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1

Protein turnover in adipose tissue from fasted or diabetic rats  

NASA Technical Reports Server (NTRS)

Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

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

1986-01-01

2

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

E-print Network

ABSTRACT DEDICATION Page ACKNOWLEDGMENTS TABLE OF CONTENTS Vi LIST OF TABLES LIST OF FIGURES CHAPTER V111 ix I INTRODUCTION II LITERATURE REVIEW III ISOLATION AND CHARACTERIZATION OF A FATTY ACID BINDING PROTEIN IN ADIPOSE TISSUE OF GALLUS... in the evolutionary differentiation of the proteins in the two species. Proteins exhibiting similar activities to FABPs have also been identified in adipose tissue of the rat by Potter et al. (1987), but these are large molecular weight proteins (40, 000 Da...

Sams, Gretchen Hubler

1990-01-01

3

Conjugated Linoleic Acid Induces Uncoupling Protein 1 in White Adipose Tissue of ob\\/ob Mice  

Microsoft Academic Search

Conjugated linoleic acid (CLA) reduces body weight and adipose mass in a variety of species. The mechanisms by which CLA depletes\\u000a adipose mass are unclear, but two independent microarray analyses indicate that in white adipose tissue (WAT), uncoupling\\u000a protein 1 (UCP1) was among genes most changed by CLA. The objective of this study was to determine whether CLA induces ectopic

Angela A. Wendel; Aparna Purushotham; Li-Fen Liu; Martha A. Belury

2009-01-01

4

Fat storage-inducing transmembrane protein 2 is required for normal fat storage in adipose tissue.  

PubMed

Triglycerides within the cytosol of cells are stored in a phylogenetically conserved organelle called the lipid droplet (LD). LDs can be formed at the endoplasmic reticulum, but mechanisms that regulate the formation of LDs are incompletely understood. Adipose tissue has a high capacity to form lipid droplets and store triglycerides. Fat storage-inducing transmembrane protein 2 (FITM2/FIT2) is highly expressed in adipocytes, and data indicate that FIT2 has an important role in the formation of LDs in cells, but whether FIT2 has a physiological role in triglyceride storage in adipose tissue remains unproven. Here we show that adipose-specific deficiency of FIT2 (AF2KO) in mice results in progressive lipodystrophy of white adipose depots and metabolic dysfunction. In contrast, interscapular brown adipose tissue of AF2KO mice accumulated few but large LDs without changes in cellular triglyceride levels. High fat feeding of AF2KO mice or AF2KO mice on the genetically obese ob/ob background accelerated the onset of lipodystrophy. At the cellular level, primary adipocyte precursors of white and brown adipose tissue differentiated in vitro produced fewer but larger LDs without changes in total cellular triglyceride or triglyceride biosynthesis. These data support the conclusion that FIT2 plays an essential, physiological role in fat storage in vivo. PMID:24519944

Miranda, Diego A; Kim, Ji-Hyun; Nguyen, Long N; Cheng, Wang; Tan, Bryan C; Goh, Vera J; Tan, Jolene S Y; Yaligar, Jadegoud; Kn, Bhanu Prakash; Velan, S Sendhil; Wang, Hongyan; Silver, David L

2014-04-01

5

Effect of prepartum protein restriction on brown adipose tissue thermogenic activity in newborn calves  

E-print Network

Brown adipose tissue (BAT) thermogenesis was evaluated in Wagyu-sired calves from Angus heifers fed isocaloric diets with adequate (PA, 10%) or restricted (PR, 5.8%) dietary protein levels during the last 150 d of gestation. At 6 h of age, calves...

Taylor, Travis Lyn

1997-01-01

6

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

PubMed Central

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

Wagner, Marek

2014-01-01

7

Changes in GDP binding to brown adipose tissue mitochondria and the uncoupling protein  

Microsoft Academic Search

Incubation in vitro of brown adipose tissue (BAT) mitochondria with divalent cations, spermine, or alkaline phosphatase led to a marked increase in the binding of (³H)GDP. The effect of Mg{sup 2+} appeared to be the most specific and led to the largest increase in GDP binding. A simplified method was developed for measuring GDP binding to purified uncoupling protein from

A. G. Swick; R. W. Swick

1988-01-01

8

Assessment of brown adipose tissue function  

PubMed Central

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

Virtue, Sam; Vidal-Puig, Antonio

2013-01-01

9

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

NASA Astrophysics Data System (ADS)

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

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

1993-03-01

10

The cellular structure and lipid/protein composition of adipose tissue surrounding chronically stimulated lymph nodes in rats.  

PubMed

To test the hypothesis that chronic immune stimulation of a peripheral lymph node induces the formation of additional mature adipocytes in adjacent adipose tissue, one popliteal lymph node of large male rats was stimulated by local injection of 10 microg or 20 microg lipopolysaccharide three times a week for 6 weeks. Adipocyte volumes in sites defined by their anatomical relations to the stimulated and homologous unstimulated popliteal lymph nodes were measured, plus adipocyte complement of the popliteal depot, and the lipid and protein content of adipocytes and adipose stroma. The higher dose of lipopolysaccharide doubled the mass of the locally stimulated lymph node and the surrounding adipose tissue enlarged by the appearance of additional mature adipocytes. Similar but smaller changes were observed in the popliteal adipose depot of the unstimulated leg and in a nodeless depot. The lipid content of the adipocytes decreased and that of the stroma increased dose-dependently in all samples measured but the changes were consistently greater in the depot surrounding the stimulated lymph node. The protein content of both adipocytes and stroma increased in samples surrounding the stimulated node. We conclude that chronic immune stimulation of lymphoid tissues induces the formation of more adipocytes in the adjacent adipose tissue. These findings suggest a mechanism for the selective hypertrophy of lymphoid-containing adipose depots in the HIV-associated adipose redistribution syndrome. PMID:12846476

Mattacks, Christine A; Sadler, Dawn; Pond, Caroline M

2003-06-01

11

Adipose Tissue as an Endocrine Organ  

Microsoft Academic Search

The discovery of leptin in the mid-1990s has focused attention on the role of proteins secreted by adipose tissue. Leptin has profound effects on appetite and energy balance, and is also involved in the regulation of neuroendocrine and immune function. Sex steroid and glucocorticoid metabolism in adipose tissue has been implicated as a determinant of body fat distribution and cardiovascular

Rexford S Ahima; JEFFREY S. FLIER

2000-01-01

12

Effects of Dietary Protein and Exercise on Brown Adipose Tissue and Energy Balance in Experimental Animals1  

Microsoft Academic Search

The effects of exercise and of dietary protein level on energy metab olism and brown adipose tissue (BAT) activity were investigated in weanling male mice. Mice were fed diets providing low (7.5%), adequate (12.5%) or high (25%) levelsof dietary protein. Half of the animals in each dietary group were given moderate exercise by swimming. The lower the level of dietary

ROMA R. HELL; PAMELA W. DIGBY

13

A reduced protein diet induces stearoyl-CoA desaturase protein expression in pig muscle but not in subcutaneous adipose tissue: relationship with intramuscular lipid formation.  

PubMed

A reduced protein diet (RPD) is known to increase the level of intramuscular lipid in pig meat with a smaller effect on the amount of subcutaneous adipose tissue. This might be due to tissue-specific activation of the expression of lipogenic enzymes by the RPD. The present study investigated the effect of a RPD, containing palm kernel oil, soyabean oil or palm oil on the activity and expression of one of the major lipogenic enzymes, stearoyl-CoA desaturase (SCD) and on the level of total lipids and the fatty acid composition of muscle and subcutaneous adipose tissue in pigs. The RPD significantly increased SCD protein expression and activity in muscle but not in subcutaneous adipose tissue. The level of MUFA and total fatty acids in muscle was also elevated when the RPD was fed, with only small changes in subcutaneous adipose tissue. A positive significant correlation between SCD protein expression and total fatty acids in muscle was found. The results suggest that an increase in intramuscular but not subcutaneous adipose tissue fatty acids under the influence of a RPD is related to tissue-specific activation of SCD expression. It is suggested that the SCD isoform spectra in pig subcutaneous adipose tissue and muscle might be different. PMID:16512947

Doran, O; Moule, S K; Teye, G A; Whittington, F M; Hallett, K G; Wood, J D

2006-03-01

14

Rat adipose-tissue glycerol phosphate acyltransferase can be inactivated by cyclic AMP-dependent protein kinase.  

PubMed Central

Rat adipose-tissue glycerol phosphate acyltransferase can be inactivated in a phosphorylation reaction catalysed by cyclic AMP-dependent protein kinase and reactivated by treatment with alkaline phosphatase. These results suggest that phosphorylation of glycerol phosphate acyltransferase may be involved in the hormonal control of esterification. PMID:217367

Nimmo, H G; Houston, B

1978-01-01

15

Leucine Deprivation Decreases Fat Mass by Stimulation of Lipolysis in White Adipose Tissue and Upregulation of Uncoupling Protein 1 (UCP1) in Brown Adipose Tissue  

PubMed Central

OBJECTIVE White adipose tissue (WAT) and brown adipose tissue (BAT) play distinct roles in adaptation to changes in nutrient availability, with WAT serving as an energy store and BAT regulating thermogenesis. We previously showed that mice maintained on a leucine-deficient diet unexpectedly experienced a dramatic reduction in abdominal fat mass. The cellular mechanisms responsible for this loss, however, are unclear. The goal of current study is to investigate possible mechanisms. RESEARCH DESIGN AND METHODS Male C57BL/6J mice were fed either control, leucine-deficient, or pair-fed diets for 7 days. Changes in metabolic parameters and expression of genes and proteins related to lipid metabolism were analyzed in WAT and BAT. RESULTS We found that leucine deprivation for 7 days increases oxygen consumption, suggesting increased energy expenditure. We also observed increases in lipolysis and expression of ?-oxidation genes and decreases in expression of lipogenic genes and activity of fatty acid synthase in WAT, consistent with increased use and decreased synthesis of fatty acids, respectively. Furthermore, we observed that leucine deprivation increases expression of uncoupling protein (UCP)-1 in BAT, suggesting increased thermogenesis. CONCLUSIONS We show for the first time that elimination of dietary leucine produces significant metabolic changes in WAT and BAT. The effect of leucine deprivation on UCP1 expression is a novel and unexpected observation and suggests that the observed increase in energy expenditure may reflect an increase in thermogenesis in BAT. Further investigation will be required to determine the relative contribution of UCP1 upregulation and thermogenesis in BAT to leucine deprivation-stimulated fat loss. PMID:19833890

Cheng, Ying; Meng, Qingshu; Wang, Chunxia; Li, Houkai; Huang, Zhiying; Chen, Shanghai; Xiao, Fei; Guo, Feifan

2010-01-01

16

The purification and characterization of a fatty acid binding protein specific to pig (Sus domesticus) adipose tissue.  

PubMed Central

Western-blot analysis using antiserum to 3T3-L1-cell fatty acid binding protein (FABP) revealed that pig adipose tissue contains a 15 kDa protein immunologically similar to the murine protein. This 15 kDa protein was purified from pig adipose tissue by sequential application of Sephadex G-50 gel filtration, cation exchange and covalent chromatography on Thiol-Sepharose-4B. The purity of the pig protein was established by two-dimensional polyacrylamide-gel electrophoresis. Isoelectric focusing indicated that the pig adipose FABP (a-FABP) exists with two charge isoforms (pI 5.1 and 5.2), both of which persist after delipidation. The N-terminus of the purified pig a-FABP was blocked; however, cleavage with CNBr allowed recovery of a 12-amino-acid peptide which was identical with the murine a-FABP sequence (residues 36-48) at 10 of 12 positions. The pig a-FABP bound 12-(9-anthroyloxy)oleic acid saturably and stoichiometrically, with an apparent dissociation constant of 1.0 microM. Northern-blot analysis using the cDNA for the murine 3T3-L1 FABP revealed that the pig a-FABP was expressed exclusively in adipose tissue. Images Fig. 1. Fig. 2. Fig. 3. Fig. 6. Fig. 7. Fig. 8. PMID:2334399

Armstrong, M K; Bernlohr, D A; Storch, J; Clarke, S D

1990-01-01

17

Concentration of rat brown adipose tissue uncoupling protein may not be correlated with ³H-GDP binding  

Microsoft Academic Search

Rats fed diets low in protein or exposed to cold show an increase in brown adipose tissue (BAT) mitochondrial ³H-GDP binding. To investigate this phenomenon further, the uncoupling protein associated with BAT function was measured immunochemically on nitrocellulose blots. Quantitation of uncoupling protein was achieved by densitometer scanning with a BioRad densitometer. Peaks were integrated with Chromatochart software and an

M. F. Henningfield; A. G. Swick; R. W. Swick

1986-01-01

18

Brown adipose tissue and thermogenesis.  

PubMed

The growing understanding of adipose tissue as an important endocrine organ with multiple metabolic functions has directed the attention to the (patho)physiology of distinct fat depots. Brown adipose tissue (BAT), in contrast to bona fide white fat, can dissipate significant amounts of chemical energy through uncoupled respiration and heat production (thermogenesis). This process is mediated by the major thermogenic factor uncoupling protein-1 and can be activated by certain stimuli, such as cold exposure, adrenergic compounds or genetic alterations. White adipose tissue (WAT) depots, however, also possess the capacity to acquire brown fat characteristics in response to thermogenic stimuli. The induction of a BAT-like cellular and molecular program in WAT has recently been termed "browning" or "beiging". Promotion of BAT activity or the browning of WAT is associated with in vivo cold tolerance, increased energy expenditure, and protection against obesity and type 2 diabetes. These preclinical observations have gained additional significance with the recent discovery that active BAT is present in adult humans and can be detected by 18fluor-deoxy-glucose positron emission tomography coupled with computed tomography. As in rodents, human BAT can be activated by cold exposure and is associated with increased energy turnover and lower body fat mass. Despite the tremendous progress in brown fat research in recent years, pharmacological concepts to harness BAT function therapeutically are currently still lacking. PMID:25390014

Fenzl, Anna; Kiefer, Florian W

2014-07-01

19

Adipose tissue biology and HIV-infection.  

PubMed

HIV-1/highly active antiretroviral therapy-associated lipodystrophy syndrome (HALS) is an adipose tissue redistribution disorder characterized by subcutaneous adipose tissue lipoatrophy, sometimes including visceral adipose tissue hypertrophy and accumulation of dorsocervical fat ('buffalo hump'). The pathophysiology of HALS appears to be multifactorial and several key pathophysiological factors associated with HALS have been identified. These include mitochondrial dysfunction, adipocyte differentiation disturbances, high adipocyte lipolysis, and adipocyte apoptosis. These alterations in adipose tissue biology expand to involve systemic metabolism through alterations in endocrine functions of adipose tissue (via disturbed adipokine release), enhanced production of pro-inflammatory cytokines and excessive free fatty-acid release due to lipolysis. The deleterious action of some antiretroviral drugs is an important factor in eliciting these alterations in adipose tissue. However, HIV-1 infection-related events and HIV-1-encoded proteins also contribute directly to the complex development of HALS through effects on adipocyte biology, or indirectly through the promotion of local inflammation in adipose tissue. PMID:21663842

Giralt, Marta; Domingo, Pere; Villarroya, Francesc

2011-06-01

20

Adipose tissue gene expression profiling reveals distinct molecular pathways that define visceral adiposity in offspring of maternal protein-restricted rats.  

PubMed

There is increasing evidence that poor early growth confers an increased risk of type 2 diabetes, hypertension, and other features of the metabolic syndrome in later life. We hypothesized that this may result from poor nutrition during early life exerting permanent effects on the structure and function of key metabolic organ systems. To study the long-term impact of early-life undernutrition on susceptibility to visceral adiposity, we used a rat model of maternal protein restriction (MPR) in which dams were fed a low-protein diet (containing 8% instead of 20% protein in control diet) throughout pregnancy and lactation. MPR offspring were born smaller than controls (offspring of dams on control diet) and in adulthood developed visceral adiposity. We compared the pattern of gene expression in visceral adipose tissue (VAT) between MPR offspring and controls with Affymetrix rat expression arrays. Of the total number of genes and expressed sequence tags analyzed (15,923 probe sets), 9,790 (61.5%) were expressed in VAT. We identified 650 transcripts as differentially expressed > or =1.5-fold in the VAT of MPR offspring. Gene ontology analysis revealed a global upregulation of genes involved in carbohydrate, lipid, and protein metabolism. A number of genes involved in adipocyte differentiation, angiogenesis, and extracellular matrix remodeling were also upregulated. However, in marked contrast to other rodent models of obesity, the expression of a large number of genes associated with inflammation was reduced in this rat model. Thus visceral adiposity in this early-life programmed rat model is marked by dynamic changes in the transcriptional profile of VAT. Our data provide new insights into the molecular mechanisms that underlie the early-life programming of visceral adiposity. PMID:15562247

Guan, Haiyan; Arany, Edith; van Beek, Jonathan P; Chamson-Reig, Astrid; Thyssen, Sandra; Hill, David J; Yang, Kaiping

2005-04-01

21

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

PubMed Central

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

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

2012-01-01

22

Exposure to fine airborne particulate matter induces macrophage infiltration, unfolded protein response, and lipid deposition in white adipose tissue  

PubMed Central

Recent epidemiological studies have suggested a link between exposure to ambient air-pollution and susceptibility to metabolic disorders such as Type II diabetes mellitus. Previously, we provided evidence that both short- and long-term exposure to concentrated ambient particulate matter with aerodynamic diameter <2.5 ?m (PM2.5) induces multiple abnormalities associated with the pathogenesis of Type II diabetes mellitus, including insulin resistance, visceral adipose inflammation, brown adipose mitochondrial adipose changes, and hepatic endoplasmic reticulum (ER) stress. In this report, we show that chronic inhalation exposure to PM2.5 (10 months exposure) induces macrophage infiltration and Unfolded Protein Response (UPR), an intracellular stress signaling that regulates cell metabolism and survival, in mouse white adipose tissue in vivo. Gene expression studies suggested that PM2.5 exposure induces two distinct UPR signaling pathways mediated through the UPR transducer inositol-requiring 1? (IRE1?): 1) ER-associated Degradation (ERAD) of unfolded or misfolded proteins, and 2) Regulated IRE1-dependent Decay (RIDD) of mRNAs. Along with the induction of the UPR pathways and macrophage infiltration, expression of genes involved in lipogenesis, adipocyte differentiation, and lipid droplet formation was increased in the adipose tissue of the mice exposed to PM2.5. In vitro study confirmed that PM2.5 can trigger phosphorylation of the UPR transducer IRE1? and activation of macrophages. These results provide novel insights into PM2.5-triggered cell stress response in adipose tissue and increase our understanding of pathophysiological effects of particulate air pollution on the development of metabolic disorders. PMID:23573366

Mendez, Roberto; Zheng, Ze; Fan, Zhongjie; Rajagopalan, Sanjay; Sun, Qinghua; Zhang, Kezhong

2013-01-01

23

Translocator Protein 18 kDa (TSPO) Is Regulated in White and Brown Adipose Tissue by Obesity  

PubMed Central

Translocator protein 18 kDa (TSPO) is an outer-mitochondrial membrane transporter which has many functions including participation in the mitochondrial permeability transition pore, regulation of reactive oxygen species (ROS), production of cellular energy, and is the rate-limiting step in the uptake of cholesterol. TSPO expression is dysregulated during disease pathologies involving changes in tissue energy demands such as cancer, and is up-regulated in activated macrophages during the inflammatory response. Obesity is associated with decreased energy expenditure, mitochondrial dysfunction, and chronic low-grade inflammation which collectively contribute to the development of the Metabolic Syndrome. Therefore, we hypothesized that dysregulation of TSPO in adipose tissue may be a feature of disease pathology in obesity. Radioligand binding studies revealed a significant reduction in TSPO ligand binding sites in mitochondrial extracts from both white (WAT) and brown adipose tissue (BAT) in mouse models of obesity (diet-induced and genetic) compared to control animals. We also confirmed a reduction in TSPO gene expression in whole tissue extracts from WAT and BAT. Immunohistochemistry in WAT confirmed TSPO expression in adipocytes but also revealed high-levels of TSPO expression in WAT macrophages in obese animals. No changes in TSPO expression were observed in WAT or BAT after a 17 hour fast or 4 hour cold exposure. Treatment of mice with the TSPO ligand PK11195 resulted in regulation of metabolic genes in WAT. Together, these results suggest a potential role for TSPO in mediating adipose tissue homeostasis. PMID:24260329

Thompson, Misty M.; Manning, H. Charles; Ellacott, Kate L. J.

2013-01-01

24

Adipose tissues and thyroid hormones  

PubMed Central

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

Obregon, Maria-Jesus

2014-01-01

25

Control of adipose tissue expandability in response to high fat diet by the insulin-like growth factor-binding protein-4.  

PubMed

Adipose tissue expansion requires growth and proliferation of adipocytes and the concomitant expansion of their stromovascular network. We have used an ex vivo angiogenesis assay to study the mechanisms involved in adipose tissue expansion. In this assay, adipose tissue fragments placed under pro-angiogenic conditions form sprouts composed of endothelial, perivascular, and other proliferative cells. We find that sprouting was directly stimulated by insulin and was enhanced by prior treatment of mice with the insulin sensitizer rosiglitazone. Moreover, basal and insulin-stimulated sprouting increased progressively over 30 weeks of high fat diet feeding, correlating with tissue expansion during this period. cDNA microarrays analyzed to identify genes correlating with insulin-stimulated sprouting surprisingly revealed only four positively correlating (Fads3, Tmsb10, Depdc6, and Rasl12) and four negatively correlating (Asph, IGFbp4, Ppm1b, and Adcyap1r1) genes. Among the proteins encoded by these genes, IGFbp4, which suppresses IGF-1 signaling, has been previously implicated in angiogenesis, suggesting a role for IGF-1 in adipose tissue expandability. Indeed, IGF-1 potently stimulated sprouting, and the presence of activated IGF-1 receptors in the vasculature was revealed by immunostaining. Recombinant IGFbp4 blocked the effects of insulin and IGF-1 on mouse adipose tissue sprouting and also suppressed sprouting from human subcutaneous adipose tissue. These results reveal an important role of IGF-1/IGFbp4 signaling in post-developmental adipose tissue expansion. PMID:24778188

Gealekman, Olga; Gurav, Kunal; Chouinard, My; Straubhaar, Juerg; Thompson, Michael; Malkani, Samir; Hartigan, Celia; Corvera, Silvia

2014-06-27

26

Heat shock proteins: in vivo heat treatments reveal adipose tissue depot-specific effects.  

PubMed

Heat treatments (HT) and the induction of heat shock proteins (HSPs) improve whole body and skeletal muscle insulin sensitivity while decreasing white adipose tissue (WAT) mass. However, HSPs in WAT have been understudied. The purpose of the present study was to examine patterns of HSP expression in WAT depots, and to examine the effects of a single in vivo HT on WAT metabolism. Male Wistar rats received HT (41C, 20 min) or sham treatment (37C), and 24 h later subcutaneous, epididymal, and retroperitoneal WAT depots (SCAT, eWAT, and rpWAT, respectively) were removed for ex vivo experiments and Western blotting. SCAT, eWAT, and rpWAT from a subset of rats were also cultured separately and received a single in vitro HT or sham treatment. HSP72 and HSP25 expression was greatest in more metabolically active WAT depots (i.e., eWAT and rpWAT) compared with the SCAT. Following HT, HSP72 increased in all depots with the greatest induction occurring in the SCAT. In addition, HSP25 increased in the rpWAT and eWAT, while HSP60 increased in the rpWAT only in vivo. Free fatty acid (FFA) release from WAT explants was increased following HT in the rpWAT only, and fatty acid reesterification was decreased in the rpWAT but increased in the SCAT following HT. HT increased insulin responsiveness in eWAT, but not in SCAT or rpWAT. Differences in HSP expression and induction patterns following HT further support the growing body of literature differentiating distinct WAT depots in health and disease. PMID:25554799

Rogers, Robert S; Beaudoin, Marie-Soleil; Wheatley, Joshua L; Wright, David C; Geiger, Paige C

2015-01-01

27

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

PubMed Central

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

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

2007-01-01

28

Differentially expressed proteins associated with myogenesis and adipogenesis in skeletal muscle and adipose tissue between bulls and steers.  

PubMed

The objective of this study was to identify some proteins associated with testosterone-related differences in myogenesis and adipogenesis between bulls and steers. Global proteins were monitored in skeletal muscle and adipose tissue from bulls (n = 20) and steers (n = 20), respectively. We identified four differentially expressed (twofold or more) proteins in skeletal muscle from bulls, myosin light chain 1 (MLC1), ankyrin repeat domain-containing protein 1 (ANKRD1) and heat shock protein beta 1 (HSPB1) that were up-regulated and cofilin 2 (CFL2) that was down-regulated, and also identified two down-regulated proteins in adipose tissue, transaldolase 1 (TALDO1) and L: -lactate dehydrogenase B chain (LDHB). In vitro, after myogenic differentiation of a bovine cell line, the mRNA expression of HSPB1 not only increased approximately tenfold in response to differentiation but threefold in response to testosterone addition, respectively, but that of ANKRD1 and CFL2 did not significantly change in response to myogenic differentiation or testosterone addition. Likewise, after adipogenic differentiation of a bovine cell line, the mRNA expression of TALDO1 and LDHB did not significantly vary in response to adipogenic differentiation or testosterone addition. Therefore, we suggest that HSPB1 could have an important role during testosterone-related myogenesis. PMID:21594731

Zhang, Qiankun; Lee, Hong-Gu; Han, Jung-A; Kang, Sang Kee; Lee, Nam Kyung; Baik, Myunggi; Choi, Yun-Jaie

2012-02-01

29

Uncoupling protein-2 (UCP2) gene expression in subcutaneous and omental adipose tissue of Asian Indians  

PubMed Central

Objective UCP2 is a mitochondrial membrane transporter expressed in white adipose tissue and involved in regulation of energy balance. In this present study, we examined the depot specific comparison of UCP2 gene expression in different metabolic states, in order to explore the potential role of UCP2 in human obesity and diabetes. We also determined UCP2s association with adiponectin and insulin resistance with different parameters of the metabolic syndrome. Methods Subcutaneous adipose tissue (SAT) and omental adipose tissues (OAT) were obtained from 69 subjects, including 23 non-obese controls, 26 obese and 20 obese T2DM patients. Metabolic syndrome and other clinical features were studied. Adiponectin and UCP2 gene expression was quantitated by Real Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Results UCP2 gene expression was significantly reduced in obese and diabetic patients compared with controls. Interestingly, we found that UCP2 gene expression was reduced more in omental fat compared with subcutaneous fat and this effect was observed only in males but not in females. Partial correlation analysis showed significant association with the obesity parameters waist circumference, insulin and HOMA-IR, the lipid parameter triglyceride and the adipokine adiponectin. Conclusion Reduced UCP2 gene expression in obese and diabetic patients and its association with obesity parameters and HOMA-IR confirms its role as a candidate gene in the study of obesity and diabetes in our population. Also, its association with triglycerides implicates its role in lipid metabolism. An association between adiponectin and UCP2 gene expression may provide us with an innovative therapeutic strategy to prevent obesity related diseases, like diabetes and CVD. PMID:23700519

Mahadik, Sujata R.; Lele, Ramchandra D.; Saranath, Dhananjaya; Seth, Anika; Parikh, Vikram

2012-01-01

30

Adipose tissue macrophages: amicus adipem?  

PubMed Central

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

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

2014-01-01

31

Obesity is associated with macrophage accumulation in adipose tissue  

PubMed Central

Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrowderived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-? expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals. PMID:14679176

Weisberg, Stuart P.; McCann, Daniel; Desai, Manisha; Rosenbaum, Michael; Leibel, Rudolph L.; Ferrante, Anthony W.

2003-01-01

32

The developmental origins of adipose tissue  

PubMed Central

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

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

2013-01-01

33

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

PubMed

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

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

2014-11-01

34

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

PubMed Central

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

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

2012-01-01

35

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

PubMed

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

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

2015-02-01

36

Adipose tissue immunity and cancer  

PubMed Central

Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete pro-inflammatory adipokines and cytokines providing a microenvironment favorable for tumor growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching toward M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumor growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumor cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumor microenvironment with more sophisticated and selective anti-tumoral drugs. PMID:24106481

Cataln, Victoria; Gmez-Ambrosi, Javier; Rodrguez, Amaia; Frhbeck, Gema

2013-01-01

37

C-Reactive Protein in Healthy Subjects: Associations With Obesity, Insulin Resistance, and Endothelial Dysfunction A Potential Role for Cytokines Originating From Adipose Tissue?  

Microsoft Academic Search

C-reactive protein, a hepatic acute phase protein largely regulated by circulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secretes interleukin-6 in vivo. In this study we have sought associations of levels of C-reactive protein and interleukin-6 with measures of obesity and of chronic infection as their putative determinants. We

John S. Yudkin; C. D. A. Stehouwer; J. J. Emeis; S. W. Coppack

38

Diets high in monounsaturated and polyunsaturated fatty acids decrease fatty acid synthase protein levels in adipose tissue but do not alter other markers of adipose function and inflammation in diet-induced obese rats.  

PubMed

This study investigates the effects of monounsaturated and polyunsaturated fatty acids from different fat sources (High Oleic Canola, Canola, Canola-Flaxseed (3:1 blend), Safflower, or Soybean Oil, or a Lard-based diet) on adipose tissue function and markers of inflammation in Obese Prone rats fed high-fat (55% energy) diets for 12 weeks. Adipose tissue fatty acid composition reflected the dietary fatty acid profiles. Protein levels of fatty acid synthase, but not mRNA levels, were lower in adipose tissue of all groups compared to the Lard group. Adiponectin and fatty acid receptors GPR41 and GPR43 protein levels were also altered, but other metabolic and inflammatory mediators in adipose tissue and serum were unchanged among groups. Overall, rats fed vegetable oil- or lard-based high-fat diets appear to be largely resistant to major phenotypic changes when the dietary fat composition is altered, providing little support for the importance of specific fatty acid profiles in the context of a high-fat diet. PMID:24411719

Enns, Jennifer E; Hanke, Danielle; Park, Angela; Zahradka, Peter; Taylor, Carla G

2014-01-01

39

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

PubMed Central

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

2014-01-01

40

Aromatase Controls Sjgren Syndrome-Like Lesions through Monocyte Chemotactic Protein-1 in Target Organ and Adipose Tissue-Associated Macrophages.  

PubMed

Several autoimmune diseases are known to develop in postmenopausal women. However, the mechanism by which estrogen deficiency influences autoimmunity is unknown. Aromatase is an enzyme that converts androgens to estrogens. Herein, we used female aromatase gene knockout (ArKO) mice as a model of estrogen deficiency to investigate the molecular mechanism that underlies the onset and development of autoimmunity. Histological analyses showed that inflammatory lesions in the lacrimal and salivary glands of ArKO mice increased with age. Adoptive transfer of spleen cells or bone marrow cells from ArKO mice into recombination activating gene 2 knockout mice failed to induce the autoimmune lesions. Expression of mRNA encoding proinflammatory cytokines and monocyte chemotactic protein-1 increased in white adipose tissue of ArKO mice and was significantly higher than that in wild-type mice. Moreover, an increased number of inflammatory M1 macrophages was observed in white adipose tissue of ArKO mice. A significantly increased monocyte chemotactic protein-1 mRNA expression of the salivary gland tissue in ArKO was found together with adiposity. Furthermore, the autoimmune lesions in a murine model of Sjgren syndrome were exacerbated by administration of an aromatase inhibitor. These results suggest that aromatase may play a key role in the pathogenesis of Sjgren syndrome-like lesions by controlling the target organ and adipose tissue-associated macrophage. PMID:25447050

Iwasa, Akihiko; Arakaki, Rieko; Honma, Naoko; Ushio, Aya; Yamada, Akiko; Kondo, Tomoyuki; Kurosawa, Emi; Kujiraoka, Satoko; Tsunematsu, Takaaki; Kudo, Yasusei; Tanaka, Eiji; Yoshimura, Noriko; Harada, Nobuhiro; Hayashi, Yoshio; Ishimaru, Naozumi

2015-01-01

41

Adipose Tissue Development, Structure and Function  

Microsoft Academic Search

\\u000a One of the earliest reports of adipose tissue was made by the Swiss naturalist Conrad Gessner in 1551 (as translated by Cannon\\u000a and Nedergaard [1]). However, the notion that adipose tissue was composed of living lipid-laden cells was hotly debated [2].\\u000a The past decades have seen a remarkable increase in our understanding of adipose biology and obesity (Fig.1). This trend

Jaswinder K. Sethi; Antonio J. Vidal-Puig

42

Adipose tissue: cell heterogeneity and functional diversity.  

PubMed

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

Esteve Rfols, Montserrat

2014-02-01

43

Adipose and mammary epithelial tissue engineering  

PubMed Central

Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast. PMID:23628872

Zhu, Wenting; Nelson, Celeste M.

2013-01-01

44

cAMP-dependent protein kinase from brown adipose tissue: temperature effects on kinetic properties and enzyme role in hibernating ground squirrels  

Microsoft Academic Search

Arousal from hibernation requires thermogenesis in brown adipose tissue, a process that is stimulated by ?-adrenergic signals,\\u000a leading to a rise in intracellular 3?,5?-cyclic adenosine monophosphate AMP (cAMP) and activating cAMP-dependent protein kinase\\u000a A (PKA) to phosphorylate a suite of target proteins and activate lipolysis and uncoupled respiration. To determine whether\\u000a specific adaptations (perhaps temperature-dependent) facilitate PKA kinetic properties or

J. A. MacDonald; K. B. Storey

1998-01-01

45

Acerola (Malpighia emarginata DC.) juice intake protects against alterations to proteins involved in inflammatory and lipolysis pathways in the adipose tissue of obese mice fed a cafeteria diet  

PubMed Central

Background Obesity has been studied as a metabolic and an inflammatory disease and is characterized by increases in the production of pro-inflammatory adipokines in the adipose tissue. To elucidate the effects of natural dietary components on the inflammatory and metabolic consequences of obesity, we examined the effects of unripe, ripe and industrial acerola juice (Malpighia emarginata DC.) on the relevant inflammatory and lipolysis proteins in the adipose tissue of mice with cafeteria diet-induced obesity. Materials/methods Two groups of male Swiss mice were fed on a standard diet (STA) or a cafeteria diet (CAF) for 13weeks. Afterwards, the CAF-fed animals were divided into five subgroups, each of which received a different supplement for one further month (water, unripe acerola juice, ripe acerola juice, industrial acerola juice, or vitamin C) by gavage. Enzyme-linked immunosorbent assays, Western blotting, a colorimetric method and histology were utilized to assess the observed data. Results The CAF water (control obese) group showed a significant increase in their adiposity indices and triacylglycerol levels, in addition to a reduced IL-10/TNF-? ratio in the adipose tissue, compared with the control lean group. In contrast, acerola juice and Vitamin C intake ameliorated the weight gain, reducing the TAG levels and increasing the IL-10/TNF-? ratio in adipose tissue. In addition, acerola juice intake led to reductions both in the level of phosphorylated JNK and to increases in the phosphorylation of I?B? and HSLser660 in adipose tissue. Conclusions Taken together, these results suggest that acerola juice reduces low-grade inflammation and ameliorates obesity-associated defects in the lipolytic processes. PMID:24495336

2014-01-01

46

Adaptations of Maternal Adipose Tissue to Lactation  

Microsoft Academic Search

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

Richard G. Vernon; Caroline M. Pond

1997-01-01

47

Increased uncoupling protein-2 mRNA abundance and glucocorticoid action in adipose tissue in the sheep fetus during late gestation is dependent on plasma cortisol and triiodothyronine.  

PubMed

The endocrine regulation of uncoupling protein-2 (UCP2), an inner mitochondrial protein, in fetal adipose tissue remains unclear. The present study aimed to determine if fetal plasma cortisol and triiodothyronine (T3) influenced the mRNA abundance of UCP2, glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) and 2 (11betaHSD2) in fetal adipose tissue in the sheep during late gestation. Perirenal-abdominal adipose tissue was sampled from ovine fetuses to which either cortisol (2-3 mg kg(-1) day(-1)) or saline was infused for 5 days up to 127-130 days gestation, or near term fetuses (i.e. 142-145 days gestation) that were either adrenalectomised (AX) or remained intact. Fetal plasma cortisol and T3 concentrations were higher in the cortisol infused animals and lower in AX fetuses compared with their corresponding control group, and increased with gestational age. UCP2 and GR mRNA abundance were significantly lower in AX fetuses compared with age-matched controls, and increased with gestational age and by cortisol infusion. Glucocorticoid action in fetal adipose tissue was augmented by AX and suppressed by cortisol infusion, the latter also preventing the gestational increase in 11betaHSD1 mRNA and decrease in 11betaHSD2 mRNA. When all treatment groups were combined, both fetal plasma cortisol and T3 concentrations were positively correlated with UCP2, GR and 11betaHSD2 mRNA abundance, but negatively correlated with 11betaHSD1 mRNA abundance. In conclusion, plasma cortisol and T3 are both required for the late gestation rise in UCP2 mRNA and differentially regulate glucocorticoid action in fetal adipose tissue in the sheep during late gestation. PMID:15961419

Gnanalingham, M G; Mostyn, A; Forhead, A J; Fowden, A L; Symonds, M E; Stephenson, T

2005-08-15

48

Increased uncoupling protein-2 mRNA abundance and glucocorticoid action in adipose tissue in the sheep fetus during late gestation is dependent on plasma cortisol and triiodothyronine  

PubMed Central

The endocrine regulation of uncoupling protein-2 (UCP2), an inner mitochondrial protein, in fetal adipose tissue remains unclear. The present study aimed to determine if fetal plasma cortisol and triiodothyronine (T3) influenced the mRNA abundance of UCP2, glucocorticoid receptor (GR) and 11?-hydroxysteroid dehydrogenase type 1 (11?HSD1) and 2 (11?HSD2) in fetal adipose tissue in the sheep during late gestation. Perirenalabdominal adipose tissue was sampled from ovine fetuses to which either cortisol (23 mg kg?1 day?1) or saline was infused for 5 days up to 127130 days gestation, or near term fetuses (i.e. 142145 days gestation) that were either adrenalectomised (AX) or remained intact. Fetal plasma cortisol and T3 concentrations were higher in the cortisol infused animals and lower in AX fetuses compared with their corresponding control group, and increased with gestational age. UCP2 and GR mRNA abundance were significantly lower in AX fetuses compared with age-matched controls, and increased with gestational age and by cortisol infusion. Glucocorticoid action in fetal adipose tissue was augmented by AX and suppressed by cortisol infusion, the latter also preventing the gestational increase in 11?HSD1 mRNA and decrease in 11?HSD2 mRNA. When all treatment groups were combined, both fetal plasma cortisol and T3 concentrations were positively correlated with UCP2, GR and 11?HSD2 mRNA abundance, but negatively correlated with 11?HSD1 mRNA abundance. In conclusion, plasma cortisol and T3 are both required for the late gestation rise in UCP2 mRNA and differentially regulate glucocorticoid action in fetal adipose tissue in the sheep during late gestation. PMID:15961419

Gnanalingham, MG; Mostyn, A; Forhead, AJ; Fowden, AL; Symonds, ME; Stephenson, T

2005-01-01

49

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

PubMed

Adipose tissue is functionally composed of brown adipose tissue and white adipose tissue. The unique thermogenic capacity of brown adipose tissue results from expression of uncoupling protein 1 in the mitochondrial inner membrane. On the basis of recent findings that adult humans have functionally active brown adipose tissue, it is now recognized as playing a much more important role in human metabolism than was previously thought. More importantly, brown-like adipocytes can be recruited in white adipose tissue upon environmental stimulation and pharmacologic treatment, and this change is associated with increased energy expenditure, contributing to a lean and healthy phenotype. Thus, the promotion of brown-like adipocyte development in white adipose tissue offers novel possibilities for the development of therapeutic strategies to combat obesity and related metabolic diseases. In this review, we summarize recent advances in understanding the molecular mechanisms involved in the recruitment of brown-like adipocyte in white adipose tissue. Copyright 2014 John Wiley & Sons, Ltd. PMID:25139773

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

2014-08-20

50

Profiling of chicken adipose tissue gene expression by genome array  

PubMed Central

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 13,23416,858 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:17594506

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

2007-01-01

51

Roles of human epicardial adipose tissue in coronary artery atherosclerosis.  

PubMed

This study examined the adipocytokine-vascular interactions and link between epicardial adipose tissue and coronary artery atherosclerosis. Thirty-four patients undergoing open heart surgery were chosen randomly, and divided into group I (non-coronary artery disease group) and group II (coronary artery disease group). Blood samples were taken through peripheral vein prior to surgery. Plasma levels of a panel of proteins (adiponectin, IL-10, TNF-?) were detected by using ELISA. Epicardial adipose tissue was taken near the proximal tract of the right coronary artery and subcutaneous adipose was taken from the leg before cardiopulmonary bypassing, adiponectin and CD68 + were detected by using RT-PCR and immunohistochemistry. Our results showed that plasma adiponectin level was significantly lower in the group II as compared with group I (P<0.05). There were no differences in plasma concentration (IL-10, TNF-?, tatal-chol, HDL-chol, LDL-chol) between group I and group II. The number of CD68+ cells in epicardial adipose tissue of group II was significantly higher than that in subcutaneous adipose tissue. Adiponectin mRNA expression was 6 fold higher in subcutaneous adipose tissue than in epicardial adipose tissue of group II (P<0.01). Furthermore, the level of adiponectin mRNA in the epicardial adipose tissue in group II was also significantly lower than in group I (P<0.05). We are led to conclude that inflammation that occurs locally in epicardial adipose tissue of CAD contributes to the pathogenesis of coronary artery disease. PMID:21063839

Chen, Xinzhong; Jiao, Zhouyang; Wang, Lei; Sun, Zongquan; Wei, Yutao; Wang, Xianguo; Xia, Dongsheng

2010-10-01

52

Macrophage recruitment in obese adipose tissue.  

PubMed

Obesity is characterized as a chronic state of low-grade inflammation with progressive immune cell infiltration into adipose tissues. Adipose tissue macrophages play critical roles in the establishment of the chronic inflammatory state and metabolic dysfunctions. The novel discovery that pro-inflammatory macrophages are recruited to obese adipose tissue prompted an increased interest in the interplay between immune cells and metabolism. Since this discovery, many works have been published investigating the factors that lead to macrophage recruitment, the phenotypic change of adipose tissue macrophages, and metabolic dysfunctions. Adipokines and chemokines are key mediators that play crucial roles in crosstalk between adipocytes and macrophages and in regulating the adipose tissue inflammation. In the present review, we discuss the obesity-mediated adipose tissue remodelling, and particularly, the role of adipokines/chemokines in macrophage recruitment to obese adipose tissue. This review provides new insights into the physiological role of these factors and identifies a potential therapeutic target for obesity and associated disorders. PMID:25586506

Bai, Y; Sun, Q

2015-02-01

53

Regulation of CD163 mRNA and soluble CD163 protein in human adipose tissue in vitro.  

PubMed

CD163-positive macrophages are highly expressed in the human adipose tissue (AT) particularly from obese individuals. However, little is known about the regulation of CD163 mRNA and the protein level of sCD163 in human AT. We aimed to examine the regulation of CD163 and sCD163 in AT. Human s.c. AT samples (n=5) were stimulated with dexamethasone (DEX; 200? nmol/l), lipopolysaccharide (LPS; 100 ?ng/ml), or DEX+LPS for various time periods up to 24? h. Gene expressions of CD163, ADAM17, IL10, and TNFA (TNF) were measured by RT-PCR. Protein levels of sCD163, IL10, and TNF? (TNF) were measured by ELISA. Furthermore, AT was separated into stromal and adipocyte fraction. We found that CD163 mRNA was strongly expressed in the stromal vascular fraction but hardly detectable in the isolated adipocytes. Incubating whole AT with DEX significantly up-regulated CD163 (P<0.001), whereas incubation with LPS had no effects on CD163 (P>0.05). By contrast, the protein level of sCD163 was not affected by DEX (P>0.05), but LPS significantly increased the level of sCD163 and TNF? (P<0.05). This might be due to the concomitant LPS stimulation of ADAM17, which is known to mediate shedding of the extracellular domains of sCD163 and TNF?. Finally, DEX significantly reduced the LPS-induced TNF? release to the incubation medium but had no effects on sCD163. We conclude that the expression of CD163 and the release of sCD163 are differentially regulated in human AT. Moreover, similar to studies on differentiated blood monocytes, TNF? and sCD163 are concomitantly released in human AT by LPS, which also up-regulate ADAM17. PMID:25074267

Fjeldborg, Karen; Mller, Holger J; Richelsen, Bjrn; Pedersen, Steen B

2014-10-01

54

Identification and Importance of Brown Adipose Tissue in Adult Humans  

PubMed Central

BACKGROUND Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. METHODS We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PETCT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery. RESULTS Substantial depots of brown adipose tissue were identified by PETCT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher 18F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P= 0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P = 0.007). CONCLUSIONS Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of 18F-FDG PETCT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism. PMID:19357406

Cypess, Aaron M.; Lehman, Sanaz; Williams, Gethin; Tal, Ilan; Rodman, Dean; Goldfine, Allison B.; Kuo, Frank C.; Palmer, Edwin L.; Tseng, Yu-Hua; Doria, Alessandro; Kolodny, Gerald M.; Kahn, C. Ronald

2010-01-01

55

Is the heat surrounding adipose tissue mitochondria warranted?  

PubMed Central

Purpose of review Mitochondrial uncoupling proteins uncouple oxidative phosphorylation. The physiological role ascribed to this process is thermoregulation. The metabolic consequence of mitochondrial respiration uncoupled from ATP production is increased substrate oxidation and metabolic rate. The recent discovery of uncoupling protein 1 (UCP1) positive mitochondria in human adipose tissue has rekindled interest in the role of UCP1 in energy balance and metabolic health. Recent findings Recently, there have been numerous reports of functional brown adipose tissue in humans. Further, data from cell and murine studies suggest that beige adipocytes can be induced within white adipose tissue. The presence of brown/beige adipocytes with mitochondria expressing UCP1 negatively correlates with adiposity. Further, activation of these adipocytes alters energy balance and substrate metabolism. However, in humans, brown fat content varies significantly. Further, although beige adipocytes can be induced in white adipose tissue of rodents, whether this is also true in humans remains unclear. Summary The presence of UCP1-positive mitochondria in human adipose tissue represents an exciting therapeutic target for treating obesity and its metabolic complications. Understanding the mechanisms governing brown fat activation will be crucial if the therapeutic potential of UCP1 is to be realized. PMID:25102333

Porter, Craig; Malagaris, Ioannis; Sidossis, Labros S.

2015-01-01

56

Protein kinase C? deficiency attenuates obesity syndrome of ob/ob mice by promoting white adipose tissue remodeling  

PubMed Central

To explore the role of leptin in PKC? action and to determine the protective potential of PKC? deficiency on profound obesity, double knockout (DBKO) mice lacking PKC? and ob genes were created, and key parameters of metabolism and body composition were studied. DBKO mice had similar caloric intake as ob/ob mice but showed significantly reduced body fat content, improved glucose metabolism, and elevated body temperature. DBKO mice were resistant to high-fat diet-induced obesity. Moreover, PKC? deficiency increased ?-adrenergic signaling by inducing expression of ?1- and ?3-adrenergic receptors (?-ARs) in white adipose tissue (WAT) of ob/ob mice. Accordingly, p38MAPK activation and expression of PGC-1? and UCP-1 were increased in WAT of DBKO mice. Consistent with results of in vivo studies, inhibition of PKC? in WAT explants from ob/ob mice also increased expression of above ?-ARs. In contrast, induction of PGC-1? and UCP-1 expression in brown adipose tissue of DBKO mice was not accompanied by changes in the expression of these ?-ARs. Collectively, these findings suggest that PKC? deficiency may prevent genetic obesity, in part, by remodeling the catabolic function of adipose tissues through ?-ARs dependent and independent mechanisms. PMID:22210924

Huang, Wei; Bansode, Rishipal R.; Bal, Naresh C.; Mehta, Madhu; Mehta, Kamal D.

2012-01-01

57

Endoplasmic reticulum stress in adipose tissue augments lipolysis  

PubMed Central

The endoplasmic reticulum (ER) is an organelle important for protein synthesis and folding, lipid synthesis and Ca2+ homoeostasis. Consequently, ER stress or dysfunction affects numerous cellular processes and has been implicated as a contributing factor in several pathophysiological conditions. Tunicamycin induces ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark of tunicamycin administration is the development of fatty livers within 2448 hrs accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce ER stress in adipose tissue that would lead to increased lipolysis and subsequently to fatty infiltration of the liver and hepatomegaly. Our results show that intraperitoneal administration of tunicamycin rapidly induced an ER stress response in adipose tissue that correlated with increased circulating free fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and lipid droplet size. Furthermore, we found that in addition to fatty infiltration of the liver as well as hepatomegaly, lipid accumulation was also present in the heart, skeletal muscle and kidney. To corroborate our findings to a clinical setting, we examined adipose tissue from burned patients where increases in lipolysis and the development of fatty livers have been well documented. We found that burned patients displayed significant ER stress within adipose tissue and that ER stress augments lipolysis in cultured human adipocytes. Our results indicate a possible role for ER stress induced lipolysis in adipose tissue as an underlying mechanism contributing to increases in circulating FFAs and fatty infiltration into other organs. PMID:25381905

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

2015-01-01

58

Endoplasmic reticulum stress in adipose tissue augments lipolysis.  

PubMed

The endoplasmic reticulum (ER) is an organelle important for protein synthesis and folding, lipid synthesis and Ca(2+) homoeostasis. Consequently, ER stress or dysfunction affects numerous cellular processes and has been implicated as a contributing factor in several pathophysiological conditions. Tunicamycin induces ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark of tunicamycin administration is the development of fatty livers within 24-48hrs accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce ER stress in adipose tissue that would lead to increased lipolysis and subsequently to fatty infiltration of the liver and hepatomegaly. Our results show that intraperitoneal administration of tunicamycin rapidly induced an ER stress response in adipose tissue that correlated with increased circulating free fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and lipid droplet size. Furthermore, we found that in addition to fatty infiltration of the liver as well as hepatomegaly, lipid accumulation was also present in the heart, skeletal muscle and kidney. To corroborate our findings to a clinical setting, we examined adipose tissue from burned patients where increases in lipolysis and the development of fatty livers have been well documented. We found that burned patients displayed significant ER stress within adipose tissue and that ER stress augments lipolysis in cultured human adipocytes. Our results indicate a possible role for ER stress induced lipolysis in adipose tissue as an underlying mechanism contributing to increases in circulating FFAs and fatty infiltration into other organs. PMID:25381905

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

2015-01-01

59

The adipose tissue in farm animals: a proteomic approach.  

PubMed

Adipose tissue is not only a tissue where energy is stored but is also involved in regulating several body functions such as appetite and energy expenditure via its endocrine activity. Moreover, it thereby modulates complex processes like reproduction, inflammation and immune response. The products secreted from adipose tissue comprise hormones and cytokines that are collectively termed as adipocytokines or "adipokines"; the discovery and characterization of new proteins secreted by adipose tissue is still ongoing and their number is thus increasing. Adipokines act in both endocrine manner as well as locally, as autocrine or paracrine effectors. Proteomics has emerged as a valuable technique to characterize both cellular and secreted proteomes from adipose tissues, including those of main cellular fractions, i.e. the adipocytes or the stromal vascular fraction containing mainly adipocyte precursors and immune cells. The scientific interest in adipose tissue is largely based on the worldwide increasing prevalence of obesity in humans; in contrast, obesity is hardly an issue for farmed animals that are fed according to their well-defined needs. Adipose tissue is nevertheless of major importance in these animals, as the adipose percentage of the bodyweight is a major determinant for the efficiency of transferring nutrients from feed into food products and thus for the economic value from meat producing animals. In dairy animals, the importance of adipose tissue is based on its function as stromal structure for the mammary gland and on its role in participating in and regulating of energy metabolism and other functions. Moreover, as pig has recently become an important model organism to study human diseases, the knowledge of adipose tissue metabolism in pig is relevant for the study of obesity and metabolic disorders. We herein provide a general overview of adipose tissue functions and its importance in farm animals. This review will summarize recent achievements in farm animal adipose tissue proteomics, mainly in cattle and pigs, but also in poultry, i.e. chicken and in farmed fish. Proteomics advancement in adipocyte cell lines, have also been included. PMID:24555890

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

2014-03-01

60

Adipose tissue plasticity from WAT to BAT and in between.  

PubMed

Adipose tissue plays an essential role in regulating energy balance through its metabolic, cellular and endocrine functions. Adipose tissue has been historically classified into anabolic white adipose tissue and catabolic brown adipose tissue. An explosion of new data, however, points to the remarkable heterogeneity among the cells types that can become adipocytes, as well as the inherent metabolic plasticity of mature cells. These data indicate that targeting cellular and metabolic plasticity of adipose tissue might provide new avenues for treatment of obesity-related diseases. This review will discuss the developmental origins of adipose tissue, the cellular complexity of adipose tissues, and the identification of progenitors that contribute to adipogenesis throughout development. We will touch upon the pathological remodeling of adipose tissue and discuss how our understanding of adipose tissue remodeling can uncover new therapeutic targets. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. PMID:23688783

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

2014-03-01

61

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

PubMed

An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPAR?-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases. PMID:25205743

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

2014-12-01

62

Differential regulation of expression of genes encoding uncoupling proteins 2 and 3 in brown adipose tissue during lactation in mice.  

PubMed Central

Thermogenic activity in brown adipose tissue (BAT) decreases during lactation; the down-regulation of the gene encoding uncoupling protein 1 (UCP1) is involved in this process. Our studies show that UCP2 mRNA expression does not change during the breeding cycle in mice. In contrast, UCP3 mRNA is down-regulated in lactation but it recovers after weaning, in parallel with UCP1 mRNA. This leads to a decrease in the content of UCP3 in BAT mitochondria during lactation. Lowering the energy-sparing necessities of lactating dams by decreasing litter size or feeding with a high-fat diet prevented the down-regulation of UCP1 mRNA and UCP3 mRNA. In most cases this resulted in a less marked decrease in UCP1 and UCP3 protein in BAT mitochondria owing to lactation. Fasting for 24 h caused a different response in UCP1 and UCP3 mRNA expression: it decreased UCP1 mRNA levels but had no effect on UCP3 mRNA abundance in virgin mice; it even increased UCP3 mRNA expression in lactating dams. These changes did not lead to modifications in UCP1 or UCP3 protein abundance. Whereas acute treatment with peroxisome-proliferator-activated receptor (PPAR)alpha and PPARgamma agonists increased UCP1 mRNA levels only in lactating dams, UCP3 mRNA expression was induced by both kinds of PPAR activator in lactating dams and by PPARalpha agonists in virgin mice. It is concluded that modifications of UCP2 mRNA levels are not part of the physiological adaptations taking place in BAT during lactation. In contrast, the down-regulation of UCP3 mRNA expression and mitochondrial UCP3 content is consistent with a role for the gene encoding UCP3 in the decrease in metabolic fuel oxidation and thermogenesis in BAT during lactation. PMID:11256954

Pedraza, N; Solanes, G; Iglesias, R; Vzquez, M; Giralt, M; Villarroya, F

2001-01-01

63

White Adipose Tissue Resilience to Insulin Deprivation and Replacement  

PubMed Central

Introduction Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Methods Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. Results The initial body weight of the rats was 4655.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Conclusion Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues. PMID:25170835

Hadji, Lilas; Berger, Emmanuelle; Soula, Hdi; Vidal, Hubert; Glon, Alain

2014-01-01

64

Patterns of gene expression in pig adipose tissue: insulin-like growth factor system proteins, neuropeptide Y (NPY), NPY receptors, neurotrophic factors and other secreted factors  

Technology Transfer Automated Retrieval System (TEKTRAN)

Total RNA was collected at slaughter from outer subcutaneous adipose tissue (OSQ) and middle subcutaneous adipose tissue (MSQ) samples from gilts at 90, 150, and 210 d ( n =5 / age). Dye labeled cDNA probes were hybridized to custom microarrays (70 mer oligonucleotides) representing over 600 pig gen...

65

Adipose tissue insulin sensitivity and macrophage recruitment  

PubMed Central

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

McCurdy, Carrie E; Klemm, Dwight J

2013-01-01

66

Stem cells and adipose tissue engineering  

Microsoft Academic Search

A large proportion of the plastic and reconstructive surgical procedures performed each year are to repair soft tissue defects that result from traumatic injury, tumor resection, and congenital defects. These defects typically result from the loss of a large volume of adipose tissue. To date, no ideal filler material which is successful in all cases has been developed. Additionally, the

Cheryl T. Gomillion; Karen J. L. Burg

2006-01-01

67

Adipose Triglyceride Lipase and Hormone-Sensitive Lipase Protein Expression Is Decreased in the Obese  

E-print Network

Adipose Triglyceride Lipase and Hormone-Sensitive Lipase Protein Expression Is Decreased discovered adipose triglyceride lipase (ATGL). The aim of the present study was to examine whether ATGL non- HSL lipase adipose triglyceride lipase (ATGL), being pre- dominantly expressed in adipose tissue

Paris-Sud XI, Université de

68

Enhanced pan-peroxisome proliferator-activated receptor gene and protein expression in adipose tissue of diet-induced obese mice treated with telmisartan.  

PubMed

Telmisartan has previously been used to target obesity, showing peroxisome proliferator-activated receptor (PPAR) ?/?-related effects in white adipose tissue (WAT). We sought to evaluate whether telmisartan enhances gene and protein expression of all PPAR isoforms in WAT and brown adipose tissue (BAT), as well as their downstream effects upon insulin resistance, adipokine profile and adaptive thermogenesis. Male C57BL/6 mice were fed standard chow (SC; 10% lipids) or high-fat diet (HF; 50% lipids) for 10weeks. Animals were then randomly allocated into the following four groups: SC, SC-T, HF and HF-T. Telmisartan [10mg(kg diet)(-1)] was administered for 4 weeks in the diet. Animals in the HF group were overweight and exhibited hypertension, insulin resistance, decreased energy expenditure, a pro-inflammatory adipokine profile and abnormal fat pad mass distribution. Animals in the HF group showed decreased expression of PPAR?, ?/? and ? in WAT and BAT, resulting in impaired glucose uptake and insufficient thermogenesis. Due to the improvement in the adipokine profile and enhanced insulin sensitivity with adequate insulin-stimulated glucose uptake after treatment with telmisartan, the activation of all PPAR isoforms in WAT was beneficial. In BAT, telmisartan induced sustained sympathetic activation, because the ?3-adrenergic receptor was induced by PPAR?/?, while uncoupling protein1 was induced by PPAR? to promote thermogenesis. Telmisartan exerted anti-obesity effects through higher pan-PPAR gene and protein expression. Upon PPAR?, ?/? and ? (pan-PPAR) agonism in adipose tissue of obese mice, telmisartan ameliorates inflammation and insulin resistance, as well as inducing non-shivering thermogenesis. Our results point to new therapeutic targets for the control of obesity and comorbidities through pan-PPAR-related effects. PMID:25326526

Penna-de-Carvalho, Aline; Graus-Nunes, Francielle; Rabelo-Andrade, Jlia; Mandarim-de-Lacerda, Carlos Alberto; Souza-Mello, Vanessa

2014-12-01

69

Lipophilic Micronutrients and Adipose Tissue Biology  

PubMed Central

Lipophilic micronutrients (LM) constitute a large family of molecules including several vitamins (A, D, E, K) and carotenoids. Their ability to regulate gene expression is becoming increasingly clear and constitutes an important part of nutrigenomics. Interestingly, adipose tissue is not only a main storage site for these molecules within the body, but it is also subjected to the regulatory effects of LM. Indeed, several gene regulations have been described in adipose tissue that could strongly impact its biology with respect to the modulation of adipogenesis, inflammatory status, or energy homeostasis and metabolism, among others. The repercussions in terms of health effects of such regulations in the context of obesity and associated pathologies represent an exciting and emerging field of research. The present review will focus on the regulatory effects of vitamin A, D, E and K as well as carotenoids on adipose tissue biology and physiology, notably in the context of obesity and associated disorders. PMID:23201837

Landrier, Jean-Franois; Marcotorchino, Julie; Tourniaire, Franck

2012-01-01

70

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

PubMed Central

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

2013-01-01

71

Altered White Adipose Tissue Protein Profile in C57BL/6J Mice Displaying Delipidative, Inflammatory, and Browning Characteristics after Bitter Melon Seed Oil Treatment  

PubMed Central

Objective We have previously shown that bitter melon seed oil (BMSO), which is rich in cis-9, trans-11, trans-13 conjugated linolenic acid, is more potent than soybean oil in attenuating body fat deposition in high-fat diet-induced obese C57BL/6J mice. The aim of this study was to obtain a comprehensive insight into how white adipose tissue (WAT) is affected by BMSO administration and to explore the underlying mechanisms of the anti-adiposity effect of BMSO. Methods and Results A proteomic approach was used to identify proteins differentially expressed in the WAT of mice fed diets with or without BMSO for 11 wks. The WAT was also analyzed histologically for morphological changes. Two-dimensional gel electrophoresis (pH 47) revealed 32 spots showing a statistically significant difference (P<0.05) in intensity in BMSO-treated mice and 30 of these were shown to code for 23 proteins (15 increased and 8 decreased expression; >2-fold change). Combined with histological evidence of macrophage infiltration and brown adipocyte recruitment, the proteomic and immunoblotting data showed that the WAT in mice subjected to long-term high dose BMSO administration was characterized by reduced caveolae formation, increased ROS insult, tissue remodeling/repair, mitochondria uncoupling, and stabilization of the actin cytoskeleton, this last change being putatively related to an increased inflammatory response. Conclusion The anti-adiposity effect of BMSO is associated with WAT delipidation, inflammation, and browning. Some novel proteins participating in these processes were identified. In addition, the BMSO-mediated WAT browning may account for the increased inflammation without causing adverse metabolic effects. PMID:24039822

Hsieh, Cheng-Hsien; Chen, Gou-Chun; Chen, Pei-Hsuan; Wu, Ting-Feng; Chao, Pei-Min

2013-01-01

72

Understanding androgen action in adipose tissue.  

PubMed

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

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

2014-09-01

73

Fructose consumption enhances glucocorticoid action in rat visceral adipose tissue.  

PubMed

The rise in consumption of refined sugars high in fructose appears to be an important factor for the development of obesity and metabolic syndrome. Fructose has been shown to be involved in genesis and progression of the syndrome through deregulation of metabolic pathways in adipose tissue. There is evidence that enhanced glucocorticoid regeneration within adipose tissue, mediated by the enzyme 11beta-hydroxysteroid dehydrogenase Type 1 (11?HSD1), may contribute to adiposity and metabolic disease. 11?HSD1 reductase activity is dependent on NADPH, a cofactor generated by hexose-6-phosphate dehydrogenase (H6PDH). We hypothesized that harmful effects of long-term high fructose consumption could be mediated by alterations in prereceptor glucocorticoid metabolism and glucocorticoid signaling in the adipose tissue of male Wistar rats. We analyzed the effects of 9-week drinking of 10% fructose solution on dyslipidemia, adipose tissue histology and both plasma and tissue corticosterone level. Prereceptor metabolism of glucocorticoids was characterized by determining 11?HSD1 and H6PDH mRNA and protein levels. Glucocorticoid signaling was examined at the level of glucocorticoid receptor (GR) expression and compartmental redistribution, as well as at the level of expression of its target genes (GR, phosphoenolpyruvate carboxyl kinase and hormone-sensitive lipase). Fructose diet led to increased 11?HSD1 and H6PDH expression and elevated corticosterone level within the adipose tissue, which was paralleled with enhanced GR nuclear accumulation. Although the animals did not develop obesity, nonesterified fatty acid and plasma triglyceride levels were elevated, indicating that fructose, through enhanced prereceptor metabolism of glucocorticoids, could set the environment for possible later onset of obesity. PMID:23253598

Bursa?, Biljana N; Djordjevic, Ana D; Vasiljevi?, Ana D; Milutinovi?, Danijela D Vojnovi?; Veli?kovi?, Nataa A; Nestorovi?, Nataa M; Mati?, Gordana M

2013-06-01

74

Vitamin D and adipose tissuemore than storage  

PubMed Central

The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OH)D), no evidence was obtained for a BMI lowering effect by higher 25(OH)D. Some of the physiological functions of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol or calcitriol) via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine, and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g., in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH)2D3, vitamin D binding proteins (VDBPs) and nuclear vitamin D receptor (VDR) after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH)2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH)2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR?/?) and CYP27B1 knock out (CYP27B1 ?/?) mouse models: Both VDR?/? and CYP27B1?/? models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH)2D3. Experimental studies demonstrate that 1,25(OH)2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases. PMID:25009502

Mutt, Shivaprakash J.; Hyppnen, Elina; Saarnio, Juha; Jrvelin, Marjo-Riitta; Herzig, Karl-Heinz

2014-01-01

75

Vitamin D and adipose tissue-more than storage.  

PubMed

The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OH)D), no evidence was obtained for a BMI lowering effect by higher 25(OH)D. Some of the physiological functions of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol or calcitriol) via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine, and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g., in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH)2D3, vitamin D binding proteins (VDBPs) and nuclear vitamin D receptor (VDR) after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH)2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH)2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR(-/-)) and CYP27B1 knock out (CYP27B1 (-/-)) mouse models: Both VDR(-/-) and CYP27B1(-/-) models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH)2D3. Experimental studies demonstrate that 1,25(OH)2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases. PMID:25009502

Mutt, Shivaprakash J; Hyppnen, Elina; Saarnio, Juha; Jrvelin, Marjo-Riitta; Herzig, Karl-Heinz

2014-01-01

76

Automatic Segmentation of Adipose Tissue from Thigh Magnetic Resonance Images  

E-print Network

, such as connective, neu- ral, adipose, skeletal and muscle tissue. They pose various challenges to standard imageAutomatic Segmentation of Adipose Tissue from Thigh Magnetic Resonance Images Senthil Purushwalkam1, Manchester Metropolitan University, UK Abstract. Automatic segmentation of adipose tissue in thigh magnetic

Li, Baihua

77

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

PubMed Central

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

2014-01-01

78

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

PubMed Central

Obesity is a global epidemic that contributes to the increasing medical burdens related to type 2 diabetes, cardiovascular disease and cancer. A better understanding of the mechanisms regulating adipose tissue expansion could lead to therapeutics that eliminate or reduce obesity-associated morbidity and mortality. The extracellular matrix (ECM) has been shown to regulate the development and function of numerous tissues and organs. However, there is little understanding of its function in adipose tissue. In this manuscript we describe the role of laminin ?4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin ?4 gene (Lama4?/?) and compared to wild-type (Lama4+/+) control animals. Lama4?/? mice exhibited reduced weight gain in response to both age and high fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin ?4 influences adipose tissue structure and function in a depot-specific manner. Alterations in laminin composition offers insight into the roll the ECM potentially plays in modulating cellular behavior in adipose tissue expansion. PMID:25310607

Movrare-Skrtic, Sofia; Kortesmaa, Jarkko; Soininen, Raija; Bergstrm, Gran; Ohlsson, Claes; Chong, Li Yen; Rozell, Bjrn; Emont, Margo; Cohen, Ronald N.; Brey, Eric M.; Tryggvason, Karl

2014-01-01

79

Phospholipase C-Related Catalytically Inactive Protein (PRIP) Regulates Lipolysis in Adipose Tissue by Modulating the Phosphorylation of Hormone-Sensitive Lipase  

PubMed Central

Phosphorylation of hormone-sensitive lipase (HSL) and perilipin by protein kinase A (PKA) promotes the hydrolysis of lipids in adipocytes. Although activation of lipolysis by PKA has been well studied, inactivation via protein phosphatases is poorly understood. Here, we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a binding partner for protein phosphatase 1 and protein phosphatase 2A (PP2A), is involved in lipolysis by regulating phosphatase activity. PRIP knockout (PRIP-KO) mice displayed reduced body-fat mass as compared with wild-type mice fed with standard chow ad libitum. Most other organs appeared normal, suggesting that mutant mice had aberrant fat metabolism in adipocytes. HSL in PRIP-KO adipose tissue was highly phosphorylated compared to that in wild-type mice. Starvation of wild-type mice or stimulation of adipose tissue explants with the catabolic hormone, adrenaline, translocated both PRIP and PP2A from the cytosol to lipid droplets, but the translocation of PP2A was significantly reduced in PRIP-KO adipocytes. Consistently, the phosphatase activity associated with lipid droplet fraction in PRIP-KO adipocytes was significantly reduced and was independent of adrenaline stimulation. Lipolysis activity, as assessed by measurement of non-esterified fatty acids and glycerol, was higher in PRIP-KO adipocytes. When wild-type adipocytes were treated with a phosphatase inhibitor, they showed a high lipolysis activity at the similar level to PRIP-KO adipocytes. Collectively, these results suggest that PRIP promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of HSL and perilipin A, thus reducing PKA-mediated lipolysis. PMID:24945349

Okumura, Toshiya; Harada, Kae; Oue, Kana; Zhang, Jun; Asano, Satoshi; Hayashiuchi, Masaki; Mizokami, Akiko; Tanaka, Hiroto; Irifune, Masahiro; Kamata, Nobuyuki; Hirata, Masato; Kanematsu, Takashi

2014-01-01

80

Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase  

Microsoft Academic Search

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

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

2004-01-01

81

Rhein protects against obesity and related metabolic disorders through liver X receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue.  

PubMed

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

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

2012-01-01

82

Salsalate activates brown adipose tissue in mice.  

PubMed

Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the present 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 (TG) 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. Treatment of differentiated T37i brown adipocytes with salsalate increased uncoupled respiration in cells. Moreover, salsalate upregulated Ucp1 expression and enhanced glycerol release, a dual effect that was abolished by inhibition of protein kinase A (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

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; Lombs, Marc; van den Hoek, Anita M; de Winther, Menno P J; Lutgens, Esther; Guigas, Bruno; Rensen, Patrick C N; Boon, Maritte R

2014-12-01

83

C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue?  

PubMed

C-reactive protein, a hepatic acute phase protein largely regulated by circulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secretes interleukin-6 in vivo. In this study we have sought associations of levels of C-reactive protein and interleukin-6 with measures of obesity and of chronic infection as their putative determinants. We have also related levels of C-reactive protein and interleukin-6 to markers of the insulin resistance syndrome and of endothelial dysfunction. We performed a cross-sectional study in 107 nondiabetic subjects: (1) Levels of C-reactive protein, and concentrations of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, were related to all measures of obesity, but titers of antibodies to Helicobacter pylori were only weakly and those of Chlamydia pneumoniae and cytomegalovirus were not significantly correlated with levels of these molecules. Levels of C-reactive protein were significantly related to those of interleukin-6 (r=0.37, P<0.0005) and tumor necrosis factor-alpha (r=0.46, P<0.0001). (2) Concentrations of C-reactive protein were related to insulin resistance as calculated from the homoeostasis model assessment model, blood pressure, HDL, and triglyceride, and to markers of endothelial dysfunction (plasma levels of von Willebrand factor, tissue plasminogen activator, and cellular fibronectin). A mean standard deviation score of levels of acute phase markers correlated closely with a similar score of insulin resistance syndrome variables (r=0.59, P<0.00005), this relationship being weakened only marginally by removing measures of obesity from the insulin resistance score (r=0.53, P<0.00005). These data suggest that adipose tissue is an important determinant of a low level, chronic inflammatory state as reflected by levels of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein, and that infection with H pylori, C pneumoniae, and cytomegalovirus is not. Moreover, our data support the concept that such a low-level, chronic inflammatory state may induce insulin resistance and endothelial dysfunction and thus link the latter phenomena with obesity and cardiovascular disease. PMID:10195925

Yudkin, J S; Stehouwer, C D; Emeis, J J; Coppack, S W

1999-04-01

84

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

PubMed Central

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

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

2013-01-01

85

Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice  

Microsoft Academic Search

Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase that has been implicated in the regulation of insulin action, as well as in other signal transduction pathways. To investigate the role of PTP-1B in vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient mice have remarkably low adiposity and are protected from diet-induced obesity. Decreased adiposity is due

LORI D. KLAMAN; OLIVIER BOSS; ODILE D. PERONI; JASON K. KIM; JENNIFER L. MARTINO; JANICE M. ZABOLOTNY; NADEEM MOGHAL; MARGARET LUBKIN; YOUNG-BUM KIM; ARLENE H. SHARPE; ALAIN STRICKER-KRONGRAD; GERALD I. SHULMAN; BENJAMIN G. NEEL; BARBARA B. KAHN

2000-01-01

86

Peptides from adipose tissue in mental disorders.  

PubMed

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

W?drychowicz, Andrzej; Zaj?c, Andrzej; Pilecki, Maciej; Ko?cielniak, Barbara; Tomasik, Przemys?aw J

2014-12-22

87

Peptides from adipose tissue in mental disorders  

PubMed Central

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.

W?drychowicz, Andrzej; Zaj?c, Andrzej; Pilecki, Maciej; Ko?cielniak, Barbara; Tomasik, Przemys?aw J

2014-01-01

88

Adipose tissue browning and metabolic health.  

PubMed

Accumulation of excess white adipose tissue (WAT) has deleterious consequences for metabolic health. The activation of brown adipose tissue (BAT), the primary organ for heat production, confers beneficial effects on adiposity, insulin resistance and hyperlipidaemia, at least in mice. As the amount of metabolically active BAT seems to be particularly low in patients with obesity or diabetes mellitus who require immediate therapy, new avenues are needed to increase the capacity for adaptive thermogenesis. In this light, we review the findings that BAT in human adults might consist of not only classic brown adipocytes but also inducible brown adipocytes (also called beige, brown-in-white, or brite adipocytes), which are phenotypically distinct from both white and brown adipocytes. Stimulating the development of beige adipocytes in WAT (so called 'browning') might reduce adverse effects of WAT and could help to improve metabolic health. This article focuses on the development and regulatory control of beige adipocytes at the transcriptional and hormonal levels. Emerging insights into the metabolic role of beige adipocytes are also discussed, along with the developments that can be expected from these promising targets for therapy of metabolic disease in the future. PMID:24146030

Bartelt, Alexander; Heeren, Joerg

2014-01-01

89

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

PubMed

This study was conducted to determine the mRNA and protein expression levels of peroxisome proliferator-activated receptors (PPARs) in visceral adipose tissue, as well as serum adipokine levels, in Sprague Dawley rats. The rats were fed either a normal (control rats) or excessive (experimental rats) intake of food for 8 or 16 weeks, then sacrificed, at which time visceral and subcutaneous adipose tissues, as well as blood samples, were collected. The mRNA and protein expression levels of PPARs in the visceral adipose tissues were determined using reverse transcription-polymerase chain reaction and Western blotting, respectively. In addition, the levels of adipokines in the serum samples were determined using commercial ELISA kits. The results revealed that at 8 weeks, the mass of subcutaneous adipose tissue was higher than that of the visceral adipose tissue in the experimental rats, but the reverse occurred at 16 weeks. Furthermore, at 16 weeks the experimental rats exhibited an upregulation of PPAR? mRNA and protein expression levels in the visceral adipose tissues, and significant increases in the serum levels of CCL2 and interleukin (IL)-6 were observed, compared with those measured at 8 weeks. In conclusion, this study demonstrated that the PPAR? expression level was likely correlated with serum levels of CCL2 and IL-6, molecules that may facilitate visceral adipose tissue accumulation. In addition, the levels of the two adipokines in the serum may be useful as surrogate biomarkers for the expression levels of PPAR? in accumulated visceral adipose tissues. PMID:25324014

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

2015-01-01

90

Adipose tissue-deprived stem cells acquire cementoblast features treated with dental follicle cell conditioned medium containing dentin non-collagenous proteins in vitro  

SciTech Connect

Highlights: {yields} In this study we examine the effects of dental follicle cell conditioned medium (DFCCM) containing dentin non-collagenous proteins (dNCPs) on differentiation of ADSCs. {yields} We examined that ADSCs treated with dNCPs/DFCCM underwent morphological changes and significantly lost their proliferative capacity. {yields} dNCPs/DFCCM enhanced the mineralization behaviour and mineralization-related marker expression of ADSCs. {yields} ADSCs acquired cementoblast features in vitro with dNCPs/DFCCM treatment. -- Abstract: Adipose tissue-derived stem cells (ADSCs), which are easily harvested and show excellent pluripotency potential, have generated considerable interest in regenerative medicine. In this study, the differentiation of ADSCs was assessed after treatment with dental follicle cell conditioned medium (DFCCM) containing dentin non-collagenous proteins (dNCPs). ADSCs exhibited a fibroblast-like morphology and high proliferative capacity. However, after treatment with dNCPs/DFCCM, ADSCs changed from a fibroblast-like to cementoblast-like morphology and significantly lost their proliferative capacity. Alkaline phosphatase activity and in vitro mineralization behaviour of ADSCs were significantly enhanced. Mineralization-related markers including cementum attachment protein, bone sialoprotein, osteocalcin, osteopontin and osteonectin were detected at mRNA or protein levels, whereas dentin sialophosphoprotein and dentin sialoprotein were not detected, implying a cementoblast-like phenotype. These results demonstrate that ADSCs acquired cementoblast features in vitro with dNCPs/DFCCM treatment and could be a potential source of cementogenic cells for periodontal regeneration.

Wen, Xiujie; Nie, Xin; Zhang, Li [Department of Stomatology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, 10 Daping Changjiang Branch Road, Yuzhong District, Chongqing 400042 (China)] [Department of Stomatology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, 10 Daping Changjiang Branch Road, Yuzhong District, Chongqing 400042 (China); Liu, Luchuan, E-mail: liuluchuan1957@126.com [Department of Stomatology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, 10 Daping Changjiang Branch Road, Yuzhong District, Chongqing 400042 (China)] [Department of Stomatology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, 10 Daping Changjiang Branch Road, Yuzhong District, Chongqing 400042 (China); Deng, Manjing, E-mail: iradeng@163.com [Department of Stomatology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, 10 Daping Changjiang Branch Road, Yuzhong District, Chongqing 400042 (China)] [Department of Stomatology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, 10 Daping Changjiang Branch Road, Yuzhong District, Chongqing 400042 (China)

2011-06-10

91

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

PubMed

New information concerning the effects of prolactin (PRL) on metabolic processes warrants reevaluation of its overall metabolic actions. PRL affects metabolic homeostasis by regulating key enzymes and transporters associated with glucose and lipid metabolism in several target organs. In the lactating mammary gland, PRL increases the production of milk proteins, lactose, and lipids. In adipose tissue, PRL generally suppresses lipid storage and adipokine release and affect adipogenesis. A specific case is made for PRL in the human breast and adipose tissues, where it acts as a circulating hormone and an autocrine/paracrine factor. Although its overall effects on body composition are both modest and species-specific, PRL may be involved in the manifestation of insulin resistance. PMID:25472532

Ben-Jonathan, Nira; Hugo, Eric

2015-01-01

92

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

PubMed

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

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

2005-09-01

93

Sleep deprivation affects inflammatory marker expression in adipose tissue  

PubMed Central

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)-? 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-? 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-? protein concentrations in MEAT and increased levels of corticosterone in serum. PMID:21034496

2010-01-01

94

Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues  

Microsoft Academic Search

Mitochondrial uncoupling protein 1 (UCP1) is usually expressed only in brown adipose tissue (BAT) and a key molecule for metabolic thermogenesis to avoid an excess of fat accumulation. However, there is little BAT in adult humans. Therefore, UCP1 expression in tissues other than BAT is expected to reduce abdominal fat. Here, we show reduction of abdominal white adipose tissue (WAT)

Hayato Maeda; Masashi Hosokawa; Tokutake Sashima; Katsura Funayama; Kazuo Miyashita

2005-01-01

95

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

SciTech Connect

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

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

2011-03-04

96

TUMOR NECROSIS FACTOR ALPHA AND GLUCOCORTICOID SYNERGISTICALLY INCREASE LEPTIN PRODUCTION IN HUMAN ADIPOSE TISSUE: ROLE FOR P38 MITOGEN-ACTIVATED PROTEIN KINASE  

Technology Transfer Automated Retrieval System (TEKTRAN)

TNF increases plasma leptin in humans in vivo, but previous studies showed it decreases leptin in vitro. The objective of this study was to determine the effect of TNF on leptin release from human adipose tissue (AT) from healthy subjects undergoing elective surgery or needle aspirations of AT at a ...

97

Brown adipose tissue: development, metabolism and beyond  

PubMed Central

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

Schulz, Tim J.; Tseng, Yu-Hua

2013-01-01

98

Effect of some medicinal plant preparations of adipose tissue metabolism.  

PubMed

Powder in fine suspension, water and alcoholic extract preparations of Cyperus Rotundus (Mustak), Iris versicolor (Haimavati) and Holoptelai integrifolia (Chirubilva) were used in adipose cell suspension and also administered orally to evaluate the effect of these plant preparations on adipose tissue metabolism in rats. The result, showed that the preparations from these medicinal plants exhibited lipolytic action to mobilize fat from adipose tissues in rats and consequently helped in the reduction of obesity. PMID:22557642

Bambhole, V D

1988-10-01

99

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

PubMed

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

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

2014-12-01

100

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...

101

Adipose tissue as an endocrine and paracrine organ  

Microsoft Academic Search

The discovery of leptin has imparted great impetus to adipose tissue research by demonstrating a more active role for the adipocyte in energy regulation. Besides leptin, however, the adipose tissue also secretes a large number other signals. Cytokine signals, TNF? and IL-6, and components of the alternative pathway of complement influence peripheral fuel storage, mobilization and combustion, as well as

V Mohamed-Ali; JH Pinkney; SW Coppack

1998-01-01

102

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 ...

103

FABP4 Dynamics in Obesity: Discrepancies in Adipose Tissue and Liver Expression Regarding Circulating Plasma Levels  

PubMed Central

Background FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. Objective In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. Methods The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. Results In obesity FABP4 expression was down-regulated (at both mRNA and protein levels), with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. Conclusion The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity. PMID:23139800

Ceperuelo-Mallafr, Victoria; Garrido-Sanchez, Lourdes; Miranda, Merce; Clemente-Postigo, Mercedes; Prez-Prez, Rafael; Peral, Belen; Cardona, Fernando; Fernndez-Real, Jose Manuel; Tinahones, Francisco J.; Vendrell, Joan

2012-01-01

104

The fatty acid esterification pathway in bovine liver and adipose tissue  

E-print Network

ADIPOSE TISSUE INCUBATIONS Souse of variation P &. 05 Glucose Breed*Glucose . 3856 . 7873 Total Calculated for nmol palmitate incorporated/1 cells. n=6 MODEL 2. USED TO DETERMINE DIFFERENCES BE~ BREEDS AND GLUCOSE FOR THE DATA IN MODEL I.../mg protein/30 min. n=7 31 RESULTS I ' . Angus steers had a larger subcutaneous adipocyte mean diameter and hence a larger mean cell volume than the Brahman steers (Table I). However, subcutaneous adipose tissue from Brahman steers tended to have a...

Wilson, John

1988-01-01

105

Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity  

Microsoft Academic Search

Obesity is related to the risk for developing non-insulin-dependent diabetes mellitus (NIDDM), hypertension, and cardiovascular disease. Visceral adipose tissue (VAT) has been proposed to mediate these relationships. Abdominal subcutaneous adipose tissue (SAT) is divided into 2 layers by a fascia, the fascia superficialis. Little is known about the radiologic anatomy or metabolic correlates of these depots. The objective of this

Steven R. Smith; Jennifer C. Lovejoy; Frank Greenway; Donna Ryan; Lilian deJonge; Jacques de la Bretonne; Julia Volafova; George A. Bray

2001-01-01

106

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

PubMed

Abstract 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

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

2014-12-01

107

Adipose-derived stem cells: Implications in tissue regeneration  

PubMed Central

Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differentiate into multiple cell lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant adipose tissue by a minimally invasive procedure, which results in a high number of cells. Therefore, ASCs are promising for regenerating tissues and organs damaged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration. PMID:25126381

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

2014-01-01

108

Perivascular adipose tissue, vascular reactivity and hypertension.  

PubMed

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-?), 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-?. It has been shown that exogenously administered TNF-? 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 to an increased amount of these proinflammatory and procontractile factors. More studies are definitely required to confirm this. 2014 S. Karger AG, Basel. PMID:24503717

Oriowo, Mabayoje A

2015-01-01

109

Epicardial Adipose Tissue Reflects the Presence of Coronary Artery Disease: Comparison with Abdominal Visceral Adipose Tissue  

PubMed Central

Accumulation of visceral adipose tissue is associated with a risk of coronary artery disease (CAD). The aim of this study was to examine whether different types of adipose tissue depot may play differential roles in the progression of CAD. Consecutive 174 patients who underwent both computed tomography (CT) and echocardiography were analyzed. Cardiac and abdominal CT scans were performed to measure epicardial and abdominal visceral adipose tissue (EAT and abdominal VAT, resp.). Out of 174 patients, 109 and 113 patients, respectively, presented coronary calcification (CC) and coronary atheromatous plaque (CP). The EAT and abdominal VAT areas were larger in patients with CP compared to those without it. Interestingly, the EAT area was larger in patients with CC compared to those without CC, whereas no difference was observed in the abdominal VAT area between patients with CC and those without. Multivariable logistic regression analysis revealed that the presence of echocardiographic EAT was an independent predictor of CP and CC, but the abdominal VAT area was not. These results suggest that EAT and abdominal VAT may play differential pathological roles in CAD. Given the importance of CC and CP, we should consider the precise assessment of CAD when echocardiographic EAT is detected.

Oikawa, Masayoshi; Owada, Takashi; Yamauchi, Hiroyuki; Yamaki, Takayoshi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

2015-01-01

110

Adipocyte differentiation of multipotent cells established from human adipose tissue  

Microsoft Academic Search

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

Anne-Marie Rodriguez; Christian Elabd; Frdric Delteil; Julien Astier; Ccile Vernochet; Perla Saint-Marc; Jolle Guesnet; Anne Guezennec; Ez-Zoubir Amri; Christian Dani; Grard Ailhaud

2004-01-01

111

GADD45? regulates the thermogenic capacity of brown adipose tissue.  

PubMed

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

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

2014-08-12

112

Timed-daily ingestion of whey protein and exercise training reduces visceral adipose tissue mass and improves insulin resistance: the PRISE study.  

PubMed

The present study examined the effects of timed ingestion of supplemental protein (20-g servings of whey protein, 3/day), added to the habitual diet of free-living overweight/obese adults and subsequently randomized to either whey protein only (P; n = 24), whey protein and resistance exercise (P + RT; n = 27), or a whey protein and multimode exercise training program [protein and resistance exercise, intervals, stretching/yoga/Pilates, endurance exercise (PRISE); n = 28]. Total and regional body composition and visceral adipose tissue (VAT) mass (dual-energy X-ray absorptiometry), insulin sensitivity [homeostasis model assessment-estimated insulin resistance (HOMA-IR)], plasma lipids and adipokines, and feelings of hunger and satiety (visual analog scales) were measured before and after the 16-wk intervention. All groups lost body weight, fat mass (FM), and abdominal fat; however, PRISE lost significantly (P < 0.01) more body weight (3.3 0.7 vs. 1.1 0.7 kg, P + RT) and FM (2.8 0.7 vs. 0.9 0.5 kg, P + RT) and gained (P < 0.05) a greater percentage of lean body mass (2 0.5 vs. 0.9 0.3 and 0.6 0.4%, P + RT and P, respectively). Only P + RT (0.1 0.04 kg) and PRISE (0.21 0.07 kg) lost VAT mass (P < 0.05). Fasting glucose decreased only in P + RT (5.1 2.5 mg/dl) and PRISE (15.3 2.1 mg/dl), with the greatest decline occurring in PRISE (P < 0.05). Similarly, HOMA-IR improved (0.6 0.3, 0.6 0.4 units), and leptin decreased (4.7 2.2, 4.7 3.1 ng/dl), and adiponectin increased (3.8 1.1, 2.4 1.1 ?g/ml) only in P + RT and PRISE, respectively, with no change in P. In conclusion, we find evidence to support exercise training and timed ingestion of whey protein added to the habitual diet of free-living overweight/obese adults, independent of caloric restriction on total and regional body fat distribution, insulin resistance, and adipokines. PMID:24833780

Arciero, Paul J; Baur, Daniel; Connelly, Scott; Ormsbee, Michael J

2014-07-01

113

Does Adipose Tissue Thermogenesis Play a Role in Metabolic Health?  

PubMed Central

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

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

2013-01-01

114

Exercise training protects against an acute inflammatory insult in mouse epididymal adipose tissue.  

PubMed

Exercise training reduces systemic and adipose tissue inflammation. However, these beneficial effects seem to be largely tied to reductions in adipose tissue mass. The purpose of the present study was to determine if exercise training confers a protective effect against an acute inflammatory challenge. We hypothesized that the induction of inflammatory markers, such as interleukin 6 (IL-6), suppressor of cytokine signaling 3 (SOCS3), and TNF-? by the beta-3 adrenergic agonist CL 316,243 would be reduced in adipose tissue from trained mice and this would be associated with reductions in transient receptor potential cation channel 4 (TRPV4), a protein recently shown to regulate the expression of proinflammatory cytokines. Exercise training (4 wk of treadmill running, 1 h/day, 5 days/wk) increased markers of skeletal muscle mitochondrial content and the induction of PPAR-gamma coactivator 1 alpha in epididymal adipose tissue. The mRNA expression of IL-6, SOCS3, and TNF? were not different in subcutaneous and epididymal adipose tissue from sedentary and trained mice; however, the CL 316,243-mediated induction of these genes was attenuated ?50% in epididymal adipose tissue from trained mice as were increases in plasma IL-6. The effects of training were not explained by reductions in lipolytic responsiveness, but were associated with decreases in TRPV4 protein content. These results highlight a previously unappreciated anti-inflammatory effect of exercise training on adipose tissue immunometabolism and underscores the value of assessing adipose tissue inflammation in the presence of an inflammatory insult. PMID:24674860

Castellani, Laura; Root-Mccaig, Jared; Frendo-Cumbo, Scott; Beaudoin, Marie-Soleil; Wright, David C

2014-05-15

115

Adipose Tissue Heterogeneity: Implication of depot differences in adipose tissue for Obesity Complications  

PubMed Central

Obesity, defined as excess fat mass, increases risks for multiple metabolic diseases, such as type 2 diabetes, cardiovascular disease and several types of cancer. Over and above fat mass per se, the pattern of fat distribution, android or truncal as compared to gynoid or peripheral, has a profound influence on systemic metabolism and hence risk for metabolic diseases. Increases in upper body adipose tissue (visceral and abdominal subcutaneous) confer an independent risk, while the quantity of gluteofemoral adipose tissue is protective. Variations in the capacity of different depots to store and release fatty acids and to produce adipokines are important determinants of fat distribution and its metabolic consequences. Depot differences in cellular composition and physiology, including innervation and blood flow, likely influence their phenotypic properties. A number of lines of evidence also support the idea that adipocytes from different anatomical depots are intrinsically different as a result of genetic or developmental events. In this chapter, we will review the phenotypic characteristics of different adipose depots and mechanisms that link their depot-specific biology to metabolic complications in men and women. PMID:23068073

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

2012-01-01

116

EFFECTS OF ADDED DIETARY PROTEIN AND FAT ON SUBCUTANEOUS ADIPOSE TISSUE OF FINSISHING LAMBS WHEN FED DIFFERING LEVELS OF DRIED DISTILLER'S GRAINS WITH SOLUBLES  

Microsoft Academic Search

The objectives of this study were to determine the effects of added dietary protein and fat in dried distiller's grains with solubles (DDGS) on s.c. adipose fatty acid (FA) profiles in finishing lambs. Sixty crossbred lambs (33.17 4.67 kg; 30 ewes; 30 wethers) were allotted into pairs (ewe and wether) and fed one of five isocaloric dietary treatments: 1)

M. L. Van Emon; A. F. Musselman; P. J. Gunn; M. K. Neary; R. P. Lemenager; E. J. Scholljegerdes

2008-01-01

117

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

PubMed

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

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

2014-10-15

118

Contrasting cellularity on fat deposition in the subcutaneous adipose tissue and longissimus lumborum muscle from lean and fat pigs under dietary protein reduction.  

PubMed

The production of pork with high amounts of intramuscular fat (IMF) without an increase in subcutaneous fat is highly desirable for the pig industry and consumers. Herein, we question the impact of dietary protein reduction (18% v. 13%) on fat deposition in the subcutaneous adipose tissue (SAT) and longissimus lumborum (LL) muscle using genetically diverse pigs for body fatness (lean v. fat). A clear effect of genotype was observed on plasma insulin (P=0.004) and leptin (P<0.001), as well as on backfat thickness (P<0.001), with the fat pigs having higher values. Accordingly, IMF was higher in the fat pigs, when compared with their lean counterparts (P=0.003), which was supported by enlarged adipocytes (P<0.001). The area of lipid droplets within the LL fibres (P=0.039) and extramyocellular lipids number (P=0.017) were increased in pigs fed reduced protein diets, regardless of genotype, which is consistent with higher levels of plasma triacylglycerols (P=0.002). The gene-expression pattern of lipogenic factors in the SAT was distinct from the LL muscle. In the SAT, PPARG expression was similar among genotypes (P>0.05), whereas in the LL muscle it was higher in the lean pigs (P=0.023), especially when fed on low protein diet (P=0.057). The CEBPA and FABP4 mRNA levels were increased in the SAT of fat pigs (P<0.001), without changes in the LL muscle (P>0.05). The influence of diet on FABP4 expression in the SAT was dependent on pig's genetic background (P=0.005). In conclusion, fat deposition was clearly influenced by genotype and, to a lesser extent, by dietary protein level, the SAT being more sensitive than the LL muscle. One can speculate that the pathways involved in lipid metabolism are downregulated in intramuscular adipocytes when compared with SAT fat cells. This result might be a direct consequence of the relatively low proportion of adipocytes found in the LL muscle. PMID:24636826

Lopes, P A; Costa, A S H; Costa, P; Pires, V M R; Madeira, M S; Achega, F; Pinto, R M A; Prates, J A M

2014-04-01

119

In vitro Differentiation of Human Adipose Tissue-Derived Stem Cells into Islet-Like Clusters Promoted by Islet Neogenesis-Associated Protein Pentadecapeptide.  

PubMed

Human adipose tissue-derived stem cells (hASCs) are considered an ideal tool for the supply of insulin-producing cells to treat diabetes mellitus, with high differentiation efficiency. Islet neogenesis-associated protein (INGAP) is an initiator of islet neogenesis, and the peptide sequence comprising amino acids 104-118, named INGAP pentadecapeptide (INGAP-PP), has been shown to increase ?-cell mass in animals and human pathological states. Here, we report a novel 4-step method to promote hASCs to differentiate into islet-like clusters (ILCs) more efficiently by adding INGAP-PP. The hASCs were isolated, purified and differentiated using a 4-step protocol including trichostatin A, INGAP-PP/scrambled peptide (Scrambled-P), dexamethasone, nicotinamide, glucagon-like peptide-1, transforming growth factor ?1 and exendin-4. Results showed that ILCs in the INGAP-PP group were more similar to the fresh islets with regard to both size and morphology and expressed significantly higher levels of both insulin and C-peptide than those in the Scrambled-P group. Moreover, the ILCs from the INGAP-PP group secreted higher levels of insulin and C-peptide than those from the Scrambled-P group in response to both a low (5.6 mM) and high (25 mM) glucose challenge and secreted 6 times more hormones under the high-glucose challenge. Real-time PCR and immunocytochemistry showed that ILCs of the INGAP-PP group expressed human pancreatic endocrine hormones and transcription factors. Transplantation of ILCs into diabetic rats partially reversed diabetes and prolonged their life span. In conclusion, the INGAP-PP protocol can efficiently induce hASCs to differentiate into ILCs in vitro, and thus hASCs could be a promising source of cells for transplantation to treat diabetes mellitus. 2014 S. Karger AG, Basel. PMID:25471531

Ren, Lili; Chen, Lijuan; Qi, Hui; Li, Furong; Gong, Feili

2014-12-01

120

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

PubMed Central

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

Reverchon, Maxime; Ram, Christelle; Cogni, Juliette; Briant, Eric; Elis, Sbastien; Guillaume, Daniel; Dupont, Jolle

2014-01-01

121

Is Adipose Tissue a Place for Mycobacterium tuberculosis Persistence?  

E-print Network

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

Paris-Sud XI, Université de

122

Polybrominated diphenyl ethers detected in human adipose tissue from Spain  

Microsoft Academic Search

Polybrominated diphenyl ethers (PBDEs) were detected in 13 human adipose tissue samples from Spain, 3 women and 10 men. Tetra-, penta- and hexabrominated diphenyl ethers were determined at ng\\/g lipid (ppb) level in all the samples. The average TeBDE level was 1.36 ng\\/g, the average PeBDE was 0.93 ng\\/g and the HxBDE 1.83 ng\\/g. Human adipose tissue levels of PBDE

M. Meneses; H. Wingfors; M. Schuhmacher; J. L. Domingo; G. Lindstrm; B. v. Bavel

1999-01-01

123

Gene expression profile of omental adipose tissue in human obesity  

Microsoft Academic Search

The aim of the present study was to gain insight into the pathophysiology of obesity by comparing the pattern of gene expression of omental adipose tissue of obese and lean volunteers using DNA microarrays. Omental adipose tissue biopsies were obtained by laparoscopic surgery from six male patients (44.26.3 yr). RNA was extracted and pooled for the obese (BMI: 37.32.5 kg\\/m2)

J. Gomez-Ambrosi; Victoria Cataln; Alberto Diez-Caballero; L. Alfonso Martnez-Cruz; Mara J. Gil; Jess Garca-Foncillas; Javier A. Cienfuegos; Javier Salvador; Jos M. Mato; Gema Frhbeck

2003-01-01

124

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

PubMed Central

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

2013-01-01

125

Central Control of Brown Adipose Tissue Thermogenesis  

PubMed Central

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

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

2011-01-01

126

New concepts in white adipose tissue physiology  

PubMed Central

Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT. PMID:24676492

Proena, A.R.G.; Serti, R.A.L.; Oliveira, A.C.; Campaa, A.B.; Caminhotto, R.O.; Chimin, P.; Lima, F.B.

2014-01-01

127

Metabolically active human brown adipose tissue derived stem cells.  

PubMed

Brown adipose tissue (BAT) plays a key role in the evolutionarily conserved mechanisms underlying energy homeostasis in mammals. It is characterized by fat vacuoles 5-10 m in diameter and expression of uncoupling protein one, central to the regulation of thermogenesis. In the human newborn, BAT depots are typically grouped around the vasculature and solid organs. These depots maintain body temperature during cold exposure by warming the blood before its distribution to the periphery. They also ensure an optimal temperature for biochemical reactions within solid organs. BAT had been thought to involute throughout childhood and adolescence. Recent studies, however, have confirmed the presence of active BAT in adult humans with depots residing in cervical, supraclavicular, mediastinal, paravertebral, and suprarenal regions. While human pluripotent stem cells have been differentiated into functional brown adipocytes in vitro and brown adipocyte progenitor cells have been identified in murine skeletal muscle and white adipose tissue, multipotent metabolically active BAT-derived stem cells from a single depot have not been identified in adult humans to date. Here, we demonstrate a clonogenic population of metabolically active BAT stem cells residing in adult humans that can: (a) be expanded in vitro; (b) exhibit multilineage differentiation potential; and (c) functionally differentiate into metabolically active brown adipocytes. Our study defines a new target stem cell population that can be activated to restore energy homeostasis in vivo for the treatment of obesity and related metabolic disorders. PMID:24420906

Silva, Francisco J; Holt, Dolly J; Vargas, Vanessa; Yockman, James; Boudina, Sihem; Atkinson, Donald; Grainger, David W; Revelo, Monica P; Sherman, Warren; Bull, David A; Patel, Amit N

2014-02-01

128

Six weeks of voluntary wheel running modulates inflammatory protein (MCP-1, IL-6, and IL-10) and DAMP (Hsp72) responses to acute stress in white adipose tissue of lean rats  

PubMed Central

To prime local tissues for dealing with potential infection or injury, exposure to an acute, intense stressor evokes increases in circulating and local tissue inflammatory proteins. Regular physical activity facilitates stress-evoked innate reactivity and modulates the expression of inflammatory proteins in immuno-metabolic tissues such as white adipose tissue (WAT). The impact of regular physical activity on stress-evoked inflammatory protein expression in WAT, however, remains unclear. To investigate this question, lean male F344 rats (150175 g) were allowed voluntary access to a running wheel for 6 weeks followed by exposure to an acute stressor (100, 1.5 mA-5 s inescapable tail shocks). Using ELISAs, corticosterone, heat shock protein 72 (Hsp72), macrophage chemoattractant protein (MCP-1), tumor necrosis factor-alpha (TNF-?), interleukin (IL)-1?, IL-6, and IL-10 concentrations were measured in plasma and subcutaneous, intraperitoneal (epididymal and retroperitoneal WAT depots) and visceral (omental and mesenteric WAT depots) WAT compartments. Acute stress increased plasma concentrations of all proteins except TNF-? and, depending upon the compartment examined, WAT concentrations of MCP-1, IL-1?, IL-6, and IL-10. Exercise ubiquitously increased IL-1? within WAT, potentiated stress-evoked Hsp72 in plasma and WAT, and differentially increased stress-evoked MCP-1, IL-6, and IL-10 within WAT. These data suggest: (a) inflammatory proteins in non-obese WAT may serve compartment-specific immune and metabolic roles important to the acute stress response and; (b) voluntary habitual exercise may optimize stress-induced augmentation of innate immune function through increases in stress-evoked Hsp72, MCP-1, IL-6, and IL-10 and decreases in IL-1?/IL10 and TNF-?/IL10 ratios within white adipose tissue. PMID:24246250

Speaker, Kristin J.; Cox, Stewart S.; Paton, Madeline M.; Serebrakian, Arman; Maslanik, Thomas; Greenwood, Benjamin N.; Fleshner, Monika

2015-01-01

129

NPC1 in human white adipose tissue and obesity  

PubMed Central

Background Genetic studies have implicated the NPC1 gene (Niemann Pick type C1) in susceptibility to obesity. Methods To assess the potential function of NPC1 in obesity, we determined its expression in abdominal white adipose tissue (WAT) in relation to obesity. NPC1 mRNA was measured by RT-qPCR in lean and obese individuals, paired samples of subcutaneous (sc) and omental (om) WAT, before and after weight loss, in isolated adipocytes and intact adipose pieces, and in primary adipocyte cultures during adipocyte differentiation. NPC1 protein was examined in isolated adipocytes. Results NPC1 mRNA was significantly increased in obese individuals in scWAT and omWAT and downregulated by weight loss. NPC1 mRNA was enriched in isolated fat cells of WAT, in scWAT versus omWAT but not modified during adipocyte differentiation. NPC1 protein mirrored expression of mRNA in lean and obese individuals. Conclusions NPC1 is highly expressed in human WAT adipocytes with increased levels in obese. These results suggest that NPC1 may play a role in adipocyte processes underlying obesity. PMID:23360456

2013-01-01

130

Alterations of gene expression and protein synthesis in co-cultured adipose tissue-derived stem cells and squamous cell-carcinoma cells: consequences for clinical applications  

PubMed Central

Introduction This is the first study evaluating the interactions of human adipose tissue derived stem cells (ADSCs) and human squamous cell carcinoma cells (SCCs), with regard to a prospective cell-based skin regenerative therapy and a thereby unintended co-localization of ADSCs and SCCs. Methods ADSCs were co-cultured with A431-SCCs and primary SCCs (pSCCs) in a transwell system, and cell-cell interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real time PCR of 229 tumor associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPS). Results of co-culture were compared to those of the respective mono-culture. Results ADSCs proliferation on the plate was significantly increased when co-cultured with A431-SCCs (P?=?0.038). PSCCs and ADSCs significantly decreased their proliferation in co-culture if cultured on the plate (P?<0.001 and P?=?0.03). The migration of pSCC was significantly increased in co-culture (P?=?0.009), as well as that of ADSCs in A431-SCC-co-culture (P?=?0.012). The invasive behavior of pSCCs and A431-SCCs was significantly increased in co-culture by a mean of 33% and 35%, respectively (P?=?0.038 and P?<0.001). Furthermore, conditioned media from co-cultured ADSC-A431-SCCs and co-cultured ADSCs-pSCCs induced tube formation in an angiogenesis assay in vitro. In A431-SCC-co-culture 36 genes were up- and 6 were down-regulated in ADSCs, in A431-SCCs 14 genes were up- and 8 genes were down-regulated. In pSCCs-co-culture 36 genes were up-regulated in ADSCs, two were down-regulated, one gene was up-regulated in pSCC, and three genes were down-regulated. Protein expression analysis revealed that three proteins were exclusively produced in co-culture (CXCL9, IL-1b, and MMP-7). In A431-SCC-co-culture the concentration of 17 proteins was significantly increased compared to the ADSCs mono-culture (2.8- to 357-fold), and 15 proteins were expressed more highly (2.8- to 1,527-fold) compared to the A431-SCCs mono-culture. In pSCC-co-culture the concentration of 10 proteins was increased compared to ADSCs-mono-culture (2.5- to 77-fold) and that of 15 proteins was increased compared to pSCC mono-culture (2.6- to 480-fold). Conclusions This is the first study evaluating the possible interactions of primary human ADSCs with human SCCs, pointing towards a doubtlessly increased oncological risk, which should not be neglected when considering a clinical use of isolated human ADSCs in skin regenerative therapies. PMID:24887580

2014-01-01

131

Switch from Stress Response to Homeobox Transcription Factors in Adipose Tissue After Profound Fat Loss  

PubMed Central

Background In obesity, impaired adipose tissue function may promote secondary disease through ectopic lipid accumulation and excess release of adipokines, resulting in systemic low-grade inflammation, insulin resistance and organ dysfunction. However, several of the genes regulating adipose tissue function in obesity are yet to be identified. Methodology/Principal Findings In order to identify novel candidate genes that may regulate adipose tissue function, we analyzed global gene expression in abdominal subcutaneous adipose tissue before and one year after bariatric surgery (biliopancreatic diversion with duodenal switch, BPD/DS) (n?=?16). Adipose tissue from lean healthy individuals was also analyzed (n?=?13). Two different microarray platforms (AB 1700 and Illumina) were used to measure the differential gene expression, and the results were further validated by qPCR. Surgery reduced BMI from 53.3 to 33.1 kg/m2. The majority of differentially expressed genes were down-regulated after profound fat loss, including transcription factors involved in stress response, inflammation, and immune cell function (e.g., FOS, JUN, ETS, C/EBPB, C/EBPD). Interestingly, a distinct set of genes was up-regulated after fat loss, including homeobox transcription factors (IRX3, IRX5, HOXA5, HOXA9, HOXB5, HOXC6, EMX2, PRRX1) and extracellular matrix structural proteins (COL1A1, COL1A2, COL3A1, COL5A1, COL6A3). Conclusions/Significance The data demonstrate a marked switch of transcription factors in adipose tissue after profound fat loss, providing new molecular insight into a dichotomy between stress response and metabolically favorable tissue development. Our findings implicate homeobox transcription factors as important regulators of adipose tissue function. PMID:20543949

Stavrum, Anne-Kristin; Stansberg, Christine; Holdhus, Rita; Hoang, Tuyen; Veum, Vivian L.; Christensen, Bjrn Jostein; Vge, Villy; Sagen, Jrn V.; Steen, Vidar M.; Mellgren, Gunnar

2010-01-01

132

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

PubMed Central

Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT), white adipose (WAT) and liver of mice in response to 24 h cold exposure at 8C. Expression of 1895 genes were significantly (P<0.05) up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and 134 genes were common between WAT and BAT, WAT and liver, and BAT and liver, respectively. We confirmed using qRT-PCR, the increased expression of a number of characteristic BAT genes during cold exposure. In both BAT and the liver, the most common direction of change in gene expression was suppression (496 genes in BAT and 590 genes in liver). Gene ontology analysis revealed for the first time significant (P<0.05) down regulation in response to cold, of genes involved in oxidoreductase activity, lipid metabolic processes and protease inhibitor activity, in both BAT and liver, but not WAT. The results reveal an unexpected importance of down regulation of cytochrome P450 gene expression and apolipoprotein, in both BAT and liver, but not WAT, in response to cold exposure. Pathway analysis suggests a model in which down regulation of the nuclear transcription factors HNF4? and PPAR? in both BAT and liver may orchestrate the down regulation of genes involved in lipoprotein and steroid metabolism as well as Phase I enzymes belonging to the cytochrome P450 group in response to cold stress in mice. We propose that the response to cold stress involves decreased gene expression in a range of cellular processes in order to maximise pathways involved in heat production. PMID:23894377

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

2013-01-01

133

Chemokine Expression in Inflamed Adipose Tissue Is Mainly Mediated by NF-?B  

PubMed Central

Immune cell infiltration of expanding adipose tissue during obesity and its role in insulin resistance has been described and involves chemokines. However, studies so far have focused on a single chemokine or its receptor (especially CCL2 and CCL5) whereas redundant functions of chemokines have been described. The objective of this work was to explore the expression of chemokines in inflamed adipose tissue in obesity. Human and mouse adipocytes were analyzed for expression of chemokines in response to inflammatory signal (TNF-?) using microarrays and gene set enrichment analysis. Gene expression was verified by qRT-PCR. Chemokine protein was determined in culture medium with ELISA. Chemokine expression was investigated in human subcutaneous adipose tissue biopsies and mechanism of chemokine expression was investigated using chemical inhibitors and cellular and animal transgenic models. Chemokine encoding genes were the most responsive genes in TNF-? treated human and mouse adipocytes. mRNA and protein of 34 chemokine genes were induced in a dose-dependent manner in the culture system. Furthermore, expression of those chemokines was elevated in human obese adipose tissue. Finally, chemokine expression was reduced by NF-?B inactivation and elevated by NF-?B activation. Our data indicate that besides CCL2 and CCL5, numerous other chemokines such as CCL19 are expressed by adipocytes under obesity-associated chronic inflammation. Their expression is regulated predominantly by NF-?B. Those chemokines could be involved in the initiation of infiltration of leukocytes into obese adipose tissue. PMID:23824685

Tourniaire, Franck; Romier-Crouzet, Beatrice; Lee, Jong Han; Marcotorchino, Julie; Gouranton, Erwan; Salles, Jerome; Malezet, Christiane; Astier, Julien; Darmon, Patrice; Blouin, Eric; Walrand, Stephane; Ye, Jianping; Landrier, Jean-Francois

2013-01-01

134

Novel findings regarding Glut-4 expression in adipose tissue and muscle in horses--a preliminary report.  

PubMed

One of the hallmarks of insulin resistance is a reduction in glucose transporter-4 (Glut-4) expression in adipose tissue but not in skeletal muscle. However, while Glut-4 has been demonstrated in skeletal and cardiac muscles in horses it has not been demonstrated in adipose tissue. The initial objectives of the present study were: (1) to test the hypothesis that Glut-4 expression would vary between selected key skeletal muscles; (2) to test the hypothesis that it would also vary between representative adipose tissue depots, and (3) to see whether expression would be greater in adipose tissue compared to muscle. Glut-4 expression was determined by Western blot using samples obtained from post mortem biopsies obtained from four muscles (gluteus medius, semitendinosus, heart, and diaphragm), and four adipose tissues (subcutaneous, retroperitoneal, mesenteric, and omental) in three horses. There were no differences (P>0.05) in Glut-4 protein expression between the muscles sampled. Likewise there were no differences (P>0.05) in Glut-4 protein expression between fat depots. There was a significant difference (P=0.03) when pooled means for Glut-4 expression in muscle (58.8+/-2.5 densitometry units) were compared with adipose tissue (115.8+/-15.7). This difference in Glut-4 expression in these two tissues with distinctly different metabolic reasons for taking up glucose may warrant further investigation to see if there are more pronounced differences in Glut-4 expression in muscle and adipose tissue in various populations of horses. PMID:17174126

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

2007-11-01

135

Estradiol Regulates Brown Adipose Tissue Thermogenesis via Hypothalamic AMPK  

PubMed Central

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

MartnezdeMorentin, PabloB.; Gonzlez-Garca, Ismael; Martins, Lus; Lage, Ricardo; Fernndez-Mallo, Diana; Martnez-Snchez, Noelia; Ruz-Pino, Francisco; Liu, Ji; Morgan, DonaldA.; Pinilla, Leonor; Gallego, Rosala; Saha, AsishK.; Kalsbeek, Andries; Fliers, Eric; Bisschop, PeterH.; Diguez, Carlos; Nogueiras, Rubn; Rahmouni, Kamal; Tena-Sempere, Manuel; Lpez, Miguel

2014-01-01

136

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

PubMed

Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. PET-CT scans recently demonstrated the existence of metabolically active BAT in adult humans, which revitalized our interest in BAT. Increasing the amount and/or activity of BAT holds tremendous promise for the treatment of obesity and its associated diseases. PGC1? is the master regulator of UCP1-mediated thermogenesis in BAT. A number of proteins have been identified to influence thermogenesis either positively or negatively through regulating the expression or transcriptional activity of PGC1?. Therefore, BAT activation can be achieved by either inducing the expression of positive regulators of PGC1? or by inhibiting the repressors of the PGC1?/UCP1 pathway. Here, we review the most important negative regulators of PGC1?/UCP1 signaling and their mechanism of action in BAT-mediated thermogenesis. PMID:24809334

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

2014-12-01

137

Enzymatic intracrine regulation of white adipose tissue  

PubMed Central

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

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

2015-01-01

138

Enzymatic intracrine regulation of white adipose tissue.  

PubMed

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

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

2014-07-01

139

Liver but not adipose tissue is responsive to the pattern of enteral feeding  

PubMed Central

Abstract Nutritional support is an important aspect of medical care, providing calories to patients with compromised nutrient intake. Metabolism has a diurnal pattern, responding to the light cycle and food intake, which in turn can drive changes in liver and adipose tissue metabolism. In this study, we assessed the response of liver and white adipose tissue (WAT) to different feeding patterns under nutritional support (total enteral nutrition or TEN). Mice received continuous isocaloric TEN for 10 days or equal calories of chow once a day (Ch). TEN was given either at a constant (CN, same infusion rate during 24 h) or variable rate (VN, 80% of calories fed at night, 20% at day). Hepatic lipogenesis and carbohydrate?responsive element?binding protein (ChREBP) expression increased in parallel with the diurnal feeding pattern. Relative to Ch, both patterns of enteral feeding increased adiposity. This increase was not associated with enhanced lipogenic gene expression in WAT; moreover, lipogenesis was unaffected by the feeding pattern. Surprisingly, leptin and adiponectin expression increased. Moreover, nutritional support markedly increased hepatic and adipose FGF21 expression in CN and VN, despite being considered a fasting hormone. In summary, liver but not WAT, respond to the pattern of feeding. While hepatic lipid metabolism adapts to the pattern of nutrient availability, WAT does not. Moreover, sustained delivery of nutrients in an isocaloric diet can cause adiposity without the proinflammatory state observed in hypercaloric feeding. Thus, the liver but not adipose tissue is responsive to the pattern of feeding behavior. PMID:24744913

Otero, Yolanda F.; Lundblad, Tammy M.; Ford, Eric A.; House, Lawrence M.; McGuinness, Owen P.

2014-01-01

140

Thalidomide Controls Adipose Tissue Inflammation Associated with High-Fat Diet-Induced Obesity in Mice.  

PubMed

Introduction: Immunosuppressant agents modulate the activity of the immune system and control adipose tissue inflammatory responses associated with obesity. Controlling adipose tissue inflammation represents an interesting option for inhibiting the low-grade inflammatory state in obese subjects and for preventing obesity-associated pathologies. In this work, we assessed the effects of thalidomide on the inflammatory response in adipose tissue as well as on systemic inflammatory marker expression in the well-established high-fat diet-induced obesity mouse model. Methods: Swiss male mice were fed a high-fat diet (60% kcal from fat) for 12 weeks and received thalidomide for the last 10 days (100 mg.kg-1). Adipokine levels were measured in serum and adipose tissue by EIA and real-time quantitative PCR, respectively. Adipose tissue infiltrating macrophages were identified by immunohistochemistry and western blot analysis of F4/80 marker expression. Other inflammatory markers, such as c-Jun N-terminal kinase (JNK) phosphorylation and monocyte chemoattractant protein-1 (MCP-1) production, were also evaluated by western blot analysis. In vitro assays using 3T3-L1 adipocytes were also conducted to evaluated adipokine release. Results: In obese mice, thalidomide administration induced a reduction in adiposity accompanied by a reduction of tumor necrosis factor-? (TNF-?), leptin and MCP-1 adipose tissue production, macrophage infiltration and JNK activation. TNF-? and leptin serum levels were also reduced by thalidomide treatment in obese mice. In vitro, the release of basal TNF-? and lipopolysaccharide (LPS)-induced MCP-1 was inhibited in 3T3-L1 cells. PMID:25441253

Nakamitsu, Patricia Zanotti; Compri, Cecilia Melleti; Fraia Pinto, Livia de; Gotardo, Erica Martins Ferreira; de Oliveira, Caroline Candida; Ribeiro, Marcelo Lima; Pedrazzoli, Jos; Gambero, Alessandra

2014-11-27

141

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

PubMed

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

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

2014-09-01

142

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

PubMed Central

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

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

2014-01-01

143

Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice[S  

PubMed Central

The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Young male mice were fed three combinations of fatty acids at three doses (0.06%, 0.2%, and 0.6%, w/w) incorporated into AIN76 diets for 7 weeks. The types of fatty acids were linoleic acid (control), an equal mixture of trans-10, cis-12 (10,12) CLA plus linoleic acid, and an equal isomer mixture of 10,12 plus cis-9, trans-11 (9,11) CLA. Mice receiving the 0.2% and 0.6% dose of 10,12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT and liver. Notably, in mice receiving 0.2% of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 (UCP1), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT. CLA-induced browning in WAT was accompanied by increases in mRNA levels of markers of inflammation. Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment. These data suggest a linkage between decreased adiposity, browning in WAT, and low-grade inflammation due to consumption of 10,12 CLA. PMID:23401602

Shen, Wan; Chuang, Chia-Chi; Martinez, Kristina; Reid, Tanya; Brown, J. Mark; Xi, Lin; Hixson, Lindsay; Hopkins, Robin; Starnes, Joseph; McIntosh, Michael

2013-01-01

144

Kidney Int . Author manuscript White adipose tissue overproduces the lipid-mobilizing factor zinc  

E-print Network

Kidney Int . Author manuscript Page /1 15 White adipose tissue overproduces the lipid-mobilizing factor zinc alpha2-glycoprotein in chronic kidney disease Caroline C. Pelletier 1 2 , Laetitia Koppe 1 2 Abstract Chronic kidney disease (CKD) is frequently associated with protein

Paris-Sud XI, Université de

145

The clinical importance of visceral adiposity: a critical review of methods for visceral adipose tissue analysis  

PubMed Central

As a result of the rising epidemic of obesity, understanding body fat distribution and its clinical implications is critical to timely treatment. Visceral adipose tissue is a hormonally active component of total body fat, which possesses unique biochemical characteristics that influence several normal and pathological processes in the human body. Abnormally high deposition of visceral adipose tissue is known as visceral obesity. This body composition phenotype is associated with medical disorders such as metabolic syndrome, cardiovascular disease and several malignancies including prostate, breast and colorectal cancers. Quantitative assessment of visceral obesity is important for evaluating the potential risk of development of these pathologies, as well as providing an accurate prognosis. This review aims to compare different methods of measuring visceral adiposity with emphasis on their advantages and drawbacks in clinical practice. PMID:21937614

Shuster, A; Patlas, M; Pinthus, J H; Mourtzakis, M

2012-01-01

146

Gene expression profiling in adipose tissue indicates different transcriptional mechanisms of liver X receptors ? and ?, respectively  

Microsoft Academic Search

The nuclear receptors liver X receptors (LXR) ? and ? are important regulators of genes involved in lipid, cholesterol, and carbohydrate metabolism and are highly expressed in mature adipocyte tissue. In this study we show that LXR? and LXR? are more expressed in brown adipose tissue and subcutaneous white adipose tissue than visceral (gonadal) adipose tissue. Furthermore, we report differences

Knut R. Steffensen; Maria Nilsson; Gertrud U. Schuster; Thomas M. Stulnig; Karin Dahlman-Wright; Jan-ke Gustafsson

2003-01-01

147

Adipose tissue fatty acids and insulin sensitivity in elderly men  

Microsoft Academic Search

Aims\\/hypothesisDietary fatty acids may affect insulin sensitivity. Adipose tissue fatty acid composition partly reflects long-term dietary\\u000a intake, but data from large studies regarding relationships with insulin sensitivity are lacking. We aimed to determine the\\u000a association between adipose tissue fatty acids and insulin sensitivity in elderly Swedish men.\\u000a \\u000a \\u000a \\u000a \\u000a MethodsIn a cross-sectional analysis of the community-based Uppsala Longitudinal Study of Adult Men

D. Iggman; J. rnlv; B. Vessby; T. Cederholm; P. Sjgren; U. Risrus

2010-01-01

148

Benefits of healthy adipose tissue in the treatment of diabetes  

PubMed Central

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

Gunawardana, Subhadra C

2014-01-01

149

Autophagic Degradation of Mitochondria in White Adipose Tissue Differentiation  

PubMed Central

Abstract Recent work has revealed that autophagy plays a significant role in the process of white adipocyte differentiation. In both in vitro and in vivo model systems, autophagy inactivation by targeted deletion of essential autophagy genes results in alterations in white adipocyte structure. In both models, postdifferentiation cells exhibit atypical morphology, with many small lipid droplets and large numbers of mitochondria, rather than the single large lipid droplet and relatively few mitochondria observed in normal white adipocytes. The role of autophagy as the primary means of the degradation of mitochondria has long been studied, and it is likely that a deficiency in the degradation of mitochondria contributes to the unusual phenotypes observed in mice with autophagy-deficient adipose tissue, including reduced adiposity, resistance to diet-induced obesity, and increased insulin sensitivity. What is not yet known is whether the process of mitochondria-specific autophagy, often referred to as mitophagy, is specifically induced during adipogenesis or if a general increase in the nonspecific autophagic degradation of mitochondria plays a role in normal adipose differentiation. Despite remaining questions, these findings not only establish the critical role of autophagy in white adipose tissue development, but also suggest that the manipulation of autophagy in adipose tissue may provide novel therapeutic opportunities for metabolic diseases. Antioxid. Redox Signal. 14, 19711978. PMID:21126221

Goldman, Scott J.; Zhang, Yong

2011-01-01

150

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

PubMed

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

Wium, Cecilie; Eggesb, Heidi B; Ueland, Thor; Michelsen, Annika E; Torjesen, Peter A; Aukrust, Pl; Birkeland, Kre

2014-11-01

151

Subcutaneous adipose tissue metabolism and pharmacology: a new investigative technique.  

PubMed

According to the Fick principle, any metabolic or hormonal exchange through a given tissue depends on the product of blood flow by arteriovenous difference. Because adipose tissue plays dual storage and endocrine roles, regulation of adipose tissue blood flow (ATBF) is of pivotal importance. Monitoring ATBF in humans can be achieved through different methodologies, such as the (133)Xe washout technique, considered to be the "gold standard", as well as microdialysis and other methods that are not well validated as of yet. This report describes a new method, called "adipose tissue microinfusion" or "ATM", which simultaneously quantifies ATBF by combining the (133)Xe washout technique together with variations of ATBF induced by local infusion of vasoactive agents. The most appropriate site for ATM investigation is the subcutaneous adipose tissue of the anterior abdominal wall. This innovative method conveniently enables the direct comparison of the effects on ATBF of any vasoactive compound, drug, or hormone against a contralateral saline control. The ATM method improves the accuracy and feasibility of physiological and pharmacological studies on the regulation of ATBF in vivo in humans. PMID:21751894

Martin, Elizabeth; Brassard, Pascal; Gagnon-Auger, Maude; Yale, Philippe; Carpentier, Andr C; Ardilouze, Jean-Luc

2011-06-01

152

Perivascular adipose tissue, potassium channels, and vascular dysfunction.  

PubMed

Perivascular adipose tissue has been recognized unequivocally as a major player in the pathology of metabolic and cardiovascular diseases. Through its production of adipokines and the release of other thus far unidentified factors, this recently discovered adipose tissue modulates vascular regulation and the myogenic response. After the discovery of its ability to diminish the vessel's response to vasoconstrictors, a new paradigm established adipose-derived relaxing factor (ADRF) as a paracrine smooth muscle cells' potassium channel opener that could potentially help combat vascular dysfunction. This review will discuss the role of ADRF in vascular dysfunction in obesity and hypertension, the different potassium channels that can be activated by this factor, and describes new pharmacological tools that can mimic the ADRF effect and thus can be beneficial against vascular dysfunction in cardiovascular disease. PMID:25012133

Tano, Jean-Yves; Schleifenbaum, Johanna; Gollasch, Maik

2014-09-01

153

Myocardial regeneration potential of adipose tissue-derived stem cells  

SciTech Connect

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 underlying mechanisms for beneficial effect on cardiac function, and safety issues.

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

2010-10-22

154

Upregulation of AMPK during cold exposure occurs via distinct mechanisms in brown and white adipose tissue of the mouse  

PubMed Central

AMPK (adenosine monophosphate-activated protein kinase), a key regulator of cellular energy metabolism and whole-body energy balance, is present in brown adipose tissue but its role in regulating the acute metabolic state and chronic thermogenic potential of this metabolically unique tissue is unknown. To address this, the AMPK signalling system in brown and white adipose tissue was studied in C57Bl/6 mice under control conditions, during acute and chronic cold exposure, and during chronic adrenergic stimulation. In control mice AMPK activity in brown adipose tissue was higher than in any tissue yet reported (3-fold the level in liver) secondary to a high level of expression of the ?1 isoform. During the first day of cold, a time of intense non-shivering thermogenesis, AMPK activity remained at basal levels. However, chronic (>7 days) cold caused a progressive increase in brown adipose tissue AMPK activity secondary to increased expression of the ?1 isoform. To investigate the signalling pathway involved, noradrenaline (norepinephrine) and the ?3-adrenergic-specific agonist CL 316, 243 were given for 14 days. This increased uncoupling protein-1 content in brown adipose tissue, but not AMPK activity. In white adipose tissue 15 days of cold increased ?1 AMPK activity 98 20%, an effect reproduced by chronic noradrenaline or CL 316 243. We conclude that chronic cold not only increases AMPK activity in brown and white adipose tissue, but that it does so via distinct signalling pathways. Our data are consistent with AMPK acting primarily as a regulator of chronic thermogenic potential in brown adipose tissue, and not in the acute activation of non-shivering thermogenesis. PMID:17272339

Mulligan, Jacob D; Gonzalez, Asensio A; Stewart, Annette M; Carey, Hannah V; Saupe, Kurt W

2007-01-01

155

Inflammatory alterations in mesenteric adipose tissue in Crohn's disease  

Microsoft Academic Search

Background & Aims: Abnormalities of fat in the mesentery including adipose tissue hypertrophy and fat wrapping have been long recognized on surgical specimens as characteristic features of Crohn's disease. However, the importance, origin, and significance of the mesenteric fat hypertrophy in this chronic inflammatory disease are unknown. Peroxisome proliferatoractivated receptor ? (PPAR?) is a crucial factor involved in the homeostasis

Pierre Desreumaux; Olivier Ernst; Karel Geboes; Luc Gambiez; Dominique Berrebi; Heide Mller-Alouf; Samira Hafraoui; Dominique Emilie; Nadine Ectors; Michel Peuchmaur; Antoine Cortot; Monique Capron; Johan Auwerx; Jean-Frdric Colombel

1999-01-01

156

Visceral adipose tissue: a critical review of intervention strategies  

Microsoft Academic Search

OBJECTIVE: To review the published literature regarding the effect of caloric restriction, pharmacologic intervention, and exercise to promote the loss of visceral adipose tissue (VAT)DESIGN: A review was conducted of published studies which measured VAT using computed tomography or magnetic resonance imaging before and after caloric restriction, pharmacologic therapy, or exercise.STUDIES REVIEWED: 23 separate studies were reviewed. Men represented 38%

JJ Zachwieja; Steven R. Smith

1999-01-01

157

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

PubMed

Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. Objective was to assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI (HP/HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic (16:1n-7), myristoleic (14:1n-5) and trans-palmitoleic acid (16:1n-7t). Negative correlation was found with baseline oleic acid (18:1n-9). Lower baseline monounsaturated fatty acids (14:1n-5, 16:1n-7 and trans 16:1n-7) in adipose tissue triglycerides predict better weight maintenance. Lower oleic acid predicts lower weight decrease. These findings suggest a specific role of monounsaturated fatty acids in weight management and as weight change predictors. PMID:23098653

Kuneov, M; Hlavat, P; Tvrzick, E; Sta?kov, B; Kalouskov, P; Viguerie, N; Larsen, T M; van Baak, M A; Jebb, S A; Martinez, J A; Pfeiffer, A F H; Kafatos, A; Handjieva-Darlenska, T; Hill, M; Langin, D; Zk, A; Astrup, A; Saris, W H M

2012-01-01

158

Fatty Acid Composition of Adipose Tissue Triglycerides After Weight Loss and Weight Maintenance: the DIOGENES Study  

PubMed Central

Summary Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. Objective was to assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI (HP/HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic (16:1n-7), myristoleic (14:1n-5) and trans-palmitoleic acid (16:1n-7t). Negative correlation was found with baseline oleic acid (18:1n-9). Lower baseline monounsaturated fatty acids (14:1n-5, 16:1n-7 and trans 16:1n-7) in adipose tissue triglycerides predict better weight maintenance. Lower oleic acid predicts lower weight decrease. These findings suggest a specific role of monounsaturated fatty acids in weight management and as weight change predictors. PMID:23098653

KUNEOV, M.; HLAVAT, P.; TVRZICK, E.; STA?KOV, B.; KALOUSKOV, P.; VIGUERIE, N.; LARSEN, T. M.; VAN BAAK, M. A.; JEBB, S. A.; MARTINEZ, J. A.; PFEIFFER, A. F. H.; KAFATOS, A.; HANDJIEVA-DARLENSKA, T.; HILL, M.; LANGIN, D.; K, A.; ASTRUP, A.; SARIS, W. H. M.

2013-01-01

159

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...

160

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...

161

An accelerated mouse model for atherosclerosis and adipose tissue inflammation  

PubMed Central

Background Obesity and particularly the metabolic syndrome, which is often associated with obesity, combine a major risk for type 2 diabetes and cardiovascular disease. Emerging evidence indicate obesity-associated subclinical inflammation primarily originating from adipose tissue as a common cause for type 2 diabetes and cardiovascular disease. However, a suitable and well-characterized mouse model to simultaneously study obesity-associated metabolic disorders and atherosclerosis is not available yet. Here we established and characterized a murine model combining diet-induced obesity and associated adipose tissue inflammation and metabolic deteriorations as well as atherosclerosis, hence reflecting the human situation of cardio-metabolic disease. Methods We compared a common high-fat diet with 0.15% cholesterol (HFC), and a high-fat, high-sucrose diet with 0.15% cholesterol (HFSC) fed to LDL receptor-deficient (LDLR-/-) mice. Insulin resistance, glucose tolerance, atherosclerotic lesion formation, hepatic lipid accumulation, and inflammatory gene expression in adipose tissue and liver were assessed. Results After 1216weeks, LDLR-/- mice fed HFSC or HFC developed significant diet-induced obesity, adipose tissue inflammation, insulin resistance, and impaired glucose tolerance compared to lean controls. Notably, HFSC-fed mice developed significantly higher adipose tissue inflammation in parallel with significantly elevated atherosclerotic lesion area compared to those on HFC. Moreover, LDLR-/- mice on HFSC showed increased insulin resistance and impaired glucose tolerance relative to those on HFC. After prolonged feeding (20weeks), however, no significant differences in inflammatory and metabolic parameters as well as atherosclerotic lesion formation were detectable any more between LDLR-/- mice fed HFSC or HFC. Conclusion The use of high sucrose rather than more complex carbohydrates in high-fat diets significantly accelerates development of obesity-driven metabolic complications and atherosclerotic plaque formation parallel to obesity-induced adipose tissue inflammation in LDLR-/- mice. Hence LDLR-/- mice fed high-fat high-sucrose cholesterol-enriched diet appear to be a suitable and time-saving animal model for cardio-metabolic disease. Moreover our results support the suggested interrelation between adipose tissue inflammation and atherosclerotic plaque formation. PMID:24438079

2014-01-01

162

Cellular regulation of bovine intramuscular adipose tissue development and composition.  

PubMed

It is well documented that grain feeding stimulates adipogenesis in beef cattle, whereas pasture feeding depresses the development of adipose tissues, including intramuscular (i.m.) adipose tissue. Additionally, production practices that depress adipocyte differentiation also limit the synthesis of MUFA. Marbling scores and MUFA increase in parallel suggesting that stearoyl-coenzyme A desaturase (SCD) gene expression is closely associated with and necessary for marbling adipocyte differentiation. Similarly, marbling scores and fatty acid indices of SCD activity are depressed in response to dietary vitamin A restriction. In bovine preadipocytes, vitamins A and D both decrease glycerol-3-phosphate dehydrogenase (GPDH) activity, an index of adipocyte differentiation, whereas incubation of bovine preadipocytes with l-ascorbic acid-2-phosphate increases GPDH activity. Exposing bovine preadipocytes to zinc also stimulates adipogenesis, putatively by inhibiting nitric oxide (NO) production. However, incubation of bovine preadipocytes with arginine, a biological precursor of NO, strongly promotes differentiation in concert with increased SCD expression. This suggests that the effect of either arginine or zinc on adipogenesis is independent of NO synthesis in bovine preadipocytes. Enhanced expression of SCD is associated with a greater accumulation of MUFA both in bovine preadipocyte cultures and during development in growing steers. In bovine preadipocytes, trans-10, cis-12 CLA strongly depresses adipocyte differentiation and SCD gene expression, thereby reducing MUFA concentrations. The bovine preadipocyte culture studies suggest that any production practice that elevates vitamins A or D or trans-10, cis-12 CLA in bovine adipose tissue will reduce i.m. adipose tissue development. Conversely, supplementation with vitamin C or zinc may promote the development of i.m. adipose tissue. PMID:18997081

Smith, S B; Kawachi, H; Choi, C B; Choi, C W; Wu, G; Sawyer, J E

2009-04-01

163

Molecular pathways linking non-shivering thermogenesis and obesity: focusing on brown adipose tissue development.  

PubMed

An increase in energy intake and/or a decrease in energy expenditure lead to fat storage, causing overweight and obesity phenotypes. The objective of this review was to analyse, for the first time using a systematic approach, all published evidence from the past 8?years regarding the molecular pathways linking non-shivering thermogenesis and obesity in mammals, focusing on mechanisms involved in brown adipose tissue development. Two major databases were scanned from 2006 to 2013 using 'brown adipose tissue' AND 'uncoupling protein-1' AND 'mammalian thermoregulation' AND 'obesity' as key words. A total of 61 articles were retrieved using the search criteria. The available research used knockout methodologies, various substances, molecules and agonist treatments, or different temperature and diet conditions, to assess the molecular pathways linking non-shivering thermogenesis and obesity. By integrating the results of the evaluated animal and human studies, our analysis identified specific molecules that enhance non-shivering thermogenesis and metabolism by: (i) stimulating 'brite' (brown-like) cell development in white adipose tissue; (ii) increasing uncoupling protein-1 expression in brite adipocytes; and (iii) augmenting brown and/or brite adipose tissue mass. The latter can be also increased through low temperature, hibernation and/or molecules involved in brown adipocyte differentiation. Cold stimuli and/or certain molecules activate uncoupling protein-1 in the existing brown adipocytes, thus increasing total energy expenditure by a magnitude proportional to the number of available brown adipocytes. Future research should address the interplay between body mass, brown adipose tissue mass, as well as the main molecules involved in brite cell development. PMID:24708171

Valente, Angelica; Jamurtas, Athanasios Z; Koutedakis, Yiannis; Flouris, Andreas D

2014-04-01

164

Morphological and receptorial changes in the epididymal adipose tissue of rats subjected to a stressful stimulus.  

PubMed

Obesity is nowadays related to other pathological conditions such as inflammation, insulin resistance, and diabetes, but little is known about the relationship between psychological stress and adipocytes. We decided to study the expression of the translocator protein (TSPO) 18-kDa, peroxisome proliferator-activated receptor-? (PPAR-?), mitochondrial uncoupling protein-1 (UCP-1), and adipocyte morphology in the adipose tissue of rats subjected to stress conditions. In our model of stress, rats fasted for 24 h were placed in a restraint cage and then immersed vertically to the level of the xiphoid process in a water bath at 23 C for 7 h. After that period, we removed the epididymal adipose tissues for the subsequent analysis. The optical and electron microscopy revealed that adipocytes of control rats formed a continuous epithelial-like cell layer; on the contrary in the adipocytes of stressed rats some cells have merged together and the number of vessels formed seems to increase. Stressed adipocytes presented unilocular cells with numerous mitochondria with a morphology ranging between that of brown adipose tissue (BAT) and white adipose tissue (WAT). Interestingly, when we investigated the subcellular distribution of UCP-1 by immunogold electron microscopy, the adipose tissue of stressed rats was positive for UCP-1. From the immunoblot analysis with anti-PPAR-? antibody, we observed an increased expression of PPAR-? in the adipocytes of stressed group compared with control group (P < 0.05). Stress induced the expression of TSPO 18-kDa receptor (B(max) = 106.45 5.87 fmol/mg proteins), which is undetectable by saturation-binding assay with [(3)H]PK 11195 in the control group. PMID:20948513

Campioli, Enrico; Carnevale, Gianluca; Avallone, Rossella; Guerra, Deanna; Baraldi, Mario

2011-04-01

165

Sex-associated differences in cold-induced UCP1 synthesis in rodent brown adipose tissue  

Microsoft Academic Search

The effects of acute and chronic acclimation to cold on uncoupling protein 1 (UCP1) levels, as well as on GDP-binding to\\u000a mitochondria, cytochrome c oxidase activity and mitochondrial protein concentration in brown adipose tissue (BAT) of intact male and female rats have\\u000a been analyzed. Results reveal that females rats are more sensitive to cold because their threshold temperature for the

Santiago Quevedo; Pilar Roca; Catalina Pic; Andreu Palou

1998-01-01

166

Morphological and Receptorial Changes in the Epididymal Adipose Tissue of Rats Subjected to a Stressful Stimulus  

Microsoft Academic Search

Obesity is nowadays related to other pathological conditions such as inflammation, insulin resistance, and diabetes, but little is known about the relationship between psychological stress and adipocytes. We decided to study the expression of the translocator protein (TSPO) 18-kDa, peroxisome proliferatoractivated receptor-? (PPAR-?), mitochondrial uncoupling protein-1 (UCP-1), and adipocyte morphology in the adipose tissue of rats subjected to stress conditions.

Enrico Campioli; Gianluca Carnevale; Rossella Avallone; Deanna Guerra; Mario Baraldi

2011-01-01

167

Hyperhomocysteinemia promotes insulin resistance by inducing endoplasmic reticulum stress in adipose tissue.  

PubMed

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

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

2013-04-01

168

Gene Delivery to Adipose Tissue Using Transcriptionally Targeted rAAV8 Vectors  

PubMed Central

In recent years, the increasing prevalence of obesity and obesity-related co-morbidities fostered intensive research in the field of adipose tissue biology. To further unravel molecular mechanisms of adipose tissue function, genetic tools enabling functional studies in vitro and in vivo are essential. While the use of transgenic animals is well established, attempts using viral and non-viral vectors to genetically modify adipocytes in vivo are rare. Therefore, we here characterized recombinant Adeno-associated virus (rAAV) vectors regarding their potency as gene transfer vehicles for adipose tissue. Our results demonstrate that a single dose of systemically applied rAAV8-CMV-eGFP can give rise to remarkable transgene expression in murine adipose tissues. Upon transcriptional targeting of the rAAV8 vector to adipocytes using a 2.2 kb fragment of the murine adiponectin (mAP2.2) promoter, eGFP expression was significantly decreased in off-target tissues while efficient transduction was maintained in subcutaneous and visceral fat depots. Moreover, rAAV8-mAP2.2-mediated expression of perilipin A a lipid-droplet-associated protein resulted in significant changes in metabolic parameters only three weeks post vector administration. Taken together, our findings indicate that rAAV vector technology is applicable as a flexible tool to genetically modify adipocytes for functional proof-of-concept studies and the assessment of putative therapeutic targets in vivo. PMID:25551639

Uhrig-Schmidt, Silke; Geiger, Matthias; Luippold, Gerd; Birk, Gerald; Mennerich, Detlev; Neubauer, Heike; Grimm, Dirk; Wolfrum, Christian; Kreuz, Sebastian

2014-01-01

169

Plasma and white adipose tissue lipid composition in marmots.  

PubMed

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

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

1990-05-01

170

Changes in adipose tissue cellularity, adipose tissue lipogenesis and muscle growth in steers administered the synthetic beta-adrenergic agonist, clenbuterol  

E-print Network

. . . . . . . 53 CHAPTER I INTRODUCTION Understanding the factors involved in the deposition of adipose tissue in economically valuable areas of the animal body continues to be a major concern of both animal scientists and animal producers. Adipose tissue... for beta-adrenergic action. Evidence that adipose tissue growth processes such as adipoblast (undifferentiated adipocyte precursor cell) and pre-adipocyte (differentiated but non lipid-filled cell) proliferation and/or differentiation are altered...

Schiavetta, Ann M

1988-01-01

171

Metabolic consequences of ENPP1 overexpression in adipose tissue  

PubMed Central

Ectonucleotide pyrophosphate phosphodiesterase (ENPP1) has been shown to negatively modulate insulin receptor and to induce cellular insulin resistance when overexpressed in various cell types. Systemic insulin resistance has also been observed when ENPP1 is overexpressed in multiple tissues of transgenic models and attributed largely to tissue insulin resistance induced in skeletal muscle and liver. Another key tissue in regulating glucose and lipid metabolism is adipose tissue (AT). Interestingly, obese patients with insulin resistance have been reported to have increased AT ENPP1 expression. However, the specific effects of ENPP1 in AT have not been studied. To better understand the specific role of AT ENPP1 on systemic metabolism, we have created a transgenic mouse model (C57/Bl6 background) with targeted overexpression of human ENPP1 in adipocytes, using aP2 promoter in the transgene construct (AdiposeENPP1-TG). Using either regular chow or pair-feeding protocol with 60% fat diet, we compared body fat content and distribution and insulin signaling in adipose, muscle, and liver tissues of AdiposeENPP1-TG and wild-type (WT) siblings. We also compared response to intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT). Our results show no changes in Adipose ENPP1-TG mice fed a regular chow diet. After high-fat diet with pair-feeding protocol, AdiposeENPP1-TG and WT mice had similar weights. However, AdiposeENPP1-TG mice developed fatty liver in association with changes in AT characterized by smaller adipocyte size and decreased phosphorylation of insulin receptor Tyr1361 and Akt Ser473. These changes in AT function and fat distribution were associated with systemic abnormalities of lipid and glucose metabolism, including increased plasma concentrations of fatty acid, triglyceride, plasma glucose, and insulin during IPGTT and decreased glucose suppression during ITT. Thus, our results show that, in the presence of a high-fat diet, ENPP1 overexpression in adipocytes induces fatty liver, hyperlipidemia, and dysglycemia, thus recapitulating key manifestations of the metabolic syndrome. PMID:21810932

Pan, Wentong; Ciociola, Ester; Saraf, Manish; Tumurbaatar, Batbayar; Tuvdendorj, Demidmaa; Prasad, Sneha; Chandalia, Manisha

2011-01-01

172

Angiotensin II stimulates sympathetic neurotransmission to adipose tissue  

PubMed Central

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 [3H]nisoxetine (NIS). At doses that lowered body weight, AngII significantly increased ISBAT [3H]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

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

2013-01-01

173

ABCD2 identifies a subclass of peroxisomes in mouse adipose tissue.  

PubMed

ATP-binding cassette transporter D2 (D2) is an ABC half transporter that is thought to promote the transport of very long-chain fatty acyl-CoAs into peroxisomes. Both D2 and peroxisomes increase during adipogenesis. Although peroxisomes are essential to both catabolic and anabolic lipid metabolism, their function, and that of D2, in adipose tissues remain largely unknown. Here, we investigated the D2 localization and the proteome of D2-containing organelles, in adipose tissue. Centrifugation of mouse adipose homogenates generated a fraction enriched with D2, but deficient in peroxisome markers including catalase, PEX19, and ABCD3 (D3). Electron microscopic imaging of this fraction confirmed the presence of D2 protein on an organelle with a dense matrix and a diameter of ?200nm, the typical structure and size of a microperoxisome. D2 and PEX19 antibodies recognized distinct structures in mouse adipose. Immunoisolation of the D2-containing compartment confirmed the scarcity of PEX19 and proteomic profiling revealed the presence of proteins associated with peroxisome, endoplasmic reticulum (ER), and mitochondria. D2 is localized to a distinct class of peroxisomes that lack many peroxisome proteins, and may associate physically with mitochondria and the ER. PMID:25446110

Liu, Xiaoxi; Liu, Jingjing; Lester, Joshua D; Pijut, Sonja S; Graf, Gregory A

2015-01-01

174

In Vivo Adeno-Associated Viral VectorMediated Genetic Engineering of White and Brown Adipose Tissue in Adult Mice  

PubMed Central

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

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

2013-01-01

175

Effect of maternal cold exposure on brown adipose tissue and thermogenesis in the neonatal lamb.  

PubMed Central

1. This study examines the effect of chronic cold exposure during pregnancy, induced by winter shearing twin-bearing ewes 4 weeks before predicted lambing date, on O2 consumption and CO2 production during non-rapid-eye-movement (REM) sleep in lambs maintained for at least 1 h at warm (28-18 degrees C) and cold (14-5 degrees C) ambient temperatures at 1, 4, 14 and 30 days of age. This was combined with measurement of the thermogenic activity (GDP binding to uncoupling protein in mitochondrial preparations) of perirenal adipose tissue from lambs immediately after birth and at 33 days of age. 2. Lambs born from shorn (cold-exposed) ewes were 15% heavier (P < 0.01) and possessed 21% (P < 0.01) more perirenal adipose tissue that contained 40% more protein and mitochondrial protein than unshorn (P < 0.05) controls. Total GDP binding in perirenal adipose tissue was 40% greater (P < 0.05) in lambs born from shorn ewes but there was no difference in lipid content of this tissue between the two groups. 3. At 1 day of age, lambs born from shorn ewes exhibited a 16% higher (P < 0.05) rate of O2 consumption (per kilogram bodyweight) at the warm temperature and a 40% greater metabolic response to the cold ambient temperature. All lambs born from shorn ewes responded to cold exposure without shivering (i.e. via non-shivering thermogenesis) whilst shivering was measured in four out of seven lambs in the unshorn group. These differences had disappeared by 4 days of age as a result of a 25% increased (P < 0.01) rate of O2 consumption in the warm in lambs born from unshorn ewes and a 20% decrease (P < 0.05) in the response to the cold in lambs from shorn ewes. Shivering during cold exposure was measured in six out of nine lambs born from shorn ewes indicating a rapid alteration in thermoregulatory responses to cold during the first few days of life. 4. The levels of GDP binding and mitochondrial protein in perirenal adipose tissue fell by one-third in both groups of lambs during the first 33 days of life whereas lipid content either increased or was unchanged. This indicated that brown adipose tissue (BAT) was developing the characteristics of white adipose tissue.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1484361

Symonds, M E; Bryant, M J; Clarke, L; Darby, C J; Lomax, M A

1992-01-01

176

Glucagon is essential for adaptive thermogenesis in brown adipose tissue.  

PubMed

Glucagon, a counterregulatory hormone to insulin, serves as a regulator of glucose homeostasis and acts in response to hypoglycemia. Earlier studies have shown that glucagon administration induces thermogenesis in experimental animal models. However, it is not known whether endogenous glucagon is involved in the regulation of brown adipose tissue (BAT) function. Here we investigated the role of glucagon in cold-induced thermogenesis in male mice deficient in proglucagon-derived peptides (GCGKO mice). Upon exposure to cold, GCGKO mice exhibited a greater decrease in rectal temperature than control mice. The cold exposure-induced increase in oxygen consumption in GCGKO mice was less than that seen in control mice. Moreover, the increase in oxygen consumption after administration of a ?3-adrenergic receptor agonist, CL-316,243, was also lesser in GCGKO than in control mice. Expression of thermogenic genes, including the gene encoding uncoupling protein 1 (Ucp1), was reduced in the BAT of GCGKO mice under ambient as well as cold conditions. Administration of glucagon restored the expression of Ucp1 mRNA in the BAT as well as the expression of the fibroblast growth factor 21 gene (Fgf21) in the liver. Supplementation with glucagon for 2 weeks resulted in higher plasma Fgf21 levels and improved responses to CL-316,243 in GCGKO mice. These results indicated that endogenous glucagon is essential for adaptive thermogenesis and that it regulates BAT function, most likely by increasing hepatic Fgf21 production. PMID:24949663

Kinoshita, Keita; Ozaki, Nobuaki; Takagi, Yusuke; Murata, Yoshiharu; Oshida, Yoshiharu; Hayashi, Yoshitaka

2014-09-01

177

Slip point of subcutaneous adipose tissue as an indicator of beef carcass quality  

E-print Network

on slip points, percentage intramuscular lipid, fatty acid composition, and MUFA:SFA ratios. Overlying s.c. adipose tissue was separated from the muscle lean, which contained intramuscular (i.m.) adipose tissue. Lipids were extracted from s.c. adipose...

Ward, Lindsay Paige

2009-05-15

178

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

PubMed Central

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

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

2008-01-01

179

An Adipoinductive Role of Inflammation in Adipose Tissue Engineering: Key Factors in the Early Development of Engineered Soft Tissues  

PubMed Central

Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNF?, LCN-2, and Interleukin 1? are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue. PMID:23231040

Lilja, Heidi E.; Morrison, Wayne A.; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Mller, Andreas; Thompson, Erik W.

2013-01-01

180

Fully automated adipose tissue measurement on abdominal CT  

NASA Astrophysics Data System (ADS)

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

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

2011-03-01

181

Therapeutic doses of multipotent stromal cells from minimal adipose tissue.  

PubMed

Low yield of adult adipose-derived multipotent stromal cells (ASC) can limit autologous cell therapy in individuals with minimal adipose tissue. In this study, ASC isolation was optimized from approximately 0.2g of feline epididymal adipose tissue for a treatment dose of 10(6)-10(7) ASCs/kg. The ASC yield was determined for three digestions, 0.1% collagenase in medium for 30min (Classic), 0.3% collagenase in buffer for 30min (New) and 0.3% collagenase in buffer for 1h (Hour). After isolation by the new tissue digestion, continuously cultured ASCs (fresh) and cells recovered and expanded after cryostorage at P0 (revitalized) were characterized up to cell passage (P) 5. Outcomes included CD9, CD29, CD44, CD90 and CD105 expression, cell doublings and doubling times, fibroblastic, adipogenic and osteogenic colony forming unit (CFU) frequency percentages and lineage-specific target gene expression after induction. The New digestion had the highest CFU yield, and about 7x10(6) ASCs/kg were available within three cell passages (P2). Compared to earlier passages, target surface antigen expression was lowest in fresh P5 cells, and fresh and revitalized P3-5 cells had slower expansion. Fresh and revitalized P1 ASCs had higher CFU frequency percentages and lineage-specific gene expression than P3. The New method described in this study was most efficient for feline epididymal ASC isolation and did not alter in vitro cell behavior. Fresh and revitalized P0-P2 feline ASCs may be most effective for preclinical and clinical trials. This study offers a potential option for ASC isolation from limited adipose tissue resources across species. PMID:24850472

Zhang, Nan; Dietrich, Marilyn A; Lopez, Mandi J

2014-08-01

182

Technical note: Alternatives to reduce adipose tissue sampling bias.  

PubMed

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

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

2014-10-01

183

Physiological activation of brown adipose tissue destabilizes thermogenin mRNA.  

PubMed

The amount of mRNA coding for the brown fat specific uncoupling protein thermogenin was followed in the brown adipose tissue of adult mice. As expected, cold exposure or norepinephrine injection caused an increase in the amount of thermogenin mRNA. However, contrary to expectation, the half-life of thermogenin mRNA was dramatically reduced, from about 18 h to about 3 h, when the mice were cold exposed. This destabilization of thermogenin mRNA was not related to the activity of protein synthesis. It was concluded that in brown adipose tissue an unusual mechanism operates which leads to a destabilization of thermogenin mRNA under the same physiological conditions which increase thermogenin gene expression. PMID:3121388

Jacobsson, A; Cannon, B; Nedergaard, J

1987-11-30

184

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

PubMed

White and brown adipose tissues (BATs), which store and burn lipids, respectively, play critical roles in energy homeostasis. Fibroblast growth factors (FGFs) are signaling proteins with diverse functions in development, metabolism, and neural function. Among 22 FGFs, FGF1, FGF10, and FGF21 play roles as adipokines, adipocyte-secreted proteins, in the development and function of white and BATs. FGF1 is a critical transducer in white adipose tissue (WAT) remodeling. The peroxisome proliferator-activated receptor ?-FGF1 axis is critical for energy homeostasis. FGF10 is essential for embryonic white adipocyte development. FGF21 activates BAT in response to cold exposure. FGF21 also stimulates the accumulation of brown-like cells in WAT during cold exposure and is an upstream effector of adiponectin, which controls systemic energy metabolism. These findings provide new insights into the roles of FGF signaling in white and BATs and potential therapeutic strategies for metabolic disorders. PMID:24605108

Ohta, Hiroya; Itoh, Nobuyuki

2014-01-01

185

Regulation of S100B in white adipose tissue by obesity in mice.  

PubMed

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

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

2014-07-01

186

Thyroid Hormone Upregulates Zinc-?2-glycoprotein Production in the Liver but Not in Adipose Tissue  

PubMed Central

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

Sim, Rafael; Hernndez, Cristina; Sez-Lpez, Cristina; Soldevila, Berta; Puig-Domingo, Manel; Selva, David M.

2014-01-01

187

Bovine dedifferentiated adipose tissue (DFAT) cells  

PubMed Central

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-assimilating adipocytes in the DMI media, with distinct lipid-droplets in the cytoplasm and with no observable lipid-free vesicles inside. Moreover, a high confluence level promoted the redifferentiation efficiency of DFAT cells. Wagyu IMF dedifferentiated DFAT cells exhibited unique adipogenesis modes in vitro, revealing a useful cell model for studying adipogenesis and lipid metabolism. PMID:23991361

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

188

Leptin is synthesized in the liver and adipose tissue of the dunlin (Calidris alpina).  

PubMed

Fat is the main source of energy for birds during a long-distance flight. Migration routes are usually divided into several steps. In stopover sites migratory birds restore energy reserves needed for continuation of migration. During a long-distance flight and when foraging at a stopover site birds should be able to assess their actual reserves accumulated in the form of fat stores. The information about energy being stored in body reserves may be provided by circulating factors involved in body mass regulation, such as adipose-derived hormone leptin. To date, little is known about the expression and potential role of leptin in birds. The aim of the present study was to determine whether leptin is synthesized in the liver and adipose tissue of the dunlin (Calidris alpina), a long-distance migrant. Western blot analysis with leptin-specific antibody detected a protein with a molecular mass of approximately 15-16 kDa in dunlin liver and adipose tissue. To our knowledge, this is the first report demonstrating leptin expression in the liver and adipose tissue of a migratory bird. This finding raises the possibility that in birds leptin may signal the status of energy reserves during migratory flight. PMID:16730725

Kochan, Zdzislaw; Karbowska, Joanna; Meissner, W?odzimierz

2006-09-15

189

Brominated dioxins and dibenzofurans in human adipose tissue. Final report  

SciTech Connect

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).

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

1990-04-11

190

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

PubMed Central

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

Viscarra, Jose Abraham; Ortiz, Rudy Martin

2013-01-01

191

Controlled release of BMP-2 using a heparin-conjugated carrier system reduces in vivo adipose tissue formation.  

PubMed

There is growing concern about unwanted effects associated with the clinical use of recombinant human bone morphogenetic protein-2 (rhBMP-2) at high concentrations, including cyst-like bone formation and excessive fatty marrow formation. We, therefore, evaluated the induction of mineralized/adipose tissue formation and the bone-healing pattern associated with the controlled release of E. coli-derived rhBMP-2 (ErhBMP-2) by a heparin-conjugated fibrin (HCF) system using ectopic and orthotopic in vivo models, respectively. In the ectopic transplantation model, mineralized tissue formed at the most superficial layer of the transplanted area and on the surfaces of grafted materials, and most of the interstitial space within the transplanted area was filled with excessive adipose tissue specifically at sites that received ErhBMP-2. However, sites that received ErhBMP-2 and HCF showed significantly increased mineralized tissue formation and decreased adipose tissue formation compared to the normal fibrin system with ErhBMP-2. In the orthotopic (calvarial defect) model, controlled release of ErhBMP-2 induced by HCF significantly reduced adipose tissue formation within the defect area compared to the clinically approved absorbable collagen sponge. From these results, it can be concluded that the use of a HCF system loaded with ErhBMP-2 may reduce adipose tissue formation and enhance mineralized tissue formation. 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014. PMID:24764177

Lee, Jung-Seok; Lee, Sun-Kyoung; Kim, Byung-Soo; Im, Gun-Il; Cho, Kyoo-Sung; Kim, Chang-Sung

2014-04-25

192

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

PubMed Central

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

2012-01-01

193

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

PubMed Central

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

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

2013-01-01

194

Effect of High-fat or High-glucose Diet on Obesity and Visceral Adipose Tissue in Mice.  

PubMed

Objective To investigate the effect of high-fat or high-glucose diet on obesity and visceral adipose tissue in C57BL/6 mice. Methods Four-week-old C57BL/6 mice were allocated into normal diet group,high-fat diet group,and high-glucose diet group according to the random number table until 20 weeks old. Body weight,epididymal adipose tissue weight,blood leptin,fat infiltration in liver,M1/M2 macrophage subtypes,and monocyte chemoattractant protein-1 mRNA in epididymal adipose tissues were measured. Results Compared with normal diet group,body weight,epididymal adipose tissue weight,and leptin concentration in high fat diet group at 20 weeks were significantly increased(P<0.05),and oil red O staining showed more prominent adipocyte infiltration in liver in high-fat diet group than those in normal diet and high-glucose diet group. However,no apparent differences were seen in high-glucose diet group at 20 weeks in terms of body weight,epididymal adipose tissue weight and leptin concentration. In high-fat diet group,the macrophages infiltration in epididymal adipose tissue increased with time and the percentage of M2 macrophage decreased in high-fat diet group than that in high-glucose diet group(P<0.05). Compared with normal diet group,monocyte chemoattractant protein-1 mRNA expression increased significantly in high-fat diet group(P<0.05). In high-glucose group,however,no significant differences were discerned(P>0.05).Conclusion High-fat diet,rather than 60% high glucose diet,will lead to obesity and macrophage infiltration in adipose tissues. PMID:25556734

Tang, Li-Li; Tang, Xiao-Han; Li, Xia; Yu, Hai-Bo; Xie, Zhi-Guo; Liu, Xin-Yuan; Zhou, Zhi-Guang

2014-12-30

195

Adipose tissue and vascular inflammation in coronary artery disease  

PubMed Central

Obesity has become an important public health issue in Western and developing countries, with well known metabolic and cardiovascular complications. In the last decades, evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences. As a consequence of the expansion of fat depots, in obese subjects, adipose tissue cells develope a phenotypic modification, which turns into a change of the secretory output. Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling, vascular biology and, moreover, participate to the systemic inflammatory response, which characterizes obesity and metabolic syndrome. This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events. A great number of adipocytokines have been described recently, linking inflammatory mileu and vascular pathology. The understanding of these pathways is crucial not only from a pathophysiological point of view, but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets. The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease. PMID:25068015

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

2014-01-01

196

Adipose tissue and vascular inflammation in coronary artery disease.  

PubMed

Obesity has become an important public health issue in Western and developing countries, with well known metabolic and cardiovascular complications. In the last decades, evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences. As a consequence of the expansion of fat depots, in obese subjects, adipose tissue cells develope a phenotypic modification, which turns into a change of the secretory output. Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling, vascular biology and, moreover, participate to the systemic inflammatory response, which characterizes obesity and metabolic syndrome. This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events. A great number of adipocytokines have been described recently, linking inflammatory mileu and vascular pathology. The understanding of these pathways is crucial not only from a pathophysiological point of view, but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets. The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease. PMID:25068015

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

2014-07-26

197

Berberine activates thermogenesis in white and brown adipose tissue.  

PubMed

Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue formation and function increases energy expenditure and hence may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicinal plant Coptis chinensis. Here we show that BBR increases energy expenditure, limits weight gain, improves cold tolerance and enhances brown adipose tissue (BAT) activity in obese db/db mice. BBR markedly induces the development of brown-like adipocytes in inguinal, but not epididymal adipose depots. BBR also increases expression of UCP1 and other thermogenic genes in white and BAT and primary adipocytes via a mechanism involving AMPK and PGC-1?. BBR treatment also inhibits AMPK activity in the hypothalamus, but genetic activation of AMPK in the ventromedial nucleus of the hypothalamus does not prevent BBR-induced weight loss and activation of the thermogenic programme. Our findings establish a role for BBR in regulating organismal energy balance, which may have potential therapeutic implications for the treatment of obesity. PMID:25423280

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

2014-01-01

198

Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPAR? activation to decrease diet-induced obesity.  

PubMed

De novo lipogenesis in adipocytes, especially with high fat feeding, is poorly understood. We demonstrate that an adipocyte lipogenic pathway encompassing fatty acid synthase (FAS) and PexRAP (peroxisomal reductase activating PPAR?) modulates endogenous PPAR? activation and adiposity. Mice lacking FAS in adult adipose tissue manifested increased energy expenditure, increased brown fat-like adipocytes in subcutaneous adipose tissue, and resistance to diet-induced obesity. FAS knockdown in embryonic fibroblasts decreased PPAR? transcriptional activity and adipogenesis. FAS-dependent alkyl ether phosphatidylcholine species were associated with PPAR? and treatment of 3T3-L1 cells with one such ether lipid increased PPAR? transcriptional activity. PexRAP, a protein required for alkyl ether lipid synthesis, was associated with peroxisomes and induced during adipogenesis. PexRAP knockdown in cells decreased PPAR? transcriptional activity and adipogenesis. PexRAP knockdown in mice decreased expression of PPAR?-dependent genes and reduced diet-induced adiposity. These findings suggest that inhibiting PexRAP or related lipogenic enzymes could treat obesity and diabetes. PMID:22863804

Lodhi, Irfan J; Yin, Li; Jensen-Urstad, Anne P L; Funai, Katsuhiko; Coleman, Trey; Baird, John H; El Ramahi, Meral K; Razani, Babak; Song, Haowei; Fu-Hsu, Fong; Turk, John; Semenkovich, Clay F

2012-08-01

199

Inhibiting Adipose Tissue Lipogenesis Reprograms Thermogenesis and PPAR? Activation to Decrease Diet-induced Obesity  

PubMed Central

SUMMARY De novo lipogenesis in adipocytes, especially with high fat feeding, is poorly understood. We demonstrate that an adipocyte lipogenic pathway encompassing fatty acid synthase (FAS) and PexRAP (Peroxisomal Reductase Activating PPAR?) modulates endogenous PPAR? activation and adiposity. Mice lacking FAS in adult adipose tissue manifested increased energy expenditure, increased brown fat-like adipocytes in subcutaneous adipose tissue, and resistance to diet-induced obesity. FAS knockdown in embryonic fibroblasts decreased PPAR? transcriptional activity and adipogenesis. FAS-dependent alkyl ether phosphatidylcholine species were associated with PPAR? and treatment of 3T3-L1 cells with one such ether lipid increased PPAR? transcriptional activity. PexRAP, a protein required for alkyl ether lipid synthesis, was associated with peroxisomes and induced during adipogenesis. PexRAP knockdown in cells decreased PPAR? transcriptional activity and adipogenesis. PexRAP knockdown in mice decreased expression of PPAR?dependent genes and reduced diet-induced adiposity. These findings suggest that inhibiting PexRAP or related lipogenic enzymes could treat obesity and diabetes. PMID:22863804

Lodhi, Irfan J.; Yin, Li; Jensen-Urstad, Anne P. L.; Funai, Katsuhiko; Coleman, Trey; Baird, John H.; El Ramahi, Meral K.; Razani, Babak; Song, Haowei; Fu-Hsu, Fong; Turk, John; Semenkovich, Clay F.

2012-01-01

200

Combined effects of insulin treatment and adipose tissue-specific agouti expression on the development?of?obesity  

PubMed Central

The agouti gene product is a secreted protein that acts in a paracrine manner to regulate coat color in mammals. Several dominant mutations at the agouti locus in mice cause the ectopic, ubiquitous expression of agouti, resulting in a condition similar to adult-onset obesity and non-insulin-dependent diabetes mellitus. The human agouti protein is 85% homologous to mouse agouti; however, unlike the mouse agouti gene, human agouti is normally expressed in adipose tissue. To address whether expression of agouti in human adipose tissue is physiologically relevant, transgenic mice were generated that express agouti in adipose tissue. Similar to most humans, these mice do not become obese or diabetic. However, we found that daily insulin injections significantly increased weight gain in the transgenic lines expressing agouti in adipose tissue, but not in nontransgenic mice. These results suggest that insulin triggers the onset of obesity and that agouti expression in adipose tissue potentiates this effect. Accordingly, the investigation of agoutis role in obesity and non-insulin-dependent diabetes mellitus in mice holds significant promise for understanding the pathophysiology of human obesity. PMID:9023357

Mynatt, R.?L.; Miltenberger, R.?J.; Klebig, M.?L.; Zemel, M.?B.; Wilkinson, J.?E.; Wilkison, W.?O.; Woychik, R.?P.

1997-01-01

201

Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway.  

PubMed

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 defined 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 ?-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 comorbidity 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. Because resulting beige/brite cells exhibit antiobesity and antidiabetic effects, nitrate may be an effective means of inducing the browning response in adipose tissue to treat the metabolic syndrome. PMID:25249574

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

2015-02-01

202

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

PubMed

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

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

2014-11-01

203

Two types of brown adipose tissue in humans  

PubMed Central

During the last years the existence of metabolically active brown adipose tissue in adult humans has been widely accepted by the research community. Its unique ability to dissipate chemical energy stored in triglycerides as heat makes it an attractive target for new drugs against obesity and its related diseases. Hence the tissue is now subject to intense research, the hypothesis being that an expansion and/or activation of the tissue is associated with a healthy metabolic phenotype. Animal studies provide evidence for the existence of at least two types of brown adipocytes. Apart from the classical brown adipocyte that is found primarily in the interscapular region where it constitutes a thermogenic organ, a second type of brown adipocyte, the so-called beige adipocyte, can appear within white adipose tissue depots. The fact that the two cell types develop from different precursors suggests that they might be recruited and stimulated by different cues and therefore represent two distinct targets for therapeutic intervention. The aim of this commentary is to discuss recent work addressing the question whether also humans possess two types of brown adipocytes and to highlight some issues when looking for molecular markers for such cells. PMID:24575372

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

2014-01-01

204

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

PubMed Central

Background Prior studies have demonstrated a link between air pollution and metabolic diseases such as type II diabetes. Changes in adipose tissue and its mitochondrial content/function are closely associated with the development of insulin resistance and attendant metabolic complications. We investigated changes in adipose tissue structure and function in brown and white adipose depots in response to chronic ambient air pollutant exposure in a rodent model. Methods Male ApoE knockout (ApoE-/-) mice inhaled concentrated fine ambient PM (PM < 2.5 ?m in aerodynamic diameter; PM2.5) or filtered air (FA) for 6 hours/day, 5 days/week, for 2 months. We examined superoxide production by dihydroethidium staining; inflammatory responses by immunohistochemistry; and changes in white and brown adipocyte-specific gene profiles by real-time PCR and mitochondria by transmission electron microscopy in response to PM2.5 exposure in different adipose depots of ApoE-/- mice to understand responses to chronic inhalational stimuli. Results Exposure to PM2.5 induced an increase in the production of reactive oxygen species (ROS) in brown adipose depots. Additionally, exposure to PM2.5 decreased expression of uncoupling protein 1 in brown adipose tissue as measured by immunohistochemistry and Western blot. Mitochondrial number was significantly reduced in white (WAT) and brown adipose tissues (BAT), while mitochondrial size was also reduced in BAT. In BAT, PM2.5 exposure down-regulated brown adipocyte-specific genes, while white adipocyte-specific genes were differentially up-regulated. Conclusions PM2.5 exposure triggers oxidative stress in BAT, and results in key alterations in mitochondrial gene expression and mitochondrial alterations that are pronounced in BAT. We postulate that exposure to PM2.5 may induce imbalance between white and brown adipose tissue functionality and thereby predispose to metabolic dysfunction. PMID:21745393

2011-01-01

205

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

Microsoft Academic Search

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

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

2011-01-01

206

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

PubMed Central

Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen FVB/N (TAg) mouse model of triple-negative breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e. during the in situ carcinoma stage). To further understand the mechanisms underlying how accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2 and Acly was found in the adipocyte, rather than the epithelial fraction. Surprisingly, metabolic gene expression was not significantly increased in visceral adipose depots of socially isolated female mice. As expected, increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin secretion from this adipose depot. Furthermore, application of media that had been cultured with isolated mouse mammary adipose tissue (conditioned media) resulted in increased proliferation of mammary cancer cells relative to group-housed conditioned media. These results suggest that exposure to a chronic stressor (social isolation) results in specific metabolic reprogramming in mammary gland adipocytes that in turn contributes to increased proliferation of adjacent pre-invasive malignant epithelial cells. Metabolites and/or tumor growth-promoting proteins secreted from adipose tissue could identify biomarkers and/or targets for preventive intervention in breast cancer. PMID:23780289

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

2013-01-01

207

Macrophage infiltration and cytokine release in adipose tissue: angiogenesis or inflammation?  

Microsoft Academic Search

The observation that obese adipose tissue was infiltrated by macrophages triggered the concept that type 2 diabetes is a low-grade inflammatory disease. In this review, we re-evaluate the role of macrophage infiltration, TNFa secretion and IKKb\\/JNK signalling in insulin resistance, and put forward the hypothesis that these intermediates are important mediators of adipose tissue angiogenesis. Expansion of adipose tissue vasculature

Lindsay E. Wu; Samantha L. Hocking; David E. James

2010-01-01

208

Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis.  

PubMed

Mitochondrial uncoupling protein 1 (UCP1) is enriched within interscapular brown adipose tissue (iBAT) and beige (also known as brite) adipose tissue, but its thermogenic potential is reduced with obesity and type 2 diabetes for reasons that are not understood. Serotonin (5-hydroxytryptamine, 5-HT) is a highly conserved biogenic amine that resides in non-neuronal and neuronal tissues that are specifically regulated via tryptophan hydroxylase 1 (Tph1) and Tph2, respectively. Recent findings suggest that increased peripheral serotonin and polymorphisms in TPH1 are associated with obesity; however, whether this is directly related to reduced BAT thermogenesis and obesity is not known. We find that Tph1-deficient mice fed a high-fat diet (HFD) are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by BAT. Small-molecule chemical inhibition of Tph1 in HFD-fed mice mimics the benefits ascribed to Tph1 genetic deletion, effects that depend on UCP1-mediated thermogenesis. The inhibitory effects of serotonin on energy expenditure are cell autonomous, as serotonin blunts ?-adrenergic induction of the thermogenic program in brown and beige adipocytes in vitro. As obesity increases peripheral serotonin, the inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities. PMID:25485911

Crane, Justin D; Palanivel, Rengasamy; Mottillo, Emilio P; Bujak, Adam L; Wang, Huaqing; Ford, Rebecca J; Collins, Andrew; Blmer, Regje M; Fullerton, Morgan D; Yabut, Julian M; Kim, Janice J; Ghia, Jean-Eric; Hamza, Shereen M; Morrison, Katherine M; Schertzer, Jonathan D; Dyck, Jason R B; Khan, Waliul I; Steinberg, Gregory R

2015-02-01

209

Up-regulation of the Sirtuin 1 (Sirt1) and peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?) genes in white adipose tissue of Id1 protein-deficient mice: implications in the protection against diet and age-induced glucose intolerance.  

PubMed

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

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

2014-10-17

210

KSRP and MicroRNA 145 are negative regulators of lipolysis in white adipose tissue.  

PubMed

White adipose tissue (WAT) releases fatty acids from stored triacylglycerol for an energy source. Here, we report that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regulates gene expression at multiple levels, enhances lipolysis in epididymal WAT (eWAT) because of the upregulation of genes promoting lipolytic activity. Expression of microRNA 145 (miR-145) is decreased because of impaired primary miR-145 processing in Ksrp(-/-) eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58, activators of lipolytic activity, and forced expression of miR-145 attenuates lipolysis. This study reveals a novel in vivo function of KSRP in controlling adipose lipolysis through posttranscriptional regulation of miR-145 expression. PMID:24732799

Lin, Yi-Yu; Chou, Chu-Fang; Giovarelli, Matteo; Briata, Paola; Gherzi, Roberto; Chen, Ching-Yi

2014-06-01

211

KSRP and MicroRNA 145 Are Negative Regulators of Lipolysis in White Adipose Tissue  

PubMed Central

White adipose tissue (WAT) releases fatty acids from stored triacylglycerol for an energy source. Here, we report that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regulates gene expression at multiple levels, enhances lipolysis in epididymal WAT (eWAT) because of the upregulation of genes promoting lipolytic activity. Expression of microRNA 145 (miR-145) is decreased because of impaired primary miR-145 processing in Ksrp?/? eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58, activators of lipolytic activity, and forced expression of miR-145 attenuates lipolysis. This study reveals a novel in vivo function of KSRP in controlling adipose lipolysis through posttranscriptional regulation of miR-145 expression. PMID:24732799

Lin, Yi-Yu; Chou, Chu-Fang; Giovarelli, Matteo; Briata, Paola; Gherzi, Roberto

2014-01-01

212

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...

213

Role of Perivascular and Visceral Adipose Tissues in Murine Models of Obesity and Atherosclerosis: A Dissertation.  

E-print Network

??Expansion of visceral adipose tissue correlates with the metabolic syndrome and increased cardiovascular risk. Hypertrophied visceral fat becomes inflamed, causing increased lipolysis, decreased triglyceride storage, (more)

Fitzgibbons, Timothy P.

2012-01-01

214

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

PubMed

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

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

2015-01-01

215

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

PubMed Central

Frequent sugar-sweetened beverage (SSB) intake has been consistently associated with increased adiposity and cardio-metabolic risk, whereas the association with diet beverages is more mixed. We examined how these beverages associate with regional abdominal adiposity measures, specifically visceral adipose tissue (VAT). In a cross-sectional analysis of 791 non-Hispanic white men and women aged 18-70 we examined how beverage consumption habits obtained from a food frequency questionnaire associate with overall and abdominal adiposity measures from MRI. With increasing frequency of SSB intake we observed increases in waist circumference (WC) and the proportion of visceral to subcutaneous abdominal adipose tissue (VAT%), with no change in total body fat (TBF %) or BMI. Greater frequency of diet beverage intake was associated with greater WC, BMI and TBF %, but was not associated with variation in visceral adiposity We conclude that increased frequency of SSB consumption is associated with a more adverse abdominal adipose tissue deposition pattern. PMID:21901024

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

2012-01-01

216

Intermuscular Adipose Tissue and Metabolic Associations in HIV Infection  

PubMed Central

Intermuscular adipose tissue (IMAT) is associated with metabolic abnormalities similar to those associated with visceral adipose tissue (VAT). Increased IMAT has been found in obese human immunodeficiency virus (HIV)-infected women. We hypothesized that IMAT, like VAT, would be similar or increased in HIV-infected persons compared with healthy controls, despite decreases in subcutaneous adipose tissue (SAT) found in HIV infection. In the second FRAM (Study of Fat Redistribution and Metabolic Change in HIV infection) exam, we studied 425 HIV-infected subjects and 211 controls (from the Coronary Artery Risk Development in Young Adults study) who had regional AT and skeletal muscle (SM) measured by magnetic resonance imaging (MRI). Multivariable linear regression identified factors associated with IMAT and its association with metabolites. Total IMAT was 51% lower in HIV-infected participants compared with controls (P = 0.003). The HIV effect was attenuated after multivariable adjustment (to ?28%, P < 0.0001 in men and ?3.6%, P = 0.70 in women). Higher quantities of leg SAT, upper-trunk SAT, and VAT were associated with higher IMAT in HIV-infected participants, with weaker associations in controls. Stavudine use was associated with lower IMAT and SAT, but showed little relationship with VAT. In multivariable analyses, regional IMAT was associated with insulin resistance and triglycerides (TGs). Contrary to expectation, IMAT is not increased in HIV infection; after controlling for demographics, lifestyle, VAT, SAT, and SM, HIV+ men have lower IMAT compared with controls, whereas values for women are similar. Stavudine exposure is associated with both decreased IMAT and SAT, suggesting that IMAT shares cellular origins with SAT. PMID:20539305

Scherzer, Rebecca; Shen, Wei; Heymsfield, Steven B.; Lewis, Cora E.; Kotler, Donald P.; Punyanitya, Mark; Bacchetti, Peter; Shlipak, Michael G.; Grunfeld, Carl

2013-01-01

217

Divergent phenotype of rat thoracic and abdominal perivascular adipose tissues.  

PubMed

Perivascular adipose tissue (PVAT) is implicated as a source of proatherogenic cytokines. Phenotypic differences in local PVAT depots may contribute to differences in disease susceptibility among arteries and even regions within an artery. It has been proposed that PVAT around the abdominal and thoracic aorta shares characteristics of white and brown adipose tissue (BAT), respectively; however, a detailed comparison of the phenotype of these PVAT depots has not been performed. Using young and older adult rats, we compared the phenotype of PVATs surrounding the abdominal and thoracic aorta to each other and also to epididymal white and subscapular BAT. Compared with young rats, older rats exhibited greater percent body fat (34.5 3.1 vs. 10.4 0.9%), total cholesterol (112.2 7.5 vs. 58.7 6.3 mg/dl), HOMA-insulin resistance (1.7 0.1 vs. 0.9 0.1 a.u.), as well as reduced ACh-induced relaxation of the aorta (maximal relaxation: 54 10 vs. 77 6%) (all P < 0.05). Expression of inflammatory genes and markers of immune cell infiltration were greater in abdominal PVAT than in thoracic PVAT, and overall, abdominal and thoracic PVATs resembled the phenotype of white adipose tissue (WAT) and BAT, respectively. Histology and electron microscopy indicated structural similarity between visceral WAT and abdominal PVAT and between BAT and thoracic PVAT. Our data provide evidence that abdominal PVAT is more inflamed than thoracic PVAT, a difference that was by and large independent of sedentary aging. Phenotypic differences in PVAT between regions of the aorta may be relevant in light of the evidence in large animals and humans that the abdominal aorta is more vulnerable to atherosclerosis than the thoracic aorta. PMID:23389108

Padilla, Jaume; Jenkins, Nathan T; Vieira-Potter, Victoria J; Laughlin, M Harold

2013-04-01

218

Brown Adipose Tissue in the Buccal Fat Pad during Infancy  

PubMed Central

Background The buccal fat pad (BFP) is an encapsulated mass of adipose tissue thought to enhance the sucking capabilities of the masticatory muscles during infancy. To date, no conclusive evidence has been provided as to the composition of the BFP in early postnatal life. Objective The purpose of this study was to examine whether the BFP of neonates and infants is primarily composed of white adipose tissue (WAT) or brown adipose tissue (BAT). Materials and Methods The percentage of fat in the BFP in 32 full-term infants (16 boys and 16 girls), aged one day to 10.6 months, was measured using magnetic resonance imaging (MRI) determinations of fat fraction. Results BFP fat fraction increased with age (r?=?0.67; P<.0001) and neonates had significantly lower values when compared to older infants; 72.69.6 vs. 91.82.4, P<.0001. Multiple regression analysis indicated that the age-dependent relationship persisted after accounting for gender, gestational age, and weight percentile (P?=?.001). Two subjects (aged one and six days) depicted a change in the MRI characteristics of the BFP from primarily BAT to WAT at follow-up examinations two to six weeks later, respectively. Histological post-mortem studies of a 3 day and 1.1 month old revealed predominantly BAT and WAT in the BFP, respectively. Conclusion The BFP is primarily composed of BAT during the first weeks of life, but of WAT thereafter. Studies are needed to investigate the contributions of BAT in the BFP to infant feeding and how it is altered by postnatal nutrition. PMID:24586852

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

2014-01-01

219

Regulation of HIF-1? activity in adipose tissue by obesity-associated factors: adipogenesis, insulin, and hypoxia  

PubMed Central

The transcription factor HIF-1? activity is increased in adipose tissue to contribute to chronic inflammation in obesity. However, its upstream and downstream events remain to be characterized in adipose tissue in obesity. We addressed this issue by investigating adipocyte HIF-1? activity in response to obesity-associated factors, such as adipogenesis, insulin, and hypoxia. In adipose tissue, both HIF-1? mRNA and protein were increased by obesity. The underlying mechanism was investigated in 3T3-L1 adipocytes. HIF-1? mRNA and protein were augmented by adipocyte differentiation. In differentiated adipocytes, insulin further enhanced HIF-1? in both levels. Hypoxia enhanced only HIF-1? protein, not mRNA. PI3K and mTOR activities are required for the HIF-1? expression. Function of HIF-1? protein was investigated in the regulation of VEGF gene transcription. ChIP assay shows that HIF-1? binds to the proximal hypoxia response element in the VEGF gene promoter, and its function is inhibited by a corepressor composed of HDAC3 and SMRT. These observations suggest that of the three obesity-associated factors, all of them are able to augment HIF-1? protein levels, but only two (adipogenesis and insulin) are able to enhance HIF-1? mRNA activity. Adipose tissue HIF-1? activity is influenced by multiple signals, including adipogenesis, insulin, and hypoxia in obesity. The transcriptional activity of HIF-1? is inhibited by HDAC3-SMRT corepressor in the VEGF gene promoter. PMID:21343542

He, Qing; Gao, Zhanguo; Yin, Jun; Zhang, Jin; Yun, Zhong

2011-01-01

220

Abnormal Mammary Adipose Tissue Environment of Brca1 Mutant Mice Show a Persistent Deposition of Highly Vascularized Multilocular Adipocytes.  

PubMed

A major challenge to breast cancer research is the identification of alterations in the architecture and composition of the breast that are associated with breast cancer progression. The aim of the present investigation was to characterize the mammary adipose phenotype from Brca1 mutant mice in the expectation that this would shed light on the role of the mammary tissue environment in the early stages of breast tumorigenesis. We observed that histological sections of mammary tissue from adult Brca1 mutant mice abnormally display small, multilocular adipocytes that are reminiscent of brown adipose tissue (BAT) as compared to wildtype mice. Using a marker for BAT, the uncoupling protein 1 (UCP1), we demonstrated that these multilocular adipose regions in Brca1 mutant mice stain positive for UCP1. Transcriptionally, UCP1 mRNA levels in the Brca1 mutant mice were elevated greater than 50-fold compared to age-matched mammary glands from wildtype mice. Indeed, BAT has characteristics that are favorable for tumor growth, including high vascularity. Therefore, we also demonstrated that the multilocular brown adipose phenotype in the mammary fat pad of Brca1 mutant mice displayed regions of increased vascularity as evidenced by a significant increase in the protein expression of CD31, a marker for angiogenesis. This Brca1 mutant mouse model should provide a physiologically relevant context to determine whether brown adipose tissue can play a role in breast cancer development. PMID:24501658

Jones, Laundette P; Buelto, Destiney; Tago, Elaine; Owusu-Boaitey, Kwadwo E

2011-12-01

221

Energy dissipation in brown adipose tissue: from mice to men.  

PubMed

In rodents, brown adipose tissue (BAT) is a metabolic organ that produces heat in response to cold and dietary intake through mitochondrial uncoupling. For long time, BAT was considered to be solely important in small mammals and infants, however recent studies have shown that BAT is also functional in adult humans. Interestingly, the presence and/or functionality of this thermogenic tissue is diminished in obese people, suggesting a link between human BAT and body weight regulation. In the last years, evidence has also emerged for the existence of adipocytes that may have an intermediate thermogenic phenotype between white and brown adipocytes, so called brite or beige adipocytes. Together, these findings have resulted in a renewed interested in (human) brown adipose tissue and pathways to increase the activity and recruitment of these thermogenic cells. Stimulating BAT hypertrophy and hyperplasia in humans could be a potential strategy to target obesity. Here we will review suggested pathways leading to BAT activation in humans, and discuss novel putative BAT activators in rodents into human perspective. PMID:23632102

Vosselman, Maarten J; van Marken Lichtenbelt, Wouter D; Schrauwen, Patrick

2013-10-15

222

Relevance of brown adipose tissue in infancy and adolescence  

PubMed Central

Brown adipose tissue (BAT) was thought to disappear after infancy. Recent studies finding BAT in patients undergoing positron emission tomography/computed tomography (PET/CT) have renewed the interest in deciphering the relevance of this tissue in humans. Available data suggests that BAT is more prevalent in children than in adults, and that its activation during adolescence is associated to significantly less gains in weight and adiposity. Data also shows that pediatric patients with metabolically-active BAT on PET/CT examinations have significantly greater muscle volume than patients with no identifiable BAT. Both the activity and the amount of BAT increase during puberty. The magnitude of the increase is higher in boys when compared to girls, and closely related to gains in muscle volume. Hence, concurrent with the great gains in skeletal muscle during infancy and puberty, all infants and adolescents accumulate large amounts of BAT. These observations are consistent with in vitro investigations suggesting close interactions between brown adipocytes, white adipocytes, and myocites. In this review, we discuss the potential role of this tissue in regulating weight and musculoskeletal development in children. PMID:23090604

Gilsanz, Vicente; Hu, Houchun H.; Kajimura, Shingo

2013-01-01

223

Coxsackie and Adenovirus Receptor is increased in adipose tissue of obese subjects: A role for adenovirus infection?  

PubMed

Context: The Coxsackie and Adenovirus Receptor (CAR) was originally identified as a common receptor for coxsackie B viruses and type C adenoviruses Objective: To investigate CAR gene expression in human adipose tissue to explore its associations with adipocyte physiology. Design and Setting: This was an ex vivo study in 91 visceral (VAT) and 109 subcutaneous adipose tissue (SAT) human samples (61 paired) obtained during elective surgical procedures Patients: Patients were recruited at the Endocrinology Service of the Hospital Universitari Dr. Josep Trueta Main outcome measure: CAR mRNA was measured in human adipose tissue samples and confirmed at protein level and in adipose tissue fractions. The effects of inflammatory stimuli on CAR gene expression were also evaluated. Results: In paired samples, CAR was 46-fold higher in VAT vs. SAT (p<0.0001), being higher also at protein level (p = 0.04). CAR was predominantly found in stromal vascular cell fraction (SVF) in both fat depots. CAR mRNA (p=0.006) and protein levels (p=0.01) in VAT were significantly increased in obese vs. non-obese subjects. In fact, CAR mRNA levels in SAT were positively associated with BMI (r=0.26; p=0.008) and percent fat mass (r=0.28; p=0.004). In VAT, MGLL, FSP27, AKAP, omentin, TKT, S14 and FABP contributed independently to CAR mRNA variation after adjusting for age and BMI. Macrophage-conditioned medium led to increased CAR gene expression in mature adipocytes in vitro. Conclusions: The increased expression of CAR in adipose tissue from obese subjects, mainly in SVFs, suggests that CAR might play a role in adipose tissue dysfunction given its dual associations with adipogenic and inflammatory genes. PMID:25459915

Serrano, Marta; Moreno, Mara; Bassols, Judit; Moreno-Navarrete, Jos Mara; Ortega, Francisco; Ricart, Wifredo; Manuel Fernndez-Real, Jos

2014-12-01

224

New Adipose Tissue Formation by Human Adipose-Derived Stem Cells with Hyaluronic Acid Gel in Immunodeficient Mice  

PubMed Central

Background: Currently available injectable fillers have demonstrated limited durability. This report proposes the in vitro culture of human adipose-derived stem cells (hASCs) on hyaluronic acid (HA) gel for in vivo growth of de novo adipose tissue. Methods: For in vitro studies, hASCs were isolated from human adipose tissue and were confirmed by multi-lineage differentiation and flow cytometry. hASCs were cultured on HA gel. The effectiveness of cell attachment and proliferation on HA gel was surveyed by inverted light microscopy. For in vivo studies, HA gel containing hASCs, hASCs without HA gel, HA gel alone were allocated and subcutaneously injected into the subcutaneous pocket in the back of nude mice (n=6) in each group. At eight weeks post-injection, the implants were harvested for histological examination by hematoxylin and eosin (H&E) stain, Oil-Red O stain and immunohistochemical staining. The human-specific Alu gene was examined. Results: hASCs were well attachment and proliferation on the HA gel. In vivo grafts showed well-organized new adipose tissue on the HA gel by histologic examination and Oil-Red O stain. Analysis of neo-adipose tissues by PCR revealed the presence of the Alu gene. This study demonstrated not only the successful culture of hASCs on HA gel, but also their full proliferation and differentiation into adipose tissue. Conclusions: The efficacy of injected filler could be permanent since the reduction of the volume of the HA gel after bioabsorption could be replaced by new adipose tissue generated by hASCs. This is a promising approach for developing long lasting soft tissue filler. PMID:25589892

Huang, Shu-Hung; Lin, Yun-Nan; Lee, Su-Shin; Chai, Chee-Yin; Chang, Hsueh-Wei; Lin, Tsai-Ming; Lai, Chung-Sheng; Lin, Sin-Daw

2015-01-01

225

Naringenin suppresses macrophage infiltration into adipose tissue in an early phase of high-fat diet-induced obesity.  

PubMed

Obese adipose tissue is characterized by increased macrophage infiltration, which results in chronic inflammation in adipose tissue and leads to obesity-related diseases such as type 2 diabetes mellitus and atherosclerosis. The regulation of macrophage infiltration into adipose tissue is an important strategy for preventing and treating obesity-related diseases. In this study, we report that naringenin, a citrus flavonoid, suppressed macrophage infiltration into adipose tissue induced by short-term (14days) feeding of a high-fat diet in mice; although naringenin did not show any differences in high-fat diet-induced changes of serum biochemical parameters in this short administration period. Naringenin suppressed monocyte chemoattractant protein-1 (MCP-1) in adipose tissue, and this effect was mediated in part through inhibition of c-Jun NH2-terminal kinase pathway. Naringenin also inhibited MCP-1 expression in adipocytes, macrophages, and a co-culture of adipocytes and macrophages. Our results suggest a mechanism by which daily consumption of naringenin may exhibit preventive effects on obesity-related diseases. PMID:25450363

Yoshida, Hiroki; Watanabe, Hideaki; Ishida, Akiko; Watanabe, Wataru; Narumi, Keiko; Atsumi, Toshiyuki; Sugita, Chihiro; Kurokawa, Masahiko

2014-10-18

226

Effect of bone morphogenetic protein 7 on differentiation of adipose derived mesenchymal stem cells into brown adipocytes in rats.  

PubMed

Objective To evaluate the effect of bone morphogenetic protein(BMP7)on the differentiation of adipose derived mesenchymal stem cells(AD-MSCs)isolated from different adipose tissues into brown adipocytes in rats. Methods Primary AD-MSCs were isolated from rate interscapular brown adipose tissue(iBAT),inguinal subcutaneous white adipose tissue(sWAT),and epididymal white adipose tissue(eWAT),respectively,and then cultivated in vitro. Differentiation of AD-MSCs into brown adipocytes was induced by BMP7. The characteristics of brown adipocytes were detected by immunofluorescence staining and oil red staining of cells. The expression levels of brown adipocyte-related genes were detected by polymerase chain reaction. Results AD-MSCs from iBAT and sWAT were differentiated into cluster multilocular cells,which were stained red by oil red "O"staining and showed uncoupling protein 1-positive by immunofluorescent staining method. AD-MSCs from eWAT had a small number of scattered multilocular cells and showed uncoupling protein 1-negative. The results of reverse transcription-polymerase chain reaction showed that the uncoupling protein 1 gene was highly expressed in the iBAT group and sWAT group but was negative in the eWAT group. Conclusion AD-MSCs isolated from different adipose tissues in rats have different gene expression profiles and differentiation potentials. PMID:25556742

Zheng, Long; Liu, Jian-Min; Wang, Jun-Xia; Li, Min-Zhi; Lian, Wei-Guang; Xie, Peng; Liu, Shu-Feng

2014-12-30

227

Soy isoflavones in nutritionally relevant amounts have varied nutrigenomic effects on adipose tissue.  

PubMed

Soy consumption has been suggested to afford protection from cardiovascular disease (CVD). Indeed, accumulated albeit controversial evidence suggests that daily consumption of ?25 g of soy protein with its associated phytochemicals intact can improve lipid profiles in hypercholesterolemic humans. However, the belief that soy foods and supplements positively impact human health has become increasingly controversial among the general public because of the reported estrogenic activities of soy isoflavones. In this study, we investigated the nutrigenomic actions of soy isoflavones (in nutritionally-relevant amounts) with a specific focus on the adipose tissue, due to its pivotal role in cardiometabolism. Young C57BL/6 mice were maintained for eight weeks under two different diet regimes: (1) purified control diet; or (2) purified control diet supplemented with 0.45 g% soybean dry purified extract (a genistein/daidzein mix). Soy isoflavones increased plasma total cholesterol concentrations and decreased triglyceride ones. Circulating leptin levels was also increased by soy consumption. Differentially expressed genes in adipose tissue were classified according to their role(s) in cellular or metabolic pathways. Our data show that soy isoflavones, administered in nutritionally-relevant amounts, have diverse nutrigenomic effects on adipose tissue. Taking into account the moderate average exposure to such molecules, their impact on cardiovascular health needs to be further investigated to resolve the issue of whether soy consumption does indeed increase or decrease cardiovascular risk. PMID:25647572

Giordano, Elena; Dvalos, Alberto; Crespo, Maria Carmen; Tom-Carneiro, Joao; Gmez-Coronado, Diego; Visioli, Francesco

2015-01-01

228

The Role of HIV and Monocytes/Macrophages in Adipose Tissue Biology  

PubMed Central

Objective To assess the role of HIV and monocytes/macrophages in adipose tissue dysregulation. Methods Cross-sectional study in 5 groups: HIV seronegative, HIV+ antiretroviral therapy (ART)-naive, HIV+ nonlipoatrophic on zidovudine- and/or stavudine-containing ART, HIV+ lipoatrophic on similar ART, and HIV+ on abacavir- or tenofovir-containing ART. HIV DNA in circulating monocyte subsets was quantitated by real-time polymerase chain reaction. Biopsied subcutaneous fat was examined for macrophage content by CD68 staining. Isolated adipocytes and macrophages were cultured and the supernatant assayed for secretory products by Luminex multiplex cytokine technology. Results Sixty-nine subjects were enrolled. Lipoatrophic subjects had higher median HIV DNA levels (270.5 copies/106 cells) in circulating peripheral CD14+CD16+ co-expressing monocyte subsets compared with subjects who were ART-naive (25.0 copies), non-lipoatrophic (15.0 copies), or on abacavir/tenofovir (57.5 copies), P < 0.01. Group differences in adipocytes and adipose macrophage content were marginal. Although adipocyte secretory products were similar, HIV-infected subjects had higher adipose macrophagederived interleukin (IL)-12p40, IL-6, IL-8, and monocyte inflammatory protein 1 alpha and lower eotaxin and interferon gamma levels than HIV seronegative subjects (P < 0.05). Within HIV-infected subjects, adipose macrophage secretory products were comparable between subjects naive with ART versus those on ART. Conclusions Circulating HIV-infected and proinflammatory CD14+CD16+ monocyte subsets contribute to the pathogenesis of HIV-associated lipoatrophy. Among HIV-infected individuals, macrophages, rather than adipocytes, are the primary source of low-grade inflammation in subcutaneous adipose tissue. HIV infection modifies these macrophages to a more proinflammatory phenotype, and these changes are not substantially mitigated by the use of ART. PMID:24091690

Shikuma, Cecilia M.; Gangcuangco, Louie Mar A.; Killebrew, Deirdre A.; LiButti, Daniel E.; Chow, Dominic C.; Nakamoto, Beau K.; Liang, Chin Yuan; Milne, Cris I.P.; Ndhlovu, Lishomwa C.; Barbour, Jason D.; Shiramizu, Bruce T.; Gerschenson, Mariana

2014-01-01

229

Relationships between Adipose Tissue and Psoriasis, with or without Arthritis  

PubMed Central

Psoriasis (Pso) is a common chronic cutaneous inflammatory disease involving the skin that is associated with serious comorbidities. Comorbidities in Pso include psoriatic arthritis (PsA), reduced quality of life, malignancy, depression, but also a constellation of associated conditions that enhance the cardiovascular (CV) risk. Indeed, obesity is common in patients with Pso or PsA and is considered to be a risk factor for the onset of these diseases. Patients with Pso and PsA share common obesity-related complications such as metabolic syndrome (MetS), dyslipidemia, diabetes or insulin resistance, and CV diseases. Chronic inflammation in Pso and PsA partially explains the development of atherosclerosis and CV diseases. In parallel, body composition is disturbed in patients with Pso or PsA, as suggested by anthropometric measurements, while an excess of abdominal adiposity is observed in PsA, enhancing the risk of MetS and CV diseases. Adipokines may link the adipose tissue to the obesity-related complications of Pso and PsA. Indeed, altered circulating levels of the adipokines leptin, adiponectin, visfatine, and resistin have been found in patients with Pso or PsA. In addition, an excess of adipose tissue may compromise the therapeutic response to traditional drugs or biological agents in Pso and PsA. This paper reviews the comorbidities that contribute to enhanced CV risk, the body composition results, and the potential role of adipokines in systemic inflammation and energetic balance in Pso and PsA. PMID:25161652

Toussirot, ric; Aubin, Franois; Dumoulin, Gilles

2014-01-01

230

Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity.  

PubMed

Beige adipocytes in white adipose tissue (WAT) are similar to classical brown adipocytes in that they can burn lipids to produce heat. Thus, an increase in beige adipocyte content in WAT browning would raise energy expenditure and reduce adiposity. Here we report that adipose-specific inactivation of Notch1 or its signaling mediator Rbpj in mice results in browning of WAT and elevated expression of uncoupling protein 1 (Ucp1), a key regulator of thermogenesis. Consequently, as compared to wild-type mice, Notch mutants exhibit elevated energy expenditure, better glucose tolerance and improved insulin sensitivity and are more resistant to high fat diet-induced obesity. By contrast, adipose-specific activation of Notch1 leads to the opposite phenotypes. At the molecular level, constitutive activation of Notch signaling inhibits, whereas Notch inhibition induces, Ppargc1a and Prdm16 transcription in white adipocytes. Notably, pharmacological inhibition of Notch signaling in obese mice ameliorates obesity, reduces blood glucose and increases Ucp1 expression in white fat. Therefore, Notch signaling may be therapeutically targeted to treat obesity and type 2 diabetes. PMID:25038826

Bi, Pengpeng; Shan, Tizhong; Liu, Weiyi; Yue, Feng; Yang, Xin; Liang, Xin-Rong; Wang, Jinghua; Li, Jie; Carlesso, Nadia; Liu, Xiaoqi; Kuang, Shihuan

2014-08-01

231

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

Microsoft Academic Search

BACKGROUND: Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP) and Triglyceride (TG) (LAT) vs High ASP and TG (HAT). Subcutaneous (SC) and omental (OM) adipose tissues (n = 21) were analysed by microarray, and

Robin E MacLaren; Wei Cui; HuiLing Lu; Serge Simard; Katherine Cianflone

2010-01-01

232

Genetic dissection of retinoid esterification and accumulation in the liver and adipose tissue  

PubMed Central

Approximately 8090% of all retinoids in the body are stored as retinyl esters (REs) in the liver. Adipose tissue also contributes significantly to RE storage. The present studies, employing genetic and nutritional interventions, explored factors that are responsible for regulating RE accumulation in the liver and adipose tissue and how these influence levels of retinoic acid (RA) and RA-responsive gene expression. Our data establish that acyl-CoA:retinol acyltransferase (ARAT) activity is not involved in RE synthesis in the liver, even when mice are nutritionally stressed by feeding a 25-fold excess retinol diet or upon ablation of cellular retinol-binding protein type I (CRBPI), which is proposed to limit retinol availability to ARATs. Unlike the liver, where lecithin:retinol acyltransferase (LRAT) is responsible for all RE synthesis, this is not true for adipose tissue where Lrat-deficient mice display significantly elevated RE concentrations. However, when CrbpI is also absent, RE levels resemble wild-type levels, suggesting a role for CrbpI in RE accumulation in adipose tissue. Although expression of several RA-responsive genes is elevated in Lrat-deficient liver, employing a sensitive liquid chromatography tandem mass spectrometry protocol and contrary to what has been assumed for many years, we did not detect elevated concentrations of all-trans-RA. The elevated RA-responsive gene expression was associated with elevated hepatic triglyceride levels and decreased expression of Ppar? and its downstream Pdk4 target, suggesting a role for RA in these processes in vivo. PMID:24186946

Wongsiriroj, Nuttaporn; Jiang, Hongfeng; Piantedosi, Roseann; Yang, Kryscilla Jian Zhang; Kluwe, Johannes; Schwabe, Robert F.; Ginsberg, Henry; Goldberg, Ira J.; Blaner, William S.

2014-01-01

233

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

SciTech Connect

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

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

2012-06-15

234

Cholesterol content of longissmus and semimembranosus muscles and associated adipose tissues from beef, pork and lamb  

E-print Network

Trim on Muscle Tissue Cholesterol . . Effect of Species on Muscle Tissue. Effect of Cooking on Muscle Tissue. . Effect of Species on Adipose Tissue Effect of Cooking on Adipose Tissue. CONCLUSIONS REFERENCES VITA . VI . . VI I . 15 . . . 15... D rmin i n f I r Lipid extracts of each fraction were saponified by the procedure described by Rhee et al. (1982b). The procedure had to be modified to use 5 ml aliquots of the lipid extract from the lean and adipose tissues. The 5 ml extract...

Dohmann, Sharon Sue

1988-01-01

235

Endogenous ways to stimulate brown adipose tissue in humans.  

PubMed

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

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

2014-02-13

236

A decade of progress in adipose tissue macrophage biology.  

PubMed

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

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

2014-11-01

237

Treating facial soft tissue deficiency: Fat grafting and adipose-derived stem cell tissue engineering  

Microsoft Academic Search

The authors outline the limitations of fat grafting. They then describe the currently available fat culturing technique and explain how options incorporating adipose-derived stem cell technologies and growth factors will provide new modalities in treating facial soft tissue deficiency.

Ali Sajjadian; Keshav Tandav Magge

2007-01-01

238

Controlled cellular energy conversion in brown adipose tissue thermogenesis  

NASA Technical Reports Server (NTRS)

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

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

1978-01-01

239

In Vitro Cartilage Tissue Engineering Using Adipose-Derived Extracellular Matrix Scaffolds Seeded with Adipose-Derived Stem Cells  

PubMed Central

Extracellular matrix (ECM) secreted from the resident cell of tissue is an ideal biomaterial evolved by nature. Cartilage is also built from well-organized ECM components in a gel-like structure with a high collagen and proteoglycan content. Here, we explored cartilage tissue engineering using ECM scaffolds seeded with stem cells. Both scaffolds and stem cells were isolated from human adipose tissue, which is abundant and easily harvested in the human body. The human ECM scaffolds contained various endogenous bioactive factors, including transforming growth factor-beta1 (TGF-?1, 87824989?pg/g, dry ECM), insulin growth factor-1 (133191388?pg/g, dry ECM), basic fibroblast growth factor (823739572?pg/g, dry ECM), and vascular endothelial growth factor (256472749?pg/g, dry ECM). A composite of ECM and stem cells was prepared and cultured in chondrogenic medium (with 10?ng/mL TGF-?1 or not) for 45 days. The volumes and weights of the composites increased during culture and the surface gradually became smooth. Cell viability remained high throughout the 45 days of in vitro culture. Composites showed the formation of cartilage-like tissue with the synthesis of cartilage-specific proteins such as collagen and glycosaminoglycan. Important chondrogenic markers were expressed including Sox-9, aggrecan, and collagen type II and XI. These results demonstrate that a cell/ECM composite containing endogenous bioactive factors could provide biochemical cues for the promotion of cartilage formation. PMID:21905881

Choi, Ji Suk; Kim, Beob Soo; Kim, Jae Dong; Choi, Young Chan; Lee, Hee Young

2012-01-01

240

Defective Apoptosis in Intestinal and Mesenteric Adipose Tissue of Crohns Disease Patients  

PubMed Central

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

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

2014-01-01

241

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

SciTech Connect

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

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

2013-08-16

242

INTERLEUKIN-6 REGULATES HUMAN ADIPOSE TISSUE LIPID METABOLISM AND LEPTIN PRODUCTION IN VITRO  

Technology Transfer Automated Retrieval System (TEKTRAN)

Adipose tissue IL-6 expression is increased in obesity and is a strong predictor of abnormalities in adipocyte and systemic metabolism. We used adipose tissue organ culture to test the direct effects of IL-6 on leptin expression, lipolysis, and lipoprotein lipase activity. To assess possible inter...

243

Crosstalk between Adipocytes and Immune Cells in Adipose Tissue Inflammation and Metabolic Dysregulation in Obesity  

PubMed Central

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

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

2014-01-01

244

Regression of brown adipose tissue mitochondrial function and structure in neonatal goats  

E-print Network

Regression of brown adipose tissue mitochondrial function and structure in neonatal goats ITZICK adipose tissue mitochondria function and structure in neonatal goats. Am. J. Physiol. 252(Endocrinol changesexhibited by rapidly regressing goat'sperirenalBAT in the 1stwk postpartumareaccompanied by dramatic

Vatnick, Itzick

245

The changed metabolic world with human brown adipose tissue: therapeutic visions.  

PubMed

That adult humans possess active brown adipose tissue potentially leads to a paradigm shift in the understanding of human metabolism and of obesity. Adaptive adrenergic thermogenesis in humans represents brown adipose tissue activity, the absence of which may contribute to middle-age obesity. PMID:20374959

Nedergaard, Jan; Cannon, Barbara

2010-04-01

246

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

Microsoft Academic Search

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

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

2009-01-01

247

LEPTIN RECEPTOR (OBR) CONTAINING HYPOTHALAMIC NEURONS PROJECTING TO DIFFERENT ADIPOSE TISSUE DEPOTS IN THE PIG  

Technology Transfer Automated Retrieval System (TEKTRAN)

The purpose of the study was to establish whether or not leptin receptors (OBR)-containing hypothalamic neurons are transsynaptically connected to the adipose tissue depots in the pig. Pseudorabies virus (PRV, Barthas K strain) was introduced in perirenal or subcutaneous adipose tissue depots in cr...

248

Comparison of Visceral Adipose Tissue Mass in Adult African Americans and Whites  

Microsoft Academic Search

Objective: Previous studies have reported racial differences in the amount of visceral adipose tissue (VAT), a risk factor for metabolic diseases. These results are equivocal and have not controlled for hormonal influences on VAT mass. This study was designed to measure the extent to which race is associated with VAT, controlling for total adipose tissue (TAT) mass and testosterone.Research Methods

Daniel J. Hoffman; ZiMian Wang; Dympna Gallagher; Steven B. Heymsfield

2005-01-01

249

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

PubMed Central

The early events that initiate inflammation in the adipose tissue during obesity are not well defined. It is unclear whether the recruitment of CD8 T cells to the adipose tissue during onset of obesity occurs through antigen-dependent or -independent processes. We have previously shown that interaction between NKG2D (natural-killer group 2, member D) and its ligand Rae-1? is sufficient to recruit cytotoxic T lymphocytes to the pancreas and induce insulitis. Here, we tested whether NKG2DNKG2D ligand interaction is also involved in obesity-induced adipose tissue inflammation and insulin resistance. We observed a significant induction of NKG2D ligand expression in the adipose tissue of obese mice, especially during the early stages of obesity. However, mice lacking NKG2D developed similar levels of insulin resistance and adipose tissue inflammation compared to control mice when placed on a high-fat diet. Moreover, overexpression of Rae-1? in the adipose tissue did not increase immune cell infiltration to the adipose tissue either in the setting of a normal or high-fat diet. These results indicate that, unlike in the pancreas, NKG2DNKG2D ligand interaction does not play a critical role in obesity-induced inflammation in the adipose tissue. PMID:25333972

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

2014-01-01

250

Tissue-Engineered Corneal Stroma by Using Autologous Adipose Derived Stem Cell Tissue and Polylacticcocglycolic Acid  

Microsoft Academic Search

\\u000a Purpose: To determine whether a polylactic-co-glycolic acid (PGLA) scaffold bearing the autologous adipose derived stem cells\\u000a (ADSC) insert could repair the defect of rabbit corneal stroma without compromising tissue transparency. Methods: ADSC were\\u000a isolated from rabbits and expanded by tissue culture. The fourth passage of cells were harvested and mixed with PLGA meterial\\u000a to form cell-scaffold constructs. After 1 week

Jiaxu Hong; Jianjiang Xu; Xinghuai Sun; Lei Cui

251

[Bone tissue restoration after tooth removal by means of tissue-engineering construction based on multipotent stromal adipose cells].  

PubMed

The paper contains clinical examples of tissue-engineering construction based on multipotent stromal adipose cells application for tooth socket healing. The method do not only prevents the bone tissue resorption but allows recreating its volume. PMID:23011331

Alekseeva, I S; Kulakov, A A; Gol'dshte?n, D V; Volkov, A V

2012-01-01

252

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

PubMed

Fatty acids containing a cyclopropane ring in their structure (cyclopropane FA) have been found in a wide variety of bacteria, a number of protozoa, and Myriapoda. Little is known about cyclopropane FA in mammal, especially in human tissues. The present study deals with the identification of cyclopropane FA in adipose tissue and serum of humans and rats. Fatty acids extracted from the adipose tissue and serum obtained from obese women during bariatric surgery were methylated and analyzed on GC-MS. We have identified: cyclopropaneoctanoic acid 2-hexyl, cyclopropaneoctanoic acid 2-octyl, cyclopropanenonanoic acid, and 2-[[2-[(2-ethylcyclopropyl)methyl]cyclopropyl]methyl] acid in human adipose tissue. We confirmed the presence of cyclopropaneoctanoic acid 2-hexyl by derivatization of FA extracted from human adipose tissue to picolinyl esters. Cyclopropaneoctanoic acid 2-hexyl was the main cyclopropane FA (approximately 0.4% of total fatty acids in human adipose tissue, and about 0.2% of total fatty acids in the serum). In adipose tissue cyclopropaneoctanoic acid 2-hexyl was found mainly in triacylglycerols, whereas in serum in phospholipids and triacylglycerols. The cyclopropaneoctanoic acid 2-hexyl has also been found in serum, and adipose tissue of rats in amounts comparable to humans. The content of cyclopropaneoctanoic acid 2-hexyl decreased in adipose tissue of rats maintained on a restricted diet for 1month. In conclusion, we demonstrated that cyclopropaneoctanoic acid 2-hexyl is present in human adipose tissue and serum. Adipose tissue cyclopropaneoctanoic acid 2-hexyl is stored mainly in triacylglycerols and the storage of this cyclopropane FA is affected by food restriction. PMID:23754307

Sledzinski, Tomasz; Mika, Adriana; Stepnowski, Piotr; Proczko-Markuszewska, Monika; Kaska, Lukasz; Stefaniak, Tomasz; Swierczynski, Julian

2013-08-01

253

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

PubMed Central

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

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

2013-01-01

254

Pioglitazone Treatment Reduces Adipose Tissue Inflammation through Reduction of Mast Cell and Macrophage Number and by Improving Vascularity  

PubMed Central

Context and Objective Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil. Design, Setting and Participants Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily). These studies were performed in a clinical research center setting. Results Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p?=?0.01), and also increased capillary density without affecting larger vessels. Pioglitazone treatment decreased total adipose macrophage number by 26%, with a 56% decrease in M1 macrophages and an increase in M2 macrophages. Mast cells were more abundant in obese versus lean subjects, and were decreased from 24 to 13 cells/mm2 (p?=?0.02) in patients treated with pioglitazone, but not in subjects treated with FO. Although there were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold. Conclusion The PPAR? agonist pioglitazone increased adipocyte size yet improved other features of adipose, increasing capillary number and reducing mast cells and inflammatory macrophages. The increase in elastin may better permit adipocyte expansion without triggering cell necrosis and an inflammatory reaction. PMID:25010722

Spencer, Michael; Yang, Lin; Adu, Akosua; Finlin, Brian S.; Zhu, Beibei; Shipp, Lindsey R.; Rasouli, Neda; Peterson, Charlotte A.; Kern, Philip A.

2014-01-01

255

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

PubMed Central

This review focuses on adipose tissue biology and introduces the concept of adipose tissue plasticity and expandability as key determinants of obesity-associated metabolic dysregulation. This concept is fundamental to our understanding of adipose tissue as a dynamic organ at the center of nutritional adaptation. Here, we summarize the current knowledge of the mechanisms by which adipose tissue can affect peripheral energy homeostasis, particularly in the context of overnutrition. Two mechanisms emerge that provide a molecular understanding for obesity-associated insulin resistance. These are a) the dysregulation of adipose tissue expandability and b) the abnormal production of adipokines. This knowledge has the potential to pave the way for novel therapeutic concepts and strategies for managing and/or correcting complications associated with obesity and the metabolic syndrome. PMID:17374880

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

2015-01-01

256

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

PubMed Central

Adipose tissue plays an essential role in metabolic homeostasis, and holds promise as an alternative depot organ in gene therapy. However, efficient methods of gene transfer into adipose tissue in vivo have yet to be established. Here we assessed the transduction efficiency to fat depots by a family of novel engineered hybrid capsid serotypes (Rec1~4) recombinant AAV vectors in comparison with natural serotypes AAV1, AAV8, and AAV9. Rec2 serotype led to widespread transduction in both brown fat and white fat with the highest efficiency among the seven serotypes tested. As a proof-of-efficacy, Rec2 serotype was used to deliver Cre recombinase to adipose tissues of insulin receptor floxed animals. Insulin receptor knockdown led to decreased fat pad mass, morphological and molecular changes in the targeted depot. These novel hybrid AAV vectors can serve as powerful tools to genetically manipulate adipose tissue and provide valuable vehicles to gene therapy targeting adipose tissue. PMID:25383359

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

2014-01-01

257

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

NASA Technical Reports Server (NTRS)

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.

Smith, R. E.

1973-01-01

258

Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.  

PubMed

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-1? production. IL-1? 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-1? signaling axis could reduce AT inflammation and insulin resistance in obesity. PMID:24807222

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

259

Model of adipose tissue cellularity dynamics during food restriction.  

PubMed

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

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

2015-01-01

260

Relationship between carcass weight, adipose tissue androstenone level and expression of the hepatic 3?-hydroxysteroid dehydrogenase in entire commercial pigs.  

PubMed

Boar taint is a major meat-quality defect in pigs and is due to excessive accumulation of skatole and androstenone in adipose tissue. The present work investigated the relationship between carcass weight, levels of skatole and androstenone in adipose tissue, and expression of the hepatic androstenone-metabolising enzyme 3?-hydroxysteroid dehydrogenase (3?-HSD), in 22 entire male and 22 entire female crossbred pigs (Large White (40%) Landrace (40%) Duroc (20%)). Animals of each gender were divided into two subgroups (11 pigs in each subgroup): (i) conventional weight (carcass weight 59 to 77 kg) and (ii) heavy weight (carcass weight 84 to 95 kg). No relationship between carcass weight and adipose tissue skatole level was found for entire male pigs (r2 = 0.013, P > 0.05). There was a significant negative relationship between carcass weight and expression of the hepatic 3?-HSD protein (r2 = 0.502, P < 0.001) and a significant negative relationship between 3?-HSD protein expression and androstenone level in adipose tissue (r2 = 0.24, P < 0.05) in entire males. No relationship was found between carcass weight and 3?-HSD protein expression in female pigs (r2 = 0.001, P > 0.05). 3?-HSD expression was 59% higher in conventional-weight male pigs when compared with heavy-weight animals (P < 0.05) and 36% higher in heavy-weight females when compared with heavy-weight males (P < 0.05). It is concluded that an increase in slaughter weight of entire commercial crossbred Large White pigs is accompanied by inhibition of expression of the hepatic 3?-HSD protein, which might result in a reduced rate of hepatic androstenone clearance with its subsequent accumulation in adipose tissue. It is suggested that regulation of pig hepatic 3?-HSD expression is under the control of sex hormones. PMID:22444808

Nicolau-Solano, S I; Whittington, F M; Wood, J D; Doran, O

2007-08-01

261

Serum Progranulin Concentrations May Be Associated With Macrophage Infiltration Into Omental Adipose Tissue  

PubMed Central

OBJECTIVEProgranulin is an important molecule in inflammatory response. Chronic inflammation is frequently associated with central obesity and associated disturbances; however, the role of circulating progranulin in human obesity, type 2 diabetes, and dyslipidemia is unknown. RESEARCH DESIGN AND METHODSFor the measurement of progranulin serum concentrations, we developed an enzyme-linked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating progranulin in a cross-sectional study of 209 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal (NGT) or impaired (IGT) glucose tolerance or type 2 diabetes before and after a 4-week physical training program. Progranulin mRNA and protein expression was measured in paired samples of omental and subcutaneous adipose tissue (adipocytes and cells of the stromal vascular fraction) from 55 lean or obese individuals. Measurement of Erk activation and chemotactic activity induced by progranulin in vitro was performed using THP-1based cell migration assays. RESULTSProgranulin serum concentrations were significantly higher in individuals with type 2 diabetes compared with NGT and in obese subjects with predominant visceral fat accumulation. Circulating progranulin significantly correlates with BMI, macrophage infiltration in omental adipose tissue, C-reactive protein (CRP) serum concentrations, A1C values, and total cholesterol. Multivariable linear regression analyses revealed CRP levels as the strongest independent predictor of circulating progranulin. The extent of in vitro progranulin-mediated chemotaxis is similar to that of monocyte chemoattractant protein-1 but independent of G?. Moreover, in type 2 diabetes, but not in IGT and NGT individuals, physical training for 4 weeks resulted in significantly decreased circulating progranulin levels. CONCLUSIONSElevated progranulin serum concentrations are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. We identified progranulin as a novel marker of chronic inflammation in obesity and type 2 diabetes that closely reflects omental adipose tissue macrophage infiltration. Physical training significantly reduces elevated circulating progranulin in patients with type 2 diabetes. PMID:19056610

Youn, Byung-Soo; Bang, Sa-Ik; Klting, Nora; Park, Ji Woo; Lee, Namseok; Oh, Ji-Eun; Pi, Kyung-Bae; Lee, Tae Hee; Ruschke, Karen; Fasshauer, Mathias; Stumvoll, Michael; Blher, Matthias

2009-01-01

262

Adipose Tissue Gene Expression of Factors Related to Lipid Processing in Obesity  

PubMed Central

Background Adipose tissue lipid storage and processing capacity can be a key factor for obesity-related metabolic disorders such as insulin resistance and diabetes. Lipid uptake is the first step to adipose tissue lipid storage. The aim of this study was to analyze the gene expression of factors involved in lipid uptake and processing in subcutaneous (SAT) and visceral (VAT) adipose tissue according to body mass index (BMI) and the degree of insulin resistance (IR). Methods and Principal Findings VLDL receptor (VLDLR), lipoprotein lipase (LPL), acylation stimulating protein (ASP), LDL receptor-related protein 1 (LRP1) and fatty acid binding protein 4 (FABP4) gene expression was measured in VAT and SAT from 28 morbidly obese patients with Type 2 Diabetes Mellitus (T2DM) or high IR, 10 morbidly obese patients with low IR, 10 obese patients with low IR and 12 lean healthy controls. LPL, FABP4, LRP1 and ASP expression in VAT was higher in lean controls. In SAT, LPL and FABP4 expression were also higher in lean controls. BMI, plasma insulin levels and HOMA-IR correlated negatively with LPL expression in both VAT and SAT as well as with FABP4 expression in VAT. FABP4 gene expression in SAT correlated inversely with BMI and HOMA-IR. However, multiple regression analysis showed that BMI was the main variable contributing to LPL and FABP4 gene expression in both VAT and SAT. Conclusions Morbidly obese patients have a lower gene expression of factors related with lipid uptake and processing in comparison with healthy lean persons. PMID:21966368

Clemente-Postigo, Mercedes; Queipo-Ortuo, Maria Isabel; Fernandez-Garcia, Diego; Gomez-Huelgas, Ricardo; Tinahones, Francisco J.; Cardona, Fernando

2011-01-01

263

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

PubMed Central

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

2014-01-01

264

The effect of ractopamine hydrochloride on gene expression in adipose tissues of finishing pigs.  

PubMed

The long-term effect of feeding the catecholamine analog ractopamine (RAC; ractopamine hydrochloride, Elanco Animal Health, Indianapolis, IN) on the expression of genes involved in energy and lipid metabolism in subcutaneous adipose tissue was studied. Large White pigs (84 kg) were fed corn- and soybean meal-based diets supplemented with 0, 20, or 60 mg/kg of RAC for 14, 28, or 42 d. Expression (mRNA abundance) in adipose tissue of sterol regulatory binding protein-1 (SREBP-1), PPAR?, PPAR?2, fatty acid synthase (FAS), glucose transporter 4 (GLUT4), and stearoyl-CoA desaturase was determined by Northern blotting. Feed intakes did not differ, and RAC (20 and 60 mg/kg) improved BW gain at d 14, 28, and 42 (P < 0.05) and increased loin eye area (measured on d 42 only; P < 0.05). Expression of SREBP-1 and PPAR?2 declined (P < 0.05) with RAC by d 28 and 42, whereas expression of PPAR? was increased (P < 0.05) on d 14, 28, and 42. After 14 d, expression of FAS and GLUT4 was decreased (P < 0.05) with 60 mg/kg of RAC, whereas both RAC concentrations attenuated FAS expression on d 28 and 42. Overall, adipose tissue stearoyl-CoA desaturase expression was not affected by RAC but showed somewhat less expression (P < 0.15) on d 28 at 60 mg/kg of RAC. Although prolonged, chronic RAC feeding most likely downregulates adipose tissue membrane ?-adrenergic receptors, mRNA abundances of anabolic lipid metabolism transcription factors, glucose transporters, and enzymes (SREBP-1, PPAR?2, FAS, GLUT4) were still attenuated up to d 42. Conversely, a transcription factor related to oxidative metabolism expression (PPAR?) was enhanced. We conclude that even after 42 d, RAC still decreased expression of lipogenic genes in adipose tissue by yet undefined cyclic adenosine monophosphate-directed mechanisms, but in contemporary lean pigs, this effect is likely of limited practical significance. PMID:21148782

Halsey, C H C; Weber, P S; Reiter, S S; Stronach, B N; Bartosh, J L; Bergen, W G

2011-04-01

265

Glycerolipid biosynthesis in rat adipose tissue. Influence of adipose-cell size and site of adipose tissue on triacylglycerol formation in lean and obese rats.  

PubMed Central

The rates of lipid formation were compared in different fat-depots from lean and obese rats by using [14C]glycerol 3-phosphate, [14C]glucose or [14C]acetate as substrates. In lean animals, subcutaneous adipose tissue showed significantly lower rates of lipid synthesis than did perirenal and gonadal fat-tissue. In obese animals, the rates of lipid synthesis were significantly higher and did not vary from one fat-depot to another. Differences in the rates of lipid formation between lean and obese rats disappeared during dietary restriction of obese animals. The isolated adipocyte preparation did not reflect the true metabolic activity of the adipose organ, since this preparation was mainly derived from smaller adipocytes that were metabolically less active than larger adipocytes. The present study suggests that it is better to use whole tissue preparations to measure lipogenesis and esterification reactions, because these measurements represent the contribution of both larger and smaller adipocytes towards lipid formation. Images PLATE 1 PLATE 2 PMID:204300

Jamdar, S C

1978-01-01

266

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

PubMed

The Rar-related orphan receptor-? (Ror?) is a nuclear receptor that regulates adiposity and is a potential regulator of energy homeostasis. We have demonstrated that the Ror?-deficient staggerer (sg/sg) mice display a lean and obesity-resistant phenotype. Adaptive Ucp1-dependent thermogenesis in beige/brite and brown adipose tissue serves as a mechanism to increase energy expenditure and resist obesity. DEXA and MRI analysis demonstrated significantly decreased total fat mass and fat/lean mass tissue ratio in male chow-fed sg/sg mice relative to wt mice. In addition, we observed increased Ucp1 expression in brown adipose and subcutaneous white adipose tissue but not in visceral adipose tissue from Ror?-deficient mice. Moreover, this was associated with significant increases in the expression of the mRNAs encoding the thermogenic genes (i.e., markers of brown and beige adipose) Ppar?, Err?, Dio2, Acot11/Bfit, Cpt1?, and Cidea in the subcutaneous adipose in the sg/sg relative to WT mice. These changes in thermogenic gene expression involved the significantly increased expression of the (cell-fate controlling) histone-lysine N-methyltransferase 1 (Ehmt1), which stabilizes the Prdm16 transcriptional complex. Moreover, primary brown adipocytes from sg/sg mice displayed a higher metabolic rate, and further analysis was consistent with increased uncoupling. Finally, core body temperature analysis and infrared thermography demonstrated that the sg/sg mice maintained greater thermal control and cold tolerance relative to the WT littermates. We suggest that enhanced Ucp1 and thermogenic gene expression/activity may be an important contributor to the lean, obesity-resistant phenotype in Ror?-deficient mice. PMID:25424999

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

2015-01-15

267

Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue  

PubMed Central

A high-fat diet (HFD) is associated with adipose inflammation, which contributes to key components of metabolic syndrome, including obesity and insulin resistance. The increased visceral adipose tissue mass associated with obesity is the result of hyperplasia and hypertrophy of adipocytes. To investigate the effects of exercise on HFD-induced metabolic disorders, male C57BL/6 mice were divided into four groups: SED (sedentary)-ND (normal diet), EX (exercise)-ND, SED-HFD, and EX-HFD. Exercise was performed on a motorized treadmill at 15 m/min, 40 min/day, and 5 day/wk for 8 wk. Exercise resulted in a decrease in abdominal fat contents and inflammation, improvements in glucose tolerance and insulin resistance, and enhancement of vascular constriction and relaxation responses. Exercise with or without HFD increased putative brown adipocyte progenitor cells in brown adipose tissue compared with groups with the same diet, with an increase in brown adipocyte-specific gene expression in brown and white adipose tissue. Exercise training enhanced in vitro differentiation of the preadipocytes from brown adipose depots into brown adipocytes and enhanced the expression of uncoupling protein 1. These findings suggest that exercise ameliorates high-fat diet-induced metabolic disorders and vascular dysfunction, and increases adipose progenitor cell population in brown adipose tissue, which might thereby contribute to enhanced functional brown adipose. PMID:21368268

Xu, Xiaohua; Ying, Zhekang; Cai, Ming; Xu, Zhaobin; Li, Yuanjing; Jiang, Silis Y.; Tzan, Kevin; Wang, Aixia; Parthasarathy, Sampath; He, Guanglong; Rajagopalan, Sanjay

2011-01-01

268

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

PubMed

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

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

2014-10-01

269

Coupling of lipolysis and de novo lipogenesis in brown, beige, and white adipose tissues during chronic ?3-adrenergic receptor activation.  

PubMed

Chronic activation of ?3-adrenergic receptors (?3-ARs) expands the catabolic activity of both brown and white adipose tissue by engaging uncoupling protein 1 (UCP1)-dependent and UCP1-independent processes. The present work examined de novo lipogenesis (DNL) and TG/glycerol dynamics in classic brown, subcutaneous "beige," and classic white adipose tissues during sustained ?3-AR activation by CL 316,243 (CL) and also addressed the contribution of TG hydrolysis to these dynamics. CL treatment for 7 days dramatically increased DNL and TG turnover similarly in all adipose depots, despite great differences in UCP1 abundance. Increased lipid turnover was accompanied by the simultaneous upregulation of genes involved in FAS, glycerol metabolism, and FA oxidation. Inducible, adipocyte-specific deletion of adipose TG lipase (ATGL), the rate-limiting enzyme for lipolysis, demonstrates that TG hydrolysis is required for CL-induced increases in DNL, TG turnover, and mitochondrial electron transport in all depots. Interestingly, the effect of ATGL deletion on induction of specific genes involved in FA oxidation and synthesis varied among fat depots. Overall, these studies indicate that FAS and FA oxidation are tightly coupled in adipose tissues during chronic adrenergic activation, and this effect critically depends on the activity of adipocyte ATGL. PMID:25193997

Mottillo, Emilio P; Balasubramanian, Priya; Lee, Yun-Hee; Weng, Changren; Kershaw, Erin E; Granneman, James G

2014-11-01

270

Panax red ginseng extract regulates energy expenditures by modulating PKA dependent lipid mobilization in adipose tissue.  

PubMed

Regulation of balance between lipid accumulation and energy consumption is a critical step for the maintenance of energy homeostasis. Here, we show that Panax red ginseng extract treatments increased energy expenditures and prevented mice from diet induced obesity. Panax red ginseng extracts strongly activated Hormone Specific Lipase (HSL) via Protein Kinase A (PKA). Since activation of HSL induces lipolysis in WAT and fatty acid oxidation in brown adipose tissue (BAT), these results suggest that Panax red ginseng extracts reduce HFD induced obesity by regulating lipid mobilization. PMID:24759232

Cho, Hae-Mi; Kang, Young-Ho; Yoo, Hanju; Yoon, Seung-Yong; Kang, Sang-Wook; Chang, Eun-Ju; Song, Youngsup

2014-05-16

271

Variations in T2* and fat content of murine brown and white adipose tissues by chemical-shift MRI  

E-print Network

between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice. Materials and Methods: A group* relaxation; Fat fraction 1. Introduction In rodents, brown adipose tissue (BAT) contributes to thermalVariations in T2* and fat content of murine brown and white adipose tissues by chemical-shift MRI

Southern California, University of

272

Relationships between dietary fatty acid composition and either melting point or fatty acid profile of adipose tissue in broilers  

Microsoft Academic Search

Data on the fatty acid composition of the diet and that of the adipose tissue in broilers were collected from the literature. The linear regression between the dietary and the adipose tissue unsaturated to saturated fatty acids ratio (U\\/S ratio) was calculated because the U\\/S ratio of adipose tissue fat determines its melting point, which is an indicator of the

F. J. Bavelaar; A. C. Beynen

2003-01-01

273

Softness and fatty acid composition of subcutaneous adipose tissue, and methylmalonic acid concentrations in the plasma of intensively reared lambs  

Microsoft Academic Search

The aim of the present work was to study the relationships between lamb growth performance, soft adipose tissue and fatty acid composition of subcutaneous adipose tissue of intensively reared lambs, and to determine if the occurrence of soft fat, and of odd numbered (Odd FA) and methyl-branched-chain fatty acids in subcutaneous adipose tissue was related to plasma concentrations of methylmalonic

V Berthelot; J Normand; P Bas; N. B Kristensen

2001-01-01

274

Tissue engineering construct on the basis of multipotent stromal adipose tissue cells and Osteomatrix for regeneration of the bone tissue.  

PubMed

We developed a new method of creation of tissue engineering constructs for regeneration of the bone tissue based on the principle of free distribution of cells in a fibrin clot within a scaffold. The tissue engineering construct includes multipotent stromal adipose tissue cells committed in osteogenic lineage, platelet-rich plasma, and resorbed material on the basis of xenogeneic bone collagen. The culture of bone progenitor cells was characterized by the main markers of osteoblastic differon. The material meets all requirements for materials intended for tissue engineering. An innovative high-technological tissue engineering product for clinical application is prepared. PMID:22803063

Bukharova, T B; Arutyunyan, I V; Shustrov, S A; Alekseeva, I S; Fedyunina, I A; Logovskaya, L V; Volkov, A V; Rzhaninova, A A; Grigor'yan, A S; Kulakov, A A; Gol'dshtein, D V

2011-11-01

275

Brown adipose tissue as a therapeutic target for human obesity.  

PubMed

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

Saito, Masayuki

2013-12-01

276

Epicardial adipose tissue: far more than a fat depot.  

PubMed

Epicardial adipose tissue (EAT) refers to the fat depot that exists on the surface of the myocardium and is contained entirely beneath the pericardium, thus surrounding and in direct contact with the major coronary arteries and their branches. EAT is a biologically active organ that may play a role in the association between obesity and coronary artery disease (CAD). Given recent advances in non-invasive imaging modalities such a multidetector computed tomography (MDCT), EAT can be accurately measured and quantified. In this review, we focus on the evidence suggesting a role for EAT as a quantifiable risk marker in CAD, as well as describe the role EAT may play in the development and vulnerability of coronary artery plaque. PMID:25610800

Talman, Andrew H; Psaltis, Peter J; Cameron, James D; Meredith, Ian T; Seneviratne, Sujith K; Wong, Dennis T L

2014-12-01

277

Epicardial adipose tissue: far more than a fat depot  

PubMed Central

Epicardial adipose tissue (EAT) refers to the fat depot that exists on the surface of the myocardium and is contained entirely beneath the pericardium, thus surrounding and in direct contact with the major coronary arteries and their branches. EAT is a biologically active organ that may play a role in the association between obesity and coronary artery disease (CAD). Given recent advances in non-invasive imaging modalities such a multidetector computed tomography (MDCT), EAT can be accurately measured and quantified. In this review, we focus on the evidence suggesting a role for EAT as a quantifiable risk marker in CAD, as well as describe the role EAT may play in the development and vulnerability of coronary artery plaque. PMID:25610800

Talman, Andrew H.; Psaltis, Peter J.; Cameron, James D.; Meredith, Ian T.; Seneviratne, Sujith K.

2014-01-01

278

Characteristics of mouse adipose tissue-derived stem cells and therapeutic comparisons between syngeneic and allogeneic adipose tissue-derived stem cell transplantation in experimental autoimmune thyroiditis.  

PubMed

Previously, we found that the intravenous administration of human adipose tissue-derived mesenchymal stem cells was a promising therapeutic option for autoimmune thyroiditis even when the cells were transplanted into a xenogeneic model without an immunosuppressant. Therefore, we explored the comparison between the therapeutic effects of syngeneic and allogeneic adipose tissue-derived stem cells on an experimental autoimmune thyroiditis mouse model. Experimental autoimmune thyroiditis was induced in C57BL/6 mice by immunization with porcine thyroglobulin. Adipose tissue-derived stem cells derived from C57BL/6 mice (syngeneic) or BALB/c mice (allogeneic) or saline as a vehicle control were administered intravenously four times weekly. Blood and tissue samples were collected 1 week after the last transplantation. Adipose tissue-derived stem cells from mice were able to differentiate into multiple lineages in vitro; however, mouse adipose tissue-derived stem cells did not have immunophenotypes identical to those from humans. Syngeneic and allogeneic administrations of adipose tissue-derived stem cells reduced thyroglobulin autoantibodies and the inflammatory immune response, protected against lymphocyte infiltration into the thyroid, and restored the Th1/Th2 balance without any adverse effects. However, different humoral immune responses were observed for infused cells from different stem cell sources. The strongest humoral immune response was induced by xenogeneic transplantation, followed by allogeneic and syngeneic administration, in that order. The stem cells were mostly found in the spleen, not the thyroid. This migration might be because the stem cells primarily function in systemic immune modulation, due to being given prior to disease induction. In this study, we confirmed that there were equal effects of adipose tissue-derived stem cells in treating autoimmune thyroiditis between syngeneic and allogeneic transplantations. PMID:23485102

Choi, Eun Wha; Shin, Il Seob; Park, So Young; Yoon, Eun Ji; Kang, Sung Keun; Ra, Jeong Chan; Hong, Sung Hwa

2014-01-01

279

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

NASA Astrophysics Data System (ADS)

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

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

280

Cloning of porcine GPIHBP1 gene and its tissue expression pattern and genetic effect on adipose traits.  

PubMed

Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is transported by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) from the interstitial spaces to the capillary lumen. Here, we cloned a cDNA and the genomic locus of the porcine GPIHBP1 gene, and investigated its tissue expression pattern and its genetic effects on adipose traits. Porcine GPIHBP1 exhibits a four-exon/three-intron structure, including a 543bp open reading frame that encodes 180 amino acids. The porcine GPIHBP1 protein shows 49%-65% homology and shares the major conserved structural domains of GPIHBP1 proteins in other mammals. Porcine GPIHBP1 mRNA levels were high in the adipose tissue, muscle and lung, and higher mRNA levels were observed in sows compared to boars in adipose tissues of the inner and outer layers of subcutaneous fat, abdominal fat, and suet fat. The mRNA expression pattern of porcine GPIHBP1 and LPL genes was similar in most tissues except for the lung. Thirty six single nucleotide polymorphisms (SNPs) were found in the porcine GPIHBP1 gene. Association analyses showed that the g.-255G>C and g.-626T>G SNPs are associated with intramuscular fat content, and that the g.-1557T>C and g.-1948G>A SNPs are associated with back fat thickness. In conclusion, porcine GPIHBP1 mRNA is abundantly expressed in the adipose tissue, muscle and lung, and gender affects GPIHBP1 mRNA expression levels; furthermore, four GPIHBP1 SNPs are genetic factors affecting adipose traits. PMID:25498336

Xu, Huaming; Tao, Xuelian; Wei, Yingying; Chen, Jianning; Xing, Shuhua; Cen, Wangmin; Wen, Anxiang; Zhu, Li; Tang, Guoqing; Li, Mingzhou; Jiang, Anan; Jiang, Yanzhi; Li, Xuewei

2015-02-25

281

Angiotensin II Receptor Blocker Ameliorates Stress-Induced Adipose Tissue Inflammation and Insulin Resistance  

PubMed Central

A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1), tumor necrosis factor-?, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT) was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs) and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results indicate that irbesartan improves stress-induced adipose tissue inflammation and insulin resistance. Our results suggests that irbesartan treatment exerts additive benefits for glucose metabolism in hypertensive patients with mental stress. PMID:25551221

Hayashi, Motoharu; Takeshita, Kyosuke; Uchida, Yasuhiro; Yamamoto, Koji; Kikuchi, Ryosuke; Nakayama, Takayuki; Nomura, Emiko; Cheng, Xian Wu; Matsushita, Tadashi; Nakamura, Shigeo; Murohara, Toyoaki

2014-01-01

282

Adipose Tissue-Derived Stem Cells and Their Application in Bone and Cartilage Tissue Engineering  

Microsoft Academic Search

The adipose tissue was considered a reserve of energy until the `80s,\\u000d\\u000a when it was found that this tissue was involved in the metabolism of sex\\u000d\\u000a steroids such as estrogens. From then on, the importance attributed to\\u000d\\u000a this tissue radically changed as it was then considered an active organ,\\u000d\\u000a involved in important functions of the human body. In 2001, for

Tommaso Rada; Rui L. Reis; Manuela E. Gomes

2009-01-01

283

Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance  

PubMed Central

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, ?3-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

Poher, Anne-Laure; Altirriba, Jordi; Veyrat-Durebex, Christelle; Rohner-Jeanrenaud, Franoise

2015-01-01

284

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

PubMed

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

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

2013-01-01

285

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

PubMed

Obesity remains a major global health concern. Understanding the metabolic influences of the obesity epidemic in the human population on maintenance of a healthy weight and metabolic profile is still of great significance. The importance and role of white adipose tissue has been long established, particularly with excess adiposity. Brown adipose tissue (BAT), however, has only recently been shown to contribute significantly to the metabolic signature of mammals outside the previously recognised role in small mammals and neonates. BAT's detection in adults has led to a renewed interest and is now considered to be a potential therapeutic target to prevent excess white fat accumulation in obesity, a theory further promoted by the recent discovery of beige fat. Adipose tissue distribution varies significantly between genders. Pre-menopausal females often show enhanced lower and peripheral fat deposition in adiposity deposition compared to the male profile of central and visceral fat accumulation with obesity. This sex disparity is partly attributed to the different effects of sex hormone profiles and interactions on the adipose tissue system. In this review, we explore this intricate relationship and show how modifications in the effects of sex hormones impact on both brown and white adipose tissues. We also discuss the impact of sex hormones on activation of the hypothalamic-pituitary-adrenal (HPA) axis and how the three pathways between adiposity, HPA and sex steroids can have a major contribution to the prevention or maintenance of obesity and therefore on overall health. PMID:25390013

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

2014-07-01

286

Proteomic Profiling of Tissue-Engineered Blood Vessel Walls Constructed by Adipose-Derived Stem Cells  

PubMed Central

Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 170115 and 126526 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels. PMID:22963350

Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang

2013-01-01

287

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

PubMed

Obesity is a state in which chronic low-grade inflammation persists in adipose tissues. Pro-inflammatory cytokines, including TNF-?, produced by adipose tissues have been implicated as active participants in the development of obesity-related diseases. Since TNF-? converting enzyme (TACE) is the major factor that induces soluble TNF-?, TACE has been noted as a pivotal regulator in this field. To reveal the role of TACE in adipose tissue inflammation, TACE-transgenic (TACE-Tg) and wild type (WT) mice were fed with high fat diet (HFD) or control diet for 16weeks. At 13weeks after the beginning of the diet, serum TNF-? and macrophage-related cytokine/chemokine levels were elevated in TACE-Tg mice fed with HFD (Tg-HFD mice), and the number of the so-called crown-like adipocyte was significantly increased in adipose tissues of Tg-HFD mice at the end of the experiment. Although macrophage infiltration was not detected in the adipose tissues at this time, fibrosis was observed around the crown-like adipocytes. These findings suggested that TACE overexpression induced macrophage infiltration and subsequent fibrosis in adipose tissues under HFD regimen. The collective evidence suggested that TACE could be a therapeutic target of HFD-induced obesity-related adipose tissue inflammation. PMID:25236578

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

2014-12-01

288

The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome?  

PubMed

Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen from adipocytes. Whereas angiotensin II promotes adipocyte growth and preadipocyte recruitment, increased secretion of angiotensinogen from adipocytes also directly contributes to the close relationship between adipose-tissue mass and blood pressure in mice. In contrast, angiotensin II acts as an antiadipogenic substance in human adipose tissue, and the total increase in adipose-tissue mass may be more important in determining human plasma angiotensinogen levels than changes within the single adipocyte. However, as increased local formation of angiotensin II in adipose tissue may be increased especially in obese hypertensive subjects, a contribution of the adipose-tissue renin-angiotensin system to the development of insulin resistance and hypertension is conceivable in humans, but not yet proven. Insulin resistance may be aggravated by the inhibition of preadipocyte recruitment, which results in the redistribution of triglycerides to the liver and skeletal muscle, and blood pressure may be influenced by local formation of angiotensin II in perivascular adipose tissue. Thus, although the mechanisms are still speculative, the beneficial effects of ACE-inhibition and angiotensin-receptor blockade on the development of type 2 diabetes in large clinical trials suggest a pathophysiological role of the adipose-tissue renin-angiotensin system in the metabolic syndrome. PMID:12676168

Engeli, Stefan; Schling, Petra; Gorzelniak, Kerstin; Boschmann, Michael; Janke, Jrgen; Ailhaud, Grard; Teboul, Michle; Massira, Florence; Sharma, Arya M

2003-06-01

289

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

PubMed Central

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

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

2014-01-01

290

Adipose Tissue Extracellular Matrix and Vascular Abnormalities in Obesity and Insulin Resistance  

PubMed Central

Context: Insulin resistance is associated with inflammation, fibrosis, and hypoxia in adipose tissue. Objective: This study was intended to better characterize the extracellular matrix (ECM) and vascularity of insulin-resistant adipose tissue. Design: Adipose expression of collagens, elastin, and angiogenic factors was assessed using real-time RT-PCR and immunohistochemistry (IHC) in abdominal sc adipose tissue. Adipocyte-macrophage coculture experiments examined the effects of polarized macrophages on adipose ECM gene expression, and the effects of collagens were measured in an angiogenesis assay. Participants and Setting: A total of 74 nondiabetic subjects participated at a University Clinical Research Center. Interventions: Interventions included baseline adipose biopsy and measurement of insulin sensitivity. Main Outcome Measures: Outcome measures included characterization of vascularity and ECM in adipose tissue. Results: CD31 (an endothelial marker) mRNA showed no significant correlation with body mass index or insulin sensitivity. In a subgroup of 17 subjects (nine obese, eight lean), CD31-positive capillary number in obese was decreased by 58%, whereas larger vessels were increased by 70%, accounting for the lack of change in CD31 expression with obesity. Using IHC, obese (compared with lean) subjects had decreased elastin and increased collagen V expression, and adipocytes cocultured with M2 macrophages had reduced elastin and increased collagen V expression. In obese subjects, collagen V was colocalized with large blood vessels, and the addition of collagen V to an angiogenesis assay inhibited endothelial budding. Conclusions: The adipose tissue from obese/insulin-resistant subjects has fewer capillaries and more large vessels as compared with lean subjects. The ECM of adipose tissue may play an important role in regulating the expandability as well as angiogenesis of adipose tissue. PMID:21994960

Spencer, Michael; Unal, Resat; Zhu, Beibei; Rasouli, Neda; McGehee, Robert E.; Peterson, Charlotte A.

2011-01-01

291

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

PubMed Central

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

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

2013-01-01

292

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...

293

Modulation of adipose tissue thermogenesis as a method for increasing energy expenditure.  

PubMed

There is a renewed interest in the role of adipose tissue in energy utilization and thermogenesis and its potential application in the treatment of metabolic disorders such as obesity and diabetes. The last few years have seen the identification of brown adipose tissue capable of metabolic activation in adult humans, the possibility of recruiting 'beige' adipocytes to increase energy expenditure, and the implication of molecules such as FGF21 and irisin in inducing increases in energy expenditure in adipose tissue. The translation of these findings into human trials to deliver safe, efficacious medicines remains a challenge. PMID:24373722

Sammons, Matthew F; Price, David A

2014-01-15

294

Interorgan signaling between adipose tissue metabolism and skeletal muscle uncoupling protein homologs: is there a role for circulating free fatty acids?  

Microsoft Academic Search

Uncoupling proteins 3 and 2 (UCP3 and UCP2) are two newly cloned genes that have been implicated in the reg- ulation of lipids as fuel substrate in skeletal muscle on the basis that their mRNA expressions are upregulated during starvation (when fat stores are being rapidly mobilized) and downregulated during the early phase of refeeding (when fat stores are being

Sonia Samec; Josiane Seydoux; Abdul G. Dulloo

1998-01-01

295

The effect of calorie restriction on insulin signaling in skeletal muscle and adipose tissue of Ames dwarf mice.  

PubMed

Long-living Ames dwarf (df/df) mice are homozygous for a mutation of the Prop1(df) gene. As a result, mice are deficient in growth hormone (GH), prolactin (PRL) and thyrotropin (TSH). In spite of the hormonal deficiencies, df/df mice live significantly longer and healthier lives compared to their wild type siblings. We studied the effects of calorie restriction (CR) on the expression of insulin signaling genes in skeletal muscle and adipose tissue of normal and df/df mice. The analysis of genes expression showed that CR differentially affects the insulin signaling pathway in these insulin target organs. Moreover, results obtained in both normal and Ames dwarf mice indicate more direct effects of CR on insulin signaling genes in adipose tissue than in skeletal muscle. Interestingly, CR reduced the protein levels of adiponectin in the epididymal adipose tissue of normal and Ames dwarf mice, while elevating adiponectin levels in skeletal muscle and plasma of normal mice only. In conclusion, our findings suggest that both skeletal muscle and adipose tissue are important mediators of insulin effects on longevity. Additionally, the results revealed divergent effects of CR on expression of genes in the insulin signaling pathway of normal and Ames dwarf mice. PMID:25411241

Wiesenborn, Denise S; Menon, Vinal; Zhi, Xu; Do, Andrew; Gesing, Adam; Wang, Zhihui; Bartke, Andrzej; Altomare, Deborah A; Masternak, Michal M

2014-10-01

296

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

SciTech Connect

Highlights: High-fat diet intake following maternal separation did not cause body weight gain. However, levels of metabolism-related molecules in adipose tissue were altered. Increased levels of prohibitin mRNA in white fat were observed. Attenuated levels of ?3-adrenergic receptor mRNA were observed in brown fat. Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. SpragueDawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 1015 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), ?3-adrenergic receptor (?3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through ?3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the ?3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

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

2013-12-06

297

The effects of dietary lipids on dendritic cells in perinodal adipose tissue during chronic mild inflammation.  

PubMed

The effects of dietary lipids on the abundance of dendritic cells in adipose tissue in anatomically defined relationships to chronically inflamed lymph nodes were investigated in mature male rats fed plain chow or chow plus 20 % sunflower-seed or fish oil. The popliteal lymph nodes were stimulated by local subcutaneous injection of 20 microg lipopolysaccharide to both hindlegs three times/week for 2 weeks. The masses of the major adipose depots and the numbers of dendritic cells emerging from perinodal adipose tissue and samples 5 and 10 mm from the popliteal lymph nodes were measured, and those from omental and mesenteric adipose tissue around and remote from lymphoid tissue, and mesenteric and popliteal lymph nodes. Dendritic cells were most numerous in the perinodal adipose tissue, with the corresponding 'remote' samples containing 25-50 % fewer such cells under all conditions studied. Dietary sunflower-seed oil increased the numbers of dendritic cells by about 17 % in all adipose samples and fish oil reduced the numbers in perinodal tissue by about 5 %. The fish-oil diet diminished responses of the intra-abdominal adipose depots to local stimulation of the popliteal node. Correlations in dendritic cell numbers were stronger between perinodal samples from different depots than between remote and perinodal samples from the same depot and after the sunflower-seed-oil diet compared with fish oil. These data show that dietary lipids modulate the number of dendritic cells in lymphoid tissue-containing adipose depots and support the hypothesis that perinodal adipose tissue interacts locally with lymphoid cells. PMID:15182392

Mattacks, Christine A; Sadler, Dawn; Pond, Caroline M

2004-06-01

298

Cerenkov luminescence imaging of interscapular brown adipose tissue.  

PubMed

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

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

2014-01-01

299

Brown adipose tissue takes up plasma triglycerides mostly after lipolysis.  

PubMed

Brown adipose tissue (BAT) produces heat by burning TGs that are stored within intracellular lipid droplets and need to be replenished by the uptake of TG-derived FA from plasma. It is currently unclear whether BAT takes up FA via uptake of TG-rich lipoproteins (TRLs), after lipolysis-mediated liberation of FA, or via a combination of both. Therefore, we generated glycerol tri[(3)H]oleate and [(14)C]cholesteryl oleate double-labeled TRL-mimicking particles with an average diameter of 45, 80, and 150 nm (representing small VLDL to chylomicrons) and injected these intravenously into male C57Bl/6J mice. At room temperature (21C), the uptake of (3)H-activity by BAT, expressed per gram of tissue, was much higher than the uptake of (14)C-activity, irrespective of particle size, indicating lipolysis-mediated uptake of TG-derived FA rather than whole particle uptake. Cold exposure (7C) increased the uptake of FA derived from the differently sized particles by BAT, while retaining the selectivity for uptake of FA over cholesteryl ester (CE). At thermoneutrality (28C), total FA uptake by BAT was attenuated, but the specificity of uptake of FA over CE was again largely retained. Altogether, we conclude that, in our model, BAT takes up plasma TG preferentially by means of lipolysis-mediated uptake of FA. PMID:25351615

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

2015-01-01

300

Transcriptomic Analysis of Brown Adipose Tissue across the Physiological Extremes of Natural Hibernation  

PubMed Central

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

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

2013-01-01

301

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

PubMed Central

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

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

2012-01-01

302

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

PubMed

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

Mardinoglu, Adil; Kampf, Caroline; Asplund, Anna; Fagerberg, Linn; Hallstrm, Bjrn M; Edlund, Karolina; Blher, Matthias; Pontn, Fredrik; Uhlen, Mathias; Nielsen, Jens

2014-11-01

303

The role of perivascular adipose tissue in vascular smooth muscle cell growth  

PubMed Central

Adipose tissue is the largest endocrine organ, producing various adipokines and many other substances. Almost all blood vessels are surrounded by perivascular adipose tissue (PVAT), which has not received research attention until recently. This review will discuss the paracrine actions of PVAT on the growth of underlying vascular smooth muscle cells (VSMCs). PVAT can release growth factors and inhibitors. Visfatin is the first identified growth factor derived from PVAT. Decreased adiponectin and increased tumour necrosis factor-? in PVAT play a pathological role for neointimal hyperplasia after endovascular injury. PVAT-derived angiotensin II, angiotensin 17, reactive oxygen species, complement component 3, NO and H2S have a paracrine action on VSMC contraction, endothelial or fibroblast function; however, their paracrine actions on VSMC growth remain to be directly verified. Factors such as monocyte chemoattractant protein-1, interleukin-6, interleukin-8, leptin, resistin, plasminogen activator inhibitor type-1, adrenomedullin, free fatty acids, glucocorticoids and sex hormones can be released from adipose tissue and can regulate VSMC growth. Most of them have been verified for their secretion by PVAT; however, their paracrine functions are unknown. Obesity, vascular injury, aging and infection may affect PVAT, causing adipocyte abnormality and inflammatory cell infiltration, inducing imbalance of PVAT-derived growth factors and inhibitors, leading to VSMC growth and finally resulting in development of proliferative vascular disease, including atherosclerosis, restenosis and hypertension. In the future, using cell-specific gene interventions and local treatments may provide definitive evidence for identification of key factor(s) involved in PVAT dysfunction-induced vascular disease and thus may help to develop new therapies. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21470202

Miao, Chao-Yu; Li, Zhi-Yong

2012-01-01

304

Adipose tissue as a source of nicotinamide N-methyltransferase and homocysteine.  

PubMed

Nicotinamide N-methyltransferase (NNMT) catalyses the conversion of nicotinamide to 1-methylnicotinamide and plays an important role in hepatic detoxification reactions. Here we show that, in addition to the liver, 3T3-L1 adipocytes as well as human and murine adipose tissue explants express high amounts of enzymatically active NNMT. NNMT mRNA levels and enzyme activity increased in 3T3-L1 cells in a differentiation-dependent manner. Homocysteine, the atherogenic product of the NNMT-catalyzed reaction, was secreted from 3T3-L1 cells or adipose tissue cultures. Homocysteine release increased during 3T3-L1 differentiation and was reduced when adipose tissue was treated with the NNMT inhibitor 1-methylnicotinamide. Nicotinic acid (NA), a widely used drug to lower elevated plasma lipid levels, induced NNMT enzyme activity in white adipose tissue of mice. In tissue culture nicotinamide treatment led to an increase in adipose tissue homocysteine secretion. These data support the concept that adipose tissue NNMT contributes to the increased plasma homocysteine levels in patients treated with NA. PMID:18996527

Riederer, Monika; Erwa, Wolfgang; Zimmermann, Robert; Frank, Sasa; Zechner, Rudolf

2009-06-01

305

Clinical Evaluation of Extracellular ADMA Concentrations in Human Blood and Adipose Tissue  

PubMed Central

Circulating asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, has been proposed as a biomarker for clinical outcome. Dimethylarginine dimethylaminohydrolase (DDAH) is the main enzyme responsible for ADMA metabolism and elimination. Adipose tissue ADMA concentrations and DDAH activity and their role in diabetes and obesity have not yet been investigated. In this study, we evaluated clinical microdialysis in combination with a sensitive analytical method (GC-MS/MS) to measure ADMA concentrations in extracellular fluid. Adipose tissue ADMA concentrations were assessed before and during an oral glucose tolerance test in lean healthy subjects and subjects with diabetes (n = 4 each), and in morbidly obese subjects before and after weight loss of 30 kg (n = 7). DDAH activity was determined in subcutaneous and visceral adipose tissue obtained during laparoscopic surgery (n = 5 paired samples). Mean interstitial ADMA concentrations did not differ between study populations (healthy 0.17 0.03 ?M; diabetic 0.21 0.03 ?M; morbidly obese 0.16 0.01 and 0.17 0.01 ?M before and after weight loss, respectively). We did not observe any response of interstitial ADMA concentrations to the oral glucose challenge. Adipose tissue DDAH activity was negligible compared to liver tissue. Thus, adipose tissue ADMA plays a minor role in NO-dependent regulation of adipose tissue blood flow and metabolism. PMID:24445256

May, Marcus; Batkai, Sandor; Zrner, Alexander A.; Tsikas, Dimitrios; Jordan, Jens; Engeli, Stefan

2014-01-01

306

Clinical evaluation of extracellular ADMA concentrations in human blood and adipose tissue.  

PubMed

Circulating asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, has been proposed as a biomarker for clinical outcome. Dimethylarginine dimethylaminohydrolase (DDAH) is the main enzyme responsible for ADMA metabolism and elimination. Adipose tissue ADMA concentrations and DDAH activity and their role in diabetes and obesity have not yet been investigated. In this study, we evaluated clinical microdialysis in combination with a sensitive analytical method (GC-MS/MS) to measure ADMA concentrations in extracellular fluid. Adipose tissue ADMA concentrations were assessed before and during an oral glucose tolerance test in lean healthy subjects and subjects with diabetes (n = 4 each), and in morbidly obese subjects before and after weight loss of 30 kg (n = 7). DDAH activity was determined in subcutaneous and visceral adipose tissue obtained during laparoscopic surgery (n = 5 paired samples). Mean interstitial ADMA concentrations did not differ between study populations (healthy 0.17 0.03 M; diabetic 0.21 0.03 M; morbidly obese 0.16 0.01 and 0.17 0.01 M before and after weight loss, respectively). We did not observe any response of interstitial ADMA concentrations to the oral glucose challenge. Adipose tissue DDAH activity was negligible compared to liver tissue. Thus, adipose tissue ADMA plays a minor role in NO-dependent regulation of adipose tissue blood flow and metabolism. PMID:24445256

May, Marcus; Batkai, Sandor; Zrner, Alexander A; Tsikas, Dimitrios; Jordan, Jens; Engeli, Stefan

2014-01-01

307

Comparison of fibrogenesis caused by dermal and adipose tissue injury in an experimental model.  

PubMed

Mammalian skin is composed of three layers, the epidermis, the dermis, and the subcutis, which is composed primarily of adipose tissue. The dermal and adipose tissues are involved simultaneously when partial and full-thickness burns occur, and often induce scar formation. However, little is known about the role of the dermis and adipose tissue injury in scar formation or the difference in fibrogenesis between the two tissues. In this study with female red Duroc pigs, we created flaps of skin with a dermal plane of injury or deeper flaps with an adipose plane of injury on the back. We compared the extent of fibrogenesis by observing the deposition of extracellular matrix as well as the characteristics of cells in the injured area. In skin flaps with a dermal level of tissue injury, scar formation that was characterized by more extracellular matrix deposition and less apoptotic myofibroblasts in the injured area was observed. Our results suggest that scar formation does not correlate with injury at the level of the adipose tissue, and that adipose tissue might serve to alleviate fibrogenesis. PMID:20409146

Yuan, Bo; Wang, Xiqiao; Wang, Zhiyong; Wei, Jun; Qing, Chun; Lu, Shuliang

2010-01-01

308

Transgenic overexpression of hexose-6-phosphate dehydrogenase in adipose tissue causes local glucocorticoid amplification and lipolysis in male mice.  

PubMed

The prereceptor activation of glucocorticoid production in adipose tissue by NADPH-dependent 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) has emerged as a potential mechanism in the pathogenesis of visceral obesity and metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) is an endoplasmic reticulum lumen-resident enzyme that generates cofactor NADPH and thus mediates 11?-HSD1 activity. To determine the role of adipose H6PDH in the prereceptor modulation of 11?-HSD1 and metabolic phenotypes, we generated a transgenic (Tg) mouse model overexpressing H6PDH under the control of the enhancer-promoter region of the adipocyte fatty acid-binding protein (aP2) gene (aP2/H6PDH Tg mice). Transgenic aP2/H6PDH mice exhibited relatively high expression of H6PDH and elevated corticosterone production with induction of 11?-HSD1 activity in adipose tissue. This increase in corticosterone production in aP2-H6PDH Tg mice resulted in mild abdominal fat accumulation with induction of C/EBP mRNA expression and slight weight gain. Transgenic aP2/H6PDH mice also exhibited fasting hyperglycemia and glucose intolerance with insulin resistance. In addition, the aP2/H6PDH Tg mice have elevated circulating free fatty acid levels with a concomitant increased adipose lipolytic action associated with elevated HSL mRNA and Ser(660) HSL phosphorylation within abdominal fat. These results suggest that increased H6PDH expression specifically in adipose tissue is sufficient to cause intra-adipose glucocorticoid production and adverse metabolic phenotypes. These findings suggest that the aP2/H6PDH Tg mice may provide a favorable model for studying the potential impact of H6PDH in the pathogenesis of human metabolic syndrome. PMID:24381005

Wang, Ying; Liu, Limei; Du, Hanze; Nagaoka, Yoshiko; Fan, Winnie; Lutfy, Kabirullah; Friedman, Theodore C; Jiang, Meisheng; Liu, Yanjun

2014-03-01

309

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

SciTech Connect

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

Miller, M.F.

1987-01-01

310

Adipose Tissue and Adrenal Glands: Novel Pathophysiological Mechanisms and Clinical Applications  

PubMed Central

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

Kargi, Atil Y.; Iacobellis, Gianluca

2014-01-01

311

Specific monoclonal antibodies against embryonic chicken adipose tissue cell membranes and their application against developing adipocytes  

E-print Network

Use of anti-adipocyte monoclonal antibodies (MAb) for reduction of fat mass in chickens was investigated in two experiments. Reduction of adipose tissue mass was obtained only in Experiment II. In Experiment I, 132 fertilized broiler chicken eggs...

Corcoran, Melinda Valdez

2002-01-01

312

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

PubMed Central

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

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

2014-01-01

313

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

E-print Network

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

Gang, Gyoung Ok

2012-10-19

314

NRG4: An Endocrine Link between Brown Adipose Tissue and Liver.  

PubMed

Brown adipose tissue (BAT) directly regulates energy homeostasis via uncoupling of mitochondrial ATP production and thermogenesis. Wang etal. (2014) now report that BAT controls liver lipogenesis via secretion of the growth factor NRG4. PMID:25565202

Pfeifer, Alexander

2015-01-01

315

Adipose Tissue Density, a Novel Biomarker Predicting Mortality Risk in Older Adults  

PubMed Central

Background. Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics. Methods. VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n = 2,735) and AGES-Reykjavik (n = 5,131), and 24 nonhuman primates (NHPs). Associations between adipose density and mortality (413 years follow-up) were assessed with Cox proportional hazards models. In NHPs, adipose density was related to serum markers and tissue characteristics. Results. Higher density adipose tissue was associated with mortality in both studies with adjustment for risk factors including adipose area, total fat, and body mass index. In women, hazard ratio and 95% CI for the densest quintile (Q5) versus least dense (Q1) for VAT density were 1.95 (1.362.80; Health ABC) and 1.88 (1.312.69; AGES-Reykjavik) and for SAT density, 1.76 (1.352.28; Health ABC) and 1.56 (1.152.11; AGES-Reykjavik). In men, VAT density was associated with mortality in Health ABC, 1.52 (1.122.08), whereas SAT density was associated with mortality in both Health ABC, 1.58 (1.212.07), and AGES-Reykjavik, 1.43 (1.071.91). Higher density adipose tissue was associated with smaller adipocytes in NHPs. There were no consistent associations with inflammation in any group. Higher density adipose tissue was associated with lower serum leptin in Health ABC and NHPs, lower leptin mRNA expression in NHPs, and higher serum adiponectin in Health ABC and NHPs. Conclusion. VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related. PMID:23707956

2014-01-01

316

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

PubMed Central

Background Modern computer tomography (CT) equipment can be used to acquire whole-body data from large animals such as pigs in minutes or less. In some circumstances, computer assisted analysis of the resulting image data can identify and measure anatomical features. The thickness of subcutaneous adipose tissue at a specific site measured by ultrasound, is used in the pig industry to assess adiposity and inform management decisions that have an impact on reproduction, food conversion performance and sow longevity. The measurement site, called "P2", is used throughout the industry. We propose that CT can be used to measure subcutaneous adipose tissue thickness and identify novel measurement sites that can be used as predictors of general adiposity. Methods Growing pigs (N = 12), were each CT scanned on three occasions. From these data the total volume of adipose tissue was determined and expressed as a proportion of total volume (fat-index). A computer algorithm was used to determined 10,201 subcutaneous adipose thickness measurements in each pig for each scan. From these data, sites were selected where correlation with fat-index was optimal. Results Image analysis correctly identified the limits of the relevant tissues and automated measurements were successfully generated. Two sites on the animal were identified where there was optimal correlation with fat-index. The first of these was located 4 intercostal spaces cranial to the caudal extremity of the last rib, the other, a further 5 intercostal spaces cranially. Conclusion The approach to image analysis reported permits the creation of various maps showing adipose thickness or correlation of thickness with other variables by location on the surface of the pig. The method identified novel adipose thickness measurement positions that are superior (as predictors of adiposity) to the site which is in current use. A similar approach could be used in other situations to quantify potential links between subcutaneous adiposity and disease or production traits. PMID:19570228

McEvoy, Fintan J; Madsen, Mads T; Nielsen, Mai B; Svalastoga, Eiliv L

2009-01-01

317

Possible involvement of glucocorticoids in 5?-dihydrotestosterone-induced PCOS-like metabolic disturbances in the rat visceral adipose tissue.  

PubMed

Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, visceral obesity and insulin resistance. We hypothesized that changes in glucocorticoid metabolism and signaling in the visceral adipose tissue may contribute to disturbances of lipid metabolism in the rat model of PCOS obtained by 5?-dihydrotestosterone (DHT) treatment of prepubertal female Wistar rats. The results confirmed that DHT treatment caused anovulation, obesity and dyslipidemia. Enhanced glucocorticoid prereceptor metabolism, assessed by elevated intracellular corticosterone and increased 11 beta-hydroxysteroid dehydrogenase type 1 mRNA and protein levels, was accompanied by glucocorticoid receptor (GR) nuclear accumulation. In concert with the increased expression of GR-regulated prolipogenic genes (lipin-1, sterol regulatory element binding protein 1, fatty acid synthase, phosphoenolpyruvate carboxykinase), histological analyses revealed hypertrophic adipocytes. The results suggest that glucocorticoids influence lipid metabolism in the visceral adipose tissue in the way that may contribute to pathogenesis of metabolic disturbances associated with PCOS. PMID:25179821

Nikoli?, Marina; Macut, Djuro; Djordjevic, Ana; Veli?kovi?, Nataa; Nestorovi?, Nataa; Bursa?, Biljana; Anti?, Ivana Boi?; Macut, Jelica Bjeki?; Mati?, Gordana; Vojnovi? Milutinovi?, Danijela

2015-01-01

318

Maternal dexamethasone administration and the maturation of perirenal adipose tissue of the neonatal sheep  

PubMed Central

Maternal dexamethasone administration promotes fetal maturation such that thermoregulation is improved following premature delivery and is thus comparable with a full term birth. In the present study we determined the impact of dexamethasone on both the mothers' metabolic status together with adipose tissue function in the newborn. Glucocorticoid action, adipokine gene expression and mitochondrial protein abundance were measured in perirenal adipose tissue of neonatal sheep that were born into either a warm (30C) or cool (15C) ambient temperature at 140 days of gestation (dGA; term ?147 dGA), either two days after maternal dexamethasone administration, or at 146 dGA for controls. Dexamethasone administration resulted in a reduction in maternal food intake in conjunction with raised plasma cortisol and free triiodothyronine. In offspring of dexamethasone administered mothers, plasma cortisol was lower and non-esterified fatty acids (NEFA) higher than controls. Glucocorticoid receptor (GR), 11?-hydroxysteroid dehydrogenase (11?-HSD1), interleukin-6 and uncoupling protein (UCP)1 and 2 mRNA together with voltage dependent anion channel, cytochrome c protein and UCP1 abundance were all increased by dexamethasone administration and being born into a cool ambient temperature. Gene expression of tumor necrosis factor ?, adiponectin and peroxisome proliferator-activated receptor transcription factor ? were unaffected by dexamethasone. The abundance of mRNA for the GR, 11?-HSD1, UCP1 and 2 mRNA together with each protein were positively correlated to plasma NEFA and negatively correlated to plasma cortisol. In conclusion, despite reduced maternal food intake dexamethasone promotes maturation of glucocorticoid action and mitochondrial protein abundance in the newborn, an adaptation dependent on delivery temperature. PMID:19279732

Gnanalingham, MG; Hyatt, MA; Bispham, J; Mostyn, A; Clarke, L; Budge, H; Stephenson, T

2008-01-01

319

Maternal dexamethasone administration and the maturation of perirenal adipose tissue of the neonatal sheep.  

PubMed

Maternal dexamethasone administration promotes fetal maturation such that thermoregulation is improved following premature delivery and is thus comparable with a full term birth. In the present study we determined the impact of dexamethasone on both the mothers' metabolic status together with adipose tissue function in the newborn. Glucocorticoid action, adipokine gene expression and mitochondrial protein abundance were measured in perirenal adipose tissue of neonatal sheep that were born into either a warm (30 degrees C) or cool (15 degrees C) ambient temperature at 140 days of gestation (dGA; term approximately 147 dGA), either two days after maternal dexamethasone administration, or at 146 dGA for controls. Dexamethasone administration resulted in a reduction in maternal food intake in conjunction with raised plasma cortisol and free triiodothyronine. In offspring of dexamethasone administered mothers, plasma cortisol was lower and non-esterified fatty acids (NEFA) higher than controls. Glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenase (11beta-HSD1), interleukin-6 and uncoupling protein (UCP)1 and 2 mRNA together with voltage dependent anion channel, cytochrome c protein and UCP1 abundance were all increased by dexamethasone administration and being born into a cool ambient temperature. Gene expression of tumor necrosis factor alpha, adiponectin and peroxisome proliferator-activated receptor transcription factor gamma were unaffected by dexamethasone. The abundance of mRNA for the GR, 11beta-HSD1, UCP1 and 2 mRNA together with each protein were positively correlated to plasma NEFA and negatively correlated to plasma cortisol. In conclusion, despite reduced maternal food intake dexamethasone promotes maturation of glucocorticoid action and mitochondrial protein abundance in the newborn, an adaptation dependent on delivery temperature. PMID:19279732

Gnanalingham, Mg; Hyatt, Ma; Bispham, J; Mostyn, A; Clarke, L; Budge, H; Symonds, Me; Stephenson, T

2008-07-01

320

Effect of conjugated linoleic acids from beef or industrial hydrogenation on growth and adipose tissue characteristics of rats  

PubMed Central

Background The conjugated linoleic acid (CLA) content of beef can be increased by supplementing appropriate beef cattle diets with vegetable oil or oil seed. Yet the effect of consumption of such beef on adipose tissue characteristics is unclear, thus the study was conducted to compare adipose tissue responses of rats to diets containing beef from steers either not provided or provided the oil supplements to alter CLA composition of the fat in muscle. Methods Effects of feeding synthetic (industrial hydrogenation) CLA or CLA from beef on growth and adipose tissue responses of weanling, male, Wistar rats (n = 56; 14 per treatment diet) were investigated in a completely randomized design experiment. Diets were: control (CON) diet containing casein and soybean oil, synthetic CLA (SCLA) diet; where 1.69% synthetic CLA replaced soybean oil, two beef-diets; CONM and CLAM, containing freeze dried beef from steers either not fed or fed 14% sunflower seeds to increase CLA content of beef. Diets were isonitrogenous (20% protein) and isocaloric. Rat weights and ad libitum intakes were recorded every 2 wk. After 9 wk, rats were fasted for 24 h, blood sampled by heart puncture, sacrificed, tissue and organs were harvested and weights recorded. The adipose tissue responses with regard to cellularity and fatty acid compositions of retroperitoneal and inguinal adipose tissue were determined. Results Body weights and gains were comparable, but organ weights as percent of body weight were greater for rats fed SCLA than CONM. Fasting blood glucose concentration was lower (p < 0.01) in rats fed SCLA than those fed CONM or CLAM. Retroperitoneal and inguinal fat weights, as percent of body weight were greater (p < 0.01) in rats fed CONM or CLAM than those fed CON or SCLA diets. Adipocyte numbers were least in retroperitoneal tissue of rats fed SCLA, while inguinal tissue cell density and total number were lower (p = 0.02) in rats fed CLAM (7.26 107 cells/g and 8.03 108 cells) than those fed CONM (28.88 107 cells/g and 32.05 108 cells, respectively). Conclusion Study suggests that dietary CLA either as synthetic or high CLA-beef may alter adipose tissue characteristics by decreasing the number of adipocytes and by decreasing the size of the tissue. PMID:19386120

He, Mao L; Mir, Priya S; Okine, Erasmus K; Napadajlo, Helen

2009-01-01

321

Positional analysis of triacylglycerols from bovine adipose tissue lipids varying in degree of unsaturation  

Microsoft Academic Search

The objective of this study was to demonstrate that changing the fatty acid composition of bovine adipose tissue concurrently\\u000a changed (i) proportions of triacylglycerol species, (ii) fatty acid composition of triacylglycerol species, and (iii) positional\\u000a distribution of the component fatty acids of the triacylglycerol species. To achieve this, we took advantage of adipose tissue\\u000a lipids, from cattle fed in Australia

Stephen B. Smith; Aijun Yang; Tom W. Larsen; Ron K. Tume

1998-01-01

322

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

E-print Network

EFFECT OF EXERCISE TRAINING AND DIETARY FAT ON RAT ADIPOSE TISSUE LIPOLYSIS AND MORPHOLOGY A Thesis by SONIA BARSTAD NEALZ Submitted to the Office of Graduate Studies of Texas ASM University in partial fulfillment of the requirements... for the degree of MASTER OF SCIENCE May 1989 Major Subject: Nutrition EFFECT OF EXERCISE TRAINING AND DIETARY FAT ON RAT ADIPOSE TISSUE LIPOLYSIS AND MORPHOLOGY A Thesis by SONIA BARSTAD NEALE Approved as to style and content by: Karen S. Kubena (Co...

Neale, Sonia Barstad

1989-01-01

323

Effects of in ovo administration of thyroid hormones on growth and adipose tissue development  

E-print Network

. Harg (Chairman of Co ittee) S. L. Pardue (Member) i~- ~ /~ J. R. Lupton (Member) C. . Cr er of Dep tment) August 1988 ABSTRACT Effects of ~n Ovo Administration of Thyroid Hormones on Growth and Adipose Tissue Development (August 1988... response of adipocytes of growing birds. CBAPTBR II LITERATURE REVIEW In all animal species the development of adipose tissue is a process of progressively differentiating cell types. First, perivascular cells differentiate into adipoblasts...

Willingham, Elizabeth J.

1988-01-01

324

Adipose Stem Cells, Tissue Engineering, and Solid Organ Transplantation and Regeneration  

Microsoft Academic Search

\\u000a In the past years, adipose tissue has spurred a wide interest as a source of adult multipotent stem cells with the potential\\u000a to change the landscape of regenerative medicine. These adipose-derived stem\\/stromal cells (ASCs) are already establishing\\u000a their effectiveness at improving organ function when delivered for cell therapy. Tissue engineering applications are also\\u000a progressing at great strides in part due

Benoit Labb; Valrie Trottier; Maryse Proulx; Caroline Vincent; Julie Fradette

325

Low Sirt1 expression, which is upregulated by fasting, in human adipose tissue from obese women  

Microsoft Academic Search

Objective:Calorie restriction increases the life span in a number of different organisms. This effect is dependent upon activation of the Sirt1 enzyme, and many of the beneficial effects of calorie restriction can be mimicked using resveratrol, which activates the Sirt1 enzyme. Nothing is known about this system in human adipose tissue; therefore, we investigated this system in human adipose tissue.Design:Sirt1

S B Pedersen; J lholm; S K Paulsen; M F Bennetzen; B Richelsen

2008-01-01

326

Alcohol Consumption and Its Relation to Visceral and Subcutaneous Adipose Tissues in Healthy Male Koreans  

Microsoft Academic Search

Aims: The purpose of the present study is to investigate the association of alcohol with visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) distribution and metabolic syndrome (MetS). Design: We conducted a cross-sectional study in 951 healthy male Korean participants who underwent health checkups. We measured the cross-sectional areas of VAT and SAT by computed tomography of the abdomen

Kyae Hyung Kim; Seung-Won Oh; Hyuktae Kwon; Jin-Ho Park; Hochun Choi; BeLong Cho

2012-01-01

327

LSD1 promotes oxidative metabolism of white adipose tissue  

PubMed Central

Exposure to environmental cues such as cold or nutritional imbalance requires white adipose tissue (WAT) to adapt its metabolism to ensure survival. Metabolic plasticity is prominently exemplified by the enhancement of mitochondrial biogenesis in WAT in response to cold exposure or ?3-adrenergic stimulation. Here we show that these stimuli increase the levels of lysine-specific demethylase 1 (LSD1) in WAT of mice and that elevated LSD1 levels induce mitochondrial activity. Genome-wide binding and transcriptome analyses demonstrate that LSD1 directly stimulates the expression of genes involved in oxidative phosphorylation (OXPHOS) in cooperation with nuclear respiratory factor 1 (Nrf1). In transgenic (Tg) mice, increased levels of LSD1 promote in a cell-autonomous manner the formation of islets of metabolically active brown-like adipocytes in WAT. Notably, Tg mice show limited weight gain when fed a high-fat diet. Taken together, our data establish LSD1 as a key regulator of OXPHOS and metabolic adaptation in WAT. PMID:24912735

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

2014-01-01

328

At the crossroad of T cells, adipose tissue, and diabetes.  

PubMed

The study of how different intracellular metabolic signaling pathways impact the control of self-immune tolerance and how metabolic dysregulation in overweight, obesity, and diabetes is able to alter self-immune tolerance are topics of intensive investigation. Recent evidence suggests that metabolic and autoimmune diseases, both characterized by chronic inflammation and an altered self-immune tolerance, are more common in affluent countries. The reasons for such phenomena are still not completely understood, but the 'metabolic pressure' induced by nutritional overload, typical of more developed countries, seems to play a role. In this context, the discovery of the adipose tissue-derived hormone leptin has shed fundamental insights on how these processes might occur. We believe that there is a strong relationship among leptin, metabolic state, and immunological self-tolerance. We hypothesize that the leptin-induced metabolic pressure sets the basis for an exaggerated immuno-inflammatory response to altered self or non-self, leading to chronic inflammation, metabolic dysregulation, and autoimmunity in subjects with risk factors (i.e. genetic predisposition, environment, sex, infectious agents, etc). Capitalizing on our joint effort and trans-disciplinary expertise in metabolism, self-tolerance, and autoimmune diseases, this review highlights key questions on the basic mechanisms governing immune tolerance in the context of metabolic and autoimmune disease susceptibility. PMID:22889219

Matarese, Giuseppe; Procaccini, Claudio; De Rosa, Veronica

2012-09-01

329

Brown adipose tissue during puberty and with aging.  

PubMed

It was previously assumed that brown adipose tissue (BAT) is present in humans only for a short period following birth, the time in which mechanisms of generating heat by way of shivering are not yet developed. Although BAT is maximally recruited in early infancy, findings in recent years have led to a new consensus that metabolically active BAT remains present in most children and many adult humans. Evidence to date supports a slow and steady decline in BAT activity throughout life, with the exception of an intriguing spike in the prevalence and volume of BAT around the time of puberty that remains poorly understood. Because BAT activity is more commonly observed in individuals with a lower body mass index, an association seen in both adult and pediatric populations, there is the exciting possibility that BAT is protective against childhood and adult obesity. Indeed, the function and metabolic relevance of human BAT is currently an area of vigorous research. The goal of this review is to summarize what is currently known about changes that occur in BAT during various stages of life, with a particular emphasis on puberty and aging. PMID:24888388

Rogers, Nicole H

2014-06-01

330

Postnatal changes in fatty acids composition of brown adipose tissue  

NASA Astrophysics Data System (ADS)

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- ?-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.

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

1992-03-01

331

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

NASA Astrophysics Data System (ADS)

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.

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

2014-10-01

332

Inflammation stimulates niacin receptor (GPR109A/HCA2) expression in adipose tissue and macrophages.  

PubMed

Many of the beneficial and adverse effects of niacin are mediated via a G protein receptor, G protein-coupled receptor 109A/hydroxycarboxylic acid 2 receptor (GPR109A/HCA2), which is highly expressed in adipose tissue and macrophages. Here we demonstrate that immune activation increases GPR109A/HCA2 expression. Lipopolysaccharide (LPS), TNF, and interleukin (IL) 1 increase GPR109A/HCA2 expression 3- to 5-fold in adipose tissue. LPS also increased GPR109A/HCA2 mRNA levels 5.6-fold in spleen, a tissue rich in macrophages. In peritoneal macrophages and RAW cells, LPS increased GPR109A/HCA2 mRNA levels 20- to 80-fold. Zymosan, lipoteichoic acid, and polyinosine-polycytidylic acid, other Toll-like receptor activators, and TNF and IL-1 also increased GPR109A/HCA2 in macrophages. Inhibition of the myeloid differentiation factor 88 or TIR-domain-containing adaptor protein inducing IFN? pathways both resulted in partial inhibition of LPS stimulation of GPR109A/HCA2, suggesting that LPS signals an increase in GPR109A/HCA2 expression by both pathways. Additionally, inhibition of NF-?B reduced the ability of LPS to increase GPR109A/HCA2 expression by ?50% suggesting that both NF-?B and non-NF-?B pathways mediate the LPS effect. Finally, preventing the LPS-induced increase in GPR109A/HCA2 resulted in an increase in TG accumulation and the expression of enzymes that catalyze TG synthesis. These studies demonstrate that inflammation stimulates GPR109A/HCA2 and there are multiple intracellular signaling pathways that mediate this effect. The increase in GPR109A/HCA2 that accompanies macrophage activation inhibits the TG accumulation stimulated by macrophage activation. PMID:25320346

Feingold, Kenneth R; Moser, Arthur; Shigenaga, Judy K; Grunfeld, Carl

2014-12-01

333

Increased systemic and adipose tissue cytokines in patients with HIV-associated lipodystrophy.  

PubMed

The lipodystrophy syndrome (adipose tissue redistribution and metabolic abnormalities) observed with highly active antiretroviral therapy (HAART) during human immunodeficiency virus (HIV) infection may be related to increased proinflammatory cytokine activity. We measured acute cytokine (TNF-alpha, IL-6, leptin), glycerol, and lactate secretion from abdominal subcutaneous adipose tissue (SAT), and systemic cytokine levels, in HIV-infected subjects with and without lipodystrophy (HIVL+ and HIVL-, respectively) and healthy non-HIV controls. Lipodystrophy was confirmed and characterized as adipose tissue redistribution in HIVL+ compared with HIVL- and controls, by dual-energy X-ray absorptiometry and by whole body MRI. TNF-alpha secretion from abdominal SAT and circulating levels of IL-6, soluble TNF receptors I and II, and insulin were elevated in HIVL+ relative to HIVL- and/or controls, particularly in HIVL+ undergoing HAART. In the HIV-infected group as a whole, IL-6 secretion from abdominal SAT and serum IL-6 were positively associated with visceral fat and were negatively associated with the relative amount of lower limb adipose tissue (P < 0.01). Decreased leptin and increased lactate secretion from abdominal SAT were specifically associated with HAART. In conclusion, increased cytokine secretion from adipose tissue and increased systemic proinflammatory cytokine activity may play a significant role in the adipose tissue remodeling and/or the metabolic abnormalities associated with the HIV-lipodystrophy syndrome in patients undergoing HAART. PMID:14532165

Johnson, Julia A; Albu, Jeanine B; Engelson, Ellen S; Fried, Susan K; Inada, Yoritaro; Ionescu, Gabriel; Kotler, Donald P

2004-02-01

334

Adipose triglyceride lipase expression in human adipose tissue and muscle. Role in insulin resistance and response to training and pioglitazone  

PubMed Central

Objective Adipose triglyceride lipase (ATGL) catalyzes the first step in adipocyte and muscle triglyceride hydrolysis, and Comparative Gene Identification-58 (CGI-58) is an essential cofactor. We studied the expression of ATGL and CGI-58 in human adipose and muscle, and examined correlations with markers of muscle fatty acid oxidation. Materials/Methods Non diabetic volunteers were studied. Subjects with impaired glucose tolerance were treated with pioglitazone or metformin for 10 weeks. Normal glucose tolerant subjects underwent a 12 week training program. We examined changes in ATGL and CGI-58 with obesity and insulin resistance, and effects of exercise and pioglitazone. Results ATGL mRNA expression showed no correlation with either body mass index (BMI) or insulin sensitivity (SI) in either adipose or muscle. However, adipose ATGL protein levels were inversely correlated with BMI (r=?0.64, p<0.02), and positively correlated with SI (r=0.67, p<0.02). In muscle, ATGL mRNA demonstrated a strong positive relationship with carnitine palmitoyltransferase I mRNA (r=0.82, p<0.0001), and the adiponectin receptors AdipoR1 mRNA (r=0.71, p<0.0001), and AdipoR2 mRNA (r=0.74, p<0.0001). Muscle CGI-58 mRNA was inversely correlated with intramyocellular triglyceride in both type 1 (r=?0.35, p<0.05) and type 2 (r=?0.40, p<0.05) fibers. Exercise training resulted in increased muscle ATGL and pioglitazone increased adipose ATGL by 31% (p<0.05). Pioglitazone also increased ATGL in adipocytes. Conclusions Adipose ATGL protein is decreased with insulin resistance and obesity, and muscle ATGL mRNA is associated with markers of fatty acid oxidation in muscle, as is CGI-58. The regulation of ATGL and CGI-58 have important implications for the control of lipotoxicity. PMID:21129760

Yao-Borengasser, Aiwei; Varma, Vijayalakshmi; Coker, Robert H.; Ranganathan, Gouri; Phanavanh, Bounleut; Rasouli, Neda; Kern, Philip A.

2010-01-01

335

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

PubMed Central

Vascular endothelial growth factor (VEGF) is critical for angiogenesis, but also has pleiotropic effects on several nonvascular cells. Our aim was to investigate the role of VEGF in brown adipose tissue (BAT). We show that VEGF expression increases 2.5-fold during differentiation of cultured murine brown adipocytes and that VEGF receptor-2 is phosphorylated, indicating VEGF signaling. VEGF increased proliferation in brown preadipocytes in vitro by 70%, and blockade of VEGF signaling using anti-VEGFR2 antibody DC101 increased brown adipocyte apoptosis, as determined by cell number and activation of caspase 3. Systemic VEGF neutralization in mice, accomplished by adenoviral expression of soluble Flt1, resulted in 7-fold increase in brown adipocyte apoptosis, mitochondrial degeneration, and increased mitophagy compared to control mice expressing a null adenovirus. Absence of the heparan sulfate-binding VEGF isoforms, VEGF164 and VEGF188, resulted in abnormal BAT development in mice at E15.5, with fewer brown adipocytes and lower mitochondrial protein compared to wild-type littermates. These results suggest a role for VEGF in brown adipocytes and preadipocytes to promote survival, proliferation, and normal mitochondria and development.Bagchi, M., Kim, L A., Boucher, J., Walshe, T. E., Kahn, C. R., D'Amore, P. A. Vascular endothelial growth factor is important for brown adipose tissue development and maintenance. PMID:23682123

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

2013-01-01

336

Adiponectin self-regulates its expression and multimerization in adipose tissue: an autocrine/paracrine mechanism?  

PubMed

Adiponectin, a 30-kDa peptide hormone discovered in the mid 1990s, is secreted abundantly and exclusively by adipose tissue. Adiponectin exists in three major forms: a low molecular weight (LMW) trimer, a medium molecular weight (MMW) hexamer, and a high molecular weight (HMW) 18-36 oligomer. The HMW oligomer has the most potent insulin-sensitizing activity therefore impaired adiponectin multimerization may lead to impaired glycemic control. Decreased ratio of HMW/total adiponectin has been observed in patients with obesity, type-2 diabetes mellitus, cardiovascular diseases and insulin resistance-related metabolic syndrome. Previous studies have indicated that berberine or aminoimidazole carboxamide ribonucleotide (AICAR)-induced activation of AMP-activated protein kinase (AMPK) suppresses the expression of adiponectin but promotes adiponectin multimerization in adipocytes. Since adiponectin activates AMPK through adiponectin receptors (AdipoRs) in the membranes of adipocytes, we speculate that adiponectin self-regulates its expression and multimerization in adipose tissue. The hypothesis suggests a potential drug target for treating insulin resistance and provides new interpretation of several clinical observations. In addition, we propose a rapid method for one-step detection of the distribution of adiponectin oligomers in approximately 30 min, based on the open sandwich immunoassay and fluorescence resonance energy transfer technology. With the development of this new method, the ratio of HMW/total adiponectin may be applied in clinical diagnosis as a novel biomarker for insulin resistance and metabolic disorders. PMID:22014406

Lin, Huan; Li, Zhen

2012-01-01

337

Differential lncRNA expression profiles in brown and white adipose tissues.  

PubMed

Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. It can serve as key co-activators of proteins involved in transcriptional regulation. Studies have found that white and brown adipocytes both originate from the mesoderm. However, it remains unclear whether lncRNAs function during adipogenesis or in energy metabolism in brown adipose tissue (BAT) and white adipose tissue (WAT). In this study, we used lncRNA microarray technology to evaluate differences in the lncRNA expression profiles of WAT and BAT. We observed 735 up-regulated and 877 down-regulated lncRNAs (fold change >4.0). To reveal the potential functions of these lncRNAs, we applied GO and pathway analyses to study the differentially expressed lncRNAs. We found that AK142386 and AK133540 may affect adipogenesis and metabolism. Our data indicate that AK142386 and AK133540 may be involved in BAT and WAT development through their target genes Hoxa3 and Acad10. Together, we have identified numerous lncRNAs and these lncRNAs can potentially serve as a required component for proper adipogenesis. PMID:25472036

Chen, Jiantao; Cui, Xianwei; Shi, Chunmei; Chen, Ling; Yang, Lei; Pang, Lingxia; Zhang, Jun; Guo, Xirong; Wang, Jiaqin; Ji, Chenbo

2014-12-01

338

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

PubMed

Obesity and diabetes mellitus are worldwide epidemics driven by the disruption in energy balance. In recent years, it was discovered that functional brown adipose tissue (BAT), once thought to exist mainly in infants, is present in adults, and can be detected during cold stimulation, and is associated with decreased adiposity. Brown fat pads were shown to be highly vascularized and metabolically active and on stimulation, they caused enhanced energy expenditure and increased glucose and fatty acid uptake. These observations drew attention to the possibility that nonshivering thermogenesis mediated by activation of BAT might be important in human energy balance and a potential tool to counter obesity. Recent investigations have revealed significant advances in the understanding of the role of BAT-mediated thermogenesis, uncovering essential knowledge on the origin, differentiation, activation, and regulation of BAT in both murine models and humans. In addition to classic BAT depots, transformation of white adipocytes into brown-like adipocytes, and the development of "beige" cells from distinct precursors, were demonstrated in different animal models and resulted in increased thermogenic activity. Several transcription factors, activating proteins, and hormones are increasingly identified as regulating the development and function of both brown-like adipocytes and classic brown fat pads. This review will summarize the evolution of research on BAT in humans, in light of the renewed scientific interest and growing body of evidence showing that recruitment and activation of BAT and browning of white adipose tissue can affect energy expenditure and may be a future feasible target in the treatment of metabolic diseases. PMID:23803970

Zafrir, B

2013-10-01

339

Inhibition of Glyceroneogenesis by Histone Deacetylase 3 Contributes to Lipodystrophy in Mice with Adipose Tissue Inflammation  

PubMed Central

We have reported that the nuclear factor-?B (NF-?B) induces chronic inflammation in the adipose tissue of p65 transgenic (Tg) mice, in which the NF-?B subunit p65 (RelA) is overexpressed from the adipocyte protein 2 (aP2) gene promoter. Tg mice suffer a mild lipodystrophy and exhibit deficiency in adipocyte differentiation. To understand molecular mechanism of the defect in adipocytes, we investigated glyceroneogenesis by examining the activity of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in adipocytes. In aP2-p65 Tg mice, Pepck expression is inhibited at both the mRNA and protein levels in adipose tissue. The mRNA reduction is a consequence of transcriptional inhibition but not alteration in mRNA stability. The Pepck gene promoter is inhibited by NF-?B, which enhances the corepressor activity through activation of histone deacetylase 3 (HDAC3) in the nucleus. HDAC3 suppresses Pepck transcription by inhibiting the transcriptional activators, peroxisome proliferator-activated receptor-?, and cAMP response element binding protein. The NF-?B activity is abolished by Hdac3 knockdown or inhibition of HDAC3 catalytic activity. In a chromatin immunoprecipitation assay, HDAC3 interacts with peroxisome proliferator-activated receptor-? and cAMP response element binding protein in the Pepck promoter when NF-?B is activated by TNF-?. These results suggest that HDAC3 mediates NF-?B activity to repress Pepck transcription. This mechanism is responsible for inhibition of glyceroneogenesis in adipocytes, which contributes to lipodystrophy in the aP2-p65 Tg mice. PMID:21406501

Zhang, Jin; Henagan, Tara M.; Gao, Zhanguo

2011-01-01

340

Human lipodystrophies: genetic and acquired diseases of adipose tissue  

PubMed Central

Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2 (AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPAR?. Importantly, lamin A/C mutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their aetiology is generally unknown, they could be associated with signs of auto-immunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardio-vascular and hepatic complications. PMID:20551664

Capeau, Jacqueline; Magr, Jocelyne; Caron-Debarle, Martine; Lagathu, Claire; Antoine, Bndicte; Brziat, Vronique; Lascols, Olivier; Bastard, Jean-Philippe; Vigouroux, Corinne

2010-01-01

341

Human lipodystrophies: genetic and acquired diseases of adipose tissue.  

PubMed

Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2(AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARgamma. Importantly, lamin A/Cmutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their etiology is generally unknown, they could be associated with signs of autoimmunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first-generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardiovascular and hepatic complications. PMID:20551664

Capeau, Jacqueline; Magr, Jocelyne; Caron-Debarle, Martine; Lagathu, Claire; Antoine, Bndicte; Brziat, Vronique; Lascols, Olivier; Bastard, Jean-Philippe; Vigouroux, Corinne

2010-01-01

342

Adiponectin induces a20 expression in adipose tissue to confer metabolic benefit.  

PubMed

Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. We detail that mice lacking Reverb? exhibit enhanced fat storage without the predicted increased WAT inflammation or loss of insulin sensitivity. In contrast to most animal models of obesity and obese human patients, Reverb?(-/-) mice exhibit elevated serum adiponectin levels and increased adiponectin secretion from WAT explants in vitro, highlighting a potential anti-inflammatory role of this adipokine in hypertrophic WAT. Indeed, adiponectin was found to suppress primary macrophage responses to lipopolysaccharide and proinflammatory fatty acids, and this suppression depended on glycogen synthase kinase 3? activation and induction of A20. Attenuated inflammatory responses in Reverb?(-/-) WAT depots were associated with tonic elevation of A20 protein and ex vivo shown to depend on A20. We also demonstrate that adipose A20 expression in obese human subjects exhibits a negative correlation with measures of insulin sensitivity. Furthermore, bariatric surgery-induced weight loss was accompanied by enhanced WAT A20 expression, which is positively correlated with increased serum adiponectin and improved metabolic and inflammatory markers, including C-reactive protein. The findings identify A20 as a mediator of adiponectin anti-inflammatory action in WAT and a potential target for mitigating obesity-related pathology. PMID:25190567

Hand, Laura E; Usan, Paola; Cooper, Garth J S; Xu, Lance Y; Ammori, Basil; Cunningham, Peter S; Aghamohammadzadeh, Reza; Soran, Handrean; Greenstein, Adam; Loudon, Andrew S I; Bechtold, David A; Ray, David W

2015-01-01

343

ENPP2 contributes to adipose tissue expansion and insulin resistance in diet-induced obesity.  

PubMed

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

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

2014-12-01

344

Angiogenic Deficiency and Adipose Tissue Dysfunction Are Associated with Macrophage Malfunction in SIRT1?/? Mice  

PubMed Central

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor ? and nuclear factor ?B. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1?/?) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1?/? mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-?) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1?/? mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1?/? mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue. PMID:22315447

Xu, Fen; Burk, David; Gao, Zhanguo; Yin, Jun; Zhang, Xia

2012-01-01

345

Directing Parthenogenetic Stem Cells Differentiate into Adipocytes for Engineering Injectable Adipose Tissue  

PubMed Central

The selection of appropriate seed cells is crucial for adipose tissue engineering. Here, we reported the stepwise induction of parthenogenetic embryonic stem cells (pESCs) to differentiate into adipogenic cells and its application in engineering injectable adipose tissue with Pluronic F-127. pESCs had pluripotent differentiation capacity and could form teratomas that include the three primary germ layers. Cells that migrated from the embryoid bodies (EBs) were selectively separated and expanded to obtain embryonic mesenchymal stem cells (eMSCs). The eMSCs exhibited similar cell surface marker expression profiles with bone morrow mesenchymal stem cells (BMSCs) and had multipotent differentiation capacity. Under the induction of dexamethasone, indomethacin, and insulin, eMSCs could differentiate into adipogenic cells with increased expression of adipose-specific genes and oil droplet depositions within the cytoplasm. To evaluate their suitability as seed cells for adipose tissue engineering, the CM-Dil labelled adipogenic cells derived from eMSCs were seeded into Pluronic F-127 hydrogel and injected subcutaneously into nude mice. Four weeks after injection, glistering and semitransparent constructs formed in the subcutaneous site. Histological observations demonstrated that new adipose tissue was successfully fabricated in the specimen by the labelled cells. The results of the current study indicated that pESCs have great potential in the fabrication of injectable adipose tissue. PMID:25587287

Liu, Wei; Yang, Xingyuan; Yan, Xingrong; Cui, Jihong; Liu, Wenguang; Sun, Mei; Rao, Yang; Chen, Fulin

2014-01-01

346

Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue  

PubMed Central

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 dietfed 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

Kosteli, Aliki; Sugaru, Eiji; Haemmerle, Guenter; Martin, Jayne F.; Lei, Jason; Zechner, Rudolf; Ferrante, Anthony W.

2010-01-01

347

Comparison of 3 T MRI and CT for the measurement of visceral and subcutaneous adipose tissue in humans  

PubMed Central

Objective CT is considered the gold standard imaging modality for measurement of visceral adipose tissue area. However, as CT imaging exposes subjects to ionising radiation, a comparable imaging technique without this exposure is desirable, such as MRI. Therefore, we compared the agreement of measures of visceral adipose tissue and subcutaneous adipose tissue area from single-slice images obtained at the umbilicus using a 3 T MRI scanner with single-slice images obtained via CT scan. Methods 64 images were obtained from 27 subjects who underwent MRI and CT scanning on the same day, after 1012 hours of fasting. Visceral and subcutaneous adipose tissue depots were manually separated and quantified using a multimodality image-processing software program. Results We found good agreement between CT and MRI for the measurement of both visceral adipose tissue and subcutaneous adipose tissue. BlandAltman difference analysis demonstrated a mean bias of ?2.9% (as a portion of total abdominal area) for visceral adipose tissue and +0.4% for subcutaneous adipose tissue, as measured by MRI compared with CT. Conclusion MRI is a safe, accurate and precise imaging modality for measuring both visceral and subcutaneous adipose tissue, making it a favourable alternative to CT for quantification of these adipose depots. PMID:22514099

Klopfenstein, B J; Kim, M S; Krisky, C M; Szumowski, J; Rooney, W D; Purnell, J Q

2012-01-01

348

Vitamin D deficiency decreases adiposity in rats and causes altered expression of uncoupling proteins and steroid receptor coactivator3.  

PubMed

The vitamin D endocrine system is functional in the adipose tissue, as demonstrated in vitro, in cultured adipocytes, and in vivo in mutant mice that developed altered lipid metabolism and fat storage in the absence of either 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or the vitamin D receptor. The aim of the present study was to examine the role of vitamin D and calcium on body adiposity in a diet-induced vitamin D deficient rat model. Vitamin D-deficient rats gained less weight and had lower amounts of visceral fat. Consistent with reduced adipose tissue mass, the vitamin D-deficient rats had low circulating levels of leptin, which reflects body fat stores. Expression of vitamin D and calcium sensing receptors, and that of genes involved in adipogenesis such as peroxisome proliferator-activated receptor, fatty acid synthase and leptin were significantly reduced in white adipose tissue of deficient rats compared to vitamin D-sufficient rats. Furthermore, the expression of uncoupling proteins (Ucp1 and Ucp2) was elevated in the white adipose tissue of the deficient rat indicative of higher energy expenditure, thereby leading to a lean phenotype. Expression of the p160 steroid receptor coactivator3 (SRC3), a key regulator of adipogenesis in white adipose tissue was decreased in vitamin D-deficient state. Interestingly, most of the changes observed in vitamin D deficient rats were corrected by calcium supplementation alone. Our data demonstrates that dietary vitamin D and calcium regulate adipose tissue function and metabolism. PMID:25132457

Bhat, Mehrajuddin; Noolu, Bindu; Qadri, Syed S Y H; Ismail, Ayesha

2014-10-01

349

Primary Hyperparathyroidism Influences the Expression of Inflammatory and Metabolic Genes in Adipose Tissue  

PubMed Central

Background Primary hyperparathyroidism (PHPT) is characterised by increased production of parathyroid hormone (PTH) resulting in elevated serum calcium levels. The influence on bone metabolism with altered bone resorption is the most studied clinical condition in PHPT. In addition to this, patients with PHPT are at increased risk of non-skeletal diseases, such as impaired insulin sensitivity, arterial hypertension and increased risk of death by cardiovascular diseases (CVD), possibly mediated by a chronic low-grade inflammation. The aim of this study was to investigate whether adipose tissue reflects the low-grade inflammation observed in PHPT patients. Methodology/Principal Findings Subcutaneous fat tissue from the neck was sampled from 16 non-obese patients with PHPT and from 16 patients operated for benign thyroid diseases, serving as weight-matched controls. RNA was extracted and global gene expression was analysed with Illumina BeadArray Technology. We found 608 differentially expressed genes (q-value<0.05), of which 347 were up-regulated and 261 were down-regulated. Gene ontology analysis showed that PHPT patients expressed increased levels of genes involved in immunity and defense (e.g. matrix metallopeptidase 9, S100 calcium binding protein A8 and A9, CD14, folate receptor 2), and reduced levels of genes involved in metabolic processes. Analysis of transcription factor binding sites present in the differentially expressed genes corroborated the up-regulation of inflammatory processes. Conclusions/Significance Our findings demonstrate that PHPT strongly influences gene regulation in fat tissue, which may result in altered adipose tissue function and release of pathogenic factors that increase the risk of CVD. PMID:21698093

Christensen, Monika H. E.; Dankel, Simon N.; Nordb, Yngve; Varhaug, Jan Erik; Alms, Bjrg; Lien, Ernst A.; Mellgren, Gunnar

2011-01-01

350

High-fat diet feeding induces sex-dependent changes in inflammatory and insulin sensitivity profiles of rat adipose tissue.  

PubMed

The aim of the study was to determine, in rats of both sexes, the effect of HF diet feeding on the expression of adipokines involved in inflammatory status and insulin sensitivity and on the levels of proteins involved in lipid handling of retroperitoneal adipose tissue. Eight-week-old Wistar rats of both sexes were fed a control diet (2.9% w/w fat) or an HF diet (30% w/w fat) for 14?weeks. Adiponectin, peroxisome proliferator-activated receptor ? and inflammatory marker mRNA levels were analyzed by real-time polymerase chain reaction. Levels of insulin receptor, glucose transporter 4, carnitine palmitoyltransferase 1, fatty acid synthase, hormone-sensitive lipase and lipoprotein lipase were determined by Western blot. HF diet feeding did not induce hyperphagia or body weight gain but did promote an increase in adiposity although only in male rats. HF diet impaired glucose tolerance and the expression of inflammatory and insulin sensitivity markers in adipose tissue of male rats, but not in female rats. Male rats seem to be more prone to disorders associated with an unbalanced composition of the diet, even in the absence of hyperphagia. In contrast, female rats counteract excessive fat intake by improving their ability to use lipid fuels, which limits adiposity and maintains insulin sensitivity. PMID:23112138

Estrany, Maria E; Proenza, Ana M; Gianotti, Magdalena; Llad, Isabel

2013-08-01

351

Epicardial adipose tissue: relationship between measurement location and metabolic syndrome.  

PubMed

Epicardial adipose tissue (EAT) is a contributing factor of metabolic syndrome (MS) and coronary artery disease (CAD). However, it is still unclear which measurement location of EAT area best reflects its cardiometabolic risk. The purpose of our study was to investigate the distribution of EAT and its relationship to the total EAT volume and MS. To assess volume and cross-sectional areas of EAT, coronary CT angiography were obtained in 256 asymptomatic subjects. The EAT areas within the threshold range of -190 to -30 Hounsfield units were measured at six representative slices. Correlations between single slice EAT areas and total EAT volumes were high across all measurement locations (correlation coefficient r > 0.80). The receiver-operator characteristic curves demonstrated EAT area at left main coronary artery (LMCA) was well discriminative for MS (AUC 0.82, p < 0.001) and CAD (AUC 0.76, p < 0.001). EAT areas across all measurement locations were significantly increased linearly with increasing number of MS components. EAT areas were significantly associated with MS at all measurement locations; the highest odds ratio (OR) between EAT area and MS was at the LMCA level (OR 5.86, p < 0.001). The OR between EAT area and coronary artery calcium was also significant in LMCA locations (OR 1.56, p = 0.042). We demonstrated that the single-slice EAT area measurement is a simple and reliable method compared with time-consuming volumetric measurements. The EAT area at LMCA level was the best single slice representing the risk of metabolic syndrome and coronary atherosclerosis. PMID:24293041

Chung, Ju-Hye; Kwon, Beom-June; Song, Sang-Wook; Ock, Sun-Myeong; Choi, Whan-Seok; Kim, Se-Hong

2014-01-01

352

Brown adipose tissue has sympathetic-sensory feedback circuits.  

PubMed

Brown adipose tissue (BAT) is an important source of thermogenesis which is nearly exclusively dependent on its sympathetic nervous system (SNS) innervation. We previously demonstrated the SNS outflow from brain to BAT using the retrograde SNS-specific transneuronal viral tract tracer, pseudorabies virus (PRV152) and demonstrated the sensory system (SS) inflow from BAT to brain using the anterograde SS-specific transneuronal viral tract tracer, H129 strain of herpes simplex virus-1. Several brain areas were part of both the SNS outflow to, and receive SS inflow from, interscapular BAT (IBAT) in these separate studies suggesting SNS-SS feedback loops. Therefore, we tested whether individual neurons participated in SNS-SS crosstalk by injecting both PRV152 and H129 into IBAT of Siberian hamsters. To define which dorsal root ganglia (DRG) are activated by BAT SNS stimulation, indicated by c-Fos immunoreactivity (IR), we prelabeled IBAT DRG innervating neurons by injecting the retrograde tracer Fast Blue (FB) followed 1 week later by intra-BAT injections of the specific ?3-adrenoceptor agonist CL316,243 in one pad and the vehicle in the contralateral pad. There were PRV152+H129 dually infected neurons across the neuroaxis with highest densities in the raphe pallidus nucleus, nucleus of the solitary tract, periaqueductal gray, hypothalamic paraventricular nucleus, and medial preoptic area, sites strongly implicated in the control of BAT thermogenesis. CL316,243 significantly increased IBAT temperature, afferent nerve activity, and c-Fos-IR in C2-C4 DRG neurons ipsilateral to the CL316,243 injections versus the contralateral side. The neuroanatomical reality of the SNS-SS feedback loops suggests coordinated and/or multiple redundant control of BAT thermogenesis. PMID:25653373

Ryu, Vitaly; Garretson, John T; Liu, Yang; Vaughan, Cheryl H; Bartness, Timothy J

2015-02-01

353

Epicardial adipose tissue thickness in patients with ankylosing spondylitis.  

PubMed

The purpose of our study was to measure epicardial adipose tissue (EAT) thickness as a novel indicator of atherosclerosis and cardiovascular risk factor in ankylosing spondylitis (AS) patients and to show the relationship with clinical parameters and inflammatory markers. Forty AS patients (42.75??12.43years) and 40 healthy individuals with no cardiovascular risk factor as the control group (43.02??14.78years) were included in the study. Carotid intima-media thickness (CIMT) and EAT thickness were measured in AS patients and the control group. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, glucose, erythrocyte sedimentation rate, urea, and blood pressure were investigated in both groups. In addition, the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were used to evaluate the association between clinical findings and CIMT and EAT in the patient group. CIMT and EAT thickness were higher in the AS patients compared to the control group. CIMT was 0.76??0.19 and 0.57??0.12mm (p?

Resorlu, Hatice; Akbal, Ayla; Resorlu, Mustafa; Gokmen, Ferhat; Ates, Can; Uysal, Fatma; Adam, Gurhan; Aylanc, Nilufer; Arslan, Muhammet; ?nceer, Besir Sahin

2015-02-01

354

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

PubMed

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

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

2014-11-01

355

Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue  

PubMed Central

Background: It is now widely accepted that the early-life nutritional environment is important in determining susceptibility to metabolic diseases. In particular, intra-uterine growth restriction followed by accelerated postnatal growth is associated with an increased risk of obesity, type-2 diabetes and other features of the metabolic syndrome. The mechanisms underlying these observations are not fully understood. Aim: Using a well-established maternal protein-restriction rodent model, our aim was to determine if exposure to mismatched nutrition in early-life programmes adipose tissue structure and function, and expression of key components of the insulin-signalling pathway. Methods: Offspring of dams fed a low-protein (8%) diet during pregnancy were suckled by control (20%)-fed dams to drive catch-up growth. This recuperated' group was compared with offspring of dams fed a 20% protein diet during pregnancy and lactation (control group). Epididymal adipose tissue from 22-day and 3-month-old control and recuperated male rats was studied using histological analysis. Expression and phosphorylation of insulin-signalling proteins and gene expression were assessed by western blotting and reverse-transcriptase PCR, respectively. Results: Recuperated offspring at both ages had larger adipocytes (P<0.001). Fasting serum glucose, insulin and leptin levels were comparable between groups but increased with age. Recuperated offspring had reduced expression of IRS-1 (P<0.01) and PI3K p110? (P<0.001) in adipose tissue. In adult recuperated rats, Akt phosphorylation (P<0.01) and protein levels of Akt-2 (P<0.01) were also reduced. Messenger RNA expression levels of these proteins were not different, indicating a post-transcriptional effect. Conclusion: Early-life nutrition programmes alterations in adipocyte cell size and impairs the protein expression of several insulin-signalling proteins through post-transcriptional mechanisms. These indices may represent early markers of insulin resistance and metabolic disease risk. PMID:23229735

Berends, L M; Fernandez-Twinn, D S; Martin-Gronert, M S; Cripps, R L; Ozanne, S E

2013-01-01

356

Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors  

PubMed Central

Purpose Adipose tissue contains a population of tumor-tropic mesenchymal progenitors, termed adipose stromal cells (ASC), which engraft in neighboring tumors to form supportive tumor stroma. We hypothesized that intra-abdominal visceral adipose tissue may contain a uniquely tumor promoting population of ASC to account for the relationship between excess visceral adipose tissue and mortality of intra-abdominal cancers. Experimental Design To investigate this, we isolated and characterized ASC from intra-abdominal omental adipose tissue (O-ASC) and characterized their effects on endometrial cancer progression as compared to subcutaneous adipose derived mesenchymal stromal cells (SC-ASC), bone marrow derived mesenchymal stromal cells (BM-MSC) and lung fibroblasts. To model chronic recruitment of ASC by tumors, cells were injected metronomically into mice bearing Hec1a xenografts. Results O-ASC expressed cell surface markers characteristic of BM-MSC and differentiated into mesenchymal lineages. Co-culture with O-ASC increased endometrial cancer cell proliferation in-vitro. Tumor tropism of O-ASC and SC-ASC for human Hec1a endometrial tumor xenografts was comparable, but O-ASC more potently promoted tumor growth. Compared with tumors in SC-ASC-injected mice, tumors in O-ASC-injected mice contained higher numbers of large tortuous desmin-positive blood vessels, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. O-ASC-exhibited enhanced motility as compared to SC-ASC in response to Hec1a secreted factors. Conclusions Visceral adipose contains a population of multipotent MSC that promote endometrial tumor growth more potently than MSC from subcutaneous adipose tissue. We propose that O-ASC recruited to tumors express specific factors that enhance tumor vascularization, promoting survival and proliferation of tumor cells. PMID:22167410

Klopp, Ann H.; Zhang, Yan; Solley, Travis; Amaya-Manzanares, Felipe; Marini, Frank; Andreeff, Michael; Debeb, Bisrat; Woodward, Wendy; Schmandt, Rosemarie; Broaddus, Russell; Lu, Karen; Kolonin, Mikhail G.

2011-01-01

357

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

PubMed

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

Bloor, Ian D; Symonds, Michael E

2014-06-01

358

Characterization of Cre recombinase models for the study of adipose tissue  

PubMed Central

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

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

2014-01-01

359

Epicardial adipose tissue thickness and plasma homocysteine in patients with metabolic syndrome and normal coronary arteries  

PubMed Central

Background Increased epicardial adipose tissue thickness and plasma homocysteine levels are associated with Metabolic Syndrome (MS) and coronary artery disease. The majority of patients with MS have subclinical or manifest coronary artery disease. The aim of this study was to evaluate the relationship between MS and plasma homocysteine levels and epicardial adipose tissue thickness in subjects without epicardial coronary artery disease. Methods Patients who underwent coronary angiography due to angina or equivocal symptoms and/or abnormal stress test results and were found to have normal coronary arteries were evaluated for the presence of MS. The study group comprised 75 patients with normal coronary arteries and MS, and the control group included 75 age-gender matched subjects without coronary artery disease or MS. Results Epicardial adipose tissue thickness (5.8??1.9mm vs. 4.3??1.6mm, p <0.001) and plasma homocysteine levels (21.6??6.1?mol/L vs. 15.1??5.8?mol/L, p <0.001) were significantly higher in the MS group. Body mass index, triglyceride level, weight, age and waist circumference were positively and HDL cholesterol level were negatively correlated with both epicardial adipose tissue thickness and plasma homocysteine level. Epicardial adipose tissue thickness had the strongest correlation with plasma homocysteine level (r?=?0.584, p?adipose tissue thickness, an increase of 3.51?mol/L (95%?CI: 2.24-4.79) in plasma homocysteine level was expected. Conclusions We observed a close relationship between MS and epicardial adipose tissue thickness and plasma homocysteine levels, even in the absence of overt coronary artery disease. PMID:24872849

2014-01-01

360

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

PubMed

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

Banerjee, A; Udin, S; Krishna, A

2011-02-01

361

Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer?  

PubMed

The relative effect of visceral and subcutaneous obesity on the risk of chronic metabolic disease has been a matter of long-term dispute. While ample data support either of the fat depots being causative or associative, valid argument for one depot often automatically belittles the other. Paradigms such as the visceral/portal hypothesis and the acquired lipodystrophy/ectopic fat storage and endocrine hypothesis have been proposed. Nevertheless, neither hypothesis alone explains the entire pathophysiological setting. Treatment of diabetes with thiazolidinediones selectively increases fat