. PMID:27144101

  2. Metabolic syndrome pathophysiology: the role of adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several physiopathological explanations for the metabolic syndrome have been proposed involving insulin resistance, chronic inflammation and ectopic fat accumulation following adipose tissue saturation. However, current concepts create several paradoxes, including limited cardiovascular risk reducti...

  3. Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.

    PubMed

    Schafer, Marissa J; White, Thomas A; Evans, Glenda; Tonne, Jason M; Verzosa, Grace C; Stout, Michael B; Mazula, Daniel L; Palmer, Allyson K; Baker, Darren J; Jensen, Michael D; Torbenson, Michael S; Miller, Jordan D; Ikeda, Yasuhiro; Tchkonia, Tamara; van Deursen, Jan M; Kirkland, James L; LeBrasseur, Nathan K

    2016-06-01

    Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16(INK4a) promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span. PMID:26983960

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

    PubMed

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

    2016-04-12

    Obesity-induced inflammation mediated by immune cells in adipose tissue appears to participate in the pathogenesis of insulin resistance. We show that natural killer (NK) cells in adipose tissue play an important role. High-fat diet (HFD) increases NK cell numbers and the production of proinflammatory cytokines, notably TNFα, in epididymal, but not subcutaneous, fat depots. When NK cells were depleted either with neutralizing antibodies or genetic ablation in E4bp4(+/-) mice, obesity-induced insulin resistance improved in parallel with decreases in both adipose tissue macrophage (ATM) numbers, and ATM and adipose tissue inflammation. Conversely, expansion of NK cells following IL-15 administration or reconstitution of NK cells into E4bp4(-/-) mice increased both ATM numbers and adipose tissue inflammation and exacerbated HFD-induced insulin resistance. These results indicate that adipose NK cells control ATMs as an upstream regulator potentially by producing proinflammatory mediators, including TNFα, and thereby contribute to the development of obesity-induced insulin resistance. PMID:27050305

  5. Direct effects of leptin on brown and white adipose tissue.

    PubMed Central

    Siegrist-Kaiser, C A; Pauli, V; Juge-Aubry, C E; Boss, O; Pernin, A; Chin, W W; Cusin, I; Rohner-Jeanrenaud, F; Burger, A G; Zapf, J; Meier, C A

    1997-01-01

    Leptin is thought to exert its actions on energy homeostasis through the long form of the leptin receptor (OB-Rb), which is present in the hypothalamus and in certain peripheral organs, including adipose tissue. In this study, we examined whether leptin has direct effects on the function of brown and white adipose tissue (BAT and WAT, respectively) at the metabolic and molecular levels. The chronic peripheral intravenous administration of leptin in vivo for 4 d resulted in a 1.6-fold increase in the in vivo glucose utilization index of BAT, whereas no significant change was found after intracerebroventricular administration compared with pair-fed control rats, compatible with a direct effect of leptin on BAT. The effect of leptin on WAT fat pads from lean Zucker Fa/ fa rats was assessed ex vivo, where a 9- and 16-fold increase in the rate of lipolysis was observed after 2 h of exposure to 0.1 and 10 nM leptin, respectively. In contrast, no increase in lipolysis was observed in the fat pads from obese fa/fa rats, which harbor an inactivating mutation in the OB-Rb. At the level of gene expression, leptin treatment for 24 h increased malic enzyme and lipoprotein lipase RNA 1.8+/-0.17 and 1.9+/-0.14-fold, respectively, while aP2 mRNA levels were unaltered in primary cultures of brown adipocytes from lean Fa/fa rats. Importantly, however, no significant effect of leptin was observed on these genes in brown adipocytes from obese fa/fa animals. The presence of OB-Rb receptors in adipose tissue was substantiated by the detection of its transcripts by RT-PCR, and leptin treatment in vivo and in vitro activated the specific STATs implicated in the signaling pathway of the OB-Rb. Taken together, our data strongly suggest that leptin has direct effects on BAT and WAT, resulting in the activation of the Jak/STAT pathway and the increased expression of certain target genes, which may partially account for the observed increase in glucose utilization and lipolysis in leptin

  6. Profiling of chicken adipose tissue gene expression by genome array

    PubMed Central

    Wang, Hong-Bao; Li, Hui; Wang, Qi-Gui; Zhang, Xin-Yu; Wang, Shou-Zhi; Wang, Yu-Xiang; Wang, Xiu-Ping

    2007-01-01

    Background Excessive accumulation of lipids in the adipose tissue is a major problem in the present-day broiler industry. However, few studies have analyzed the expression of adipose tissue genes that are involved in pathways and mechanisms leading to adiposity in chickens. Gene expression profiling of chicken adipose tissue could provide key information about the ontogenesis of fatness and clarify the molecular mechanisms underlying obesity. In this study, Chicken Genome Arrays were used to construct an adipose tissue gene expression profile of 7-week-old broilers, and to screen adipose tissue genes that are differentially expressed in lean and fat lines divergently selected over eight generations for high and low abdominal fat weight. Results The gene expression profiles detected 13,234–16,858 probe sets in chicken adipose tissue at 7 weeks, and genes involved in lipid metabolism and immunity such as fatty acid binding protein (FABP), thyroid hormone-responsive protein (Spot14), lipoprotein lipase(LPL), insulin-like growth factor binding protein 7(IGFBP7) and major histocompatibility complex (MHC), were highly expressed. In contrast, some genes related to lipogenesis, such as leptin receptor, sterol regulatory element binding proteins1 (SREBP1), apolipoprotein B(ApoB) and insulin-like growth factor 2(IGF2), were not detected. Moreover, 230 genes that were differentially expressed between the two lines were screened out; these were mainly involved in lipid metabolism, signal transduction, energy metabolism, tumorigenesis and immunity. Subsequently, real-time RT-PCR was performed to validate fifteen differentially expressed genes screened out by the microarray approach and high consistency was observed between the two methods. Conclusion Our results establish the groundwork for further studies of the basic genetic control of growth and development of chicken adipose tissue, and will be beneficial in clarifying the molecular mechanism of obesity in chickens. PMID

  7. Pericoronary adipose tissue: a novel therapeutic target in obesity-related coronary atherosclerosis.

    PubMed

    Mazurek, Tomasz; Opolski, Grzegorz

    2015-01-01

    Inflammation plays a crucial role in the development and destabilization of atherosclerotic plaques in coronary vessels. Adipose tissue is considered to act in paracrine manner, which modulates a number of physiological and pathophysiological processes. Perivascular adipose tissue has developed specific properties that distinguish it from the fat in other locations. Interestingly, its activity depends on several metabolic conditions associated with insulin resistance and weight gain. Particularly in obesity perivascular fat seems to change its character from a protective to a detrimental one. The present review analyzes literature in terms of the pathophysiology of atherosclerosis, with particular emphasis on inflammatory processes. Additionally, the authors summarize data about confirmed paracrine activity of visceral adipose tissue and especially about pericoronary fat influence on the vascular wall. The contribution of adiponectin, leptin and resistin is addressed. Experimental and clinical data supporting the thesis of outside-to-inside signaling in the pericoronary milieu are further outlined. Clinical implications of epicardial and pericoronary adipose tissue activity are also evaluated. The role of pericoronary adipose tissue in obesity-related atherosclerosis is highlighted. In conclusion, the authors discuss potential therapeutical implications of these novel phenomena, including adipokine imbalance in pericoronary adipose tissue in the setting of obesity, the influence of lifestyle and diet modification, pharmaceutical interventions and the growing role of microRNAs in adipogenesis, insulin resistance and obesity. Key teaching points: • adipose tissue as a source of inflammatory mediators • changes in the vascular wall as a result of outside-to-inside signaling • anatomy, physiology, and clinical implications of epicardial and pericoronary adipose tissue activity • adipokines and their role in obesity-related atherosclerosis • therapeutic

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

    PubMed Central

    Salas, Anna; Noé, Véronique; Ciudad, Carlos J; Romero, M Mar; Remesar, Xavier; Esteve, Montserrat

    2007-01-01

    Background Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Results Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFα) values showed overexpression (198%). Conclusion Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism. PMID:17725831

  9. Adipose-derived stem cell differentiation as a basic tool for vascularized adipose tissue engineering.

    PubMed

    Volz, Ann-Cathrin; Huber, Birgit; Kluger, Petra J

    2016-01-01

    The development of in vitro adipose tissue constructs is highly desired to cope with the increased demand for substitutes to replace damaged soft tissue after high graded burns, deformities or tumor removal. To achieve clinically relevant dimensions, vascularization of soft tissue constructs becomes inevitable but still poses a challenge. Adipose-derived stem cells (ASCs) represent a promising cell source for the setup of vascularized fatty tissue constructs as they can be differentiated into adipocytes and endothelial cells in vitro and are thereby available in sufficiently high cell numbers. This review summarizes the currently known characteristics of ASCs and achievements in adipogenic and endothelial differentiation in vitro. Further, the interdependency of adipogenesis and angiogenesis based on the crosstalk of endothelial cells, stem cells and adipocytes is addressed at the molecular level. Finally, achievements and limitations of current co-culture conditions for the construction of vascularized adipose tissue are evaluated. PMID:26976717

  10. Visceral adipose tissue modulates mammalian longevity.

    PubMed

    Muzumdar, Radhika; Allison, David B; Huffman, Derek M; Ma, Xiaohui; Atzmon, Gil; Einstein, Francine H; Fishman, Sigal; Poduval, Aruna D; McVei, Theresa; Keith, Scott W; Barzilai, Nir

    2008-06-01

    Caloric restriction (CR) can delay many age-related diseases and extend lifespan, while an increase in adiposity is associated with enhanced disease risk and accelerated aging. Among the various fat depots, the accrual of visceral fat (VF) is a common feature of aging, and has been shown to be the most detrimental on metabolic syndrome of aging in humans. We have previously demonstrated that surgical removal of VF in rats improves insulin action; thus, we set out to determine if VF removal affects longevity. We prospectively studied lifespan in three groups of rats: ad libitum-fed (AL-fed), CR (Fed 60% of AL) and a group of AL-fed rats with selective removal of VF at 5 months of age (VF-removed rats). We demonstrate that compared to AL-fed rats, VF-removed rats had a significant increase in mean (p < 0.001) and maximum lifespan (p < 0.04) and significant reduction in the incidence of severe renal disease (p < 0.01). CR rats demonstrated the greatest mean and maximum lifespan (p < 0.001) and the lowest rate of death as compared to AL-fed rats (0.13). Taken together, these observations provide the most direct evidence to date that a reduction in fat mass, specifically VF, may be one of the possible underlying mechanisms of the anti-aging effect of CR. PMID:18363902

  11. Ghrelin receptor regulates adipose tissue inflammation in aging

    PubMed Central

    Buras, Eric D.; Yu, Kaijiang; Wang, Ruitao; Smith, C. Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr−/− mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsr−/− mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsr−/− mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance. PMID:26837433

  12. Perivascular adipose tissue contains functional catecholamines

    PubMed Central

    Ayala-Lopez, Nadia; Martini, Marisa; Jackson, William F; Darios, Emma; Burnett, Robert; Seitz, Bridget; Fink, Gregory D; Watts, Stephanie W

    2014-01-01

    The sympathetic nervous system and its neurotransmitter effectors are undeniably important to blood pressure control. We made the novel discovery that perivascular adipose tissue (PVAT) contains significant concentrations of catecholamines. We hypothesized that PVAT contains sufficient releasable catecholamines to affect vascular function. High-pressure liquid chromatography, isometric contractility, immunohistochemistry, whole animal approaches, and pharmacology were used to test this hypothesis. In normal rat thoracic aorta and superior mesenteric artery, the indirect sympathomimetic tyramine caused a concentration-dependent contraction that was dependent on the presence of PVAT. Tyramine stimulated release of norepinephrine (NA), dopamine (DA) and the tryptamine serotonin (5-hydroxytryptamine [5-HT]) from PVAT isolated from both arteries. In both arteries, tyramine-induced concentration-dependent contraction was rightward-shifted and reduced by the noradrenaline transporter inhibitor nisoxetine (1 μmol/L), the vesicular monoamine transporter inhibitor tetrabenazine (10 μmol/L), and abolished by the α adrenoreceptor antagonist prazosin (100 nmol/L). Inhibitors of the DA and 5-HT transporter did not alter tyramine-induced, PVAT-dependent contraction. Removal of the celiac ganglion as a neuronal source of catecholamines for superior mesenteric artery PVAT did not significantly reduce the maximum or shift the concentration-dependent contraction to tyramine. Electrical field stimulation of the isolated aorta was not affected by the presence of PVAT. These data suggest that PVAT components that are independent of sympathetic nerves can release NA in a tyramine-sensitive manner to result in arterial contraction. Because PVAT is intimately apposed to the artery, this raises the possibility of local control of arterial function by PVAT catecholamines. PMID:24904751

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

    PubMed Central

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

    2013-01-01

    Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT), white adipose (WAT) and liver of mice in response to 24 h cold exposure at 8°C. Expression of 1895 genes were significantly (P<0.05) up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and 134 genes were common between WAT and BAT, WAT and liver, and BAT and liver, respectively. We confirmed using qRT-PCR, the increased expression of a number of characteristic BAT genes during cold exposure. In both BAT and the liver, the most common direction of change in gene expression was suppression (496 genes in BAT and 590 genes in liver). Gene ontology analysis revealed for the first time significant (P<0.05) down regulation in response to cold, of genes involved in oxidoreductase activity, lipid metabolic processes and protease inhibitor activity, in both BAT and liver, but not WAT. The results reveal an unexpected importance of down regulation of cytochrome P450 gene expression and apolipoprotein, in both BAT and liver, but not WAT, in response to cold exposure. Pathway analysis suggests a model in which down regulation of the nuclear transcription factors HNF4α and PPARα in both BAT and liver may orchestrate the down regulation of genes involved in lipoprotein and steroid metabolism as well as Phase I enzymes belonging to the cytochrome P450 group in response to cold stress in mice. We propose that the response to cold stress involves decreased gene expression in a range of cellular processes in order to maximise pathways involved in heat production. PMID:23894377

  14. The metabolic syndrome as a concept of adipose tissue disease.

    PubMed

    Oda, Eiji

    2008-07-01

    The metabolic syndrome is a constellation of interrelated metabolic risk factors that appear to directly promote the development of diabetes and cardiovascular disease. However, in 2005, the American Diabetes Association and the European Association for the Study of Diabetes jointly stated that no existing definition of the metabolic syndrome meets the criteria of a syndrome, and there have been endless debates on the pros and cons of using the concept of this syndrome. The controversy may stem from confusion between the syndrome and obesity. Obesity is an epidemic, essentially contagious disease caused by an environment of excess nutritional energy and reinforced by deeply rooted social norms. The epidemic of obesity should be prevented or controlled by social and political means, similar to the approaches now being taken to combat global warming. The diagnosis of metabolic syndrome is useless for this public purpose. The purpose of establishing criteria for diagnosing metabolic syndrome is to find individuals who are at increased risk of diabetes and cardiovascular disease and who require specific therapy including diet and exercise. The syndrome may be an adipose tissue disease different from obesity; in that case, it would be characterized by inflammation clinically detected through systemic inflammatory markers such as high-sensitivity C-reactive protein and insulin resistance reflecting histological changes in adipose tissue. However, many problems in defining the optimal diagnostic criteria remain unresolved. PMID:18957797

  15. Contribution of adipose tissue to health span and longevity.

    PubMed

    Huffman, Derek M; Barzilai, Nir

    2010-01-01

    Adipose tissue accounts for approximately 20% (lean) to >50% (in extreme obesity) of body mass and is biologically active through its secretion of numerous peptides and release and storage of nutrients such as free fatty acids. Studies in rodents and humans have revealed that body fat distribution, including visceral fat (VF), subcutaneous (SC) fat and ectopic fat are critical for determining the risk posed by obesity. Specific depletion or expansion of the VF depot using genetic or surgical strategies in animal models has proven to have direct effects on metabolic characteristics and disease risk. In humans, there is compelling evidence that abdominal obesity most strongly predicts mortality risk, while in rats, surgical removal of VF improves mean and maximum life span. There is also growing evidence that fat deposition in ectopic depots such as skeletal muscle and liver can cause lipotoxicity and impair insulin action. Conversely, expansion of SC adipose tissue may confer protection from metabolic derangements by serving as a 'metabolic sink' to limit both systemic lipids and the accrual of visceral and ectopic fat. Treatments targeting the prevention of fat accrual in these harmful depots should be considered as a primary target for improving human health span and longevity. PMID:20703052

  16. Exercise Regulation of Marrow Adipose Tissue

    PubMed Central

    Pagnotti, Gabriel M.; Styner, Maya

    2016-01-01

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

  17. Exercise Regulation of Marrow Adipose Tissue.

    PubMed

    Pagnotti, Gabriel M; Styner, Maya

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

    Adipose tissue functions in terms of energy homeostasis as a rheostat for blood triglyceride, regulating its concentration, in response to external stimuli. In addition it acts as a barometer to inform the central nervous system of energy levels which can vary dramatically between meals and according to energy demand. Here a metabolomic approach, combining both Mass Spectrometry and Nuclear Magnetic Resonance spectroscopy, was used to analyse both white and brown adipose tissue in mice with adipocyte-specific deletion of Arntl (also known as Bmal1), a gene encoding a core molecular clock component. The results are consistent with a peripheral circadian clock playing a central role in metabolic regulation of both brown and white adipose tissue in rodents and show that Arntl induced global changes in both tissues which were distinct for the two types. In particular, anterior subcutaneous white adipose tissue (ASWAT) tissue was effected by a reduction in the degree of unsaturation of fatty acids, while brown adipose tissue (BAT) changes were associated with a reduction in chain length. In addition the aqueous fraction of metabolites in BAT were profoundly affected by Arntl disruption, consistent with the dynamic role of this tissue in maintaining body temperature across the day/night cycle and an upregulation in fatty acid oxidation and citric acid cycle activity to generate heat during the day when rats are inactive (increases in 3-hydroxybutyrate and glutamate), and increased synthesis and storage of lipids during the night when rats feed more (increased concentrations of glycerol, choline and glycerophosphocholine). PMID:25907923

  19. Gene expression profiling in adipose tissue from growing broiler chickens

    PubMed Central

    Hausman, Gary J; Barb, C Rick; Fairchild, Brian D; Gamble, John; Lee-Rutherford, Laura

    2014-01-01

    In this study, total RNA was collected from abdominal adipose tissue samples obtained from ten broiler chickens at 3, 4, 5, and 6 weeks of age and prepared for gene microarray analysis with Affymetrix GeneChip Chicken Genome Arrays (Affymetrix) and quantitative real-time PCR analysis. Studies of global gene expression in chicken adipose tissue were initiated since such studies in many animal species show that adipose tissue expresses and secretes many factors that can influence growth and physiology. Microarray results indicated 333 differentially expressed adipose tissue genes between 3 and 6 wk, 265 differentially expressed genes between 4 and 6 wk and 42 differentially expressed genes between 3 and 4 wk. Enrichment scores of Gene Ontology Biological Process categories indicated strong age upregulation of genes involved in the immune system response. In addition to microarray analysis, quantitative real-time PCR analysis was used to confirm the influence of age on the expression of adipose tissue CC chemokine ligands (CCL), toll-like receptor (TLR)-2, lipopolysaccharide-induced TNF factor (LITAF), chemokine (C-C motif) receptor 8 (CCR8), and several other genes. Between 3 and 6 wk of age CCL5, CCL1, and CCR8 expression increased (P = 0.0001) with age. Furthermore, TLR2, CCL19, and LITAF expression increased between 4 and 6 wk of age (P = 0.001). This is the first demonstration of age related changes in CCL, LITAF, and TLR2 gene expression in chicken adipose tissue. Future studies are needed to elucidate the role of these adipose tissue genes in growth and the immune system. PMID:26317054

  20. Enzymatic intracrine regulation of white adipose tissue.

    PubMed

    DiSilvestro, David; Petrosino, Jennifer; Aldoori, Ayat; Melgar-Bermudez, Emiliano; Wells, Alexandra; Ziouzenkova, Ouliana

    2014-07-01

    Abdominal fat formation has become a permanent risk factor for metabolic syndrome and various cancers in one-third of the world's population of obese and even lean patients. Formation of abdominal fat involves additional mechanisms beyond an imbalance in energy intake and expenditure, which explains systemic obesity. In this review, we briefly summarized autonomous regulatory circuits that locally produce hormones from inactive precursors or nutrients for intra-/auto-/paracrine signaling in white adipose depots. Enzymatic pathways activating steroid and thyroid hormones in adipose depots were compared with enzymatic production of retinoic acid from vitamin A. We discussed the role of intracrine circuits in fat-depot functions and strategies to reduce abdominal adiposity through thermogenic adipocytes with interrupted generation of retinoic acid. PMID:25390015

  1. Enzymatic intracrine regulation of white adipose tissue

    PubMed Central

    DiSilvestro, David; Petrosino, Jennifer; Aldoori, Ayat; Melgar-Bermudez, Emiliano; Wells, Alexandra; Ziouzenkova, Ouliana

    2015-01-01

    Abdominal fat formation has become a permanent risk factor for metabolic syndrome and various cancers in one-third of the world's population of obese and even lean patients. Formation of abdominal fat involves additional mechanisms beyond an imbalance in energy intake and expenditure, which explains systemic obesity. In this review, we briefly summarized autonomous regulatory circuits that locally produce hormones from inactive precursors or nutrients for intra-/auto-/paracrine signaling in white adipose depots. Enzymatic pathways activating steroid and thyroid hormones in adipose depots were compared with enzymatic production of retinoic acid from vitamin A. We discussed the role of intracrine circuits in fat-depot functions and strategies to reduce abdominal adiposity through thermogenic adipocytes with interrupted generation of retinoic acid. PMID:25390015

  2. Adipocyte glucocorticoid receptor has a minor contribution in adipose tissue growth.

    PubMed

    Desarzens, Sébastien; Faresse, Nourdine

    2016-07-01

    The glucocorticoids bind and activate both the glucocorticoid receptor (GR) as well as the mineralocorticoid receptor in adipocytes. Despite several studies to determine the function of these two receptors in mediating glucocorticoids effects, their relative contribution in adipose tissue expansion and obesity is unclear. To investigate the effect of GR in adipose tissue function, we generated an adipocyte-specific Gr-knockout mouse model (Gr(ad-ko)). These mice were submitted either to a standard diet or a high-fat high sucrose diet. We found that adipocyte-specific deletion of Gr did not affect body weight gain or adipose tissue formation and distribution. However, the lack of Gr in adipocyte promotes a diet-induced inflammation determined by higher pro-inflammatory genes expression and macrophage infiltration in the fat pads. Surprisingly, the adipose tissue inflammation in Gr(ad-ko) mice was not correlated with insulin resistance or dyslipidemia, but with disturbed glucose tolerance. Our data demonstrate that adipocyte-specific ablation of Gr in vivo may affect the adipose tissue function but not its expansion during a high calorie diet. PMID:27106108

  3. The Effect of Marine Derived n-3 Fatty Acids on Adipose Tissue Metabolism and Function

    PubMed Central

    Todorčević, Marijana; Hodson, Leanne

    2015-01-01

    Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity. PMID:26729182

  4. Chromosome localization analysis of genes strongly expressed in human visceral adipose tissue.

    PubMed

    Yang, Yi-Sheng; Song, Huai-Dong; Shi, Wen-Jing; Hu, Ren-Ming; Han, Ze-Guang; Chen, Jia-Lun

    2002-06-01

    To understand fully the physiologic functions of visceral adipose tissue and to provide a basis for the identification of novel genes related to obesity and insulin resistance, the gene expression profiling of human visceral adipose tissue was established by using cDNA array. The characterization and chromosome localization of 400 expressed sequence tags (ESTs) strongly expressed in visceral adipose tissue were analyzed by searching PubMed, UniGene, the Human Genome Draft Database, and Location Data Base. Two hundred eighty-nine clones were classified into known genes among the 400 ESTs strongly expressed in the tissue. Among them, <20% have been previously reported to be expressed in adipose tissue. The chromosome localization of 389 ESTs strongly expressed in visceral adipose tissue showed that their relative abundance was significantly increased on chromosomes 1, 16, 19, 20, and 22 compared with the expected distribution of the same number of random genes. The intrachromosome distribution of the genes strongly expressed in visceral adipose tissue was concentrated in certain regions, such as 1p36.2-1p36.3, 6p21.3-6p22.1, 19p13.3 and 19q13.1. Among them, the region of 1p36.2-1p36.3 appeared to be specific for visceral adipose tissue. Interestingly, some genes playing an important role in the pathogenesis of insulin signal transduction and adipocyte differentiation, such as tumor necrosis factor-alpha and its receptors; CCAAT/enhancer-binding proteina; and phosphoinositide-3-kinase, regulatory subunit, polypeptide 2 (p85beta), were also localized in the concentrated regions, which may provide clues to identifying novel genes closely related to adipocyte function with potential pathophysiologic implications. PMID:12166625

  5. Galectin-3 inhibition prevents adipose tissue remodelling in obesity.

    PubMed

    Martínez-Martínez, E; Calvier, L; Rossignol, P; Rousseau, E; Fernández-Celis, A; Jurado-López, R; Laville, M; Cachofeiro, V; López-Andrés, N

    2016-06-01

    Extracellular matrix remodelling of the adipose tissue has a pivotal role in the pathophysiology of obesity. Galectin-3 (Gal-3) is increased in obesity and mediates inflammation and fibrosis in the cardiovascular system. However, the effects of Gal-3 on adipose tissue remodelling associated with obesity remain unclear. Male Wistar rats were fed either a high-fat diet (33.5% fat) or a standard diet (3.5% fat) for 6 weeks. Half of the animals of each group were treated with the pharmacological inhibitor of Gal-3, modified citrus pectin (MCP; 100 mg kg(-1) per day) in the drinking water. In adipose tissue, obese animals presented an increase in Gal-3 levels that were accompanied by an increase in pericellular collagen. Obese rats exhibited higher adipose tissue inflammation, as well as enhanced differentiation degree of the adipocytes. Treatment with MCP prevented all the above effects. In mature 3T3-L1 adipocytes, Gal-3 (10(-8 )m) treatment increased fibrosis, inflammatory and differentiation markers. In conclusion, Gal-3 emerges as a potential therapeutic target in adipose tissue remodelling associated with obesity and could have an important role in the development of metabolic alterations associated with obesity. PMID:26853916

  6. Adipose tissue-liver axis in alcoholic liver disease.

    PubMed

    Wang, Zhi-Gang; Dou, Xiao-Bing; Zhou, Zhan-Xiang; Song, Zhen-Yuan

    2016-02-15

    Alcoholic liver disease (ALD) remains an important health problem worldwide. The disease spectrum is featured by early steatosis, steatohepatitis (steatosis with inflammatory cells infiltration and necrosis), with some individuals ultimately progressing to fibrosis/cirrhosis. Although the disease progression is well characterized, no effective therapies are currently available for the treatment in humans. The mechanisms underlying the initiation and progression of ALD are multifactorial and complex. Emerging evidence supports that adipose tissue dysfunction contributes to the pathogenesis of ALD. In the first part of this review, we discuss the mechanisms whereby chronic alcohol exposure contributed to adipose tissue dysfunction, including cell death, inflammation and insulin resistance. It has been long known that aberrant hepatic methionine metabolism is a major metabolic abnormality induced by chronic alcohol exposure and plays an etiological role in the pathogenesis of ALD. The recent studies in our group documented the similar metabolic effect of chronic alcohol drinking on methionine in adipose tissue. In the second part of this review, we also briefly discuss the recent research progress in the field with a focus on how abnormal methionine metabolism in adipose tissue contributes to adipose tissue dysfunction and liver damage. PMID:26909225

  7. Adipose tissue-liver axis in alcoholic liver disease

    PubMed Central

    Wang, Zhi-Gang; Dou, Xiao-Bing; Zhou, Zhan-Xiang; Song, Zhen-Yuan

    2016-01-01

    Alcoholic liver disease (ALD) remains an important health problem worldwide. The disease spectrum is featured by early steatosis, steatohepatitis (steatosis with inflammatory cells infiltration and necrosis), with some individuals ultimately progressing to fibrosis/cirrhosis. Although the disease progression is well characterized, no effective therapies are currently available for the treatment in humans. The mechanisms underlying the initiation and progression of ALD are multifactorial and complex. Emerging evidence supports that adipose tissue dysfunction contributes to the pathogenesis of ALD. In the first part of this review, we discuss the mechanisms whereby chronic alcohol exposure contributed to adipose tissue dysfunction, including cell death, inflammation and insulin resistance. It has been long known that aberrant hepatic methionine metabolism is a major metabolic abnormality induced by chronic alcohol exposure and plays an etiological role in the pathogenesis of ALD. The recent studies in our group documented the similar metabolic effect of chronic alcohol drinking on methionine in adipose tissue. In the second part of this review, we also briefly discuss the recent research progress in the field with a focus on how abnormal methionine metabolism in adipose tissue contributes to adipose tissue dysfunction and liver damage. PMID:26909225

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

    PubMed

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

    2013-10-01

    Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity. PMID:23885012

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

    NASA Astrophysics Data System (ADS)

    Macho, Ladislav; Kvetn̆anský, Richard; Ficková, Mária

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

  10. Feast and famine: Adipose tissue adaptations for healthy aging.

    PubMed

    Lettieri Barbato, Daniele; Aquilano, Katia

    2016-07-01

    Proper adipose tissue function controls energy balance with favourable effects on metabolic health and longevity. The molecular and metabolic asset of adipose tissue quickly and dynamically readapts in response to nutrient fluctuations. Once delivered into cells, nutrients are managed by mitochondria that represent a key bioenergetics node. A persistent nutrient overload generates mitochondrial exhaustion and uncontrolled reactive oxygen species ((mt)ROS) production. In adipocytes, metabolic/molecular reorganization is triggered culminating in the acquirement of a hypertrophic and hypersecretory phenotype that accelerates aging. Conversely, dietary regimens such as caloric restriction or time-controlled fasting endorse mitochondrial functionality and (mt)ROS-mediated signalling, thus promoting geroprotection. In this perspective view, we argued some important molecular and metabolic aspects related to adipocyte response to nutrient stress. Finally we delineated hypothetical routes by which molecularly and metabolically readapted adipose tissue promotes healthy aging. PMID:27223996

  11. In vivo Analysis of White Adipose Tissue in Zebrafish

    PubMed Central

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

    2016-01-01

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

  12. Recent Advances in Proteomic Studies of Adipose Tissues and Adipocytes

    PubMed Central

    Kim, Eun Young; Kim, Won Kon; Oh, Kyoung-Jin; Han, Baek Soo; Lee, Sang Chul; Bae, Kwang-Hee

    2015-01-01

    Obesity is a chronic disease that is associated with significantly increased levels of risk of a number of metabolic disorders. Despite these enhanced health risks, the worldwide prevalence of obesity has increased dramatically over the past few decades. Obesity is caused by the accumulation of an abnormal amount of body fat in adipose tissue, which is composed mostly of adipocytes. Thus, a deeper understanding of the regulation mechanism of adipose tissue and/or adipocytes can provide a clue for overcoming obesity-related metabolic diseases. In this review, we describe recent advances in the study of adipose tissue and/or adipocytes, focusing on proteomic approaches. In addition, we suggest future research directions for proteomic studies which may lead to novel treatments of obesity and obesity-related diseases. PMID:25734986

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

    PubMed Central

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

    2013-01-01

    Adipose tissues are closely connected with the immune system. It has been suggested that metabolic syndromes such as type 2 diabetes, arteriosclerosis and liver steatosis can be attributed to adipose tissue inflammation characterized by macrophage infiltration. To understand a physiological and pathological role of natural killer T (NKT) cells on inflammation in adipose tissue, we characterized a subset of NKT cells in abdominal and subcutaneous adipose tissues in C57BL/6J mice fed normal or high-fat diets. NKT cells comprised a larger portion of lymphocytes in adipose tissues compared with the spleen and peripheral blood, with epididymal adipose tissue having the highest number of NKT cells. Furthermore, some NKT cells in adipose tissues expressed higher levels of CD69 and intracellular interferon-γ, whereas the Vβ repertoires of NKT cells in adipose tissues were similar to other cells. In obese mice fed a high-fat diet, adipose tissue inflammation had little effect on the Vβ repertoire of NKT cells in epididymal adipose tissues. We speculate that the NKT cells in adipose tissues may form an equivalent subset in other tissues and that these subsets are likely to participate in adipose tissue inflammation. Additionally, the high expression level of CD69 and intracellular IFN-γ raises the possibility that NKT cells in adipose tissue may be stimulated by some physiological mechanism. PMID:24172196

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

    PubMed

    Yamada, Tomoya; Higuchi, Mikito; Nakanishi, Naoto

    2015-08-01

    Adipose tissue growth is associated with preadipocyte proliferation and differentiation. Telomere length is a biological marker for cell proliferation. Preadipocyte factor-1 (pref-1) is specifically expressed in preadipocytes and acts as a molecular gatekeeper of adipogenesis. In the present study, we investigated the fat depot-specific differences in telomere length and pref-1 gene expression in various anatomical sites (subcutaneous, intramuscular and visceral) of fattening Wagyu cattle. Visceral adipose tissue expressed higher pref-1 mRNA than did subcutaneous and intramuscular adipose tissues. The telomere length in visceral adipose tissue tended to be longer than that of subcutaneous and intramuscular adipose tissues. The telomere length of adipose tissue was not associated with adipocyte size from three anatomical sites. No significant correlation was found between the pref-1 mRNA level and the subcutaneous adipocyte size. In contrast, the pref-1 mRNA level was negatively correlated with the intramuscular and visceral adipocyte size. These results suggest that anatomical sites of adipose tissue affect the telomere length and expression pattern of the pref-1 gene in a fat depot-specific manner. PMID:26067555

  15. Elevated Endoplasmic Reticulum Stress Response Contributes to Adipose Tissue Inflammation in Aging.

    PubMed

    Ghosh, Amiya Kumar; Garg, Sanjay Kumar; Mau, Theresa; O'Brien, Martin; Liu, Jianhua; Yung, Raymond

    2015-11-01

    Adipose tissue inflammation has been linked to age-related metabolic diseases. However, the underlying mechanisms are poorly understood. Adipose tissue inflammation and insulin resistance in diet associated obesity has been correlated with aberrant endoplasmic reticulum (ER) stress. This study was undertaken to test our hypothesis that increased ER stress response contributes to age-associated adipose tissue inflammation. We found elevated ER stress response in adipose tissue of old (18-20 months) compared to young (4-6 months) mice. Elevated ER stress markers BIP (GRP78), CHOP, cleaved-ATF-6, phospho-IRE1α, and XBP-1 were observed in old compared to young adipose tissue stromal cells. Additionally, old adipose tissue stromal cells were more sensitive to an ER stress inducer, thapsigargin. Similar experiments with adipose tissue macrophages showed elevated Chop and Bip expression in old adipose tissue macrophages when induced with thapsigargin. Treatment of chemical chaperone 4-phenyle-butyric acid alleviated ER stress in adipose tissue stromal cells and adipose tissue macrophages and attenuated the production of IL-6 and MCP-1 by adipose tissue stromal cells, and TNF-α by adipose tissue macrophages from both young and old mice. Finally, old mice fed with 4-phenyle-butyric acid have reduced expression of ER stress and inflammatory cytokine genes. Our data suggests that an exaggerated ER stress response in aging adipose tissue contributes to age-associated inflammation that can be mitigated by treatment with chemical chaperones. PMID:25324219

  16. Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet-induced obesity rats.

    PubMed

    Torres-Villalobos, Gonzalo; Hamdan-Pérez, Nashla; Díaz-Villaseñor, Andrea; Tovar, Armando R; Torre-Villalvazo, Ivan; Ordaz-Nava, Guillermo; Morán-Ramos, Sofía; Noriega, Lilia G; Martínez-Benítez, Braulio; López-Garibay, Alejandro; Torres-Landa, Samuel; Ceballos-Cantú, Juan C; Tovar-Palacio, Claudia; Figueroa-Juárez, Elizabeth; Hiriart, Marcia; Medina-Santillán, Roberto; Castillo-Hernández, Carmen; Torres, Nimbe

    2016-09-01

    Long-term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet-induced obesity (DIO) rat models: one using a high-fat diet (HFD) and the other using a high-carbohydrate diet (HCHD). Autologous SAT transplant reduced hypertrophic adipocytes, improved insulin sensitivity, reduced hepatic lipid content, and fasting serum-free fatty acids (FFAs) concentrations in the two DIO models. In addition, the reductions in FFAs and glycerol were accompanied by a greater reduction in lipolysis, assessed via the phosphorylation status of HSL, in the transplanted adipose tissue localized in the omentum compared with that localized in the retroperitoneal compartment. Therefore, the improvement in hepatic lipid content after autologous SAT transplant may be partially attributed to a reduction in lipolysis in the transplanted adipose tissue in the omentum due to the direct drainage of FFAs into the liver. The HCHD resulted in elevated fasting and postprandial serum insulin levels, which were dramatically reduced by the autologous SAT transplant. In conclusion, the specific intraabdominal localization of the autologous SAT transplant improved the carbohydrate and lipid metabolism of adipose tissue in obese rats and selectively corrected the metabolic parameters that are dependent on the type of diet used to generate the DIO model. PMID:27582062

  17. Persistent organic pollutants meet adipose tissue hypoxia: does cross-talk contribute to inflammation during obesity?

    PubMed

    Myre, M; Imbeault, P

    2014-01-01

    Lipophilic persistent organic pollutants (POPs) accumulate in lipid-rich tissues such as human adipose tissue. This is particularly problematic in individuals with excess adiposity, a physiological state that may be additionally characterized by local adipose tissue hypoxia. Hypoxic patches occur when oxygen diffusion is insufficient to reach all hypertrophic adipocytes. POPs and hypoxia independently contribute to the development of adipose tissue-specific and systemic inflammation often associated with obesity. Inflammation is induced by increased proinflammatory mediators such as tumour necrosis factor-alpha, interleukin-6, and monocyte chemotactic protein-1, as well as reduced adiponectin release, an anti-inflammatory and insulin-sensitizing adipokine. The aryl hydrocarbon receptor (AhR) mediates the cellular response to some pollutants, while hypoxia responses occur through the oxygen-sensitive transcription factor hypoxia-inducible factor (HIF)-1. There is some overlap between the two signalling pathways since both require a common subunit called the AhR nuclear translocator. As such, it is unclear how adipocytes respond to simultaneous POP and hypoxia exposure. This brief review explores the independent contribution of POPs and adipose tissue hypoxia as factors underlying the inflammatory response from adipocytes during obesity. It also highlights that the combined effect of POPs and hypoxia through the AhR and HIF-1 signalling pathways remains to be tested. PMID:23998203

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

    SciTech Connect

    Bai, Xiaowen; Alt, Eckhard

    2010-10-22

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

  19. Simple and longstanding adipose tissue engineering in rabbits.

    PubMed

    Tsuji, Wakako; Inamoto, Takashi; Ito, Ran; Morimoto, Naoki; Tabata, Yasuhiko; Toi, Masakazu

    2013-03-01

    Adipose tissue engineering for breast reconstruction can be performed for patients who have undergone breast surgery. We have previously confirmed adipogenesis in mice implanted with type I collagen sponge with controlled release of fibroblast growth factor 2 (FGF2) and human adipose tissue-derived stem cells. However, in order to use this approach to treat breast cancer patients, a large amount of adipose tissue is needed, and FGF2 is not readily available. Thus, we aimed to regenerate large amounts of adipose tissue without FGF2 for a long period. Under general anesthesia, cages made of polypropylene mesh were implanted into the rabbits' bilateral fat pads. Each cage was 10 mm in radius and 10 mm in height. Minced type I collagen sponge was injected as a scaffold into the cage. Regenerated tissue in the cage was examined with ultrasonography, and the cages were harvested 3, 6, and 12 months after the implantation. Ultrasonography revealed a gradually increasing homogeneous high-echo area in the cage. Histology of the specimen was assessed with hematoxylin and eosin staining. The percentages of regenerated adipose tissue area were 76.2 ± 13.0 and 92.8 ± 6.6 % at 6 and 12 months after the implantation, respectively. Our results showed de novo adipogenesis 12 months after the implantation of only type I collagen sponge inside the space. Ultrasonography is a noninvasive and useful method of assessing the growth of the tissue inside the cage. This simple method could be a promising clinical modality in breast reconstruction. PMID:23114565

  20. Bone marrow adipose tissue: formation, function and regulation.

    PubMed

    Suchacki, Karla J; Cawthorn, William P; Rosen, Clifford J

    2016-06-01

    The human body requires an uninterrupted supply of energy to maintain metabolic homeostasis and energy balance. To sustain energy balance, excess consumed calories are stored as glycogen, triglycerides and protein, allowing the body to continue to function in states of starvation and increased energy expenditure. Adipose tissue provides the largest natural store of excess calories as triglycerides and plays an important role as an endocrine organ in energy homeostasis and beyond. This short review is intended to detail the current knowledge of the formation and role of bone marrow adipose tissue (MAT), a largely ignored adipose depot, focussing on the role of MAT as an endocrine organ and highlighting the pharmacological agents that regulate MAT. PMID:27022859

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. Inhibin betaB expression in murine adipose tissue and its regulation by leptin, insulin and dexamethasone.

    PubMed

    Hoggard, N; Cruickshank, M; Moar, K M; Barrett, P; Bashir, S; Miller, J D B

    2009-10-01

    Inhibin betaB (INHBB; coding for the activin betaB subunit) has previously been identified in both human and rodent adipose tissue and using Taqman real-time PCR with specific primers we confirm the expression of INHBB mRNA in rodent adipose tissue. Expression of INHBB in murine epididymal adipose tissue was higher than in any of the other tissues studied and appears to be regulated by changes in energy balance and leptin. It was increased fourfold in the epididymal fat depot of ob/ob mice compared with the same fat depot in lean mice. The i.p. administration of leptin in obese ob/ob mice decreases the expression of INHBB. In human adipose tissue, INHBB is reduced by weight loss. In keeping with this, we demonstrate that INHBB expression in murine adipose tissue is decreased in fasting and increased upon refeeding. We show that INHBB is expressed in both the mature adipocyte and the stromal vascular fraction of adipose tissue. INHBB increases with the differentiation of pre-adipocytes into mature adipocytes in the 3T3-L1 cell line. In differentiated 3T3-L1 adipocytes, where receptors to activin have been previously reported, insulin increases the expression of INHBB, while dexamethasone decreases the expression of INHBB when compared with untreated control cells. Taken together, these results suggest that the regulation of INHBB expression in adipose tissue may play a physiological role in energy balance or the insulin insensitivity associated with obesity. PMID:19491194

  4. Functions of AMP-activated protein kinase in adipose tissue

    PubMed Central

    Daval, Marie; Foufelle, Fabienne; Ferré, Pascal

    2006-01-01

    AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Its functions have been extensively studied in muscles and liver. AMPK stimulates pathways which increase energy production (glucose transport, fatty acid oxidation) and switches off pathways which consume energy (lipogenesis, protein synthesis, gluconeogenesis). This has led to the concept that AMPK has an interesting pharmaceutical potential in situations of insulin resistance and it is indeed the target of existing drugs and hormones which improve insulin sensitivity. Adipose tissue is a key player in energy metabolism through the release of substrates and hormones involved in metabolism and insulin sensitivity. Activation of AMPK in adipose tissue can be achieved through situations such as fasting and exercise. Leptin and adiponectin as well as hypoglycaemic drugs are activators of adipose tissue AMPK. This activation probably involves changes in the AMP/ATP ratio and the upstream kinase LKB1. When activated, AMPK limits fatty acid efflux from adipocytes and favours local fatty acid oxidation. Since fatty acids have a key role in insulin resistance, especially in muscles, activating AMPK in adipose tissue might be found to be beneficial in insulin-resistant states, particularly as AMPK activation also reduces cytokine secretion in adipocytes. PMID:16709632

  5. Colonic Macrophages "Remote Control" Adipose Tissue Inflammation and Insulin Resistance.

    PubMed

    Biswas, Subhra K; Bonecchi, Raffaella

    2016-08-01

    The early events linking diet-induced adipose tissue inflammation and insulin resistance remain poorly understood. In this issue of Cell Metabolism, Kawano et al. (2016) show that infiltration of colonic pro-inflammatory macrophages orchestrated by the intestinal CCL2/CCR2 axis kick-starts this process during high-fat-diet feeding. PMID:27508866

  6. Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

    PubMed

    Tsoli, Maria; Swarbrick, Michael M; Robertson, Graham R

    2016-06-01

    Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL. Studies into how these lipases contribute to fat loss in cancer cachexia have revealed the prominent role for ATGL in initiating lipolysis during adipose tissue atrophy, together with links between tumour-derived factors and the signalling pathways that control lipid flux within fat cells. The recent findings of increased thermogenesis in brown fat during cancer cachexia indicate that metabolically active adipose tissue contributes to the imbalance in energy homeostasis involved in catabolic wasting. Such energetically futile use of fatty acids liberated from adipose tissue to generate heat represents a maladaptive response in conjunction with anorexia experienced by cancer patients. As IL-6 release by tumours provokes lipolysis and activates the thermogenic programme in brown fat, this review explores the overlap in dysregulated metabolic processes due to inflammatory mediators in cancer cachexia and other disease states characterised by elevated cytokines such as obesity and diabetes. PMID:26529279

  7. Adipocyte Death, Adipose Tissue Remodeling and Obesity Complications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the role of adipocyte death in obesity-induced adipose tissue (AT) inflammation and obesity complications. Male C57BL/6 mice were fed a high fat diet for 20 weeks to induce obesity. Every four weeks, insulin resistance (IR) was assessed by intraperitoneal...

  8. Matrix-Assisted Transplantation of Functional Beige Adipose Tissue.

    PubMed

    Tharp, Kevin M; Jha, Amit K; Kraiczy, Judith; Yesian, Alexandra; Karateev, Grigory; Sinisi, Riccardo; Dubikovskaya, Elena A; Healy, Kevin E; Stahl, Andreas

    2015-11-01

    Novel, clinically relevant, approaches to shift energy balance are urgently needed to combat metabolic disorders such as obesity and diabetes. One promising approach has been the expansion of brown adipose tissues that express uncoupling protein (UCP) 1 and thus can uncouple mitochondrial respiration from ATP synthesis. While expansion of UCP1-expressing adipose depots may be achieved in rodents via genetic and pharmacological manipulations or the transplantation of brown fat depots, these methods are difficult to use for human clinical intervention. We present a novel cell scaffold technology optimized to establish functional brown fat-like depots in vivo. We adapted the biophysical properties of hyaluronic acid-based hydrogels to support the differentiation of white adipose tissue-derived multipotent stem cells (ADMSCs) into lipid-accumulating, UCP1-expressing beige adipose tissue. Subcutaneous implantation of ADMSCs within optimized hydrogels resulted in the establishment of distinct UCP1-expressing implants that successfully attracted host vasculature and persisted for several weeks. Importantly, implant recipients demonstrated elevated core body temperature during cold challenges, enhanced respiration rates, improved glucose homeostasis, and reduced weight gain, demonstrating the therapeutic merit of this highly translatable approach. This novel approach is the first truly clinically translatable system to unlock the therapeutic potential of brown fat-like tissue expansion. PMID:26293504

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

    PubMed

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

    2013-05-01

    During postnatal development of mice distinct white adipose tissue depots display a transient appearance of brown-like adipocytes. These brite (brown in white) adipocytes share characteristics with classical brown adipocytes including a multilocular appearance and the expression of the thermogenic protein uncoupling protein 1. In this study, we compared two inbred mouse strains 129S6sv/ev and C57BL6/N known for their different propensity to diet-induced obesity. We observed transient browning in retroperitoneal and inguinal adipose tissue depots of these two strains. From postnatal day 10 to 20 the increase in the abundance of multilocular adipocytes and uncoupling protein 1 expression was higher in 129S6sv/ev than in C57BL6/N pups. The parallel increase in the mass of the two fat depots was attenuated during this browning period. Conversely, epididymal white and interscapular brown adipose tissue displayed a steady increase in mass during the first 30 days of life. In this period, 129S6sv/ev mice developed a significantly higher total body fat mass than C57BL6/N. Thus, while on a local depot level a high number of brite cells is associated with the attenuation of adipose tissue expansion the strain comparison reveals no support for a systemic impact on energy balance. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease. PMID:23376694

  10. Ablation of the Id2 Gene Results in Altered Circadian Feeding Behavior, and Sex-Specific Enhancement of Insulin Sensitivity and Elevated Glucose Uptake in Skeletal Muscle and Brown Adipose Tissue

    PubMed Central

    Mathew, Deepa; Zhou, Peng; Pywell, Cameron M.; van der Veen, Daan R.; Shao, Jinping; Xi, Yang; Bonar, Nicolle A.; Hummel, Alyssa D.; Chapman, Sarah; Leevy, W. Matthew; Duffield, Giles E.

    2013-01-01

    Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our earlier studies have demonstrated a role for ID2 in the input pathway, core clock function and output pathways of the mouse circadian system. We have also reported that Id2 null (Id2−/−) mice are lean with low gonadal white adipose tissue deposits and lower lipid content in the liver. These results coincided with altered or disrupted circadian expression profiles of liver genes including those involved in lipid metabolism. In the present phenotypic study we intended to decipher, on a sex-specific basis, the role of ID2 in glucose metabolism and in the circadian regulation of activity, important components of energy balance. We find that Id2−/− mice exhibited altered daily and circadian rhythms of feeding and locomotor activity; activity profiles extended further into the late night/dark phase of the 24-hr cycle, despite mice showing reduced total locomotor activity. Also, male Id2−/− mice consumed a greater amount of food relative to body mass, and displayed less weight gain. Id2−/− females had smaller adipocytes, suggesting sexual-dimorphic programing of adipogenesis. We observed increased glucose tolerance and insulin sensitivity in male Id2−/− mice, which was exacerbated in older animals. FDG-PET analysis revealed increased glucose uptake by skeletal muscle and brown adipose tissue of male Id2−/− mice, suggesting increased glucose metabolism and thermogenesis in these tissues. Reductions in intramuscular triacylglycerol and diacylglycerol were detected in male Id2−/− mice, highlighting its possible mechanistic role in enhanced insulin sensitivity in these mice. Our findings indicate a role for ID2 as a regulator of glucose and lipid metabolism, and in the circadian control of feeding/locomotor behavior; and contribute to the understanding of the development of obesity and diabetes, particularly in shift

  11. Adipose tissue fatty acid metabolism during pregnancy in swine.

    PubMed

    McNamara, J P; Dehoff, M H; Collier, R J; Bazer, F W

    1985-08-01

    In vitro adipose tissue fatty acid pool size (POOL), fatty acid release (FAR) and esterification (EST) were measured in peritoneal (PFP) and subcutaneous mammary (MFP) fat pads of swine at d 15, 30, 45, 60, 75, 90, 105 and 112 of pregnancy. Plasma free fatty acids (FFA) and triglycerides (TG) were not altered by stage of pregnancy. Basal EST in PFP was generally constant across pregnancy with a peak at d 75. Basal EST in MFP was elevated at d 30, 75 and 112. Esterification in response to norepinephrine stimulus (NE) was lower than basal rates in both fat depots. Basal FAR was constant throughout pregnancy in PFP, but elevated at d 75 and 90 in MFP. Fatty acid release in response to NE was biphasic with peaks at d 30 and in late pregnancy (in MFP, micromolar FAR in response to NE was 69.3% greater on d 75 to 112 than on d 45 to 60). Basal POOL was constant throughout pregnancy in both depots and lower than NE-stimulated POOL. All responses to NE were greater in MFP than in PFP, indicating that adipose tissue surrounding the developing mammary gland had higher metabolic activity and a greater response to NE than peritoneal adipose. Changes in fatty acid metabolism during pregnancy in swine are temporally related to published values for plasma steroids, fetal growth and mammary development. Metabolic adaptations in adipose and mannary epithelial tissue occur in synchrony with changing plasma estrogen concentrations, redirecting energy flow from maternal adipose tissue toward developing mammary and fetal tissue. PMID:4044440

  12. Adipose tissue thickness does not affect the electromechanical delay.

    PubMed

    Stock, Matt S; Thompson, Brennan J

    2016-03-01

    During voluntary contractions in humans, the subcutaneous tissues between surface electrodes and active motor units have been shown to attenuate surface electromyographic (EMG) signal amplitude. The purpose of this investigation was to examine the relationship between adipose tissue thickness and the electromechnical delay (EMD) during maximal voluntary contractions (MVCs). Thirty-two healthy women (mean  ±  SD age  =  21  ±  2 years; mass  =  60.7  ±  11.5 kg; height  =  161.7  ±  7.5 cm; dual-energy x-ray absorptiometry body-fat percentage  =  33.1  ±  9.9%) performed MVCs of the right leg extensors while bipolar surface EMG signals were detected from the vastus lateralis muscle. EMD was calculated as the time (ms) between EMG and torque onsets. B-mode ultrasonography was used to determine adipose tissue thickness over the same location of the vastus lateralis where the EMG sensor was placed. Partial correlation was used to examine the relationship between adipose tissue thickness and EMD while statistically removing the influence of peak torque, EMG amplitude, and vastus lateralis muscle thickness. The partial correlation demonstrated no relationship between adipose tissue thickness and EMD (r  =  -0.010, p  =  0.956). Collectively, these findings demonstrated that adiposity does not influence the estimation of EMD. PMID:26910060

  13. Association between subcutaneous white adipose tissue and serum 25-hydroxyvitamin D in overweight and obese adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Cholecalciferol is known to be deposited in human adipose tissue, but the distribution of 25-hydroxyvitamin D (25(OH)D) in adipose tissue is not known. Objectives: To determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons an...

  14. Flow cytometry on the stromal-vascular fraction of white adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose tissue contains cell types other than adipocytes that may contribute to complications linked to obesity. For example, macrophages have been shown to infiltrate adipose tissue in response to a high-fat diet. Isolation of the stromal-vascular fraction of adipose tissue allows one to use flow c...

  15. The effect of insulin on porcine adipose tissue lipogenesis.

    PubMed

    Mersmann, H J

    1989-01-01

    1. This laboratory and others have not been able to demonstrate consistent insulin stimulation of glucose incorporation into lipid by porcine adipose tissue in vitro. 2. A multiplicity of tissue handling procedures, additions to the incubation medium, and pig size (age) did not allow the expression of a consistent and substantial insulin stimulation. 3. It is suggested that the twofold or greater stimulation of glucose metabolism observed occasionally in this laboratory results from pig genetics, husbandry, or seasonal effects. PMID:2514071

  16. The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our data demonstrate that estrogens, estrogen receptor-alpha (ERalpha), and estrogen receptor-ßeta (ERßeta) regulate adipose tissue distribution, inflammation, fibrosis, and glucose homeostasis, by determining that alphaERKO mice have increased adipose tissue inflammation and fibrosis prior to obesi...

  17. Metabolic remodeling of white adipose tissue in obesity

    PubMed Central

    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

    2014-01-01

    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 V̇o2, V̇co2, 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

  18. Adipose-specific lipoprotein lipase deficiency more profoundly affects brown than white fat biology.

    PubMed

    Garcia-Arcos, Itsaso; Hiyama, Yaeko; Drosatos, Konstantinos; Bharadwaj, Kalyani G; Hu, Yunying; Son, Ni Huiping; O'Byrne, Sheila M; Chang, Chuchun L; Deckelbaum, Richard J; Takahashi, Manabu; Westerterp, Marit; Obunike, Joseph C; Jiang, Hongfeng; Yagyu, Hiroaki; Blaner, William S; Goldberg, Ira J

    2013-05-17

    Adipose fat storage is thought to require uptake of circulating triglyceride (TG)-derived fatty acids via lipoprotein lipase (LpL). To determine how LpL affects the biology of adipose tissue, we created adipose-specific LpL knock-out (ATLO) mice, and we compared them with whole body LpL knock-out mice rescued with muscle LpL expression (MCK/L0) and wild type (WT) mice. ATLO LpL mRNA and activity were reduced, respectively, 75 and 70% in gonadal adipose tissue (GAT), 90 and 80% in subcutaneous tissue, and 84 and 85% in brown adipose tissue (BAT). ATLO mice had increased plasma TG levels associated with reduced chylomicron TG uptake into BAT and lung. ATLO BAT, but not GAT, had altered TG composition. GAT from MCK/L0 was smaller and contained less polyunsaturated fatty acids in TG, although GAT from ATLO was normal unless LpL was overexpressed in muscle. High fat diet feeding led to less adipose in MCK/L0 mice but TG acyl composition in subcutaneous tissue and BAT reverted to that of WT. Therefore, adipocyte LpL in BAT modulates plasma lipoprotein clearance, and the greater metabolic activity of this depot makes its lipid composition more dependent on LpL-mediated uptake. Loss of adipose LpL reduces fat accumulation only if accompanied by greater LpL activity in muscle. These data support the role of LpL as the "gatekeeper" for tissue lipid distribution. PMID:23542081

  19. Angptl4 links α-cell proliferation following glucagon receptor inhibition with adipose tissue triglyceride metabolism

    PubMed Central

    Ben-Zvi, Danny; Barrandon, Ornella; Hadley, Stephanie; Blum, Barak; Peterson, Quinn P.; Melton, Douglas A.

    2015-01-01

    Type 2 diabetes is characterized by a reduction in insulin function and an increase in glucagon activity that together result in hyperglycemia. Glucagon receptor antagonists have been developed as drugs for diabetes; however, they often increase glucagon plasma levels and induce the proliferation of glucagon-secreting α-cells. We find that the secreted protein Angiopoietin-like 4 (Angptl4) is up-regulated via Pparγ activation in white adipose tissue and plasma following an acute treatment with a glucagon receptor antagonist. Induction of adipose angptl4 and Angptl4 supplementation promote α-cell proliferation specifically. Finally, glucagon receptor antagonist improves glycemia in diet-induced obese angptl4 knockout mice without increasing glucagon levels or α-cell proliferation, underscoring the importance of this protein. Overall, we demonstrate that triglyceride metabolism in adipose tissue regulates α-cells in the endocrine pancreas. PMID:26621734

  20. Angiotensin II Stimulates Sympathetic Neurotransmission to Adipose Tissue.

    PubMed

    King, Victoria L; English, Victoria L; Bharadwaj, Kalyani; Cassis, Lisa A

    2013-08-01

    Angiotensin II (AngII) facilitates sympathetic neurotransmission by regulating norepinephrine (NE) synthesis, release and uptake. These effects of AngII contribute to cardiovascular control. Previous studies in our laboratory demonstrated that chronic AngII infusion decreased body weight of rats. We hypothesized that AngII facilitates sympathetic neurotransmission to adipose tissue and may thereby decrease body weight. The effect of chronic AngII infusion on the NE uptake transporter and NE turnover was examined in metabolic (interscapular brown adipose tissue, ISBAT; epididymal fat, EF) and cardiovascular tissues (left ventricle, LV; kidney) of rats. To examine the uptake transporter saturation isotherms were performed using [(3)H]nisoxetine (NIS). At doses that lowered body weight, AngII significantly increased ISBAT [(3)H]NIS binding density. To quantify NE turnover, alpha-methyl-para-tyrosine (AMPT) was injected in saline-infused, AngII-infused, or saline-infused rats that were pair-fed to food intake of AngII-infused rats. AngII significantly increased the rate of NE decline in all tissues compared to saline. The rate of NE decline in EF was increased to a similar extent by AngII and by pair-feeding. In rats administered AngII and propranolol, reductions in food and water intake and body weight were eliminated. These data support the hypothesis that AngII facilitates sympathetic neurotransmission to adipose tissue. Increased sympathetic neurotransmission to adipose tissue following AngII exposure is suggested to contribute to reductions in body weight. PMID:24224084

  1. Vitamin D Regulates Fatty Acid Composition in Subcutaneous Adipose Tissue Through Elovl3.

    PubMed

    Ji, Lijuan; Gupta, Mihir; Feldman, Brian J

    2016-01-01

    Fatty acids (FAs) are a major energy source in the body. White adipose tissue (WAT) is a primary site where FAs are stored as triacylglycerols. Brown adipose tissue also stores and recruits FAs as a carbon source for uncoupled β-oxidation during thermogenesis. The deletion of the vitamin D nuclear hormone receptor (VDR) gene in mice (VDRKO) results in a lean WAT phenotype with increased levels of expression of the brown adipose tissue marker Ucp1 in the WAT. However, the impact of vitamin D/VDR on FA composition in WAT has not been explored in detail. To address this question, we examined the FA composition of sc and visceral white adipose depots of VDRKO mice. We found that the levels of a subset of saturated and monounsaturated FAs of C18-C24 are specifically increased in the sc adipose depot in VDRKO mice. We revealed that a specific elongase enzyme (Elovl3), which has an important role in brown fat biology, is directly regulated by VDR and likely contributes to the altered FA composition in VDRKO mice. We also demonstrate that Elovl3 is regulated by vitamin D in vivo and tissue specifically in the sc WAT depot. We discovered that regulation of Elovl3 expression is mediated by ligand-dependent VDR occupancy of a negative-response element in the promoter proximal region of the Elovl3 gene. These data suggest that vitamin D/VDR tissue specifically modulates FA composition in sc WAT through direct regulation of Elovl3 expression. PMID:26488808

  2. Comparative analysis of the human hepatic and adipose tissue transcriptomes during LPS-induced inflammation leads to the identification of differential biological pathways and candidate biomarkers

    PubMed Central

    2011-01-01

    Background Insulin resistance (IR) is accompanied by chronic low grade systemic inflammation, obesity, and deregulation of total body energy homeostasis. We induced inflammation in adipose and liver tissues in vitro in order to mimic inflammation in vivo with the aim to identify tissue-specific processes implicated in IR and to find biomarkers indicative for tissue-specific IR. Methods Human adipose and liver tissues were cultured in the absence or presence of LPS and DNA Microarray Technology was applied for their transcriptome analysis. Gene Ontology (GO), gene functional analysis, and prediction of genes encoding for secretome were performed using publicly available bioinformatics tools (DAVID, STRING, SecretomeP). The transcriptome data were validated by proteomics analysis of the inflamed adipose tissue secretome. Results LPS treatment significantly affected 667 and 483 genes in adipose and liver tissues respectively. The GO analysis revealed that during inflammation adipose tissue, compared to liver tissue, had more significantly upregulated genes, GO terms, and functional clusters related to inflammation and angiogenesis. The secretome prediction led to identification of 399 and 236 genes in adipose and liver tissue respectively. The secretomes of both tissues shared 66 genes and the remaining genes were the differential candidate biomarkers indicative for inflamed adipose or liver tissue. The transcriptome data of the inflamed adipose tissue secretome showed excellent correlation with the proteomics data. Conclusions The higher number of altered proinflammatory genes, GO processes, and genes encoding for secretome during inflammation in adipose tissue compared to liver tissue, suggests that adipose tissue is the major organ contributing to the development of systemic inflammation observed in IR. The identified tissue-specific functional clusters and biomarkers might be used in a strategy for the development of tissue-targeted treatment of insulin resistance

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

    PubMed Central

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

    2013-01-01

    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-1α. 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

  4. Radioisotopic method for the measurement of lipolysis in small samples of human adipose tissue

    SciTech Connect

    Leibel, R.L.; Hirsch, J.; Berry, E.M.; Gruen, R.K.

    1984-01-01

    To facilitate the study of adrenoreceptor response in small needle biopsy samples of human subcutaneous adipose tissue, we developed a dual radioisotopic technique for measuring lipolysis rate. Aliquots (20-75 mg) of adipose tissue fragments were incubated in a buffered albumin medium containing (/sup 3/H)palmitate and (/sup 14/C)glucose, each of high specific activity. In neutral glycerides synthesized in this system, (/sup 14/C)glucose is incorporated exclusively into the glyceride-glycerol moiety and /sup 3/H appears solely in the esterified fatty acid. Alpha-2 and beta-1 adrenoreceptor activation of tissue incubated in this system does not alter rates of /sup 14/C-labeled glyceride accumulation, but does produce a respective increase or decrease in the specific activity of fatty acids esterified into newly synthesized glycerides. This alteration in esterified fatty acid specific activity is reflected in the ratio of /sup 14/C:/sup 3/H in newly synthesized triglycerides extracted from the incubated adipose tissue. There is a high correlation (r . 0.90) between the /sup 14/C:/sup 3/H ratio in triglycerides and the rate of lipolysis as reflected in glycerol release into the incubation medium. The degree of adrenoreceptor activation by various concentrations of lipolytic and anti-lipolytic substances can be assessed by comparing this ratio in stimulated tissue to that characterizing unstimulated tissue or the incubation medium. This technique permits the study of very small, unweighed tissue biopsy fragments, the only limitation on sensitivity being the specific activity of the medium glucose and palmitate. It is, therefore, useful for serial examinations of adipose tissue adrenoreceptor dose-response characteristics under a variety of clinical circumstances.

  5. Brown adipose tissue development and metabolism in ruminants.

    PubMed

    Smith, S B; Carstens, G E; Randel, R D; Mersmann, H J; Lunt, D K

    2004-03-01

    We conducted several experiments to better understand the relationship between brown adipose tissue (BAT) metabolism and thermogenesis. In Exp. 1, we examined perirenal (brown) and sternum s.c. adipose tissue in 14 Wagyu x Angus neonates infused with norepinephrine (NE). Perirenal adipocytes contained numerous large mitochondria with well-differentiated cristae; sternum s.c. adipocytes contained a few, small mitochondria, with poorly developed cristae. Lipogenesis from acetate was high in BAT but barely detectable in sternum s.c. adipose tissue. In Exp. 2, we compared perirenal and tailhead adipose tissues between NE-infused Angus (n = 6) and Brahman (n = 7) newborn calves. Brahman BAT contained two-to-three times as many total beta-receptors as Angus BAT. The mitochondrial UCP1:28S rRNA ratio was greater in Brahman BAT than in BAT from Angus calves. Lipogenesis from acetate and glucose again was high, but lipogenesis from palmitate was barely detectable. Tail-head s.c. adipose tissue from both breed types contained adipocytes with distinct brown adipocyte morphology. In Exp. 3, three fetuses of each breed type were taken at 96, 48, 24, 14, and 6 d before expected parturition, and at parturition. Lipogenesis from acetate and glucose in vitro decreased 97% during the last 96 d of gestation in both breed types, whereas the UCP1 gene expression tripled during gestation in both breed types. At birth, palmitate esterification was twice as high in Angus than in Brahman BAT and was at least 100-fold higher than in BAT from NE-infused calves from Exp. 2. Uncoupling protein-1 mRNA was readily detectable in tailhead s.c. adipose tissue in all fetal samples. In Exp. 4, male Brahman and Angus calves (n = 5 to 7 per group) were assigned to 1) newborn treatment (15 h of age), 2) 48 h of warm exposure (22 degrees C) starting at 15 h of age, or 3) 48 h of cold exposure (4 degrees C) starting at 15 h of age. Brahman BAT adipocytes shrank with cold exposure, whereas Angus BAT

  6. Identification of intracellular peptides in rat adipose tissue: Insights into insulin resistance.

    PubMed

    Berti, Denise A; Russo, Lilian C; Castro, Leandro M; Cruz, Lilian; Gozzo, Fábio C; Heimann, Joel C; Lima, Fabio B; Oliveira, Ariclécio C; Andreotti, Sandra; Prada, Patrícia O; Heimann, Andrea S; Ferro, Emer S

    2012-08-01

    Intracellular peptides generated by the proteasome and oligopeptidases have been suggested to function in signal transduction and to improve insulin resistance in mice fed a high-caloric diet. The aim of this study was to identify specific intracellular peptides in the adipose tissue of Wistar rats that could be associated with the physiological and therapeutic control of glucose uptake. Using semiquantitative mass spectrometry and LC/MS/MS analyses, we identified ten peptides in the epididymal adipose tissue of the Wistar rats; three of these peptides were present at increased levels in rats that were fed a high-caloric Western diet (WD) compared with rats fed a control diet (CD). The results of affinity chromatography suggested that in the cytoplasm of epididymal adipose tissue from either WD or CD rats, distinctive proteins bind to these peptides. However, despite the observed increase in the WD animals, the evaluated peptides increased insulin-stimulated glucose uptake in 3T3-L1 adipocytes treated with palmitate. Thus, intracellular peptides from the adipose tissue of Wistar rats can bind to specific proteins and facilitate insulin-induced glucose uptake in 3T3-L1 adipocytes. PMID:22740317

  7. Abalation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aging is associated with increased adiposity in white adipose tissues and impaired thermogenesis in brown adipose tissues; both contribute to increased incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating orexigenic hormone that promotes adiposity. In this study, we show ...

  8. Visceral periadventitial adipose tissue regulates arterial tone of mesenteric arteries.

    PubMed

    Verlohren, Stefan; Dubrovska, Galyna; Tsang, Suk-Ying; Essin, Kirill; Luft, Friedrich C; Huang, Yu; Gollasch, Maik

    2004-09-01

    Periadventitial adipose tissue produces vasoactive substances that influence vascular contraction. Earlier studies addressed this issue in aorta, a vessel that does not contribute to peripheral vascular resistance. We tested the hypothesis that periadventitial adipose tissue modulates contraction of smaller arteries more relevant to blood pressure regulation. We studied mesenteric artery rings surrounded by periadventitial adipose tissue from adult male Sprague-Dawley rats. The contractile response to serotonin, phenylephrine, and endothelin I was markedly reduced in intact vessels compared with vessels without periadventitial fat. The contractile response to U46619 or depolarizing high K+-containing solutions (60 mmol/L) was similar in vessels with and without periadventitial fat. The K+ channel opener cromakalim induced relaxation of vessels precontracted by serotonin but not by U46619 or high K+-containing solutions (60 mmol/L), suggesting that K+ channels are involved. The intracellular membrane potential of smooth muscle cells was more hyperpolarized in intact vessels than in vessels without periadventitial fat. Both the anticontractile effect and membrane hyperpolarization of periadventitial fat were abolished by inhibition of delayed-rectifier K+ (K(v)) channels with 4-aminopyridine (2 mmol/L) or 3,4-diaminopyridine (1 mmol/L). Blocking other K+ channels with glibenclamide (3 micromol/L), apamin (1 micromol/L), iberiotoxin (100 nmol/L), tetraethylammonium ions (1 mmol/L), tetrapentylammonium ions (10 micromol/L), or Ba2+ (3 micromol/L) had no effect. Longitudinal removal of half the perivascular tissue reduced the anticontractile effect of fat by almost 50%, whereas removal of the endothelium had no effect. We suggest that visceral periadventitial adipose tissue controls mesenteric arterial tone by inducing vasorelaxation via K(v) channel activation in vascular smooth muscle cells. PMID:15302842

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

    PubMed

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

    2016-01-01

    Adipose tissue lipolysis produces glycerol and nonesterified fatty acids (NEFA) that serve as energy sources during nutrient scarcity. Adipose tissue lipolysis is tightly regulated and excessive lipolysis causes hepatic steatosis, as NEFA released from adipose tissue constitutes a major source of TG in the liver of patients with nonalcoholic fatty liver diseases. Here we show that the liver-enriched transcription factor CREBH is activated by TG accumulation and induces FGF21, which suppresses adipose tissue lipolysis, ameliorating hepatic steatosis. CREBH-deficient mice developed severe hepatic steatosis due to increased adipose tissue lipolysis, when fasted or fed a high-fat low-carbohydrate ketogenic diet. FGF21 production was impaired in CREBH-deficient mice, and adenoviral overexpression of FGF21 suppressed adipose tissue lipolysis and improved hepatic steatosis in these mice. Thus, our results uncover a negative feedback loop in which CREBH regulates NEFA flux from adipose tissue to the liver via FGF21. PMID:27301791

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

    PubMed Central

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

    2016-01-01

    Adipose tissue lipolysis produces glycerol and nonesterified fatty acids (NEFA) that serve as energy sources during nutrient scarcity. Adipose tissue lipolysis is tightly regulated and excessive lipolysis causes hepatic steatosis, as NEFA released from adipose tissue constitutes a major source of TG in the liver of patients with nonalcoholic fatty liver diseases. Here we show that the liver-enriched transcription factor CREBH is activated by TG accumulation and induces FGF21, which suppresses adipose tissue lipolysis, ameliorating hepatic steatosis. CREBH-deficient mice developed severe hepatic steatosis due to increased adipose tissue lipolysis, when fasted or fed a high-fat low-carbohydrate ketogenic diet. FGF21 production was impaired in CREBH-deficient mice, and adenoviral overexpression of FGF21 suppressed adipose tissue lipolysis and improved hepatic steatosis in these mice. Thus, our results uncover a negative feedback loop in which CREBH regulates NEFA flux from adipose tissue to the liver via FGF21. PMID:27301791

  11. Adipogenic differentiation state-specific gene expression as related to bovine carcass adiposity.

    PubMed

    Pickworth, C L; Loerch, S C; Velleman, S G; Pate, J L; Poole, D H; Fluharty, F L

    2011-02-01

    Genetic regulation of the site of fat deposition is not well defined. The objective of this study was to investigate adipogenic differentiation state-specific gene expression in feedlot cattle (>75% Angus; <25% Simmental parentage) of varying adipose accretion patterns. Four groups of 4 steers were selected via ultrasound for the following adipose tissue characteristics: low subcutaneous-low intramuscular (LSQ-LIM), low subcutaneous-high intramuscular (LSQ-HIM), high subcutaneous-low intramuscular (HSQ-LIM), and high subcutaneous-high intramuscular (HSQ-HIM). Adipose tissue from the subcutaneous (SQ) and intramuscular (IM) depots was collected at slaughter. The relative expression of adipogenic genes was evaluated using quantitative PCR. Data were analyzed using the mixed model of SAS, and gene expression data were analyzed using covariate analysis with ribosomal protein L19 as the covariate. No interactions (P > 0.10) were observed between IM and SQ adipose tissue depots for any of the variables measured. Therefore, only the main effects of high and low accretion within a depot and the effects of depot are reported. Steers with LIM had smaller mean diameter IM adipocytes (P < 0.001) than HIM steers. Steers with HSQ had larger mean diameter SQ adipocytes (P < 0.001) than LSQ. However, there were no differences (P > 0.10) in any of the genes measured due to high or low adipose accretion. Preadipogenic delta-like kinase1 mRNA was greater in the IM than the SQ adipose tissue; conversely, differentiating and adipogenic genes, lipoprotein lipase, PPARγ, fatty acid synthetase, and fatty acid binding protein 4 were greater (P < 0.001) in the SQ than the IM depot. Intramuscular adipocytes were smaller than SQ adipocytes and had greater expression of the preadipogenic gene, indicating that more hyperplasia was occurring. Meanwhile, SQ adipose tissue contained much larger (P < 0.001) adipocytes that had a greater expression (P < 0.001) of differentiating and adipogenic

  12. Bovine dedifferentiated adipose tissue (DFAT) cells

    PubMed Central

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

    2013-01-01

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

  13. Adipose tissue development in extramuscular and intramuscular depots in meat animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cellular and metabolic aspects of developing intramuscular adipose tissue and other adipose tissue depots have been studied including examination of the expression of a number of genes. Depot dependent or depot “marker” genes such as stearoyl-CoA desaturase and leptin for subcutaneous adipose ti...

  14. Regulation of G0/G1 switch gene 2 (G0S2) expression in human adipose tissue.

    PubMed

    Skopp, Alexander; May, Marcus; Janke, Juergen; Kielstein, Heike; Wunder, Ruth; Flade-Kuthe, Ricarda; Kuthe, Andreas; Jordan, Jens; Engeli, Stefan

    2016-05-01

    The G0/G1 switch gene 2 (G0S2) protein attenuated adipose triglyceride lipase (ATGL) activity and decreased lipolysis in rodent and human adipocytes. We hypothesized that G0S2 mRNA expression in human adipose tissue is influenced by depot, adipocyte size, body weight and caloric intake. Adipose tissue samples were obtained during abdominal surgery and by needle biopsy before and 3 h after an extended glucose load in lean subjects. G0S2 mRNA was 7× higher expressed in mature human adipocytes compared to the stromavascular fraction. Cell size inversely correlated with G0S2 mRNA expression in both, subcutaneous and omental adipose depots. G0S2 mRNA expression was 75% higher in subcutaneous compared to omental adipose tissue. Obesity was associated with lower G0S2 mRNA expression in subcutaneous adipose tissue. Acute glucose ingestion after an overnight fast did not significantly increase G0S2 expression in subcutaneous adipose tissue. In conclusion, differences in G0S2 expression may explain depot-specific and obesity-associated differences in lipolysis on the molecular level. PMID:26707160

  15. Brown adipose tissue: physiological function and evolutionary significance.

    PubMed

    Oelkrug, R; Polymeropoulos, E T; Jastroch, M

    2015-08-01

    In modern eutherian (placental) mammals, brown adipose tissue (BAT) evolved as a specialized thermogenic organ that is responsible for adaptive non-shivering thermogenesis (NST). For NST, energy metabolism of BAT mitochondria is increased by activation of uncoupling protein 1 (UCP1), which dissipates the proton motive force as heat. Despite the presence of UCP1 orthologues prior to the divergence of teleost fish and mammalian lineages, UCP1's significance for thermogenic adipose tissue emerged at later evolutionary stages. Recent studies on the presence of BAT in metatherians (marsupials) and eutherians of the afrotherian clade provide novel insights into the evolution of adaptive NST in mammals. In particular studies on the 'protoendothermic' lesser hedgehog tenrec (Afrotheria) suggest an evolutionary scenario linking BAT to the onset of eutherian endothermy. Here, we review the physiological function and distribution of BAT in an evolutionary context by focusing on the latest research on phylogenetically distinct species. PMID:25966796

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

    SciTech Connect

    Hirai, Yukio; Tomokuni, Katsumaro )

    1991-08-01

    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.

  17. Mechanisms of perivascular adipose tissue dysfunction in obesity.

    PubMed

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

    2013-01-01

    Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT) was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important number of adipocyte-derived factors with physiological and pathophysiological paracrine vasoactive effects have been identified. PVAT undergoes structural and functional changes in obesity. During early diet-induced obesity, an adaptative overproduction of vasodilator factors occurs in PVAT, probably aimed at protecting vascular function. However, in established obesity, PVAT loses its anticontractile properties by an increase of contractile, oxidative, and inflammatory factors, leading to endothelial dysfunction and vascular disease. The aim of this review is to focus on PVAT dysfunction mechanisms in obesity. PMID:24307898

  18. Mechanisms of Perivascular Adipose Tissue Dysfunction in Obesity

    PubMed Central

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

    2013-01-01

    Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT) was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important number of adipocyte-derived factors with physiological and pathophysiological paracrine vasoactive effects have been identified. PVAT undergoes structural and functional changes in obesity. During early diet-induced obesity, an adaptative overproduction of vasodilator factors occurs in PVAT, probably aimed at protecting vascular function. However, in established obesity, PVAT loses its anticontractile properties by an increase of contractile, oxidative, and inflammatory factors, leading to endothelial dysfunction and vascular disease. The aim of this review is to focus on PVAT dysfunction mechanisms in obesity. PMID:24307898

  19. Thermogenic potential and physiological relevance of human epicardial adipose tissue

    PubMed Central

    Chechi, K; Richard, D

    2015-01-01

    Epicardial adipose tissue is a unique fat depot around the heart that shares a close anatomic proximity and vascular supply with the myocardium and coronary arteries. Its accumulation around the heart, measured using various imaging modalities, has been associated with the onset and progression of coronary artery disease in humans. Epicardial adipose tissue is also the only fat depot around the heart that is known to express uncoupling protein 1 at both mRNA and protein levels in the detectable range. Recent advances have further indicated that human epicardial fat exhibits beige fat-like features. Here we provide an overview of the physiological and pathophysiological relevance of human epicardial fat, and further discuss whether its thermogenic properties can serve as a target for the therapeutic management of coronary heart disease in humans. PMID:27152172

  20. Adipose tissue is a regulated source of interleukin-10.

    PubMed

    Juge-Aubry, Cristiana E; Somm, Emmanuel; Pernin, Agnès; Alizadeh, Navid; Giusti, Vittorio; Dayer, Jean-Michel; Meier, Christoph A

    2005-03-21

    White adipose tissue (WAT) is the source of pro- and anti-inflammatory cytokines and we have recently shown that this tissue is a major source of the anti-inflammatory interleukin (IL)-1 receptor antagonist (IL-1Ra). We now aimed at identifying additional adipose-derived cytokines, which might serve as regulators of IL-1Ra. We demonstrate here for the first time that the antiinflammatory cytokine IL-10 is secreted by human WAT explants and that it is up-regulated by LPS and TNF-alpha in vitro, as well as in obesity in humans (2- and 6-fold increase in subcutaneous and visceral WAT, respectively) and rodents (4-fold increase). PMID:15749027

  1. Fully automated adipose tissue measurement on abdominal CT

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

    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.

  2. Inhibition of Sam68 triggers adipose tissue browning.

    PubMed

    Zhou, Junlan; Cheng, Min; Boriboun, Chan; Ardehali, Mariam M; Jiang, Changfei; Liu, Qinghua; Han, Shuling; Goukassian, David A; Tang, Yao-Liang; Zhao, Ting C; Zhao, Ming; Cai, Lu; Richard, Stéphane; Kishore, Raj; Qin, Gangjian

    2015-06-01

    Obesity is associated with insulin resistance and type 2 diabetes; molecular mechanisms that promote energy expenditure can be utilized for effective therapy. Src-associated in mitosis of 68 kDa (Sam68) is potentially significant, because knockout (KO) of Sam68 leads to markedly reduced adiposity. In the present study, we sought to determine the mechanism by which Sam68 regulates adiposity and energy homeostasis. We first found that Sam68 KO mice have a significantly reduced body weight as compared to controls, and the difference is explained entirely by decreased adiposity. Interestingly, these effects were not mediated by a difference in food intake; rather, they were associated with enhanced physical activity. When they were fed a high-fat diet, Sam68 KO mice gained much less body weight and fat mass than their WT littermates did, and they displayed an improved glucose and insulin tolerance. In Sam68 KO mice, the brown adipose tissue (BAT), inguinal, and epididymal depots were smaller, and their adipocytes were less hypertrophied as compared to their WT littermates. The BAT of Sam68 KO mice exhibited reduced lipid stores and expressed higher levels of Ucp1 and key thermogenic and fatty acid oxidation genes. Similarly, depots of inguinal and epididymal white adipose tissue (WAT) in Sam68 KO mice appeared browner, their multilocular Ucp1-positive cells were much more abundant, and the expression of Ucp1, Cidea, Prdm16, and Ppargc1a genes was greater as compared to WT controls, which suggests that the loss of Sam68 also promotes WAT browning. Furthermore, in all of the fat depots of the Sam68 KO mice, the expression of M2 macrophage markers was up-regulated, and that of M1 markers was down-regulated. Thus, Sam68 plays a crucial role in controlling thermogenesis and may be targeted to combat obesity and associated disorders. PMID:25934704

  3. Inhibition of Sam68 triggers adipose tissue browning

    PubMed Central

    Zhou, Junlan; Cheng, Min; Boriboun, Chan; Ardehali, Mariam Mina; Jiang, Changfei; Liu, Qinghua; Han, Shuling; Goukassian, David A.; Tang, Yao-Liang; Zhao, Ting C.; Zhao, Ming; Cai, Lu; Richard, Stéphane; Kishore, Raj; Qin, Gangjian

    2015-01-01

    Obesity is associated with insulin resistance and type 2 diabetes; molecular mechanisms promoting energy expenditure may be utilized for effective therapy. Src-associated-in-mitosis-of-68kDa (Sam68) is potentially significant because knockout (KO) of Sam68 leads to markedly-reduced adiposity. Here we sought to determine the mechanism by which Sam68 regulates adiposity and energy homeostasis. We firstly found in Sam68-KO mice a significantly-reduced body weight with the difference explained entirely by decreased adiposity. Interestingly, these effects were not mediated by a difference in food intake, but rather associated with enhanced physical activity. When fed high-fat diet, Sam68-KO mice gained much lesser body weight and fat mass as compared to wild-type (WT) littermates and displayed an improved glucose and insulin tolerance. The brown adipose tissue (BAT), inguinal and epididymal depots are smaller and their adipocytes less hypertrophy in Sam68-KO mice than in WT littermates. The BAT of Sam68-KO mice exhibited reduced lipid stores and expressed higher levels of Ucp1 and key thermogenic and fatty-acid-oxidation genes. Similarly, depots of inguinal and epididymal white adipose tissue (WAT) in Sam68-KO mice appeared browner, their multilocular Ucp1-positive cells were much more abundant, and the expression of Ucp1, Cidea, Prdm16 and Ppargc1a genes was greater as compared to WT controls, suggesting that loss of Sam68 also promotes WAT browning. Furthermore, in all fat depots of Sam68-KO mice, the expression of M2 macrophage markers were upregulated and M1 markers downregulated. Thus Sam68 plays a crucial role in the control of thermogenesis and may be targeted to combat obesity and associated disorders. PMID:25934704

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

    PubMed

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

    2015-11-01

    Selection of broiler chickens for growth has led to increased adipose tissue accretion. To investigate the post-hatch development of adipose tissue, the abdominal, clavicular, and subcutaneous adipose tissue depots were collected from broiler chicks at 4 and 14 days post-hatch. As a percent of body weight, abdominal fat increased (P<0.001) with age. At day 4, clavicular and subcutaneous fat depots were heavier (P<0.003) than abdominal fat whereas at day 14, abdominal and clavicular weighed more (P<0.003) than subcutaneous fat. Adipocyte area and diameter were greater in clavicular and subcutaneous than abdominal fat at 4 and 14 days post-hatch (P<0.001). Glycerol-3-phosphate dehydrogenase (G3PDH) activity increased (P<0.001) in all depots from day 4 to 14, and at both ages was greatest in subcutaneous, intermediate in clavicular, and lowest in abdominal fat (P<0.05). In clavicular fat, peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein (CEBP)α, CEBPβ, fatty acid synthase (FASN), fatty acid binding protein 4 (FABP4), lipoprotein lipase (LPL), neuropeptide Y (NPY), and NPY receptor 5 (NPYR5) mRNA increased and NPYR2 mRNA decreased from day 4 to 14 (P<0.001). Thus, there are site-specific differences in broiler chick adipose development, with larger adipocytes and greater G3PDH activity in subcutaneous fat at day 4, more rapid growth of abdominal fat, and clavicular fat intermediate for most traits. Adipose tissue expansion was accompanied by changes in gene expression of adipose-associated factors. PMID:26263851

  5. Mechanoresponsive musculoskeletal tissue differentiation of adipose-derived stem cells.

    PubMed

    Trumbull, Andrew; Subramanian, Gayathri; Yildirim-Ayan, Eda

    2016-01-01

    Musculoskeletal tissues are constantly under mechanical strains within their microenvironment. Yet, little is understood about the effect of in vivo mechanical milieu strains on cell development and function. Thus, this review article outlines the in vivo mechanical environment of bone, muscle, cartilage, tendon, and ligaments, and tabulates the mechanical strain and stress in these tissues during physiological condition, vigorous, and moderate activities. This review article further discusses the principles of mechanical loading platforms to create physiologically relevant mechanical milieu in vitro for musculoskeletal tissue regeneration. A special emphasis is placed on adipose-derived stem cells (ADSCs) as an emerging valuable tool for regenerative musculoskeletal tissue engineering, as they are easily isolated, expanded, and able to differentiate into any musculoskeletal tissue. Finally, it highlights the current state-of-the art in ADSCs-guided musculoskeletal tissue regeneration under mechanical loading. PMID:27103394

  6. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche1

    PubMed Central

    Templeton, Zach S.; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V.; Tamaresis, John S.; Bachmann, Michael H.; Lee, Kitty; Maloney, William J.; Contag, Christopher H.; King, Bonnie L.

    2015-01-01

    BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. PMID:26696367

  7. Sleep deprivation affects inflammatory marker expression in adipose tissue

    PubMed Central

    2010-01-01

    Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation. Methods The study consisted of two groups: a control (C) group and a paradoxical sleep deprivation by 96 h (PSD) group. Ten rats were randomly assigned to either the control group (C) or the PSD. Mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissue, liver and serum were collected following completion of the PSD protocol. Levels of interleukin (IL)-6, interleukin (IL)-10 and tumour necrosis factor (TNF)-α were analysed in MEAT and RPAT, and leptin, adiponectin, glucose, corticosterone and lipid profile levels were analysed in serum. Results IL-6 levels were elevated in RPAT but remained unchanged in MEAT after PSD. IL-10 protein concentration was not altered in either depot, and TNF-α levels decreased in MEAT. Glucose, triglycerides (TG), VLDL and leptin decreased in serum after 96 hours of PSD; adiponectin was not altered and corticosterone was increased. Conclusion PSD decreased fat mass and may modulate the cytokine content in different depots of adipose tissue. The inflammatory response was diminished in both depots of adipose tissue, with increased IL-6 levels in RPAT and decreased TNF-α protein concentrations in MEAT and increased levels of corticosterone in serum. PMID:21034496

  8. Brown adipose tissue transplantation ameliorates polycystic ovary syndrome.

    PubMed

    Yuan, Xiaoxue; Hu, Tao; Zhao, Han; Huang, Yuanyuan; Ye, Rongcai; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Zhou, Huiqiao; Dong, Meng; Zhao, Jun; Wang, Haibin; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu; Chen, Zi-Jiang

    2016-03-01

    Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS. PMID:26903641

  9. Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

    PubMed Central

    Yuan, Xiaoxue; Hu, Tao; Zhao, Han; Huang, Yuanyuan; Ye, Rongcai; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Zhou, Huiqiao; Dong, Meng; Zhao, Jun; Wang, Haibin; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu; Chen, Zi-Jiang

    2016-01-01

    Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS. PMID:26903641

  10. Central neural control of thermoregulation and brown adipose tissue.

    PubMed

    Morrison, Shaun F

    2016-04-01

    Central neural circuits orchestrate the homeostatic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response. This review summarizes the experimental underpinnings of our current model of the CNS pathways controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction controlling heat loss, and shivering and brown adipose tissue for thermogenesis. The activation of these effectors is regulated by parallel but distinct, effector-specific, core efferent pathways within the CNS that share a common peripheral thermal sensory input. Via the lateral parabrachial nucleus, skin thermal afferent input reaches the hypothalamic preoptic area to inhibit warm-sensitive, inhibitory output neurons which control heat production by inhibiting thermogenesis-promoting neurons in the dorsomedial hypothalamus that project to thermogenesis-controlling premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, that descend to provide the excitation of spinal circuits necessary to drive thermogenic thermal effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus sympathetic premotor neurons controlling cutaneous vasoconstriction. The model proposed for central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation and elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation. PMID:26924538

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

    PubMed

    Siegel-Axel, D I; Häring, H U

    2016-03-01

    Type 2 diabetes and its major risk factor, obesity, are an increasing worldwide health problem. The exact mechanisms that link obesity with insulin resistance, type 2 diabetes, hypertension, cardiovascular complications and renal diseases, are still not clarified sufficiently. Adipose tissue in general is an active endocrine and paracrine organ that may influence the development of these disorders. Excessive body fat in general obesity may also cause quantitative and functional alterations of specific adipose tissue compartments. Beside visceral and subcutaneous fat depots which exert systemic effects by the release of adipokines, cytokines and hormones, there are also locally acting fat depots such as peri- and epicardial fat, perivascular fat, and renal sinus fat. Perivascular adipose tissue is in close contact with the adventitia of large, medium and small diameter arteries, possesses unique features differing from other fat depots and may act also independently of general obesity. An increasing number of studies are dealing with the "good" or "bad" characteristics and functions of normally sized and dramatically increased perivascular fat mass in lean or heavily obese individuals. This review describes the origin of perivascular adipose tissue, its different locations, the dual role of a physiological and unphysiological fat mass and its impact on diabetes, cardiovascular and renal diseases. Clinical studies, new imaging methods, as well as basic research in cell culture experiments in the last decade helped to elucidate the various aspects of the unique fat compartment. PMID:26995737

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

    PubMed

    Galván-Portillo, Marcia; Jiménez-Gutiérrez, Carlos; Torres-Sánchez, Luisa; López-Carrillo, Lizbeth

    2002-01-01

    This article analyzes food consumption in relation to levels of DDE (the principal metabolite of DDT) in the adipose tissue of 207 Mexican women residing in States with high and low exposure to DDT. Data on the women's dietary habits and childbearing history were obtained from a personal interview. Adipose tissue DDE levels were measured by gas-liquid chromatography and compared by analysis of variance (ANOVA) and multiple linear regression. Adipose tissue DDE levels increased significantly with age (p = 0.005) and residence in coastal areas (p = 0.002) and non-significantly with the consumption of onion, cauliflower, prickly pear, squash blossoms, sweet corn, broad beans, chili pepper sauce, ham, and fish. Even so, during breastfeeding there was a non-significant reduction in these levels. The findings suggest that certain foods serve as vehicles for DDE residues and confirm that breastfeeding is a mechanism for the elimination of this insecticide, which accumulates over the years in the human body. PMID:11923886

  13. Positive Association Between Adipose Tissue and Bone Stiffness.

    PubMed

    Berg, R M; Wallaschofski, H; Nauck, M; Rettig, R; Markus, M R P; Laqua, R; Friedrich, N; Hannemann, A

    2015-07-01

    Obesity is often considered to have a protective effect against osteoporosis. On the other hand, several recent studies suggest that adipose tissue may have detrimental effects on bone quality. We therefore aimed to investigate the associations between body mass index (BMI), waist circumference (WC), visceral adipose tissue (VAT) or abdominal subcutaneous adipose tissue (SAT), and bone stiffness. The study involved 2685 German adults aged 20-79 years, who participated in either the second follow-up of the population-based Study of Health in Pomerania (SHIP-2) or the baseline examination of the SHIP-Trend cohort. VAT and abdominal SAT were quantified by magnetic resonance imaging. Bone stiffness was assessed by quantitative ultrasound (QUS) at the heel (Achilles InSight, GE Healthcare). The individual risk for osteoporotic fractures was determined based on the QUS-derived stiffness index and classified in low, medium, and high risk. Linear regression models, adjusted for sex, age, physical activity, smoking status, risky alcohol consumption, diabetes, and height (in models with VAT or abdominal SAT as exposure), revealed positive associations between BMI, WC, VAT or abdominal SAT, and the QUS variables broadband-ultrasound attenuation or stiffness index. Moreover, BMI was positively associated with speed of sound. Our study shows that all anthropometric measures including BMI and, WC as well as abdominal fat volume are positively associated with bone stiffness in the general population. As potential predictors of bone stiffness, VAT and abdominal SAT are not superior to easily available measures like BMI or WC. PMID:25929703

  14. Characterization of peripheral circadian clocks in adipose tissues.

    PubMed

    Zvonic, Sanjin; Ptitsyn, Andrey A; Conrad, Steven A; Scott, L Keith; Floyd, Z Elizabeth; Kilroy, Gail; Wu, Xiying; Goh, Brian C; Mynatt, Randall L; Gimble, Jeffrey M

    2006-04-01

    First described in the suprachiasmatic nucleus, circadian clocks have since been found in several peripheral tissues. Although obesity has been associated with dysregulated circadian expression profiles of leptin, adiponectin, and other fat-derived cytokines, there have been no comprehensive analyses of the circadian clock machinery in adipose depots. In this study, we show robust and coordinated expression of circadian oscillator genes (Npas2, Bmal1, Per1-3, and Cry1-2) and clock-controlled downstream genes (Rev-erb alpha, Rev-erb beta, Dbp, E4bp4, Stra13, and Id2) in murine brown, inguinal, and epididymal (BAT, iWAT, and eWAT) adipose tissues. These results correlated with respective gene expression in liver and the serum markers of circadian function. Through Affymetrix microarray analysis, we identified 650 genes that shared circadian expression profiles in BAT, iWAT, and liver. Furthermore, we have demonstrated that temporally restricted feeding causes a coordinated phase-shift in circadian expression of the major oscillator genes and their downstream targets in adipose tissues. The presence of circadian oscillator genes in fat has significant metabolic implications, and their characterization may have potential therapeutic relevance with respect to the pathogenesis and treatment of diseases such as obesity, type 2 diabetes, and the metabolic syndrome. PMID:16567517

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-01-01

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

  17. Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue DCs

    PubMed Central

    Kuan, Emma L.; Ivanov, Stoyan; Bridenbaugh, Eric A.; Victora, Gabriel; Wang, Wei; Childs, Ed W.; Platt, Andrew M.; Jakubzick, Claudia V.; Mason, Robert J.; Gashev, Anatoliy A.; Nussenzweig, Michel; Swartz, Melody A.; Dustin, Michael L.; Zawieja, David C.; Randolph, Gwendalyn J.

    2015-01-01

    Collecting lymphatic vessels (CLVs), surrounded by fat and endowed with contractile muscle and valves, transport lymph from tissues after it is absorbed into lymphatic capillaries. CLVs are not known to participate in immune responses. Here, we observed that the inherent permeability of CLVs allowed broad distribution of lymph components within surrounding fat for uptake by adjacent macrophages and dendritic cells (DCs) that actively interacted with CLVs. Endocytosis of lymph-derived antigens by these cells supported recall T cell responses in the fat and also generated antigen-bearing DCs for emigration into adjacent lymph nodes. Enhanced recruitment of DCs to inflammation-reactive lymph nodes significantly relied on adipose tissue DCs to maintain sufficient numbers of antigen-bearing DCs as the lymph node expanded. Thus, CLVs coordinate inflammation and immunity within adipose depots and foster the generation of an unexpected pool of APCs for antigen transport into the adjacent lymph node. PMID:25917096

  18. Adipose tissue n-3 fatty acids and metabolic syndrome

    PubMed Central

    Cespedes, Elizabeth; Baylin, Ana; Campos, Hannia

    2014-01-01

    Background Evidence regarding the relationship of n-3 fatty acids (FA) to type 2 diabetes (T2D) and metabolic syndrome components (MetS) is inconsistent. Objective To examine associations of adipose tissue n-3 FA with MetS. Design We studied 1611 participants without prior history of diabetes or heart disease who were participants in a population-based case-control study of diet and heart disease (The Costa Rica Heart Study). We calculated prevalence ratios (PR) and 95% confidence intervals (CI) for MetS by quartile of n-3 FA in adipose tissue derived mainly from plants [α-Linolenic acid (ALA)], fish [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], or metabolism [docosapentaenoic acid (DPA), as well as the EPA:ALA ratio, a surrogate marker of delta-6 desaturase activity]. Results N-3 FA levels in adipose tissue were associated with MetS prevalence in opposite directions. The PR (95% CI) for the highest compared to the lowest quartile adjusted for age, sex, BMI, residence, lifestyle, diet and other fatty acids were 0.60 (0.44, 0.81) for ALA, 1.43 (1.12, 1.82) for EPA, 1.63 (1.22, 2.18) for DPA, and 1.47 (1.14, 1.88) for EPA:ALA, all p for trend <0.05. Although these associations were no longer significant (except DPA) after adjustment for BMI, ALA and DPA were associated with lower glucose and higher triglyceride levels, p<0.05 (respectively). Conclusions These results suggest that ALA could exert a modest protective benefit, while EPA and DHA are not implicated in MetS. The positive associations for DPA and MetS could reflect higher delta-6 desaturase activity caused by increased adiposity. PMID:25097001

  19. Effect of diet on microRNA expression in ovine subcutaneous and visceral adipose tissues.

    PubMed

    Meale, S J; Romao, J M; He, M L; Chaves, A V; McAllister, T A; Guan, L L

    2014-08-01

    Knowledge of the molecular mechanisms that regulate ovine adipogenesis is very limited. MicroRNAs (miRNA) have been reported as one of the regulatory mechanisms of adipogenesis. This study aimed to compare the expression of miRNA related to ovine adipogenesis in different adipose depots and to investigate whether their expression is affected by dietary fatty acid composition. We also investigated the role of miRNA in adipogenic gene regulation. Subcutaneous and visceral adipose tissue samples were collected at slaughter from 12 Canadian Arcott lambs fed a barley-based finishing diet where an algae meal (DHA-Gold; Schizochytrium spp.) replaced flax oil and barley grain at 0 or 3% DM (n = 6). Total RNA from each tissue was subjected to quantitative real time (qRT-) PCR analysis to determine the expression of 15 selected miRNA including 11 identified from bovine adipose tissues and 4 conserved between bovine and ovine species. MicroRNAs were differentially expressed according to diet in each tissue depot (miR-142-5p and miR-376d) in visceral and miR-142-5p, miR-92a, and miR-378 in subcutaneous adipose tissue; P ≤ 0.05) and in each tissue depot depending on diet (miR-101, miR-106, miR-136, miR-16b, miR-196a-1, miR-2368*, miR-2454, miR-296, miR-376d, miR-378, and miR-92a in both control and DHA-G diets and miR-478 in control; P ≤ 0.05). Six miRNA were subjected to functional analysis and 3 genes of interest (ACSL1, PPARα, and C/EBPα) were validated by qRT-PCR. Both diet and tissue depot affected expression levels of all 3 genes (P < 0.05). miR-101, miR-106, and miR-136 were negatively correlated with their respective predicted gene targets C/EBPα, PPARα, and ACSL1 in subcutaneous adipose tissue of lambs fed DHA-G. Yet miR-142-5p and miR-101 showed no correlation with ACSL1 or C/EBPα. The variability in expression patterns of miRNA across adipose depots reflects the tissue specific nature of adipogenic regulation. Although the examined miRNA appear to be

  20. Polychlorinated biphenyl (PCB) partitioning between adipose tissue and serum

    SciTech Connect

    Brown, J.F. Jr.; Lawton, R.W.

    1984-09-01

    It has been recently suggested that variabilities in the partitioning of chronically retained lipophilic xenobiotics between adipose tissue and serum may be relatable to variations in the lipid content of the serum. Here, the authors present theoretical considerations and experimental data showing that this is indeed the case for polychlorinated biphenyls (PCBs) in humans. At equilibrium, in the absence of active transport, any lipophilic substance must distribute itself among body tissues in such a way that its chemical activity and also its chemical potential are the same at all points. In order to verify the theoretical relationships, three sorts of data relating to serum PCB levels in a human population were examined.

  1. Commonality versus specificity among adiposity traits in normal-weight and moderately overweight adults

    PubMed Central

    Raja, GK; Sarzynski, MA; Katzmarzyk, PT; Johnson, WD; Tchoukalova, Y; Smith, SR; Bouchard, C

    2014-01-01

    BACKGROUND Many adiposity traits have been related to health complications and premature death. These adiposity traits are intercorrelated but their underlying structure has not been extensively investigated. We report on the degree of commonality and specificity among multiple adiposity traits in normal-weight and moderately overweight adult males and females (mean body mass index (BMI) = 22.9 kg m−2, s.d. = 2.4). METHODS A total of 75 healthy participants were assessed for a panel of adiposity traits including leg, arm, trunk, total fat masses and visceral adipose tissue (VAT) derived from dual energy X-ray absorptiometry (DXA), hepatic and muscle lipids from proton magnetic resonance spectroscopy, fat cell volume from an abdominal subcutaneous adipose tissue biopsy (n = 36) and conventional anthropometry (BMI and waist girth). Spearman’s correlations were calculated and were subjected to factor analysis. RESULTS Arm, leg, trunk and total fat masses correlated positively (r = 0.78–0.95) with each other. VAT correlated weakly with fat mass indicators (r = 0.24–0.31). Intrahepatic lipids (IHL) correlated weakly with all fat mass traits (r = 0.09–0.34), whereas correlations between DXA depots and intramyocellular lipids (IMCL) were inconsequential. The four DXA fat mass measures, VAT, IHL and IMCL depots segregated as four independent factors that accounted for 96% of the overall adiposity variance. BMI and waist girth were moderately correlated with the arm, leg, trunk and total fat and weakly with VAT, IHL and IMCL. CONCLUSION Adiposity traits share a substantial degree of commonality, but there is considerable specificity across the adiposity variance space. For instance, VAT, IHL and IMCL are typically poorly correlated with each other and are poorly to weakly associated with the other adiposity traits. The same is true for BMI and waist girth, commonly used anthropometric indicators of adiposity. These results do not support the view that it will be

  2. Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction.

    PubMed

    Pfeiffer, Susanne; Krüger, Jacqueline; Maierhofer, Anna; Böttcher, Yvonne; Klöting, Nora; El Hajj, Nady; Schleinitz, Dorit; Schön, Michael R; Dietrich, Arne; Fasshauer, Mathias; Lohmann, Tobias; Dreßler, Miriam; Stumvoll, Michael; Haaf, Thomas; Blüher, Matthias; Kovacs, Peter

    2016-01-01

    Recently, a genome-wide analysis identified DNA methylation of the HIF3A (hypoxia-inducible factor 3A) as strongest correlate of BMI. Here we tested the hypothesis that HIF3A mRNA expression and CpG-sites methylation in adipose tissue (AT) and genetic variants in HIF3A are related to parameters of AT distribution and function. In paired samples of subcutaneous AT (SAT) and visceral AT (VAT) from 603 individuals, we measured HIF3A mRNA expression and analyzed its correlation with obesity and related traits. In subgroups of individuals, we investigated the effects on HIF3A genetic variants on its AT expression (N = 603) and methylation of CpG-sites (N = 87). HIF3A expression was significantly higher in SAT compared to VAT and correlated with obesity and parameters of AT dysfunction (including CRP and leucocytes count). HIF3A methylation at cg22891070 was significantly higher in VAT compared to SAT and correlated with BMI, abdominal SAT and VAT area. Rs8102595 showed a nominal significant association with AT HIF3A methylation levels as well as with obesity and fat distribution. HIF3A expression and methylation in AT are fat depot specific, related to obesity and AT dysfunction. Our data support the hypothesis that HIF pathways may play an important role in the development of AT dysfunction in obesity. PMID:27346320

  3. Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction

    PubMed Central

    Pfeiffer, Susanne; Krüger, Jacqueline; Maierhofer, Anna; Böttcher, Yvonne; Klöting, Nora; El Hajj, Nady; Schleinitz, Dorit; Schön, Michael R.; Dietrich, Arne; Fasshauer, Mathias; Lohmann, Tobias; Dreßler, Miriam; Stumvoll, Michael; Haaf, Thomas; Blüher, Matthias; Kovacs, Peter

    2016-01-01

    Recently, a genome-wide analysis identified DNA methylation of the HIF3A (hypoxia-inducible factor 3A) as strongest correlate of BMI. Here we tested the hypothesis that HIF3A mRNA expression and CpG-sites methylation in adipose tissue (AT) and genetic variants in HIF3A are related to parameters of AT distribution and function. In paired samples of subcutaneous AT (SAT) and visceral AT (VAT) from 603 individuals, we measured HIF3A mRNA expression and analyzed its correlation with obesity and related traits. In subgroups of individuals, we investigated the effects on HIF3A genetic variants on its AT expression (N = 603) and methylation of CpG-sites (N = 87). HIF3A expression was significantly higher in SAT compared to VAT and correlated with obesity and parameters of AT dysfunction (including CRP and leucocytes count). HIF3A methylation at cg22891070 was significantly higher in VAT compared to SAT and correlated with BMI, abdominal SAT and VAT area. Rs8102595 showed a nominal significant association with AT HIF3A methylation levels as well as with obesity and fat distribution. HIF3A expression and methylation in AT are fat depot specific, related to obesity and AT dysfunction. Our data support the hypothesis that HIF pathways may play an important role in the development of AT dysfunction in obesity. PMID:27346320

  4. Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue

    PubMed Central

    2012-01-01

    Background Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue. Methods Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject. Results Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot. Conclusions Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue. PMID:22974251

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

    PubMed

    Bennetzen, Marianne Faurholt

    2011-04-01

    suggest that the ECS is reduced in adipose tissue in obesity. Our results do not support the hypothesis of hyperactivity of the ECS in human obesity. Possible future treatment of obesity with CBR1 antagonist could involve cyclic treatment of specific peripheral compounds. PMID:21466769

  6. Impaired Mitochondrial Biogenesis in Adipose Tissue in Acquired Obesity.

    PubMed

    Heinonen, Sini; Buzkova, Jana; Muniandy, Maheswary; Kaksonen, Risto; Ollikainen, Miina; Ismail, Khadeeja; Hakkarainen, Antti; Lundbom, Jesse; Lundbom, Nina; Vuolteenaho, Katriina; Moilanen, Eeva; Kaprio, Jaakko; Rissanen, Aila; Suomalainen, Anu; Pietiläinen, Kirsi H

    2015-09-01

    Low mitochondrial number and activity have been suggested as underlying factors in obesity, type 2 diabetes, and metabolic syndrome. However, the stage at which mitochondrial dysfunction manifests in adipose tissue after the onset of obesity remains unknown. Here we examined subcutaneous adipose tissue (SAT) samples from healthy monozygotic twin pairs, 22.8-36.2 years of age, who were discordant (ΔBMI >3 kg/m(2), mean length of discordance 6.3 ± 0.3 years, n = 26) and concordant (ΔBMI <3 kg/m(2), n = 14) for body weight, and assessed their detailed mitochondrial metabolic characteristics: mitochondrial-related transcriptomes with dysregulated pathways, mitochondrial DNA (mtDNA) amount, mtDNA-encoded transcripts, and mitochondrial oxidative phosphorylation (OXPHOS) protein levels. We report global expressional downregulation of mitochondrial oxidative pathways with concomitant downregulation of mtDNA amount, mtDNA-dependent translation system, and protein levels of the OXPHOS machinery in the obese compared with the lean co-twins. Pathway analysis indicated downshifting of fatty acid oxidation, ketone body production and breakdown, and the tricarboxylic acid cycle, which inversely correlated with adiposity, insulin resistance, and inflammatory cytokines. Our results suggest that mitochondrial biogenesis, oxidative metabolic pathways, and OXPHOS proteins in SAT are downregulated in acquired obesity, and are associated with metabolic disturbances already at the preclinical stage. PMID:25972572

  7. Central Nervous System Regulation of Brown Adipose Tissue

    PubMed Central

    Morrison, Shaun F.; Madden, Christopher J.

    2015-01-01

    Thermogenesis, the production of heat energy, in brown adipose tissue is a significant component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature in many species from mouse to man and plays a key role in elevating body temperature during the febrile response to infection. The sympathetic neural outflow determining brown adipose tissue (BAT) thermogenesis is regulated by neural networks in the CNS which increase BAT sympathetic nerve activity in response to cutaneous and deep body thermoreceptor signals. Many behavioral states, including wakefulness, immunologic responses, and stress, are characterized by elevations in core body temperature to which central command-driven BAT activation makes a significant contribution. Since energy consumption during BAT thermogenesis involves oxidation of lipid and glucose fuel molecules, the CNS network driving cold-defensive and behavioral state-related BAT activation is strongly influenced by signals reflecting the short and long-term availability of the fuel molecules essential for BAT metabolism and, in turn, the regulation of BAT thermogenesis in response to metabolic signals can contribute to energy balance, regulation of body adipose stores and glucose utilization. This review summarizes our understanding of the functional organization and neurochemical influences within the CNS networks that modulate the level of BAT sympathetic nerve activity to produce the thermoregulatory and metabolic alterations in BAT thermogenesis and BAT energy expenditure that contribute to overall energy homeostasis and the autonomic support of behavior. PMID:25428857

  8. Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue.

    PubMed

    Ma, Xinran; Xu, Lingyan; Mueller, Elisabetta

    2016-03-22

    Glucocorticoids (GCs) are widely prescribed anti-inflammatory agents, but their chronic use leads to undesirable side effects such as excessive expansion of adipose tissue. We have recently shown that the forkhead box protein A3 (Foxa3) is a calorie-hoarding factor that regulates the selective enlargement of epididymal fat depots and suppresses energy expenditure in a nutritional- and age-dependent manner. It has been demonstrated that Foxa3 levels are elevated in adipose depots in response to high-fat diet regimens and during the aging process; however no studies to date have elucidated the mechanisms that control Foxa3's expression in fat. Given the established effects of GCs in increasing visceral adiposity and in reducing thermogenesis, we assessed the existence of a possible link between GCs and Foxa3. Computational prediction analysis combined with molecular studies revealed that Foxa3 is regulated by the glucocorticoid receptor (GR) in preadipocytes, adipocytes, and adipose tissues and is required to facilitate the binding of the GR to its target gene promoters in fat depots. Analysis of the long-term effects of dexamethasone treatment in mice revealed that Foxa3 ablation protects mice specifically against fat accretion but not against other pathological side effects elicited by this synthetic GC in tissues such as liver, muscle, and spleen. In conclusion our studies provide the first demonstration, to our knowledge, that Foxa3 is a direct target of GC action in adipose tissues and point to a role of Foxa3 as a mediator of the side effects induced in fat tissues by chronic treatment with synthetic steroids. PMID:26957608

  9. White adipose tissue cells and the progression of cachexia: inflammatory pathways

    PubMed Central

    Neves, Rodrigo X.; Rosa‐Neto, José Cesar; Yamashita, Alex S.; Matos‐Neto, Emidio M.; Riccardi, Daniela M. R.; Lira, Fabio S.; Batista, Miguel L.

    2015-01-01

    Abstract Background Cachexia is a systemic syndrome leading to body wasting, systemic inflammation, and to metabolic chaos. It is a progressive condition, and little is known about its dynamics. Detection of the early signs of the disease may lead to the attenuation of the associated symptoms. The white adipose tissue is an organ with endocrine functions, capable of synthesising and secreting a plethora of proteins, including cytokines, chemokines, and adipokines. It is well established that different adipose tissue depots demonstrate heterogeneous responses to physiological and pathological stimuli. The present study aimed at providing insight into adipocyte involvement in inflammation along the progression of cachexia. Methods Eight‐weeks‐old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 × 107 cells in 1.0 mL; tumour‐bearing, T) or Phosphate‐buffered saline (control, C). The retroperitoneal, epididymal, and mesenteric adipose pads were excised on Days 0, 7, and 14 post‐tumour cell injection, and the adipocytes were isolated. Results Mesenteric and epididymal adipocytes showed up‐regulation of IL‐1β protein expression and activation of the inflammasome pathway, contributing for whole tissue inflammation. The stromal vascular fraction of the retroperitoneal adipose tissue, on the other hand, seems to be the major contributor for the inflammation in this specific pad. Conclusion Adipocytes seem to play a relevant role in the establishment of white adipose tissue inflammation, through the activation of the NF‐κB and inflammasome pathways. In epididymal adipocytes, induction of the inflammasome may be detected already on Day 7 post‐tumour cell inoculation.

  10. Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue

    PubMed Central

    Ma, Xinran; Xu, Lingyan; Mueller, Elisabetta

    2016-01-01

    Glucocorticoids (GCs) are widely prescribed anti-inflammatory agents, but their chronic use leads to undesirable side effects such as excessive expansion of adipose tissue. We have recently shown that the forkhead box protein A3 (Foxa3) is a calorie-hoarding factor that regulates the selective enlargement of epididymal fat depots and suppresses energy expenditure in a nutritional- and age-dependent manner. It has been demonstrated that Foxa3 levels are elevated in adipose depots in response to high-fat diet regimens and during the aging process; however no studies to date have elucidated the mechanisms that control Foxa3’s expression in fat. Given the established effects of GCs in increasing visceral adiposity and in reducing thermogenesis, we assessed the existence of a possible link between GCs and Foxa3. Computational prediction analysis combined with molecular studies revealed that Foxa3 is regulated by the glucocorticoid receptor (GR) in preadipocytes, adipocytes, and adipose tissues and is required to facilitate the binding of the GR to its target gene promoters in fat depots. Analysis of the long-term effects of dexamethasone treatment in mice revealed that Foxa3 ablation protects mice specifically against fat accretion but not against other pathological side effects elicited by this synthetic GC in tissues such as liver, muscle, and spleen. In conclusion our studies provide the first demonstration, to our knowledge, that Foxa3 is a direct target of GC action in adipose tissues and point to a role of Foxa3 as a mediator of the side effects induced in fat tissues by chronic treatment with synthetic steroids. PMID:26957608

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

    PubMed Central

    Yuan, Yi

    2015-01-01

    Summary: Our bodies are subjected to various mechanical forces, which in turn affect both the structure and function of our bodies. In particular, these mechanical forces play an important role in tissue growth and regeneration. Adipocytes and adipose-derived stem cells are both mechanosensitive and mechanoresponsive. The aim of this review is to summarize the relationship between mechanobiology and adipogenesis. PubMed was used to search for articles using the following keywords: mechanobiology, adipogenesis, adipose-derived stem cells, and cytoskeleton. In vitro and in vivo experiments have shown that adipogenesis is strongly promoted/inhibited by various internal and external mechanical forces, and that these effects are mediated by changes in the cytoskeleton of adipose-derived stem cells and/or various signaling pathways. Thus, adipose tissue engineering could be enhanced by the careful application of mechanical forces. It was shown recently that mature adipose tissue regenerates in an adipose tissue-engineering chamber. This observation has great potential for the reconstruction of soft tissue deficiencies, but the mechanisms behind it remain to be elucidated. On the basis of our understanding of mechanobiology, we hypothesize that the chamber removes mechanical force on the fat that normally impose high cytoskeletal tension. The reduction in tension in adipose stem cells triggers their differentiation into adipocytes. The improvement in our understanding of the relationship between mechanobiology and adipogenesis means that in the near future, we may be able to increase or decrease body fat, as needed in the clinic, by controlling the tension that is loaded onto fat. PMID:26894003

  12. The effects of cryopreservation on cells isolated from adipose, bone marrow and dental pulp tissues.

    PubMed

    Davies, O G; Smith, A J; Cooper, P R; Shelton, R M; Scheven, B A

    2014-10-01

    The effects of cryopreservation on mesenchymal stem cell (MSC) phenotype are not well documented; however this process is of increasing importance for regenerative therapies. This study examined the effect of cryopreservation (10% dimethyl-sulfoxide) on the morphology, viability, gene-expression and relative proportion of MSC surface-markers on cells derived from rat adipose, bone marrow and dental pulp. Cryopreservation significantly reduced the number of viable cells in bone marrow and dental pulp cell populations but had no observable effect on adipose cells. Flow cytometry analysis demonstrated significant increases in the relative expression of MSC surface-markers, CD90 and CD29/CD90 following cryopreservation. sqRT-PCR analysis of MSC gene-expression demonstrated increases in pluripotent markers for adipose and dental pulp, together with significant tissue-specific increases in CD44, CD73-CD105 following cryopreservation. Cells isolated from different tissue sources did not respond equally to cryopreservation with adipose tissue representing a more robust source of MSCs. PMID:25127874

  13. Mest and Sfrp5 are biomarkers for healthy adipose tissue.

    PubMed

    Jura, Magdalena; Jarosławska, Julia; Chu, Dinh Toi; Kozak, Leslie P

    2016-05-01

    Obesity depends on a close interplay between genetic and environmental factors. However, it is unknown how these factors interact to cause changes in the obese condition during the progression of obesity from the neonatal to the aged individual. We have utilized Mest and Sfrp5 genes, two genes highly correlated with adipose tissue expansion in diet-induced obesity, to characterize the obese condition during development of 2 genetic models of obesity. A model for the early onset of obesity was presented by leptin-deficient mice (ob/ob), whereas late onset of obesity was induced with high-fat diet (HFD) consumption in C57BL/6J mice with inherent risk of obesity (DIO). We correlated obese and diabetic phenotypes with Mest and Sfrp5 gene expression profiles in subcutaneous fat during pre-weaning, pre-adulthood and adulthood. A rapid development of obesity began in ob/ob mice immediately after weaning at 21 days of age, whereas the obesity of DIO mice was not evident until after 2 months of age. Even after 5 months of HFD treatment, the adiposity index of DIO mice was lower than in ob/ob mice at 2 months of age. In both obesity models, the expression of Mest and Sfrp5 genes increased in parallel with fat mass expansion; however, gene expression proceeded to decrease when the adiposity reached a plateau. The reduction in the expression of genes of caveolae structure and glucose metabolism were also suppressed in the aging adipose tissue. The analysis of fat mass and adipocyte size suggests that reduction in Mest and Sfrp5 is more sensitive to the age of the fat than its morphology. The balance of factors controlling fat deposition can be evaluated in part by the differential expression profiles of Mest and Sfrp5 genes with functions linked to fat deposition as long as there is an active accumulation of fat mass. PMID:26001362

  14. Moderate caloric restriction during gestation in rats alters adipose tissue sympathetic innervation and later adiposity in offspring.

    PubMed

    García, Ana Paula; Palou, Mariona; Sánchez, Juana; Priego, Teresa; Palou, Andreu; Picó, Catalina

    2011-01-01

    Maternal prenatal undernutrition predisposes offspring to higher adiposity in adulthood. Mechanisms involved in these programming effects, apart from those described in central nervous system development, have not been established. Here we aimed to evaluate whether moderate caloric restriction during early pregnancy in rats affects white adipose tissue (WAT) sympathetic innervation in the offspring, and its relationship with adiposity development. For this purpose, inguinal and retroperitoneal WAT (iWAT and rpWAT, respectively) were analyzed in male and female offspring of control and 20% caloric-restricted (from 1-12 d of pregnancy) (CR) dams. Body weight (BW), the weight, DNA-content, morphological features and the immunoreactive tyrosine hydroxylase and Neuropeptide Y area (TH+ and NPY+ respectively, performed by immunohistochemistry) of both fat depots, were studied at 25 d and 6 m of age, the latter after 2 m exposure to high fat diet. At 6 m of life, CR males but not females, exhibited greater BW, and greater weight and total DNA-content in iWAT, without changes in adipocytes size, suggesting the development of hyperplasia in this depot. However, in rpWAT, CR males but not females, showed larger adipocyte diameter, with no changes in DNA-content, suggesting the development of hypertrophy. These parameters were not different between control and CR animals at the age of 25 d. In iWAT, both at 25 d and 6 m, CR males but not females, showed lower TH(+) and NPY(+), suggesting lower sympathetic innervation in CR males compared to control males. In rpWAT, at 6 m but not at 25 d, CR males but not females, showed lower TH(+) and NPY(+). Thus, the effects of caloric restriction during gestation on later adiposity and on the differences in the adult phenotype between internal and subcutaneous fat depots in the male offspring may be associated in part with specific alterations in sympathetic innervation, which may impact on WAT architecture. PMID:21364997

  15. Moderate Caloric Restriction during Gestation in Rats Alters Adipose Tissue Sympathetic Innervation and Later Adiposity in Offspring

    PubMed Central

    García, Ana Paula; Palou, Mariona; Sánchez, Juana; Priego, Teresa; Palou, Andreu; Picó, Catalina

    2011-01-01

    Maternal prenatal undernutrition predisposes offspring to higher adiposity in adulthood. Mechanisms involved in these programming effects, apart from those described in central nervous system development, have not been established. Here we aimed to evaluate whether moderate caloric restriction during early pregnancy in rats affects white adipose tissue (WAT) sympathetic innervation in the offspring, and its relationship with adiposity development. For this purpose, inguinal and retroperitoneal WAT (iWAT and rpWAT, respectively) were analyzed in male and female offspring of control and 20% caloric-restricted (from 1–12 d of pregnancy) (CR) dams. Body weight (BW), the weight, DNA-content, morphological features and the immunoreactive tyrosine hydroxylase and Neuropeptide Y area (TH+ and NPY+ respectively, performed by immunohistochemistry) of both fat depots, were studied at 25 d and 6 m of age, the latter after 2 m exposure to high fat diet. At 6 m of life, CR males but not females, exhibited greater BW, and greater weight and total DNA-content in iWAT, without changes in adipocytes size, suggesting the development of hyperplasia in this depot. However, in rpWAT, CR males but not females, showed larger adipocyte diameter, with no changes in DNA-content, suggesting the development of hypertrophy. These parameters were not different between control and CR animals at the age of 25 d. In iWAT, both at 25 d and 6 m, CR males but not females, showed lower TH+ and NPY+, suggesting lower sympathetic innervation in CR males compared to control males. In rpWAT, at 6 m but not at 25 d, CR males but not females, showed lower TH+ and NPY+. Thus, the effects of caloric restriction during gestation on later adiposity and on the differences in the adult phenotype between internal and subcutaneous fat depots in the male offspring may be associated in part with specific alterations in sympathetic innervation, which may impact on WAT architecture. PMID:21364997

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

    PubMed Central

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

    2006-01-01

    Background The manner in which fat depot volumes and distributions, particularly the adipose tissue (AT) between the muscles, vary by race is unknown. Objective The objective was to quantify a previously unstudied and novel intermuscular AT (IMAT) depot and subcutaneous AT, visceral AT (VAT), and total-body skeletal muscle mass in healthy sedentary African American (AA), Asian, and white adults by whole-body magnetic resonance imaging. IMAT is the AT between muscles and within the boundary of the muscle fascia. Design Analyses were conducted on 227 women [AA (n = 79): body mass index (BMI; in kg/m2), 29.0 ± 5.5; age, 45.7 ± 16.9 y; Asian (n = 38): BMI, 21.7 ± 2.9; age, 47.2 ± 19.9 y; whites (n = 110): BMI, 24.9 ± 5.4; age, 43.7 ± 16.2 y]) and 111 men [AA (n = 39): BMI, 25.6 ± 3.2; age, 45.5 ± 18.8 y; Asian (n = 13): BMI, 24.9 ± 2.5; age, 45.6 ± 25.0 y; white (n = 59): BMI, 25.8 ± 3.8; age 44.5 ± 16.3 y]. Results IMAT depots were not significantly different in size between race groups at low levels of adiposity; however, with increasing adiposity, AAs had a significantly greater increment in the proportion of total AT (TAT) than did the whites and Asians (58, 46, and 44 g IMAT/kg TAT, respectively; P = 0.001). VAT depots were not significantly different in size at low levels of adiposity but, with increasing adiposity, VAT accumulation was greater than IMAT accumulation in the Asians and whites; no significant differences were observed in AAs. Conclusion Race differences in AT distribution extend to IMAT, a depot that may influence race-ethnicity differences in dysglycemia. PMID:15817870

  17. Energy metabolism and biochemical features of adipose tissues in ICR mice after long-term calorie-restricted diet.

    PubMed

    Mizonova, O V; Elsukova, E I; Medvedev, L N

    2013-10-01

    Long-term calorie-restricted diet (8 weeks, 60% of control food intake) was followed by an increase in thermogenic activity of interscapular brown fat. The relative amount of DNA and protein and the rate of oxygen consumption increased and tissue-specific marker of brown fat (uncoupling protein UCP1) appeared in significantly reduced deep-pink abdominal adipose tissue. PMID:24288756

  18. The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling.

    PubMed

    Kwon, H-J; Kim, S-N; Kim, Y-A; Lee, Y-H

    2016-01-01

    Cellular plasticity in adipose tissue involves adipocyte death, its clearance, and de novo adipogenesis, enabling homeostatic turnover and adaptation to metabolic challenges; however, mechanisms regulating these serial events are not fully understood. The present study investigated the roles of arachidonate 15-lipoxygenase (Alox15) in the clearance of dying adipocytes by adipose tissue macrophages. First, upregulation of Alox15 expression and apoptotic adipocyte death in gonadal white adipose tissue (gWAT) were characterized during adipose tissue remodeling induced by β3-adrenergic receptor stimulation. Next, an in vitro reconstruction of adipose tissue macrophages and apoptotic adipocytes recapitulated adipocyte clearance by macrophages and demonstrated that macrophages co-cultured with apoptotic adipocytes increased the expression of efferocytosis-related genes. Genetic deletion and pharmacological inhibition of Alox15 diminished the levels of adipocyte clearance by macrophages in a co-culture system. Gene expression profiling of macrophages isolated from gWAT of Alox15 knockout (KO) mice demonstrated distinct phenotypes, especially downregulation of genes involved in lipid uptake and metabolism compared to wild-type mice. Finally, in vivo β3-adrenergic stimulation in Alox15 KO mice failed to recruit crown-like structures, a macrophage network clearing dying adipocytes in gWAT. Consequently, in Alox15 KO mice, proliferation/differentiation of adipocyte progenitors and β3-adrenergic remodeling of gWAT were impaired compared to wild-type control mice. Collectively, our data established a pivotal role of Alox15 in the resolution of adipocyte death and in adipose tissue remodeling. PMID:27362803

  19. Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browning.

    PubMed

    Bartelt, Alexander; Weigelt, Clara; Cherradi, M Lisa; Niemeier, Andreas; Tödter, Klaus; Heeren, Joerg; Scheja, Ludger

    2013-05-01

    Efficient storage of dietary and endogenous fatty acids is a prerequisite for a healthy adipose tissue function. Lipoprotein lipase (LPL) is the master regulator of fatty acid uptake from triglyceride-rich lipoproteins. In addition to LPL-mediated fatty acid uptake, adipocytes are able to synthesize fatty acids from non-lipid precursor, a process called de novo lipogenesis (DNL). As the physiological relevance of fatty acid uptake versus DNL for brown and white adipocyte function remains unclear, we studied the role of adipocyte LPL using adipocyte-specific LPL knockout animals (aLKO). ALKO mice displayed a profound increase in DNL-fatty acids, especially palmitoleate and myristoleate in brown adipose tissue (BAT) and white adipose tissue (WAT) depots while essential dietary fatty acids were markedly decreased. Consequently, we found increased expression in adipose tissues of genes encoding DNL enzymes (Fasn, Scd1, and Elovl6) as well as the lipogenic transcription factor carbohydrate response element binding protein-β. In a high-fat diet (HFD) study aLKO mice were characterized by reduced adiposity and improved plasma insulin and adipokines. However, neither glucose tolerance nor inflammatory markers were ameliorated in aLKO mice compared to controls. No signs of increased BAT activation or WAT browning were detected in aLKO mice either on HFD or after 1 week of β3-adrenergic stimulation using CL316,243. We conclude that despite a profound increase in DNL-derived fatty acids, proposed to be metabolically favorable, aLKO mice are not protected from metabolic disease per se. In addition, induction of DNL alone is not sufficient to promote browning of WAT. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease. PMID:23228690

  20. Male Bovine GH Transgenic Mice Have Decreased Adiposity With an Adipose Depot-Specific Increase in Immune Cell Populations

    PubMed Central

    Benencia, Fabian; Harshman, Stephanie; Duran-Ortiz, Silvana; Lubbers, Ellen R.; List, Edward O.; Householder, Lara; Al-Naeeli, Mawadda; Liang, Xiaoyu; Welch, Lonnie; Kopchick, John J.

    2015-01-01

    White adipose tissue (WAT) is composed of mature adipocytes and a stromal vascular fraction (SVF), which contains a variety of cells, including immune cells that vary among the different WAT depots. Growth hormone (GH) impacts immune function and adiposity in an adipose depot-specific manner. However, its effects on WAT immune cell populations remain unstudied. Bovine GH transgenic (bGH) mice are commonly used to study the in vivo effects of GH. These giant mice have an excess of GH action, impaired glucose metabolism, decreased adiposity, increased lean mass, and a shortened lifespan. Therefore, the purpose of this study was to characterize the WAT depot-specific differences in immune cell populations in the presence of excess GH in vivo. Three WAT depots were assessed: inguinal (sc), epididymal (EPI), and mesenteric (MES). Subcutaneous and MES bGH WAT depots showed a significantly higher number of total SVF cells, yet only MES bGH WAT had higher leukocyte counts compared with control samples. By means of flow cytometry analysis of the SVF, we detected greater macrophage and regulatory T-cell infiltration in sc and MES bGH WAT depots compared with controls. However, no differences were observed in the EPI WAT depot. RNA-sequencing confirmed significant alterations in pathways related to T-cell infiltration and activation in the sc depot with fewer significant changes in the EPI bGH WAT depot. These findings collectively point to a previously unrecognized role for GH in influencing the distribution of WAT immune cell populations in a depot-specific manner. PMID:25521584

  1. Advantages of Sheep Infrapatellar Fat Pad Adipose Tissue Derived Stem Cells in Tissue Engineering

    PubMed Central

    Vahedi, Parviz; Soleimanirad, Jafar; Roshangar, Leila; Shafaei, Hajar; Jarolmasjed, Seyedhosein; Nozad Charoudeh, Hojjatollah

    2016-01-01

    Purpose: The goal of this study has been to evaluate adipose tissue derived stem cells (ADSCs) from infrapatellar fat pad and characterize their cell surface markers using anti-human antibodies, as adipose tissue derived stem cells (ADSCs) have great potential for cellular therapies to restore injured tissues. Methods: Adipose tissue was obtained from infrapatellar fat pad of sheep. Surface markers evaluated by flow cytometry. In order to evaluate cell adhesion, the Polycaprolactone (PCL) was sterilized under Ultraviolet (UV) light and about 1×105 cells were seeded on PCL. Then, ASCs- PCL construct were evaluated by Scanning Electron Microscopy (Mira3 Te Scan, Czech Republic). Results: We showed that adipose tissue derived stem cells (ADSCs) maintain their fibroblastic-like morphology during different subcultures and cell adhesion. They were positive for CD44 and CD90 markers and negative for CD31 and Cd45 markers by human antibodies. Conclusion: Our results suggest that ASCs surface markers can be characterized by anti-human antibodies in sheep. As stem cells, they can be used in tissue engineering. PMID:27123425

  2. Subcutaneous and gonadal adipose tissue transcriptome differences in lean and obese female dogs.

    PubMed

    Grant, Ryan W; Vester Boler, Brittany M; Ridge, Tonya K; Graves, Thomas K; Swanson, Kelly S

    2013-12-01

    Canine obesity leads to shortened life span and increased disease incidence. Adipose tissue depots are known to have unique metabolic and gene expression profiles in rodents and humans, but few comparisons of depot gene expression have been performed in the dog. Using microarray technology, our objective was to identify differentially expressed genes and enriched functional pathways between subcutaneous and gonadal adipose of lean and obese dogs to better understand the pathogenesis of obesity in the dog. Because no depot × body weight status interactions were identified in the microarray data, depot differences were the primary focus. A total of 946 and 703 transcripts were differentially expressed (FDR P < 0.05) between gonadal and subcutaneous adipose tissue in obese and lean dogs respectively. Of the adipose depot-specific differences in gene expression, 162 were present in both lean and obese dogs, with the majority (85%) expressed in the same direction. Both lean and obese dog gene lists had enrichment of the complement and coagulation cascade and systemic lupus erythematosus pathways. Obese dogs had enrichment of lysosome, extracellular matrix-receptor interaction, renin-angiotensin system and hematopoietic cell lineage pathways. Lean dogs had enrichment of glutathione metabolism and synthesis and degradation of ketone bodies. We have identified a core set of genes differentially expressed between subcutaneous and gonadal adipose tissue in dogs regardless of body weight. These genes contribute to depot-specific differences in immune function, extracellular matrix remodeling and lysosomal function and may contribute to the physiological differences noted between depots. PMID:23713485

  3. Dioxins and dibenzofurans in adipose tissue of US Vietnam veterans and controls

    SciTech Connect

    Kang, H.K.; Watanabe, K.K.; Breen, J.; Remmers, J.; Conomos, M.G.; Stanley, J.; Flicker, M. )

    1991-03-01

    The primary reason for concern about the adverse effects of exposure to Agent Orange is attributable to its toxic contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or dioxin. We studied adipose tissues from 36 Vietnam veterans, a similar group of 79 non-Vietnam veterans, and 80 civilians; the tissue specimens were selected from the 8,000 archived tissues collected from the non-institutionalized general population by the US Environmental Protection Agency. The geometric mean (+/- standard deviation) dioxin levels in adipose tissue for Vietnam veterans, non-Vietnam veterans, and civilian controls were 11.7 (+/- 1.7), 10.9 (+/- 1.7), and 12.4 (+/- 1.9) parts per trillion on a lipid weight basis, respectively. The mean levels for these groups were not significantly different from each other with or without adjustment for age of individuals, body mass index, and specimen collection year. In addition, none of the surrogate measures of Agent Orange exposure such as military branch, service within specific geographic region, military occupation, and troop location in relation to recorded Agent Orange spray was associated with the dioxin levels in adipose tissue of Vietnam veterans. Our results suggest that heavy exposure to Agent Orange or dioxin for most US troops was unlikely.

  4. Hybrid adipogenic implants from adipose stem cells for soft tissue reconstruction in vivo.

    PubMed

    Moioli, Eduardo K; Chen, Mo; Yang, Rujing; Shah, Bhranti; Wu, June; Mao, Jeremy J

    2010-11-01

    A critical barrier in tissue regeneration is scale-up. Bioengineered adipose tissue implants have been limited to ∼10  mm in diameter. Here, we devised a 40-mm hybrid implant with a cellular layer encapsulating an acellular core. Human adipose-derived stem cells (ASCs) were seeded in alginate. Poly(ethylene)glycol-diacrylate (PEGDA) was photopolymerized into 40-mm-diameter dome-shaped gel. Alginate-ASC suspension was painted onto PEGDA surface. Cultivation of hybrid constructs ex vivo in adipogenic medium for 28 days showed no delamination. Upon 4-week in vivo implantation in athymic rats, hybrid implants well integrated with host subcutaneous tissue and could only be surgically separated. Vascularized adipose tissue regenerated in the thin, painted alginate layer only if ASC-derived adipogenic cells were delivered. Contrastingly, abundant fibrous tissue filled ASC-free alginate layer encapsulating the acellular PEGDA core in control implants. Human-specific peroxisome proliferator-activated receptor-γ (PPAR-γ) was detected in human ASC-seeded implants. Interestingly, rat-specific PPAR-γ was absent in either human ASC-seeded or ASC-free implants. Glycerol content in ASC-delivered implants was significantly greater than that in ASC-free implants. Remarkably, rat-specific platelet/endothelial cell adhesion molecule (PECAM) was detected in both ASC-seeded and ASC-free implants, suggesting anastomosis of vasculature in bioengineered tissue with host blood vessels. Human nuclear staining revealed that a substantial number of adipocytes were of human origin, whereas endothelial cells of vascular wall were of chemaric human and nonhuman (rat host) origins. Together, hybrid implant appears to be a viable scale-up approach with volumetric retention attributable primarily to the acellular biomaterial core, and yet has a biologically viable cellular interface with the host. The present 40-mm soft tissue implant may serve as a biomaterial tissue expander for

  5. Configuration of Fibrous and Adipose Tissues in the Cavernous Sinus

    PubMed Central

    Liang, Liang; Gao, Fei; Xu, Qunyuan; Zhang, Ming

    2014-01-01

    Objective Three-dimensional anatomical appreciation of the matrix of the cavernous sinus is one of the crucial necessities for a better understanding of tissue patterning and various disorders in the sinus. The purpose of this study was to reveal configuration of fibrous and adipose components in the cavernous sinus and their relationship with the cranial nerves and vessels in the sinus and meningeal sinus wall. Materials and Methods Nineteen cadavers (8 females and 11 males; age range, 54–89 years; mean age, 75 years) were prepared as transverse (6 sets), coronal (3 sets) and sagittal (10 sets) plastinated sections that were examined at both macroscopic and microscopic levels. Results Two types of the web-like fibrous networks were identified and localized in the cavernous sinus. A dural trabecular network constituted a skeleton-frame in the sinus and contributed to the sleeves of intracavernous cranial nerves III, IV, V1, V2 and VI. A fine trabecular network, or adipose tissue, was the matrix of the sinus and was mainly distributed along the medial side of the intracavernous cranial nerves, forming a dumbbell-shaped adipose zone in the sinus. Conclusions This study revealed the nature, fine architecture and localization of the fine and dural trabecular networks in the cavernous sinus and their relationship with intracavernous cranial nerves and vessels. The results may be valuable for better understanding of tissue patterning in the cranial base and better evaluation of intracavernous disorders, e.g. the growth direction and extent of intracavernous tumors. PMID:24586578

  6. Examination of adipose depot-specific PPAR moieties

    SciTech Connect

    Dodson, M.V.; Vierck, J.L.; Hausman, G.J.; Guan, L.L.; Fernyhough, M.E.; Poulos, S.P.; Mir, P.S.; Jiang, Z.

    2010-04-02

    Molecular mechanisms of peroxisome proliferator activated receptors (PPARs) are being defined rapidly, as illustrated by the volume of papers published. Much of the research is directed towards a clinical end-point/application; however, the non-homogeneous nature of adipose depots in laboratory animals is spurring similar research in domestic meat animals (such as beef cattle). Moreover, the size of adipose depots in meat animals remains an attractive feature for using them to obtain cells for PPAR research. Examination of meat-animal depot-specific PPAR moieties may provide novel information about adipocyte regulation that might be extrapolated to all animals.

  7. Stromal vascular progenitors in adult human adipose tissue

    PubMed Central

    Zimmerlin, Ludovic; Donnenberg, Vera S.; Pfeifer, Melanie E.; Meyer, E. Michael; Péault, Bruno; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    Background The in vivo progenitor of culture-expanded mesenchymal-like adipose-derived stem cells (ADSC) remains elusive, owing in part to the complex organization of stromal cells surrounding the small vessels, and the rapidity with which adipose stromal vascular cells adopt a mesenchymal phenotype in vitro. Methods Immunohistostaining of intact adipose tissue was used to identify 3 markers (CD31, CD34, CD146) which together unambiguously discriminate histologically distinct inner and outer rings of vessel-associated stromal cells, as well as capillary and small vessel endothelial cells. These markers were used in multiparameter flow cytometry in conjunction with stem/progenitor markers (CD90, CD117) to further characterize stromal vascular fraction (SVF) subpopulations. Two mesenchymal and two endothelial populations were isolated by high speed flow cytometric sorting, expanded in short term culture and tested for adipogenesis. Results The inner layer of stromal cells in contact with small vessel endothelium (pericytes) was CD146+/α-SMA+/CD90±/CD34−/CD31−; the outer adventitial stromal ring (designated supra adventitial-adipose stromal cells, SA-ASC) was CD146−/α-SMA−/CD90+/CD34+/CD31−. Capillary endothelial cells were CD31+/CD34+/CD90+ (endothelial progenitor), while small vessel endothelium was CD31+/CD34−/CD90− (endothelial mature). Flow cytometry confirmed these expression patterns and revealed a CD146+/CD90+/CD34+/CD31− pericyte subset that may be transitional between pericytes and SA-ASC. Pericytes had the most potent adipogenic potential, followed by the more numerous SA-ASC. Endothelial populations had significantly reduced adipogenic potential compared to unsorted expanded SVF cells. Conclusions In adipose tissue perivascular stromal cells are organized in two discrete layers, the innermost consisting of CD146+/CD34− pericytes, and the outermost of CD146−/CD34+ SA-ASC, both of which have adipogenic potential in culture. A CD146+/CD

  8. Hepatic ANGPTL3 regulates adipose tissue energy homeostasis

    PubMed Central

    Wang, Yan; McNutt, Markey C.; Banfi, Serena; Levin, Michael G.; Holland, William L.; Gusarova, Viktoria; Gromada, Jesper; Cohen, Jonathan C.; Hobbs, Helen H.

    2015-01-01

    Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein and endothelial lipase whose physiological function has remained obscure. Here we show that ANGPTL3 plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state. This conclusion emerged from studies of Angptl3−/− mice. Whereas feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no increase occurred in fed Angptl3−/− animals. Despite the reduction in delivery to and retention of TG in WAT, fat mass was largely preserved by a compensatory increase in de novo lipogenesis in Angptl3−/− mice. Glucose uptake into WAT was increased 10-fold in KO mice, and tracer studies revealed increased conversion of glucose to fatty acids in WAT but not liver. It is likely that the increased uptake of glucose into WAT explains the increased insulin sensitivity associated with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism make it an attractive therapeutic target. PMID:26305978

  9. Hepatic ANGPTL3 regulates adipose tissue energy homeostasis.

    PubMed

    Wang, Yan; McNutt, Markey C; Banfi, Serena; Levin, Michael G; Holland, William L; Gusarova, Viktoria; Gromada, Jesper; Cohen, Jonathan C; Hobbs, Helen H

    2015-09-15

    Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein and endothelial lipase whose physiological function has remained obscure. Here we show that ANGPTL3 plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state. This conclusion emerged from studies of Angptl3(-/-) mice. Whereas feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no increase occurred in fed Angptl3(-/-) animals. Despite the reduction in delivery to and retention of TG in WAT, fat mass was largely preserved by a compensatory increase in de novo lipogenesis in Angptl3(-/-) mice. Glucose uptake into WAT was increased 10-fold in KO mice, and tracer studies revealed increased conversion of glucose to fatty acids in WAT but not liver. It is likely that the increased uptake of glucose into WAT explains the increased insulin sensitivity associated with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism make it an attractive therapeutic target. PMID:26305978

  10. Patterns of gene expression in pig adipose tissue: transforming growth factors, interferons, interleukins and apolipoproteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Total RNA was collected at slaughter from outer s.c. adipose tissue (OSQ), middle s.c. adipose tissue (MSQ), ovary, uterus, hypothalamus, and pituitary tissues samples from gilts at 90, 150, and 210 d ( n =5 / age). Dye labeled cDNA probes were hybridized to custom microarrays (70 mer oligonucleotid...

  11. Differences in In Vivo Cellular Kinetics in Abdominal and Femoral Subcutaneous Adipose Tissue in Women.

    PubMed

    White, Ursula A; Fitch, Mark D; Beyl, Robbie A; Hellerstein, Marc K; Ravussin, Eric

    2016-06-01

    The accumulation of fat in upper-body (abdominal) adipose tissue is associated with obesity-related cardiometabolic diseases, whereas lower-body (gluteal and femoral) fat may be protective. Studies suggest physiological and molecular differences between adipose depots and depot-specific cellular mechanisms of adipose expansion. We assessed in vivo cellular kinetics in subcutaneous adipose tissue from the abdominal (scABD) and femoral (scFEM) depots using an 8-week incorporation of deuterium ((2)H) from (2)H2O into the DNA of adipocytes and preadipocytes in 25 women with overweight or obesity. DNA synthesis rates denote new cell formation of preadipocytes and adipocytes in each depot. Formation of adipocytes was positively correlated to that of preadipocytes in the scABD and scFEM depots and was related to percent body fat in each depot. Notably, preadipocytes and adipocytes had higher formation rates in the scFEM depot relative to the scABD. This method to assess in vivo adipogenesis will be valuable to evaluate adipocyte kinetics in individuals with varying body fat distributions and degrees of metabolic health and in response to a variety of interventions, such as diet, exercise, or pharmacological treatment. PMID:26993068

  12. A method for long-term live imaging of tissue macrophages in adipose tissue explants.

    PubMed

    Gericke, Martin; Weyer, Ulrike; Braune, Julia; Bechmann, Ingo; Eilers, Jens

    2015-06-01

    Obesity is frequently associated with a chronic low-grade inflammation within adipose tissue (AT). Although classical signs of inflammation are missing in AT inflammation, there is a significant increase in macrophages and, to a lesser extent, other immune cells, such as T cells, B cells, mast cells, and neutrophils. The spatial and temporal activation of these cells as well as their accumulation in the AT seem to be tightly linked to so-called crown-like structures (CLS). CLS are accumulations of adipose tissue macrophages (ATMs) around dead adipocytes and are thought to reflect a scavenger response. At present, data on the life cycle of CLS are missing. To better understand the cellular events underlying AT inflammation, we developed an approach that allows long-term imaging of ATMs, adipocytes, and CLS within live AT explants. We tested three putative reporter mouse lines for myeloid cells in regard to their suitability for live imaging. Thereby, we identified ATMs from CSF1R-eGFP mice to exhibit the most robust expression of eGFP. AT explants from these mice allowed stable live imaging for more than 7 days without significant phototoxicity. Long-term imaging thus revealed the accumulation of ATMs around dying adipocytes, migration of ATMs within AT, and also the degradation of the lipid remnants of perishing adipocytes. The observed behavior of ATMs in the context of AT inflammation is in line with previous studies but for the first time provides data on the specific behavior of individual ATMs and on the life cycle of CLS with unprecedented spatiotemporal resolution. PMID:25874903

  13. Adipose tissue chromium and vanadium disbalance in high-fat fed Wistar rats.

    PubMed

    Tinkov, Alexey A; Popova, Elizaveta V; Polyakova, Valentina S; Kwan, Olga V; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-01-01

    The primary objective of the current study is to investigate the relationship between adipose tissue chromium and vanadium content and adipose tissue dysfunction in a model of diet-induced obesity. A total of 26 female Wistar rats were fed either standard or high-fat diet (31.6% of fat from total caloric content) for 3 months. High-fat-feeding resulted in 21 and 33% decrease in adipose tissue chromium and vanadium content, respectively. No change was seen in hair chromium or vanadium levels. Statistical analysis revealed a significant inverse correlation of adipose tissue Cr and V with animal morphometric parameters and adipocyte size. Significant inverse dependence was observed between adipose tissue Cr and V and serum leptin and proinflammatory cytokines' levels. At the same time, adipose tissue Cr and V levels were characterized by positive correlation between serum adiponectin and adiponectin/leptin ratio. Adipose tissue Cr and V were inversely correlated (p<0.05) with insulin and homeostatic model assessment insulin resistance index (HOMA-IR) levels. Cr and V concentrations were not correlated with serum glucose in either high-fat fed or control rats; however, both serum glucose and HOMA-IR levels were significantly higher in high-fat fed, compared to control, rats. The results allow to hypothesize that impairment of adipose tissue Cr and V content plays a certain role in the development of adipose tissue endocrine dysfunction in obesity. PMID:25194956

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

    PubMed

    Jones, Cameron L; Achuthan, Ajit; Erath, Byron D

    2015-02-01

    This study demonstrates the effect of a substrate layer of adipose tissue on the modal response of the vocal folds, and hence, on the mechanics of voice production. Modal analysis is performed on the vocal fold structure with a lateral layer of adipose tissue. A finite element model is employed, and the first six mode shapes and modal frequencies are studied. The results show significant changes in modal frequencies and substantial variation in mode shapes depending on the strain rate of the adipose tissue. These findings highlight the importance of considering adipose tissue in computational vocal fold modeling. PMID:25698044

  15. Targeting adipose tissue in the treatment of obesity-associated diabetes.

    PubMed

    Kusminski, Christine M; Bickel, Perry E; Scherer, Philipp E

    2016-09-01

    Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of effective long-term glucose control. In this Review, we provide an overview of the role of adipose tissue in metabolic homeostasis and assess emerging novel therapeutic strategies targeting adipose tissue, including adipokine-based strategies, promotion of white adipose tissue beiging as well as reduction of inflammation and fibrosis. PMID:27256476

  16. In vivo adeno-associated viral vector-mediated genetic engineering of white and brown adipose tissue in adult mice.

    PubMed

    Jimenez, Veronica; Muñoz, Sergio; Casana, Estefania; Mallol, Cristina; Elias, Ivet; Jambrina, Claudia; Ribera, Albert; Ferre, Tura; Franckhauser, Sylvie; Bosch, Fatima

    2013-12-01

    Adipose tissue is pivotal in the regulation of energy homeostasis through the balance of energy storage and expenditure and as an endocrine organ. An inadequate mass and/or alterations in the metabolic and endocrine functions of adipose tissue underlie the development of obesity, insulin resistance, and type 2 diabetes. To fully understand the metabolic and molecular mechanism(s) involved in adipose dysfunction, in vivo genetic modification of adipocytes holds great potential. Here, we demonstrate that adeno-associated viral (AAV) vectors, especially serotypes 8 and 9, mediated efficient transduction of white (WAT) and brown adipose tissue (BAT) in adult lean and obese diabetic mice. The use of short versions of the adipocyte protein 2 or uncoupling protein-1 promoters or micro-RNA target sequences enabled highly specific, long-term AAV-mediated transgene expression in white or brown adipocytes. As proof of concept, delivery of AAV vectors encoding for hexokinase or vascular endothelial growth factor to WAT or BAT resulted in increased glucose uptake or increased vessel density in targeted depots. This method of gene transfer also enabled the secretion of stable high levels of the alkaline phosphatase marker protein into the bloodstream by transduced WAT. Therefore, AAV-mediated genetic engineering of adipose tissue represents a useful tool for the study of adipose pathophysiology and, likely, for the future development of new therapeutic strategies for obesity and diabetes. PMID:24043756

  17. In Vivo Adeno-Associated Viral Vector–Mediated Genetic Engineering of White and Brown Adipose Tissue in Adult Mice

    PubMed Central

    Jimenez, Veronica; Muñoz, Sergio; Casana, Estefania; Mallol, Cristina; Elias, Ivet; Jambrina, Claudia; Ribera, Albert; Ferre, Tura; Franckhauser, Sylvie; Bosch, Fatima

    2013-01-01

    Adipose tissue is pivotal in the regulation of energy homeostasis through the balance of energy storage and expenditure and as an endocrine organ. An inadequate mass and/or alterations in the metabolic and endocrine functions of adipose tissue underlie the development of obesity, insulin resistance, and type 2 diabetes. To fully understand the metabolic and molecular mechanism(s) involved in adipose dysfunction, in vivo genetic modification of adipocytes holds great potential. Here, we demonstrate that adeno-associated viral (AAV) vectors, especially serotypes 8 and 9, mediated efficient transduction of white (WAT) and brown adipose tissue (BAT) in adult lean and obese diabetic mice. The use of short versions of the adipocyte protein 2 or uncoupling protein-1 promoters or micro-RNA target sequences enabled highly specific, long-term AAV-mediated transgene expression in white or brown adipocytes. As proof of concept, delivery of AAV vectors encoding for hexokinase or vascular endothelial growth factor to WAT or BAT resulted in increased glucose uptake or increased vessel density in targeted depots. This method of gene transfer also enabled the secretion of stable high levels of the alkaline phosphatase marker protein into the bloodstream by transduced WAT. Therefore, AAV-mediated genetic engineering of adipose tissue represents a useful tool for the study of adipose pathophysiology and, likely, for the future development of new therapeutic strategies for obesity and diabetes. PMID:24043756

  18. Aromatase overexpression in dysfunctional adipose tissue links obesity to postmenopausal breast cancer.

    PubMed

    Wang, Xuyi; Simpson, Evan R; Brown, Kristy A

    2015-09-01

    The number of breast cancer cases has increased in the last a few decades and this is believed to be associated with the increased prevalence of obesity worldwide. The risk of breast cancer increases with age beyond menopause and the relationship between obesity and the risk of breast cancer in postmenopausal women is well established. The majority of postmenopausal breast cancers are estrogen receptor (ER) positive and estrogens produced in the adipose tissue promotes tumor formation. Obesity results in the secretion of inflammatory factors that stimulate the expression of the aromatase enzyme, which converts androgens into estrogens in the adipose tissue. Evidence demonstrating a link between obesity and breast cancer has led to the investigation of metabolic pathways as novel regulators of estrogen production, including pathways that can be targeted to inhibit aromatase specifically within the breast. This review aims to present some of the key findings in this regard. PMID:26209254

  19. Gene silencing in adipose tissue macrophages regulates whole-body metabolism in obese mice.

    PubMed

    Aouadi, Myriam; Tencerova, Michaela; Vangala, Pranitha; Yawe, Joseph C; Nicoloro, Sarah M; Amano, Shinya U; Cohen, Jessica L; Czech, Michael P

    2013-05-14

    Adipose tissue (AT) inflammation and infiltration by macrophages is associated with insulin resistance and type 2 diabetes in obese humans, offering a potential target for therapeutics. However, whether AT macrophages (ATMs) directly contribute to systemic glucose intolerance has not been determined. The reason is the lack of methods to ablate inflammatory genes expressed in macrophages specifically localized within AT depots, leaving macrophages in other tissues unaffected. Here we report that i.p. administration of siRNA encapsulated by glucan shells in obese mice selectively silences genes in epididymal ATMs, whereas macrophages within lung, spleen, kidney, heart, skeletal muscle, subcutaneous (SubQ) adipose, and liver are not targeted. Such administration of GeRPs to silence the inflammatory cytokines TNF-α or osteopontin in epididymal ATMs of obese mice caused significant improvement in glucose tolerance. These data are consistent with the hypothesis that cytokines produced by ATMs can exacerbate whole-body glucose intolerance. PMID:23630254

  20. [Functional exploration of brown adipose tissue using beta3 agonists].

    PubMed

    Bertin, R; de Marco, F; Blancher, G; Portet, R

    1994-06-01

    In view to utilize beta 3 adrenoceptor agonists for the investigation of body lipid metabolism, a study of the effects of BRL 37344 on the functional activity of the brown adipose tissue was performed in the Rat. It is known that this tissue is the principal site of heat production for nonshivering thermogenesis mainly due to the oxidation of fatty acids under the control of norepinephrine (NA) released from the sympathetic nervous system. In order to stimulate the activity of the tissue, rats were reared at 16 degrees C. When they were one month old, they were divided in two groups; one group received a surgical sympathectomy of the interscapular brown adipose tissue (TABI) (S group); the other group was sham-operated (T group). The resting metabolism was estimated by the continuous measurement of O2 consumption and CO2 release, at an ambient temperature of 25 degrees C. The animal capacity for nonshivering thermogenesis was determined by increased O2 consumption following i.p. administration of NA or BRL 37344. In the S group a large decrease in TABI NA content and a decrease in resting metabolism were observed. In both groups VO2 was increased by the two drugs; the increase was linearly related to the dose of BRL (between 2.5 to 10 micrograms/kg); but it was 3 times as high in the T group as in the S group. Moreover, the effect of BRL was 40 fold greater than the effect of NA. These results seem to indicate that, in cold reared rats, a part of nonshivering thermogenesis may be mediated by the beta 3 receptors of the brown fat. It may be concluded that the rats born in cold conditions are good models to study the role of beta 3 receptors in the energetic activity of this tissue very profuse in infant but not in adult man. PMID:7994586

  1. Identification of a novel peptide ligand targeting visceral adipose tissue via transdermal route by in vivo phage display.

    PubMed

    Lee, Nam Kyung; Kim, Hong Shin; Kim, Kyung Hyun; Kim, Eun-Bae; Cho, Chong Su; Kang, Sang Kee; Choi, Yun Jaie

    2011-11-01

    To find novel peptide ligands targeting visceral adipose tissue (visceral fat) via transdermal route, in vivo phage display screening was conducted by dermal administration of a phage-peptide library to rats and a peptide sequence, CGLHPAFQC (designated as TDA1), was identified as a targeting ligand to visceral adipose tissue through the consecutive transdermal biopannings. Adipocyte-specific affinity and transdermal activity of the TDA1 were validated in vitro and targeting ability of the dermally administered TDA1 to visceral adipose tissue was also confirmed in vivo. TDA1 was effectively translocated into systemic circulation after dermal administration and selectively targeted visceral adipose tissue without any preference to other organs tested. Fluorescent microscopic analysis revealed that the TDA1 could be specifically localized in the hair follicles of the skin, as well as in the visceral adipose tissue. Thus, we inferred that dermally administered TDA1 would first access systemic circulation via hair follicles as its transdermal route and then could target visceral fat effectively. The overall results suggest that the TDA1 peptide could be potentially applied as a homing moiety for delivery of anti-obesity therapeutics to visceral fat through the convenient transdermal pathway. PMID:21999821

  2. NAMPT-Mediated NAD(+) Biosynthesis in Adipocytes Regulates Adipose Tissue Function and Multi-organ Insulin Sensitivity in Mice.

    PubMed

    Stromsdorfer, Kelly L; Yamaguchi, Shintaro; Yoon, Myeong Jin; Moseley, Anna C; Franczyk, Michael P; Kelly, Shannon C; Qi, Nathan; Imai, Shin-Ichiro; Yoshino, Jun

    2016-08-16

    Obesity is associated with adipose tissue dysfunction and multi-organ insulin resistance. However, the mechanisms of such obesity-associated systemic metabolic complications are not clear. Here, we characterized mice with adipocyte-specific deletion of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting NAD(+) biosynthetic enzyme known to decrease in adipose tissue of obese and aged rodents and people. We found that adipocyte-specific Nampt knockout mice had severe insulin resistance in adipose tissue, liver, and skeletal muscle and adipose tissue dysfunction, manifested by increased plasma free fatty acid concentrations and decreased plasma concentrations of a major insulin-sensitizing adipokine, adiponectin. Loss of Nampt increased phosphorylation of CDK5 and PPARγ (serine-273) and decreased gene expression of obesity-linked phosphorylated PPARγ targets in adipose tissue. These deleterious alterations were normalized by administering rosiglitazone or a key NAD(+) intermediate, nicotinamide mononucleotide (NMN). Collectively, our results provide important mechanistic and therapeutic insights into obesity-associated systemic metabolic derangements, particularly multi-organ insulin resistance. PMID:27498863

  3. Inorganic Nitrate Promotes the Browning of White Adipose Tissue through the Nitrate-Nitrite-Nitric Oxide Pathway

    PubMed Central

    Roberts, Lee D; Ashmore, Tom; Kotwica, Aleksandra O; Murfitt, Steven A; Fernandez, Bernadette O; Feelisch, Martin; Griffin, Julian L

    2015-01-01

    Inorganic nitrate was once considered an oxidation end-product of nitric oxide metabolism with little biological activity. However, recent studies have demonstrated that dietary nitrate can modulate mitochondrial function in man and is effective in reversing features of the metabolic syndrome in mice. Using a combined histological, metabolomics, and transcriptional and protein analysis approach we mechanistically define that nitrate not only increases the expression of thermogenic genes in brown-adipose tissue but also induces the expression of brown adipocyte-specific genes and proteins in white adipose tissue, substantially increasing oxygen consumption and fatty acid β-oxidation in adipocytes. Nitrate induces these phenotypic changes through a mechanism distinct from known physiological small molecule activators of browning, the recently identified nitrate-nitrite-nitric oxide pathway. The nitrate-induced browning effect was enhanced in hypoxia, a serious co-morbidity affecting white adipose tissue in obese individuals, and corrected impaired brown adipocyte-specific gene expression in white adipose tissue in a murine model of obesity. Since resulting beige/brite cells exhibit anti-obesity and anti-diabetic effects, nitrate may be an effective means of inducing the browning response in adipose tissue to treat the metabolic syndrome. PMID:25249574

  4. Sustained regeneration of high-volume adipose tissue for breast reconstruction using computer aided design and biomanufacturing.

    PubMed

    Chhaya, Mohit Prashant; Melchels, Ferry Petrus Wilhelmus; Holzapfel, Boris Michael; Baldwin, Jeremy Grant; Hutmacher, Dietmar Werner

    2015-06-01

    Adipose tissue engineering offers a promising alternative to the current breast reconstruction options. Here we investigated patient-specific breast scaffolds fabricated from poly(d,l)-lactide polymer with pore sizes>1 mm for their potential in long-term sustained regeneration of high volume adipose tissue. An optimised scaffold geometry was modelled in silico via a laser scanning data set from a patient who underwent breast reconstruction surgery. After the design process scaffolds were fabricated using an additive manufacturing technology termed fused deposition modelling. Breast-shaped scaffolds were seeded with human umbilical cord perivascular cells and cultured under static conditions for 4 weeks and subsequently 2 weeks in a biaxial rotating bioreactor. These in vitro engineered constructs were then seeded with human umbilical vein endothelial cells and implanted subcutaneously into athymic nude rats for 24 weeks. Angiogenesis and adipose tissue formation were observed throughout all constructs at all timepoints. The percentage of adipose tissue compared to overall tissue area increased from 37.17% to 62.30% between week 5 and week 15 (p<0.01), and increased to 81.2% at week 24 (p<0.01), while the seeded endothelial cells self-organised to form a functional capillary network. The presented approach of fabricating customised scaffolds using 3D scans represents a facile approach towards engineering clinically relevant volumes of adipose tissue for breast reconstruction. PMID:25818460

  5. Lipid storage by adipose tissue macrophages regulates systemic glucose tolerance

    PubMed Central

    Aouadi, Myriam; Vangala, Pranitha; Yawe, Joseph C.; Tencerova, Michaela; Nicoloro, Sarah M.; Cohen, Jessica L.; Shen, Yuefei

    2014-01-01

    Proinflammatory pathways in adipose tissue macrophages (ATMs) can impair glucose tolerance in obesity, but ATMs may also be beneficial as repositories for excess lipid that adipocytes are unable to store. To test this hypothesis, we selectively targeted visceral ATMs in obese mice with siRNA against lipoprotein lipase (LPL), leaving macrophages within other organs unaffected. Selective silencing of ATM LPL decreased foam cell formation in visceral adipose tissue of obese mice, consistent with a reduced supply of fatty acids from VLDL hydrolysis. Unexpectedly, silencing LPL also decreased the expression of genes involved in fatty acid uptake (CD36) and esterification in ATMs. This deficit in fatty acid uptake capacity was associated with increased circulating serum free fatty acids. Importantly, ATM LPL silencing also caused a marked increase in circulating fatty acid-binding protein-4, an adipocyte-derived lipid chaperone previously reported to induce liver insulin resistance and glucose intolerance. Consistent with this concept, obese mice with LPL-depleted ATMs exhibited higher hepatic glucose production from pyruvate and glucose intolerance. Silencing CD36 in ATMs also promoted glucose intolerance. Taken together, the data indicate that LPL secreted by ATMs enhances their ability to sequester excess lipid in obese mice, promoting systemic glucose tolerance. PMID:24986598

  6. Algorithms for muscle oxygenation monitoring corrected for adipose tissue thickness

    NASA Astrophysics Data System (ADS)

    Geraskin, Dmitri; Platen, Petra; Franke, Julia; Kohl-Bareis, Matthias

    2007-07-01

    The measurement of skeletal muscle oxygenation by NIRS methods is obstructed by the subcutaneous adipose tissue which might vary between < 1 mm to more than 12 mm in thickness. A new algorithm is developed to minimize the large scattering effect of this lipid layer on the calculation of muscle haemoglobin / myoglobin concentrations. First, we demonstrate by comparison with ultrasound imaging that the optical lipid signal peaking at 930 nm is a good predictor of the adipose tissue thickness (ATT). Second, the algorithm is based on measurements of the wavelength dependence of the slope ΔA/Δρ of attenuation A with respect to source detector distance ρ and Monte Carlo simulations which estimate the muscle absorption coefficient based on this slope and the additional information of the ATT. Third, we illustrate the influence of the wavelength dependent transport scattering coefficient of the new algorithm by using the solution of the diffusion equation for a two-layered turbid medium. This method is tested on experimental data measured on the vastus lateralis muscle of volunteers during an incremental cycling exercise under normal and hypoxic conditions (corresponding to 0, 2000 and 4000 m altitude). The experimental setup uses broad band detection between 700 and 1000 nm at six source-detector distances. We demonstrate that the description of the experimental data as judged by the residual spectrum is significantly improved and the calculated changes in oxygen saturation are markedly different when the ATT correction is included.

  7. Local proliferation initiates macrophage accumulation in adipose tissue during obesity

    PubMed Central

    Zheng, C; Yang, Q; Cao, J; Xie, N; Liu, K; Shou, P; Qian, F; Wang, Y; Shi, Y

    2016-01-01

    Obesity-associated chronic inflammation is characterized by an accumulation of adipose tissue macrophages (ATMs). It is generally believed that those macrophages are derived from peripheral blood monocytes. However, recent studies suggest that local proliferation of macrophages is responsible for ATM accumulation. In the present study, we revealed that both migration and proliferation contribute to ATM accumulation during obesity development. We show that there is a significant increase in ATMs at the early stage of obesity, which is largely due to an enhanced in situ macrophage proliferation. This result was obtained by employing fat-shielded irradiation and bone marrow reconstitution. Additionally, the production of CCL2, a pivotal chemoattractant of monocytes, was not found to be increased at this stage, corroborating with a critical role of proliferation. Nonetheless, as obesity proceeds, the role of monocyte migration into adipose tissue becomes more significant and those new immigrants further proliferate locally. These proliferating ATMs mainly reside in crown-like structures formed by macrophages surrounding dead adipocytes. We further showed that IL-4/STAT6 is a driving force for ATM proliferation. Therefore, we demonstrated that local proliferation of resident macrophages contributes to ATM accumulation during obesity development and has a key role in obesity-associated inflammation. PMID:27031964

  8. Local proliferation initiates macrophage accumulation in adipose tissue during obesity.

    PubMed

    Zheng, C; Yang, Q; Cao, J; Xie, N; Liu, K; Shou, P; Qian, F; Wang, Y; Shi, Y

    2016-01-01

    Obesity-associated chronic inflammation is characterized by an accumulation of adipose tissue macrophages (ATMs). It is generally believed that those macrophages are derived from peripheral blood monocytes. However, recent studies suggest that local proliferation of macrophages is responsible for ATM accumulation. In the present study, we revealed that both migration and proliferation contribute to ATM accumulation during obesity development. We show that there is a significant increase in ATMs at the early stage of obesity, which is largely due to an enhanced in situ macrophage proliferation. This result was obtained by employing fat-shielded irradiation and bone marrow reconstitution. Additionally, the production of CCL2, a pivotal chemoattractant of monocytes, was not found to be increased at this stage, corroborating with a critical role of proliferation. Nonetheless, as obesity proceeds, the role of monocyte migration into adipose tissue becomes more significant and those new immigrants further proliferate locally. These proliferating ATMs mainly reside in crown-like structures formed by macrophages surrounding dead adipocytes. We further showed that IL-4/STAT6 is a driving force for ATM proliferation. Therefore, we demonstrated that local proliferation of resident macrophages contributes to ATM accumulation during obesity development and has a key role in obesity-associated inflammation. PMID:27031964

  9. The Gq signalling pathway inhibits brown and beige adipose tissue

    PubMed Central

    Klepac, Katarina; Kilić, Ana; Gnad, Thorsten; Brown, Loren M.; Herrmann, Beate; Wilderman, Andrea; Balkow, Aileen; Glöde, Anja; Simon, Katharina; Lidell, Martin E.; Betz, Matthias J.; Enerbäck, Sven; Wess, Jürgen; Freichel, Marc; Blüher, Matthias; König, Gabi; Kostenis, Evi; Insel, Paul A.; Pfeifer, Alexander

    2016-01-01

    Brown adipose tissue (BAT) dissipates nutritional energy as heat via the uncoupling protein-1 (UCP1) and BAT activity correlates with leanness in human adults. Here we profile G protein-coupled receptors (GPCRs) in brown adipocytes to identify druggable regulators of BAT. Twenty-one per cent of the GPCRs link to the Gq family, and inhibition of Gq signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of Gq signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of Gq signalling in brown adipocytes. Expression of a constitutively active Gq protein in mice reduces UCP1 expression in BAT, whole-body energy expenditure and the number of brown-like/beige cells in white adipose tissue (WAT). Furthermore, expression of Gq in human WAT inversely correlates with UCP1 expression. Thus, our data indicate that Gq signalling regulates brown/beige adipocytes and inhibition of Gq signalling may be a novel therapeutic approach to combat obesity. PMID:26955961

  10. Endogenous ways to stimulate brown adipose tissue in humans.

    PubMed

    Broeders, Evie; Bouvy, Nicole D; van Marken Lichtenbelt, Wouter D

    2015-03-01

    Obesity is the result of disequilibrium between energy intake and energy expenditure (EE). Successful long-term weight loss is difficult to achieve with current strategies for the correction of this caloric imbalance. Non-shivering thermogenesis (NST) in brown adipose tissue (BAT) is a possible therapeutic target for the prevention and treatment of obesity and associated metabolic diseases. In recent years, more knowledge about the function and stimulation of bat has been obtained. The sympathetic nervous system (SNS) is currently seen as the main effector for brown fat function. Also, interplay between the thyroid axis and SNS plays an important role in BAT thermogenesis. Almost daily new pathways for the induction of BAT thermogenesis and 'browning' of white adipose tissue (WAT) are identified. Especially the activation of BAT via endogenous pathways has received strong scientific attention. Here we will discuss the relevance of several pathways in activating BAT and their implications for the treatment of obesity. In this review we will focus on the discussion of the most promising endocrine and paracrine pathways to stimulate BAT, by factors and pathways that naturally occur in the human body. PMID:24521443

  11. Ultrastructure of the adipose tissue matrix in children with malnutrition.

    PubMed

    Alexa, A; Drăgan, M; Popa, I; Raica, M; Dema, E

    1995-01-01

    Bioptic fragments of adipose white tissue taken from trochanterian area from children of 2-22 months old were ultrastructurally investigated. Children were of both sexes, 5 normal and 22 with clinical diagnosis of malnutrition. There were studied many interadipocyte spaces signalling out in cases with malnutrition modifications of different components, some of them related with the degree of malnutrition. There were noted: disorganisation and disappearance of basal membranes of capillaries and glycolema; modifications of endothelial cells with lesions of the capillary wall and free degraded red blood cells; disorganization of the ground substance in small areas or sometimes extended to all matrix of the space; collagen fibres reduced in number and size, and in two cases the presence of collagen fibrils with severe lesions, realeasing an electrondense material, fibrinoid-like; matrix infiltration, in some cases with lipids. In only one interadipocyte space a synaptic button was noted in contact with capillary. In malnutrition lesions of cellular elements of the white adipose tissue the following were observed: adipocytes, fibroblasts, fibrocytes, endothelial cells, mast cells--which in their turn are responsible for modifications of macromolecular structures of the extracellular matrix--glycosaminoglycans, proteoglycans, components of which biosyntheses are cell-dependent. PMID:8772367

  12. Adipose atrophy in cancer cachexia: morphologic and molecular analysis of adipose tissue in tumour-bearing mice.

    PubMed

    Bing, C; Russell, S; Becket, E; Pope, M; Tisdale, M J; Trayhurn, P; Jenkins, J R

    2006-10-23

    Extensive loss of adipose tissue is a hallmark of cancer cachexia but the cellular and molecular basis remains unclear. This study has examined morphologic and molecular characteristics of white adipose tissue in mice bearing a cachexia-inducing tumour, MAC16. Adipose tissue from tumour-bearing mice contained shrunken adipocytes that were heterogeneous in size. Increased fibrosis was evident by strong collagen-fibril staining in the tissue matrix. Ultrastructure of 'slimmed' adipocytes revealed severe delipidation and modifications in cell membrane conformation. There were major reductions in mRNA levels of adipogenic transcription factors including CCAAT/enhancer binding protein alpha (C/EBPalpha), CCAAT/enhancer binding protein beta, peroxisome proliferator-activated receptor gamma, and sterol regulatory element binding protein-1c (SREBP-1c) in adipose tissue, which was accompanied by reduced protein content of C/EBPalpha and SREBP-1. mRNA levels of SREBP-1c targets, fatty acid synthase, acetyl CoA carboxylase, stearoyl CoA desaturase 1 and glycerol-3-phosphate acyl transferase, also fell as did glucose transporter-4 and leptin. In contrast, mRNA levels of peroxisome proliferators-activated receptor gamma coactivator-1alpha and uncoupling protein-2 were increased in white fat of tumour-bearing mice. These results suggest that the tumour-induced impairment in the formation and lipid storing capacity of adipose tissue occurs in mice with cancer cachexia. PMID:17047651

  13. Use of Ferritin Expression, Regulated by Neural Cell-Specific Promoters in Human Adipose Tissue-Derived Mesenchymal Stem Cells, to Monitor Differentiation with Magnetic Resonance Imaging In Vitro

    PubMed Central

    Mo, Cuiping; Mu, Shuhua; Jiang, Xiaogang; Li, Xiaoyun; Zhong, Shizhen; Zhao, Zhenfu; Zhou, Guangqian

    2015-01-01

    The purpose of this study was to establish a method for monitoring the neural differentiation of stem cells using ferritin transgene expression, under the control of a neural-differentiation-inducible promoter, and magnetic resonance imaging (MRI). Human adipose tissue-derived mesenchymal stem cells (hADMSCs) were transduced with a lentivirus containing the human ferritin heavy chain 1 (FTH1) gene coupled to one of three neural cell-specific promoters: human synapsin 1 promoter (SYN1p, for neurons), human glial fibrillary acidic protein promoter (GFAPp, for astrocytes), and human myelin basic protein promoter (MBPp, for oligodendrocytes). Three groups of neural-differentiation-inducible ferritin-expressing (NDIFE) hADMSCs were established: SYN1p-FTH1, GFAPp-FTH1, and MBPp-FTH1. The proliferation rate of the NDIFE hADMSCs was evaluated using a Cell Counting Kit-8 assay. Ferritin expression was assessed with western blotting and immunofluorescent staining before and after the induction of differentiation in NDIFE hADMSCs. The intracellular iron content was measured with Prussian blue iron staining and inductively coupled plasma mass spectrometry. R2 relaxation rates were measured with MRI in vitro. The proliferation rates of control and NDIFE hADMSCs did not differ significantly (P > 0.05). SYN1p-FTH1, GFAPp-FTH1, and MBPp-FTH1 hADMSCs expressed specific markers of neurons, astrocytes, and oligodendrocytes, respectively, after neural differentiation. Neural differentiation increased ferritin expression twofold, the intracellular iron content threefold, and the R2 relaxation rate two- to threefold in NDIFE hADMSCs, resulting in notable hypointensity in T2-weighted images (P < 0.05). These results were cross-validated. Thus, a link between neural differentiation and MRI signals (R2 relaxation rate) was established in hADMSCs. The use of MRI and neural-differentiation-inducible ferritin expression is a viable method for monitoring the neural differentiation of h

  14. Retention of sedentary obese visceral white adipose tissue phenotype with intermittent physical activity despite reduced adiposity.

    PubMed

    Wainright, Katherine S; Fleming, Nicholas J; Rowles, Joe L; Welly, Rebecca J; Zidon, Terese M; Park, Young-Min; Gaines, T'Keaya L; Scroggins, Rebecca J; Anderson-Baucum, Emily K; Hasty, Alyssa H; Vieira-Potter, Victoria J; Padilla, Jaume

    2015-09-01

    Regular physical activity is effective in reducing visceral white adipose tissue (AT) inflammation and oxidative stress, and these changes are commonly associated with reduced adiposity. However, the impact of multiple periods of physical activity, intercalated by periods of inactivity, i.e., intermittent physical activity, on markers of AT inflammation and oxidative stress is unknown. In the present study, 5-wk-old male C57BL/6 mice were randomized into three groups (n = 10/group): sedentary, regular physical activity, and intermittent physical activity, for 24 wk. All animals were singly housed and fed a diet containing 45% kcal from fat. Regularly active mice had access to voluntary running wheels throughout the study period, whereas intermittently active mice had access to running wheels for 3-wk intervals (i.e., 3 wk on/3 wk off) throughout the study. At death, regular and intermittent physical activity was associated with similar reductions in visceral AT mass (approximately -24%, P < 0.05) relative to sedentary. However, regularly, but not intermittently, active mice exhibited decreased expression of visceral AT genes related to inflammation (e.g., monocyte chemoattractant protein 1), immune cell infiltration (e.g., CD68, CD11c, F4/80, CD11b/CD18), oxidative stress (e.g., p47 phagocyte oxidase), and endoplasmic reticulum stress (e.g., CCAAT enhancer-binding protein homologous protein; all P < 0.05). Furthermore, regular, but not intermittent, physical activity was associated with a trend toward improvement in glucose tolerance (P = 0.059). Collectively, these findings suggest that intermittent physical activity over a prolonged period of time may lead to a reduction in adiposity but with retention of a sedentary obese white AT and metabolic phenotype. PMID:26180183

  15. Visceral adipose tissue: emerging role of gluco- and mineralocorticoid hormones in the setting of cardiometabolic alterations

    PubMed Central

    Boscaro, Marco; Giacchetti, Gilberta; Ronconi, Vanessa

    2012-01-01

    Several clinical and experimental lines of evidence have highlighted the detrimental effects of visceral adipose tissue excess on cardiometabolic parameters. Besides, recent findings have shown the effects of gluco-and mineralocorticoid hormones on adipose tissue and have also underscored the interplay existing between such adrenal steroids and their respective receptors in the modulation of adipose tissue biology. While the fundamental role played by glucocorticoids on adipocyte differentiation and storage was already well known, the relevance of the mineralocorticoids in the physiology of the adipose organ is of recent acquisition. The local and systemic renin–angiotensin–aldosterone system (RAAS) acting on adipose tissue seems to contribute to the development of the cardiometabolic phenotype so that its modulation can have deep impact on human health. A better understanding of the pathophysiology of the adipose organ is of crucial importance in order to identify possible therapeutic approaches that can avoid the development of such cardiovascular and metabolic sequelae. PMID:22804097

  16. Controlled cellular energy conversion in brown adipose tissue thermogenesis

    NASA Technical Reports Server (NTRS)

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

    1978-01-01

    Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

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

    PubMed Central

    Marcus, Robin L.; Addison, Odessa; Dibble, Leland E.; Foreman, K. Bo; Morrell, Glen; LaStayo, Paul

    2012-01-01

    Objective. Intramuscular adipose tissue (IMAT) and sarcopenia may adversely impact mobility function and physical activity. This study determined the association of locomotor muscle structure and function with mobility function in older adults. Method. 109 older adults with a variety of comorbid disease conditions were examined for thigh muscle composition via MRI, knee extensor strength via isometric dynamometry, and mobility function. The contribution of strength, quadriceps lean tissue, and IMAT to explaining the variability in mobility function was examined using multivariate linear regression models. Results. The predictors as a group contributed 27–45% of the variance in all outcome measures; however, IMAT contributed between 8–15% of the variance in all four mobility variables, while lean explained only 5% variance in only one mobility measure. Conclusions. Thigh IMAT, a newly identified muscle impairment appears to be a potent muscle variable related to the ability of older adults to move about in their community. PMID:22500231

  18. Encapsulation Thermogenic Preadipocytes for Transplantation into Adipose Tissue Depots

    PubMed Central

    Xu, Lu; Shen, Qiwen; Mao, Zhongqi; Lee, L. James; Ziouzenkova, Ouliana

    2015-01-01

    Cell encapsulation was developed to entrap viable cells within semi-permeable membranes. The engrafted encapsulated cells can exchange low molecular weight metabolites in tissues of the treated host to achieve long-term survival. The semipermeable membrane allows engrafted encapsulated cells to avoid rejection by the immune system. The encapsulation procedure was designed to enable a controlled release of bioactive compounds, such as insulin, other hormones, and cytokines. Here we describe a method for encapsulation of catabolic cells, which consume lipids for heat production and energy dissipation (thermogenesis) in the intra-abdominal adipose tissue of obese mice. Encapsulation of thermogenic catabolic cells may be potentially applicable to the prevention and treatment of obesity and type 2 diabetes. Another potential application of catabolic cells may include detoxification from alcohols or other toxic metabolites and environmental pollutants. PMID:26066392

  19. aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose tissue is one of the major sites for fatty acid synthesis and lipid storage. We generated adipose (fat)-specific ACC1 knockout (FACC1KO) mice using the aP2-Cre/loxP system. FACC1KO mice showed prenatal growth retardation; after weaning, however, their weight gain was comparable to that of wi...

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

    PubMed Central

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

    2016-01-01

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

  1. Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals.

    PubMed

    Zhu, Yi; Gao, Yong; Tao, Caroline; Shao, Mengle; Zhao, Shangang; Huang, Wei; Yao, Ting; Johnson, Joshua A; Liu, Tiemin; Cypess, Aaron M; Gupta, Olga; Holland, William L; Gupta, Rana K; Spray, David C; Tanowitz, Herbert B; Cao, Lei; Lynes, Matthew D; Tseng, Yu-Hua; Elmquist, Joel K; Williams, Kevin W; Lin, Hua V; Scherer, Philipp E

    2016-09-13

    "Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels. Blocking of Cx43 channels by 18α-glycyrrhetinic acid decreases POMC-activation-induced adipose tissue beiging. Adipocyte-specific deletion of Cx43 reduces WAT beiging to a level similar to that observed in denervated fat pads. In contrast, overexpression of Cx43 is sufficient to promote beiging even with mild cold stimuli. These data reveal the importance of cell-to-cell communication, effective in cold-induced WAT beiging, for the propagation of limited neuronal inputs in adipose tissue. PMID:27626200

  2. Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome.

    PubMed

    Kokosar, Milana; Benrick, Anna; Perfilyev, Alexander; Fornes, Romina; Nilsson, Emma; Maliqueo, Manuel; Behre, Carl Johan; Sazonova, Antonina; Ohlsson, Claes; Ling, Charlotte; Stener-Victorin, Elisabet

    2016-01-01

    Genetic and epigenetic factors may predispose women to polycystic ovary syndrome (PCOS), a common heritable disorder of unclear etiology. Here we investigated differences in genome-wide gene expression and DNA methylation in adipose tissue from 64 women with PCOS and 30 controls. In total, 1720 unique genes were differentially expressed (Q < 0.05). Six out of twenty selected genes with largest expression difference (CYP1B1, GPT), genes linked to PCOS (RAB5B) or type 2 diabetes (PPARG, SVEP1), and methylation (DMAP1) were replicated in a separate case-control study. In total, 63,213 sites (P < 0.05) and 440 sites (Q < 0.15) were differently methylated. Thirty differentially expressed genes had corresponding changes in 33 different DNA methylation sites. Moreover, a total number of 1913 pairs of differentially expressed "gene-CpG" probes were significantly correlated after correction for multiple testing and corresponded with 349 unique genes. In conclusion, we identified a large number of genes and pathways that are affected in adipose tissue from women with PCOS. We also identified specific DNA methylation pathways that may affect mRNA expression. Together, these novel findings show that women with PCOS have multiple transcriptional and epigenetic changes in adipose tissue that are relevant for development of the disease. PMID:26975253

  3. Pref-1 and adipokine expression in adipose tissues of GK and Zucker rats.

    PubMed

    Barbu, Andreea; Hedlund, Gabriella Persdotter; Lind, Jenny; Carlsson, Carina

    2009-02-27

    In view of the central role of preadipocyte factor-1, adiponectin and leptin in white adipose tissue function, the aim of the present study was to analyze the mRNA expression of these proteins and of the inflammatory markers interleukin-6 and tumor necrosis factor-alpha in visceral and subcutaneous fat pads of rats with different metabolic disorders. We demonstrated highly divergent expression of preadipocyte factor-1, upregulated expression of adiponectin, interleukin-6 and TNF-alpha mRNA in adipose tissues of the diabetic Goto Kakizaki rat compared to the obese Zucker rat. This was correlated to an increased number of large adipocytes and serum levels of adiponectin. Furthermore, in all four strains studied (as above plus Wistar Furth and Zucker Lean), significant heterogeneity was evident in adipokine expression within specific adipose tissues previously defined as belonging to the visceral or subcutaneous fat depots. These results suggest that significantly increased levels of inflammation and redistribution of adipocyte size are mechanisms contributing to the development of type 2 diabetes in the GK rat. PMID:19084046

  4. Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome

    PubMed Central

    Kokosar, Milana; Benrick, Anna; Perfilyev, Alexander; Fornes, Romina; Nilsson, Emma; Maliqueo, Manuel; Behre, Carl Johan; Sazonova, Antonina; Ohlsson, Claes; Ling, Charlotte; Stener-Victorin, Elisabet

    2016-01-01

    Genetic and epigenetic factors may predispose women to polycystic ovary syndrome (PCOS), a common heritable disorder of unclear etiology. Here we investigated differences in genome-wide gene expression and DNA methylation in adipose tissue from 64 women with PCOS and 30 controls. In total, 1720 unique genes were differentially expressed (Q < 0.05). Six out of twenty selected genes with largest expression difference (CYP1B1, GPT), genes linked to PCOS (RAB5B) or type 2 diabetes (PPARG, SVEP1), and methylation (DMAP1) were replicated in a separate case-control study. In total, 63,213 sites (P < 0.05) and 440 sites (Q < 0.15) were differently methylated. Thirty differentially expressed genes had corresponding changes in 33 different DNA methylation sites. Moreover, a total number of 1913 pairs of differentially expressed “gene-CpG” probes were significantly correlated after correction for multiple testing and corresponded with 349 unique genes. In conclusion, we identified a large number of genes and pathways that are affected in adipose tissue from women with PCOS. We also identified specific DNA methylation pathways that may affect mRNA expression. Together, these novel findings show that women with PCOS have multiple transcriptional and epigenetic changes in adipose tissue that are relevant for development of the disease. PMID:26975253

  5. The role of perivascular adipose tissue in vasoconstriction, arterial stiffness, and aneurysm

    PubMed Central

    Villacorta, Luis

    2015-01-01

    Since the “rediscovery” of brown adipose tissue in adult humans, significant scientific efforts are being pursued to identify the molecular mechanisms to promote a phenotypic change of white adipocytes into brown-like cells, a process called “browning”. It is well documented that white adipose tissue (WAT) mass and factors released from WAT influence the vascular function and positively correlate with cardiac arrest, stroke, and other cardiovascular complications. Similar to other fat depots, perivascular adipose tissue (PVAT) is an active endocrine organ and anatomically surrounds vessels. Both brown-like and white-like PVAT secrete various adipokines, cytokines, and growth factors that either prevent or promote the development of cardiovascular diseases (CVDs) depending on the relative abundance of each type and their bioactivity in the neighboring vasculature. Notably, pathophysiological conditions, such as obesity, hypertension, or diabetes, induce the imbalance of PVAT-derived vasoactive products that promote the infiltration of inflammatory cells. This then triggers derangements in vascular smooth muscle cells and endothelial cell dysfunction, resulting in the development of vascular diseases. In this review, we discuss the recent advances on the contribution of PVAT in CVDs. Specifically, we summarize the current proposed roles of PVAT in relationship with vascular contractility, endothelial dysfunction, neointimal formation, arterial stiffness, and aneurysm. PMID:25719334

  6. The role for adipose tissue in weight regain after weight loss.

    PubMed

    MacLean, P S; Higgins, J A; Giles, E D; Sherk, V D; Jackman, M R

    2015-02-01

    Weight regain after weight loss is a substantial challenge in obesity therapeutics. Dieting leads to significant adaptations in the homeostatic system that controls body weight, which promotes overeating and the relapse to obesity. In this review, we focus specifically on the adaptations in white adipose tissues that contribute to the biological drive to regain weight after weight loss. Weight loss leads to a reduction in size of adipocytes and this decline in size alters their metabolic and inflammatory characteristics in a manner that facilitates the clearance and storage of ingested energy. We present the hypothesis whereby the long-term signals reflecting stored energy and short-term signals reflecting nutrient availability are derived from the cellularity characteristics of adipose tissues. These signals are received and integrated in the hypothalamus and hindbrain and an energy gap between appetite and metabolic requirements emerges and promotes a positive energy imbalance and weight regain. In this paradigm, the cellularity and metabolic characteristics of adipose tissues after energy-restricted weight loss could explain the persistence of a biological drive to regain weight during both weight maintenance and the dynamic period of weight regain. PMID:25614203

  7. Adipose Tissue Fatty Acid Patterns and Changes in Anthropometry: A Cohort Study

    PubMed Central

    Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre; Schmidt, Erik Berg; Tjønneland, Anne; Sørensen, Thorkild I. A.; Overvad, Kim

    2011-01-01

    Introduction Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns in adipose tissue fatty acids and changes in anthropometry. Methods 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC), and WC controlled for changes in body mass index (WCBMI), adjusting for confounders. Results 7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men and women, respectively. Fatty acid patterns with high levels of TFA tended to be positively associated with changes in weight and WC for both sexes. Patterns with high levels of n-6 LC-PUFA tended to be negatively associated with changes in weight and WC in men, and positively associated in women. Associations with patterns with high levels of n-3 LC-PUFA were dependent on the context of the rest of the fatty acid pattern. Conclusions Adipose tissue fatty acid patterns with high levels of TFA may be linked to weight gain, but patterns with high n-3 LC-PUFA did not appear to be linked to weight loss. Associations depended on characteristics of the rest of the pattern. PMID:21811635

  8. Phthalate is associated with insulin resistance in adipose tissue of male rat: role of antioxidant vitamins.

    PubMed

    Rajesh, Parsanathan; Sathish, Sampath; Srinivasan, Chinnapaiyan; Selvaraj, Jayaraman; Balasubramanian, Karundevi

    2013-03-01

    Diethyl hexyl phthalate (DEHP) is a plasticizer, commonly used in a variety of products, including lubricants, perfumes, hairsprays and cosmetics, construction materials, wood finishers, adhesives, floorings and paints. DEHP is an endocrine disruptor and it has a continuum of influence on various organ systems in human beings and experimental animals. However, specific effects of DEHP on insulin signaling in adipose tissue are not known. Adult male albino rats of Wistar strain were divided into four groups. Control, DEHP treated (dissolved in olive oil at a dose of 10, and 100 mg/kg body weight, respectively, once daily through gastric intubations for 30 days) and DEHP + vitamin E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubations for 30 days. After the completion of treatment, adipose tissue was dissected out to assess various parameters. DEHP treatment escalated H(2)O(2) and hydroxyl radical levels as well as lipid peroxidation in the adipose tissue. DEHP impaired the expression of insulin signaling molecules and their phosphorelay pathways leading to diminish plasma membrane GLUT4 level and thus decreased glucose uptake and oxidation. Blood glucose level was elevated as a result of these changes. Supplementation of vitamins (C & E) prevented the DEHP-induced changes. It is concluded that DEHP-induced ROS and lipid peroxidation disrupts the insulin signal transduction in adipose tissue and favors glucose intolerance. Antioxidant vitamins have a protective role against the adverse effect of DEHP. PMID:22991202

  9. Decellularized Extracellular Matrix Derived from Porcine Adipose Tissue as a Xenogeneic Biomaterial for Tissue Engineering

    PubMed Central

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

    2012-01-01

    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 α-Gal were significantly reduced. However, abundant ECM components, such as collagen (332.9±12.1 μg/mg ECM dry weight), sulfated glycosaminoglycan (GAG, 85±0.7 μg/mg ECM dry weight), and elastin (152.6±4.5 μg/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

  10. Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

    PubMed Central

    Kooijman, Sander; van den Berg, Rosa; Ramkisoensing, Ashna; Boon, Mariëtte R.; Kuipers, Eline N.; Loef, Marieke; Zonneveld, Tom C. M.; Lucassen, Eliane A.; Sips, Hetty C. M.; Chatzispyrou, Iliana A.; Houtkooper, Riekelt H.; Meijer, Johanna H.; Coomans, Claudia P.; Biermasz, Nienke R.; Rensen, Patrick C. N.

    2015-01-01

    Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity. PMID:25964318

  11. BROWN ADIPOSE TISSUE FUNCTION IN SHORT-CHAIN ACYL-COA DEHYDROGENASE DEFICIENT MICE

    PubMed Central

    Skilling, Helen; Coen, Paul M.; Fairfull, Liane; Ferrell, Robert E.; Goodpaster, Bret H.; Vockley, Jerry; Goetzman, Eric S.

    2010-01-01

    Brown adipose tissue is a highly specialized organ that uses mitochondrial fatty acid oxidation to fuel nonshivering thermogenesis. In mice, mutations in the acyl-CoA dehydrogenase family of fatty acid oxidation genes are associated with sensitivity to cold. Brown adipose tissue function has not previously been characterized in these knockout strains. Short-chain acyl-CoA dehydrogenase (SCAD) deficient mice were found to have increased brown adipose tissue mass as well as modest cardiac hypertrophy. Uncoupling protein-1 was reduced by 70% in brown adipose tissue and this was not due to a change in mitochondrial number, nor was it due to decreased signal transduction through protein kinase A which is known to be a major regulator of uncoupling protein-1 expression. PKA activity and in vitro lipolysis were normal in brown adipose tissue, although in white adipose tissue a modest increase in basal lipolysis was seen in SCAD−/ − mice. Finally, an in vivo norepinephrine challenge of brown adipose tissue thermogenesis revealed normal heat production in SCAD−/− mice. These results suggest that reduced brown adipose tissue function is not the major factor causing cold sensitivity in acyl-CoA dehydrogenase knockout strains. We speculate that other mechanisms such as shivering capacity, cardiac function, and reduced hepatic glycogen stores are involved. PMID:20727852

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

    PubMed Central

    Dordevic, Aimee L.; Pendergast, Felicity J.; Morgan, Han; Villas-Boas, Silas; Caldow, Marissa K.; Larsen, Amy E.; Sinclair, Andrew J.; Cameron-Smith, David

    2015-01-01

    Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD)); body mass index (BMI) 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water), carbohydrate (maltodextrin) or lipid (dairy-cream). Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h), as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03) and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001) decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed. PMID:26140541

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

    PubMed Central

    Park, Byung Young; Lee, Hyunghee; Woo, Sangee; Yoon, Miso; Kim, Jeongjun; Hong, Yeonhee; Lee, Hee Suk; Park, Eun Kyu; Hahm, Jong Cheon; Kim, Jin Woo; Shin, Soon Shik; Kim, Min-Young; Yoon, Michung

    2015-01-01

    It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors. PMID:26599360

  14. Methyl-ß-cyclodextrin alters adipokine gene expression and glucose metabolism in swine adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if metabolic stress as induced by methyl-ß-cyclodextrin (MCD) can alter cytokine expression in neonatal swine adipose tissue explants. Subcutaneous adipose tissue explants (100 ± 10 mg) were prepared from 21 day old pigs. Explants were incubated in medium 199 s...

  15. Adipose tissue infiltration in normal-weight subjects and its impact on metabolic function.

    PubMed

    Moreno-Indias, Isabel; Oliva-Olivera, Wilfredo; Omiste, Antonio; Castellano-Castillo, Daniel; Lhamyani, Said; Camargo, Antonio; Tinahones, Francisco J

    2016-06-01

    Discordant phenotypes, metabolically healthy obese and unhealthy normal-weight individuals, are always interesting to provide important insights into the mechanistic link between adipose tissue dysfunction and associated metabolic alterations. Macrophages can release factors that impair the proper activity of the adipose tissue. Thus, studying subcutaneous and visceral adipose tissues, we investigated for the first time the differences in monocyte/macrophage infiltration, inflammation, and adipogenesis of normal-weight subjects who differed in their degree of metabolic syndrome. The study included 92 normal-weight subjects who differed in their degree of metabolic syndrome. Their anthropometric and biochemical parameters were measured. RNA from subcutaneous and visceral adipose tissues was isolated, and mRNA expression of monocyte/macrophage infiltration (CD68, CD33, ITGAM, CD163, EMR-1, CD206, MerTK, CD64, ITGAX), inflammation (IL-6, tumor necrosis factor alpha [TNFα], IL-10, IL-1b, CCL2, CCL3), and adipogenic and lipogenic capacity markers (PPARgamma, FABP4) were measured. Taken together, our data provide evidence of a different degree of macrophage infiltration between the adipose tissues, with a higher monocyte/macrophage infiltration in subcutaneous adipose tissue in metabolically unhealthy normal-weight subjects, whereas visceral adipose tissue remained almost unaffected. An increased macrophage infiltration of adipose tissue and its consequences, such as a decrease in adipogenesis function, may explain why both the obese and normal-weight subjects can develop metabolic diseases or remain healthy. PMID:26829067

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

    PubMed

    Dordevic, Aimee L; Pendergast, Felicity J; Morgan, Han; Villas-Boas, Silas; Caldow, Marissa K; Larsen, Amy E; Sinclair, Andrew J; Cameron-Smith, David

    2015-07-01

    Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD)); body mass index (BMI) 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water), carbohydrate (maltodextrin) or lipid (dairy-cream). Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h), as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03) and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001) decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed. PMID:26140541

  17. Brown adipose tissue. III. Effect of ethanol, nicotine and caffeine exposure.

    PubMed

    Sidlo, J; Zaviacic, M; Trutzová, H

    1996-05-01

    Brown adipose tissue is known to be the most important organ for generating heat in non-shivering thermogenesis. Process of thermogenesis and thermoregulation may be affected by many drugs. The paper deals with actual literary data of effect of ethanol, nicotine and caffeine on brown adipose tissue, heat production and its regulation in experimental animals and in human. PMID:9560910

  18. Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

    PubMed

    Blüher, Matthias

    2016-09-01

    The worldwide obesity epidemic has become a major health concern, because it contributes to higher mortality due to an increased risk for noncommunicable diseases including cardiovascular diseases, type 2 diabetes, musculoskeletal disorders and some cancers. Insulin resistance may link accumulation of adipose tissue in obesity to metabolic diseases, although the underlying mechanisms are not completely understood. In the past decades, data from human studies and transgenic animal models strongly suggested correlative, but also causative associations between activation of proinflammatory pathways and insulin resistance. Particularly chronic inflammation in adipose tissue seems to play an important role in the development of obesity-related insulin resistance. On the other hand, adipose tissue inflammation has been shown to be essential for healthy adipose tissue expansion and remodelling. However, whether adipose tissue inflammation represents a consequence or a cause of impaired insulin sensitivity remains an open question. A better understanding of the molecular pathways linking excess adipose tissue storage to chronic inflammation and insulin resistance may provide the basis for the future development of anti-inflammatory treatment strategies to improve adverse metabolic consequences of obesity. In this review, potential mechanisms of adipose tissue inflammation and how adipose tissue inflammation may cause insulin resistance are discussed. PMID:27503945

  19. Impact of runting on adipokine gene expression in neonatal pig adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effects of runting on adipokines in neonatal adipose tissue. Pigs were selected as runts (R) by birth weight < 1 kg and compared to littermates (C) of mean litter weight. Subcutaneous (SQ) and perirenal (PR) adipose tissues were collected at d1 (n = 5), d7 (n = 7) or d21 (n...

  20. Human Adipose Tissue Is a Source of Multipotent Stem CellsD⃞

    PubMed Central

    Zuk, Patricia A.; Zhu, Min; Ashjian, Peter; De Ugarte, Daniel A.; Huang, Jerry I.; Mizuno, Hiroshi; Alfonso, Zeni C.; Fraser, John K.; Benhaim, Prosper; Hedrick, Marc H.

    2002-01-01

    Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression. PMID:12475952

  1. Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.

    PubMed

    Nagareddy, Prabhakara R; Kraakman, Michael; Masters, Seth L; Stirzaker, Roslynn A; Gorman, Darren J; Grant, Ryan W; Dragoljevic, Dragana; Hong, Eun Shil; Abdel-Latif, Ahmed; Smyth, Susan S; Choi, Sung Hee; Korner, Judith; Bornfeldt, Karin E; Fisher, Edward A; Dixit, Vishwa Deep; Tall, Alan R; Goldberg, Ira J; Murphy, Andrew J

    2014-05-01

    Obesity is associated with infiltration of macrophages into adipose tissue (AT), contributing to insulin resistance and diabetes. However, relatively little is known regarding the origin of AT macrophages (ATMs). We discovered that murine models of obesity have prominent monocytosis and neutrophilia, associated with proliferation and expansion of bone marrow (BM) myeloid progenitors. AT transplantation conferred myeloid progenitor proliferation in lean recipients, while weight loss in both mice and humans (via gastric bypass) was associated with a reversal of monocytosis and neutrophilia. Adipose S100A8/A9 induced ATM TLR4/MyD88 and NLRP3 inflammasome-dependent IL-1β production. IL-1β interacted with the IL-1 receptor on BM myeloid progenitors to stimulate the production of monocytes and neutrophils. These studies uncover a positive feedback loop between ATMs and BM myeloid progenitors and suggest that inhibition of TLR4 ligands or the NLRP3-IL-1β signaling axis could reduce AT inflammation and insulin resistance in obesity. PMID:24807222

  2. Model of adipose tissue cellularity dynamics during food restriction.

    PubMed

    Soula, H A; Géloën, A; Soulage, C O

    2015-01-01

    Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases related to obesity. Size of fat cells depends on the balance of synthesis and mobilization of lipids and can undergo important variations throughout the life of the organism. These variations usually occur when storing and releasing lipids according to energy demand. In particular when confronted to severe food restriction, adipocyte releases its lipid content via a process called lipolysis. We propose a mathematical model that combines cell diameter distribution and lipolytic response to show that lipid release is a surface (radius squared) limited mechanism. Since this size-dependent rate affects the cell׳s shrinkage speed, we are able to predict the cell size distribution evolution when lipolysis is the only factor at work: such as during an important food restriction. Performing recurrent surgical biopsies on rats, we measured the evolution of adipose cell size distribution for the same individual throughout the duration of the food restriction protocol. We show that our microscopic model of size dependent lipid release can predict macroscopic size distribution evolution. PMID:25196549

  3. Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue.

    PubMed

    Kamble, Prasad G; Pereira, Maria J; Sidibeh, Cherno O; Amini, Sam; Sundbom, Magnus; Börjesson, Joey Lau; Eriksson, Jan W

    2016-05-15

    The adipokine lipocalin 2 is linked to obesity and metabolic disorders. However, its role in human adipose tissue glucose and lipid metabolism is not explored. Here we show that the synthetic glucocorticoid dexamethasone dose-dependently increased lipocalin 2 gene expression in subcutaneous and omental adipose tissue from pre-menopausal females, while it had no effect in post-menopausal females or in males. Subcutaneous adipose tissue from both genders treated with recombinant human lipocalin 2 showed a reduction in protein levels of GLUT1 and GLUT4 and in glucose uptake in isolated adipocytes. In subcutaneous adipose tissue, lipocalin 2 increased IL-6 gene expression whereas expression of PPARγ and adiponectin was reduced. Our findings suggest that lipocalin 2 can contribute to insulin resistance in human adipose tissue. In pre-menopausal females, it may partly mediate adverse metabolic effects exerted by glucocorticoid excess. PMID:26973291

  4. Adipose-Specific Disruption of Signal Transducer and Activator of Transcription 3 Increases Body Weight and Adiposity

    PubMed Central

    Cernkovich, Erin R.; Deng, Jianbei; Bond, Michael C.; Combs, Terry P.; Harp, Joyce B.

    2008-01-01

    To determine the role of STAT3 in adipose tissue, we used Cre-loxP DNA recombination to create mice with an adipocyte-specific disruption of the STAT3 gene (ASKO mice). aP2-Cre-driven disappearance of STAT3 expression occurred on d 6 of adipogenesis, a time point when preadipocytes have already undergone conversion to adipocytes. Thus, this knockout model examined the role of STAT3 in mature but not differentiating adipocytes. Beginning at 9 wk of age, ASKO mice weighed more than their littermate controls and had increased adipose tissue mass, associated with adipocyte hypertrophy, but not adipocyte hyperplasia, hyperphagia, or reduced energy expenditure. Leptin-induced, but not isoproterenol-induced, lipolysis was impaired in ASKO adipocytes, which may partially explain the increased cell size. Despite reduced adiponectin and increased liver triacylglycerol, ASKO mice displayed normal glucose tolerance. Overall, these findings demonstrate that adipocyte STAT3 regulates body weight homeostasis in part through direct effects of leptin on adipocytes. PMID:18096662

  5. Insulin Mediated 14C-Glucose Incorporation Into Adipose Tissue: An Undergraduate Biochemistry Experiment

    ERIC Educational Resources Information Center

    Landman, A. D.; Eskin, N. A. M.

    1975-01-01

    Describes an experiment in which rat adipose tissue samples are exposed to labeled glucose; insulin is added to one sample. Subsequent scintillation counting demonstrates the ability of insulin to facilitate the entry of glucose into the tissue. (MLH)

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

    NASA Technical Reports Server (NTRS)

    Smith, R. E.

    1973-01-01

    The thermogenetic capacities of brown adipose tissue were studied on marmots, rats and monkeys in response to cold exposure. All experiments indicated that the brown fat produced heat and slowed the cooling of tissues.

  7. Neurotrophic Features of Human Adipose Tissue-Derived Stromal Cells: In Vitro and In Vivo Studies

    PubMed Central

    Lattanzi, Wanda; Geloso, Maria Concetta; Saulnier, Nathalie; Giannetti, Stefano; Puglisi, Maria Ausiliatrice; Corvino, Valentina; Gasbarrini, Antonio; Michetti, Fabrizio

    2011-01-01

    Due to its abundance, easy retrieval, and plasticity characteristics, adipose-tissue-derived stromal cells (ATSCs) present unquestionable advantages over other adult-tissue-derived stem cells. Based on the in silico analysis of our previous data reporting the ATSC-specific expression profiles, the present study attempted to clarify and validate at the functional level the expression of the neurospecific genes expressed by ATSC both in vitro and in vivo. This allowed evidencing that ATSCs express neuro-specific trophins, metabolic genes, and neuroprotective molecules. They were in fact able to induce neurite outgrowth in vitro, along with tissue-specific commitment along the neural lineage and the expression of the TRKA neurotrophin receptor in vivo. Our observation adds useful information to recent evidence proposing these cells as a suitable tool for cell-based applications in neuroregenerative medicine. PMID:22219658

  8. Orexin receptor expression in human adipose tissue: effects of orexin-A and orexin-B.

    PubMed

    Digby, J E; Chen, J; Tang, J Y; Lehnert, H; Matthews, R N; Randeva, H S

    2006-10-01

    Orexin-A and orexin-B, via their receptors orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R) have been shown to play a role in the regulation of feeding, body weight, and energy expenditure. Adipose tissue also contributes significantly to the maintenance of body weight by interacting with a complex array of bioactive peptides; however, there are no data as yet on the expression of orexin components in adipose tissue. We, therefore, analyzed the expression of OX1R and OX2R in human adipose tissue and determined functional responses to orexin-A and orexin-B. OX1R and OX2R mRNA expression was detected in subcutaneous (s.c.) and omental adipose tissue and in isolated adipocytes. Protein for OX1R and OX2R was also detected in whole adipose tissue sections and lysates. Treatment with orexin-A, and orexin-B (100 nM, 24 h) resulted in a significant increase in peroxisome proliferator-activated receptors gamma-2 mRNA expression in s.c. adipose tissue (P < 0.05). Hormone sensitive lipase mRNA was significantly reduced in omental adipose tissue with orexin-A and orexin-B treatment (P < 0.05). Glycerol release from omental adipose tissue was also significantly reduced with orexin-A treatment (P < 0.05). These findings demonstrate for the first time the presence of functional orexin receptors in human adipose tissue and suggest a role for orexins in adipose tissue metabolism and adipogenesis. PMID:17065396

  9. Brown adipose tissue: The heat is on the heart.

    PubMed

    Thoonen, Robrecht; Hindle, Allyson G; Scherrer-Crosbie, Marielle

    2016-06-01

    The study of brown adipose tissue (BAT) has gained significant scientific interest since the discovery of functional BAT in adult humans. The thermogenic properties of BAT are well recognized; however, data generated in the last decade in both rodents and humans reveal therapeutic potential for BAT against metabolic disorders and obesity. Here we review the current literature in light of a potential role for BAT in beneficially mediating cardiovascular health. We focus mainly on BAT's actions in obesity, vascular tone, and glucose and lipid metabolism. Furthermore, we discuss the recently discovered endocrine factors that have a potential beneficial role in cardiovascular health. These BAT-secreted factors may have a favorable effect against cardiovascular risk either through their metabolic role or by directly affecting the heart. PMID:27084389

  10. White Adipose Tissue Browning: A Double-edged Sword.

    PubMed

    Abdullahi, Abdikarim; Jeschke, Marc G

    2016-08-01

    The study of white adipose tissue (WAT) 'browning' has become a 'hot topic' in various acute and chronic metabolic conditions, based on the idea that WAT browning might be able to facilitate weight loss and improve metabolic health. However, this view cannot be translated into all areas of medicine. Recent studies identified effects of browning associated with adverse outcomes, and as more studies are being conducted, a very different picture has emerged about WAT browning and its detrimental effect in acute and chronic hypermetabolic conditions. Therefore, the notion that browning is supposedly beneficial may be inadequate. In this review we analyze how and why browning in chronic hypermetabolic associated diseases can be detrimental and lead to adverse outcomes. PMID:27397607

  11. Effect of diethylstilboestrol on adipose-tissue lipids

    PubMed Central

    Sink, J. D.; Huston, C. K.; Shigley, J. W.

    1965-01-01

    1. The effect of diethylstilboestrol on the fatty acid composition of adipose-tissue lipids of the ox (Bos taurus) was studied. 2. The capsula adiposa (perirenal) was shown to contain more total saturated fatty acids, whereas more total unsaturated fatty acids were found in the panniculus adiposus (subcutaneous). 3. Significantly more stearic acid and linolenic acid were obtained from the capsula adiposa, whereas the panniculus adiposus contained more myristoleic acid, palmitoleic acid and oleic acid. 4. Implanting diethylstilboestrol significantly increased the deposition of the saturated fatty acids, particularly stearic acid. 5. A decrease in the deposition of total unsaturated fatty acids, myristoleic acid, palmitoleic acid and linoleic acid can also be attributed to the diethylstilboestrol treatment. PMID:16749140

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

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

    Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

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

    PubMed Central

    Tremblay, Angelo; Picard-Deland, Éliane; Panahi, Shirin; Marette, André

    2015-01-01

    Obesity is generally considered as an excess body fat that increases the risk to develop ergonomic, metabolic, and psychosocial problems. As suggested in this paper, body fat gain is also a protective adaptation that prevents body lipotoxicity, contributes to the secretion of molecules involved in metabolic regulation, and dilutes lipid soluble persistent organic pollutants. Recent literature shows that this protective role of adipose tissue is more solicited in a modern context in which unsuspected factors can affect energy balance to a much greater extent than what is generally perceived by health care professionals. These factors include short sleep duration, demanding mental work, and chemical pollution whose impact is more detectable in a context dominated by economic productivity and competitiveness. Since these factors might also include the increase in atmospheric CO2, it is likely that obesity prevention will need the support of a promotion in sustainable development, whether it is for human health, and well-being or global ecological protection. PMID:26074821

  14. Activation of brown adipose tissue mitochondrial GDP binding sites

    SciTech Connect

    Swick, A.G.

    1987-01-01

    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.

  15. Adipose tissue gene expression and metabolic health of obese adults.

    PubMed

    Das, S K; Ma, L; Sharma, N K

    2015-05-01

    Obese subjects with a similar body mass index (BMI) exhibit substantial heterogeneity in gluco- and cardiometabolic heath phenotypes. However, defining genes that underlie the heterogeneity of metabolic features among obese individuals and determining metabolically healthy and unhealthy phenotypes remain challenging. We conducted unsupervised hierarchical clustering analysis of subcutaneous adipose tissue transcripts from 30 obese men and women ⩾40 years old. Despite similar BMIs in all subjects, we found two distinct subgroups, one metabolically healthy (group 1) and one metabolically unhealthy (group 2). Subjects in group 2 showed significantly higher total cholesterol (P=0.005), low-density lipoprotein cholesterol (P=0.006), 2-h insulin during oral glucose tolerance test (P=0.015) and lower insulin sensitivity (SI, P=0.029) compared with group 1. We identified significant upregulation of 141 genes (for example, MMP9 and SPP1) and downregulation of 17 genes (for example, NDRG4 and GINS3) in group 2 subjects. Intriguingly, these differentially expressed transcripts were enriched for genes involved in cardiovascular disease-related processes (P=2.81 × 10(-11)-3.74 × 10(-02)) and pathways involved in immune and inflammatory response (P=8.32 × 10(-5)-0.04). Two downregulated genes, NDRG4 and GINS3, have been located in a genomic interval associated with cardiac repolarization in published GWASs and zebra fish knockout models. Our study provides evidence that perturbations in the adipose tissue gene expression network are important in defining metabolic health in obese subjects. PMID:25520251

  16. Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering.

    PubMed

    Tan, Huaping; Ramirez, Christina M; Miljkovic, Natasa; Li, Han; Rubin, J Peter; Marra, Kacey G

    2009-12-01

    A series of thermosensitive copolymer hydrogels, aminated hyaluronic acid-g-poly(N-isopropylacrylamide) (AHA-g-PNIPAAm), were synthesized by coupling carboxylic end-capped PNIPAAm (PNIPAAm-COOH) to AHA through amide bond linkages. AHA was prepared by grafting adipic dihydrazide to the HA backbone and PNIPAAm-COOH copolymer was synthesized via a facile thermo-radical polymerization technique by polymerization of NIPAAm using 4,4'-azobis(4-cyanovaleric acid) as an initiator, respectively. The structure of AHA and AHA-g-PNIPAAm copolymer was determined by (1)H NMR. Two AHA-g-PNIPAAm copolymers with different weight ratios of PNIPAAm on the applicability of injectable hydrogels were characterized. The lower critical solution temperature (LCST) of AHA-g-PNIPAAm copolymers in PBS were measured as approximately 30 degrees C by rheological analysis, regardless of the grafting degrees. Enzymatic resistance of AHA-g-PNIPAAm hydrogels with 28% and 53% of PNIPAAm in 100U/mL hyaluronidase/PBS at 37 degrees C was 12.3% and 37.6% over 28 days, respectively. Equilibrium swelling ratios of AHA-g-PNIPAAm hydrogels with 28% of PNIPAAm were 21.5, and significantly decreased to 13.3 with 53% of PNIPAAm in PBS at 37 degrees C. Results from SEM observations confirm a porous 3D AHA-g-PNIPAAm hydrogel structure with interconnected pores after freeze-drying and the pore diameter depends on the weight ratios of PNIPAAm. Encapsulation of human adipose-derived stem cells (ASCs) within hydrogels showed the AHA-g-PNIPAAm copolymers were noncytotoxic and preserved the viability of the entrapped cells. A preliminary in vivo study demonstrated the usefulness of the AHA-g-PNIPAAm copolymer as an injectable hydrogel for adipose tissue engineering. This newly described thermoresponsive AHA-g-PNIPAAm copolymer demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications. PMID:19783043

  17. Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering

    PubMed Central

    Tan, Huaping; Ramirez, Christina M.; Miljkovic, Natasa; Li, Han; Rubin, J. Peter; Marra, Kacey G.

    2009-01-01

    A series of thermosensitive copolymer hydrogels, aminated hyaluronic acid-g-poly(N-isopropylacrylamide) (AHA-g-PNIPAAm), were synthesized by coupling carboxylic end-capped PNIPAAm (PNIPAAm-COOH) to AHA through amide bond linkages. AHA was prepared by grafting adipic dihydrazide to the HA backbone and PNIPAAm-COOH copolymer was synthesized via a facile thermo-radical polymerization technique by polymerization of NIPAAm using 4,4′-azobis(4-cyanovaleric acid) as an initiator, respectively. The structure of AHA and AHA-g-PNIPAAm copolymer was determined by 1H NMR. Two AHA-g-PNIPAAm copolymers with different weight ratios of PNIPAAm on the applicability of injectable hydrogels were characterized. The lower critical solution temperature (LCST) of AHA-g-PNIPAAm copolymers in PBS were measured as ~30°C by rheological analysis, regardless of the grafting degrees. Enzymatic resistance of AHA-g-PNIPAAm hydrogels with 28% and 53% of PNIPAAm in 100U/mL hyaluronidase/PBS at 37°C was 12.3% and 37.6% over 28 days, respectively. Equilibrium swelling ratios of AHA-g-PNIPAAm hydrogels with 28% of PNIPAAm were 21.5, and significantly decreased to 13.3 with 53% of PNIPAAm in PBS at 37°C. Results from SEM observations confirm a porous 3D AHA-g-PNIPAAm hydrogel structure with interconnected pores after freeze-drying and the pore diameter depends on the weight ratios of PNIPAAm. Encapsulation of human adipose-derived stem cells (ASCs) within hydrogels showed the AHA-g-PNIPAAm copolymers were noncytotoxic and preserved the viability of the entrapped cells. A preliminary in vivo study demonstrated the usefulness of the AHA-g-PNIPAAm copolymer as an injectable hydrogel for adipose tissue engineering. This newly described thermoresponsive AHA-g-PNIPAAm copolymer demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications. PMID:19783043

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

    PubMed Central

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

    2014-01-01

    Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a “brite” transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with “browning,” as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes. PMID:24549398

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

    PubMed

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

    2014-04-15

    Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a "brite" transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with "browning," as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes. PMID:24549398

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

    SciTech Connect

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

    2013-08-16

    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 α, peroxisome proliferator-activated receptor γ, 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.

  1. Quantitative Analysis of Lower Leg Adipose Tissue Distribution in Youth with Myelomeningocele.

    PubMed

    Lorenzana, Daniel J; Mueske, Nicole M; Ryan, Deirdre D; Van Speybroeck, Alexander L; Wren, Tishya A L

    2016-07-01

    Children with myelomeningocele have a high prevalence of obesity and excess fat accumulation in their lower extremities. However, it is not known if this is subcutaneous or intramuscular fat, the latter of which has been associated with insulin resistance and metabolic disorders. This study quantified lower leg bone, muscle, and adipose tissue volume in children with myelomeningocele, classifying adipose as subcutaneous or muscle-associated. Eighty-eight children with myelomeningocele and 113 children without myelomeningocele underwent lower leg computed tomographic scans. Subcutaneous and muscle-associated adipose were classified based on location relative to the crural fascia. No differences were seen in subcutaneous adipose. Higher level disease severity was associated with increased muscle-associated adipose volume and decreased muscle volume. Bone volume tended to decrease with higher levels of involvement. Increases in lower leg adiposity in children with myelomeningocele are primarily attributable to accumulation of muscle-associated adipose, which may signify increased risk for metabolic disorders. PMID:26961265

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

    PubMed Central

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

    2015-01-01

    The adipose tissue can make important contributions to immune function. Nevertheless, only a limited number of reports have investigated in lean hosts the immune response elicited in this tissue upon infection. Previous studies suggested that the intracellular protozoan Neospora caninum might affect adipose tissue physiology. Therefore, we investigated in mice challenged with this protozoan if immune cell populations within adipose tissue of different anatomical locations could be differently affected. Early in infection, parasites were detected in the adipose tissue and by 7 days of infection increased numbers of macrophages, regulatory T (Treg) cells and T-bet+ cells were observed in gonadal, mesenteric, omental and subcutaneous adipose tissue. Increased expression of interferon-γ was also detected in gonadal adipose tissue of infected mice. Two months after infection, parasite DNA was no longer detected in these tissues, but T helper type 1 (Th1) cell numbers remained above control levels in the infected mice. Moreover, the Th1/Treg cell ratio was higher than that of controls in the mesenteric and subcutaneous adipose tissue. Interestingly, chronically infected mice presented a marked increase of serum leptin, a molecule that plays a role in energy balance regulation as well as in promoting Th1-type immune responses. Altogether, we show that an apicomplexa parasitic infection influences immune cellular composition of adipose tissue throughout the body as well as adipokine production, still noticed at a chronic phase of infection when parasites were already cleared from that particular tissue. This strengthens the emerging view that infections can have long-term consequences for the physiology of adipose tissue. PMID:25581844

  3. Inflammatory phenotyping identifies CD11d as a gene markedly induced in white adipose tissue in obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In severe obesity, white adipose tissue (WAT) inflammation and macrophage infiltration are believed to contribute to WAT and whole-body insulin resistance. Specific players involved in triggering and maintaining inflammation (i.e., those regulating adipokine release and WAT macrophage recruitment, ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. Fyn Deficiency Promotes a Preferential Increase in Subcutaneous Adipose Tissue Mass and Decreased Visceral Adipose Tissue Inflammation

    PubMed Central

    Lee, Ting-Wen A.; Kwon, Hyokjoon; Zong, Haihong; Yamada, Eijiro; Vatish, Manu; Pessin, Jeffrey E.; Bastie, Claire C.

    2013-01-01

    Previous studies have demonstrated that Fyn knockout (FynKO) mice on a standard chow diet display increased glucose clearance and whole-body insulin sensitivity associated with decreased adiposity resulting from increased fatty acid use and energy expenditure. Surprisingly, however, despite a similar extent of adipose tissue (AT) mass accumulation on a high-fat diet, the FynKO mice remained fully glucose tolerant and insulin sensitive. Physiologic analyses demonstrated that the FynKO mice had a combination of skewed AT expansion into the subcutaneous compartment rather than to the visceral depot, reduced AT inflammation associated with reduced T-cell and macrophage infiltration, and increased proportion of anti-inflammatory M2 macrophages. These data demonstrate that Fyn is an important regulator of whole-body integrative metabolism that coordinates AT expansion, inflammation, and insulin sensitivity in states of nutrient excess. These data further suggest that inhibition of Fyn function may provide a novel target to prevent AT inflammation, insulin resistance, and the dyslipidemia components of the metabolic syndrome. PMID:23321073

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

    PubMed Central

    2012-01-01

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

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

    PubMed Central

    He, Yunfan; Lu, Feng

    2016-01-01

    Adipose stem cells have prominent implications in tissue regeneration due to their abundance and relative ease of harvest from adipose tissue and their abilities to differentiate into mature cells of various tissue lineages and secrete various growth cytokines. Development of tissue engineering techniques in combination with various carrier scaffolds and adipose stem cells offers great potential in overcoming the existing limitations constraining classical approaches used in plastic and reconstructive surgery. However, as most tissue engineering techniques are new and highly experimental, there are still many practical challenges that must be overcome before laboratory research can lead to large-scale clinical applications. Tissue engineering is currently a growing field of medical research; in this review, we will discuss the progress in research on biomaterials and scaffolds for tissue engineering applications using adipose stem cells. PMID:26977158

  8. Evaluation of cartilage, synovium and adipose tissue as cellular sources for osteochondral repair.

    PubMed

    Innes, J F; Gordon, C; Vaughan-Thomas, A; Rhodes, N P; Clegg, P D

    2013-09-01

    Osteochondral lesions are a major cause of pain and disability in several species including dogs, horses and human beings. The objective of this study was to assess three potential sources of canine cells for their osteochondral regenerative potential. Cartilage, synovium and adipose tissue cells were grown in pellet culture in chondrogenic or osteogenic media. Cartilage-derived pellets displayed the best chondrogenic differentiation as indicated by significantly higher COL2A1 and SOX9 mRNA expression, greater glycosaminoglycan content, and higher retention of Safranin-O stain compared to the synovium and adipose-derived cells. Following application of the osteogenic media, all three cell sources exhibited small areas of positive alizarin red staining. Poor intracellular alkaline phosphatase activity was found in all three cell types when stimulated although osteocalcin and RUNX2 expression were significantly increased. Cells isolated and cultured from canine articular cartilage retained their specific chondrocytic phenotype. Furthermore, canine adipocytes and synovial cells did not undergo chondrogenic differentiation and did not exhibit evidence of multipotency. Although osteogenic differentiation was initiated at a genomic level, phenotypic osteoblastic differentiation was not observed. The findings of this study suggest that cells isolated from canine adipose tissue and synovium are sub-optimal substitutes for chondrocytes when engineering articular cartilage in vitro. PMID:23886701

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. Exploration of steroidogenesis-related genes in testes, ovaries, adrenals, liver and adipose tissue in pigs.

    PubMed

    Robic, Annie; Feve, Katia; Louveau, Isabelle; Riquet, Juliette; Prunier, Armelle

    2016-08-01

    To explore the metabolism of steroids in the pig species, a qualitative PCR analysis was performed for the main transcript of 27 genes involved in steroid metabolism. We compared samples of testes, adipose tissue and liver from immature and peripubertal males, adrenal cortex from peripubertal males, ovaries from cyclic females and adipose tissue from peripubertal females. Some genes were shown to have a tissue-specific expression. Two of them were expressed only in testes, ovaries and adrenals: CYP11A1 and CYP11B. The CYP21 and HSD17B3 genes, were expressed respectively only in adrenals and only in testes. Very few differences were observed between transcriptional patterns of peripubertal testes and adrenal glands as well as between male and female fat tissues. However, the expression of genes involved in the sulfonation of steroids was higher in testes than in adrenals from males. Main differences between ovaries and testes were observed for HSD17B1/2/3, AKR1C-pig6 and sulfotransferase genes (SULT2A1/SULT2B1). The present study shows that the SRD5A2 and CYP21 genes were not involved in the testicular biosynthesis of androstenone. It also shows that porcine adrenal glands produce essentially corticosteroids and that fat tissue is unable to produce de novo steroids. PMID:27436769

  11. Voluntary physical activity abolishes the proliferative tumor growth microenvironment created by adipose tissue in animals fed a high fat diet.

    PubMed

    Theriau, Christopher F; Shpilberg, Yaniv; Riddell, Michael C; Connor, Michael K

    2016-07-01

    The molecular mechanisms behind the obesity-breast cancer association may be regulated via adipokine secretion by white adipose tissue. Specifically, adiponectin and leptin are altered with adiposity and exert antagonistic effects on cancer cell proliferation. We set out to determine whether altering adiposity in vivo via high fat diet (HFD) feeding changed the tumor growth supporting nature of adipose tissue and whether voluntary physical activity (PA) could ameliorate these HFD-dependent effects. We show that conditioned media (CM) created from the adipose tissue of HFD fed animals caused an increase in the proliferation of MCF7 cells compared with cells exposed to CM prepared from the adipose of lean chow diet fed counterparts. This increased proliferation was driven within the MCF7 cells by an HFD-dependent antagonism between AMP-activated protein kinase (AMPK) and protein kinase B (Akt) signaling pathways, decreasing p27 protein levels via reduced phosphorylation at T198 and downregulation of adiponectin receptor 1 (AdipoR1). PA can ameliorate these proliferative effects of HFD-CM on MCF7 cells, increasing p27(T198) by AMPK, reducing pAkt(T308), and increasing AdipoR1, resulting in cell cycle withdrawal in a manner that depends on the PA intensity. High physical activity (>3 km/day) completely abolished the effects of HFD feeding. In addition, AdipoR1 overexpression mimics the effects of exercise, abolishing the proliferative effects of the HFD-CM on MCF7 cells and further enhancing the antiproliferative effects of PA on the HFD-CM. Thus voluntary PA represents a means to counteract the proliferative effects of adipose tissue on breast cancers in obese patients. PMID:27150834

  12. Arteriovenous differences across human adipose and forearm tissues after overnight fast.

    PubMed

    Coppack, S W; Frayn, K N; Humphreys, S M; Whyte, P L; Hockaday, T D

    1990-04-01

    Measurements of arteriovenous differences across subcutaneous abdominal tissue (mainly adipose) and deep forearm tissue (mainly muscle) were made on 25 occasions in normal subjects after an overnight fast. Adipose tissue was shown to be strongly lipolytic (releasing nonesterified fatty acids and glycerol), to clear circulating triacylglycerol, glucose, ketone bodies and acetate, and to produce lactate. Uptake of circulating carbohydrate and ketones was sufficient to account for only 51% of the adipose tissue oxygen consumption, implying that adipose tissue utilizes fuel(s) stored within it. The mean fractional re-esterification rate of fatty acids in adipose tissue was 13% to 19%. Arteriovenous differences were converted to fluxes of carbon atoms to compare the movements of different fuels. (Amino acids were not included in these calculations.) Adipose tissue after an overnight fast was a net exporter of carbon, whereas in resting muscle the uptake of carbon atoms from circulating carbohydrate and lipid fuels approximately balanced the CO2 production. Fatty acids were the main form in which carbon left adipose tissue, and the main source of carbon atoms entering the resting forearm. PMID:2109165

  13. Adipose tissue monomethyl branched chain fatty acids and insulin sensitivity: effects of obesity and weight loss

    PubMed Central

    Su, Xiong; Magkos, Faidon; Zhou, Dequan; Eagon, J. Christopher; Fabbrini, Elisa; Okunade, Adewole L.; Klein, Samuel

    2014-01-01

    Objective An increase in circulating branched-chain amino acids (BCAA) is associated with insulin resistance. Adipose tissue is a potentially important site for BCAA metabolism. We evaluated whether monomethyl branched chain fatty acids (mmBCFA) in adipose tissue, which are likely derived from BCAA catabolism, are associated with insulin sensitivity. Design and Methods Insulin-stimulated glucose disposal was determined by using the hyperinsulinemic-euglycemic clamp procedure with stable isotope glucose tracer infusion, in 9 lean and 9 obese subjects, and in a separate group of 9 obese subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery (38% weight loss). Adipose tissue mmBCFA content was measured in tissue biopsies taken in the basal state. Results Total adipose tissue mmBCFA content was ~30% lower in obese than lean subjects (P = 0.02), and increased by ~65% after weight loss in the RYGB group (P = 0.01). Adipose tissue mmBCFA content correlated positively with skeletal muscle insulin sensitivity (R2 = 35%, P = 0.01, n = 18). Conclusions These results demonstrate a novel association between adipose tissue mmBCFA content and obesity-related insulin resistance. Additional studies are needed to determine whether the association between adipose tissue mmBCFA and muscle insulin sensitivity is causal or a simple association. PMID:25328153

  14. Comparative lipoplasty analysis of in vivo-treated adipose tissue.

    PubMed

    Rohrich, R J; Morales, D E; Krueger, J E; Ansari, M; Ochoa, O; Robinson, J; Beran, S J

    2000-05-01

    A comparative histologic and chemical analysis was undertaken of adipose tissue treated in vivo with traditional, ultrasound-assisted, and external ultrasound-assisted lipoplasty. A series of six healthy women undergoing elective liposuction according to the superwet technique using a 1:1 infiltration ratio with the estimated quantity of fat to be removed was included in the study. Four separate regions on each patient were treated independently in vivo with traditional liposuction, internal ultrasound-assisted liposuction, or external ultrasound-assisted liposuction for 7 minutes. External massage was used as a control. Four separate specimens of adipose tissue from each patient were assessed for cellular disruption using blinded histologic evaluation. The remainder of tissue was centrifuged to separate the aqueous phase from the cellular components and then spectrophotometrically analyzed for creatinine kinase and glycerol 3-phosphate dehydrogenase activity as markers of cellular disruption. Histologic analysis confirmed 70 to 90 percent cellular disruption with internal ultrasound-assisted liposuction. Suction-assisted and external ultrasound-assisted liposuction showed 5 to 25 percent disruption, whereas massage controls showed only 5 percent. Only internal ultrasound-assisted liposuction showed 5 to 20 percent thermal liquefaction. Absorbance analysis showed creatine kinase activity (sigma units) greatest in ultrasound-exposed tissue. Both external and internal ultrasound-assisted liposuction gave creatine kinase levels 28 to 33 percent greater than suction-assisted liposuction, which varied only 10 percent from controls. Glycerol 3-phosphate dehydrogenase activity was 44 percent greater for internal ultrasound-assisted liposuction than that detected with suction-assisted liposuction. Glycerol 3-phosphate dehydrogenase activity with external ultrasound-assisted liposuction and massage did not vary much from each other, at only 14 percent and 11 percent

  15. Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of Humans With Type 2 Diabetes

    PubMed Central

    Beavers, Lisa S.; Conner, Laura J.; Corominola, Helena; Johnson, Dwayne; Hammond, Craig D.; Rafaeloff-Phail, Ronit; Seng, Thomas; Suter, Todd M.; Sluka, James P.; Ravussin, Eric; Gadski, Robert A.; Caro, Jose F.

    2000-01-01

    We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFα and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes. PMID:11469400

  16. CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity.

    PubMed

    Morris, David L; Oatmen, Kelsie E; Mergian, Taleen A; Cho, Kae Won; DelProposto, Jennifer L; Singer, Kanakadurga; Evans-Molina, Carmella; O'Rourke, Robert W; Lumeng, Carey N

    2016-06-01

    Obesity activates both innate and adaptive immune responses in adipose tissue, but the mechanisms critical for regulating these responses remain unknown. CD40/CD40L signaling provides bidirectional costimulatory signals between antigen-presenting cells and CD4(+) T cells, and CD40L expression is increased in obese humans. Therefore, we examined the contribution of CD40 to the progression of obesity-induced inflammation in mice. CD40 was highly expressed on adipose tissue macrophages in mice, and CD40/CD40L signaling promoted the expression of antigen-presenting cell markers in adipose tissue macrophages. When fed a high fat diet, Cd40-deficient mice had reduced accumulation of conventional CD4(+) T cells (Tconv: CD3(+)CD4(+)Foxp3(-)) in visceral fat compared with wild-type mice. By contrast, the number of regulatory CD4(+) T cells (Treg: CD3(+)CD4(+)Foxp3(+)) in lean and obese fat was similar between wild-type and knockout mice. Adipose tissue macrophage content and inflammatory gene expression in fat did not differ between obese wild-type and knockout mice; however, major histocompatibility complex class II and CD86 expression on adipose tissue macrophages was reduced in visceral fat from knockout mice. Similar results were observed in chimeric mice with hematopoietic Cd40-deficiency. Nonetheless, neither whole body nor hematopoietic disruption of CD40 ameliorated obesity-induced insulin resistance in mice. In human adipose tissue, CD40 expression was positively correlated with CD80 and CD86 expression in obese patients with type 2 diabetes. These findings indicate that CD40 signaling in adipose tissue macrophages regulates major histocompatibility complex class II and CD86 expression to control the expansion of CD4(+) T cells; however, this is largely dispensable for the development of obesity-induced inflammation and insulin resistance in mice. PMID:26658005

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

    PubMed Central

    Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

    2015-01-01

    Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

  18. Serially Transplanted Nonpericytic CD146(-) Adipose Stromal/Stem Cells in Silk Bioscaffolds Regenerate Adipose Tissue In Vivo.

    PubMed

    Frazier, Trivia P; Bowles, Annie; Lee, Stephen; Abbott, Rosalyn; Tucker, Hugh A; Kaplan, David; Wang, Mei; Strong, Amy; Brown, Quincy; He, Jibao; Bunnell, Bruce A; Gimble, Jeffrey M

    2016-04-01

    Progenitors derived from the stromal vascular fraction (SVF) of white adipose tissue (WAT) possess the ability to form clonal populations and differentiate along multiple lineage pathways. However, the literature continues to vacillate between defining adipocyte progenitors as "stromal" or "stem" cells. Recent studies have demonstrated that a nonpericytic subpopulation of adipose stromal cells, which possess the phenotype, CD45(-) /CD31(-) /CD146(-) /CD34(+) , are mesenchymal, and suggest this may be an endogenous progenitor subpopulation within adipose tissue. We hypothesized that an adipose progenitor could be sorted based on the expression of CD146, CD34, and/or CD29 and when implanted in vivo these cells can persist, proliferate, and regenerate a functional fat pad over serial transplants. SVF cells and culture expanded adipose stromal/stem cells (ASC) ubiquitously expressing the green fluorescent protein transgene (GFP-Tg) were fractionated by flow cytometry. Both freshly isolated SVF and culture expanded ASC were seeded in three-dimensional silk scaffolds, implanted subcutaneously in wild-type hosts, and serially transplanted. Six-week WAT constructs were removed and evaluated for the presence of GFP-Tg adipocytes and stem cells. Flow cytometry, quantitative polymerase chain reaction, and confocal microscopy demonstrated GFP-Tg cell persistence, proliferation, and expansion, respectively. Glycerol secretion and glucose uptake assays revealed GFP-Tg adipose was metabolically functional. Constructs seeded with GFP-Tg SVF cells or GFP-Tg ASC exhibited higher SVF yields from digested tissue, and higher construct weights, compared to nonseeded controls. Constructs derived from CD146(-) CD34(+) -enriched GFP-Tg ASC populations exhibited higher hemoglobin saturation, and higher frequency of GFP-Tg cells than unsorted or CD29(+) GFP-Tg ASC counterparts. These data demonstrated successful serial transplantation of nonpericytic adipose-derived progenitors that can

  19. The adipose tissue to serum dichlorodiphenyldichloroethane (DDE) ratio: Some methodological considerations

    SciTech Connect

    Lopez-Carrillo, L. . National Inst. of Public Health John D. and Catherine T. MacArthur Foundation ); Torres-Sanchez, L.; Lopez-Cervantes, M. . National Inst. of Public Health); Blair, A. ); Cebrian, M.E.; Uribe, M. . Center for Research and Advanced Studies)

    1999-08-01

    Dichlorodiphenyldichloroethane (DDE) adipose tissue level has been regarded as a preferred indicator of accumulated human exposure to DDT; however, blood sera are more feasible to obtain and analyze than adipose tissue samples. Inconsistent and scarce information exists in relation to the adipose tissue/serum DDE ratio. As a part of a hospital-based case-control study performed in Mexico City from 1994 to 1996, 198 paired serum and adipose tissue samples were obtained from 72 women with histologically confirmed breast cancer and 126 women with benign breast disease. Both adipose tissue and serum DDE levels were determined by gas-liquid chromatography and reported as ppb lipid weight (ng/g) as well as wet basis (ng/ml). Results showed that the adipose tissue/serum DDE ratio (ADSE) varies according to the type of information (lipid vs wet basis, arithmetic vs geometric means) used for its estimation. ADSE gets a value near 1 (1.1) only when the geometric DDE levels in lipid basis are used for its estimation. The correlation between DDE serum and adipose tissue levels was found (r = 0.364, P < 0.001). The ADSE did not vary by disease status, nor was it altered by parity, history of breast-feeding, and other reproductive characteristics. The authors endorse the use of venipuncture instead of biopsy as a way to estimate DDT body burden levels in further research.

  20. The role of adipose tissue in mediating the beneficial effects of dietary fish oil

    PubMed Central

    Puglisi, Michael J.; Hasty, Alyssa H.; Saraswathi, Viswanathan

    2010-01-01

    Fish oil improves several features of metabolic syndrome such as dyslipidemia, insulin resistance and hepatic steatosis. Fish oil may mediate some of its beneficial effects by modulating the storage and/or secretory functions of adipose tissue. The storage of triglycerides in adipose tissue is regulated by the availability of free fatty acids as well as the degree of lipolysis in adipose tissue. Fish oil has been shown to reduce lipolysis in several studies indicating improved triglyceride storage. Importantly, adipose tissue secretes a variety of adipokines and fish oil feeding is associated with remarkable changes in the plasma levels of two key adipokines, adiponectin and leptin. Much attention has been focused on the contribution of adiponectin in fish oil mediated improvements in metabolic syndrome. However, emerging evidence also indicates a role of leptin in modulating the components of the metabolic syndrome upon fish oil feeding. In addition to improving the storage and secretory functions of adipose tissue, fish oil, and the n-3 fatty acids found in fish oil, has been shown to reduce inflammation in adipose tissue. These effects may be in part a result of activation of peroxisome proliferator-activated receptor γ or inhibition of toll-like receptor 4. Thus, there is compelling evidence that fish oil mediates its beneficial effects on metabolic syndrome by improving adipose tissue storage and secretory functions and by reducing inflammation. PMID:21145721

  1. Development of the Mouse Dermal Adipose Layer Occurs Independently of Subcutaneous Adipose Tissue and Is Marked by Restricted Early Expression of FABP4

    PubMed Central

    Ambler, Carrie A.; Manning, Craig B.; Jahoda, Colin A. B.

    2013-01-01

    The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16) the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis), under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot. PMID:23555789

  2. Activation of prostaglandin E2-EP4 signaling reduces chemokine production in adipose tissue.

    PubMed

    Tang, Eva H C; Cai, Yin; Wong, Chi Kin; Rocha, Viviane Z; Sukhova, Galina K; Shimizu, Koichi; Xuan, Ge; Vanhoutte, Paul M; Libby, Peter; Xu, Aimin

    2015-02-01

    Inflammation of adipose tissue induces metabolic derangements associated with obesity. Thus, determining ways to control or inhibit inflammation in adipose tissue is of clinical interest. The present study tested the hypothesis that in mouse adipose tissue, endogenous prostaglandin E2 (PGE2) negatively regulates inflammation via activation of prostaglandin E receptor 4 (EP4). PGE2 (5-500 nM) attenuated lipopolysaccharide-induced mRNA and protein expression of chemokines, including interferon-γ-inducible protein 10 and macrophage-inflammatory protein-1α in mouse adipose tissue. A selective EP4 antagonist (L161,982) reversed, and two structurally different selective EP4 agonists [CAY10580 and CAY10598] mimicked these actions of PGE2. Adipose tissue derived from EP4-deficient mice did not display this response. These findings establish the involvement of EP4 receptors in this anti-inflammatory response. Experiments performed on adipose tissue from high-fat-fed mice demonstrated EP4-dependent attenuation of chemokine production during diet-induced obesity. The anti-inflammatory actions of EP4 became more important on a high-fat diet, in that EP4 activation suppressed a greater variety of chemokines. Furthermore, adipose tissue and systemic inflammation was enhanced in high-fat-fed EP4-deficient mice compared with wild-type littermates, and in high-fat-fed untreated C57BL/6 mice compared with mice treated with EP4 agonist. These findings provide in vivo evidence that PGE2-EP4 signaling limits inflammation. In conclusion, PGE2, via activation of EP4 receptors, functions as an endogenous anti-inflammatory mediator in mouse adipose tissue, and targeting EP4 may mitigate adipose tissue inflammation. PMID:25510249

  3. Toxicological Function of Adipose Tissue: Focus on Persistent Organic Pollutants

    PubMed Central

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

    2012-01-01

    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

  4. Cerenkov luminescence imaging of interscapular brown adipose tissue.

    PubMed

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

    2014-01-01

    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

  5. Organochlorine pesticides and PCBs in human adipose tissues in Poland

    SciTech Connect

    Ludwicki, J.K.; Goralczyk, K. )

    1994-03-01

    Most of the persistent organochlorine (OC) pesticides, excluding lindane, were banned in Poland in 1975/76. The first restrictions concerning the use and marketing of lindane (gamma-HCH) became effective in 1980 and were gradually extended until it's agricultural use was ultimately banned in 1989. Unfortunately, there are no detailed data on the use and release of PCBs to the environment in Poland. The former studies showed that in the late seventies the concentrations of OC pesticides and their metabolites in men reached considerable high levels. Despite of the restrictions or bans of these pesticides in most of the countries of the temperate climate, they still circulate in various food chains and eventually concentrate in man. Many authors claim an uneven distribution of the OC compounds in the population and report different levels in men and women and also some relations between OC compounds levels in fat tissues and age. Environmental contamination also plays an important role in the magnitude of OC compounds levels in man. The aim of this paper is to present the actual concentrations of HCB, p,p[prime]-DDT, p,p[prime]-DDE, isomers of HCH (alpha, beta, gamma), and PCBs in human adipose tissues particularly regarding age and sex as possible factors influencing the levels of these compounds and to contribute to the general discussion on the distribution patterns of the organochlorine compounds in the population. 12 refs., 3 tabs.

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

    SciTech Connect

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

    1987-11-01

    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.

  7. Impaired Thermogenesis and a Molecular Signature for Brown Adipose Tissue in Id2 Null Mice.

    PubMed

    Zhou, Peng; Robles-Murguia, Maricela; Mathew, Deepa; Duffield, Giles E

    2016-01-01

    Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated that Id2 null mice have sex-specific elevated glucose uptake in brown adipose tissue (BAT). Here we further explored the role of Id2 in the regulation of core body temperature over the circadian cycle and the impact of Id2 deficiency on genes involved in insulin signaling and adipogenesis in BAT. We discovered a reduced core body temperature in Id2-/- mice. Moreover, in Id2-/- BAT, 30 genes including Irs1, PPARs, and PGC-1s were identified as differentially expressed in a sex-specific pattern. These data provide valuable insights into the impact of Id2 deficiency on energy homeostasis of mice in a sex-specific manner. PMID:27144179

  8. Impaired Thermogenesis and a Molecular Signature for Brown Adipose Tissue in Id2 Null Mice

    PubMed Central

    Zhou, Peng; Robles-Murguia, Maricela; Mathew, Deepa; Duffield, Giles E.

    2016-01-01

    Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated that Id2 null mice have sex-specific elevated glucose uptake in brown adipose tissue (BAT). Here we further explored the role of Id2 in the regulation of core body temperature over the circadian cycle and the impact of Id2 deficiency on genes involved in insulin signaling and adipogenesis in BAT. We discovered a reduced core body temperature in Id2−/− mice. Moreover, in Id2−/− BAT, 30 genes including Irs1, PPARs, and PGC-1s were identified as differentially expressed in a sex-specific pattern. These data provide valuable insights into the impact of Id2 deficiency on energy homeostasis of mice in a sex-specific manner. PMID:27144179

  9. Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Menopause promotes central obesity, adipose tissue (AT) inflammation and insulin resistance (IR). Both obesity and the loss of estrogen can activate innate and adaptive immune cells (macrophages (M's), T-cells). The respective impacts of weight gain and loss of ovarian hormones on AT inflammation an...

  10. Central Neural Regulation of Brown Adipose Tissue Thermogenesis and Energy Expenditure

    PubMed Central

    Tupone, Domenico

    2014-01-01

    SUMMARY Thermogenesis, the production of heat energy, is the specific, neurally-regulated, metabolic function of brown adipose tissue (BAT) and contributes to the maintenance of body temperature during cold exposure and to the elevated core temperature during several behavioral states, including wakefulness, the acute phase response (fever), and stress. BAT energy expenditure requires metabolic fuel availability and contributes to energy balance. This review summarizes the functional organization and neurochemical influences within the CNS networks governing the level of BAT sympathetic nerve activity to produce the thermoregulatory and metabolically-driven alterations in BAT thermogenesis and energy expenditure that contribute to overall energy homeostasis. PMID:24630813

  11. Brown Adipose Tissue Harbors a Distinct Sub-Population of Regulatory T Cells

    PubMed Central

    Medrikova, Dasa; Sijmonsma, Tjeerd P.; Sowodniok, Katharina; Richards, David M.; Delacher, Michael; Sticht, Carsten; Gretz, Norbert; Schafmeier, Tobias; Feuerer, Markus; Herzig, Stephan

    2015-01-01

    Regulatory T (Treg) cells are critical determinants of both immune responses and metabolic control. Here we show that systemic ablation of Treg cells compromised the adaptation of whole-body energy expenditure to cold exposure, correlating with impairment in thermogenic marker gene expression and massive invasion of pro-inflammatory macrophages in brown adipose tissue (BAT). Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature. As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress. PMID:25714366

  12. Disabled homolog 2 controls macrophage phenotypic polarization and adipose tissue inflammation

    PubMed Central

    Adamson, Samantha E.; Moravec, Radim; Senthivinayagam, Subramanian; Montgomery, Garren; Chen, Wenshu; Han, Jenny; Sharma, Poonam R.; Mullins, Garrett R.; Gorski, Stacey A.; Cooper, Jonathan A.; Kadl, Alexandra; Enfield, Kyle; Braciale, Thomas J.; Harris, Thurl E.

    2016-01-01

    Acute and chronic tissue injury results in the generation of a myriad of environmental cues that macrophages respond to by changing their phenotype and function. This phenotypic regulation is critical for controlling tissue inflammation and resolution. Here, we have identified the adaptor protein disabled homolog 2 (DAB2) as a regulator of phenotypic switching in macrophages. Dab2 expression was upregulated in M2 macrophages and suppressed in M1 macrophages isolated from both mice and humans, and genetic deletion of Dab2 predisposed macrophages to adopt a proinflammatory M1 phenotype. In mice with myeloid cell–specific deletion of Dab2 (Dab2fl/fl Lysm-Cre), treatment with sublethal doses of LPS resulted in increased proinflammatory gene expression and macrophage activation. Moreover, chronic high-fat feeding exacerbated adipose tissue inflammation, M1 polarization of adipose tissue macrophages, and the development of insulin resistance in DAB2-deficient animals compared with controls. Mutational analyses revealed that DAB2 interacts with TNF receptor–associated factor 6 (TRAF6) and attenuates IκB kinase β–dependent (IKKβ-dependent) phosphorylation of Ser536 in the transactivation domain of NF-κB p65. Together, these findings reveal that DAB2 is critical for controlling inflammatory signaling during phenotypic polarization of macrophages and suggest that manipulation of DAB2 expression and function may hold therapeutic potential for the treatment of acute and chronic inflammatory disorders. PMID:26927671

  13. Adipose mesenchymal stem cells in the field of bone tissue engineering

    PubMed Central

    Romagnoli, Cecilia; Brandi, Maria Luisa

    2014-01-01

    Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians. Current failures of autografts and allografts in many pathological conditions have prompted researchers to find new biomaterials able to promote bone repair or regeneration with specific characteristics of biocompatibility, biodegradability and osteoinductivity. Recent advancements for tissue regeneration in bone defects have occurred by following the diamond concept and combining the use of growth factors and mesenchymal stem cells (MSCs). In particular, a more abundant and easily accessible source of MSCs was recently discovered in adipose tissue. These adipose stem cells (ASCs) can be obtained in large quantities with little donor site morbidity or patient discomfort, in contrast to the invasive and painful isolation of bone marrow MSCs. The osteogenic potential of ASCs on scaffolds has been examined in cell cultures and animal models, with only a few cases reporting the use of ASCs for successful reconstruction or accelerated healing of defects of the skull and jaw in patients. Although these reports extend our limited knowledge concerning the use of ASCs for osseous tissue repair and regeneration, the lack of standardization in applied techniques makes the comparison between studies difficult. Additional clinical trials are needed to assess ASC therapy and address potential ethical and safety concerns, which must be resolved to permit application in regenerative medicine. PMID:24772241

  14. Disabled homolog 2 controls macrophage phenotypic polarization and adipose tissue inflammation.

    PubMed

    Adamson, Samantha E; Griffiths, Rachael; Moravec, Radim; Senthivinayagam, Subramanian; Montgomery, Garren; Chen, Wenshu; Han, Jenny; Sharma, Poonam R; Mullins, Garrett R; Gorski, Stacey A; Cooper, Jonathan A; Kadl, Alexandra; Enfield, Kyle; Braciale, Thomas J; Harris, Thurl E; Leitinger, Norbert

    2016-04-01

    Acute and chronic tissue injury results in the generation of a myriad of environmental cues that macrophages respond to by changing their phenotype and function. This phenotypic regulation is critical for controlling tissue inflammation and resolution. Here, we have identified the adaptor protein disabled homolog 2 (DAB2) as a regulator of phenotypic switching in macrophages. Dab2 expression was upregulated in M2 macrophages and suppressed in M1 macrophages isolated from both mice and humans, and genetic deletion of Dab2 predisposed macrophages to adopt a proinflammatory M1 phenotype. In mice with myeloid cell-specific deletion of Dab2 (Dab2fl/fl Lysm-Cre), treatment with sublethal doses of LPS resulted in increased proinflammatory gene expression and macrophage activation. Moreover, chronic high-fat feeding exacerbated adipose tissue inflammation, M1 polarization of adipose tissue macrophages, and the development of insulin resistance in DAB2-deficient animals compared with controls. Mutational analyses revealed that DAB2 interacts with TNF receptor-associated factor 6 (TRAF6) and attenuates IκB kinase β-dependent (IKKβ-dependent) phosphorylation of Ser536 in the transactivation domain of NF-κB p65. Together, these findings reveal that DAB2 is critical for controlling inflammatory signaling during phenotypic polarization of macrophages and suggest that manipulation of DAB2 expression and function may hold therapeutic potential for the treatment of acute and chronic inflammatory disorders. PMID:26927671

  15. Adiposity, lipogenesis, and fatty acid composition of subcutaneous and intramuscular adipose tissues of Brahman and Angus crossbred cattle.

    PubMed

    Campbell, E M G; Sanders, J O; Lunt, D K; Gill, C A; Taylor, J F; Davis, S K; Riley, D G; Smith, S B

    2016-04-01

    The objective of this study was to demonstrate differences in aspects of adipose tissue cellularity, lipid metabolism, and fatty and cholesterol composition in Angus and Brahman crossbred cattle. We hypothesized that in vitro measures of lipogenesis would be greater in three-fourths Angus progeny than in three-fourths Brahman progeny, especially in intramuscular (i.m.) adipose tissue. Progeny ( = 227) were fed a standard, corn-based diet for approximately 150 d before slaughter. Breed was considered to be the effect of interest and was forced into the model. There were 9 breed groups including all 4 kinds of three-fourths Angus calves: Angus bulls Angus-sired F cows ( = 32), Angus bulls Brahman-sired F cows ( = 20), Brahman-sired F bulls Angus cows ( = 24), and Angus-sired F bulls Angus cows ( = 20). There were all 4 kinds of three-fourths Brahman calves: Brahman bulls Brahman-sired F cows ( = 21), Brahman bulls Angus-sired F cows ( = 43), Brahman-sired F bulls Brahman cows ( = 26), and Angus-sired F bulls Brahman cows ( = 13). Additionally, F calves (one-half Brahman and one-half Angus) were produced only from Brahman-sired F bulls Angus-sired F cows ( = 28). Contrasts were calculated when breed was an important fixed effect, using the random effect family(breed) as the error term. Most contrasts were nonsignificant ( > 0.10). Those that were significant ( < 0.05) included cholesterol concentration of subcutaneous (s.c.) adipose tissue (three-fourths Angus > F, three-fourths Brahman > F, and three-fourths crossbred progeny combined > F), s.c. adipocyte volume (three-fourths Angus > F and three-fourths bloods combined > F), lipogenesis from acetate in s.c. adipose tissue (three-fourths Brahman calves from Brahman dams > three-fourths Brahman calves from F dams), and percentage 18:3-3 in s.c. adipose tissue (three-fourths Brahman calves from Brahman-sired F dams < three-fourths Brahman calves from Angus-sired F dams). Intramuscular adipocyte volume ( < 0.001) was

  16. Mapping, expression and regulation of the TRα gene in porcine adipose tissue.

    PubMed

    Cai, Z-W; Sheng, Y-F; Zhang, L-F; Wang, Y; Jiang, X-L; Lv, Z-Z; Xu, N-Y

    2011-01-01

    Thyroid hormone receptors (TR) are members of the nuclear receptor superfamily. There are at least two TR isoforms, TRα and TRβ. The TRα isoform plays a critical role in mediating the action of thyroid hormone in adipose tissue. We mapped the porcine TRα gene to chromosome 12 p11-p13, by using the ImpRH panel. We examined tissue-localization of TRα and determined expression patterns of TRα in porcine adipose tissue with quantitative real-time PCR. TRα was expressed in all tissues, including heart, liver, spleen, stomach, pancreas, brain, small intestine, skeletal muscle, and subcutaneous adipose tissue. In the adipose tissue, the expression of TRα decreased postnatally. Compared to Yorkshire pigs, Jinhua pigs had significantly lower expression levels of TRα gene in the subcutaneous fat tissue. The expression levels of β2-AR, HSL and ATGL were also significantly lower in Jinhua pigs than in Yorkshire pigs. However, no significant differences in PPARγ and SREBP-1C expression levels were found between Jinhua and Yorkshire pigs. Incubation of porcine adipose tissue explants with high doses of isoproterenol (100 and 1000 nM) significantly increased the expression levels of TRα. We conclude that there is considerable evidence that TRα plays an important role in fat deposition in porcine adipose tissue. PMID:21751158

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

    PubMed

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

    2015-01-01

    Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia - before severe fat loss - in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition. PMID:25457061

  18. Granulocyte/Macrophage Colony-stimulating Factor-dependent Dendritic Cells Restrain Lean Adipose Tissue Expansion.

    PubMed

    Pamir, Nathalie; Liu, Ning-Chun; Irwin, Angela; Becker, Lev; Peng, YuFeng; Ronsein, Graziella E; Bornfeldt, Karin E; Duffield, Jeremy S; Heinecke, Jay W

    2015-06-01

    The physiological roles of macrophages and dendritic cells (DCs) in lean white adipose tissue homeostasis have received little attention. Because DCs are generated from bone marrow progenitors in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF), we used GM-CSF-deficient (Csf2(-/-)) mice fed a low fat diet to test the hypothesis that adipose tissue DCs regulate the development of adipose tissue. At 4 weeks of age, Csf2(-/-) mice had 75% fewer CD45(+)Cd11b(+)Cd11c(+)MHCII(+) F4/80(-) DCs in white adipose tissue than did wild-type controls. Furthermore, the Csf2(-/-) mice showed a 30% increase in whole body adiposity, which persisted to adulthood. Adipocytes from Csf2(-/-) mice were 50% larger by volume and contained higher levels of adipogenesis gene transcripts, indicating enhanced adipocyte differentiation. In contrast, adipogenesis/adipocyte lipid accumulation was inhibited when preadipocytes were co-cultured with CD45(+)Cd11b(+)Cd11c(+)MHCII(+)F4/80(-) DCs. Medium conditioned by DCs, but not by macrophages, also inhibited adipocyte lipid accumulation. Proteomic analysis revealed that matrix metalloproteinase 12 and fibronectin 1 were greatly enriched in the medium conditioned by DCs compared with that conditioned by macrophages. Silencing fibronectin or genetic deletion of matrix metalloproteinase 12 in DCs partially reversed the inhibition of adipocyte lipid accumulation. Our observations indicate that DCs residing in adipose tissue play a critical role in suppressing normal adipose tissue expansion. PMID:25931125

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

    PubMed

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

    2015-01-01

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

  20. Perivascular adipose tissue in vascular function and disease: a review of current research and animal models

    PubMed Central

    Brown, Nicholas K.; Zhou, Zhou; Zhang, Jifeng; Zeng, Rong; Wu, Jiarui; Eitzman, Daniel T.; Chen, Y. Eugene; Chang, Lin

    2014-01-01

    Perivascular adipose tissue (PVAT), long assumed to be nothing more than vessel-supporting connective tissue, is now understood to be an important, active component of the vasculature, with integral roles in vascular health and disease. PVAT is an adipose tissue with similarities to both brown and white adipose tissue, although recent evidence suggests that PVAT develops from its own precursors. Like other adipose tissue depots, PVAT secretes numerous biologically active substances that can act in both autocrine and paracrine fashion. PVAT has also proven to be involved in vascular inflammation. While PVAT can support inflammation during atherosclerosis via macrophage accumulation, emerging evidence suggests that PVAT also has anti-atherosclerotic properties related to its abilities to induce non-shivering thermogenesis and metabolize fatty acids. We here discuss the accumulated knowledge of PVAT biology, and related research on models of hypertension and atherosclerosis. PMID:24833795

  1. Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease.

    PubMed

    Fuster, José J; Ouchi, Noriyuki; Gokce, Noyan; Walsh, Kenneth

    2016-05-27

    Obesity is causally linked with the development of cardiovascular disorders. Accumulating evidence indicates that cardiovascular disease is the collateral damage of obesity-driven adipose tissue dysfunction that promotes a chronic inflammatory state within the organism. Adipose tissues secrete bioactive substances, referred to as adipokines, which largely function as modulators of inflammation. The microenvironment of adipose tissue will affect the adipokine secretome, having actions on remote tissues. Obesity typically leads to the upregulation of proinflammatory adipokines and the downregulation of anti-inflammatory adipokines, thereby contributing to the pathogenesis of cardiovascular diseases. In this review, we focus on the microenvironment of adipose tissue and how it influences cardiovascular disorders, including atherosclerosis and ischemic heart diseases, through the systemic actions of adipokines. PMID:27230642

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  3. Lipid signaling in adipose tissue: Connecting inflammation & metabolism.

    PubMed

    Masoodi, Mojgan; Kuda, Ondrej; Rossmeisl, Martin; Flachs, Pavel; Kopecky, Jan

    2015-04-01

    Obesity-associated low-grade inflammation of white adipose tissue (WAT) contributes to development of insulin resistance and other disorders. Accumulation of immune cells, especially macrophages, and macrophage polarization from M2 to M1 state, affect intrinsic WAT signaling, namely anti-inflammatory and proinflammatory cytokines, fatty acids (FA), and lipid mediators derived from both n-6 and n-3 long-chain PUFA such as (i) arachidonic acid (AA)-derived eicosanoids and endocannabinoids, and (ii) specialized pro-resolving lipid mediators including resolvins derived from both eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), lipoxins (AA metabolites), protectins and maresins (DHA metabolites). In this respect, potential differences in modulating adipocyte metabolism by various lipid mediators formed by inflammatory M1 macrophages typical of obese state, and non-inflammatory M2 macrophages typical of lean state remain to be established. Studies in mice suggest that (i) transient accumulation of M2 macrophages could be essential for the control of tissue FA levels during activation of lipolysis, (ii) currently unidentified M2 macrophage-borne signaling molecule(s) could inhibit lipolysis and re-esterification of lipolyzed FA back to triacylglycerols (TAG/FA cycle), and (iii) the egress of M2 macrophages from rebuilt WAT and removal of the negative feedback regulation could allow for a full unmasking of metabolic activities of adipocytes. Thus, M2 macrophages could support remodeling of WAT to a tissue containing metabolically flexible adipocytes endowed with a high capacity of both TAG/FA cycling and oxidative phosphorylation. This situation could be exemplified by a combined intervention using mild calorie restriction and dietary supplementation with EPA/DHA, which enhances the formation of "healthy" adipocytes. This article is part of a Special Issue entitled Oxygenated metabolism of PUFA: analysis and biological relevance." PMID:25311170

  4. Adipose-Derived Stem Cells in Functional Bone Tissue Engineering: Lessons from Bone Mechanobiology

    PubMed Central

    Bodle, Josephine C.; Hanson, Ariel D.

    2011-01-01

    This review aims to highlight the current and significant work in the use of adipose-derived stem cells (ASC) in functional bone tissue engineering framed through the bone mechanobiology perspective. Over a century of work on the principles of bone mechanosensitivity is now being applied to our understanding of bone development. We are just beginning to harness that potential using stem cells in bone tissue engineering. ASC are the primary focus of this review due to their abundance and relative ease of accessibility for autologous procedures. This article outlines the current knowledge base in bone mechanobiology to investigate how the knowledge from this area has been applied to the various stem cell-based approaches to engineering bone tissue constructs. Specific emphasis is placed on the use of human ASC for this application. PMID:21338267

  5. Aberrant Accumulation of Undifferentiated Myeloid Cells in the Adipose Tissue of CCR2-Deficient Mice Delays Improvements in Insulin Sensitivity

    PubMed Central

    Gutierrez, Dario A.; Kennedy, Arion; Orr, Jeb S.; Anderson, Emily K.; Webb, Corey D.; Gerrald, William K.; Hasty, Alyssa H.

    2011-01-01

    OBJECTIVE Mice with CCR2 deficiency are protected from insulin resistance but only after long periods of high-fat diet (HFD) feeding, despite the virtual absence of circulating inflammatory monocytes. We performed a time course study in mice with hematopoietic and global CCR2 deficiency to determine adipose tissue–specific mechanisms for the delayed impact of CCR2 deficiency on insulin resistance. RESEARCH DESIGN AND METHODS Mice with global or hematopoietic CCR2 deficiency (CCR2−/− and BM-CCR2−/−, respectively) and wild-type controls (CCR2+/+ and BM-CCR2+/+, respectively) were placed on an HFD for 6, 12, and 20 weeks. Adipose tissue myeloid populations, degree of inflammation, glucose tolerance, and insulin sensitivity were assessed. RESULTS Flow cytometry analysis showed that two different populations of F4/80+ myeloid cells (CD11bloF4/80lo and CD11bhiF4/80hi) accumulated in the adipose tissue of CCR2−/− and BM-CCR2−/− mice after 6 and 12 weeks of HFD feeding, whereas only the CD11bhiF4/80hi population was detected in the CCR2+/+ and BM-CCR2+/+ controls. After 20 weeks of HFD feeding, the CD11bloF4/80lo cells were no longer present in the adipose tissue of CCR2−/− mice, and only then were improvements in adipose tissue inflammation detected. Gene expression and histological analysis of the CD11bloF4/80lo cells indicated that they are a unique undifferentiated monocytic inflammatory population. The CD11bloF4/80lo cells are transiently found in wild-type mice, but CCR2 deficiency leads to the aberrant accumulation of these cells in adipose tissue. CONCLUSIONS The discovery of this novel adipose tissue monocytic cell population provides advances toward understanding the pleiotropic role of CCR2 in monocyte/macrophage accumulation and regulation of adipose tissue inflammation. PMID:21926275

  6. Regulation of Microvascular Function by Adipose Tissue in Obesity and Type 2 Diabetes: Evidence of an Adipose-Vascular Loop

    PubMed Central

    Zhang, Hanrui; Zhang, Cuihua

    2009-01-01

    In recent years, the general concept has emerged that chronic low-grade inflammation is the condition linking excessive development of adipose tissue and obesity-associated pathologies such as type 2 diabetes and cardiovascular diseases. Obesity and type 2 diabetes are characterized by a diminished production of protective factors such as adiponectin and increased detrimental adipocytokines such as leptin, resistin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), and monocyte chemoattractant protein-1 (MCP-1) by adipose tissue. Moreover, the evidence that the growth of the fat mass is associated with an accumulation of adipose tissue macrophages and T-lymphocytes has raised the hypothesis that the development of an inflammatory process within the growing fat mass is a primary event involved in the genesis of systemic metabolic and vascular alterations. This crosstalk of adipocyte, macrophage, lymphocyte, endothelial cells, and vascular smooth muscle cells contribute to the production of various cytokines, chemokines, and hormone-like factors, which actively participate in the regulation of vascular function by an endocrine and/or paracrine pattern. Thus, the signaling from perivascular adipose to the blood vessels is emerging as a potential therapeutic target for obesity and diabetes-associated vascular dysfunction. PMID:20098632

  7. Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue

    SciTech Connect

    Bacay, A.C.; Mantyh, C.R.; Vigna, S.R.; Mantyh, P.W. )

    1988-09-01

    To explore the possibility that atrial natriuretic factor (ANF) is involved in thermoregulation we used quantitative receptor autoradiography and homogenate receptor binding assays to identify ANF bindings sites in neonatal rat and sheep brown adipose tissue, respectively. Using quantitative receptor autoradiography were were able to localize high levels of specific binding sites for {sup 125}I-rat ANF in neonatal rat brown adipose tissue. Homogenate binding assays on sheep brown fat demonstrated that the radioligand was binding to the membrane fraction and that the specific binding was not due to a lipophilic interaction between {sup 125}I-rat ANF and brown fat. Specific binding of {sup 125}I-rat ANF to the membranes of brown fat cells was inhibited by unlabeled rat ANF with a Ki of 8.0 x 10(-9) M, but not by unrelated peptides. These studies demonstrate that brown fat cells express high levels of ANF receptor binding sites in neonatal rat and sheep and suggest that ANF may play a role in thermoregulation.

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

    PubMed Central

    Ritter, Andreas; Friemel, Alexandra; Fornoff, Friderike; Adjan, Mouhib; Solbach, Christine

    2015-01-01

    Adipose-derived stem cells are capable of differentiating into multiple cell types and thus considered useful for regenerative medicine. However, this differentiation feature seems to be associated with tumor initiation and metastasis raising safety concerns, which requires further investigation. In this study, we isolated adipose-derived stem cells from subcutaneous as well as from visceral adipose tissues of the same donor and systematically compared their features. Although being characteristic of mesenchymal stem cells, subcutaneous adipose-derived stem cells tend to be spindle form-like and are more able to home to cancer cells, whereas visceral adipose-derived stem cells incline to be “epithelial”-like and more competent to differentiate. Moreover, compared to subcutaneous adipose-derived stem cells, visceral adipose-derived stem cells are more capable of promoting proliferation, inducing the epithelial-to-mesenchymal transition, enhancing migration and invasion of breast cancer cells by cell-cell contact and by secreting interleukins such as IL-6 and IL-8. Importantly, ASCs affect the low malignant breast cancer cells MCF-7 more than the highly metastatic MDA-MB-231 cells. Induction of the epithelial-to-mesenchymal transition is mediated by the activation of multiple pathways especially the PI3K/AKT signaling in breast cancer cells. BCL6, an important player in B-cell lymphoma and breast cancer progression, is crucial for this transition. Finally, this transition fuels malignant properties of breast cancer cells and render them resistant to ATP competitive Polo-like kinase 1 inhibitors BI 2535 and BI 6727. PMID:26439686

  9. Biochemical properties of porcine white adipose tissue mitochondria and relevance to fatty acid oxidation.

    PubMed

    Koekemoer, T C; Oelofsen, W

    2001-07-01

    The capacity of white adipose tissue mitochondria to support a high beta-oxidative flux was investigated by comparison to liver mitochondria. Based on marker enzyme activities and electron microscopy, the relative purity of the isolated mitochondria was similar thus allowing a direct comparison on a protein basis. The results confirm the comparable capacity of adipose tissue and liver mitochondria for palmitoyl-carnitine oxidation. Relative to liver, both citrate synthase and alpha-ketoglutarate dehydrogenase were increased 7.87- and 10.38-fold, respectively. In contrast, adipose tissue NAD-isocitrate dehydrogenase was decreased (2.85-fold). Such modifications in the citric acid cycle are expected to severely restrict citrate oxidation in porcine adipose tissue. Except for cytochrome c oxidase, activities of the enzyme complexes comprising the electron transport chain were not significantly different. The decrease in adipose cytochrome c oxidase activity could partly be attributed to a decreased inner membrane as suggested by lipid and enzyme analysis. In addition, Western blotting indicated that adipose and liver mitochondria possess similar quantities of cytochrome c oxidase protein. Taken together these results indicate that not only is the white adipose tissue protoplasm relatively rich in mitochondria, but that these mitochondria contain comparable enzymatic machinery to support a relatively high beta-oxidative rate. PMID:11435134

  10. Tissue specific regulation of lipogenesis by thyroid hormone

    SciTech Connect

    Blennemann, B.; Freake, H. )

    1990-02-26

    Thyroid hormone stimulates long chain fatty acid synthesis in rat liver by increasing the amounts of key lipogenic enzymes. Sparse and conflicting data exist concerning its action on this pathway in other tissues. The authors recently showed that, in contrast to liver, hypothyroidism stimulates lipogenesis in brown adipose tissue and have now systematically examined the effects of thyroid state on fatty acid synthesis in other rat tissues. Lipogenesis was assessed by tritiated water incorporation. Euthyroid hepatic fatty acid synthesis (16.6um H/g/h) was reduced to 30% in hypothyroid rats and increased 3 fold in hyperthyroidism. Lipogenesis was detected in euthyroid kidney and heart and these levels were also stimulated by thyroid hormone treatment. Brown adipose tissue was unique in showing increased lipogenesis in the hypothyroid state. Hyperthyroid levels were not different from euthyroid. Effects in white adipose tissue were small and inconsistent. Brain, skin and lung were all lipogenically active, but did not respond to changes in thyroid state. Low but detectable levels of fatty acid synthesis were measured in muscle, which also were non-responsive. A wide spectrum of responses to thyroid hormone are seen in different rat tissues and thus the pathway of long chain fatty acid synthesis would appear to be an excellent model for examining the tissue specific regulation of gene expression by thyroid hormone.

  11. Collagen-hyaluronic acid scaffolds for adipose tissue engineering.

    PubMed

    Davidenko, N; Campbell, J J; Thian, E S; Watson, C J; Cameron, R E

    2010-10-01

    Three-dimensional (3-D) in vitro models of the mammary gland require a scaffold matrix that supports the development of adipose stroma within a robust freely permeable matrix. 3-D porous collagen-hyaluronic acid (HA: 7.5% and 15%) scaffolds were produced by controlled freeze-drying technique and crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride. All scaffolds displayed uniform, interconnected pore structure (total porosity approximately 85%). Physical and chemical analysis showed no signs of collagen denaturation during the formation process. The values of thermal characteristics indicated that crosslinking occurred and that its efficiency was enhanced by the presence of HA. Although the crosslinking reduced the swelling of the strut material in water, the collagen-HA matrix as a whole tended to swell more and show higher dissolution resistance than pure collagen samples. The compressive modulus and elastic collapse stress were higher for collagen-HA composites. All the scaffolds were shown to support the proliferation and differentiation 3T3-L1 preadipocytes while collagen-HA samples maintained a significantly increased proportion of cycling cells (Ki-67+). Furthermore, collagen-HA composites displayed significantly raised Adipsin gene expression with adipogenic culture supplementation for 8 days vs. control conditions. These results indicate that collagen-HA scaffolds may offer robust, freely permeable 3-D matrices that enhance mammary stromal tissue development in vitro. PMID:20466086

  12. Visceral adipose tissue differences in black and white women.

    PubMed

    Conway, J M; Yanovski, S Z; Avila, N A; Hubbard, V S

    1995-04-01

    Fat distribution and metabolic variables were studied in 8 black and 10 white age- and weight-matched obese women undergoing a 6-mo weight-reducing regimen. Fat patterning was determined by using anthropometry and computed tomography to quantitate total, subcutaneous, and visceral adipose tissue (VAT) areas at the L2-L3 and L4-L5 levels of the lumbar spine, before, during, and after a modified fast. Black women had smaller depots of VAT than white women at both the L2-L3 (P = 0.004) and L4-L5 (P = 0.054) sites. Differences persisted after an average 17.2-kg weight loss. Although waist-hip ratio was similar in both groups, black women had 23% less VAT than white women (P = 0.007). Black women had significantly lower plasma glucose (P = 0.031) and triglycerides (P = 0.006) with significantly higher plasma high-density-lipoprotein concentrations (P < 0.001). Data from this study suggest that racial differences exist in VAT and metabolic risk factors for obesity-related illness. PMID:7702017

  13. Physiological adaptations in adipose tissue of Brahman vs Angus heifers.

    PubMed

    Sprinkle, J E; Hansard, H S; Warrington, B G; Holloway, J W; Wu, G; Smith, S B

    1998-03-01

    Nonpregnant yearling Brahman (n = 12) and Angus (n = 12) heifers were equally allocated to two dietary treatments in a replicated study to examine responses in lipid metabolism to nutritional treatments consisting of a moderate energy diet (2.0 Mcal ME/kg) fed at maintenance and a 2.5 x maintenance high-energy diet (2.4 Mcal ME/kg) fed for 30 d. In vitro lipogenesis and the activities of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) were determined in perianal subcutaneous adipose tissue biopsies at the start and end of the trial. At the start of the trial, breeds had similar (P > .10) rates of lipogenesis and LPL activity. Brahman had greater (P < .05) HSL activity than Angus at the start of the trial and tended (P < .07) to have greater HSL activity at the end. Diet did not influence (P > .10) HSL activity. Heifers on the high-energy, higher-intake diet had greater lipogenesis (P < .001) and LPL activity (P < .01) than those on the moderate-energy diet. Inclusion of body condition score (BCS) nested within breed as a covariate explained breed differences for lipogenesis (P < .05). Thus, by including the covariate, the two breeds had similar (P > .10) rates of lipogenesis at the end of the trial. When adjusted for BCS nested within breed, Brahman had greater (P < .05) LPL activity than Angus. PMID:9535333

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

    PubMed Central

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

    2016-01-01

    Abstract The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation. PMID:27385482

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

    PubMed

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

    2016-01-01

    The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation. PMID:27385482

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

    NASA Astrophysics Data System (ADS)

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

    1992-03-01

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

  17. Uric acid secretion from adipose tissue and its increase in obesity.

    PubMed

    Tsushima, Yu; Nishizawa, Hitoshi; Tochino, Yoshihiro; Nakatsuji, Hideaki; Sekimoto, Ryohei; Nagao, Hirofumi; Shirakura, Takashi; Kato, Kenta; Imaizumi, Keiichiro; Takahashi, Hiroyuki; Tamura, Mizuho; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Iichiro

    2013-09-20

    Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity. PMID:23913681

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

    PubMed Central

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

    2012-01-01

    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

  19. Dietary Fructose Activates Insulin Signaling and Inflammation in Adipose Tissue: Modulatory Role of Resveratrol

    PubMed Central

    Pektas, Mehmet Bilgehan; Koca, Halit Bugra; Sadi, Gokhan; Akar, Fatma

    2016-01-01

    The effects of high-fructose diet on adipose tissue insulin signaling and inflammatory process have been poorly documented. In this study, we examined the influences of long-term fructose intake and resveratrol supplementation on the expression of genes involved in insulin signaling and the levels of inflammatory cytokines and sex hormones in the white adipose tissues of male and female rats. Consumption of high-fructose diet for 24 weeks increased the expression of genes involved in insulin signaling including IR, IRS-1, IRS-2, Akt, PI3K, eNOS, mTOR, and PPARγ, despite induction of proinflammatory markers, iNOS, TNFα, IL-1β, IL-18, MDA, and ALT, as well as anti-inflammatory factors, IL-10 and Nrf2 in adipose tissues from males and females. Total and free testosterone concentrations of adipose tissues were impaired in males but increased in females, although there were no changes in their blood levels. Resveratrol supplementation markedly restored the levels of MDA, IL6, IL-10, and IL-18, as well as iNOS, Nrf2, and PI3K mRNA, in adipose tissues of both genders. Dietary fructose activates both insulin signaling and inflammatory pathway in the adipose tissues of male and female rats proposing no correlation between the tissue insulin signaling and inflammation. Resveratrol has partly modulatory effects on fructose-induced changes. PMID:27066503

  20. IMPROVED METHOD FOR HEXACHLOROBENZENE AND MIREX DETERMINATION WITH HEXACHLOROBENZENE CONFIRMATION IN ADIPOSE TISSUE: COLLABORATIVE STUDY

    EPA Science Inventory

    A previously published method for determination and confirmation of hexachlorobenzene (HCB) in adipose tissue was also applied to mirex residues. A modified procedure for both residues was collaboratively studied by 12 laboratories. The procedure specifies direct application of a...

  1. Adipogenesis in fetal pig subcutaneous adipose tissue: Remarkable developmental features before the onset of adipogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The collection of investigations indicate the importance of adipose tissue architecture to vasculogenesis and angiogenesis during adipogenesis is reviewed. Early in development the architecture and vascular structure develops before overt adipocyte differentiation. Adipocyte development and the exp...

  2. Adipose Tissue and Adrenal Glands: Novel Pathophysiological Mechanisms and Clinical Applications

    PubMed Central

    Kargi, Atil Y.; Iacobellis, Gianluca

    2014-01-01

    Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or “adipokines” have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of “cross talk” between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals. PMID:25018768

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

    PubMed

    Jung, Chien-Cheng; Su, Huey-Jen

    2016-05-01

    The purpose of this study was to study whether allergen exposure can induce inflammation and lower the anti-inflammation levels in serum and in adipose tissues, and further develop cardiovascular injury. Our data showed that heart rate was significantly higher in the OVA-challenged mice compared to control mice. Moreover, there were higher expressions of pro-inflammation genes in the OVA-challenged mice in adipose tissues, and the expressions of anti-inflammation genes were lower. The levels of inflammation mediators were associated in serum and adipose tissues. The level of circulatory injury lactate dehydrogenase was significantly associated with the levels of E-selectin, resistin and adiponectin in the serum. The hematoxylin and eosin and immunohistochemistry stains indicated the OVA-challenged mice had higher levels of inflammation. In summary, the current study demonstrated allergen exposure can cause cardiovascular injury, and inflammatory mediators in adipose tissues play an important role in the pathogenesis of cardiovascular injury. PMID:27004794

  4. IMPROVED RECOVERY OF HEXACHLOROBENZENE IN ADIPOSE TISSUE WITH A MODIFIED MICRO MULTIRESIDUE PROCEDURE

    EPA Science Inventory

    Using the described methodology the recovery of hexachlorobenzene from adipose tissue was significantly increased over that normally obtained with other multiresidue procedures. The recovery of other commonly encountered chlorinated hydrocarbon pesticides was not affected nor was...

  5. Loss of subcutaneous adipose tissue in HIV-associated lipodystrophy is not due to accelerated apoptosis.

    PubMed

    Mynarcik, Dennis; Wei, Lin-Xiang; Komaroff, Eugene; Ferris, Robert; McNurlan, Margaret; Gelato, Marie

    2005-01-01

    HIV-associated lipodystrophy is characterized by a loss of adipose tissue from the subcutaneous compartment. Previously reported data suggested that this loss of adipose tissue was the result of an increased rate of apoptosis in subcutaneous adipose tissue. The present study examined the rate of apoptosis in subcutaneous adipose tissue with a sensitive ligase-mediated polymerase chain reaction technique to amplify DNA ladders. Individuals with HIV lipodystrophy were compared with HIV-infected subjects without lipodystrophy and subjects without HIV disease. Although apoptosis was observed in subjects with HIV lipodystrophy, there was no difference in the frequency of individuals with apoptosis among those with HIV lipodystrophy (10/22), those with HIV but no lipodystrophy (13/25), and subjects without HIV disease (13/27). PMID:15608525

  6. Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice.

    PubMed

    Trindade, Sandra; Rijo-Ferreira, Filipa; Carvalho, Tânia; Pinto-Neves, Daniel; Guegan, Fabien; Aresta-Branco, Francisco; Bento, Fabio; Young, Simon A; Pinto, Andreia; Van Den Abbeele, Jan; Ribeiro, Ruy M; Dias, Sérgio; Smith, Terry K; Figueiredo, Luisa M

    2016-06-01

    Trypanosoma brucei is an extracellular parasite that causes sleeping sickness. In mammalian hosts, trypanosomes are thought to exist in two major niches: early in infection, they populate the blood; later, they breach the blood-brain barrier. Working with a well-established mouse model, we discovered that adipose tissue constitutes a third major reservoir for T. brucei. Parasites from adipose tissue, here termed adipose tissue forms (ATFs), can replicate and were capable of infecting a naive animal. ATFs were transcriptionally distinct from bloodstream forms, and the genes upregulated included putative fatty acid β-oxidation enzymes. Consistent with this, ATFs were able to utilize exogenous myristate and form β-oxidation intermediates, suggesting that ATF parasites can use fatty acids as an external carbon source. These findings identify the adipose tissue as a niche for T. brucei during its mammalian life cycle and could potentially explain the weight loss associated with sleeping sickness. PMID:27237364

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

    PubMed Central

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

    1983-01-01

    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

  8. PDGFRα signaling drives adipose tissue fibrosis by targeting progenitor cell plasticity.

    PubMed

    Iwayama, Tomoaki; Steele, Cameron; Yao, Longbiao; Dozmorov, Mikhail G; Karamichos, Dimitris; Wren, Jonathan D; Olson, Lorin E

    2015-06-01

    Fibrosis is a common disease process in which profibrotic cells disturb organ function by secreting disorganized extracellular matrix (ECM). Adipose tissue fibrosis occurs during obesity and is associated with metabolic dysfunction, but how profibrotic cells originate is still being elucidated. Here, we use a developmental model to investigate perivascular cells in white adipose tissue (WAT) and their potential to cause organ fibrosis. We show that a Nestin-Cre transgene targets perivascular cells (adventitial cells and pericyte-like cells) in WAT, and Nestin-GFP specifically labels pericyte-like cells. Activation of PDGFRα signaling in perivascular cells causes them to transition into ECM-synthesizing profibrotic cells. Before this transition occurs, PDGFRα signaling up-regulates mTOR signaling and ribosome biogenesis pathways and perturbs the expression of a network of epigenetically imprinted genes that have been implicated in cell growth and tissue homeostasis. Isolated Nestin-GFP(+) cells differentiate into adipocytes ex vivo and form WAT when transplanted into recipient mice. However, PDGFRα signaling opposes adipogenesis and generates profibrotic cells instead, which leads to fibrotic WAT in transplant experiments. These results identify perivascular cells as fibro/adipogenic progenitors in WAT and show that PDGFRα targets progenitor cell plasticity as a profibrotic mechanism. PMID:26019175

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

    PubMed

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

    2014-11-01

    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 α-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

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

    NASA Astrophysics Data System (ADS)

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

    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.

  11. PDGFRα signaling drives adipose tissue fibrosis by targeting progenitor cell plasticity

    PubMed Central

    Iwayama, Tomoaki; Steele, Cameron; Yao, Longbiao; Dozmorov, Mikhail G.; Karamichos, Dimitris; Wren, Jonathan D.

    2015-01-01

    Fibrosis is a common disease process in which profibrotic cells disturb organ function by secreting disorganized extracellular matrix (ECM). Adipose tissue fibrosis occurs during obesity and is associated with metabolic dysfunction, but how profibrotic cells originate is still being elucidated. Here, we use a developmental model to investigate perivascular cells in white adipose tissue (WAT) and their potential to cause organ fibrosis. We show that a Nestin-Cre transgene targets perivascular cells (adventitial cells and pericyte-like cells) in WAT, and Nestin-GFP specifically labels pericyte-like cells. Activation of PDGFRα signaling in perivascular cells causes them to transition into ECM-synthesizing profibrotic cells. Before this transition occurs, PDGFRα signaling up-regulates mTOR signaling and ribosome biogenesis pathways and perturbs the expression of a network of epigenetically imprinted genes that have been implicated in cell growth and tissue homeostasis. Isolated Nestin-GFP+ cells differentiate into adipocytes ex vivo and form WAT when transplanted into recipient mice. However, PDGFRα signaling opposes adipogenesis and generates profibrotic cells instead, which leads to fibrotic WAT in transplant experiments. These results identify perivascular cells as fibro/adipogenic progenitors in WAT and show that PDGFRα targets progenitor cell plasticity as a profibrotic mechanism. PMID:26019175

  12. Adipose-Derived Stem Cell Delivery for Adipose Tissue Engineering: Current Status and Potential Applications in a Tissue Engineering Chamber Model.

    PubMed

    Zhan, Weiqing; Tan, Shaun S; Lu, Feng

    2016-08-01

    In reconstructive surgery, there is a clinical need for adequate implants to repair soft tissue defects caused by traumatic injury, tumor resection, or congenital abnormalities. Adipose tissue engineering may provide answers to this increasing demand. This study comprehensively reviews current approaches to adipose tissue engineering, detailing different cell carriers under investigation, with a special focus on the application of adipose-derived stem cells (ASCs). ASCs act as building blocks for new tissue growth and as modulators of the host response. Recent studies have also demonstrated that the implantation of a hollow protected chamber, combined with a vascular pedicle within the fat flaps provides blood supply and enables the growth of large-volume of engineered soft tissue. Conceptually, it would be of value to co-regulate this unique chamber model with adipose-derived stem cells to obtain a greater volume of soft tissue constructs for clinical use. Our review provides a cogent update on these advances and details the generation of possible fat substitutes. PMID:27075632

  13. Lactobacillus gasseri SBT2055 inhibits adipose tissue inflammation and intestinal permeability in mice fed a high-fat diet.

    PubMed

    Kawano, Michio; Miyoshi, Masaya; Ogawa, Akihiro; Sakai, Fumihiko; Kadooka, Yukio

    2016-01-01

    The probiotic Lactobacillus gasseri SBT2055 (LG2055) has anti-obesity effects. Obesity is closely correlated with inflammation in adipose tissue, and maintaining adipose tissue in a less-inflamed state requires intestinal integrity or a barrier function to protect the intestine from the disruption that can be caused by a high-fat diet (HFD). Here, we examined the anti-inflammatory and intestinal barrier-protecting effects of LG2055 in C57BL/6 mice fed a normal-fat diet (NFD), HFD, or the HFD containing LG2055 (HFD-LG) for 21 weeks. HFD-LG intake significantly prevented HFD-induced increases in body weight, visceral fat mass, and the ratio of inflammatory-type macrophages to anti-inflammatory ones in adipose tissue. Mice fed the HFD showed higher intestinal permeability to a fluorescent dextran administered by oral administration and an elevated concentration of antibodies specific to lipopolysaccharides (LPS) in the blood compared with those fed the NFD, suggesting an increased penetration of the gut contents into the systemic circulation. These elevations of intestinal permeability and anti-LPS antibody levels were significantly suppressed in mice fed the HFD-LG. Moreover, treatment with LG2055 cells suppressed an increase in the cytokine-induced permeability of Caco-2 cell monolayers. These results suggest that LG2055 improves the intestinal integrity, reducing the entry of inflammatory substances like LPS from the intestine, which may lead to decreased inflammation in adipose tissue. PMID:27293560

  14. Severe Burn Injury Induces Thermogenically Functional Mitochondria in Murine White Adipose Tissue.

    PubMed

    Porter, Craig; Herndon, David N; Bhattarai, Nisha; Ogunbileje, John O; Szczesny, Bartosz; Szabo, Csaba; Toliver-Kinsky, Tracy; Sidossis, Labros S

    2015-09-01

    Chronic cold exposure induces functionally thermogenic mitochondria in the inguinal white adipose tissue (iWAT) of mice. Whether this response occurs in pathophysiological states remains unclear. The purpose of this study was to determine the impact of severe burn trauma on iWAT mitochondrial function in mice. Male BALB/c mice (10-12 weeks) received full-thickness scald burns to ∼30% of the body surface area. Inguinal white adipose tissue was harvested from mice at 1, 4, 10, 20, and 40 days postinjury. Total and uncoupling protein 1 (UCP1)-dependent mitochondrial thermogenesis were determined in iWAT. Citrate synthase activity was determined as a proxy of mitochondrial abundance. Immunohistochemistry was performed to assess iWAT morphology and UCP1 expression. Uncoupling protein 1-dependent respiration was significantly greater at 4 and 10 days after burn compared with sham, peaking at 20 days after burn (P < 0.001). Citrate synthase activity was threefold greater at 4, 10, 20, and 40 days after burn versus sham (P < 0.05). Per mitochondrion, UCP1 function increased after burn trauma (P < 0.05). After burn trauma, iWAT exhibited numerous multilocular lipid droplets that stained positive for UCP1. The current findings demonstrate the induction of thermogenically competent mitochondria within rodent iWAT in a model of severe burn trauma. These data identify a specific pathology that induces the browning of white adipose tissue in vivo and may offer a mechanistic explanation for the chronic hypermetabolism observed in burn victims. PMID:26009824

  15. Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance

    PubMed Central

    Poher, Anne-Laure; Altirriba, Jordi; Veyrat-Durebex, Christelle; Rohner-Jeanrenaud, Françoise

    2015-01-01

    Presence of brown adipose tissue (BAT), characterized by the expression of the thermogenic uncoupling protein 1 (UCP1), has recently been described in adult humans. UCP1 is expressed in classical brown adipocytes, as well as in “beige cells” in white adipose tissue (WAT). The thermogenic activity of BAT is mainly controlled by the sympathetic nervous system. Endocrine factors, such as fibroblast growth factor 21 (FGF21) and bone morphogenic protein factor-9 (BMP-9), predominantly produced in the liver, were shown to lead to activation of BAT thermogenesis, as well as to “browning” of WAT. This was also observed in response to irisin, a hormone secreted by skeletal muscles. Different approaches were used to delineate the impact of UCP1 on insulin sensitivity. When studied under thermoneutral conditions, UCP1 knockout mice exhibited markedly increased metabolic efficiency due to impaired thermogenesis. The impact of UCP1 deletion on insulin sensitivity in these mice was not reported. Conversely, several studies in both rodents and humans have shown that BAT activation (by cold exposure, β3-agonist treatment, transplantation and others) improves glucose tolerance and insulin sensitivity. Interestingly, similar results were obtained by adipose tissue-specific overexpression of PR-domain-containing 16 (PRDM16) or BMP4 in mice. The mediators of such beneficial effects seem to include FGF21, interleukin-6, BMP8B and prostaglandin D2 synthase. Interestingly, some of these molecules can be secreted by BAT itself, indicating the occurrence of autocrine effects. Stimulation of BAT activity and/or recruitment of UCP1-positive cells are therefore relevant targets for the treatment of obesity/type 2 diabetes in humans. PMID:25688211

  16. Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice

    PubMed Central

    Wei, H; Averill, M M; McMillen, T S; Dastvan, F; Mitra, P; Subramanian, S; Tang, C; Chait, A; LeBoeuf, R C

    2014-01-01

    Background: Obesity is associated with reduced levels of circulating high-density lipoproteins (HDLs) and its major protein, apolipoprotein (apo) A-I. As a result of the role of HDL and apoA-I in cellular lipid transport, low HDL and apoA-I may contribute directly to establishing or maintaining the obese condition. Methods: To test this, male C57BL/6 wild-type (WT), apoA-I deficient (apoA-I−/−) and apoA-I transgenic (apoA-Itg/tg) mice were fed obesogenic diets (ODs) and monitored for several clinical parameters. We also performed cell culture studies. Results: ApoA-I−/− mice gained significantly more body weight and body fat than WT mice over 20 weeks despite their reduced food intake. During a caloric restriction regime imposed on OD-fed mice, apoA-I deficiency significantly inhibited the loss of body fat as compared with WT mice. Reduced body fat loss with caloric restriction in apoA-I−/− mice was associated with blunted stimulated adipose tissue lipolysis as verified by decreased levels of phosphorylated hormone-sensitive lipase (p-HSL) and lipolytic enzyme mRNA. In contrast to apoA-I−/− mice, apoA-Itg/tg mice gained relatively less weight than WT mice, consistent with other reports. ApoA-Itg/tg mice showed increased adipose tissue lipolysis, verified by increased levels of p-HSL and lipolytic enzyme mRNA. In cell culture studies, HDL and apoA-I specifically increased catecholamine-induced lipolysis possibly through modulating the adipocyte plasma membrane cholesterol content. Conclusions: Thus, apoA-I and HDL contribute to modulating body fat content by controlling the extent of lipolysis. ApoA-I and HDL are key components of lipid metabolism in adipose tissue and constitute new therapeutic targets in obesity. PMID:24567123

  17. The Use of Silk as a Scaffold for Mature, Sustainable Unilocular Adipose 3D Tissue Engineered Systems.

    PubMed

    Abbott, Rosalyn D; Wang, Rebecca Y; Reagan, Michaela R; Chen, Ying; Borowsky, Francis E; Zieba, Adam; Marra, Kacey G; Rubin, J Peter; Ghobrial, Irene M; Kaplan, David L

    2016-07-01

    There is a critical need for monitoring physiologically relevant, sustainable, human adipose tissues in vitro to gain new insights into metabolic diseases. To support long-term culture, a 3D silk scaffold assisted culture system is developed that maintains mature unilocular adipocytes ex vivo in coculture with preadipocytes, endothelial cells, and smooth muscle cells obtained from small volumes of liquefied adipose samples. Without the silk scaffold, adipose tissue explants cannot be sustained in long-term culture (3 months) due to their fragility. Adjustments to media components are used to tune lipid metabolism and proliferation, in addition to responsiveness to an inflammatory stimulus. Interestingly, patient specific responses to TNFα stimulation are observed, providing a proof-of-concept translational technique for patient specific disease modeling in the future. In summary, this novel 3D scaffold assisted approach is required for establishing physiologically relevant, sustainable, human adipose tissue systems from small volumes of lipoaspirate, making this methodology of great value to studies of metabolism, adipokine-driven diseases, and other diseases where the roles of adipocytes are only now becoming uncovered. PMID:27197588

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

    PubMed

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

    2016-01-01

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

  19. Weight Gain Alters Adiponectin Receptor 1 Expression on Adipose Tissue-Resident Helios+ Regulatory T Cells.

    PubMed

    Ramos-Ramírez, P; Malmhäll, C; Johansson, K; Lötvall, J; Bossios, A

    2016-04-01

    Adipose tissue produces multiple mediators that modulate the immune response. Adiponectin is an adipocyte-derived cytokine that exhibits metabolic and anti-inflammatory effects. Adiponectin acts through binding to adiponectin receptor 1 and 2 (AdipoR1/AdipoR2). AdipoR1 is ubiquitously expressed, whereas AdipoR2 is restricted to skeletal muscle and liver. AdipoR1 expression has been reported on a small percentage of T cells; nevertheless, it is still unknown whether Foxp3(+) regulatory T cells (Tregs) express AdipoR1. Recently, it has been shown that Tregs accumulate in adipose tissue and that they play a potential role in modulating adipose tissue inflammation. Our aim was to evaluate AdipoR1 expression in adipose tissue-resident Tregs and to evaluate the effect of weight gain on this expression. Male C57BL/6 mice were fed with a high-fat diet for 14 weeks (to develop overweight) or 21 weeks (to develop obesity). Mice on a standard diet were used as age-matched controls. Helios expression was evaluated as a marker to discriminate thymic-derived from peripherally induced Tregs. The majority of Tregs in both adipose tissue and the spleen expressed Helios. Adipose tissue Tregs expressed higher levels of AdipoR1 than Tregs in the spleen. AdipoR1 expression on adipose tissue Helios(+) Tregs was negatively correlated with epididymal fat. Overall, we show that AdipoR1 is expressed on adipose tissue-resident Tregs, mainly Helios(+) Tregs, and that this expression is dependent on weight and fat accumulation. Because both adiponectin and Tregs play roles in anti-inflammatory mechanisms, our data propose a new mechanism through which weight gain might alter immunoregulation. PMID:26900653

  20. Using gene expression to predict differences in the secretome of human omental vs. subcutaneous adipose tissue.

    PubMed

    Hoggard, Nigel; Cruickshank, Morven; Moar, Kim-Marie; Bashir, Shabina; Mayer, Claus-Dieter

    2012-06-01

    The objective of this study was to characterize differences in the secretome of human omental compared with subcutaneous adipose tissue using global gene expression profiling. Gene expression was measured using Affymetrix microarrays (Affymetrix, Santa Clara, CA) in subcutaneous and omental adipose tissue in two independent experiments (n = 5 and n = 3 independent subjects; n = 16 arrays in total, 2 for each subject). Predictive bioinformatic algorithms were employed to identify secreted proteins. Microarray analysis identified 22 gene probe sets whose expression was significantly different with a fold change (FC) greater than 5 in expression in both experiments between omental and subcutaneous adipose tissue. Using bioinformatic predictive programs 11 of these 22 probe sets potentially coded for secreted proteins. Pathway network analysis of the secreted proteins showed that three of the proteins are part of a common pathway network. These proteins gremlin 1 (GREM1), pleiotrophin (PTN), and secretory leukocyte peptidase inhibitor (SLPI) are expressed respectively 43×, 23×, and 5× in omental adipose tissue relative to subcutaneous adipose tissue as determined by real-time PCR. The presence of GREM1, PTN, and SLPI protein in human adipose tissue was confirmed by western blotting. All three proteins are expressed in the human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cell line. The expression of GREM1, PTN, and SLPI changed with the differentiation of the preadipocytes into mature adipocytes. Gene expression coupled with predictive bioinformatic algorithms have identified several genes coding for secreted proteins which are expressed differently in omental adipose tissue compared to subcutaneous adipose tissue proving a valid alternative approach to help further define the adipocyte secretome. PMID:22286531

  1. Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure

    PubMed Central

    Sun, Kai; Kusminski, Christine M.; Luby-Phelps, Kate; Spurgin, Stephen B.; An, Yu A.; Wang, Qiong A.; Holland, William L.; Scherer, Philipp E.

    2014-01-01

    We recently reported that local overexpression of VEGF-A in white adipose tissue (WAT) protects against diet-induced obesity and metabolic dysfunction. The observation that VEGF-A induces a “brown adipose tissue (BAT)-like” phenotype in WAT prompted us to further explore the direct function of VEGF-A in BAT. We utilized a doxycycline (Dox)-inducible, brown adipocyte-specific VEGF-A transgenic overexpression model to assess direct effects of VEGF-A in BAT in vivo. We observed that BAT-specific VEGF-A expression increases vascularization and up-regulates expression of both UCP1 and PGC-1α in BAT. As a result, the transgenic mice show increased thermogenesis during chronic cold exposure. In diet-induced obese mice, introducing VEGF-A locally in BAT rescues capillary rarefaction, ameliorates brown adipocyte dysfunction, and improves deleterious effects on glucose and lipid metabolism caused by a high-fat diet challenge. These results demonstrate a direct positive role of VEGF-A in the activation and expansion of BAT. PMID:24944907

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  3. Phenotypical heterogeneity linked to adipose tissue dysfunction in patients with Type 2 diabetes.

    PubMed

    Barchetta, Ilaria; Angelico, Francesco; Del Ben, Maria; Di Martino, Michele; Cimini, Flavia Agata; Bertoccini, Laura; Polimeni, Licia; Catalano, Carlo; Fraioli, Antonio; Del Vescovo, Riccardo; Morini, Sergio; Baroni, Marco Giorgio; Cavallo, Maria Gisella

    2016-10-01

    Adipose tissue (AT) inflammation leads to increased free fatty acid (FFA) efflux and ectopic fat deposition, but whether AT dysfunction drives selective fat accumulation in specific sites remains unknown. The aim of the present study was to investigate the correlation between AT dysfunction, hepatic/pancreatic fat fraction (HFF, PFF) and the associated metabolic phenotype in patients with Type 2 diabetes (T2D). Sixty-five consecutive T2D patients were recruited at the Diabetes Centre of Sapienza University, Rome, Italy. The study population underwent clinical examination and blood sampling for routine biochemistry and calculation of insulin secretion [homoeostasis model assessment of insulin secretion (HOMA-β%)] and insulin-resistance [homoeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance (ADIPO-IR)] indexes. Subcutaneous (SAT) and visceral (VAT) AT area, HFF and PFF were determined by magnetic resonance. Some 55.4% of T2D patients had non-alcoholic fatty liver disease (NAFLD); they were significantly younger and more insulin-resistant than non-NAFLD subjects. ADIPO-IR was the main determinant of HFF independently of age, sex, HOMA-IR, VAT, SAT and predicted severe NAFLD with the area under the receiver operating characteristic curve (AUROC)=0.796 (95% confidence interval: 0.65-0.94, P=0.001). PFF was independently associated with increased total adiposity but did not correlate with AT dysfunction, insulin resistance and secretion or NAFLD. The ADIPO-IR index was capable of predicting NAFLD independently of all confounders, whereas it did not seem to be related to intrapancreatic fat deposition; unlike HFF, higher PFF was not associated with relevant alterations in the metabolic profile. In conclusion, the presence and severity of AT dysfunction may drive ectopic fat accumulation towards specific targets, such as VAT and liver, therefore evaluation of AT dysfunction may contribute to the identification of different

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

    PubMed Central

    2013-01-01

    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 receptorγ (PPARγ) in adipose tissue; increases for PPARα 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

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

    PubMed

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

    2015-09-01

    Obesity is associated with the accumulation of pro-inflammatory cells in visceral adipose tissue (VAT), which is an important underlying cause of insulin resistance and progression to diabetes mellitus type 2 (DM2). Although the role of pro-inflammatory cytokines in disease development is established, the initiating events leading to immune cell activation remain elusive. Lean adipose tissue is predominantly populated with regulatory cells, such as eosinophils and type 2 innate lymphocytes. These cells maintain tissue homeostasis through the excretion of type 2 cytokines, such as IL-4, IL-5, and IL-13, which keep adipose tissue macrophages (ATMs) in an anti-inflammatory, M2-like state. Diet-induced obesity is associated with the loss of tissue homeostasis and development of type 1 inflammatory responses in VAT, characterized by IFN-γ. A key event is a shift of ATMs toward an M1 phenotype. Recent studies show that obesity-induced adipocyte hypertrophy results in upregulated surface expression of stress markers. Adipose stress is detected by local sentinels, such as NK cells and CD8(+) T cells, which produce IFN-γ, driving M1 ATM polarization. A rapid accumulation of pro-inflammatory cells in VAT follows, leading to inflammation. In this review, we provide an overview of events leading to adipose tissue inflammation, with a special focus on adipose homeostasis and the obesity-induced loss of homeostasis which marks the initiation of VAT inflammation. PMID:26220361

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

    PubMed

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

    2012-01-01

    Several metabolic disturbances during obesity are associated with adipose tissue-altered functions. Adipocytes contain the renin-angiotensin system (RAS), which regulates signalling pathways that control angiogenesis via Akt in an autocrine fashion. Soya protein (Soy) consumption modifies the gene expression pattern in adipose tissue, resulting in an improved adipocyte function. Therefore, the aim of the present work is to study whether dietary Soy regulates the expression of RAS and angiogenesis-related genes and its association with the phosphorylated state of Akt in the adipose tissue of obese rats. Animals were fed a 30 % Soy or casein (Cas) diet containing 5 or 25 % fat for 160 d. mRNA abundance was studied in the adipose tissue, and Akt phosphorylation and hormone release were measured in the primary adipocyte culture. The present results show that Soy treatment in comparison with Cas consumption induces lower angiotensin release and increased insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption varies the expression of RAS and angiogenesis-related genes, which maintain cell size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus, adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken together, these findings suggest that Soy can be used as a dietary strategy to preserve adipocyte functionality and to prevent obesity abnormalities. PMID:21736766

  7. The Ubiquitin Ligase Siah2 Regulates Obesity-induced Adipose Tissue Inflammation

    PubMed Central

    Kilroy, Gail; Carter, Lauren E.; Newman, Susan; Burk, David H.; Manuel, Justin; Möller, Andreas; Bowtell, David D.; Mynatt, Randall L.; Ghosh, Sujoy; Floyd, Z. Elizabeth

    2015-01-01

    Objective Chronic, low-grade adipose tissue inflammation associated with adipocyte hypertrophy is an important link in the relationship between obesity and insulin resistance. Although ubiquitin ligases regulate inflammatory processes, the role of these enzymes in metabolically driven adipose tissue inflammation is relatively unexplored. Herein, we examined the effect of the ubiquitin ligase Siah2 on obesity-related adipose tissue inflammation. Methods Wild-type and Siah2KO mice were fed a low or high fat diet for 16 weeks. Indirect calorimetry, body composition, glucose and insulin tolerance were assayed along with glucose and insulin levels. Gene and protein expression, immunohistochemistry, adipocyte size distribution and lipolysis were also analyzed. Results Enlarged adipocytes in obese Siah2KO mice are not associated with obesity-induced insulin resistance. Proinflammatory gene expression, stress kinase signaling, fibrosis and crown-like structures are reduced in the Siah2KO adipose tissue and Siah2KO adipocytes are more responsive to insulin-dependent inhibition of lipolysis. Loss of Siah2 increases expression of PPARγ target genes involved in lipid metabolism and decreases expression of proinflammatory adipokines regulated by PPARγ. Conclusions Siah2 links adipocyte hypertrophy with adipocyte dysfunction and recruitment of proinflammatory immune cells to adipose tissue. Selective regulation of PPARγ activity is a Siah2-mediated mechanism contributing to obesity-induced adipose tissue inflammation. PMID:26380945

  8. Antipsychotics-induced metabolic alterations: focus on adipose tissue and molecular mechanisms.

    PubMed

    Gonçalves, Pedro; Araújo, João Ricardo; Martel, Fátima

    2015-01-01

    The use of antipsychotic drugs for the treatment of mood disorders and psychosis has increased dramatically over the last decade. Despite its consumption being associated with beneficial neuropsychiatric effects in patients, atypical antipsychotics (which are the most frequently prescribed antipsychotics) use is accompanied by some secondary adverse metabolic effects such as weight gain, dyslipidemia and glucose intolerance. The molecular mechanisms underlying these adverse effects are not fully understood but have been suggested to involve a dysregulation of adipose tissue homeostasis. As such, the aim of this paper is to review and discuss the role of adipose tissue in the development of secondary adverse metabolic effects induced by atypical antipsychotics. Data analyzed in this article suggest that atypical antipsychotics may increase adipose tissue (particularly visceral adipose tissue) lipogenesis, differentiation/hyperplasia, pro-inflammatory mediator secretion and insulin resistance and decrease adipose tissue lipolysis. Consequently, patients receiving antipsychotic medication could be at risk of developing obesity, type 2 diabetes and cardiovascular disease. A better knowledge of the impact of these drugs on adipose tissue homeostasis may unveil strategies to develop novel antipsychotic drugs with less adverse metabolic effects and to develop adjuvant therapies (e.g. behavioral and nutritional therapies) to neuropsychiatric patients receiving antipsychotic medication. PMID:25523882

  9. Prognostic Impact of Changes in Adipose Tissue Areas after Colectomy in Colorectal Cancer Patients.

    PubMed

    Choe, Eun Kyung; Park, Kyu Joo; Ryoo, Seung Bum; Moon, Sang Hui; Oh, Heung Kwon; Han, Eon Chul

    2016-10-01

    There have been few studies assessing the changes in the body components of patients after colectomy in colorectal cancer (CRC). The purpose of this study was to verify the trends in the adipose tissue areas of CRC patients before and after surgery and to determine their clinical relevance. Computed tomography (CT)-assessed subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) areas were recorded before and after curative resection in stage I to III CRC patients. Changes in the adipose tissue were assessed by calculating the difference in the adipose tissue area between preoperative CT and the most recent postoperative CT, which is disease-free state. Regarding obesity before surgery, there were no prognostic effect of body mass index (BMI), VAT and SAT, and 47.3% of patients had increases in VAT after colectomy. By multivariate analysis, adjusting sex, age, stage, differentiation, VAT change was the only obesity related factor to predict the prognosis, that patients who had increase in VAT after colectomy had better overall survival (HR, 0.557; 95% CI, 0.317-0.880) and disease-free survival (HR, 0.602; 95% CI, 0.391-0.927). BMI and SAT change had no significant association. In subgroup analysis of stage III CRC patients, VAT change had significance for prognosis only in patients who had adjuvant chemotherapy but not in those who did not receive postoperative chemotherapy. Increase in visceral adipose tissue after surgery is a favorable predictor of prognosis for CRC patients. PMID:27550485

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

    PubMed Central

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

    2012-01-01

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

  11. Quantifying adipose and fibroglandular breast tissue properties using MRI-guided NIR tomography

    NASA Astrophysics Data System (ADS)

    Brooksby, Ben; Srinivasan, Subhadra; Pogue, Brian W.; Jiang, Shudong; Dehghani, Hamid; Kogel, Christine; Weaver, John; Poplack, Steven P.; Pearlman, Justin D.; Paulsen, Keith D.

    2005-04-01

    Hybrid NIR-MRI imaging has been used in a clinical breast imaging system to characterize breast tissue properties. The multi-spectral, frequency-domain tomography system operates inside a clinical scanner via long silica-glass optical fiber bundles and using a non-magnetic fiber-patient interface attached to a high resolution MR breast coil. Sixteen fiber bundles are positioned around the circumference of the female breast yielding 240 measurements of light transmission (amplitude and phase) at six optical wavelengths from 660-850nm through up to 12 cm of tissue. From optical measurements, we use a Newton-type algorithm to reconstruct images of tissue optical properties (absorption and scattering), and physiological tissue features such as oxy-hemoglobin [Hb-O2], deoxy-hemoglobin concentrations [Hb-R], water concentration [water], scattering amplitude, and scattering power. We are exploring the synergistic benefits of a combined NIR-MRI data set, specifically the ways in which MRI (i.e. high spatial resolution) can be used to enhance NIR (i.e. high contrast resolution) image reconstruction. A priori knowledge can be applied to image reconstruction in the form of spatial and spectral constraints to improve spatial resolution, contrast, and quantitative accuracy of NIR images. In vivo results suggest that this combined system can accurately quantify contrast between the properties of tissues present in the breast (i.e. adipose and fibroglandular) regardless of their varied and complex spatial organization. For a group of healthy female volunteers, we observe greater contrast between the properties of adipose and glandular tissues when we use MR-guidance than when we do not, and values of total hemoglobin and water content are more consistent with what is physiologically expected.

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

    PubMed

    Kraunsøe, Regitze; Boushel, Robert; Hansen, Christina Neigaard; Schjerling, Peter; Qvortrup, Klaus; Støckel, Mikael; Mikines, Kári J; Dela, Flemming

    2010-06-15

    Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O(2) s(1) mg(1), respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue. PMID:20421291

  13. Effect of dietary vitamin E supplements on cholesteryl ester transfer activity in hamster adipose tissue.

    PubMed

    Shen, G X; Novak, C; Angel, A

    1996-08-01

    Increased concentration of cholesteryl ester transfer protein (CETP) in plasma favours a lipoprotein profile characterized by a reduced high density lipoprotein (HDL) cholesterol. Previous studies have demonstrated that a diet high in cholesterol and saturated fat (HCSF) is associated with elevated plasma CETP and increased release of cholesterol ester transfer activity (CETA) from hamster adipose tissue incubated in vitro. The present study investigated the effects of vitamin E (Vit.E) ingestion on plasma CETP activity and adipose tissue CETA in Syrian Golden hamsters. A regular diet supplemented by the addition of 1% cholesterol and 10% coconut oil (w/w) was associated with a time-dependent increase in plasma CETP activity and increased release of adipose CETA following incubation of fragments of perirenal adipose tissue. Vit.E ingestion (100 mg/kg body weight per day for 8 weeks) suppressed 85% of the increase of CETA released from cultured hamster adipose tissue and 70% of the increase of plasma CETP activity induced by the HCSF diet. Significant decreases in plasma total and LDL cholesterol and an increase in HDL cholesterol were found in hamsters receiving the HCSF diet plus Vit.E compared to the animals on the HCSF diet alone. In the hamsters on regular chow, Vit.E ingestion alone did not significantly alter adipose tissue CETA, plasma CETP activity or plasma lipoproteins. The results indicate that Vit.E prevents the HCSF diet-induced increase in plasma CETP activity, probably via a reduction of CETA secretion from hamster adipose tissue. This suggests that Vit.E supplementation may help to ameliorate the dyslipidemia caused by a HCSF diet through its inhibitory influence on CETP production in adipose tissue. PMID:8830934

  14. Nutritional and exercise interventions variably affect estrogen receptor expression in the adipose tissue of male rats.

    PubMed

    Metz, Lore; Gerbaix, Maude; Masgrau, Aurélie; Guillet, Christelle; Walrand, Stéphane; Boisseau, Nathalie; Boirie, Yves; Courteix, Daniel

    2016-03-01

    Energy-dense food consumption and lack of physical activity are implicated in the development of the current obesity epidemic. The role of estrogen in adiposity and fuel partitioning is mediated mainly though the estrogen receptor α (ERα) isoform. We hypothesized that nutritional adaptation and exercise training, either individually or combined, could impact ERα expression in adipose tissue relative to glucose tolerance. Seventy-two Wistar rats were submitted to a high-fat, high-sucrose (HF-HS) diet for 16weeks. The first phase of our study was to investigate the effect of an HF-HS diet on whole-body glucose tolerance, as well as on body composition and ERα expression in different adipose tissues. Second, we investigated the effect of switching to a well-balanced diet, with or without exercise training for 8 weeks, on those same parameters. After the first part of this study, HF-HS-fed rats were fatter (8%) than control rats. Despite a decrease in glucose tolerance, ERα expression in adipose tissues was not significantly altered by an HF-HS diet. The return to a well-balanced diet significantly increased ERα expression in perirenal and epididymal adipose tissue, but there was no effect of diet or exercise training on whole-body glucose tolerance. The present findings suggest that diet is a powerful modulator of ERα expression in adipose tissue, as nutritional modulation after an HF-HS diet strongly affects ERα expression, particularly in perirenal and epididymal adipose tissue. However, ERα expression in adipose tissue does not appear to be associated with whole-body glucose tolerance. PMID:26923515

  15. Lipocalin 2, a Regulator of Retinoid Homeostasis and Retinoid-mediated Thermogenic Activation in Adipose Tissue.

    PubMed

    Guo, Hong; Foncea, Rocio; O'Byrne, Sheila M; Jiang, Hongfeng; Zhang, Yuanyuan; Deis, Jessica A; Blaner, William S; Bernlohr, David A; Chen, Xiaoli

    2016-05-20

    We have recently characterized the role of lipocalin 2 (Lcn2) as a new adipose-derived cytokine in the regulation of adaptive thermogenesis via a non-adrenergic pathway. Herein, we explored a potential non-adrenergic mechanism by which Lcn2 regulates thermogenesis and lipid metabolism. We found that Lcn2 is a retinoic acid target gene, and retinoic acid concurrently stimulated UCP1 and Lcn2 expression in adipocytes. Lcn2 KO mice exhibited a blunted effect of all-trans-retinoic acid (ATRA) on body weight and fat mass, lipid metabolism, and retinoic acid signaling pathway activation in adipose tissue under the high fat diet-induced obese condition. We further demonstrated that Lcn2 is required for the full action of ATRA on the induction of UCP1 and PGC-1α expression in brown adipocytes and the restoration of cold intolerance in Lcn2 KO mice. Interestingly, we discovered that Lcn2 KO mice have decreased levels of retinoic acid and retinol in adipose tissue. The protein levels of STRA6 responsible for retinol uptake were significantly decreased in adipose tissue. The retinol transporter RBP4 was increased in adipose tissue but decreased in the circulation, suggesting the impairment of RBP4 secretion in Lcn2 KO adipose tissue. Moreover, Lcn2 deficiency abolished the ATRA effect on RBP4 expression in adipocytes. All the data suggest that the decreased retinoid level and action are associated with impaired retinol transport and storage in adipose tissue in Lcn2 KO mice. We conclude that Lcn2 plays a critical role in regulating metabolic homeostasis of retinoids and retinoid-mediated thermogenesis in adipose tissue. PMID:27008859

  16. Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles.

    PubMed

    Xue, Yuan; Xu, Xiaoyang; Zhang, Xue-Qing; Farokhzad, Omid C; Langer, Robert

    2016-05-17

    The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vasculature, angiogenesis offers a potential target for the treatment of obesity-associated disorders. Here we construct two peptide-functionalized nanoparticle (NP) platforms to deliver either Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) activator rosiglitazone (Rosi) or prostaglandin E2 analog (16,16-dimethyl PGE2) to adipose tissue vasculature. These NPs were engineered through self-assembly of a biodegradable triblock polymer composed of end-to-end linkages between poly(lactic-coglycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and an endothelial-targeted peptide. In this system, released Rosi promotes both transformation of white adipose tissue (WAT) into brown-like adipose tissue and angiogenesis, which facilitates the homing of targeted NPs to adipose angiogenic vessels, thereby amplifying their delivery. We show that i.v. administration of these NPs can target WAT vasculature, stimulate the angiogenesis that is required for the transformation of adipose tissue, and transform WAT into brown-like adipose tissue, by the up-regulation of angiogenesis and brown adipose tissue markers. In a diet-induced obese mouse model, these angiogenesis-targeted NPs have inhibited body weight gain and modulated several serological markers including cholesterol, triglyceride, and insulin, compared with the control group. These findings suggest that angiogenesis-targeting moieties with angiogenic stimulator-loaded NPs could be incorporated into effective therapeutic regimens for clinical treatment of obesity and other metabolic diseases. PMID:27140638

  17. Adipose tissue dysfunction and its effects on tumor metabolism

    PubMed Central

    Diedrich, Jonathan; Gusky, Halina Chkourko; Podgorski, Izabela

    2016-01-01

    Growing by an alarming rate in the Western world, obesity has become a condition associated with a multitude of diseases such as diabetes, metabolic syndrome and various cancers. Generally viewed as an abnormal accumulation of hypertrophied adipocytes, obesity is also a poor prognostic factor for recurrence and chemoresistance in cancer patients. With more than two-thirds of the adult population in the United States considered clinically overweight or obese, it is critical that the relationship between obesity and cancer is further emphasized and elucidated. Adipocytes are highly metabolically active cells, which, through release of adipokines and cytokines and activation of endocrine and paracrine pathways, affect processes in neighboring and distant cells, altering their normal homeostasis. This work will examine specifically how adipocyte-derived factors regulate the cellular metabolism of malignant cells within the tumor niche. Briefly, tumor cells undergo metabolic pressure towards a more glycolytic and hypoxic state through a variety of metabolic regulators and signaling pathways, i.e., phosphoinositol-3 kinase (PI3K), hypoxia-inducible factor-1 alpha (HIF-1α), and c-MYC signaling. Enhanced glycolysis and high lactate production are hallmarks of tumor progression largely because of a process known as the Warburg effect. Herein, we review the latest literature pertaining to the body of work on the interactions between adipose and tumor cells, and underlining the changes in cancer cell metabolism that have been targeted by the currently available treatments. PMID:25781550

  18. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue

    PubMed Central

    Kosteli, Aliki; Sugaru, Eiji; Haemmerle, Guenter; Martin, Jayne F.; Lei, Jason; Zechner, Rudolf; Ferrante, Anthony W.

    2010-01-01

    Obesity elicits an immune response characterized by myeloid cell recruitment to key metabolic organs, including adipose tissue. However, the response of immune cells to nonpathologic metabolic stimuli has been less well studied, and the factors that regulate the metabolic-dependent accumulation of immune cells are incompletely understood. Here we characterized the response of adipose tissue macrophages (ATMs) to weight loss and fasting in mice and identified a role for lipolysis in ATM recruitment and accumulation. We found that the immune response to weight loss was dynamic; caloric restriction of high-fat diet–fed mice led to an initial increase in ATM recruitment, whereas ATM content decreased following an extended period of weight loss. The peak in ATM number coincided with the peak in the circulating concentrations of FFA and adipose tissue lipolysis, suggesting that lipolysis drives ATM accumulation. Indeed, fasting or pharmacologically induced lipolysis rapidly increased ATM accumulation, adipose tissue chemoattractant activity, and lipid uptake by ATMs. Conversely, dietary and genetic manipulations that reduced lipolysis decreased ATM accumulation. Depletion of macrophages in adipose tissue cultures increased expression of adipose triglyceride lipase and genes regulated by FFA, and increased lipolysis. These data suggest that local lipid fluxes are central regulators of ATM recruitment and that once recruited, ATMs form lipid-laden macrophages that can buffer local increases in lipid concentration. PMID:20877011

  19. Alternative Mechanism for White Adipose Tissue Lipolysis after Thermal Injury

    PubMed Central

    Diao, Li; Patsouris, David; Sadri, Ali-Reza; Dai, Xiaojing; Amini-Nik, Saeid; Jeschke, Marc G

    2015-01-01

    Extensively burned patients often suffer from sepsis, a complication that enhances postburn hypermetabolism and contributes to increased incidence of multiple organ failure, morbidity and mortality. Despite the clinical importance of burn sepsis, the molecular and cellular mechanisms of such infection-related metabolic derangements and organ dysfunction are still largely unknown. We recently found that upon endoplasmic reticulum (ER) stress, the white adipose tissue (WAT) interacts with the liver via inflammatory and metabolic signals leading to profound hepatic alterations, including hepatocyte apoptosis and hepatic fatty infiltration. We therefore hypothesized that burn plus infection causes an increase in lipolysis of WAT after major burn, partially through induction of ER stress, contributing to hyperlipidemia and profound hepatic lipid infiltration. We used a two-hit rat model of 60% total body surface area scald burn, followed by intraperitoneal (IP) injection of Pseudomonas Aeruginosa-derived lipopolysaccharide (LPS) 3 d postburn. One day later, animals were euthanized and liver and epididymal WAT (EWAT) samples were collected for gene expression, protein analysis and histological study of inflammasome activation, ER stress, apoptosis and lipid metabolism. Our results showed that burn plus LPS profoundly increased lipolysis in WAT associated with significantly increased hepatic lipid infiltration. Burn plus LPS augmented ER stress by upregulating CHOP and activating ATF6, inducing NLRP3 inflammasome activation and leading to increased apoptosis and lipolysis in WAT with a distinct enzymatic mechanism related to inhibition of AMPK signaling. In conclusion, burn sepsis causes profound alterations in WAT and liver that are associated with changes in organ function and structure. PMID:26736177

  20. Quantification of adipose tissue in a rodent model of obesity

    NASA Astrophysics Data System (ADS)

    Johnson, David H.; Flask, Chris; Wan, Dinah; Ernsberger, Paul; Wilson, David L.

    2006-03-01

    Obesity is a global epidemic and a comorbidity for many diseases. We are using MRI to characterize obesity in rodents, especially with regard to visceral fat. Rats were scanned on a 1.5T clinical scanner, and a T1W, water-spoiled image (fat only) was divided by a matched T1W image (fat + water) to yield a ratio image related to the lipid content in each voxel. The ratio eliminated coil sensitivity inhomogeneity and gave flat values across a fat pad, except for outlier voxels (> 1.0) due to motion. Following sacrifice, fat pad volumes were dissected and measured by displacement in canola oil. In our study of 6 lean (SHR), 6 dietary obese (SHR-DO), and 9 genetically obese rats (SHROB), significant differences in visceral fat volume was observed with an average of 29+/-16 ml increase due to diet and 84+/-44 ml increase due to genetics relative to lean control with a volume of 11+/-4 ml. Subcutaneous fat increased 14+/-8 ml due to diet and 198+/-105 ml due to genetics relative to the lean control with 7+/-3 ml. Visceral fat strongly correlated between MRI and dissection (R2 = 0.94), but MRI detected over five times the subcutaneous fat found with error-prone dissection. Using a semi-automated images segmentation method on the ratio images, intra-subject variation was very low. Fat pad composition as estimated from ratio images consistently differentiated the strains with SHROB having a greater lipid concentration in adipose tissues. Future work will include in vivo studies of diet versus genetics, identification of new phenotypes, and corrective measures for obesity; technical efforts will focus on correction for motion and automation in quantification.

  1. Data on the phospholipid fatty acyl composition of retroperitoneal white adipose tissue in ad libitum fed and fasted mice.

    PubMed

    Marks, Kristin A; Marvyn, Phillip M; Henao, Juan J Aristizabal; Bradley, Ryan M; Stark, Ken D; Duncan, Robin E

    2016-06-01

    Data are presented on the fatty acyl composition of phospholipid from retroperitoneal white adipose tissue of female mice that were either given ad libitum access to food or fasted for 16 h overnight prior to sacrifice. Our data show that total adipose phospholipid concentrations were more than 2-fold higher in the fasted animals compared with the fed animals (33.48±7.40 versus 16.57±4.43 μg phospholipid fatty acids/100 mg tissue). Concentrations of several individual phospholipid fatty acyl species, including palmitic acid (16:0), vaccenic acid (18:1n-7), linoleic acid (18:2n-6), dihomo-gamma-linolenic acid (20:3n-6), arachidonic acid (20:4n-6), eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3), as well as total phospholipid saturated fatty acids, n-6 polyunsaturated fatty acids and n-3 polyunsaturated fatty acids, were significantly higher in adipose tissue from the fasted animals compared with the fed animals. However, when the relative abundance of phospholipid fatty acyl species was analyzed, only 20:4n-6 was specifically enriched (by ~2.5-fold) in adipose phospholipid with fasting. PMID:27014729

  2. Dietary fatty acid composition alters 11β-hydroxysteroid dehydrogenase type 1 gene expression in rat retroperitoneal white adipose tissue.

    PubMed

    Vara Prasad, Sakamuri S S; Jeya Kumar, Shanmugam S; Kumar, Putcha Uday; Qadri, Syed S Y H; Vajreswari, Ayyalasomayajula

    2010-01-01

    The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies intracellular glucocorticoid action by converting inactive glucocorticoids to their active forms in vivo. Adipose-specific overexpression of 11β-HSD1 induces metabolic syndrome in mice, whereas 11β-HSD1 null mice are resistant to it. Dietary trans and saturated fatty acids (TFAs and SFAs) are involved in the development of metabolic syndrome, whereas polyunsaturated fatty acids (PUFA) offer protection against this. Here, we report the effects of chronic feeding of different diets containing vanaspati (TFA rich), palm oil (SFA rich) and sunflower oil (PUFA rich) at 10%level on 11β-HSD1 gene expression in rat retroperitoneal adipose tissue. 11β-HSD1 gene expression was significantly higher in TFA rich diet-fed rats compared to SFA rich diet-fed rats, which in turn was significantly higher than PUFA rich diet-fed rats. Similar trend was observed in the expression of CCAAT-enhancer binding protein-α (C/EBP-α), the main transcription factor required for the expression of 11β-HSD1. We propose that TFAs and SFAs increase local amplification of glucocorticoid action in adipose tissue by upregulating 11β-HSD1 by altering C/EBP-α-gene expression. The increased levels of glucocorticoids in adipose tissue may lead to development of obesity and insulin resistance, thereby increasing the risk of developing metabolic syndrome. PMID:20932307

  3. MECHANISMS IN ENDOCRINOLOGY: Brown adipose tissue in humans: regulation and metabolic significance.

    PubMed

    Thuzar, Moe; Ho, Ken K Y

    2016-07-01

    The recent discovery that functional brown adipose tissue (BAT) persists in adult humans has enkindled a renaissance in metabolic research, with a view of harnessing its thermogenic capacity to combat obesity. This review focuses on the advances in the regulation and the metabolic significance of BAT in humans. BAT activity in humans is stimulated by cold exposure and by several factors such as diet and metabolic hormones. BAT function is regulated at two levels: an acute process involving the stimulation of the intrinsic thermogenic activity of brown adipocytes and a chronic process of growth involving the proliferation of pre-existing brown adipocytes or differentiation to brown adipocytes of adipocytes from specific white adipose tissue depots. BAT activity is reduced in the obese, and its stimulation by cold exposure increases insulin sensitivity and reduces body fat. These observations provide strong evidence that BAT plays a significant role in energy balance in humans and has the potential to be harnessed as a therapeutic target for the management of obesity. PMID:27220620

  4. GADD45γ regulates the thermogenic capacity of brown adipose tissue.

    PubMed

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

    2014-08-12

    The coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 α (PGC-1α) is widely considered a central transcriptional regulator of adaptive thermogenesis in brown adipose tissue (BAT). However, mice lacking PGC-1α 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-1α, as read-out in a high-throughput genome-wide cDNA screen, we identify here growth arrest and DNA-damage-inducible protein 45 γ (GADD45γ) as a cold-induced activator of uncoupling protein 1 (UCP1) and oxidative capacity in BAT. Mice lacking Gadd45γ have defects in Ucp1 induction and the thermogenic response to cold. GADD45γ works by activating MAPK p38, which is a potent activator of ERRβ and ERRγ transcriptional function. GADD45γ activates ERRγ independently of PGC-1 coactivators, yet synergizes with PGC-1α to induce the thermogenic program. Our findings elucidate a previously unidentified GADD45γ/p38/ERRγ 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

  5. GADD45γ regulates the thermogenic capacity of brown adipose tissue

    PubMed Central

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

    2014-01-01

    The coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 α (PGC-1α) is widely considered a central transcriptional regulator of adaptive thermogenesis in brown adipose tissue (BAT). However, mice lacking PGC-1α 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-1α, as read-out in a high-throughput genome-wide cDNA screen, we identify here growth arrest and DNA-damage-inducible protein 45 γ (GADD45γ) as a cold-induced activator of uncoupling protein 1 (UCP1) and oxidative capacity in BAT. Mice lacking Gadd45γ have defects in Ucp1 induction and the thermogenic response to cold. GADD45γ works by activating MAPK p38, which is a potent activator of ERRβ and ERRγ transcriptional function. GADD45γ activates ERRγ independently of PGC-1 coactivators, yet synergizes with PGC-1α to induce the thermogenic program. Our findings elucidate a previously unidentified GADD45γ/p38/ERRγ 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

  6. Measurement of subcutaneous adipose tissue development in children by the optical device LIPOMETER

    NASA Astrophysics Data System (ADS)

    Moeller, Reinhard; Horejsi, Renate; Sudi, Karl; Berg, Aloys; Reibnegger, Gilbert; Tafeit, Erwin

    2001-10-01

    The new optical device LIPOMETER enables the non-invasive, quick and save determination of the thickness of subcutantous adipose tissue (SAT) layers (in nm) at any site of the human body. The topographic specification of 15 evenly distributed body sites allows the precise measurement of subcutaneous body fat distribution, so called subcutaneous adipose tissue topopgraphy (SAT-Top). SAT-Top was determined in more than 1000 children aging from 7 to 21 yr. We describe the SAT-Top development of these subjects through different age groups and the differences between male and female SAT-Top development in each age group. SAT layer profiles (medians of the 15 body sites) for boys and girls in age group (7-9 yr) show a very similar pattern for both sexes, followed by decreasing SAT layer thicknesses in boys and increasing values in girls in the subsequent age groups. Between age group 3 (11-13 yr) and age group 7 (19- 21 yr) male and female SAT-Top is significantly different in (almost) all body sites. We present a precise description of SAT-Top development in boys and girls, providing a basis for further investigations in different fields such as obesity, sport sciences or metabolic disorders, and suggesting the LIPOMETER technique as an appropriate measurement tool.

  7. The localization and differential expression of Serum Amyloid A in bovine liver and adipose tissue depots.

    PubMed

    Ceciliani, Fabrizio; Soler, Laura; Grilli, Guido; Marques, Andreia T; Giudice, Chiara; Lecchi, Cristina

    2015-11-15

    In this article the localization of the acute phase protein Serum Amyloid A (SAA) in different depots of bovine adipose tissue (AT) and liver is reported. Quantitative (Real Time) PCR was paired to immunohistochemistry after the production of a specific polyclonal antibody. SAA's mRNA was found in all analyzed AT depots included in the present study, the AT located in the withers being the major source of SAA mRNA. A polyclonal antibody was raised against bovine SAA and was used to validate gene expression analyses. Western Blotting confirmed that SAA is present in all the seven adipose tissue depots include in the present experiment. Anti-SAA polyclonal antibody also stained diffusely adipocytes. In liver, intracytoplasmic immunolabeling was observed in hepatocytes. Staining was generally mild and not diffuse: negative hepatocytes were intermixed with positive ones. A positive intracytoplasmic immunostaining was occasionally observed in endothelial cells lining small blood vessels within AT septa and liver parenchyma. Our data confirm that bovine AT may provide an important source of SAA in healthy subjects. It remains to be determined which is the contribution of AT in the serum concentration of SAA. PMID:26319890

  8. Orthogonal factor coefficient development of subcutaneous adipose tissue topography (SAT-Top) in girls and boys.

    PubMed

    Tafeit, E; Möller, R; Sudi, K; Horejsi, R; Berg, A; Reibnegger, G

    2001-05-01

    The new optical device Lipometer allows noninvasive, quick, and safe determination of the thickness of subcutaneous adipose tissue (SAT) layers (in mm) at any site of the human body. The specification of 15 evenly distributed body sites enables the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Top was measured in 980 children aged 7-19 years. In this paper we describe the degree to which SAT-Top body sites are intercorrelated. We consider whether a meaningful reduction of data is possible using factor analysis, which factors can be extracted, and how SAT-Top data of children can be added to a factor value plot, depicting the essential results of age-dependent subcutaneous fat development. SAT layers situated on the same body area provide correlation coefficients up to +r = 0.91. Two factors are extracted: factor 1, containing all upper body sites (from neck to hip); and factor 2, consisting of all leg body sites. When all 980 children are divided into three age groups in a factor value plot, the first age group (7-11 years) shows almost equal SAT-Top development in boys and girls. Afterwards, for the consecutive age groups 2 (11-15 years) and 3 (15-19 years), the age-dependent subcutaneous fat development of boys and girls progresses into nearly orthogonal directions. PMID:11309750

  9. α-Tocopherol adipose tissue stores are depleted after burn injury in pediatric patients123

    PubMed Central

    Leonard, Scott W; Traber, Daniel L; Traber, Lillian D; Gallagher, James; Bobe, Gerd; Jeschke, Marc G; Finnerty, Celeste C; Herndon, David

    2010-01-01

    Background: We previously showed that thermal injury depletes plasma vitamin E in pediatric burn patients; however, plasma changes may reflect immediate alterations in vitamin E nutriture. Adipose tissue α-tocopherol concentrations are generally accepted to reflect long-term vitamin E status. Objective: To test the hypothesis that thermal injury depletes body stores of vitamin E, α-tocopherol concentrations were measured in adipose tissue samples. Design: Pediatric patients (n = 8) were followed up to 1 y after burn injury. Surgically obtained samples were collected at various intervals and stored at −80°C in a biorepository. α- and γ-Tocopherols, cholesterol, and triglycerides were measured in the same tissue aliquot. Results: During the first week after injury, adipose tissue α-tocopherol concentrations were within the expected normal range of 199 ± 40 nmol/g adipose tissue but were substantially lower at weeks 2 and 3 (133 ± 13 and 109 ± 8 nmol/g adipose