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1

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

SciTech Connect

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

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

1985-11-01

2

Detecting protein carbonylation in adipose tissue and in cultured adipocytes.  

PubMed

Reactive oxygen species-mediated attack of the acyl chains of polyunsaturated fatty acids and triglycerides leads to the formation of lipid hydroperoxides. Lipid hydroperoxides are subject to nonenzymatic Fenton chemistry producing a variety of reactive aldehydes that covalently modify proteins in a reaction referred to as protein carbonylation. Given the significant content of triglycerides in fat tissue, adipose proteins are among the most heavily carbonylated. The laboratory has utilized two methodologies for the detection of protein carbonylation in tissue- and cell-based samples. The first utilizes biotin coupled to a hydrazide moiety and takes advantage of the numerous biotin detection systems. The second method utilizes an anti 4-hydroxy-trans-2,3-nonenal (4-HNE)-directed antibody that can detect both 4-HNE and the corresponding 4-oxo derivative when the samples are reduced. Using such methods, we have evaluated the profile of carbonylated proteins in epididymal white adipose tissue and 3T3-L1 adipocytes using both methods. In addition, we have investigated the effects of two antidiabetic drugs, pioglitazone and metformin, on protein carbonylation in 3T3-L1 adipocytes. Overall, the biotin hydrazide method is rapid, inexpensive, and easy to use, but its usefulness is limited because it detects a wide variety of carbonylated derivatives, which makes assignments of individual proteins difficult. Compared to the biotin hydrazide method, the anti-HNE antibody method detects specific proteins more readily but identifies only a subset of carbonylated proteins. As such, the combination of both methods allows for a comprehensive evaluation of protein carbonylation plus provides a means towards identification of specific carbonylation targets. PMID:24529443

Xu, Qinghui; Hahn, Wendy S; Bernlohr, David A

2014-01-01

3

Brown adipose tissue  

PubMed Central

Obesity is currently a global pandemic, and is associated with increased mortality and co-morbidities including many metabolic diseases. Obesity is characterized by an increase in adipose mass due to increased energy intake, decreased energy expenditure, or both. While white adipose tissue is specialized for energy storage, brown adipose tissue has a high concentration of mitochondria and uniquely expresses uncoupling protein 1, enabling it to be specialized for energy expenditure and thermogenesis. Although brown fat was once considered only necessary in babies, recent morphological and imaging studies have provided evidence that, contrary to prior belief, this tissue is present and active in adult humans. In recent years, the topic of brown adipose tissue has been reinvigorated with many new studies regarding brown adipose tissue differentiation, function and therapeutic promise. This review summarizes the recent advances, discusses the emerging questions and offers perspective on the potential therapeutic applications targeting this tissue.

Townsend, Kristy; Tseng, Yu-Hua

2012-01-01

4

Insulin regulates the unfolded protein response in human adipose tissue.  

PubMed

Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from ? 35 to ? 1,450 pmol/L). The insulin-induced UPR was not due to increased glucose uptake/metabolism and oxidative stress. It was associated, however, with increased protein synthesis, with accumulation of ubiquitination associated proteins, and with multiple posttranslational protein modifications (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations), some of which are potential causes for ER stress. These results reveal a new physiologic role of insulin and provide a putative mechanism for the development of ER stress in obesity. They may also have clinical and therapeutic implications, e.g., in diabetic patients treated with high doses of insulin. PMID:24130338

Boden, Guenther; Cheung, Peter; Salehi, Sajad; Homko, Carol; Loveland-Jones, Catherine; Jayarajan, Senthil; Stein, T Peter; Williams, Kevin Jon; Liu, Ming-Lin; Barrero, Carlos A; Merali, Salim

2014-03-01

5

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

6

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

7

cAMP-positive regulation of angiotensinogen gene expression and protein secretion in rat adipose tissue.  

PubMed

The adipose renin-angiotensin system (RAS) has been assigned to participate in the control of adipose tissue development and in the pathogenesis of obesity-related hypertension. In adipose cells, the biological responses to beta-adrenergic stimulation are mediated by an increase in intracellular cAMP. Because cAMP is known to promote adipogenesis and because an association exists between body fat mass, hypertension, and increased sympathetic stimulation, we examined the influence of cAMP on angiotensinogen (ATG) expression and secretion in rat adipose tissue. Exposure of primary cultured differentiated preadipocytes to the cAMP analog 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) or cAMP-stimulating agents (forskolin and IBMX) results in a significant increase in ATG mRNA levels. In adipose tissue fragments, 8-BrcAMP also increases ATG mRNA levels and protein secretion, but not in the presence of the protein kinase A inhibitor H89. The addition of isoproterenol, known to stimulate the synthesis of intracellular cAMP via beta-adrenoreceptors, had the same stimulatory effect on ATG expression and secretion. These results indicate that cAMP in vitro upregulates ATG expression and secretion in rat adipose tissue via the protein kinase A-dependent pathway. Further studies are required to determine whether this regulatory pathway is activated in human obesity, where increased sympathetic tone is frequently observed, and to elucidate the importance of adipose ATG to the elevated blood pressure observed in this pathological state. PMID:14761874

Serazin, Valérie; Dieudonné, Marie-Noelle; Morot, Mireille; de Mazancourt, Philippe; Giudicelli, Yves

2004-03-01

8

Surface protein characterization of human adipose tissue-derived stromal cells  

Microsoft Academic Search

Human bone marrow stromal cells are a multipotent population of cells capable of differentiating into a number of mesodermal lineages as well as supporting hematopoeisis. Their distinct protein and gene expression phenotype is well characterized in the literature. Human adipose tissue presents an alternative source of multipotent stromal cells. In this study, we have defined the phenotype of the human

Stan Gronthos; Dawn M. Franklin; Holly A. Leddy; Pamela G. Robey; Robert W. Storms; Jeffrey M. Gimble

2001-01-01

9

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

Microsoft Academic Search

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

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

1993-01-01

10

The role of AMP-activated protein kinase in regulating white adipose tissue metabolism.  

PubMed

AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that plays a major role in the maintenance of energy homeostasis in various organs and tissues. When activated, AMPK can induce substrate catabolism and shut down energy-consuming anabolic pathways to increase intracellular ATP availability. Even though most of these effects have been described in muscle and liver, several studies have provided compelling evidence that AMPK also plays an important role in the regulation of white adipose tissue (WAT) glucose and lipid metabolism. In fact, the effects of acute and chronic AMPK activation in the WAT induce profound changes in adiposity with important implications for the treatment of obesity and its related metabolic disorders. This review discusses the role of AMPK in the regulation of white adipocyte metabolism with respect to energy storage and release, gene expression, mitochondrial biogenesis, oxidative capacity, cell differentiation, and the potential impact on whole-body adiposity and energy homeostasis. PMID:22750051

Ceddia, R B

2013-02-25

11

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.

Wagner, Marek

2014-01-01

12

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.

Virtue, Sam; Vidal-Puig, Antonio

2013-01-01

13

Prolactin and adipose tissue.  

PubMed

The pituitary lactogenic hormone prolactin (PRL) exerts various physiological actions in humans and rodents via its binding to a membrane receptor. Beside its role in lactation and reproduction, accumulating evidence suggests that PRL has a crucial impact on energy balance by acting on two key players, the pancreas and the adipose tissue. Adipose tissue is now recognized as an endocrine organ and its metabolic activity appears to play an important role in pathophysiology such as obesity and diabetes. White adipocytes store excess of energy in the form of triglycerides for future need while brown adipocytes metabolize lipids and glucose to produce heat, highlighting their different metabolic functionality. The plasticity of white adipose tissue, by the emergence of beige adipocytes, appears to be essential in energy homeostasis. PRL receptor deficient mice provided direct evidence that PRL signaling is involved in the regulation of adipogenesis affecting energy balance and metabolic adaptation most notably during development. Moreover, it was demonstrated that PRL signaling participates to brown adipose tissue differentiation and function, opening novel understanding of hormonal regulation of energy balance. This review summarizes our current knowledge about PRL signaling and its role on adipose tissue. PMID:24120689

Carré, Nadège; Binart, Nadine

2014-02-01

14

Immunohistochemical Localization of Leptin and Uncoupling Protein in White and Brown Adipose Tissue  

Microsoft Academic Search

Leptin is synthesized exclusively by adipocytes and acts on the hypothalamus to regulate energy balance. Previous messenger RNA expression studies demonstrated that leptin is expressed in white adipocytes and also in brown adipose tissue, however expression in brown fat is markedly lower than in white fat. This suggests the possibility that leptin expression in brown adipose tissue is due to

SAVERIO CINTI; ROBERT C. FREDERICH; M. CRISTINA; RITA DE MATTEIS; JEFFREY S. FLIER; BRADFORD B. LOWELL

1997-01-01

15

Targeting adipose tissue  

PubMed Central

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

2012-01-01

16

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

PubMed Central

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

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

2013-01-01

17

Decreased RB1 mRNA, protein, and activity reflect obesity-induced altered adipogenic capacity in human adipose tissue.  

PubMed

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

Moreno-Navarrete, José María; Petrov, Petar; Serrano, Marta; Ortega, Francisco; García-Ruiz, Estefanía; Oliver, Paula; Ribot, Joan; Ricart, Wifredo; Palou, Andreu; Bonet, M Luisa; Fernández-Real, José Manuel

2013-06-01

18

Inflammation and insulin resistance exert dual effects on adipose tissue tumor protein 53 expression.  

PubMed

Objective:The purpose of this study was to investigate the expression of human adipose tissue protein 53 (p53) in subjects who varied widely in terms of obesity and insulin resistance. We also analyzed different in vivo and in vitro models to try to comprehend the associations found in humans.Methods:p53 was analyzed in human adipose and isolated adipocytes, in high fat-fed and GLP-1R KO mice, during in vitro adipogenesis, and in adipocytes after high glucose, rosiglitazone and inflammatory conditions. The effects of surgery-induced weight loss and ex vivo metformin were also evaluated.Results:Omental (OM) p53 gene expression (+27%, P=0.001) and protein (+11%, P=0.04) were increased in obese subjects and high fat diet-induced obese mice (+86%, P=0.018). Although the obesity-associated inflammatory milieu was associated with increased OM p53, this was negatively related to insulin resistance and glycated hemoglobin, and positively with biomarkers for insulin sensitivity. Multiple linear regression analyses revealed that glycated hemoglobin (P<0.0001) and body mass index (P=0.048) contributed independently to explain 13.7% (P<0.0001) of the OM p53 variance. Accordingly, the improvement of insulin sensitivity with surgery-induced weight loss (+51%, P=0.01) and metformin (+42%, P=0.02) led to increased adipose p53. While the glucose-intolerant GLP-1R KO mice showed decreased mesenteric p53 (-45.4%, P=0.017), high glucose led to decreased p53 in pre-adipocytes (-27%, P<0.0001). Inflammatory treatments led to increased p53 (+35%, P<0.0001), while Rs downregulated this expression (-40%, P=0.005) in mature adipocytes.Conclusion:Inflammation and insulin resistance exert dual effects on adipose p53, which seems to be the final result of these opposing forces. PMID:23999197

Ortega, F J; Moreno-Navarrete, J M; Mayas, D; Serino, M; Rodriguez-Hermosa, J I; Ricart, W; Luche, E; Burcelin, R; Tinahones, F J; Frühbeck, G; Mingrone, G; Fernández-Real, J M

2014-05-01

19

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

PubMed

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

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

2012-11-01

20

Comparison of messenger RNA distribution for 60 proteins in fat cells vs the nonfat cells of human omental adipose tissue  

Microsoft Academic Search

The messenger RNA (mRNA) distribution of 60 proteins was examined in the 3 fractions obtained by collagenase digestion (fat cells and the nonfat cells comprising the tissue remaining after collagenase digestion [matrix] and the stromovascular cells) of omental adipose tissue obtained from morbidly obese women undergoing bariatric surgery. Fat cells were enriched by at least 3-fold as compared with nonfat

John N. Fain; Ben Buehrer; Suleiman W. Bahouth; David S. Tichansky; Atul K. Madan

2008-01-01

21

Renaissance of Brown Adipose Tissue  

Microsoft Academic Search

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

D. Tews; M. Wabitsch

2011-01-01

22

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

PubMed

Adipose tissues regulate metabolism, reproduction, and life span. The development and growth of adipose tissue are due to increases of both adipocyte cell size and cell number; the latter is mediated by adipocyte progenitors. Various markers have been used to identify either adipocyte progenitors or mature adipocytes. The fatty acid binding protein 4 (FABP4), commonly known as adipocyte protein 2 (aP2), has been extensively used as a marker for differentiated adipocytes. However, whether aP2 is expressed in adipogenic progenitors is controversial. Using Cre/LoxP-based cell lineage tracing in mice, we have identified a population of aP2-expressing progenitors in the stromal vascular fraction (SVF) of both white and brown adipose tissues. The aP2-lineage progenitors reside in the adipose stem cell niche and express adipocyte progenitor markers, including CD34, Sca1, Dlk1, and PDGFR?. When isolated and grown in culture, the aP2-expressing SVF cells proliferate and differentiate into adipocytes upon induction. Conversely, ablation of the aP2 lineage greatly reduces the adipogenic potential of SVF cells. When grafted into wild-type mice, the aP2-lineage progenitors give rise to adipose depots in recipient mice. Therefore, the expression of aP2 is not limited to mature adipocytes, but also marks a pool of undifferentiated progenitors associated with the vasculature of adipose tissues. Our finding adds to the repertoire of adipose progenitor markers and points to a new regulator of adipose plasticity. PMID:23047894

Shan, Tizhong; Liu, Weiyi; Kuang, Shihuan

2013-01-01

23

The OB protein (leptin) pathway--a link between adipose tissue mass and central neural networks.  

PubMed

OB protein (also known as leptin), a previously unknown protein signal, is secreted from adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks that regulate ingestive behavior and energy balance. OB protein provides a communication link from fat tissue and the brain. Rapidly accumulating evidence suggests that OB protein appears to play a major role in the control of body fat stores through coordinated regulation of feeding behavior, metabolism, autonomic nervous system and body energy balance in rodents, primates and humans. The field has rapidly moved from cloning of the ob gene to demonstration of complex regulation of ob gene expression in adipose tissue in rats and humans, and then the demonstration of potent biological activity of OB protein in ob/ob, diet-induced, and lean mice as well as obese and lean rats but not in db/db obese mice. A significant milestone was our demonstration that central administration of OB protein lead to reductions in food intake, body weight and alterations in metabolism consistent with activation of the autonomic nervous system. These findings were followed by the identification of a central binding site for labelled OB protein in the choroid plexus in ob/ob, db/db and lean mice as well as lean and obese Zucker rats. The expression cloning of a central receptor, OB-R, from the mouse choroid plexus soon followed. The OB-R receptor was found to be expressed in the choroid plexus, the hypothalamus as well as several peripheral tissues. OB-R exists in multiple forms; the two major forms are a short form (with a truncated intracellular domain) and long form (with the complete intracellular domain). The long form is thought to be the form that signals and mediates the biological effects of OB protein. Initial in situ hybridization studies have demonstrated the mRNA for the long form OB-R receptor to be localized to the hypothalamus as well as peripheral sites. Recently, it was demonstrated that the db gene encodes the OB-R receptor. Evidence has been provided for a specific transport system for OB protein to cross the blood-brain-barrier and enter the brain of mice, rats and humans. The rate of transport can be decreased by high plasma concentrations of OB protein. Thus, reduced entry of OB protein to the brain may be one of the mechanisms of reduced sensitivity of the OB protein pathway in obese individuals. OB protein appears to also play a role in the important neuroendocrine adaptive responses to fasting and in the control of reproduction. Therapeutic approaches to the treatment of obesity based on OB protein ranging from OB protein by injection to OB-R receptor agonists and to upregulation of OB signalling pathways are under intense investigation. PMID:9013731

Campfield, L A; Smith, F J; Burn, P

1996-12-01

24

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

National Technical Information Service (NTIS)

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

G. A. Leveille

1966-01-01

25

Biochemistry of adipose tissue: an endocrine organ  

PubMed Central

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

Coelho, Marisa; Oliveira, Teresa

2013-01-01

26

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

Microsoft Academic Search

The objective of this study was to identify some proteins associated with testosterone-related differences in myogenesis and\\u000a 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,\\u000a myosin light chain 1 (MLC1), ankyrin repeat

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

27

Adipose tissue angiogenesis in obesity.  

PubMed

Adipose tissue is the most plastic tissue in all multicellular organisms, being constantly remodelled along with weight gain and weight loss. Expansion of adipose tissue must be accompanied by that of its vascularisation, through processes of angiogenesis, whereas weight loss is associated with the regression of blood vessels. Adipose tissue is thus among the tissues that have the highest angiogenic capacities. These changes of the vascular bed occur through close interactions of adipocytes with blood vessels, and involve several angiogenic factors. This review presents studies that are the basis of our understanding of the regulation of adipose tissue angiogenesis. The growth factors that are involved in the processes of angiogenesis and vascular regression are discussed with a focus on their potential modulation for the treatment of obesity. The hypothesis that inflammation of adipose tissue and insulin resistance could be related to altered angiogenesis in adipose tissue is presented, as well as the beneficial or deleterious effect of inhibition of adipose tissue angiogenesis on metabolic diseases. PMID:23595655

Lemoine, Amal Y; Ledoux, Séverine; Larger, Etienne

2013-10-01

28

Effect of Dietary Calcium and Dairy Proteins on the Adipose Tissue Gene Expression Profile in Diet-Induced Obesity  

Microsoft Academic Search

Background\\/Aims: Calcium and dairy proteins have been postulated to explain why the intake of dairy products correlates inversely with body mass index in several populations. We have shown that a high-calcium diet with whey protein attenuates weight gain and now we describe the effects of this diet on adipose tissue gene expression. Methods: Nine-week-old C57Bl\\/6J mice were divided into two

Taru K. Pilvi; Markus Storvik; Marjut Louhelainen; Saara Merasto; Riitta Korpela; Eero M. Mervaala

2008-01-01

29

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

PubMed

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

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

2012-01-01

30

In vivo Adipose Tissue Regeneration by Adipose-Derived Stromal Cells Isolated from GFP Transgenic Mice  

Microsoft Academic Search

We have previously demonstrated that pluripotent stem cells can be obtained from green fluorescence protein (GFP) transgenic mouse adipose tissue. In this study, we sought to determine whether adipose tissue regeneration can be induced in vivo using adipose-derived stromal cells (ASCs) from GFP mice. ASCs were isolated from inguinal fat pads of GFP mice, as described in our previous publication.

Hiroshi Mizuno; Yurie Itoi; Satoko Kawahara; Rei Ogawa; Satoshi Akaishi; Hiko Hyakusoku

2008-01-01

31

Advances in adipose tissue metabolism  

Microsoft Academic Search

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

M Lafontan

2008-01-01

32

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

PubMed Central

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

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

2007-01-01

33

Increased Expression of the Tail-Anchored Membrane Protein SLMAP in Adipose Tissue from Type 2 Tally Ho Diabetic Mice  

PubMed Central

The tail-anchored membrane protein, sarcolemmal membrane associated protein (SLMAP) is encoded to a single gene that maps to the chromosome 3p14 region and has also been reported in certain diabetic populations. Our previous studies with db/db mice shown that a deregulation of SLMAP expression plays an important role in type 2 diabetes. Male Tally Ho mice were bred to present with either normoglycemia (NG) or hyperglycemia (HG). Abdominal adipose tissue from male Tally Ho mice of the HG group was found to have a significantly lower expression of the membrane associated glucose transporter-4 (GLUT-4) and higher expression of SLMAP compared to tissue from NG mice. There were 3 isoforms expressed in the abdominal adipose tissue, but only 45?kDa isoform of SLMAP was associated with the GLUT-4 revealed by immunoprecipitation data. Knock down studies using SLMAP siRNA with adipocytes resulted in a significant reduction in SLMAP and a decrease in glucose uptake. Thus, SLMAP may be an important regulator of glucose uptake or involved in GLUT-4 fusion/translocation into the plasma membrane of mouse abdominal adipose tissue and changes in SLMAP expression are linked to hyperglycemia and diabetes.

Chen, Xiaoliang; Ding, Hong

2011-01-01

34

Increased expression of the tail-anchored membrane protein SLMAP in adipose tissue from type 2 Tally Ho diabetic mice.  

PubMed

The tail-anchored membrane protein, sarcolemmal membrane associated protein (SLMAP) is encoded to a single gene that maps to the chromosome 3p14 region and has also been reported in certain diabetic populations. Our previous studies with db/db mice shown that a deregulation of SLMAP expression plays an important role in type 2 diabetes. Male Tally Ho mice were bred to present with either normoglycemia (NG) or hyperglycemia (HG). Abdominal adipose tissue from male Tally Ho mice of the HG group was found to have a significantly lower expression of the membrane associated glucose transporter-4 (GLUT-4) and higher expression of SLMAP compared to tissue from NG mice. There were 3 isoforms expressed in the abdominal adipose tissue, but only 45?kDa isoform of SLMAP was associated with the GLUT-4 revealed by immunoprecipitation data. Knock down studies using SLMAP siRNA with adipocytes resulted in a significant reduction in SLMAP and a decrease in glucose uptake. Thus, SLMAP may be an important regulator of glucose uptake or involved in GLUT-4 fusion/translocation into the plasma membrane of mouse abdominal adipose tissue and changes in SLMAP expression are linked to hyperglycemia and diabetes. PMID:21785580

Chen, Xiaoliang; Ding, Hong

2011-01-01

35

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

PubMed

Maternal low-protein diets result in lower birth weight followed by accelerated catch-up growth that is accompanied by the development of obesity and glucose intolerance in later life. Whether postnatal high-fat (HF) diets further contribute to the development of obesity and insulin resistance in offspring by affecting adipose tissue metabolism and DNA methylation is currently unknown. Obese-prone Sprague-Dawley rats were fed 8% low protein (LP) or 20% normal protein diets for 3 wk prior to conception and throughout pregnancy and lactation to investigate whether prenatal LP and postnatal HF diets affect the rate of adipose tissue growth, insulin-like growth factor 2 (Igf2) expression, and DNA methylation in male offspring. At weaning, the offspring were fed 10% normal fat or 45% HF diets for 12 wk. The adipose tissue growth rate was increased (up to 26-fold) by the LP prenatal and HF postnatal diets. Adipose tissue Igf2 mRNAs and DNA methylation were increased by the LP prenatal and HF postnatal diets. The LP prenatal and HF postnatal diet increased the number of small adipocytes in adipose tissue and decreased insulin sensitivity. These findings suggest that prenatal LP and postnatal HF intake result in adipose tissue catch-up growth through alterations in the expression of the Igf2 gene and DNA methylation within adipocytes. These alterations in adiposity are accompanied by an increased risk of development of type 2 diabetes. PMID:23946348

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

2013-10-01

36

Autophagy in adipose tissue biology.  

PubMed

Obesity, which predisposes individuals to type II diabetes and cardiovascular diseases, results from accumulation of white adipose tissue (WAT). WAT comprises mainly white adipocytes that have a unique cellular structure in which almost the entire intracellular space is occupied by one single lipid droplet. The cytoplasm envelopes this lipid droplet and occupies negligible space. Differentiation of WAT, or adipogenesis, requires dramatic cytoplasmic reorganization, including a dynamic change in mitochondrial mass. Autophagy is a major cytoplasmic degradation pathway and a primary pathway for mitochondrial degradation. Recent studies indicate that autophagy is implicated in adipogenesis. In this review, we summarize our current knowledge on autophagy in adipose tissue biology, with the emphasis on its role in mitochondrial degradation. Adipose tissue is a central component for whole-body energy homeostasis regulation. Advancement in this research area may provide novel venues for the intervention of obesity and obesity related diseases. PMID:23017672

Zhang, Yong; Zeng, Xiangang; Jin, Shengkan

2012-12-01

37

Adipose tissue remodeling and obesity  

PubMed Central

To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited capacity to expand in a non-transformed state. As such, the tissue requires potent mechanisms to remodel, acutely and chronically. Adipocytes can rapidly reach the diffusional limit of oxygen during growth; hypoxia is therefore an early determinant that limits healthy expansion. Proper expansion requires a highly coordinated response among many different cell types, including endothelial precursor cells, immune cells, and preadipocytes. There are therefore remarkable similarities between adipose expansion and growth of solid tumors, a phenomenon that presents both an opportunity and a challenge, since pharmacological interventions supporting healthy adipose tissue adaptation can also facilitate tumor growth.

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

2011-01-01

38

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 marrow–derived 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.

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

2003-01-01

39

Impact of intrauterine growth retardation and early protein intake on growth, adipose tissue, and the insulin-like growth factor system in piglets.  

PubMed

Small birth weight and excess of early protein intake are suspected to enhance later adiposity. The present study was undertaken to determine the impact of diets differing in protein content on short-term growth, adipose tissue development, and the insulin-like growth factor (IGF) system in piglets. Normal (NW) and small (SW) birth weight piglets were fed milk-replacers formulated to provide an adequate (AP) or a high protein (HP) supply between 7 and 28 d of age. The fractional growth rate was higher (p < 0.01) in SW than in NW piglets. At 7 d of age, the lower (p < 0.05) weight of perirenal adipose tissue relative to body mass in SW than in NW piglets did not involve significant changes in plasma IGF-I, leptin, or insulin-like growth factor binding protein levels, but involved differences (p < 0.05) in the expression of IGF-I and leptin in adipose tissue. Growth rates did not differ between AP and HP piglets. At 28 d of age, HP piglets had lower (p < 0.001) relative perirenal adipose tissue weight but did not differ clearly from AP piglets with regard to the IGF system. It remains to be determined whether piglets fed such a high protein intake will stay subsequently with a low adiposity. PMID:18703996

Morise, Anne; Sève, Bernard; Macé, Katherine; Magliola, Corinne; Le Huërou-luron, Isabelle; Louveau, Isabelle

2009-01-01

40

Adipose Tissue Dysfunction in Humans: A Potential Role for the Transmembrane Protein ENPP1  

PubMed Central

Context: Adipose tissue (AT) helps to regulate body fat partitioning and systemic lipid/glucose metabolism. We have recently reported lipid/glucose metabolism abnormalities and increased liver triglyceride content in an AT-selective transgenic model overexpressing ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1), the AdiposeENPP1-Tg mouse. Objective: The aim of the study was to test the translational hypothesis that AT-ENPP1 overexpression associates with AT dysfunction (changes in AT gene expression, plasma fatty acid, and adipokine levels), increased liver triglyceride deposition, and systemic insulin resistance in humans. Design/Setting/Participants: A total of 134 young normoglycemic men and women were subjected to body composition studies, hyperinsulinemic-euglycemic clamps, and AT needle biopsy. Twenty men also had liver/muscle nuclear magnetic resonance spectroscopy. Main Outcome Measures: Predetermined measures included AT expression of ENPP1 and other lipid metabolism/inflammation genes, plasma adipokines, and nonesterified fatty acid (NEFA) levels, liver/muscle triglyceride content, and the systemic glucose disposal rate. Results: After statistical adjustment for body fat content, increasing AT-ENPP1 was associated with up-regulation of genes involved in NEFA metabolism and inflammation, increased postabsorptive NEFA levels, decreased plasma adiponectin, increased liver triglyceride content, and systemic insulin resistance in men. In women, there were no changes in plasma adiponectin, NEFAs, or glucose disposal rate associated with increasing AT-ENPP1, despite increased expression of lipid metabolism and inflammation genes in AT. Conclusions: Increased AT-ENPP1 is associated with AT dysfunction, increased liver triglyceride deposition, and systemic insulin resistance in young normoglycemic men. These findings are concordant with the AdiposeENPP1-Tg phenotype and identify a potential target of therapy for health complications of AT dysfunction, including type 2 diabetes and cardiovascular disease.

Chandalia, Manisha; Davila, Himara; Pan, Wentong; Szuszkiewicz, Magdalena; Tuvdendorj, Demidmaa; Livingston, Edward H.

2012-01-01

41

Resolution of adipose tissue inflammation.  

PubMed

The presence of the so-called "low-grade" inflammatory state is recognized as a critical event in adipose tissue dysfunction in obesity. This chronic "low-grade" inflammation in white adipose tissue is powerfully augmented through the infiltration of macrophages, which, together with adipocytes, perpetuate a vicious cycle of macrophage recruitment and secretion of free fatty acids and deleterious adipokines that predispose the development of obesity-related comorbidities, such as insulin resistance and nonalcoholic fatty liver disease. In the last decade, many factors have been identified that contribute to mounting uncontrolled inflammation in obese adipose tissue. Among them, bioactive lipid mediators derived from the cyclooxygenase and 5-lipoxygenase pathways, which convert the omega-6-polyunsaturated fatty acid (PUFA) arachidonic acid into potent proinflammatory eicosanoids (i.e., prostaglandins [PGs] and leukotrienes), have emerged. Interestingly, the same lipid mediators that initially trigger the inflammatory response also signal the termination of inflammation by stimulating the biosynthesis of anti-inflammatory and proresolving lipid autacoids. This review discusses the current status, characteristics, and progress in this class of "stop signals", including the lipoxins, which were the first identified omega-6 PUFA-derived lipid mediators with potent anti-inflammatory properties; the recently described omega-3 PUFA-derived lipid mediators resolvins and protectins; and the cyclopentenone PGs of the D series. Special emphasis is given to the participation of these bioactive lipid autacoids in the resolution of adipose tissue inflammation and in preventing the development of obesity-related complications. PMID:20454765

González-Périz, Ana; Clària, Joan

2010-01-01

42

pH-temperature interactions on protein function and hibernation: GDP binding to brown adipose tissue mitochondria  

Microsoft Academic Search

1.[3H]GDP binding to the uncoupling protein of brown adipose tissue was determined on mitochondria isolated from hibernating European hamsters, at two temperatures, 35 and 15°C, and four values of25pH (pH corrected to 25°C): 6.4, 6.8, 7.2 and 7.6, encompassing the physiological range of pH. Buffer composition was adjusted to get the same pH-temperature relationship as for mammalian blood, in which

A. Malan; E. Mioskowski

1988-01-01

43

The Dietary Protein/Carbohydrate Ratio Differentially Modifies Lipogenesis and Protein Synthesis in the Mammary Gland, Liver and Adipose Tissue during Gestation and Lactation  

PubMed Central

During gestation and lactation, a series of metabolic changes that are affected by the diet occurs in various organs of the mother. However, little is known about how the dietary protein (DP)/carbohydrate (DCH) ratio regulates the expression of metabolic genes in the mother. Therefore, the purpose of this work was to study the effect of consuming different percentages of DP/DCH, specifically 10/73, 20/63 and 30/53%, on the expression of genes involved in lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation in dams. While the amount of weight gained during gestation was similar for all groups, only dams fed with 30/53% DP/DCH maintained their weight during lactation. In the mammary gland, the expression of the genes involved in lipogenesis, specifically SREBP1 and FAS, was dramatically increased, and the expression of the genes involved in protein synthesis, such as mTOR1, and the phosphorylation of its target protein, S6K, were also increased throughout pregnancy and lactation, regardless of the concentration of DP/DCH. In the liver and adipose tissue, the expression of the genes and proteins involved in lipid metabolism was dependent on the proportion of DP/DCH. The consumption of a low-protein/high-carbohydrate diet increased the expression of lipogenic genes in the liver and adipose tissue and the amount of lipid deposition in the liver. Conversely, the consumption of a high-protein/low-carbohydrate diet increased the expression of genes involved in amino acid oxidation in the liver during gestation. The metabolic adaptations reflected by the changes in the expression of metabolic genes indicate that the mammary gland has a priority for milk synthesis, whereas the adaptations in the liver and adipose tissue are responsible for providing nutrients to the mammary gland to sustain milk synthesis.

Velazquez-Villegas, Laura A.; Tovar, Armando R.; Lopez-Barradas, Adriana M.; Torres, Nimbe

2013-01-01

44

Intrinsic Depot-Specific Differences in the Secretome of Adipose Tissue, Preadipocytes, and Adipose Tissue-Derived Microvascular Endothelial Cells  

PubMed Central

OBJECTIVE Visceral adipose tissue (VAT) is more closely linked to insulin resistance than subcutaneous adipose tissue (SAT). We conducted a quantitative analysis of the secretomes of VAT and SAT to identify differences in adipokine secretion that account for the adverse metabolic consequences of VAT. RESEARCH DESIGN AND METHODS We used lectin affinity chromatography followed by comparison of isotope-labeled amino acid incorporation rates to quantitate relative differences in the secretomes of VAT and SAT explants. Because adipose tissue is composed of multiple cell types, which may contribute to depot-specific differences in secretion, we isolated preadipocytes and microvascular endothelial cells (MVECs) and compared their secretomes to those from whole adipose tissue. RESULTS Although there were no discrete depot-specific differences in the secretomes from whole adipose tissue, preadipocytes, or MVECS, VAT exhibited an overall higher level of protein secretion than SAT. More proteins were secreted in twofold greater abundance from VAT explants compared with SAT explants (59% versus 21%), preadipocytes (68% versus 0%), and MVECs (62% versus 15%). The number of proteins in the whole adipose tissue secretome was greater than the sum of its cellular constituents. Finally, almost 50% of the adipose tissue secretome was composed of factors with a role in angiogenesis. CONCLUSIONS VAT has a higher secretory capacity than SAT, and this difference is an intrinsic feature of its cellular components. In view of the number of angiogenic factors in the adipose tissue secretome, we propose that VAT represents a more readily expandable tissue depot.

Hocking, Samantha L.; Wu, Lindsay E.; Guilhaus, Michael; Chisholm, Donald J.; James, David E.

2010-01-01

45

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.

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

2013-01-01

46

Chronic Alcohol Exposure Stimulates Adipose Tissue Lipolysis in Mice  

PubMed Central

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

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

2012-01-01

47

Cellular and Molecular Aspects of Adipose Tissue  

Microsoft Academic Search

\\u000a Adipose tissue is a dynamic ‘hard-working’ tissue that awaits extensive studies. It does not merely function as a fat-storage\\u000a region; adipose tissue also plays a major role in the formation of body shapes, which determine attractiveness in humans.\\u000a Moreover, adipose tissue secretes molecules that direct brain processes.\\u000a \\u000a \\u000a The importance of adipose tissue is not limited to its physiologic roles; it

Tahsin Murad Aktan; Selcuk Duman; Bulent Cihantimur

48

Sex differences in adipose tissue  

PubMed Central

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

Fuente-Martin, Esther; Argente-Arizon, Pilar; Ros, Purificacion; Argente, Jesus; Chowen, Julie A

2013-01-01

49

Perivascular adipose tissue and coronary vascular disease.  

PubMed

Coronary perivascular adipose tissue is a naturally occurring adipose tissue depot that normally surrounds the major coronary arteries on the surface of the heart. Although originally thought to promote vascular health and integrity, there is a growing body of evidence to support that coronary perivascular adipose tissue displays a distinct phenotype relative to other adipose depots and is capable of producing local factors with the potential to augment coronary vascular tone, inflammation, and the initiation and progression of coronary artery disease. The purpose of the present review is to outline previous findings about the cardiovascular effects of coronary perivascular adipose tissue and the potential mechanisms by which adipose-derived factors may influence coronary vascular function and the progression of atherogenesis. PMID:24790142

Owen, Meredith Kohr; Noblet, Jillian N; Sassoon, Daniel J; Conteh, Abass M; Goodwill, Adam G; Tune, Johnathan D

2014-08-01

50

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

PubMed

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

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

2012-06-01

51

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

52

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

PubMed Central

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

2014-01-01

53

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 Ràfols, Montserrat

2014-02-01

54

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.

Zhu, Wenting; Nelson, Celeste M.

2013-01-01

55

Decreased AMP-activated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans  

PubMed Central

Inflammation and infiltration of immune cells in white adipose tissue have been implicated in the development of obesity-associated insulin resistance. Likewise, dysregulation of the fuel-sensing enzyme AMP-activated protein kinase (AMPK) has been proposed as a pathogenetic factor for these abnormalities based on both its links to insulin action and its anti-inflammatory effects. In this study, we examined the relationships between AMPK activity, the expression of multiple inflammatory markers in visceral (mesenteric and omental) and abdominal subcutaneous adipose tissue, and whole-body insulin sensitivity in morbidly obese patients (BMI 48 ± 1.9 kg/m2) undergoing gastric bypass surgery. AMPK activity was assessed by western-blots (P-AMPK/T-AMPK) and mRNA levels of various markers of inflammation by qRT-PCR. Patients were stratified as insulin sensitive obese or insulin resistant obese according to their HOMA-IR values. The results indicate that AMPK activity is lower in visceral than in subcutaneous abdominal adipose tissue of these patients and that this is associated with an increased expression of multiple inflammatory genes. They also revealed that AMPK activity is lower in adipose tissue of obese patients who are insulin resistant (HOMA-IR > 2.3) than in BMI-matched insulin sensitive subjects. Furthermore, this difference was evident in all three fat depots. In conclusion, the data suggest that there are close links between reduced AMPK activity and inflammation in white adipose tissue, and whole-body insulin resistance in obese humans. Whether adipose tissue AMPK dysregulation is a causal factor for the development of the inflammation and insulin resistance remains to be determined.

Gauthier, Marie-Soleil; O'Brien, Elena L; Bigornia, Sherman; Mott, Melanie; Cacicedo, Jose M; Xu, X. Julia; Gokce, Noyan; Apovian, Caroline; Ruderman, Neil

2011-01-01

56

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 13,234–16,858 probe sets in chicken adipose tissue at 7 weeks, and genes involved in lipid metabolism and immunity such as fatty acid binding protein (FABP), thyroid hormone-responsive protein (Spot14), lipoprotein lipase(LPL), insulin-like growth factor binding protein 7(IGFBP7) and major histocompatibility complex (MHC), were highly expressed. In contrast, some genes related to lipogenesis, such as leptin receptor, sterol regulatory element binding proteins1 (SREBP1), apolipoprotein B(ApoB) and insulin-like growth factor 2(IGF2), were not detected. Moreover, 230 genes that were differentially expressed between the two lines were screened out; these were mainly involved in lipid metabolism, signal transduction, energy metabolism, tumorigenesis and immunity. Subsequently, real-time RT-PCR was performed to validate fifteen differentially expressed genes screened out by the microarray approach and high consistency was observed between the two methods. Conclusion Our results establish the groundwork for further studies of the basic genetic control of growth and development of chicken adipose tissue, and will be beneficial in clarifying the molecular mechanism of obesity in chickens.

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

2007-01-01

57

Adipose Tissue Sensitivity to Radiation Exposure  

PubMed Central

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

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

2009-01-01

58

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

PubMed

We have previously shown in in vivo experiments that adipose tissue glyceroneogenesis is increased in rats adapted to a high-protein, carbohydrate-free (HP) diet. The objectives of the present study were (1) to verify if the increased glyceroneogenic activity is also observed in isolated adipocytes and (2) to investigate the role of preformed fatty acids in the production of the increased adipose tissue glyceroneogenesis. Control rats received a balanced diet, with the same lipid content of the HP diet. Glyceroneogenic activity was found to be higher in adipocytes from HP rats than in controls, as evidenced by increased rates of conversion of pyruvate and lactate to triacylglycerol (TAG)-glycerol. Administration of Triton WR 1339, which blocks the removal of TAG incorporated into circulating lipoproteins, to HP diet-adapted rats caused a significant reduction in the incorporation of 14C-pyruvate into TAG-glycerol by adipose tissue, which was accompanied by a marked inhibition of phosphoenolpyruvate carboxykinase activity, the key enzyme of glyceroneogenesis. The inhibitory effect of Triton on TAG-glycerol synthesis by adipose tissue was also observed in vivo, after administration of 3H2O. Adaptation to the HP diet induced a marked increase in the activity of retroperitoneal and epididymal fat LPL, which was restored to control values 24 hours after replacement of the HP diet by the balanced diet. The data suggest that in rats adapted to a carbohydrate-free diet, adipose tissue glyceroneogenesis is activated by an increased use of diet-derived fatty acids. PMID:16324924

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

2006-01-01

59

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.

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

2001-01-01

60

Organochlorine Pesticide Residues in Human Adipose Tissue.  

National Technical Information Service (NTIS)

The article presents findings of selected organochlorine residues for surveys conducted on human adipose tissue during fiscal years 1970, 1971, and 1972. The residues selected for presentation in this paper were beta-benzene hexachloride, total DDT equiva...

F. W. Kutz A. R. Yobs S. C. Strassman

1976-01-01

61

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

62

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

63

The Dipeptidyl Peptidase-4 Inhibitor Des-Fluoro-Sitagliptin Regulates Brown Adipose Tissue Uncoupling Protein Levels in Mice with Diet-Induced Obesity  

PubMed Central

Objective Dipeptidyl peptidase (DPP)-4 is responsible for the degradation of several peptides that contain an alanine or proline at the penultimate position or position P1. DPP-4 inhibitors (DPP-4is) have protective effects against type-2 diabetes and several metabolic disorders. Methods In the present study, we examined the effects of des-fluoro-sitagliptin (DFS), a DDP-4i, on body adiposity and levels of peroxisome proliferator-activated receptor (PPAR)-?, PPAR-? coactivator-1 (PGC-1), and uncoupling proteins (UCPs) in mice with diet-induced obesity. Results Treatment with DFS dose-dependently decreased the weight of white adipose tissue and serum levels of glucose, compared with controls, without influencing food intake (P<0.05). Additionally, DFS treatment increased the levels of PPAR-?, PGC-1, and UCPs in brown adipose tissue (BAT), and of PPAR-? and UCP3 in skeletal muscle (P<0.05). Furthermore, the effects on BAT PGC-1 and muscle PPAR-? levels were attenuated by treatment with the glucagon-like peptide 1 (GLP-1) antagonist exendin (9–39). Interestingly, hypothalamic levels of proopiomelanocortin (POMC) were increased by DFS treatment and the effects of DFS on PPAR-?, PGC-1, and UCP levels were attenuated in melanocortin (MC)-4 receptor-deficient mice. Conclusions In conclusion, high-dose DFS appeared to regulate body adiposity and UCPs in mice with diet-induced obesity, at least partly through a GLP-1 and/or MC-4 pathway.

Shimasaki, Takanobu; Masaki, Takayuki; Mitsutomi, Kimihiko; Ueno, Daisuke; Gotoh, Koro; Chiba, Seiichi; Kakuma, Tetsuya; Yoshimatsu, Hironobu

2013-01-01

64

Macrophage Content in Subcutaneous Adipose Tissue  

PubMed Central

OBJECTIVE— In severely obese individuals and patients with diabetes, accumulation and activation of macrophages in adipose tissue has been implicated in the development of obesity-associated complications, including insulin resistance. We sought to determine whether in a healthy population, adiposity, sex, age, or insulin action is associated with adipose tissue macrophage content (ATMc) and/or markers of macrophage activation. RESEARCH DESIGN AND METHODS— Subcutaneous ATMc from young adult Pima Indians with a wide range of adiposity (13–46% body fat, by whole-body dual-energy X-ray absorptiometry) and insulin action (glucose disposal rate 1.6–9 mg/kg estimated metabolic body size/min, by glucose clamp) were measured. We also measured expression in adipose tissue of factors implicated in macrophage recruitment and activation to determine any association with ATMc and insulin action. RESULTS— ATMc, as assessed by immunohistochemistry (Mphi) and by macrophage-specific gene expression (CD68, CD11b, and CSF1R), were correlated with percent body fat, age, and female sex. Gene expression of CD68, CD11b, and CSF1R but not Mphi was correlated negatively with glucose disposal rate but not after adjustment for percent body fat, age, and sex. However, adipose tissue expression of plasminogen activator inhibitor type-1 (PAI-1) and CD11 antigen-like family member C (CD11c), markers produced by macrophages, were negatively correlated with adjusted glucose disposal rate (r = ?0.28, P = 0.05 and r = ?0.31, P = 0.03). CONCLUSIONS— ATMc is correlated with age and adiposity but not with insulin action independent of adiposity in healthy human subjects. However, PAI-1 and CD11c expression are independent predictors of insulin action, indicating a possible role for adipose tissue macrophage activation.

Ortega Martinez de Victoria, Emilio; Xu, Xiaoyuan; Koska, Juraj; Francisco, Ann Marie; Scalise, Michael; Ferrante, Anthony W.; Krakoff, Jonathan

2009-01-01

65

TAF7L modulates brown adipose tissue formation  

PubMed Central

Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (UCP1). Previously, we reported that the TATA-binding protein associated factor 7L (TAF7L) is an important regulator of white adipose tissue (WAT) differentiation. In this study, we show that TAF7L also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, TAF7L-containing TFIID complexes associate with PPAR? to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that the presence of the tissue-specific TAF7L subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification. DOI: http://dx.doi.org/10.7554/eLife.02811.001

Zhou, Haiying; Wan, Bo; Grubisic, Ivan; Kaplan, Tommy; Tjian, Robert

2014-01-01

66

Echocardiographic Assessment of Epicardial Adipose Tissue - A Marker of Visceral Adiposity  

PubMed Central

Visceral adipose tissue predicts an unfavorable cardiovascular and metabolic risk profile in humans. Existing methods to assess visceral adipose tissue have been limited. Thus, echocardiographic assessment of epicardial adipose tissue as a marker of visceral adiposity was suggested. The technique has been shown to be a very reliable method and an excellent measure of visceral adiposity. In this article, epicardial adipose tissue’s localization on the heart, function, method of assessment and reliability as a marker of visceral adiposity is briefly reviewed. Areas of the technique requiring further study are identified.

Singh, Navneet; Singh, Harleen; Khanijoun, Harleen K; Iacobellis, Gianluca

2007-01-01

67

Effect of premature aging on murine adipose tissue.  

PubMed

To evaluate the effect of aging on adipose tissue development, subcutaneous (SC) and gonadal (GON) white and peri-aortic brown adipose tissues were analyzed of 10 and 30 week old mice deficient in the clock gene Bmal1 (brain and muscle arnt like protein 1) (Bmal1(-/-)) and wild-type littermates (Bmal1(+/+)) kept on a standard fat diet. At both ages, daily food intake was significantly decreased for Bmal1(-/-) mice, associated with reduced hypothalamic expression of PPAR?. Between 10 and 30 weeks of age, the total body weight of Bmal1(+/+) mice increased significantly, but that of Bmal1(-/-) mice did not change. Whereas for Bmal1(+/+) mice, both SC and GON fat mass increased with age, these decreased for Bmal1(-/-) mice. This was associated with increased adipocyte size with age for Bmal1(+/+) but not for Bmal1(-/-) mice. Adipose tissue related angiogenesis was not affected by genotype or aging. Peri-aortic brown adipose tissue mass in 30 week old Bmal1(-/-) mice was significantly reduced as compared to age-matched Bmal1(+/+) mice. Comparison of gene expression profiles in SC and GON adipose tissues of both genotypes revealed very marked effects of Bmal1 gene deletion in itself on PAI-1 (4- to 13-fold downregulation), whereas the associated effect of premature aging was striking for leptin (90- to 130-fold downregulation). Thus, premature aging in Bmal1(-/-) mice kept on normal chow was associated with reduced adiposity. PMID:22265801

Hemmeryckx, Bianca; Hoylaerts, Marc F; Lijnen, H Roger

2012-03-01

68

Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats  

Microsoft Academic Search

Conjugation of bile acids (BAs) to the amino acids taurine or glycine increases their solubility and promotes liver BA secretion. Supplementing diets with taurine or glycine modulates BA metabolism and enhances fecal BA excretion in rats. However, it is still unclear whether dietary proteins varying in taurine and glycine contents alter BA metabolism, and thereby modulate the recently discovered systemic

Bjørn Liaset; Lise Madsen; Qin Hao; Gabriel Criales; Gunnar Mellgren; Hanns-Ulrich Marschall; Philip Hallenborg; Marit Espe; Livar Frøyland; Karsten Kristiansen

2009-01-01

69

[New anatomo clinic approach of adipose tissue].  

PubMed

For a long time, adipose tissue was supposed to be inert with only a function of long-term energetic reserve. The obesity, abnormal accumulation of fat, for its part has always been considered the sole result of hyperphagia, itself secondary to a lack of willingness of the subject. This article focuses on the multiple aspects and functions of the different fatty tissues. One must distinguish brown adipose tissue (AT) and the white AT. This includes visceral fat and subcutaneous AT, which itself is divided into two sectors, a genetic fat and grease that we called ecological. The brown adipose tissue has essentially a function of thermogenesis. Visceral adipose tissue (VAT), from a certain volume, behaves as true endocrine gland acting on glycemic and lipid function. In addition to its role of energy reserve, the sub cutaneous AT has a mechanical role of shock absorber and fabric slip. We will emphasize finally the genetic aspect still too misunderstood and underestimated that regulates the different functions of the adipose tissue. PMID:22795958

Dardour, J-C

2012-10-01

70

Limited and excess protein intake of pregnant gilts differently affects body composition and cellularity of skeletal muscle and subcutaneous adipose tissue of newborn and weanling piglets  

Microsoft Academic Search

Aim  This study investigated whether dietary protein intake less (50%) or greater (250%) than requirements throughout gestation\\u000a differently affects offspring body composition and cellular properties of skeletal muscle and subcutaneous adipose tissue\\u000a (SCAT).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Primiparous gilts were fed iso-energetic diets containing adequate (22 AP), high (21 HP), or low (19 LP) protein contents.\\u000a Newborn (n = 166) and weanling piglets cross-fostered to sows fed

Charlotte Rehfeldt; Louis Lefaucheur; Jana Block; Bernd Stabenow; Ralf Pfuhl; Winfried Otten; Cornelia C. Metges; Claudia Kalbe

71

Porous decellularized adipose tissue foams for soft tissue regeneration.  

PubMed

To design tissue-specific bioscaffolds with well-defined properties and 3-D architecture, methods were developed for preparing porous foams from enzyme-solubilized human decellularized adipose tissue (DAT). Additionally, a technique was established for fabricating "bead foams" comprised of interconnected networks of porous DAT beads fused through a controlled freeze-thawing and lyophilization procedure. In characterization studies, the foams were stable without the need for chemical crosslinking, with properties that could be tuned by controlling the protein concentration and freezing rate during synthesis. Adipogenic differentiation studies with human adipose-derived stem cells (ASCs) suggested that stiffness influenced ASC adipogenesis on the foams. In support of our previous work with DAT scaffolds and microcarriers, the DAT foams and bead foams strongly supported adipogenesis and were also adipo-inductive, as demonstrated by glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity, endpoint RT-PCR analysis of adipogenic gene expression, and intracellular lipid accumulation. Adipogenic differentiation was enhanced on the microporous DAT foams, potentially due to increased cell-cell interactions in this group. In vivo assessment in a subcutaneous Wistar rat model demonstrated that the DAT bioscaffolds were well tolerated and integrated into the host tissues, supporting angiogenesis and adipogenesis. The DAT-based foams induced a strong angiogenic response, promoted inflammatory cell migration and gradually resorbed over the course of 12 weeks, demonstrating potential as scaffolds for wound healing and soft tissue regeneration. PMID:23384795

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

2013-04-01

72

Adipose tissue insulin sensitivity and macrophage recruitment  

PubMed Central

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

McCurdy, Carrie E; Klemm, Dwight J

2013-01-01

73

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

PubMed Central

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

2014-01-01

74

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

PubMed Central

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

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

2012-01-01

75

[Use of adipose tissue in regenerative medicine].  

PubMed

Adipose tissue is abundant and well known for its involvement in obesity and associated metabolic disorders. Its uses in regenerative medicine recently attracted many investigators, as large amounts of this tissue can be easily obtained using liposuction and it contains several populations of immature cells. The largest pool of such cells corresponds to immature stromal cells, called adipose-derived stromal cells (ADSCs). These cells are purified after proteolytic digestion of adipose tissue and selection by an adherent step. ADSCs display many common features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but with some specific features, among which a greater angiogenic potential. This potential is now investigating at clinical level to treat critical ischemic hindlimb by autologous cells. Other potentials are also investigated and the treatment of fistula associated or not with Crohn's disease is reaching now phase III level. PMID:21397545

Casteilla, L; Planat-Benard, V; Bourin, P; Laharrague, P; Cousin, B

2011-04-01

76

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.

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

2012-01-01

77

Injectable Biomaterials for Adipose Tissue Engineering  

PubMed Central

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

Young, D. Adam; Christman, Karen L.

2012-01-01

78

Visceral Adiposity Index: An Indicator of Adipose Tissue Dysfunction  

PubMed Central

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

2014-01-01

79

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.

2013-01-01

80

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

PubMed Central

Background The metabolic implications of intermuscular adipose tissue (IMAT) are poorly understood compared to those of visceral adipose tissue (VAT) even though the absolute quantities of both depots are similar in many individuals. Objective The aim was to determine the independent relationship between whole-body IMAT and cardiovascular risk factor parameters. Design Whole body magnetic resonance imaging (MRI) was used to quantify total skeletal muscle (SM), total adipose tissue (TAT) of which IMAT, defined as the AT visible by MRI within the boundary of the muscle fascia, is a sub-component. Fasting serum measures (n = 262) of glucose, total cholesterol (T-Chol), high-density lipoprotein cholesterol (HDL-Chol), triglycerides (TG), protein bound glucose (PBG, n = 206) and insulin (n = 119) were acquired in healthy African-American (AA, n = 78) and Caucasian (Ca, n = 109) women (body mass index (BMI) 26.5±5.7 kg/m2; 44.4±16.4 years) and men (39 AA, 62 Ca; BMI 25.6±3.5 kg/m2; 45.6±17.4 years). General linear models identified the independent effects of IMAT after covarying for SM, VAT, TAT, race, sex and two-way interactions. Results Significant independent associations were observed for IMAT with glucose (P < 0.001), PBG (P < 0.001) and T-Chol (P < 0.05). The association of IMAT with cholesterol differed by race in such a manner that for a unit increase in IMAT, T-Chol increased more rapidly in Ca compared to AA (P < 0.05). TG, HDL-Chol and insulin had no independent association with IMAT. Conclusion The strong independent associations of IMAT with fasting glucose and PBG suggest that IMAT may be related to glucose metabolism; however, IMAT is also associated with T-Chol in Ca.

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

2009-01-01

81

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 4–7) 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.

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

2013-01-01

82

Metabolic Development of Porcine Fetal Adipose Tissue  

Microsoft Academic Search

The influence of neural and endocrine status upon the metabolic activity and insulin responses of developing adipose tissue of fetal swine was examined. Central neural and endocrine regulation were removed by decapitation of fetuses at 45 days of gestation. Decapitated (decap) fetuses and intact littermates were removed at 65, 85 or 110 days of gestation. Fatty acid synthesis from glucose

T. G. Ramsay; G. J. Hausman; R. J. Martin

1988-01-01

83

Id transcriptional regulators in adipogenesis and adipose tissue metabolism.  

PubMed

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

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

2014-01-01

84

Upregulation of bone morphogenetic protein GDF-3/Vgr-2 expression in adipose tissue of FABP4/aP2 null mice.  

PubMed

High-fat-fed C57Bl/6J FABP4/aP2 null mice develop obesity but not the related hyperglycemia or hyperinsulinemia characteristic of type II diabetes. FABP4/aP2 protein's function to bind fatty acids in the adipocytes may promote total body energy homeostasis by linking energy depots to the ability to express signaling molecules similar to leptin. To test this hypothesis, proteomic analysis of serum proteins from high-fat-fed wild-type and FABP4/aP2 null mice revealed that the GDF-3/Vgr-2 protein, a bone morphogenetic protein, was upregulated in C57Bl/6J FABP4/aP2 null mice. The increase in serum GDF-3/Vgr-2 protein was correlated with a 27-fold increase in adipose GDF-3/Vgr-2 mRNA. In contrast, leptin expression was unaltered between FABP4/aP2 null and wild-type animals. The expression of GDF-3/Vgr-2 mRNA was not substantially different in adipose tissue of db/db and tb/tb mice compared to wild-type controls. The expression of GDF-3/Vgr-2 mRNA was dependent upon the age and diet of the animals, declining as a function of age in high-fat-fed wild-type animals while increasing in the FABP4/aP2 null strain. These results identify GDF-3/Vgr-2 as an age- and fat-regulated, adipose-derived cytokine suggesting a linkage between adipocyte fatty acid metabolism and the expression of the bone morphogenetic family of differentiation regulators. PMID:11396990

Witthuhn, B A; Bernlohr, D A

2001-05-01

85

Vitamin D and adipose tissue--more 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.

Mutt, Shivaprakash J.; Hypponen, Elina; Saarnio, Juha; Jarvelin, Marjo-Riitta; Herzig, Karl-Heinz

2014-01-01

86

Vitamin D and adipose tissue-more than storage.  

PubMed

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

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

2014-01-01

87

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

PubMed

Chromatin immunoprecipitation (ChIP) has become a central method when studying in vivo protein-DNA interactions, with the major challenge being the hope to capture "authentic" interactions. While ChIP protocols have been optimized for use with specific cell types and tissues including adipose tissue-derived cells, a working ChIP protocol addressing the challenges imposed by fresh whole human adipose tissue has not been described. Utilizing human paired omental and subcutaneous adipose tissue obtained during elective abdominal surgeries, we have carefully identified and optimized individual steps in the ChIP protocol employed directly on fresh tissue fragments. We describe a complete working protocol for using ChIP on whole adipose tissue fragments. Specific steps required adaptation of the ChIP protocol to human whole adipose tissue. In particular, a cross-linking step was performed directly on fresh small tissue fragments. Nuclei were isolated before releasing chromatin, allowing better management of fat content; a sonication protocol to obtain fragmented chromatin was optimized. We also demonstrate the high sensitivity of immunoprecipitated chromatin from adipose tissue to freezing. In conclusion, we describe the development of a ChIP protocol optimized for use in studying whole human adipose tissue, providing solutions for the unique challenges imposed by this tissue. Unraveling protein-DNA interaction in whole human adipose tissue will likely contribute to elucidating molecular pathways contributing to common human diseases such as obesity and type 2 diabetes. PMID:24002573

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

2013-11-01

88

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

89

Feeding of buckwheat protein extract reduces hepatic triglyceride concentration, adipose tissue weight, and hepatic lipogenesis in rats  

Microsoft Academic Search

The objective of this study was to examine effects of feeding buchwheat protein extract (BWPE) on hepatic and plasma lipids, fat pad weights and activities of enzymes relating to lipid metabolism in tissues of rats. Rats were fed a semipurified diet containing either buckwheat protein extract or casein for 3 weeks. Food consumption and growth rate were unaffected by dietary

Jun Kayashita; Iwao Shimaoka; Misao Nakajoh; Norihisa Kato

1996-01-01

90

Adipose tissue biology and cardiomyopathy: translational implications.  

PubMed

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

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

2012-12-01

91

Selection of Aptamers Specific for Adipose Tissue  

PubMed Central

Background Obesity has reached epidemic proportions, affecting more than one tenth of the world’s population. As such, adipose tissue is being increasingly recognized as an important therapeutic target for obesity and related metabolic disorders. While many potential targets of adipose tissue have been established and drugs developed, very few of those drugs specifically target adipose tissue without affecting other tissue. This results from a limited knowledge of both cell-surface markers and physicochemical traits specific to adipocytes that might otherwise be exploited by circulating drugs. Methodology/Principal Findings Here we report the use of cell-SELEX technology to select two aptamers that can specifically recognize mature adipocytes: adipo-1 and adipo-8. Adipo-8 shows high affinity for differentiated, mature 3T3-L1 adipocytes with a Kd value of 17.8±5.1 nM. The binding was sustained upon incubation at 37°C and insulin stimulation, but was lost upon trypsin treatment. The binding ability was also verified on frozen tissue slides with low background fluorescence and isolated adipocytes. Conclusions/Significance Aptamer adipo-8 selected from a random library appears to bind to mature differentiated adipocytes specifically. This aptamer holds great promise as a molecular recognition tool for adipocyte biomarker discovery or for targeted delivery of molecules to adipocytes.

Liu, Jun; Liu, Huixia; Sefah, Kwame; Liu, Bo; Pu, Ying; Van Simaeys, Dimitri; Tan, Weihong

2012-01-01

92

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.

2014-01-01

93

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.

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

94

Adipose Tissue Quantification by Imaging Methods: A Proposed Classification  

PubMed Central

Recent advances in imaging techniques and understanding of differences in the molecular biology of adipose tissue has rendered classical anatomy obsolete, requiring a new classification of the topography of adipose tissue. Adipose tissue is one of the largest body compartments, yet a classification that defines specific adipose tissue depots based on their anatomic location and related functions is lacking. The absence of an accepted taxonomy poses problems for investigators studying adipose tissue topography and its functional correlates. The aim of this review was to critically examine the literature on imaging of whole body and regional adipose tissue and to create the first systematic classification of adipose tissue topography. Adipose tissue terminology was examined in over 100 original publications. Our analysis revealed inconsistencies in the use of specific definitions, especially for the compartment termed “visceral” adipose tissue. This analysis leads us to propose an updated classification of total body and regional adipose tissue, providing a well-defined basis for correlating imaging studies of specific adipose tissue depots with molecular processes.

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

2007-01-01

95

Cardiac surgery increases serum concentrations of adipocyte fatty acid-binding protein and its mRNA expression in circulating monocytes but not in adipose tissue.  

PubMed

Adipocyte fatty acid binding protein (A-FABP) is a novel adipokine involved in the regulation of lipid and glucose metabolism and inflammation. To evaluate its potential role in the development of postoperative hyperglycemia and insulin resistance we assessed A-FABP serum concentrations and mRNA expression in skeletal and myocardial muscle, subcutaneous and epicardial adipose tissue and peripheral monocytes in 11 diabetic and 20 age- and sex-matched non-diabetic patients undergoing elective cardiac surgery. Baseline serum A-FABP did not differ between the groups (31.1+/-5.1 vs. 25.9+/-4.6 ng/ml, p=0.175). Cardiac surgery markedly increased serum A-FABP in both groups with a rapid peak at the end of surgery followed by a gradual decrease to baseline values during the next 48 h with no significant difference between the groups at any timepoint. These trends were analogous to postoperative excursions of plasma glucose, insulin and selected proinflammatory markers. Cardiac surgery increased A-FABP mRNA expression in peripheral monocytes, while no effect was observed in adipose tissue or muscle. Our data suggest that circulating A-FABP might be involved in the development of acute perioperative stress response, insulin resistance and hyperglycemia of critically ill irrespectively of the presence of diabetes mellitus. PMID:24182337

Kotulak, T; Drapalova, J; Lips, M; Lacinova, Z; Kramar, P; Riha, H; Netuka, I; Maly, J; Blaha, J; Lindner, J; Svacina, S; Mraz, M; Haluzik, M

2014-01-01

96

The KRAB Zinc Finger Protein RSL1 Modulates Sex-Biased Gene Expression in Liver and Adipose Tissue To Maintain Metabolic Homeostasis  

PubMed Central

Krüppel-associated box zinc finger proteins (KRAB-ZFPs) are a huge family of vertebrate-specific repressors that modify gene expression in an epigenetic manner. Despite a well-defined repression mechanism, few biological roles or gene targets of KRAB-ZFP are known. Regulator of sex-limitation 1 (RSL1) is a mouse KRAB-ZFP that enforces male-predominant expression in the liver, affecting body mass and pubertal timing. Here we show that female but not male Rsl1?/? mice gain more weight than wild-type mice on a high-fat diet (HFD) and that key liver and white adipose tissue (WAT) metabolic genes are altered in both Rsl1?/? sexes in response to dietary stress. Expression profiling of Rsl1-sensitive genes in liver and WAT indicates that RSL1 accentuates sex-biased gene expression in liver but greatly diminishes it in WAT. RSL1 expression solely in liver is sufficient to limit diet-induced weight gain and suppress lipogenic genes in WAT, indicating that RSL1 balances metabolism via liver-to-adipose-tissue communication. RSL1's effects on adult physiology exemplify a significant modulatory capacity of KRAB-ZFPs, in the absence of which there is widespread metabolic dysregulation. This ability to buffer against gene expression noise, coupled with extensive individual genetic variation, highlights the enormous potential of KRAB-Zfp genes as candidate risk factors for complex diseases.

Krebs, Christopher J.; Zhang, Deqiang; Yin, Lei

2014-01-01

97

Procyanidins target mesenteric adipose tissue in Wistar lean rats and subcutaneous adipose tissue in Zucker obese rat.  

PubMed

Visceral and subcutaneous adipose depots have different metabolic roles that may be involved in the development of obesity-related pathologies. Procyanidins have beneficial effects on insulin resistance, and they target adipose tissue. We analyse whether procyanidins exert different effects, depending on the adipose tissue depot, and whether these effects show a relation to the amount of phenolic compound in the tissue. We studied the effects of a grape seed procyanidin extract (GSPE) treatment at the transcriptional level on genes expressed differentially between mesenteric and subcutaneous adipose tissue depots and genes previously shown to be targets of procyanidins. Procyanidins target mesenteric adipose tissue in Wistar lean rats but subcutaneous adipose tissue in Zucker obese rats. Non-modified structures also accumulated, preferentially in the same respective tissues that were responsive to GSPE. Thus, procyanidins target and accumulate differently in mesenteric and subcutaneous adipose tissue depots, depending on the metabolic condition of the animal model. PMID:23768342

Ardévol, A; Motilva, M J; Serra, A; Blay, M; Pinent, M

2013-11-01

98

Melatonin stimulates Growth of Brown Adipose Tissue  

Microsoft Academic Search

IN small mammals brown adipose tissue (BAT) is an important site of non-shivering heat production1,2. Its mass increases during cold adaptation together with the ability to produce heat (ref. 3 and G. H., unpublished), thus improving cold tolerance4. In the golden hamster, Hoffman et al.5 also found an increase of BAT weight following exposure to short photoperiods. The pineal hormone

Gerhard Heldmaier; Klaus Hoffmann

1974-01-01

99

Vasodilator signals from perivascular adipose tissue  

PubMed Central

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

Gollasch, Maik

2012-01-01

100

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.

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

101

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

PubMed

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; Kopchick, John J

2013-03-01

102

Central leptin regulates total ceramide content and sterol regulatory element binding protein-1C proteolytic maturation in rat white adipose tissue.  

PubMed

Obesity and type 2 diabetes are associated with insulin and leptin resistance, and increased ceramide contents in target tissues. Because the adipose tissue has become a central focus in these diseases, and leptin-induced increases in insulin sensitivity may be related to effects of leptin on lipid metabolism, we investigated herein whether central leptin was able to regulate total ceramide levels and the expression of enzymes involved in ceramide metabolism in rat white adipose tissue (WAT). After 7 d central leptin treatment, the total content of ceramides was analyzed by quantitative shotgun lipidomics mass spectrometry. The effects of leptin on the expression of several enzymes of the sphingolipid metabolism, sterol regulatory element binding protein (SREBP)-1c, and insulin-induced gene 1 (INSIG-1) in this tissue were studied. Total ceramide levels were also determined after surgical WAT denervation. Central leptin infusion significantly decreased both total ceramide content and the long-chain fatty acid ceramide species in WAT. Concomitant with these results, leptin decreased the mRNA levels of enzymes involved in de novo ceramide synthesis (SPT-1, LASS2, LASS4) and ceramide production from sphingomyelin (SMPD-1/2). The mRNA levels of enzymes of ceramide degradation (Asah1/2) and utilization (sphingomyelin synthase, ceramide kinase, glycosyl-ceramide synthase, GM3 synthase) were also down-regulated. Ceramide-lowering effects of central leptin were prevented by local autonomic nervous system denervation of WAT. Finally, central leptin treatment markedly increased INSIG-1 mRNA expression and impaired SREBP-1c activation in epididymal WAT. These observations indicate that in vivo central leptin, acting through the autonomic nervous system, regulates total ceramide levels and SREBP-1c proteolytic maturation in WAT, probably contributing to improve the overall insulin sensitivity. PMID:18801905

Bonzón-Kulichenko, Elena; Schwudke, Dominik; Gallardo, Nilda; Moltó, Eduardo; Fernández-Agulló, Teresa; Shevchenko, Andrej; Andrés, Antonio

2009-01-01

103

Effects of Ang II Receptor Blocker Irbesartan on Adipose Tissue Function in Mice with Metabolic Disorders  

PubMed Central

Recent studies indicate that the functional renin-angiotensin system (RAS) exists in the adipose tissue. The adipose tissue RAS is proposed in the pathophysiology of metabolic disorders. In the present study, we examined therapeutic effects of irbesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders without any dietary loading, with our focus on the analysis on possible effect of irbesartan on the adipose tissue. The treatment with irbesartan significantly lowered systolic blood pressure with a concomitant decrease in body weight in KKAy mice. In addition, irbesartan significantly decreased the adipose leptin mRNA expression and tended to decrease IL-6 mRNA expression in the adipose tissue of KKAy mice. Furthermore irbesartan preserved the adipose gene expression of AT1R-associated protein (ATRAP), an endogenous inhibitory molecule of tissue AT1R signaling, with a concomitant tendency of up-regulation of adipose tissue ATRAP/AT1R ratio. Collectively, these results suggest that the irbesartan-induced beneficial suppressive effect on the leptin-IL-6 axis in the adipose tissue in KKAy mice is partly mediated by a trend of up-regulation of the adipose ATRAP/AT1R ratio as one of pleiotropic effects of irbesartan.

Maeda, Akinobu; Tamura, Kouichi; Wakui, Hiromichi; Ohsawa, Masato; Azushima, Kengo; Uneda, Kazushi; Kobayashi, Ryu; Tsurumi-Ikeya, Yuko; Kanaoka, Tomohiko; Dejima, Toru; Ohki, Koji; Haku, Sona; Yamashita, Akio; Umemura, Satoshi

2014-01-01

104

Effects of Ang II Receptor Blocker Irbesartan on Adipose Tissue Function in Mice with Metabolic Disorders.  

PubMed

Recent studies indicate that the functional renin-angiotensin system (RAS) exists in the adipose tissue. The adipose tissue RAS is proposed in the pathophysiology of metabolic disorders. In the present study, we examined therapeutic effects of irbesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders without any dietary loading, with our focus on the analysis on possible effect of irbesartan on the adipose tissue. The treatment with irbesartan significantly lowered systolic blood pressure with a concomitant decrease in body weight in KKAy mice. In addition, irbesartan significantly decreased the adipose leptin mRNA expression and tended to decrease IL-6 mRNA expression in the adipose tissue of KKAy mice. Furthermore irbesartan preserved the adipose gene expression of AT1R-associated protein (ATRAP), an endogenous inhibitory molecule of tissue AT1R signaling, with a concomitant tendency of up-regulation of adipose tissue ATRAP/AT1R ratio. Collectively, these results suggest that the irbesartan-induced beneficial suppressive effect on the leptin-IL-6 axis in the adipose tissue in KKAy mice is partly mediated by a trend of up-regulation of the adipose ATRAP/AT1R ratio as one of pleiotropic effects of irbesartan. PMID:24834011

Maeda, Akinobu; Tamura, Kouichi; Wakui, Hiromichi; Ohsawa, Masato; Azushima, Kengo; Uneda, Kazushi; Kobayashi, Ryu; Tsurumi-Ikeya, Yuko; Kanaoka, Tomohiko; Dejima, Toru; Ohki, Koji; Haku, Sona; Yamashita, Akio; Umemura, Satoshi

2014-01-01

105

Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue.  

PubMed

Fatty acid synthase (FAS), a nutritionally regulated lipogenic enzyme, is transcriptionally controlled by ADD1/SREBP1c (adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c), through insulin-mediated stimulation of ADD1/SREBP1c expression. Progesterone exerts lipogenic effects on adipocytes, and FAS is highly induced in breast tumor cell lines upon progesterone treatment. We show here that progesterone up-regulates ADD1/SREBP1c expression in the MCF7 breast cancer cell line and the primary cultured preadipocyte from rat parametrial adipose tissue. In MCF7, progesterone induced ADD1/SREBP1c and Metallothionein II (a well known progesterone-regulated gene) mRNAs, with comparable potency. In preadipocytes, progesterone increased ADD1/SREBP1c mRNA dose-dependently, but not SREBP1a or SREBP2. Run-on experiments demonstrated that progesterone action on ADD1/SREBP1c was primarily at the transcriptional level. The membrane-bound and mature nuclear forms of ADD1/SREBP1 protein accumulated in preadipocytes cultured with progesterone, and FAS induction could be abolished by adenovirus-mediated overexpression of a dominant negative form of ADD1/SREBP1 in these cells. Finally, in the presence of insulin, progesterone was unable to up-regulate ADD1/SREBP1c mRNA in preadipocytes, whereas its effect was restored after 24 h of insulin deprivation. Together these results demonstrate that ADD1/SREBP1c is controlled by progesterone, which, like insulin, acts by increasing ADD1/SREBP1c gene transcription. This provides a potential mechanism for the lipogenic actions of progesterone on adipose tissue. PMID:11278421

Lacasa, D; Le Liepvre, X; Ferre, P; Dugail, I

2001-04-13

106

Intercellular signaling between adipose tissue and muscle tissue  

Microsoft Academic Search

Adipose and muscle tissues undergo regulated growth and differentiation processes that are modulated by a wide range of factors. The interactions between myogenic cells and adipocytes play a significant role in growth and development, including the rate and extent of myogenesis, muscle growth, adipogenesis, lipogenesis\\/lipolysis, and in the utilization of energy substrates. Important hormones and growth factors involved in the

T. A. Kokta; M. V. Dodson; A. Gertler; R. A. Hill

2004-01-01

107

The immune cells in adipose tissue.  

PubMed

Although the pathological role of the immune system in several metabolic disorders, including type 1 diabetes mellitus (T1DM) and Addison's disease, has long been recognized and studied, only in the last decade has it become apparent that the immune system plays a broad and more subtle role in local and systemic metabolism. It is now apparent that the immune system monitors and responds to specific metabolic cues in both pathologic and non-pathologic settings through a set of processes dubbed immunometabolism. Expansion of adipose tissue mass, activation of lipolysis, eating a high fat diet and even non-shivering thermogenesis all lead to the recruitment and activation of immune cells in key metabolic tissues. The responses are complex and not completely defined, and indeed, as is typical of rapidly evolving research areas, there are some conflicting reports, especially related to the metabolic consequences of manipulation of immune function. However, what is clear is the consensus that metabolic processes, especially obesity and obesity-related complications, activate both the innate and adaptive arms of the immune system. Canonical immune processes consist of discrete steps: surveillance, recognition, effector action and resolution. Over the last decade evidence for each part of the immune response has been found at the intersection of the immune system with metabolism. Although evidence for immune surveillance and modulation of metabolism has been found in the liver, muscle, hypothalamus and pancreas, immune cell function has been most intensively studied and best understood in adipose tissue where studies continue to provide insights into the intersection of the metabolic and immune systems. Here we review the modulation of immune cell populations in adipose tissue and discuss regulatory processes implicated in controlling the interface between metabolism and immunologic function. PMID:24003919

Ferrante, A W

2013-09-01

108

Adipose tissue as an endocrine organ.  

PubMed

Adipose tissue plays a critical role in energy homeostasis, not only in storing triglycerides, but also responding to nutrient, neural, and hormonal signals and secreting adipokines that control feeding, thermogenesis, immunity, and neuroendocrine function. A rise in leptin signals satiety to the brain through receptors in hypothalamic and brainstem neurons. Leptin activates tyrosine kinase, Janus kinase 2, and signal transducer and activator of transcription 3, leading to increased levels of anorexigenic peptides, e.g., alpha-melanocyte stimulating hormone and cocaine- and amphetamine-regulated transcript, and inhibition of orexigenic peptides, e.g., neuropeptide Y and agouti-related peptide. Obesity is characterized by hyperleptinemia and hypothalamic leptin resistance, partly caused by induction of suppressor of cytokine signaling-3. Leptin falls rapidly during fasting and potently stimulates appetite, reduces thermogenesis, and mediates the inhibition of thyroid and reproductive hormones and activation of the hypothalamic-pituitary-adrenal axis. These actions are integrated by the paraventicular hypothalamic nucleus. Leptin also decreases glucose and stimulates lipolysis through central and peripheral pathways involving AMP-activated protein kinase (AMPK). Adiponectin is secreted exclusively by adipocytes and has been linked to glucose, lipid, and cardiovascular regulation. Obesity, diabetes, and atherosclerosis have been associated with reduced adiponectin levels, whereas adiponectin treatment reverses these abnormalities partly through activation of AMPK in liver and muscle. Administration of adiponectin in the brain recapitulates the peripheral actions to increase fatty acid oxidation and insulin sensitivity and reduce glucose. Although putative adiponectin receptors are widespread in peripheral organs and brain, it is uncertain whether adiponectin acts exclusively through these targets. As with leptin, adiponectin requires the central melanocortin pathway. Furthermore, adiponectin stimulates fatty acid oxidation and reduces glucose and lipids, at least in part, by activating AMPK in muscle and liver. PMID:17021375

Ahima, Rexford S

2006-08-01

109

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.

2010-01-01

110

trans Fatty Acid Isomers in Adipose Tissue Have Divergent Associations with Adiposity in Humans  

Microsoft Academic Search

The aim of this study was to evaluate the association between adipose tissue trans-fatty acid isomers and adiposity. This cross-sectional study included 1,785 subjects from Costa Rica. Fatty acid concentrations\\u000a (as a percentage of the total fatty acids) in subcutaneous adipose tissue were assessed by gas–liquid chromatography. Dietary\\u000a intakes were assessed with a food frequency questionnaire. Multivariate linear regression models

Liesbeth A. Smit; Walter C. Willett; Hannia Campos

2010-01-01

111

Human adipose tissue extract induces angiogenesis and adipogenesis in vitro.  

PubMed

The induction of adequate vascularization, a major challenge in tissue engineering, has been tried with numerous methods but with unsatisfactory results. Adipose tissue, an active endocrine organ with dense vasculature, secretes a wide number of angiogenic and adipogenic factors and seems an attractive source for these bioactive factors. We produced a novel cell-free extract from mature human adipose tissue (adipose tissue extract [ATE]) and analyzed the ability of this extract to induce angiogenesis and adipogenesis in vitro and studied the cytokine and growth factor composition of ATE with ELISA and cytokine array. We demonstrate that ATE, when added as cell culture supplement, effectively induced triglyceride accumulation in human adipose stem cells at concentrations from 200??g/mL upward in less than a week and caused elevated levels of adipocyte differentiation markers (proliferator-activated receptor gamma and acyl-CoA-binding protein) when treated with at least 350??g/mL of ATE. ATE induced angiogenesis from 450??g/mL upward after a week in vitro. ATE contained numerous angiogenic and adipogenic factors, for example, vascular endothelial growth factor, basic fibroblast growth factor, interleukin-6, adiponectin, angiogenin, leptin, and insulin-like growth factor-I, as well as lower levels of a wide variety of other cytokines. We here present a novel cell-free angiogenesis- and adipogenesis-inducing agent that is cell-free and easy to produce, and its effect is dose dependent and its composition can be easily modified. Therefore, ATE is a promising novel agent to be used for angiogenesis induction to overcome the challenge of vascularization and for adipogenesis induction in a wide variety of tissue engineering applications in vitro and in vivo. ATE is also efficient for reproduction and modeling of natural adipogenesis in vitro for, for example, obesity and diabetes studies. PMID:21902602

Sarkanen, Jertta-Riina; Kaila, Ville; Mannerström, Bettina; Räty, Sari; Kuokkanen, Hannu; Miettinen, Susanna; Ylikomi, Timo

2012-01-01

112

Using gene expression to predict differences in the secretome of human omental vs. subcutaneous adipose tissue.  

PubMed

The objective of this study was to characterize differences in the secretome of human omental compared with subcutaneous adipose tissue using global gene expression profiling. Gene expression was measured using Affymetrix microarrays (Affymetrix, Santa Clara, CA) in subcutaneous and omental adipose tissue in two independent experiments (n = 5 and n = 3 independent subjects; n = 16 arrays in total, 2 for each subject). Predictive bioinformatic algorithms were employed to identify secreted proteins. Microarray analysis identified 22 gene probe sets whose expression was significantly different with a fold change (FC) greater than 5 in expression in both experiments between omental and subcutaneous adipose tissue. Using bioinformatic predictive programs 11 of these 22 probe sets potentially coded for secreted proteins. Pathway network analysis of the secreted proteins showed that three of the proteins are part of a common pathway network. These proteins gremlin 1 (GREM1), pleiotrophin (PTN), and secretory leukocyte peptidase inhibitor (SLPI) are expressed respectively 43×, 23×, and 5× in omental adipose tissue relative to subcutaneous adipose tissue as determined by real-time PCR. The presence of GREM1, PTN, and SLPI protein in human adipose tissue was confirmed by western blotting. All three proteins are expressed in the human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cell line. The expression of GREM1, PTN, and SLPI changed with the differentiation of the preadipocytes into mature adipocytes. Gene expression coupled with predictive bioinformatic algorithms have identified several genes coding for secreted proteins which are expressed differently in omental adipose tissue compared to subcutaneous adipose tissue proving a valid alternative approach to help further define the adipocyte secretome. PMID:22286531

Hoggard, Nigel; Cruickshank, Morven; Moar, Kim-Marie; Bashir, Shabina; Mayer, Claus-Dieter

2012-06-01

113

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

114

Brain-Adipose Tissue Neural Crosstalk1  

PubMed Central

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

Bartness, Timothy J.; Song, C. Kay

2007-01-01

115

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.

Schulz, Tim J.; Tseng, Yu-Hua

2013-01-01

116

Compensatory increase in lipogenic gene expression in adipose tissue of transgenic mice expressing constitutively active AMP-activated protein kinase-alpha1 in liver.  

PubMed

We previously described a line of transgenic mice selectively expressing constitutively active AMPK-?1 under the control of liver-specific human apoE promoter with the hepatic control region sequence. In the short-term activation, the CA-AMPK-?1 transgenic mice at age 10-12weeks exhibited normal hepatic triglyceride content as compared to wild-type mice due to compensatory increase in mRNA expression of genes in the cholesterol and fatty acid synthesis pathways. But it was not known whether the lipogenic gene expression in white adipose tissue also changed. Here we characterized mRNA expression profile of main lipogenic genes in the cholesterol and fatty acid biosynthesis pathway in white adipose tissue. The data show that short-term chronic activation of AMPK in liver caused marked compensatory increase in lipogenic gene expression both in liver due to induction of Srebp-2 and in white adipose tissue due to upregulation of Srebp-1c. These results support the notion that in addition to its well-recognized function for fat storage adipose tissue can play an adaptive role in fatty acid synthesis when fatty acid synthesis is severely reduced in liver, the main lipogenic organ in mammals. PMID:21820413

Knowles, Christi; Liu, Zhi-Mei; Yang, Jian

2011-08-26

117

Combined effects of dietary arginine, leucine and protein levels on fatty acid composition and gene expression in the muscle and subcutaneous adipose tissue of crossbred pigs.  

PubMed

The cumulative effects of dietary arginine, leucine and protein levels on fat content, fatty acid composition and mRNA levels of genes controlling lipid metabolism in pig longissimus lumborum muscle and subcutaneous adipose tissue (SAT) were investigated. The experiment was performed on fifty-four intact male pigs (Duroc × Pietrain × Large White × Landrace crossbred), with a live weight ranging from 59 to 92 kg. The pigs were randomly assigned to one of six experimental treatments (n 9). The treatments followed a 2 × 3 factorial arrangement, with two levels of arginine supplementation (0 v. 1 %) and three levels of a basal diet (normal protein diet, NPD; reduced protein diet, RPD; reduced protein diet to achieve 2 % of leucine, RPDL). The results showed that dietary arginine supplementation did not affect the intramuscular fat (IMF) content and back fat thickness, but increased the total fat in SAT. This effect was associated with an increase in fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) mRNA levels in SAT, which suggests that arginine might be involved in the differential regulation of some key lipogenic genes in pig muscle and SAT. The increase in IMF content under the RPD, with or without leucine supplementation, was accompanied by increased FASN and SCD mRNA levels. Arginine supplementation did not influence the percentage of main fatty acids, while the RPD had a significant effect on fatty acid composition in both tissues. Leucine supplementation of RPD did not change IMF, total fat of SAT and back fat thickness, but increased 16 : 0 and 18 : 1cis-9 and decreased 18 : 2n-6 in muscle. PMID:24502766

Madeira, Marta S; Pires, Virgínia M R; Alfaia, Cristina M; Luxton, Richard; Doran, Olena; Bessa, Rui J B; Prates, José A M

2014-05-01

118

Prospective influences of circadian clocks in adipose tissue and metabolism  

Microsoft Academic Search

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

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

2010-01-01

119

Adipose tissue volume determination in males by computed tomography and 40K.  

PubMed

Seventeen healthy male volunteers with weights ranging from 54 to 145 kg were examined with a Philips Tomoscan 310. The upper attenuation limit of adipose tissue was determined to be -30 HU. The lower attenuation limit was set to -190 HU. Regional and total adipose tissue volumes were calculated from the adipose tissue areas of 22 scans and from the distances between these scans. Three different mathematical formulas were used, which all gave similar results. The adipose tissue area of several trunk scans, as well as the elbow, showed very high correlations (r greater than 0.96) versus the volume determinations based on 22 scans. The visceral adipose tissue area of scan L2-L3 showed a higher correlation (r = 0.986) than any other single scan versus the visceral adipose tissue volume. Total adipose tissue volume determinations with ten selected scans correlated very closely with the results obtained from 22 scans (r = 0.997). The adipose tissue volume of the head and neck region was 1.9 +/- 1.0 per cent of the total volume. Corresponding figures for other regions were: arms 6.8 +/- 1.0 per cent, legs 29.0 +/- 7.3 per cent, subcutaneous part of the trunk 41.4 +/- 7.4 per cent and the visceral region 20.9 +/- 7.0 per cent. With greater total adipose tissue volumes the percentage of the subcutaneous adipose tissue of the trunk increased (r = 0.686; P less than 0.005). There was a very strong negative relationship between the fractional amount of adipose tissue in the legs and in the trunk (r = 0.993, P less than 0.001). The potassium contents of fat-free mass and lean body mass were deduced to be 64.7 and 71.0 mmol/kg, respectively. These calculations were based on adipose tissue volume determinations by computed tomography, on 40K measurements and on the assumption that the volume proportions of fat, water and protein in adipose tissue were 85:13.7:1.3. By using computed tomography (CT) as a standard an optimal weight (W) for height (H) index was constructed by using an iterative correlation technique. The optimal index, i.e. highest correlation and lowest error versus ATCT was found for W/H0.9. PMID:3391740

Kvist, H; Chowdhury, B; Sjöström, L; Tylén, U; Cederblad, A

1988-01-01

120

Epicardial adipose tissue adiponectin expression is related to intracoronary adiponectin levels.  

PubMed

The role of adiponectin and epicardial adipose tissue in coronary artery disease (CAD) is a subject of debate. Whether plasma adiponectin concentration in the coronary circulation is locally modulated by the epicardial fat is still unexplored. We evaluated the hypothesis whether intracoronary plasma adiponectin levels are related to adiponectin expression in epicardial adipose tissue in vivo in patients with CAD and without CAD (non-CAD). We examined 12 patients with CAD who required CABG and 10 patients with non-CAD who underwent cardiac surgery for valve replacement. Plasma levels of adiponectin were measured in peripheral vein circulation and in left coronary artery (LCA) during coronary angiography. Epicardial adipose tissue biopsy for adiponectin protein extraction was performed during cardiac surgery in both CAD and non-CAD subjects. Adiponectin protein expression in epicardial adipose tissue was lower in patients with CAD than in those with non-CAD (0.45+/-0.4 vs. 1.1+/-1.0, p<0.05). LCA plasma adiponectin levels significantly correlated with epicardial adipose tissue adiponectin protein expression (r=0.68, p=0.02) in all subjects. Peripheral adiponectin levels and epicardial fat adiponectin protein expression were the best correlates of LCA adiponectin, r (2)=0.49, p<0.01, p<0.05, respectively). Our study showed that intracoronary adiponectin levels reflect systemic adiponectin levels. Epicardial adipose tissue could partially contribute to adiponectin levels in the coronary circulation. PMID:19003726

Iacobellis, G; di Gioia, Cira Rosaria Tiziana; di Gioia, C R Tiziana; Cotesta, D; Petramala, L; Travaglini, C; De Santis, V; Vitale, D; Tritapepe, L; Letizia, C

2009-03-01

121

Cellular and molecular factors in adipose tissue growth and obesity.  

PubMed

Heparin-binding growth factors related to basic fibroblast growth factor are major determinants of the cellular clonal composition of adipose tissue. By providing and maintaining varying complements of preadipocytes in different fat depots, these factors contribute to the varying sizes and functions of different regions, including the hypercellularity in appreciable obesity. Thus, differing levels and activities of the heparin-binding growth factors contribute to variations in depots within the same individual and between individuals, in lean and obese states. In contrast to regional differences in adiposity, which are accounted by factors resident in adipose tissue, we believe that obesity results from a generalized energy overload. According to our concept, there are genetic variations in cytoskeletal activity and thus differing quantities of energy are utilized for biomechanical processes. In a reciprocal relationship, the higher the cytoskeletal activity, the lesser the energy available for chemical energy storage, mainly in the form of triglyceride in adipocytes. At the extreme of "supermassive" obesity, a mutation in a gene related to a cytoskeletal protein would lead to appreciable dampening of cytoskeletal activity, with consequently the greatest quantity of energy remaining available for eventual triglyceride storage. Moreover, the new concept, for which we have have increasing experimental evidence, invokes a hypothalamic-efferent neural-cytoskeletal pathway, which would modulate the activity of the cytoskeleton. PMID:8249690

Roncari, D A; Hamilton, B S

1993-01-01

122

Cyclic Nucleotides Converge on Brown Adipose Tissue Differentiation  

NSDL National Science Digital Library

Brown adipose tissue (BAT) is rich in mitochondria and can uncouple oxidative phosphorylation to produce heat as a by-product of fatty acid metabolism. This thermogenic effect helps to maintain body temperature and also plays a critical role in energy homeostasis and the regulation of body weight. Both cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) contribute to the intracellular regulation of mitochondrial biogenesis and the differentiation of BAT. New evidence has defined the essential role of the cGMP-dependent protein kinase I in a pathway that modulates the RhoA-ROCK pathway and insulin receptor signaling to elicit BAT differentiation and stimulate thermogenesis.

Paul S. Amieux (University of Washington;Department of Pharmacology REV); G. Stanley McKnight (University of Washington;Department of Pharmacology REV)

2010-01-12

123

Membrane Potential of Brown Adipose Tissue  

PubMed Central

Membrane potentials were recorded in isolated segments of interscapular brown adipose tissue from rats. After equilibration at 29°C in Krebs-Ringer bicarbonate buffer a mean value of -51 ± 4 mv (SD) was found. This level could be maintained for up to 5 hr. The mean effective membrane resistance was 1.35 ± 0.45 megohm. The membrane potential was a function of the extracellular potassium concentration. Ouabain (10-6-10-3 M) and incubation in K-free buffer produced progressive depolarization. Epinephrine and norepinephrine in concentrations as low as 10-8 g/ml produced a prompt depolarization. Cooling of the tissue and lowering of the oxygen tension caused a marked and reversible decrease in the membrane potential. In tissue obtained from cold-adapted rats, the membrane potential was considerably diminished. 6Assuming that the membrane potential is some function of the Na permeability of the plasma membrane it is suggested that an increase in the rate of active Na-K transport and ensuing ADP formation might contribute to the increase in respiration seen during exposure to thermogenic stimuli.

Girardier, L.; Seydoux, J.; Clausen, T.

1968-01-01

124

Adipose tissue remodeling in lipedema: adipocyte death and concurrent regeneration.  

PubMed

Lipedema is a disease with unknown etiology presenting as bilateral and symmetric enlargement of the lower extremities due to subcutaneous deposition of the adipose tissue. Here we describe the histopathological features of the lipedema tissue and nonaffected adipose tissue obtained from a typical patient with severe lipedema. Immunohistochemical analyses indicated degenerative and regenerative changes of the lipedema tissue, characterized by crown-like structures (necrotizing adipocytes surrounded by infiltrating CD68+ macrophages; a feature commonly seen in obese adipose tissue) and proliferation of adipose-derived stem/progenitor/stromal cells (Ki67+CD34+ cells), respectively. These findings suggested increased adipogenesis in the lipedema tissue, which may further lead to hypoxia similar to that seen in obesity, resulting in adipocyte necrosis and macrophage recruitment. The confinement to the lower extremities and the difference from systemic obesity warrants further elucidation in future studies. PMID:19281484

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

2009-12-01

125

Troglitazone action is independent of adipose tissue.  

PubMed Central

We have investigated the antidiabetic action of troglitazone in aP2/DTA mice, whose white and brown fat was virtually eliminated by fat-specific expression of diphtheria toxin A chain. aP2/DTA mice had markedly suppressed serum leptin levels and were hyperphagic, but did not gain excess weight. aP2/DTA mice fed a control diet were hyperlipidemic, hyperglycemic, and had hyperinsulinemia indicative of insulin-resistant diabetes. Treatment with troglitazone alleviated the hyperglycemia, normalized the tolerance to intraperitoneally injected glucose, and significantly decreased elevated insulin levels. Troglitazone also markedly decreased the serum levels of cholesterol, triglycerides, and free fatty acids both in wild-type and aP2/DTA mice. The decrease in serum triglycerides in aP2/DTA mice was due to a marked reduction in VLDL- and LDL-associated triglyceride. In skeletal muscle, triglyceride levels were decreased in aP2/DTA mice compared with controls, but glycogen levels were increased. Troglitazone treatment decreased skeletal muscle, but not hepatic triglyceride and increased hepatic and muscle glycogen content in wild-type mice. Troglitazone decreased muscle glycogen content in aP2/DTA mice without affecting muscle triglyceride levels. The levels of peroxisomal proliferator-activated receptor gamma mRNA in liver increased slightly in aP2/DTA mice and were not changed by troglitazone treatment. The results demonstrate that insulin resistance and diabetes can occur in animals without significant adipose deposits. Furthermore, troglitazone can alter glucose and lipid metabolism independent of its effects on adipose tissue.

Burant, C F; Sreenan, S; Hirano, K; Tai, T A; Lohmiller, J; Lukens, J; Davidson, N O; Ross, S; Graves, R A

1997-01-01

126

Differential effects of bone morphogenetic protein-2 and transforming growth factor-beta 1 on gene expression of collagen-modifying enzymes in human adipose tissue-derived mesenchymal stem cells  

Microsoft Academic Search

Adipose tissue–derived mesenchymal stem cells (AT-MSCs) in combination with bone morphogenetic protein-2 (BMP-2) or transforming growth factor-?1 (TGF-?1) are under evaluation for bone tissue engineering. Posttranslational modification of type I collagen is essential for functional bone tissue with adequate physical and mechanical properties. We investigated whether BMP-2 (10–100ng\\/mL) and\\/or TGF-?1 (1–10ng\\/mL) affect gene expression of ?2(I) procollagen and collagen-modifying enzymes,

Marlene Knippenberg; Marco N. Helder; Behrouz Zandieh Doulabi; Ruud A. Bank; Paul I. J. M. Wuisman; Jenneke Klein-Nulend

2009-01-01

127

Omental and subcutaneous adipose tissue steroid levels in obese men  

Microsoft Academic Search

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8–62.2 years (average BMI value of 46.3±12.7kg\\/m2). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were

Chantal Bélanger; Frédéric-Simon Hould; Stéfane Lebel; Simon Biron; Gaétan Brochu; André Tchernof

2006-01-01

128

?-Carotene conversion products and their effects on adipose tissue  

Microsoft Academic Search

Recent epidemiological data suggest that ?-carotene may be protective against metabolic diseases in which adipose tissue plays\\u000a a key role. Adipose tissue constitutes the major ?-carotene storage tissue and its functions have been shown to be modulated\\u000a in response to ?-carotene breakdown products, especially retinal produced after cleavage by ?-carotene 15,15?-monooxygenase\\u000a (BCMO1), and retinoic acid arising from oxidation of retinal.

Franck Tourniaire; Erwan Gouranton; Johannes von Lintig; Jaap Keijer; M. Luisa Bonet; Jaume Amengual; Georg Lietz; Jean-François Landrier

2009-01-01

129

Cell Supermarket: Adipose Tissue as a Source of Stem Cells  

PubMed Central

Adipose tissue is derived from numerous sources, and in recent years this tissue 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 and scientific applications. The focus of this paper is to reflect on this area of research and to provide a list of potential (future) research areas.

Dodson, M.V.; Wei, S.; Duarte, M.; Du, M.; Jiang, Z.; Hausman, G.J.; Bergen, W.G.

2013-01-01

130

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

131

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

PubMed

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

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

2014-05-01

132

Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis  

PubMed Central

Tumor-associated stroma is typified by a persistent, non-resolving inflammatory response that enhances tumor angiogenesis, growth and metastasis. Inflammation in tumors is instigated by heterotypic interactions between malignant tumor cells, vascular endothelium, fibroblasts, immune and inflammatory cells. We found that tumor-associated adipocytes also contribute to inflammation. We have analyzed peritumoral adipose tissue in a syngeneic mouse melanoma model. Compared to control adipose tissue, adipose tissue juxtaposed to implanted tumors exhibited reduced adipocyte size, extensive fibrosis, increased angiogenesis and a dense macrophage infiltrate. A mouse cytokine protein array revealed up-regulation of inflammatory mediators including IL-6, CXCL1, MCP-1, MIP-2 and TIMP-1 in peritumoral versus counterpart adipose tissues. CD11b+ macrophages contributed strongly to the inflammatory activity. These macrophages were isolated from peritumoral adipose tissue and found to overexpress ARG1, NOS2, CD301, CD163, MCP-1 and VEGF, which are indicative of both M1 and M2 polarization. Tumors implanted at a site distant from subcutaneous, anterior adipose tissue were strongly growth-delayed, had fewer blood vessels and were less populated by CD11b+ macrophages. In contrast to normal adipose tissue, micro-dissected peritumoral adipose tissue explants launched numerous vascular sprouts when cultured in an ex vivo model. Thus, inflamed tumor-associated adipose tissue fuels the growth of malignant cells by acting as a proximate source for vascular endothelium and activated pro-inflammatory cells, in particular macrophages.

Wagner, Marek; Bjerkvig, Rolf; Wiig, Helge; Melero-Martin, Juan M.; Lin, Ruei-Zeng; Klagsbrun, Michael

2013-01-01

133

Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue  

Microsoft Academic Search

Aims\\/hypothesis  Increasing the expression of the brown adipose tissue-specific gene uncoupling protein-1 (Ucp1) is a potential target for treating obesity. We investigated the role of DNA methylation and histone modification in Ucp1 expression in adipose cell lines and ex vivo murine adipose tissues.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Methylation state of the Ucp1 enhancer was studied using bisulphite mapping in murine adipose cell lines, and tissue

A. Shore; A. Karamitri; P. Kemp; J. R. Speakman; M. A. Lomax

2010-01-01

134

Tissue-specific nutritional regulation of angiotensinogen in adipose tissue.  

PubMed

Recent studies have found that angiotensinogen is expressed in white and brown fat pads, and adipocytes have been implicated as a primary source of angiotensinogen in several other tissues. The functional significance of this unexpected expression is unknown. To address this, we studied angiotensinogen messenger RNA (mRNA) expression and angiotensinogen secretion in adipose tissue and isolated adipocytes comparing fasted and refed rodents and those with genetic obesity with normal controls. Control 2-month-old Sprague-Dawley rats, those fasted for 3 days, or those fasted for 2 days and refed for 6 days were killed, and adipocytes were isolated from epididymal fat pads using collagenase digestion. Angiotensinogen mRNA was reduced to 14.6 +/- 2.3% of control levels under fasted conditions and increased to 228 +/- 53% of control levels after refeeding. Angiotensinogen release from adipocytes was reduced to 33% of control levels by fasting and increased to 183% by refeeding. These effects of fasting and refeeding on angiotensinogen regulation were tissue specific since liver angiotensinogen mRNA and serum angiotensinogen concentrations were unaffected. Systolic blood pressure, however, was modulated by fasting and refeeding in a manner parallel to adipocyte angiotensinogen expression. In related experiments, angiotensinogen secretion per epididymal fat pad of the ob/ob mouse model of obesity was increased an average of 3.4-fold compared with control. We conclude angiotensinogen expression in white adipocytes is regulated nutritionally in a tissue-specific manner. We propose that adipocyte angiotensinogen could play a previously unrecognized role in regulating adipose tissue blood supply and thereby fatty acid efflux from fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1555865

Frederich, R C; Kahn, B B; Peach, M J; Flier, J S

1992-04-01

135

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.

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

2014-01-01

136

Isolation of Adipose Tissue Immune Cells  

PubMed Central

The discovery of increased macrophage infiltration in the adipose tissue (AT) of obese rodents and humans has led to an intensification of interest in immune cell contribution to local and systemic insulin resistance. Isolation and quantification of different immune cell populations in lean and obese AT is now a commonly utilized technique in immunometabolism laboratories; yet extreme care must be taken both in stromal vascular cell isolation and in the flow cytometry analysis so that the data obtained is reliable and interpretable. In this video we demonstrate how to mince, digest, and isolate the immune cell-enriched stromal vascular fraction. Subsequently, we show how to antibody label macrophages and T lymphocytes and how to properly gate on them in flow cytometry experiments. Representative flow cytometry plots from low fat-fed lean and high fat-fed obese mice are provided. A critical element of this analysis is the use of antibodies that do not fluoresce in channels where AT macrophages are naturally autofluorescent, as well as the use of proper compensation controls.

Orr, Jeb S.; Kennedy, Arion J.; Hasty, Alyssa H.

2013-01-01

137

New concepts in white adipose tissue physiology.  

PubMed

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

Proença, A R G; Sertié, R A L; Oliveira, A C; Campaña, A B; Caminhotto, R O; Chimin, P; Lima, F B

2014-02-01

138

Adipose tissue lymphocytes: types and roles.  

PubMed

Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development. PMID:20358356

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

2009-12-01

139

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.

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

2011-01-01

140

Morphological and inflammatory changes in visceral adipose tissue during obesity.  

PubMed

Obesity is a major health burden worldwide and is a major factor in the development of insulin resistance and metabolic complications such as type II diabetes. Chronic nutrient excess leads to visceral adipose tissue (VAT) expansion and dysfunction in an active process that involves the adipocytes, their supporting matrix, and immune cell infiltrates. These changes contribute to adipose tissue hypoxia, adipocyte cell stress, and ultimately cell death. Accumulation of lymphocytes, macrophages, and other immune cells around dying adipocytes forms the so-called "crown-like structure", a histological hallmark of VAT in obesity. Cross talk between immune cells in adipose tissue dictates the overall inflammatory response, ultimately leading to the production of pro-inflammatory mediators which directly induce insulin resistance in VAT. In this review, we summarize recent studies demonstrating the dramatic changes that occur in visceral adipose tissue during obesity leading to low-grade chronic inflammation and metabolic disease. PMID:24356782

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

2014-03-01

141

Breast Cancer and Estrogen Biosynthesis in Adipose Tissue.  

National Technical Information Service (NTIS)

We seek to identify the cellular and molecular mechanisms responsible for the regulation of aromatase expression in the breast cancer and surrounding adipose tissue. As previously reported, we completed most of the studies proposed under four specific aim...

S. E. Bulun

1997-01-01

142

Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance  

PubMed Central

Low-grade inflammation in obesity is associated with accumulation of the macrophage-derived cytokine osteopontin (OPN) in adipose tissue and induction of local as well as systemic insulin resistance. Since glucose-dependent insulinotropic polypeptide (GIP) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate OPN expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13 ± 0.04 vs. 0.04 ± 0.01, P < 0.05) and correlated inversely with measures of insulin sensitivity (r = ?0.24, P = 0.001). A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with a lower amount of the exon 9–containing isoform required for transmembrane activity. Carriers of the A allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone but also as a trigger of inflammation and insulin resistance in adipose tissue. Carriers of the GIPR rs10423928 A allele showed protective properties via reduced GIP effects. Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions.

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

2013-01-01

143

Regional differences in adipose tissue metabolism in obese men  

Microsoft Academic Search

We examined omental and subcutaneous adipose tissue adipocyte size, and lipolysis and lipoprotein lipase (LPL) activity in a sample of 33 men aged 22.6 to 61.2 years and with a body mass index ranging from 24.6 to 79.1 kg\\/m2. We tested the hypothesis that lipolysis rates would be higher in the omental fat depot than in subcutaneous adipose tissue and

Ariane Boivin; Gaétan Brochu; Simon Marceau; Picard Marceau; Frédéric-Simon Hould; André Tchernof

2007-01-01

144

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. Lindström; B. v. Bavel

1999-01-01

145

Pioglitazone induces apoptosis of macrophages in human adipose tissue  

Microsoft Academic Search

Metabolic syndrome and type 2 diabetes mellitus areassociatedwithanincreasednumberofmacrophagecells that infiltrate white adipose tissue (WAT). Previously, we demonstrated that the treatment of subjects with impaired glucose tolerance (IGT) with the peroxisome proliferator- activated receptor g (PPARg) agonist pioglitazone resulted inadecreaseinmacrophage numberinadiposetissue.Here, adipose tissue samples from IGT subjects treated with piog- litazone were examined for apoptosis with terminal deoxy- nucleotidyl transferase-mediated dUTP-biotin

Angela M. Bodles; Vijayalakshmi Varma; Aiwei Yao-Borengasser; Bounleut Phanavanh; Charlotte A. Peterson; Robert E. McGehee; Neda Rasouli; Martin Wabitsch; Philip A. Kern

2006-01-01

146

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

147

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

PubMed Central

Background Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver; these include reduced insulin-stimulated glucose transport, reduced expression of GLUT4, altered expression of adipokines, and adipocyte hypertrophy. Animal studies have shown that expansion of adipose tissue alone is not sufficient to cause systemic insulin resistance in the absence of adipose tissue metabolic dysfunction. To determine if this holds true for humans, we studied the relationship between insulin resistance and markers of adipose tissue dysfunction in non-obese individuals. Method 32 non-obese first-degree relatives of Type 2 diabetic patients were recruited. Glucose tolerance was determined by an oral glucose tolerance test and insulin sensitivity was measured with the hyperinsulinaemic-euglycaemic clamp. Blood samples were collected and subcutaneous abdominal adipose tissue biopsies obtained for gene/protein expression and adipocyte cell size measurements. Results Our findings show that also in non-obese individuals low insulin sensitivity is associated with signs of adipose tissue metabolic dysfunction characterized by low expression of GLUT4, altered adipokine profile and enlarged adipocyte cell size. In this group, insulin sensitivity is positively correlated to GLUT4 mRNA (R?=?0.49, p?=?0.011) and protein (R?=?0.51, p?=?0.004) expression, as well as with circulating adiponectin levels (R?=?0.46, 0?=?0.009). In addition, insulin sensitivity is inversely correlated to circulating RBP4 (R?=??0.61, 0?=?0.003) and adipocyte cell size (R?=??0.40, p?=?0.022). Furthermore, these features are inter-correlated and also associated with other clinical features of the metabolic syndrome in the absence of obesity. No association could be found between the hypertrophy-associated adipocyte dysregulation and HIF-1alpha in this group of non-obese individuals. Conclusions In conclusion, these findings support the concept that it is not obesity per se, but rather metabolic dysfunction of adipose tissue that is associated with systemic insulin resistance and the metabolic syndrome.

2012-01-01

148

Impacts of Visceral Adipose Tissue and Subcutaneous Adipose Tissue on Metabolic Risk Factors in Middle-aged Japanese  

Microsoft Academic Search

Regional fat distribution rather than overall fat volume has been considered to be important to understanding the link between obesity and metabolic disorders. We aimed to evaluate the independent associations of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with metabolic risk factors in apparently healthy middle-aged Japanese. Participants were 1,119 men and 854 women aged 38–60 years who

Rie Oka; Katsuyuki Miura; Masaru Sakurai; Koshi Nakamura; Kunimasa Yagi; Susumu Miyamoto; Tadashi Moriuchi; Hiroshi Mabuchi; Junji Koizumi; Hideki Nomura; Yoshiyu Takeda; Akihiro Inazu; Atsushi Nohara; Masa-aki Kawashiri; Shinya Nagasawa; Junji Kobayashi; Masakazu Yamagishi

2010-01-01

149

Germline Ablation of VGF Increases Lipolysis in White Adipose Tissue  

PubMed Central

Targeted deletion of VGF, a neuronal and endocrine secreted protein and neuropeptide precursor, produces a lean, hypermetabolic mouse that is resistant to diet-, lesion-, and genetically-induced obesity and diabetes. We hypothesized that increased sympathetic nervous system activity in Vgf?/Vgf? knockout mice is responsible for increased energy expenditure and decreased fat storage, and that increased beta-adrenergic receptor stimulation induces lipolysis in white adipose tissue (WAT) of Vgf?/Vgf? mice. We found that fat mass was markedly reduced in Vgf?/Vgf? mice. Within knockout WAT, phosphorylation of protein kinase A (PKA) substrate increased in males and females, phosphorylation of hormone sensitive lipase (HSL) (Ser563) increased in females, and levels of adipose triglyceride lipase (ATGL), comparative gene identification-58 (CGI-58), and phospho-perilipin, were higher in male Vgf?/Vgf? WAT compared to wild type, consistent with increased lipolysis. The phosphorylation of AMP-activated protein kinase (AMPK) (Thr172) and levels of the AMPK kinase, transforming growth factor ?-activated kinase 1 (TAK-1), were decreased. This was associated with a decrease in HSL Ser565 phosphorylation, the site phosphorylated by AMPK, in both male and female Vgf?/Vgf? WAT. No significant differences in phosphorylation of cAMP response element binding protein (CREB) or the p42/44 mitogen-activated protein kinase (MAPK) were noted. Despite this evidence supporting increased cAMP signaling and lipolysis, lipogenesis as assessed by fatty acid synthase (FAS) protein expression and phosphorylated acetyl-CoA carboxylase (pACC) was not decreased. Our data suggest that the VGF precursor or selected VGF-derived peptides dampen sympathetic outflow pathway activity to WAT to regulate fat storage and lipolysis.

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

2012-01-01

150

Proteomic Analysis of Human Adipose Tissue After Rosiglitazone Treatment Shows Coordinated Changes to Promote Glucose Uptake  

Microsoft Academic Search

The aim of this study was to identify potential protein targets for insulin sensitization in human adipose tissue using unbiased proteomic approaches. Ten moderately obese, but otherwise healthy, subjects were treated with rosiglitazone 4 mg b.i.d. for 14 days and global protein and gene expression changes were monitored. Proteomic analysis revealed distinct up- or downregulation (greater than twofold) in 187

Meftun Ahmed; Matt J. Neville; Mariola J. Edelmann; Benedikt M. Kessler; Fredrik Karpe

2010-01-01

151

Adipose Tissue Regeneration: A State of the Art  

PubMed Central

Adipose tissue pathologies and defects have always represented a reconstructive challenge for plastic surgeons. In more recent years, several allogenic and alloplastic materials have been developed and used as fillers for soft tissue defects. However, their clinical use has been limited by further documented complications, such as foreign-body reactions potentially affecting function, degradation over time, and the risk for immunogenicity. Tissue-engineering strategies are thus being investigated to develop methods for generating adipose tissue. This paper will discuss the current state of the art in adipose tissue engineering techniques, exploring the biomaterials used, stem cells application, culture strategies, and current regulatory framework that are in use are here described and discussed.

Casadei, Alessandro; Epis, Roberta; Ferroni, Letizia; Tocco, Ilaria; Gardin, Chiara; Bressan, Eriberto; Sivolella, Stefano; Vindigni, Vincenzo; Pinton, Paolo; Mucci, Giuseppe; Zavan, Barbara

2012-01-01

152

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

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 (150-175g) were allowed voluntary access to a running wheel for 6weeks followed by exposure to an acute stressor (100, 1.5mA-5s 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

2014-07-01

153

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.

2014-01-01

154

Transcriptional factors that promote formation of white adipose tissue  

PubMed Central

Adipocytes are highly specialized cells that play a major role in energy homeostasis in vertebrate organisms. Excess adipocyte size or number is a hallmark of obesity, which is currently a global epidemic. Obesity is a major risk factor for the development of type II diabetes (T2DM), cardiovascular disease, and hypertension. Obesity and its related disorders result in dysregulation of the mechanisms that control the expression of metabolic and endocrine related genes in adipocytes. Therefore, understanding adipocyte differentiation is relevant not only for gaining insight into the pathogenesis of metabolic diseases, but also for identifying proteins or pathways which might be appropriate targets for pharmacological interventions. Significant advances towards an understanding of the regulatory processes involved in adipocyte differentiation have largely been made by the identification of transcription factors that contribute to the adipogenic process. It is important to note that the developmental origin of white and brown fat is distinct and different precursor cells are involved in the generation of these different types of adipose tissue (reviewed in Lefterova and Lazar, 2009; Seale et al., 2009). Several transcription factors, notably PPAR?, several members of the C/EBP and KLF families, STAT5, and SREBP-1c, have been shown to have significant roles in promoting adipogenesis. More comprehensive reviews on negative and positive regulators of adipogenesis have been published in the past year (reviewed in Christodoulides et al., 2009; Lefterova and Lazar, 2009). Though many proteins are known to negatively regulate adipogenesis, including Wnts, KLFs, the E2F family of transcription factors, CHOP, Delta-interacting protein A, ETO/MTG8, and members of the GATA and forkhead transcription factor families, this review will focus on transcription factors that positively impact the development of white adipose tissue.

White, Ursula A.; Stephens, Jacqueline M.

2011-01-01

155

Transcriptional factors that promote formation of white adipose tissue.  

PubMed

Adipocytes are highly specialized cells that play a major role in energy homeostasis in vertebrate organisms. Excess adipocyte size or number is a hallmark of obesity, which is currently a global epidemic. Obesity is a major risk factor for the development of type II diabetes (T2DM), cardiovascular disease, and hypertension. Obesity and its related disorders result in dysregulation of the mechanisms that control the expression of metabolic and endocrine related genes in adipocytes. Therefore, understanding adipocyte differentiation is relevant not only for gaining insight into the pathogenesis of metabolic diseases, but also for identifying proteins or pathways which might be appropriate targets for pharmacological interventions. Significant advances towards an understanding of the regulatory processes involved in adipocyte differentiation have largely been made by the identification of transcription factors that contribute to the adipogenic process. It is important to note that the developmental origin of white and brown fat is distinct and different precursor cells are involved in the generation of these different types of adipose tissue (reviewed in Lefterova and Lazar, 2009; Seale et al., 2009). Several transcription factors, notably PPAR gamma, several members of the C/EBP and KLF families, STAT5, and SREBP-1c, have been shown to have significant roles in promoting adipogenesis. More comprehensive reviews on negative and positive regulators of adipogenesis have been published in the past year (reviewed in Christodoulides et al., 2009; Lefterova and Lazar, 2009). Though many proteins are known to negatively regulate adipogenesis, including Wnts, KLFs, the E2F family of transcription factors, CHOP, Delta-interacting protein A, ETO/MTG8, and members of the GATA and forkhead transcription factor families, this review will focus on transcription factors that positively impact the development of white adipose tissue. PMID:19733624

White, Ursula A; Stephens, Jacqueline M

2010-04-29

156

White adipose tissue overproduces the lipid-mobilizing factor zinc ?2-glycoprotein in chronic kidney disease.  

PubMed

Chronic kidney disease (CKD) is frequently associated with protein-energy wasting, a recognized strong predictive factor of mortality. Zinc ?2-glycoprotein (ZAG) is a new adipokine involved in body weight control through its lipid-mobilizing activity. Here we tested whether the uremic environment in CKD could alter ZAG production by white adipose tissue and contribute to CKD-associated metabolic disturbances. Compared with normal plasma, uremic plasma induced a significant increase in ZAG synthesis (124%), was associated with a significant increase in basal lipolysis (31%), and significantly blunted lipogenesis (-53%) in 3T3-L1 adipocytes in vitro. In 5/6 nephrectomized rats and mice in vivo, there was a significant decrease in white adipose tissue accretion (-44% and -43%, respectively) and a significantly higher white adipose tissue content of ZAG protein than in sham-operated, pair-fed control animals (498% and 106%, respectively). Subcutaneous white adipose tissue biopsies from patients with end-stage renal disease exhibited a higher content of ZAG (573%) than age-matched controls. Thus, the ZAG content is increased in white adipose tissue from patients or animal models with CKD. Overproduction of ZAG in CKD could be a major contributor to metabolic disturbances associated with CKD. PMID:23423258

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

2013-05-01

157

Brain insulin controls adipose tissue lipolysis and lipogenesis  

PubMed Central

SUMMARY White adipose tissue (WAT) dysfunction plays a key role in the pathogenesis of type 2 diabetes (DM2). Unrestrained WAT lipolysis results in increased fatty acid release leading to insulin resistance and lipotoxicity, while impaired de novo lipogenesis in WAT decreases the synthesis of insulin sensitizing fatty acid species like palmitoleate. Here we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague Dawley rats increases WAT lipogenic protein expression, and inactivates hormone sensitive lipase (Hsl) and suppresses lipolysis. Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and in particular hypothalamic insulin action play a pivotal role in WAT functionality.

Scherer, Thomas; O'Hare, James; Diggs-Andrews, Kelly; Schweiger, Martina; Cheng, Bob; Lindtner, Claudia; Zielinski, Elizabeth; Vempati, Prashant; Su, Kai; Dighe, Shveta; Milsom, Thomas; Puchowicz, Michelle; Scheja, Ludger; Zechner, Rudolf; Fisher, Simon J.; Previs, Stephen F.; Buettner, Christoph

2011-01-01

158

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.

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

2014-01-01

159

The evolution of the adipose tissue: a neglected enigma.  

PubMed

The complexity of the anatomical distribution and functions of adipose tissue (AT) has been rarely analyzed in an evolutionary perspective. From yeast to man lipid droplets are stored mainly in the form of triglycerides in order to provide energy during periods when energy demands exceed caloric intake. This simple scenario is in agreement with the recent discovery of a highly conserved family of proteins for fat storage in both unicellular and multicellular organisms. However, the evolutionary history of organs such as the fat body in insects, playing a role in immunity and other functions besides energy storage and thermal insulation, and of differently distributed subtypes of AT in vertebrates is much less clear. These topics still await a systematic investigation using up-to-date technologies and approaches that would provide information useful for understanding the role of different AT subtypes in normal/physiological conditions or in metabolic pathologies of humans. PMID:21781968

Ottaviani, Enzo; Malagoli, Davide; Franceschi, Claudio

2011-10-01

160

Germline ablation of VGF increases lipolysis in white adipose tissue.  

PubMed

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

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

2012-11-01

161

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

PubMed Central

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

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

2014-01-01

162

Adipose tissue insulin resistance due to loss of PI3K p110? leads to decreased energy expenditure and obesity.  

PubMed

Adipose tissue is a highly insulin-responsive organ that contributes to metabolic regulation. Insulin resistance in the adipose tissue affects systemic lipid and glucose homeostasis. Phosphoinositide 3-kinase (PI3K) mediates downstream insulin signaling in adipose tissue, but its physiological role in vivo remains unclear. Using Cre recombinase driven by the aP2 promoter, we created mice that lack the class 1A PI3K catalytic subunit p110? or p110? specifically in the white and brown adipose tissue. The loss of p110?, not p110?, resulted in increased adiposity, glucose intolerance and liver steatosis. Mice lacking p110? in adipose tissue exhibited a decrease in energy expenditure but no change in food intake or activity compared with control animals. This low energy expenditure is a consequence of low cellular respiration in the brown adipocytes caused by a decrease in expression of key mitochondrial genes including uncoupling protein-1. These results illustrate a critical role of p110? in the regulation of energy expenditure through modulation of cellular respiration in the brown adipose tissue and suggest that compromised insulin signaling in adipose tissue might be involved in the onset of obesity. PMID:24691033

Nelson, Victoria L B; Jiang, Ya-Ping; Dickman, Kathleen G; Ballou, Lisa M; Lin, Richard Z

2014-05-15

163

Comparison of Dorsocervical With Abdominal Subcutaneous Adipose Tissue in Patients With and Without Antiretroviral Therapy-Associated Lipodystrophy  

PubMed Central

OBJECTIVE Combination antiretroviral therapy (cART) is associated with lipodystrophy, i.e., loss of subcutaneous adipose tissue in the abdomen, limbs, and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulate in this region (buffalo hump). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1–infected cART-treated patients with (cART+LD+) and without (cART+LD?) lipodystrophy. RESEARCH DESIGN AND METHODS We used histology, microarray, PCR, and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n = 21) and cART+LD? (n = 11). RESULTS Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA; copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD?. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical versus abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot. CONCLUSIONS Because mtDNA is depleted even in the nonatrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal subcutaneous adipose tissue is in expression of homeobox genes.

Sevastianova, Ksenia; Sutinen, Jussi; Greco, Dario; Sievers, Meline; Salmenkivi, Kaisa; Perttila, Julia; Olkkonen, Vesa M.; Wagsater, Dick; Lidell, Martin E.; Enerback, Sven; Eriksson, Per; Walker, Ulrich A.; Auvinen, Petri; Ristola, Matti; Yki-Jarvinen, Hannele

2011-01-01

164

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

PubMed

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

2014-02-01

165

Cytomegalovirus infection of adipose tissues induces steatitis in adult mice.  

PubMed Central

Young adult mice infected with MCMV were shown to develop inflammatory lesions in the peripancreatic and salivary gland adipose tissues. MCMV replication was detected by immunoperoxidase staining and electron microscopy in adipocytes, fibroblasts, endothelial cells and pericytes in brown and white adipose tissues. More infected cells were detected in C3H mice than in BALB/c, BALB.B, BALB.K or C57BL/6 mice. Peripancreatic steatitis consisted of a monocytic infiltrate surrounding focal necrosis of adipocytes, the severity of which was influenced by the route of inoculation, virus dose, and genetic susceptibility to disseminated MCMV-disease. C57BL/6 mice showed the greatest susceptibility with severe coalescing focal inflammation around areas of coagulative necrosis. Salivary gland adipose tissues exhibited lymphocytic steatitis, which was reduced in Nu/Nu mice. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8

Price, P.; Eddy, K. S.; Papadimitriou, J. M.; Robertson, T. A.; Shellam, G. R.

1990-01-01

166

Developmental Programming of Fetal Skeletal Muscle and Adipose Tissue Development  

PubMed Central

All important developmental milestones are accomplished during the fetal stage, and nutrient fluctuation during this stage produces lasting effects on offspring health, so called fetal programming or developmental programming. The fetal stage is critical for skeletal muscle development, as well as adipose and connective tissue development. Maternal under-nutrition at this stage affects the proliferation of myogenic precursor cells and reduces the number of muscle fibers formed. Maternal over-nutrition results in impaired myogenesis and elevated adipogenesis. Because myocytes, adipocytes and fibrocytes are all derived from mesenchymal stem cells, molecular events which regulate the commitment of stem cells to different lineages directly impact fetal muscle and adipose tissue development. Recent studies indicate that microRNA is intensively involved in myogenic and adipogenic differentiation from mesenchymal stem cells, and epigenetic changes such as DNA methylation are expected to alter cell lineage commitment during fetal muscle and adipose tissue development.

Yan, Xu; Zhu, Mei-Jun; Dodson, Michael V.; Du, Min

2013-01-01

167

Mechanisms of Inflammatory Responses in Obese Adipose Tissue  

PubMed Central

The fields of immunology and metabolism are rapidly converging on adipose tissue. During obesity, many immune cells infiltrate or populate in adipose tissue and promote a low-grade chronic inflammation. Studies to date have suggested that perturbation of inflammation is critically linked to nutrient metabolic pathways and to obesity-associated complications such as insulin resistance and type 2 diabetes. Despite these advances, however, many open questions remain including how inflammatory responses are initiated and maintained, how nutrients impact the function of various immune populations, and how inflamma-tory responses affect systemic insulin sensitivity. Here we review recent studies on the roles of various immune cells at different phases of obesity and discuss molecular mechanisms underlying obesity-associated inflammation. Better understanding of the events occurring in adipose tissue will provide insights into the pathophysiological role of inflammation in obesity and shed light on the pathogenesis of obesity-associated metabolic syndrome.

Sun, Shengyi; Ji, Yewei; Kersten, Sander; Qi, Ling

2014-01-01

168

Adipose tissue cellularity and lipolysis. Response to exercise and cortisol treatment.  

PubMed Central

Male rats a 5 wk of age were subjected to 13 wk of intensive treadmill running to study the effect of exercise on adipose tissue cellularity and lipolysis. Untrained controls of the same age remained sedentary in their cages for the duration of the experiment. Adipocyte numbers were similar in eqidiymal fat pads from trained and untrained rats (12.7 plus or minus 1.3 X 10(6) vs. 15.3 plus or minus 1.3 X 10(6) cells/pad), however trained rats had smaller fat pads containing smaller cells (0.09 plus of minus 0.01 vs. 0.20 plus or minus 0.04 mug triglyceride/cell). Adipocytes from trained rats possessed greater epinephrine-sensitive lipase activity than sedentary rats on a per cell, per milligram protein, per gram adipose tissue, or per fat pad basis. Although the smaller cells of the trained rats had greater epinephrine-sensitive lipase activity than the larger cells of the untrained rats, lipolysis was positively correlated with cell size within both treatment groups. Cortisol treatment of intact animals did not significantly affect in vitro adipose tissue lipolysis. The results of this study indicate that exercise training increased the potential of adipose tissue cells to release free fatty acids in response to epinephrine stimulation. Exercise training initiated at 5 wk of age had only a small effect on adipose tissue cell numbers but significantly decreased cell size.

Askew, E W; Huston, R L; Plopper, C G; Hecker, A L

1975-01-01

169

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.

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

2014-01-01

170

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

PubMed

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

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

2005-10-01

171

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.

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

172

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

PubMed

Our data demonstrate that estrogens, estrogen receptor-? (ER?), and estrogen receptor-? (ER?) regulate adipose tissue distribution, inflammation, fibrosis, and glucose homeostasis, by determining that ?ERKO mice have increased adipose tissue inflammation and fibrosis prior to obesity onset. Selective deletion of adipose tissue ER? in adult mice using a novel viral vector technology recapitulated the findings in the total body ER? null mice. Generation of a novel mouse model, lacking ER? specifically from adipocytes (AdipoER?), demonstrated increased markers of fibrosis and inflammation, especially in the males. Additionally, we found that the beneficial effects of estrogens on adipose tissue require adipocyte ER?. Lastly, we determined the role of ER? in regulating inflammation and fibrosis, by breeding the AdipoER? into the ?ERKO background and found that in the absence of adipocyte ER?, ER? has a protective role. These data suggest that adipose tissue and adipocyte ER? protects against adiposity, inflammation, and fibrosis in both males and females. PMID:24049737

Davis, Kathryn E; D Neinast, Michael; Sun, Kai; M Skiles, William; D Bills, Jessica; A Zehr, Jordan; Zeve, Daniel; D Hahner, Lisa; W Cox, Derek; M Gent, Lana; Xu, Yong; V Wang, Zhao; A Khan, Sohaib; Clegg, Deborah J

2013-01-01

173

Fat body, fat pad and adipose tissues in invertebrates and vertebrates: the nexus  

PubMed Central

The fat body in invertebrates was shown to participate in energy storage and homeostasis, apart from its other roles in immune mediation and protein synthesis to mention a few. Thus, sharing similar characteristics with the liver and adipose tissues in vertebrates. However, vertebrate adipose tissue or fat has been incriminated in the pathophysiology of metabolic disorders due to its role in production of pro-inflammatory cytokines. This has not been reported in the insect fat body. The link between the fat body and adipose tissue was examined in this review with the aim of determining the principal factors responsible for resistance to inflammation in the insect fat body. This could be the missing link in the prevention of metabolic disorders in vertebrates, occasioned by obesity.

2014-01-01

174

Chagas disease, adipose tissue and the metabolic syndrome  

PubMed Central

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

Nagajyothi, Fnu; Desruisseaux, Mahalia S; Weiss, Louis M; Chua, Streamson; Albanese, Chris; Machado, Fabiana S; Esper, Lisia; Lisanti, Michael P; Teixeira, Mauro M; Scherer, Philipp E; Tanowitz, Herbert B

2010-01-01

175

Mechanisms of Disease: adipocytokines and visceral adipose tissue—emerging role in intestinal and mesenteric diseases  

Microsoft Academic Search

Adipose tissue has long been regarded as a passive type of connective tissue that stores energy as triglycerides and releases energy as free fatty acids, however, this point of view has now changed. The wide variety of products expressed and secreted by adipose tissue, such as adiponectin, leptin, and resistin, mean that the total adipose tissue mass can be defined

Jürgen Schölmerich; Christa Büchler; Andreas Schäffler

2005-01-01

176

Effect of dietary vitamin E supplements on cholesteryl ester transfer activity in hamster adipose tissue  

Microsoft Academic Search

Increased concentration of cholesteryl ester transfer protein (CETP) in plasma favours a lipoprotein profile characterized by a reduced high density lipoprotein (HDL) cholesterol. Previous studies have demonstrated that a diet high in cholesterol and saturated fat (HCSF) is associated with elevated plasma CETP and increased release of cholesterol ester transfer activity (CETA) from hamster adipose tissue incubated in vitro. The

Garry X. Shen; Christopher Novak; Aubie Angel

1996-01-01

177

Two-stage nucleotide binding mechanism and its implications to H+ transport inhibition of the uncoupling protein from brown adipose tissue mitochondria.  

PubMed

The uncoupling protein (UCP) from brown adipose tissue mitochondria is the simplest H+ translocator known. H+ transport is regulated by fatty acids as activators and by pruine nucleotides as inhibitors. Nucleotide binding again is strongly influenced by the pH [Klingenberg, M. (1988) Biochemistry 27, 781-791]. Previously, by using fluorescent 2'-O-dansyl (DANS) derivatives of purine nucleotides, a two-stage binding mechanism was unraveled with a slow transition from a loose into a tight conformational state in the isolated UCP [Huang, S.-G., & Klingenberg, M. (1995) Biochemistry 34, 349-360]. Whereas with the unsubstituted nucleotides the transition to the tight state is nearly complete, various DANS and DAN (dimethylaminonaphthoyl) nucleotides bind more to the loose state. Here we investigated the relationships between the two-stage nucleotide binding and the inhibition of the H+ transport activity in reconstituted proteoliposomes. Further, limited tryptic digestion was used as an indicator of conformational change induced by the nucleotide binding in the isolated protein. The inhibition of H+ transport activity in reconstituted UCP proteoliposomes correlated only with the fraction of tight state of nucleotide binding. Unsubstituted nucleotides (ATP, GTP, and ADP) as well as DANSGTP inhibit fully the H+ transport, whereas DANSATP and DANSADP inhibit only to about 50%, and DANSAMP is nearly ineffective. Even for the loose conformational state the nucleotide derivatives exhibit considerable affinity. This allows DANSAMP to replace prebound ATP from UCP and relieve the inhibition of H+ transport by reversing the distribution of UCP from the tight into the loose conformational state. The pH dependence of the fraction of nucleotide binding in the tight state correlates closely with the pH dependence of the degree of H+ transport inhibition. Titration with DANS nucleotides of UCP incorporated into phospholipid vesicles revealed that over 70% of binding sites had an affinity comparable with that for the isolated UCP while the remaining sites displayed substantially lower affinity, due to nonhomogeneity of the reconstituted system. The sensitivity against trypsin digestion is inversely correlated with the fraction of nucleotide binding in the tight state. Whereas unsubstituted nucleotides and DANSGTP protect strongly against trypsinolysis, DANSATP and DANSADP do only partially, and DANSAMP does not at all. The counteracting influences of the DANS substitution are shown with DANSAMP, which has an affinity comparable to that of DANSATP or DANSADP but cannot form the tight inhibited complex. These data show that nucleotide binding only in the tight state is associated with a strong conformational change, which further causes an inhibition of H+ transport. In conclusion, UCP can exist in a loose noninhibited and a tight inhibited conformational state. The equilibrium between these two conformations is shifted to the tight state with unsubstituted nucleotides but remains to variable degrees in the loose state with DANS and DAN derivatives. The DANS group hinders progressively the transition to the tight state as the binding affinity of the underlying nucleotide decreases. PMID:8672485

Huang, S G; Klingenberg, M

1996-06-18

178

Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies.  

PubMed

Adipose tissue is now recognized to have a multitude of functions that are of importance in the regulation of energy balance and substrate metabolism. Different hormones, in particular insulin and catecholamines, govern the storage and utilization of energy in the triglyceride depots. In addition, adipocytes produce several different substances with endocrine or paracrine functions, which regulate the overall energetic homeostasis. With excess energy storage, obesity develops, leading to increased risk for type 2 diabetes and cardiovascular disease. The distribution of body fat appears to be even more important than the total amount of fat. Abdominal and, in particular, visceral adiposity is strongly linked to insulin resistance, type 2 diabetes, hypertension and dyslipidaemia, leading to increased risk of cardiovascular disease. The adverse metabolic impact of visceral fat has been attributed to distinct biological properties of adipocytes in this depot compared with other adipose tissue depots. Indeed, regional variations in the metabolic activity of fat cells have been observed. Furthermore, expression studies aiming at defining the unique biological properties of adipose tissues from distinct anatomical sites have identified depot-related differences in the protein content of fat-produced molecules. In this review we wish to summarize important results from the literature and also some recent data from our own work. The main scope is to describe the biological functions of adipose tissue, and to focus on metabolic, hormonal, and signalling differences between fat depots. PMID:15654917

Giorgino, F; Laviola, L; Eriksson, J W

2005-01-01

179

Omental and subcutaneous adipose tissue steroid levels in obese men.  

PubMed

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism. PMID:16762384

Bélanger, Chantal; Hould, Frédéric-Simon; Lebel, Stéfane; Biron, Simon; Brochu, Gaétan; Tchernof, André

2006-08-01

180

Mechanisms of Obesity and Related Pathologies: The Macro- and Microcirculation of Adipose Tissue  

PubMed Central

SUMMARY Adipose tissue is an endocrine organ made up of adipocytes, various stromal cells including many immune cells, and an endothelial network. Adipose secretory products, collectively referred to as adipokines, have been identified as contributors to the negative consequences of adipose tissue expansion including cardiovascular disease, diabetes, and cancer. Systemic circulation provides transport capabilities for adipokines and fuels for proper adipose tissue function. The adipose tissue microcirculation is heavily impacted by adipose tissue expansion. A subset of adipokines can induce endothelial dysfunction. Furthermore, angiogenesis is necessary to counter hypoxia arising as a result of tissue expansion. Tumors, such as invasive lesions in the mammary gland, co-opt the adipose tissue microvasculature for local growth and metastatic growth and lymphatic circulation provides an important route for lipid transport. Here, we review this area that has not received a lot of attention and focus on the established and potential interplay between adipose tissue and the microvascular endothelium.

Rutkowski, Joseph M.; Davis, Kathryn E.; Scherer, Philipp E.

2010-01-01

181

Effects of breed and adipose depot location on responsiveness and sensitivity to adrenergic stimulation in ovine adipose tissue.  

PubMed

Karakul tail adipose tissue had the smallest adipocytes, and this tissue was also the least lipolytically responsive. However, lipolytic responsiveness did not vary with breed or depot when expressed per gram of tissue. Sensitivity to isoproterenol and epinephrine was higher in tissues of the Karakul than of the Outaouais breed of sheep. As well, there was evidence for alpha-antilipolytic action in Karakul but not Outaouais adipose tissue. The Karakul breed is a unique model for the study of adipocyte metabolism in that a wide range of adipocyte volumes exist within an individual, and the Karakul adipose tissue appears to be particularly sensitive to adrenergic regulation. PMID:8983166

Gilson, T L; Kennedy, A D; Rampersand, T

1996-09-01

182

[Removal of petrous bone cholesteatoma and obliteration with adipose tissue].  

PubMed

Three cases of petrous bone cholesteatoma removed through translabyrinthine-cochlear approach with the surgical defect obliterated by using adipose tissue covered with superficial temporalis fasia flap were reported. The average follow-up period was two years without any sign of recurrence. The etiology, diagnosis and methods of surgical treatment were discussed. PMID:8745468

Yu, Z; Wang, T; Ding, S

1995-01-01

183

Feeding in infancy, adipose tissue cellularity and obesity.  

PubMed

Female Sprague-Dawley rats were raised in litters of four (L4), nine (L9) and 24 (L24). The well nourished L4 rats grew insignificantly larger, heavier and fatter than the L9 controls; the underfed L24 rats remained small and stunted, and had absolutely and relatively less adipose tissue than the L4 and L9 rats. Approximately half of the rats of these three groups were fed a high-fat diet from age 18 to 43 weeks. Almost all of the rats in the fat-fed groups became obese. The amount of adipose tissue expressed as percent body weight was essentially the same in all three fat-fed groups, with the greatest relative enlargement of fat stores and increase in fat cell number in the 24-litter rats. The results show that the feeding pattern during adult life is of greater importance than early feeding experiences. The literature regarding overfeeding and underfeeding during early life is reviewed; it confirms that early overfeeding does not predispose to obesity in later life and that early underfeeding does not prevent or diminish the development of nutritional obesity and adipose tissue hypercellularity. Early underfeeding seems to affect more the regulation of the feeding behavior than the intrinsic functions and growth potential of adipose tissue; it may even stimulate the development of obesity. PMID:6505056

Hausberger, F X; Volz, J E

1984-07-01

184

Obesity and polymorphisms in genes regulating human adipose tissue  

Microsoft Academic Search

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

I Dahlman; P Arner

2007-01-01

185

Understanding adipose tissue development from transgenic animal models  

Microsoft Academic Search

The World Health Organization has recognized obesity as a health problem of pandemic proportions. Re- cent work led to major breakthroughs in the understand- ing of the molecular basis of adipose tissue development with the cloning and characterization of numerous genes involved in fat cell differentiation and metabolism. Trans- genesis has proved very useful in establishing the physio- logical roles

Philippe Valet; Geneviève Tavernier; Isabelle Castan-Laurell; Jean Sébastien Saulnier-Blache; Dominique Langin

186

Human omental and subcutaneous adipose tissue exhibit specific lipidomic signatures.  

PubMed

Despite their differential effects on human metabolic pathophysiology, the differences in omental and subcutaneous lipidomes are largely unknown. To explore this field, liquid chromatography coupled with mass spectrometry was used for lipidome analyses of adipose tissue samples (visceral and subcutaneous) selected from a group of obese subjects (n=38). Transcriptomics and in vitro studies in adipocytes were used to confirm the pathways affected by location. The analyses revealed the existence of obesity-related specific lipidome signatures in each of these locations, attributed to selective enrichment of specific triglycerides, glycerophospholipids, and sphingolipids, because these were not observed in adipose tissues from nonobese individuals. The changes were compatible with subcutaneous enrichment in pathways involved in adipogenesis, triacylglyceride synthesis, and lipid droplet formation, as well as increased ?-oxidation. Marked differences between omental and subcutaneous depots in obese individuals were seen in the association of lipid species with metabolic traits (body mass index and insulin sensitivity). Targeted studies also revealed increased cholesterol (?56%) and cholesterol epoxide (?34%) concentrations in omental adipose tissue. In view of the effects of cholesterol epoxide, which induced enhanced expression of adipocyte differentiation and ?-oxidation genes in human omental adipocytes, a novel role for cholesterol epoxide as a signaling molecule for differentiation is proposed. In summary, in obesity, adipose tissue exhibits a location-specific differential lipid profile that may contribute to explaining part of its distinct pathogenic role. PMID:24265485

Jové, Mariona; Moreno-Navarrete, José María; Pamplona, Reinald; Ricart, Wifredo; Portero-Otín, Manuel; Fernández-Real, José Manuel

2014-03-01

187

Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction.  

PubMed

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

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

2014-01-01

188

Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects  

Microsoft Academic Search

To evaluate the expression of the renin-angiotensin system (RAS) genes in visceral (VAT) and subcutaneous adipose tissue (SAT) in normotensive subjects with different body mass index (BMI). Adipose tissue was obtained from 22 normotensive (12 normal weight and 10 overweight) patients during surgery for colecystectomy. Angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), angiotensin converting enzyme (ACE) mRNA, and protein

Gilberta Giacchetti; Emanuela Faloia; Barbara Mariniello; Cipriana Sardu; Cristina Gatti; Maria Angela Camilloni; Mario Guerrieri; Franco Mantero

2002-01-01

189

Influence of prolonged fasting on monoamine oxidase and semicarbazide-sensitive amine oxidase activities in rat white adipose tissue  

Microsoft Academic Search

Monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) activities are very high in white adipose tissue\\u000a (WAT). SSAO, also known as Vascular Adhesion Protein-1 in vessels, is present at the surface of fat cells and independent\\u000a approaches have evidenced its impressive increase during adipogenesis. However, the factors that might regulate the expression\\u000a SSAO and MAO in adipose tissue are still

Z. Iffiú-Soltész; D. Prévot; C. Carpéné

2009-01-01

190

Lessons on Conditional Gene Targeting in Mouse Adipose Tissue  

PubMed Central

Conditional gene targeting has been extensively used for in vivo analysis of gene function in adipocyte cell biology but often with debate over the tissue specificity and the efficacy of inactivation. To directly compare the specificity and efficacy of different Cre lines in mediating adipocyte specific recombination, transgenic Cre lines driven by the adipocyte protein 2 (aP2) and adiponectin (Adipoq) gene promoters, as well as a tamoxifen-inducible Cre driven by the aP2 gene promoter (iaP2), were bred to the Rosa26R (R26R) reporter. All three Cre lines demonstrated recombination in the brown and white fat pads. Using different floxed loci, the individual Cre lines displayed a range of efficacy to Cre-mediated recombination that ranged from no observable recombination to complete recombination within the fat. The Adipoq-Cre exhibited no observable recombination in any other tissues examined, whereas both aP2-Cre lines resulted in recombination in endothelial cells of the heart and nonendothelial, nonmyocyte cells in the skeletal muscle. In addition, the aP2-Cre line can lead to germline recombination of floxed alleles in ?2% of spermatozoa. Thus, different “adipocyte-specific” Cre lines display different degrees of efficiency and specificity, illustrating important differences that must be taken into account in their use for studying adipose biology.

Lee, Kevin Y.; Russell, Steven J.; Ussar, Siegfried; Boucher, Jeremie; Vernochet, Cecile; Mori, Marcelo A.; Smyth, Graham; Rourk, Michael; Cederquist, Carly; Rosen, Evan D.; Kahn, Barbara B.; Kahn, C. Ronald

2013-01-01

191

Expression of adrenomedullin in adipose tissue of lean and obese women  

Microsoft Academic Search

Objective: Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide, was shown recently to be expressed by adipose tissue. The aim of our study was to investigate the precise localization of AM within human adipose tissue, and to examine AM regulation in obesity. Design: Subcutaneous (SC) and omental (OM) adipose tissues from 9 lean and 13 obese women were profiled for

O Paulmyer-Lacroix; R Desbriere; V Achard; M-C Alessi; F Boudouresque; V Vuaroqueaux; M Labuhn; A Dutour; M Grino

2006-01-01

192

Magnetic resonance spectroscopy investigations of brown adipose tissue and isolated brown adipocytes  

Microsoft Academic Search

Brown adipose tissue and collagenase-isolated brown adipocytes were investigated in rats by means of 'H and 1% nuclear magnetic resonance spectroscopy. After chloroform- methanol extraction of brown adipose tissue, proton and natural abundance I3C spectra of the chloroform fraction showed resonances attributable to triglycerides, and were qualitatively similar to those of the corresponding fraction of white adipose tissue. By means

Carlo Zancanaro; Rita Nano; Carla Marchioro; Andrea Sbarbati; Andrea Boicelli; Francesco Osculati

193

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

Kunešová, M; Hlavatý, P; Tvrzická, E; Sta?ková, B; Kalousková, 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; Zák, A; Astrup, A; Saris, W H M

2012-01-01

194

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.

KUNESOVA, M.; HLAVATY, P.; TVRZICKA, E.; STANKOVA, B.; KALOUSKOVA, P.; VIGUERIE, N.; LARSEN, T. M.; VAN BAAK, M. A.; JEBB, S. A.; MARTINEZ, J. A.; PFEIFFER, A. F. H.; KAFATOS, A.; HANDJIEVA-DARLENSKA, T.; HILL, M.; LANGIN, D.; ZAK, A.; ASTRUP, A.; SARIS, W. H. M.

2013-01-01

195

Central angiotensin II has catabolic action at white and brown adipose tissue.  

PubMed

Considerable evidence implicates the renin-angiotensin system (RAS) in the regulation of energy balance. To evaluate the role of the RAS in the central nervous system regulation of energy balance, we used osmotic minipumps to chronically administer angiotensin II (Ang II; icv; 0.7 ng/min for 24 days) to adult male Long-Evans rats, resulting in reduced food intake, body weight gain, and adiposity. The decrease in body weight and adiposity occurred relative to both ad libitum- and pair-fed controls, implying that reduced food intake in and of itself does not underlie all of these effects. Consistent with this, rats administered Ang II had increased whole body heat production and oxygen consumption. Additionally, chronic icv Ang II increased uncoupling protein-1 and ?(3)-adrenergic receptor expression in brown adipose tissue and ?3-adrenergic receptor expression in white adipose tissue, which is suggestive of enhanced sympathetic activation and thermogenesis. Chronic icv Ang II also increased hypothalamic agouti-related peptide and decreased hypothalamic proopiomelanocortin expression, consistent with a state of energy deficit. Moreover, chronic icv Ang II increased the anorectic corticotrophin- and thyroid-releasing hormones within the hypothalamus. These results suggest that Ang II acts in the brain to promote negative energy balance and that contributing mechanisms include an alteration in the hypothalamic circuits regulating energy balance, a decrease in food intake, an increase in energy expenditure, and an increase in sympathetic activation of brown and white adipose tissue. PMID:21862725

de Kloet, Annette D; Krause, Eric G; Scott, Karen A; Foster, Michelle T; Herman, James P; Sakai, Randall R; Seeley, Randy J; Woods, Stephen C

2011-12-01

196

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.

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

2007-01-01

197

Energy metabolism of adipose tissue--physiological aspects and target in obesity treatment.  

PubMed

Body fat content is controlled, at least in part, by energy charge of adipocytes. In vitro studies indicated that lipogenesis as well as lipolysis depend on cellular ATP levels. Respiratory uncoupling may, through the depression of ATP synthesis, control lipid metabolism of adipose cells. Expression of some uncoupling proteins (UCP2 and UCP5) as well as other protonophoric transporters can be detected in the adipose tissue. Expression of other UCPs (UCP1 and UCP3) can be induced by pharmacological treatments that reduce adiposity. A negative correlation between the accumulation of fat and the expression of UCP2 in adipocytes was also found. Ectopic expression of UCP1 in the white fat of aP2-Ucp1 transgenic mice mitigated obesity induced by genetic or dietary factors. In these mice, changes in lipid metabolism of adipocytes were associated with the depression of intracellular energy charge. Recent data show that AMP-activated protein kinase may be involved in the complex changes elicited by respiratory uncoupling in adipocytes. Changes in energy metabolism of adipose tissue may mediate effects of treatments directed against adiposity, dyslipidemia, and insulin resistance. PMID:15119952

Kopecký, J; Rossmeisl, M; Flachs, P; Brauner, P; Sponarová, J; Matejková, O; Prazák, T; R?zicková, J; Bardová, K; Kuda, O

2004-01-01

198

Hypertrophy and hyperplasia of abdominal adipose tissues in women  

Microsoft Academic Search

Objective:To examine the expression of selected transcription factors involved in adipogenesis and genes related to lipid metabolism in abdominal subcutaneous and omental fat tissue.Research design and methods:We obtained subcutaneous and omental adipose tissue samples from 40 women undergoing abdominal hysterectomies (age: 47±5 years; BMI 27.9±5.3 kg\\/m2). We measured isolated adipocyte size and metabolism, and detailed measures of body fat accumulation

R Drolet; C Richard; A D Sniderman; J Mailloux; M Fortier; C Huot; C Rhéaume; A Tchernof

2008-01-01

199

Circadian Regulation of Lipid Mobilization in White Adipose Tissues  

PubMed Central

In mammals, a network of circadian clocks regulates 24-h rhythms of behavior and physiology. Circadian disruption promotes obesity and the development of obesity-associated disorders, but it remains unclear to which extent peripheral tissue clocks contribute to this effect. To reveal the impact of the circadian timing system on lipid metabolism, blood and adipose tissue samples from wild-type, Clock?19, and Bmal1?/? circadian mutant mice were subjected to biochemical assays and gene expression profiling. We show diurnal variations in lipolysis rates and release of free fatty acids (FFAs) and glycerol into the blood correlating with rhythmic regulation of two genes encoding the lipolysis pacemaker enzymes, adipose triglyceride (TG) lipase and hormone-sensitive lipase, by self-sustained adipocyte clocks. Circadian clock mutant mice show low and nonrhythmic FFA and glycerol blood content together with decreased lipolysis rates and increased sensitivity to fasting. Instead circadian clock disruption promotes the accumulation of TGs in white adipose tissue (WAT), leading to increased adiposity and adipocyte hypertrophy. In summary, circadian modulation of lipolysis rates regulates the availability of lipid-derived energy during the day, suggesting a role for WAT clocks in the regulation of energy homeostasis.

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

2013-01-01

200

The formation of brown adipose tissue induced by transgenic over-expression of PPAR?2.  

PubMed

Brown adipose tissue (BAT) is specialized to dissipate energy as heat, therefore reducing fat deposition and counteracting obesity. Brown adipocytes arise from myoblastic progenitors during embryonic development by the action of transcription regulator PRDM16 binding to PPAR?, which promotes BAT-like phenotype in white adipose tissue. To investigate the capability of converting white adipose tissue to BAT or browning by PPAR? in vivo, we generated transgenic mice with over-expressed PPAR?2. The transgenic mice showed strong brown fat features in subcutaneous fat in morphology and histology. To provide molecular evidences on browning characteristics of the adipose tissue, we employed quantitative real-time PCR to determine BAT-specific gene expressions. The transgenic mice had remarkably elevated mRNA level of UCP1, Elovl3, PGC1? and Cebp? in subcutaneous fat. Compared with wild-type mice, UCP1 protein levels were increased significantly in transgenic mice. ATP concentration was slightly decreased in the subcutaneous fat of transgenic mice. Western blotting analysis also confirmed that phosphorylated AMPK and ACC proteins were significantly (P<0.01) increased in the transgenic mice. Therefore, this study demonstrated that over-expression of PPAR?2 in skeletal muscle can promote conversion of subcutaneous fat to brown fat formation, which can have beneficial effects on increasing energy metabolisms and combating obesity. PMID:24642257

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

2014-04-18

201

Expression of PPAR-? in adipose tissue of rats with polycystic ovary syndrome induced by DHEA.  

PubMed

The objective of this study was to investigate the expression of peroxisome proliferator-activated receptor-? (PPAR-?) in adipose tissue of the rat model of polycystic ovary syndrome (PCOS), induced by dehydroepiandrosterone (DHEA). Sixteen sexually immature Sprague-Dawley female rats were randomly assigned to the DHEA (n=8) or control (n=8) group. Adipose tissue was collected from the two rat groups following subcutaneous injection of DHEA in the DHEA group and a standard laboratory diet in the control group for 20 consecutive days. Reverse transcription polymerase chain reaction and western blot analysis were performed to detect expression of PPAR-? at the mRNA and protein level in the adipose tissue. Both PPAR-? mRNA and protein levels were decreased in the adipose tissue of DHEA?induced PCOS rats compared to the control group. This decrease was significant (P<0.01). These results suggest that the pathogenesis of PCOS, which shares a number of common features with hyperandrogenemia, may involve the lipid metabolism pathway through inhibition of PPAR-?. PMID:24425206

Wang, Yu-Xia; Zhu, Wei-Jie; Xie, Bao-Guo

2014-03-01

202

A correlation study of organochlorine levels in serum, breast adipose tissue, and gluteal adipose tissue among breast cancer cases in India.  

PubMed

We used data from a breast cancer pilot study carried out in Kerala, India in 1997, for which organochlorine levels were measured in three biological media, blood serum, breast adipose tissue, and gluteal adipose tissue, of 37 fasting breast cancer cases (pretreatment). Our objective was to investigate the relationships between organochlorine concentrations in different biological media. Gas-liquid chromatography determined serum, breast adipose, and gluteal adipose tissue levels of dichlorodiphenyltricholorethane, dichlorodiphenyldichloroethane, beta-benzene hexachloride, and polychlorinated biphenyl (PCB) congeners, PCB-153 and PCB-180. Correlation plots were made and Spearman correlation coefficients (r) calculated for breast adipose tissue versus serum, gluteal adipose tissue versus serum, and breast adipose versus gluteal adipose tissue. We also examined paired ratios of all summary statistics. There were strong correlations among serum, breast adipose tissue, and gluteal adipose tissue concentrations for most organochlorines analyzed, one exception being gluteal versus serum for PCB-153. The correlations for all other comparisons ranged from r = 0.65 to 0.94. Serum (ng/g) versus adipose ratios approached 1:1 for most of the organochlorine pesticide comparisons and did not vary by summary statistic. To our knowledge, this is the first study to use three different media from fasting subjects and to comprehensively investigate the relationship between organochlorines measured across the three media for both organochlorine pesticides and PCBs. These data indicate that blood serum reflects the present body burden of a range of organochlorines to the same extent as adipose tissue, and they support the view that serum may be collected in lieu of adipose tissue to obtain similar information. However, such measurements are a combination of both recent exposures and past exposures, which have metabolized slowly and may still persist. Therefore, investigators should use caution when assigning a level as lifetime body burden. PMID:15894661

Rusiecki, Jennifer A; Matthews, Aleyama; Sturgeon, Susan; Sinha, Rashmi; Pellizzari, Edo; Zheng, Tongzhang; Baris, Dalsu

2005-05-01

203

Effect of dietary polyphenols from hop (Humulus lupulus L.) pomace on adipose tissue mass, fasting blood glucose, hemoglobin A1c, and plasma monocyte chemotactic protein-1 levels in OLETF rats.  

PubMed

Hop (Humulus lupulus L.) pomace contains procyanidin-rich polyphenols, which are large oligomeric compounds of catechin. We studied the effect of high dose (1%) of dietary hop pomace polyphenols (HPs) in Otsuka Long-EvansTokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. By 70 days, the rats fed HPs tended to have a lower body weight and reduced mesenteric white adipose tissue weight than the rats fed a control diet. Triglyceride levels in both plasma and liver tended to be lower in the HPs-fed group than in the control group. Dietary HPs substantially suppressed the activities of hepatic fatty acid synthetase, glucose-6-phosphate dehydrogenase, and malic enzyme, through the suppression of SREBP1c mRNA expression in OLETF rats. Moreover, in the HPs-fed group, monocyte chemotactic protein-1 (MCP-1) expression and fasting blood glucose levels at 40 days, and hemoglobin A1c (HbA1c) levels at 70 days were significantly lower than those in the control group. Thus, dietary HPs may exert an ameliorative function on hepatic fatty acid metabolism, glucose metabolism, and inflammatory response accompanying the increase of the adipose tissue mass in OLETF rats. PMID:23648402

Yui, Kazuki; Uematsu, Hiroki; Muroi, Keisuke; Ishii, Kazuhiro; Baba, Minako; Osada, Kyoichi

2013-01-01

204

Enhanced ZAG production by subcutaneous adipose tissue is linked to weight loss in gastrointestinal cancer patients  

PubMed Central

Background: Profound loss of adipose tissue is a hallmark of cancer cachexia. Zinc-?2-glycoprotein (ZAG), a recently identified adipokine, is suggested as a candidate in lipid catabolism. Methods: In the first study, eight weight-stable and 17 cachectic cancer patients (weight loss ?5% in previous 6 months) were recruited. Zinc-?2-glycoprotein mRNA and protein expression were assessed in subcutaneous adipose tissue (SAT), subcutaneous adipose tissue morphology was examined and serum ZAG concentrations were quantified. In the second cohort, ZAG release by SAT was determined in 18 weight-stable and 15 cachectic cancer patients. The effect of ZAG on lipolysis was evaluated in vitro. Results: Subcutaneous adipose tissue remodelling in cancer cachexia was evident through shrunken adipocytes with increased fibrosis. In cachectic cancer patients, ZAG mRNA was upregulated (2.7-fold, P=0.028) while leptin mRNA decreased (2.2-fold, P=0.018); serum ZAG levels were found to be unaffected. Zinc-?2-glycoprotein mRNA correlated positively with weight loss (r=0.51, P=0.01) and serum glycerol levels (r=0.57, P=0.003). Zinc-?2-glycoprotein release by SAT was also elevated in cachectic patients (1.5-fold, P=0.024) and correlated with weight loss (r=0.50, P=0.003). Recombinant ZAG stimulated lipolysis in human adipocytes. Conclusions: Zinc-?2-glycoprotein expression and secretion by adipose tissue is enhanced in cachectic cancer patients. Given its lipid-mobilising effect, ZAG may contribute to adipose atrophy associated with cancer cachexia in human beings.

Mracek, T; Stephens, N A; Gao, D; Bao, Y; Ross, J A; Ryden, M; Arner, P; Trayhurn, P; Fearon, K C H; Bing, C

2011-01-01

205

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

206

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

PubMed Central

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

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

2013-01-01

207

Regional differences in adipose tissue metabolism in obese men.  

PubMed

We examined omental and subcutaneous adipose tissue adipocyte size, and lipolysis and lipoprotein lipase (LPL) activity in a sample of 33 men aged 22.6 to 61.2 years and with a body mass index ranging from 24.6 to 79.1 kg/m2. We tested the hypothesis that lipolysis rates would be higher in the omental fat depot than in subcutaneous adipose tissue and that this difference would persist across the spectrum of abdominal adiposity values. Omental and subcutaneous adipose tissue samples were obtained during surgery. Adipocytes were isolated by collagenase digestion. Adipocyte size and LPL activity as well as basal, isoproterenol-, forskolin-, and dibutyryl cyclic adenosine monophosphate-stimulated lipolysis were measured. Although adipocytes from both fat compartments were larger in obese subjects, no difference was observed in the size of omental vs subcutaneous fat cells. Lipoprotein lipase activity, expressed as a function of cell number, was significantly higher in omental than in subcutaneous fat tissue (P<.005). Basal lipolysis and lipolytic responses to isoproterenol, forskolin, or dibutyryl cyclic adenosine monophosphate, expressed either as a function of cell number or as a fold response over basal levels, were not significantly different in omental vs subcutaneous fat cells. When stratifying the sample in tertiles of waist circumference, adipocyte diameter was similar in the omental and subcutaneous depots for all adiposity values. Omental adipocyte size reached a plateau in the 2 upper tertiles of waist circumference, that is, from a waist circumference of 125 cm and above. Lipoprotein lipase activity was significantly higher in omental cells in the middle tertile of waist circumference (P=.05), and no regional difference was noted in lipolysis values across waist circumference tertiles. In conclusion, in normal-weight to morbidly obese men, although adipocyte size and lipolysis tended to increase with higher waist circumference, no difference was observed between the omental and subcutaneous fat depot. PMID:17379013

Boivin, Ariane; Brochu, Gaétan; Marceau, Simon; Marceau, Picard; Hould, Frédéric-Simon; Tchernof, André

2007-04-01

208

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

PubMed Central

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

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

2012-01-01

209

Ceramide metabolism is affected by obesity and diabetes in human adipose tissue.  

PubMed

Ceramide is involved in development of insulin resistance. However, there are no data on ceramide metabolism in human adipose tissue. The aim of our study was to examine sphingolipid metabolism in fat tissue from obese nondiabetic (n?=?11), obese diabetic (n?=?11), and lean nondiabetic (n?=?8) subjects. The content of ceramide (Cer), dihydroceramide (dhCer), sphingosine (SPH), sphinganine (SPA), sphingosine-1-phosphate (S1P; pmol/mg of protein), the expression (mRNA) and activity of key enzymes responsible for Cer metabolism: serine palmitoyltransferase (SPT), neutral and acidic sphingomyelinase (nSMase and aSMase, respectively), and neutral and acidic ceramidase (nCDase and aCDase, respectively) were examined in human adipose tissue. The contents of SPA and Cer were significantly lower whereas the content of dhCer was higher in both obese groups than the respective values in the lean subjects. The expression of examined enzymes was elevated in both obese groups. The SPT and CDases activity increased whereas aSMase activity deceased in both obese groups. We have found correlation between adipose tissue Cer content and plasma adiponectin concentration (r?=?0.69, P?adipose tissue. PMID:21437908

B?achnio-Zabielska, A U; Pu?ka, M; Baranowski, M; Niko?ajuk, A; Zabielski, P; Górska, M; Górski, J

2012-02-01

210

Adipose tissue stem cells: the great WAT hope  

PubMed Central

The past decade has witnessed an explosion in research into adipose tissue stem cells (ASCs), facilitated by their ease of isolation from white adipose tissue (WAT) and fueled by their therapeutic potential. Recent developments have extended ASC multipotency to include endodermal and ectodermal cell types, along with generation of induced pluripotent stem cells. This expanding multipotency has been paralleled by burgeoning translational applications, ranging from tissue engineering to anti-cancer therapy, that are currently subject to clinical trials. However, this promise is tempered by potential pitfalls, such as tumorigenicity, and is further undermined by lingering uncertainties regarding the very identity of ASCs. Confronting these issues will be essential if we are to bypass the pitfalls and develop the promises of ASCs.

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

2012-01-01

211

Adipose tissue stem cells: the great WAT hope.  

PubMed

The past decade has witnessed an explosion in research into adipose tissue stem cells (ASCs), facilitated by their ease of isolation from white adipose tissue (WAT) and fueled by their therapeutic potential. Recent developments have extended ASC multipotency to include endodermal and ectodermal cell types, as well as the generation of induced pluripotent stem cells. This expanding multipotency has been paralleled by burgeoning translational applications, ranging from tissue engineering to anti-cancer therapy, that are currently subject to clinical trials. However, this promise is tempered by potential pitfalls, such as tumorigenicity, and is further undermined by lingering uncertainties regarding the precise identity of ASCs. Confronting these issues will be essential if we are to bypass the pitfalls and develop the promises of ASCs. PMID:22417866

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

2012-06-01

212

On the relevance of brown adipose tissue in children.  

PubMed

The visualization of brown adipose tissue (BAT) in pediatric patients undergoing positron emission tomography/computed tomography (PET/CT) examinations is dependent on multiple physiologic and technical factors, such as age, sexual maturity, fat accumulation, disease status, medications, plasma glucose concentration, radiotracer dosage, acquisition parameters, and season and temperature during examinations. Evidence also suggests that children with metabolically active BAT have significantly greater muscle volume than those without visualized BAT, and that in both boys and girls, the amount of BAT increases during puberty. Hence, concurrent with the gains in skeletal muscle during infancy and puberty, all infants and adolescents have large amounts of BAT. New magnetic resonance imaging (MRI) techniques that discern the cytological differences between brown and white adipose tissue will likely provide the platform to reliably measure BAT in healthy subjects and determine the relevance of this tissue in humans. PMID:23909713

Ponrartana, Skorn; Hu, Houchun H; Gilsanz, Vicente

2013-10-01

213

Adipose Tissue Biology and Cardiomyopathy-Translational Implications  

PubMed Central

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

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

2012-01-01

214

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.

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

2013-01-01

215

Adipose tissue attracts and protects acute lymphoblastic leukemia cells from chemotherapy  

PubMed Central

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

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

2013-01-01

216

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

PubMed Central

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

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

2014-01-01

217

Autophagy in adipose tissue and the beta cell: implications for obesity and diabetes.  

PubMed

Autophagy is a lysosomal degradation pathway recycling intracellular long-lived proteins and damaged organelles, thereby maintaining cellular homeostasis. In addition to inflammatory processes, autophagy has been implicated in the regulation of adipose tissue and beta cell functions. In obesity and type 2 diabetes autophagic activity is modulated in a tissue-dependent manner. In this review we discuss the regulation of autophagy in adipose tissue and beta cells, exemplifying tissue-specific dysregulation of autophagy and its implications for the pathophysiology of obesity and type 2 diabetes. We will highlight common themes and outstanding gaps in our understanding, which need to be addressed before autophagy could be envisioned as a therapeutic target for the treatment of obesity and diabetes. PMID:24795087

Stienstra, Rinke; Haim, Yulia; Riahi, Yael; Netea, Mihai; Rudich, Assaf; Leibowitz, Gil

2014-08-01

218

Down-regulation of Zac1 gene expression in rat white adipose tissue by androgens.  

PubMed

ZAC1 is a zinc-finger protein transcription factor, a transcriptional cofactor for nuclear receptors, and a co-activator of nuclear receptors, which interacts with multiple signaling pathways affecting apoptosis, cell cycle arrest, and metabolism. Some data suggest that ZAC1 regulates the expression of genes associated with function of adipose tissue. Since there is no information about the levels of Zac1 gene expression in white adipose tissue (WAT), and the expression of several genes associated with metabolic function of WAT is significantly lower in male than female animals, we have examined: (a) the relative ZAC1 mRNA levels in some organs/tissues, including three main depots of WAT, in 3-month-old male rats; (b) the relative ZAC1 mRNA levels in WAT of male and female rats; (c) the effect of orchidectomy and orchidectomy with concomitant testosterone treatment on ZAC1 mRNA and protein levels; (d) the effect of ovariectomy and ovariectomy with concomitant 17?-estradiol treatment on ZAC1 mRNA levels; (e) the effect of dihydrotestosterone on ZAC1 mRNA levels in isolated adipocytes. Our results indicate that: (a) ZAC1 mRNA levels are relatively high in WAT in comparison with other organs/tissues; (b) ZAC1 mRNA levels in subcutaneous WAT are approximately 2-fold lower than in epididymal and retroperitoneal adipose tissue; (c) ZAC1 mRNA levels in WAT of adult female rats are approximately 2-fold higher than in male rats; (d) testosterone is inversely related to ZAC1 mRNA and protein levels in WAT of male rats; and (e) dihydrotestosterone decreases the ZAC1 mRNA levels in adipocytes in dose dependent manner. In conclusion, Zac1 gene is highly expressed in white adipose tissue of adult rats. Androgens could play an important role in down-regulation of the ZAC1 mRNA and protein levels in rats. PMID:24316431

Mirowska, Agnieszka; Sledzinski, Tomasz; Smolenski, Ryszard T; Swierczynski, Julian

2014-03-01

219

Metabolically Favorable Remodeling of Human Adipose Tissue by Human Adenovirus Type 36  

PubMed Central

OBJECTIVE—Experimental infection of rats with human adenovirus type 36 (Ad-36) promotes adipogenesis and improves insulin sensitivity in a manner reminiscent of the pharmacologic effect of thiozolinediones. To exploit the potential of the viral proteins as a therapeutic target for treating insulin resistance, this study investigated the ability of Ad-36 to induce metabolically favorable changes in human adipose tissue. RESEARCH DESIGN AND METHODS—We determined whether Ad-36 increases glucose uptake in human adipose tissue explants. Cell-signaling pathways targeted by Ad-36 to increase glucose uptake were determined in the explants and human adipose–derived stem cells. Ad-2, a nonadipogenic human adenovirus, was used as a negative control. As a proof of concept, nondiabetic and diabetic subjects were screened for the presence of Ad-36 antibodies to ascertain if natural Ad-36 infection predicted improved glycemic control. RESULTS—Ad-36 increased glucose uptake by adipose tissue explants obtained from nondiabetic and diabetic subjects. Without insulin stimulation, Ad-36 upregulated expressions of several proadipogenic genes, adiponectin, and fatty acid synthase and reduced the expression of inflammatory cytokine macrophage chemoattractant protein-1 in a phosphotidylinositol 3-kinase (PI3K)-dependent manner. In turn, the activation of PI3K by Ad-36 was independent of insulin receptor signaling but dependent on Ras signaling recruited by Ad-36. Ad-2 was nonadipogenic and did not increase glucose uptake. Natural Ad-36 infection in nondiabetic and diabetic subjects was associated with significantly lower fasting glucose levels and A1C, respectively. CONCLUSIONS—Ad-36 proteins may provide novel therapeutic targets that remodel human adipose tissue to a more metabolically favorable profile.

Rogers, Pamela M.; Mashtalir, Nazar; Rathod, Miloni A.; Dubuisson, Olga; Wang, Zhong; Dasuri, Kumar; Babin, Scott; Gupta, Alok; Markward, Nathan; Cefalu, William T.; Dhurandhar, Nikhil V.

2008-01-01

220

Niacin Increases Adiponectin and Decreases Adipose Tissue Inflammation in High Fat Diet-Fed Mice  

PubMed Central

Aims To determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. Materials and Methods Male C57BL/6 mice were placed on a control or high-fat diet (HFD) and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2?/? (niacin receptor?/?) mice. Results Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2?/? mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPAR? C/EBP? or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription) in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-L?, or DsbA-L (key ER chaperones involved in adiponectin production and secretion). However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1? in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice. Conclusions Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expression in a niacin receptor-dependent manner.

Wanders, Desiree; Graff, Emily C.; White, B. Douglas; Judd, Robert L.

2013-01-01

221

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

PubMed

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

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

2011-06-01

222

Culture of isolated human adipocytes and isolated adipose tissue.  

PubMed

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

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

2012-01-01

223

Axl deficiency does not affect adipogenesis or adipose tissue development.  

PubMed

To evaluate a potential role of Axl, the high-affinity receptor of growth arrest-specific protein 6 (GAS6) in adiposity, murine embryonic fibroblasts (MEF) derived from mice with genetic deficiency of Axl (Axl(-/-)) or wild-type littermates (Axl(+/+)) were differentiated into mature adipocytes. In addition, Axl(-/-) and Axl(+/+) mice were kept on standard fat diet (SFD) or on high-fat diet (HFD) for 15 weeks. Deficiency of Axl in MEF did not affect differentiation, as shown by a similar uptake of Oil Red O and expression of the adipogenic markers aP2 and peroxisome proliferator activator receptor ? (PPAR?) at the end of the differentiation. In the first 7 weeks of HFD feeding, Axl(-/-) mice gained less weight than their wild-type littermates. Weight gain for both genotypes on either SFD of HFD over 15 weeks was, however, not significantly different, resulting in comparable body weights, as well as subcutaneous (s.c.) and gonadal (GON) fat mass. Adipocyte size in the fat tissues was not affected by Axl deficiency. Gene expression analysis indicated that the absence of Axl in vivo may be compensated for by the other TAM family members Mer and Tyro3. Glucose and insulin tolerance tests (ITT) in Axl(-/-) and Axl(+/+) mice did not reveal significant differences in glucose homeostasis. Thus, Axl deficiency had no significant effect on adipogenesis in vitro or in vivo. PMID:22187042

Scroyen, Ilse; Frederix, Liesbeth; Lijnen, H Roger

2012-06-01

224

A familiar stranger: CD34 expression and putative functions in SVF cells of adipose tissue  

PubMed Central

Human adipose tissue obtained by liposuction is easily accessible and an abundant potential source of autologous cells for regenerative medicine applications. After digestion of the tissue and removal of differentiated adipocytes, the so-called stromal vascular fraction (SVF) of adipose, a mix of various cell types, is obtained. SVF contains mesenchymal fibroblastic cells, able to adhere to culture plastic and to generate large colonies in vitro, that closely resemble bone marrow-derived colony forming units-fibroblastic, and whose expanded progeny, adipose mesenchymal stem/stromal cells (ASC), show strong similarities with bone marrow mesenchymal stem cells. The sialomucin CD34, which is well known as a hematopoietic stem cell marker, is also expressed by ASC in native adipose tissue but its expression is gradually lost upon standard ASC expansion in vitro. Surprisingly little is known about the functional role of CD34 in the biology and tissue forming capacity of SVF cells and ASC. The present editorial provides a short introduction to the CD34 family of sialomucins and reviews the data from the literature concerning expression and function of these proteins in SVF cells and their in vitro expanded progeny.

Scherberich, Arnaud; Di Maggio, Nunzia Di; McNagny, Kelly M

2013-01-01

225

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.

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

226

Genomic and epigenomic regulation of adipose tissue inflammation in obesity.  

PubMed

Chronic inflammation of adipose tissue is viewed as a hallmark of obesity and contributes to the development of type 2 diabetes and cardiovascular disease. According to current models, nutrient excess causes metabolic and structural changes in adipocytes, which initiate transcriptional programs leading to the expression of inflammatory molecules and the subsequent recruitment of immune cells. Recent advances in deciphering the underlying mechanisms revealed that key regulatory events occur at the genomic and epigenomic levels. Here we review these advances because they offer a better understanding of the mechanisms behind the complex obesogenic program in adipose tissue, and because they may help in defining new therapeutic strategies that prevent, restrict, and resolve inflammation in the context of obesity. PMID:24169451

Toubal, Amine; Treuter, Eckardt; Clément, Karine; Venteclef, Nicolas

2013-12-01

227

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

228

A peptide probe for targeted brown adipose tissue imaging  

PubMed Central

The presence of brown adipose tissue (BAT) responsible for thermogenic energy dissipation has been revealed in adult humans and has high clinical importance. Due to limitations of current methods for BAT detection, analyzing the abundance and localization of BAT in the body has remained challenging. Here, we screen a combinatorial peptide library in mice and characterize a peptide (with the sequence CPATAERPC) that selectively binds to the vascular endothelium of BAT, but not of intraperitoneal white adipose tissue (WAT). We show that in addition to BAT, this peptide probe also recognizes the vasculature of BAT-like depots of subcutaneous WAT. Our results indicate that the CPATAERPC peptide localizes to BAT even in the absence of sympathetic nervous system stimulation. Finally, we demonstrate that this probe can be used to identify BAT depots in mice by whole body near-infrared (NIR) fluorescence imaging.

Azhdarinia, Ali; Daquinag, Alexes C.; Tseng, Chieh; Ghosh, Sukhen C.; Ghosh, Pradip; Amaya-Manzanares, Felipe; Sevick-Muraca, Eva; Kolonin, Mikhail G.

2013-01-01

229

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

NASA Astrophysics Data System (ADS)

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

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

2006-01-01

230

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

PubMed

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

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

2014-08-01

231

Magnetic resonance properties of brown and white adipose tissues  

PubMed Central

Purpose To explore the MR (magnetic resonance) signatures of brown adipose tissue (BAT) compared to white adipose tissue (WAT) using single-voxel MR spectroscopy. Materials and Methods 1H MR STEAM spectra were acquired from a 3 Tesla clinical whole body scanner from seven excised murine adipose tissue samples of BAT (n = 4) and WAT (n = 3). Spectra were acquired at multiple TEs and TIs to measure the T1, T2, and T2-corrected peak areas. A theoretical triglyceride model characterized the fat in terms of number of double bonds (ndb) and number of methylene-interrupted double bonds (nmidb). Results Negligible differences between WAT and BAT were seen in the T1 and T2 of fat and the T2 of water. However, the water fraction in BAT was higher (48.5%) compared to WAT (7.1%) and the T1 of water was lower in BAT (618 ms) compared to WAT (1053 ms). The fat spectrum also differed, indicating lower levels of unsaturated triglycerides in BAT (ndb = 2.7, nmidb = 0.7) compared to WAT (ndb = 3.3, nmidb = 1.0). Conclusions We have demonstrated that there are several key MR-based signatures of BAT and WAT that may allow differentiation on MR imaging.

Hamilton, Gavin; Smith, Daniel L.; Bydder, Mark; Nayak, Krishna S.; Hu, Houchun H.

2011-01-01

232

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

PubMed

Neuropeptide Y (NPY) is an orexigenic neuropeptide that plays a role in regulating adiposity by promoting energy storage in white adipose tissue and inhibiting brown adipose tissue activation in mammals. This review describes mechanisms underlying NPY's effects on adipose tissue energy metabolism, with an emphasis on cellular proliferation, adipogenesis, lipid deposition, and lipolysis in white adipose tissue, and brown fat activation and thermogenesis. In general, NPY promotes adipocyte differentiation and lipid accumulation, leading to energy storage in adipose tissue, with effects mediated mainly through NPY receptor sub-types 1 and 2. This review highlights hypothalamus-sympathetic nervous system-adipose tissue innervation and adipose tissue-hypothalamus feedback loops as pathways underlying these effects. Potential sources of NPY that mediate adipose effects include the bloodstream, sympathetic nerve terminals that innervate the adipose tissue, as well as adipose tissue-derived cells. Understanding the role of central vs. peripherally-derived NPY in whole-body energy balance could shed light on mechanisms underlying the pathogenesis of obesity. This information may provide some insight into searching for alternative therapeutic strategies for the treatment of obesity and associated diseases. PMID:24959194

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

2014-01-01

233

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

PubMed Central

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

2014-01-01

234

Inflammation and adipose tissue: effects of progressive load training in rats  

PubMed Central

Introduction Cytokines (IL-6, IL-10 and TNF-?) are increased after exhaustive exercise in the rat retroperitoneal (RPAT) and mesenteric adipose tissue (MEAT) pads. On the other hand, these cytokines show decreased expression in these depots in response to a chronic exercise protocol. However, the effect of exercise with overload combined with a short recovery period on pro- and anti-inflammatory cytokine expression is unknown. In the present study, we investigated the regulation of cytokine production in the adipose tissue of rats after an overtraining-inducing exercise protocol. Methods Male Wistar rats were divided into four groups: Control (C), Trained (Tr), Overtrained (OT) and recovered overtrained (R). Cytokines (IL-6, TNF-? and IL-10) levels and Toll Like Receptor 4 (TLR4), Nuclear Factor kBp65 (NF-kBp65), Hormone Sensitive Lipase (HSL) and, Perilipin protein expression were assessed in the adipose tissue. Furthermore, we analysed plasma lipid profile, insulin, testosterone, corticosterone and endotoxin levels, and liver triacylglycerol, cytokine content, as well as apolipoprotein B (apoB) and TLR4 expression in the liver. Results OT and R groups exhibited reduced performance accompanied by lower testosterone and increased corticosterone and endotoxin levels when compared with the control and trained groups. IL-6 and IL-10 protein levels were increased in the adipose tissue of the group allowed to recover, in comparison with all the other studied groups. TLR-4 and NF-kBp65 were increased in this same group when compared with both control and trained groups. The protein expression of HSL was increased and that of Perilipin, decreased in the adipose in R in relation to the control. In addition, we found increased liver and serum TAG, along with reduced apoB protein expression and IL-6 and IL-10 levels in the of R in relation to the control and trained groups. Conclusion In conclusion, we have shown that increases in pro-inflammatory cytokines in the adipose tissue after an overtraining protocol may be mediated via TLR-4 and NF-kBp65 signalling, leading to an inflammatory state in this tissue.

2010-01-01

235

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

PubMed Central

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

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

2014-01-01

236

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

PubMed

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

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

2014-01-01

237

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

PubMed Central

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

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

2011-01-01

238

Expression of 11?-hydroxysteroid dehydrogenase type 1 in visceral and subcutaneous adipose tissues of patients with polycystic ovary syndrome is associated with adiposity.  

PubMed

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance (IR) and central obesity. The impact of adipose tissue cortisol reactivation by 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) on markers of obesity and IR was assessed in PCOS patients. Eighty-five PCOS patients and 43 controls were enrolled for subcutaneous adipose tissue biopsy; 25/85 patients and 29/43 controls underwent also visceral adipose tissue biopsy. HSD11B1 gene expression and expression of lipid metabolism genes were measured in subcutaneous and visceral adipose tissues. Anthropometric and biochemical markers of IR and PCOS were also assessed. HSD11B1 expression in visceral and subcutaneous adipose tissue was increased in PCOS patients compared to controls (p<0.05). After BMI adjustment, the difference was no longer significant. In PCOS patients, visceral HSD11B1 expression correlated positively with waist circumference (p=0.001), BMI (p=0.002), plasma insulin (p<0.05), systolic blood pressure (p=0.003), and lipoprotein lipase (LPL), hormone-sensitive lipase (LIPE) and peroxisome-proliferator activated receptor ? gene expression. Subcutaneous HSD11B1 expression correlated positively with BMI, waist circumference (p<0.001 for both) and HOMA-IR (p=0.003), and negatively with LPL, LIPE, adiponectin and glucose transporter GLUT4 gene expression. HSD11B1 expression in both depots showed a negative correlation with plasma HDL-cholesterol (p<0.03) and a positive one with C-reactive protein (p<0.001). In multiple regression analysis, HSD11B1 expression in visceral adipose tissue was most prominently associated with waist circumference, and that in subcutaneous adipose tissue with BMI (p<0.001 for both). Our results show that PCOS is not associated with increased HSD11B1 expression once adiposity is controlled for. Increased expression of this gene correlates with markers of adiposity and predicts IR and an unfavorable metabolic profile, independently of PCOS. PMID:21147223

Mlinar, Barbara; Marc, Janja; Jensterle, Mojca; Bokal, Eda Vrta?nik; Jerin, Aleš; Pfeifer, Marija

2011-02-01

239

Cellular and molecular large-scale features of fetal adipose tissue: is bovine perirenal adipose tissue brown?.  

PubMed

Epidemiological and fetal programming studies point to the role of fetal growth in adult adipose tissue (AT) mass in large mammals. Despite the incidence of fetal AT growth for human health and animal production outcomes, there is still a lack of relevant studies. We determined the cellular and large-scale-molecular features of bovine fetal perirenal AT sampled at 110, 180, 210, and 260 days post-conception (dpc) with the aim of identifying key cellular and molecular events in AT growth. The increase in AT weight from 110 to 260 dpc resulted from an increase in adipocyte volume and particularly adipocyte number that were concomitant with temporal changes in the abundance of 142 proteins revealed by proteomics. At 110 and 180 dpc, we identified proteins such as TCP1, FKBP4, or HSPD1 that may regulate adipocyte precursor proliferation by controlling cell-cycle progression and/or apoptosis or delaying PPAR?-induced differentiation. From 180 dpc, the up-regulation of PPAR?-induced proteins, lipogenic and lipolytic enzymes, and adipokine expression may underpin the differentiation and increase in adipocyte volume. Also from 180 dpc, we unexpectedly observed up-regulations in the ?-subunit of ATP synthase, which is normally bypassed in brown AT, as well as in aldehyde dehydrogenases ALDH2 and ALDH9A1, which were predominantly expressed in mouse white AT. These results, together with the observed abundant unilocular adipocytes at 180 and 260 dpc, strongly suggest that fetal bovine perirenal AT has much more in common with white than with brown AT. PMID:21678425

Taga, Hajer; Chilliard, Yves; Meunier, Bruno; Chambon, Christophe; Picard, Brigitte; Zingaretti, Maria C; Cinti, Saverio; Bonnet, Muriel

2012-04-01

240

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.

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

2013-01-01

241

Regulation of S100B in white adipose tissue by obesity in mice  

PubMed Central

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

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

2014-01-01

242

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

PubMed Central

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.

Ohta, Hiroya; Itoh, Nobuyuki

2014-01-01

243

Effects of breed and adipose depot location on responsiveness and sensitivity to adrenergic stimulation in ovine adipose tissue  

Microsoft Academic Search

Karakul tail adipose tissue had the smallest adipocytes, and this tissue was also the least lipolytically responsive. However, lipolytic responsiveness did not vary with breed or depot when expressed per gram of tissue. Sensitivity to isoproterenol and epinephrine was higher in tissues of the Karakul than of the Outaouais breed of sheep. As well, there was evidence for alpha-antilipolytic action

T. L. Gilson; A. D. Kennedy; T. Rampersand

1996-01-01

244

Adjustment of directly measured adipose tissue volume in infants  

PubMed Central

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

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

2014-01-01

245

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

Microsoft Academic Search

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

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

2006-01-01

246

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; Calabrò, Raffaele; Calabrò, Paolo

2014-07-26

247

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.

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

2014-01-01

248

Relationships between the hypothalamus and adipose tissue mass.  

PubMed

The brain, particularly certain nuclei of the hypothalamus and their neural connections, have a major influence on energy balance, through effects on both food intake and energy expenditure. As summarized in Table 1, there are indeed extensive interactions between the hypothalamus and adipose tissue, the predominate site of storage of chemical energy. Structural, and possibly functional, abnormalities of the neural structures facilitate the development of obesity. This review has described four components of the interactive system. Two of these components are still partly conjectural; while we have increasing experimental support, the hypothalamic-pituitary-adipose axis and the hypothalamic-efferent neural-cytoskeletal pathway are the subject of continuing intense investigation. More complete knowledge of the pathophysiology of obesity will, in turn, facilitate prevention and treatment of corpulence, as well as such frequent associations as non-insulin dependent diabetes mellitus. PMID:1927695

Roncari, D A

1991-01-01

249

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

PubMed

Protein carbonylation is the covalent modification of proteins by ?,?-unsaturated aldehydes produced by nonenzymatic lipid peroxidation of polyunsaturated fatty acids. The most widely studied aldehyde product of lipid peroxidation, trans-4-hydroxy-2-nonenal (4-HNE), is associated with obesity-induced metabolic dysfunction and has demonstrated reactivity toward key proteins involved in cellular function. However, 4-HNE is only one of many lipid peroxidation products and the lipid aldehyde profile in adipose tissue has not been characterized. To further understand the role of oxidative stress in obesity-induced metabolic dysfunction, a novel LC-MS/MS method was developed to evaluate aldehyde products of lipid peroxidation and applied to the analysis of adipose tissue. 4-HNE and trans-4-oxo-2-nonenal (4-ONE) were the most abundant aldehydes present in adipose tissue. In high fat-fed C57Bl/6J and ob/ob mice the levels of lipid peroxidation products were increased 5- to 11-fold in epididymal adipose, unchanged in brown adipose, but decreased in subcutaneous adipose tissue. Epididymal adipose tissue of high fat-fed mice also exhibited increased levels of proteins modified by 4-HNE and 4-ONE, whereas subcutaneous adipose tissue levels of these modifications were decreased. High fat feeding of C57Bl/6J mice resulted in decreased expression of a number of genes linked to antioxidant biology selectively in epididymal adipose tissue. Moreover, TNF? treatment of 3T3-L1 adipocytes resulted in decreased expression of GSTA4, GPx4, and Prdx3 while upregulating the expression of SOD2. These results suggest that inflammatory cytokines selectively downregulate antioxidant gene expression in visceral adipose tissue, resulting in elevated lipid aldehydes and increased protein carbonylation. PMID:23726997

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

2013-10-01

250

Osteopontin Deletion Prevents the Development of Obesity and Hepatic Steatosis via Impaired Adipose Tissue Matrix Remodeling and Reduced Inflammation and Fibrosis in Adipose Tissue and Liver in Mice  

PubMed Central

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

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

2014-01-01

251

Adipose tissues from various anatomical sites are characterized by different patterns of gene expression and regulation.  

PubMed Central

We have shown previously the presence of brown adipocytes among white fat pads, and proposed the existence of a spectrum of adipose depots according to the abundance of brown fat cells [Cousin, Cinti, Morroni, Raimbault, Ricquier, Pénicaud and Casteilla (1992) J. Cell Sci. 103, 931-942]. In this study, we tried to characterize this spectrum better. We determined in several adipose depots (i) the richness of pre-adipose cells, as assessed by A2COL6 mRNA levels; (ii) whether a fat pad was characterized by a pattern of mRNA expression; (iii) whether this pattern was close related to abundance of brown adipocytes, and (iv) whether the regulation of this pattern by catecholamines under cold exposure or beta-agonist treatment was similar in the different pads. This was achieved by studying proteins involved in glucose and lipid metabolism such as insulin-sensitive glucose transporter (GLUT4), fatty acid synthase, lipoprotein lipase and fatty acid binding protein aP2, as well as beta 3-adrenergic-receptor expression. Among white adipose depots, the periovarian fat pad was characterized by the highest content of pre-adipocytes and of brown adipocytes, and inguinal fat by the highest lipogenic activity potential. There was no close correlation between beta 3-adrenergic-receptor expression and brown adipocyte content in the tissues, as measured by the degree of uncoupling protein (UCP) gene expression. However, in pads expressing UCP mRNA, mRNA levels of beta 3-adrenergic receptor and other markers were increased in parallel. Under cold exposure or beta 3-agonist treatment, a specific up-regulation of GLUT4 expression was observed in interscapular brown adipose tissue. The regional difference described in this study, could participate in preferential fat-pad growth under physiological conditions as well as in pathological situations. Images Figure 1

Cousin, B; Casteilla, L; Dani, C; Muzzin, P; Revelli, J P; Penicaud, L

1993-01-01

252

Diversity of lipid mediators in human adipose tissue depots  

PubMed Central

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

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

2013-01-01

253

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.

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

2014-01-01

254

The Fine Structure of Brown Adipose Tissue in the Newborn Mouse and Rat  

PubMed Central

Interscapular fat from newborn rats and mice was fixed in buffered 1 per cent osmium tetroxide and thin sections of the methacrylate-embedded tissue were studied with the electron microscope. The findings have reaffirmed the epithelioid character of brown adipose tissue, and have provided additional information on the relation of its cells to each other and to the rich capillary bed. For the most part, the earlier description of the fine structure of brown adipose cells by Lever, has been confirmed, but our observations on the mitochondria and their relation to fat droplets have led us to different conclusions concerning the role of these organelles in lipogenesis. Mitochondria were often found to be very closely associated with lipide inclusions, but no actual communication between the two was observed and no evidence was found to support the hypothesis that mitochondria are transformed into lipide droplets. Large dense bodies which showed a highly ordered fine structure suggesting a crystalline protein were seen in the matrix of some mitochondria. The cytoplasm of the adipose cells contained fine granules that seemed to be of two kinds: particles of uniform size (?150 A) and appreciable density that are believed to be ribonucleoprotein, and granules of lower density and more variable size that are tentatively interpreted as a form of glycogen. The Golgi complex of the adipose cells was small and the endoplasmic reticulum almost entirely absent. The significance of the poor development of these organelles is discussed in relation to current concepts of their function.

Napolitano, Leonard; Fawcett, Don

1958-01-01

255

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

PubMed

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

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

2014-04-01

256

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

PubMed Central

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

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

2012-01-01

257

Adipose tissue engineering using adipose-derived stem cells enclosed within an injectable carboxymethylcellulose-based hydrogel.  

PubMed

In situ gelation of an aqueous solution of carboxymethylcellulose derivative bearing phenolic hydroxyl groups (CMC-Ph) that contained suspended adipose-derived stem cells (ASCs) was studied in vitro and in vivo for evaluating feasibility in adipose tissue-engineering strategies. The rat ASCs that were enclosed in the CMC-Ph gels through a horseradish peroxidase-catalysed reaction showed 92.8% viability, good proliferation and adipogenic differentiation in vitro. Ten weeks after the subcutaneous injection of ASCs-suspending CMC-Ph for in situ gelation, clearly visible new vascularized adipose tissue formed at the injection site. The number of blood vessels and the area occupied by adipose tissues were five and eight times larger, respectively, than those found in the implanted acellular gel. The adipogenesis and neovascularization were further enhanced by incorporation of fibroblast growth factor into the CMC-Ph gel containing ASCs. PMID:22489051

Ogushi, Yuko; Sakai, Shinji; Kawakami, Koei

2013-11-01

258

Metabolic recovery of adipose tissue is associated with improvement in insulin resistance in a model of experimental diabetes.  

PubMed

Obesity and insulin resistance are highly correlated with metabolic disturbances. Both the excess and lack of adipose tissue can lead to severe insulin resistance and diabetes. Adipose tissue plays an active role in energy homeostasis, hormone secretion, and other proteins that affect insulin sensitivity, appetite, energy balance, and lipid metabolism. Rats with streptozotocin-induced diabetes during the neonatal period develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, and insulin resistance in adulthood. Low body weight and reduced epididymal (EP) fat mass were also seen in this model. The aim of this study was to investigate the glucose homeostasis and metabolic repercussions on the adipose tissue following chronic treatment with antidiabetic drugs in these animals. In the 4th week post birth, diabetic animals started an 8-week treatment with pioglitazone, metformin, or insulin. Animals were then killed, EP fat pads were excised, and blood samples were collected for biological and biochemical assays. Pioglitazone and insulin treatments, but not metformin, reduced hyperglycemia, polydipsia, and polyphagia. Although all antidiabetic therapies improved insulin sensitivity, this was particularly noteworthy in the pioglitazone-treated rats. Furthermore, a recovery of adipose mass and insulin levels were observed in pioglitazone- and insulin-, but not metformin-treated animals. Treatments with insulin or pioglitazone were able to correct significantly, but not completely, the metabolic abnormalities, parallel to full recovery of adipose mass, indicating that not only the low insulin levels but also the lack of adipose tissue might play a significant role on the pathophysiology of this particular diabetes model. PMID:18451064

Takada, Julie; Fonseca-Alaniz, Miriam Helena; de Campos, Tarcila Beatriz Ferraz; Andreotti, Sandra; Campana, Amanda Baron; Okamoto, Maristela; Borges-Silva, Cristina das Neves; Machado, Ubiratan Fabres; Lima, Fabio Bessa

2008-07-01

259

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

PubMed Central

We have previously demonstrated that the small leucine-rich proteoglycan decorin may play a role in adipose tissue homeostasis and the pathophysiology of obesity. Biglycan is highly similar in structure to decorin, therefore we hypothesized it would have a similar expression profile and role to decorin in adipose tissue. Real time polymerase chain reaction was used to measure biglycan mRNA levels in adipose tissue from normal glucose tolerant and impaired glucose tolerant and type 2 diabetic (T2D) Psammomys obesus. Biglycan mRNA was found to be highly expressed in adipose tissue, and gene expression was significantly higher in visceral compared to subcutaneous adipose tissue, with elevated levels in obese, T2D compared to lean normal glucose tolerant P. obesus (P < 0.04). Biglycan mRNA was predominantly expressed by stromal/vascular cells of fractionated adipose tissue (P = 0.023). Biglycan expression in adipose tissue, particularly in the obese state, was markedly upregulated. Collectively, our data suggest that the small leucine-rich proteoglycan family proteins biglycan and decorin may play a role in the development of obesity and T2D, possibly by facilitating expansion of adipose tissue mass.

Bolton, Kristy; Segal, David; Walder, Ken

2012-01-01

260

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

PubMed

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

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

2014-01-01

261

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

PubMed Central

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

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

2014-01-01

262

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

263

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

PubMed

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

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

2013-11-01

264

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.

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

265

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.

2011-01-01

266

Divergent phenotype of rat thoracic and abdominal perivascular adipose tissues  

PubMed Central

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.

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

2013-01-01

267

Intermuscular adipose tissue and metabolic associations in HIV infection.  

PubMed

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

2011-02-01

268

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.

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

269

Adipose stem cells used to reconstruct 13 cases with cranio-maxillofacial hard-tissue defects.  

PubMed

Although isolated reports of hard-tissue reconstruction in the cranio-maxillofacial skeleton exist, multipatient case series are lacking. This study aimed to review the experience with 13 consecutive cases of cranio-maxillofacial hard-tissue defects at four anatomically different sites, namely frontal sinus (3 cases), cranial bone (5 cases), mandible (3 cases), and nasal septum (2 cases). Autologous adipose tissue was harvested from the anterior abdominal wall, and adipose-derived stem cells were cultured, expanded, and then seeded onto resorbable scaffold materials for subsequent reimplantation into hard-tissue defects. The defects were reconstructed with either bioactive glass or ?-tricalcium phosphate scaffolds seeded with adipose-derived stem cells (ASCs), and in some cases with the addition of recombinant human bone morphogenetic protein-2. Production and use of ASCs were done according to good manufacturing practice guidelines. Follow-up time ranged from 12 to 52 months. Successful integration of the construct to the surrounding skeleton was noted in 10 of the 13 cases. Two cranial defect cases in which nonrigid resorbable containment meshes were used sustained bone resorption to the point that they required the procedure to be redone. One septal perforation case failed outright at 1 year because of the postsurgical resumption of the patient's uncontrolled nasal picking habit. PMID:24558162

Sándor, George K; Numminen, Jura; Wolff, Jan; Thesleff, Tuomo; Miettinen, Aimo; Tuovinen, Veikko J; Mannerström, Bettina; Patrikoski, Mimmi; Seppänen, Riitta; Miettinen, Susanna; Rautiainen, Markus; Öhman, Juha

2014-04-01

270

Mitochondrial fission: firing up mitochondria in brown adipose tissue.  

PubMed

Brown adipose tissue (BAT) is an important site for energy expenditure, for instance to generate heat in times of cold exposure. BAT expansion and activation can increase energy dissipation of an organism. This involves the coordinated activation of mitochondrial metabolism and heat generation through uncoupling of oxidative phosphorylation. In this issue of The EMBO Journal, the Shirihai group uncovers a novel potentiation pathway for BAT energy expenditure. Changes in mitochondrial dynamics, in particular mitochondrial fission, act in synergy with fatty acid-induced uncoupling to activate BAT metabolism in response to the hormone norepinephrine. PMID:24480477

Gao, Arwen W; Houtkooper, Riekelt H

2014-03-01

271

From the epicardial adipose tissue to vulnerable coronary plaques  

PubMed Central

Thin cap fibroatheromas (TCFAs) are thought to be the most common underlying substrate in patients suffering acute coronary thrombotic events. Recently, an interesting association between TCFAs and a particular depot of visceral fat called epicardial adipose tissue (EAT) has been suggested. In this article, we discuss some basic and clinical aspects of this association and then briefly review some of the pathophysiological characteristics attributed to EAT that explain why this particular depot of fat has been attracting the attention of the cardiological scientific community in recent years. Finally we discuss the value of optical coherence tomography in the diagnosis of TCFAs and the role of multislice computed tomography to assess EAT.

Echavarria-Pinto, Mauro; Hernando, Lorenzo; Alfonso, Fernando

2013-01-01

272

The relationship between functional vasodilatation in adipose tissue and prostaglandin  

PubMed Central

1. Earlier it had been found that during fat mobilization there was an increased blood flow in the adipose tissue and the tissue contained a vasodilator substance. 2. Extract of an activated fat pad contained 3 to 25 times as much activity as the contralateral resting fat pad. 3. The following findings suggest that the vasodilator substance is prostagladin E2: (a) It caused contractions of the guinea-pig ileum which were not reduced by mepyramine, but were reduced by atropine. (b) It caused a prolonged vasodilator response when injected closearterially to the epigastric fat pad. (c) It was eluted from a silicic acid column by a solvent system which is known to elute prostaglandins of the E series but not those of the F series. (d) Its indices of discrimination were similar to those of prostaglandin E's when assayed on three different pharmacological preparations. (e) On thin-layer chromatography it behaved more like prostaglandin E2 than E1. 4. Neither prostaglandin E1 nor prostaglandin E2 inhibited the release of free fatty acids from the rabbit epigastric fat pad by ACTH1-24. 5. It seems likely that prostaglandin E2 is responsible for the vasodilatation accompanying fat mobilization from adipose tissue.

Bowery, N. G.; Lewis, G. P.; Matthews, J.

1970-01-01

273

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.

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

2013-01-01

274

Effects of Cortisol and Growth Hormone on Lipolysis in Human Adipose Tissue  

Microsoft Academic Search

The in vitro effects of cortisol and GH on basal and stimulated lipolysis in human adipose tissue were studied using a tissue incu- bation technique. After preincubation for 3 days in control medium containing insulin, adipose tissue pieces were exposed to cortisol for 3 days. GH was added to the cortisol-containing medium during the last 24 h (day 6). Adipocytes

MALIN OTTOSSON; PETER LONNROTH; PER BJORNTORP; STAFFAN EDEN

275

Influence of adipose tissue thickness on near infrared spectroscopic signal in the measurement of human muscle  

Microsoft Academic Search

The aim of this study was to clarify the influence of subcutaneous adipose tissue (AT) thickness on near-infrared (NIR) optical density and the penetration depth of light in muscle tissue in vivo. The thickness of adipose tissue in the leg was measured using ultrasonography in 12 young subjects. Optical densities (OD) at 775, 807, and 827 nm were measured when

Sachiko Homma; Tetsuo Fukunaga; Atsuko Kagaya

1996-01-01

276

Does subcutaneous adipose tissue behave as an (anti-)thixotropic material?  

Microsoft Academic Search

Although subcutaneous adipose tissue undergoes large deformations on a daily basis, there is no adequate mechanical model to describe the transfer of mechanical load from the skin throughout the tissue to deeper layers. In order to develop such a non-linear model, a set of experimental data is required. Accordingly, this study examines the long term behavior of adipose tissue under

Marion Geerligs; Gerrit W. M. Peters; Paul A. J. Ackermans; Cees W. J. Oomens; Frank P. T. Baaijens

2010-01-01

277

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

PubMed Central

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

2010-01-01

278

Isolation and growth of adipose tissue-derived stem cells.  

PubMed

Fat tissue provides a rich and easily accessible supply of stem cells that feature the general differentiation potential and plasticity of mesenchymal stem cells. These stem cells, variably designated adipose-derived stem cells (ASCs), hold a great promise for regeneration in vivo and tissue engineering. In order to be able to obtain ASC preparations suitable for basic investigations as well as development of future therapeutic protocols, it is important that the critical isolation steps are properly carried out. Here, we describe in detail enzyme-based procedure for isolation and propagation of ASCs from the human subcutaneous fat tissue that is also adaptable to several animal species. The critical steps and impact of possible modifications on the final outcome are discussed, and useful hints are provided to streamline the troubleshooting. PMID:21431509

Zachar, Vladimir; Rasmussen, Jeppe Grøndahl; Fink, Trine

2011-01-01

279

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

PubMed Central

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.

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

2013-01-01

280

Brown adipose tissue regulates glucose homeostasis and insulin sensitivity.  

PubMed

Brown adipose tissue (BAT) is known to function in the dissipation of chemical energy in response to cold or excess feeding, and also has the capacity to modulate energy balance. To test the hypothesis that BAT is fundamental to the regulation of glucose homeostasis, we transplanted BAT from male donor mice into the visceral cavity of age- and sex-matched recipient mice. By 8-12 weeks following transplantation, recipient mice had improved glucose tolerance, increased insulin sensitivity, lower body weight, decreased fat mass, and a complete reversal of high-fat diet-induced insulin resistance. Increasing the quantity of BAT transplanted into recipient mice further improved the metabolic effects of transplantation. BAT transplantation increased insulin-stimulated glucose uptake in vivo into endogenous BAT, white adipose tissue (WAT), and heart muscle but, surprisingly, not skeletal muscle. The improved metabolic profile was lost when the BAT used for transplantation was obtained from Il6-knockout mice, demonstrating that BAT-derived IL-6 is required for the profound effects of BAT transplantation on glucose homeostasis and insulin sensitivity. These findings reveal a previously under-appreciated role for BAT in glucose metabolism. PMID:23221344

Stanford, Kristin I; Middelbeek, Roeland J W; Townsend, Kristy L; An, Ding; Nygaard, Eva B; Hitchcox, Kristen M; Markan, Kathleen R; Nakano, Kazuhiro; Hirshman, Michael F; Tseng, Yu-Hua; Goodyear, Laurie J

2013-01-01

281

Brown adipose tissue regulates glucose homeostasis and insulin sensitivity  

PubMed Central

Brown adipose tissue (BAT) is known to function in the dissipation of chemical energy in response to cold or excess feeding, and also has the capacity to modulate energy balance. To test the hypothesis that BAT is fundamental to the regulation of glucose homeostasis, we transplanted BAT from male donor mice into the visceral cavity of age- and sex-matched recipient mice. By 8–12 weeks following transplantation, recipient mice had improved glucose tolerance, increased insulin sensitivity, lower body weight, decreased fat mass, and a complete reversal of high-fat diet–induced insulin resistance. Increasing the quantity of BAT transplanted into recipient mice further improved the metabolic effects of transplantation. BAT transplantation increased insulin-stimulated glucose uptake in vivo into endogenous BAT, white adipose tissue (WAT), and heart muscle but, surprisingly, not skeletal muscle. The improved metabolic profile was lost when the BAT used for transplantation was obtained from Il6–knockout mice, demonstrating that BAT-derived IL-6 is required for the profound effects of BAT transplantation on glucose homeostasis and insulin sensitivity. These findings reveal a previously under-appreciated role for BAT in glucose metabolism.

Stanford, Kristin I.; Middelbeek, Roeland J.W.; Townsend, Kristy L.; An, Ding; Nygaard, Eva B.; Hitchcox, Kristen M.; Markan, Kathleen R.; Nakano, Kazuhiro; Hirshman, Michael F.; Tseng, Yu-Hua; Goodyear, Laurie J.

2012-01-01

282

S-Glutathionylation of Hepatic and Visceral Adipose Proteins Decreases in Obese Rats  

PubMed Central

A number of clinical and biochemical studies demonstrate that obesity and insulin resistance are associated with increases in oxidative stress and inflammation. Paradoxically, insulin sensitivity can be enhanced by oxidative inactivation of cysteine residues of phosphatases, and inflammation can be reduced by S-glutathionylation with formation of protein-glutathione mixed disulfides (PSSG). Although oxidation of protein-bound thiols (PSH) is increased in multiple diseases, it is not known whether there are changes in PSH oxidation species in obesity. In this work, we tested the hypothesis that obesity is associated with decreased levels of proteins containing oxidized protein thiols. We examined tissue levels of protein sulfenic acids (PSOH) and PSSG in liver, visceral adipose tissue, and skeletal muscle derived from glucose intolerant, obese-prone Sprague-Dawley rats. Our data indicate that decreases in PSSG content occurred in liver (44%) and adipose (26%) but not skeletal muscle in obese rats fed a 45% fat-calorie diet versus lean rats fed a 10% fat-calorie diet. PSOH content did not change in the tissue between the two groups. The activity of the enzyme glutaredoxin (GLRX) responsible for reversal of PSSG formation did not change in muscle and liver between the two groups. However, levels of GLRX1 were elevated 70% in the adipose tissue of the obese, 45% fat calorie-fed rats. These are the first data to link changes in S-glutathionylation and GLRX1 to adipose tissue in the obese and demonstrate that redox changes in thiol status occur in adipose tissue as a result of obesity.

Picklo, Matthew J.; Idso, Joseph P.; Jackson, Matthew I.

2012-01-01

283

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

PubMed

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

Boscaro, Marco; Giacchetti, Gilberta; Ronconi, Vanessa

2012-08-01

284

Maternal parity and its effect on adipose tissue deposition and endocrine sensitivity in the postnatal sheep  

PubMed Central

Maternal parity influences size at birth, postnatal growth and body composition with firstborn infants being more likely to be smaller with increased fat mass, suggesting that adiposity is set in early life. The precise effect of parity on fat mass and its endocrine sensitivity remains unclear and was, therefore, investigated in the present study. We utilised an established sheep model in which perirenal–abdominal fat mass (the major fat depot in the neonatal sheep) increases ?10-fold over the first month of life and focussed on the impact of parity on glucocorticoid sensitivity and adipokine expression in the adipocyte. Twin-bearing sheep of similar body weight and adiposity that consumed identical diets were utilised, and maternal blood samples were taken at 130 days of gestation. One offspring from each twin pair was sampled at 1 day of age, coincident with the time of maximal recruitment of uncoupling protein 1 (UCP1), whilst its sibling was sampled at 1 month, when UCP1 had disappeared. Plasma leptin was lower in nulliparous mothers than in multiparous mothers, and offspring of nulliparous mothers possessed more adipose tissue with increased mRNA abundance of leptin, glucocorticoid receptor and UCP2, adaptations that persisted up to 1 month of age when gene expression for interleukin-6 and adiponectin was also raised. The increase in fat mass associated with firstborn status is therefore accompanied by a resetting of the leptin and glucocorticoid axis within the adipocyte. Our findings emphasise the importance of parity in determining adipose tissue development and that firstborn offspring have an increased capacity for adipogenesis which may be critical in determining later adiposity.

Hyatt, M A; Keisler, D H; Budge, H; Symonds, M E

2010-01-01

285

UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity  

PubMed Central

Background The uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis. Methodology/Principal Findings Here we report that cyclooxygenase (COX) activity and prostaglandin E2 (PGE2) are crucially involved in induction of UCP1 expression in inguinal white adipocytes, but not in classic interscapular brown adipocytes. Cold-induced expression of UCP1 in inguinal white adipocytes was repressed in COX2 knockout (KO) mice and by administration of the COX inhibitor indomethacin in wild-type mice. Indomethacin repressed ?-adrenergic induction of UCP1 expression in primary inguinal adipocytes. The use of PGE2 receptor antagonists implicated EP4 as a main PGE2 receptor, and injection of the stable PGE2 analog (EP3/4 agonist) 16,16 dm PGE2 induced UCP1 expression in inguinal white adipose tissue. Inhibition of COX activity attenuated diet-induced UCP1 expression and increased energy efficiency and adipose tissue mass in obesity-resistant mice kept at thermoneutrality. Conclusions/Significance Our findings provide evidence that induction of UCP1 expression in white adipose tissue, but not in classic interscapular brown adipose tissue is dependent on cyclooxygenase activity. Our results indicate that cyclooxygenase-dependent induction of UCP1 expression in white adipose tissues is important for diet-induced thermogenesis providing support for a surprising role of COX activity in the control of energy balance and obesity development.

Madsen, Lise; Pedersen, Lone M.; Lillefosse, Haldis Haukaas; Fjaere, Even; Bronstad, Ingeborg; Hao, Qin; Petersen, Rasmus K.; Hallenborg, Philip; Ma, Tao; De Matteis, Rita; Araujo, Pedro; Mercader, Josep; Bonet, M. Luisa; Hansen, Jacob B.; Cannon, Barbara; Nedergaard, Jan; Wang, Jun; Cinti, Saverio; Voshol, Peter; D?skeland, Stein Ove; Kristiansen, Karsten

2010-01-01

286

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

PubMed Central

Objective: The aim was to investigate adipose tissue vascular and metabolic effects of an adrenaline infusion in vivo in subjects with and without type 2 diabetes mellitus (T2DM). Design: Clinical intervention study with 1-h intravenous adrenaline infusion. Subjects: Eight male overweight T2DM subjects and eight male weight-matched, non-T2DM subjects were studied before, during and after an 1-h intravenous adrenaline infusion. Adipose tissue blood flow (ATBF) was determined by 133Xenon wash-out technique, and microvascular volume in the adipose tissue was studied by contrast-enhanced ultrasound imaging. Adipose tissue fluxes of glycerol, non-esterified fatty acids (NEFA), triacylglycerol and glucose were measured by Fick's principle after catherisation of a radial artery and a vein draining the abdominal, subcutaneous adipose tissue. Results: ATBF increased similarly in both groups during the adrenaline infusion. One hour post adrenaline, ATBF was still increased in overweight T2DM subjects. Adrenaline increased microvascular volume in non-T2DM subjects while this response was impaired in overweight T2DM subjects. Adrenaline-induced increase in lipolysis was similar in both groups, but NEFA output from adipose tissue was delayed in overweight T2DM subjects. Glucose uptake in adipose tissue increased in non-T2DM subjects during adrenaline infusion but was unchanged in overweight T2DM subjects. This results in a delayed excess release of NEFA from the adipose tissue in overweight T2DM subjects after cessation of the adrenaline infusion. Conclusion: Capillaries in the adipose tissue are recruited by adrenaline in non-T2DM subjects; however, this response is impaired in overweight T2DM subjects. NEFA, released in adipose tissue during adrenaline stimulation, is insufficiently re-esterified in situ in overweight T2DM subjects, probably owing to increased ATBF after adrenaline infusion and inability to increase adipose tissue glucose uptake.

Tobin, L; Simonsen, L; Galbo, H; Bulow, J

2012-01-01

287

Adipose tissue volume determinations in women by computed tomography: technical considerations.  

PubMed

Eight healthy female volunteers with weights ranging from 46 to 119 kg were examined with a Philips Tomoscan 310 in order to determine the amount of adipose tissue. From analysis of 'attenuation profiles' at the thigh and trunk levels the attenuation interval of adipose tissue was determined to be -190 HU to -30 HU. The adipose tissue volume was calculated from the adipose tissue area of 22 scans and from the distances between these scans. Three different mathematical models were tested which all gave similar results. The adipose tissue surface of the L4-L5 scan showed a higher correlation (r = 0.991) than any other single scan versus the 22-scan-based adipose tissue volume. The adipose tissue volume had to be calculated from nine selected slices in order to agree closely with the results based on 22 scans (r = 0.999) in each individual case. The adipose tissue volume of the head and neck region was 1.7 +/- 0.24 per cent of the total volume, while corresponding figures for other regions were: arms 7.5 +/- 1.2 per cent, legs 31.8 +/- 5.6 per cent, subcutaneous part of the trunk 48.9 +/- 5.1 per cent and visceral region 10.2 +/- 1.7 per cent. The relative amount of subcutaneous trunk adipose tissue increased with increasing adipose tissue volumes while that of legs, and of head and neck tended to decrease. The relative amount of visceral fat was not significantly dependent on the total adipose tissue volume in these eight women. PMID:3710689

Kvist, H; Sjöström, L; Tylén, U

1986-01-01

288

CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients.  

PubMed

The purpose of this study was to determine the core biological processes perturbed in the subcutaneous adipose tissue of familial combined hyperlipidemia (FCHL) patients. Annotation of FCHL and control microarray datasets revealed a distinctive FCHL transcriptome, characterized by gene expression changes regulating five overlapping systems: the cytoskeleton, cell adhesion and extracellular matrix; vesicular trafficking; lipid homeostasis; and cell cycle and apoptosis. Expression values for the cell-cycle inhibitor CDKN2B were increased, replicating data from an independent FCHL cohort. In 3T3-L1 cells, CDKN2B knockdown induced C/EBP? expression and lipid accumulation. The minor allele at SNP site rs1063192 (C) was predicted to create a perfect seed for the human miRNA-323b-5p. A miR-323b-5p mimic significantly reduced endogenous CDKN2B protein levels and the activity of a CDKN2B 3'UTR luciferase reporter carrying the rs1063192 C allele. Although the allele displayed suggestive evidence of association with reduced CDKN2B mRNA in the MuTHER adipose tissue dataset, family studies suggest the association between increased CDKN2B expression and FCHL-lipid abnormalities is driven by factors external to this gene locus. In conclusion, from a comparative annotation analysis of two separate FCHL adipose tissue transcriptomes and a subsequent focus on CDKN2B, we propose that dysfunctional adipogenesis forms an integral part of FCHL pathogenesis. PMID:24103848

Horswell, Stuart D; Fryer, Lee G D; Hutchison, Claire E; Zindrou, Dlear; Speedy, Helen E; Town, Margaret-M; Duncan, Emma J; Sivapackianathan, Rasheeta; Patel, Hetal N; Jones, Emma L; Braithwaite, Adam; Salm, Max P A; Neuwirth, Claire K Y; Potter, Elizabeth; Anderson, Jonathan R; Taylor, Kenneth M; Seed, Mary; Betteridge, D John; Crook, Martin A; Wierzbicki, Anthony S; Scott, James; Naoumova, Rossi P; Shoulders, Carol C

2013-12-01

289

Mechanisms of Chronic State of Inflammation as Mediators That Link Obese Adipose Tissue and Metabolic Syndrome  

PubMed Central

The metabolic syndrome is a cluster of cardiometabolic alterations that include the presence of arterial hypertension, insulin resistance, dyslipidemia, and abdominal obesity. Obesity is associated with a chronic inflammatory response, characterized by abnormal adipokine production, and the activation of proinflammatory signalling pathways resulting in the induction of several biological markers of inflammation. Macrophage and lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Adiponectin can either act directly on macrophages to shift polarization and/or prime human monocytes into alternative M2-macrophages with anti-inflammatory properties. Meanwhile, the chronic inflammation in adipose tissue is regulated by a series of transcription factors, mainly PPARs and C/EBPs, that in conjunction regulate the expression of hundreds of proteins that participate in the metabolism and storage of lipids and, as such, the secretion by adipocytes. Therefore, the management of the metabolic syndrome requires the development of new therapeutic strategies aimed to alter the main genetic pathways involved in the regulation of adipose tissue metabolism.

Fuentes, Eduardo; Fuentes, Francisco; Badimon, Lina; Palomo, Ivan

2013-01-01

290

Human Adipose Tissue Is a Source of Multipotent Stem CellsD?  

PubMed Central

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

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

2002-01-01

291

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

PubMed Central

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

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

2009-01-01

292

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

293

Adipose Tissue Exosome-Like Vesicles Mediate Activation of Macrophage-Induced Insulin Resistance  

PubMed Central

OBJECTIVE We sought to determine whether exosome-like vesicles (ELVs) released from adipose tissue play a role in activation of macrophages and subsequent development of insulin resistance in a mouse model. RESEARCH DESIGN AND METHODS ELVs released from adipose tissue were purified by sucrose gradient centrifugation and labeled with green fluorescent dye and then intravenously injected into B6 ob/ob mice (obese model) or B6 mice fed a high-fat diet. The effects of injected ELVs on the activation of macrophages were determined through analysis of activation markers by fluorescence-activated cell sorter and induction of inflammatory cytokines using an ELISA. Glucose tolerance and insulin tolerance were also evaluated. Similarly, B6 mice with different gene knockouts including TLR2, TLR4, MyD88, and Toll-interleukin-1 receptor (TIR) domain–containing adaptor protein inducing interferon-? (TRIF) were also used for testing their responses to the injected ELVs. RESULTS ELVs are taken up by peripheral blood monocytes, which then differentiate into activated macrophages with increased secretion of tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6). Injection of obELVs into wild-type C57BL/6 mice results in the development of insulin resistance. When the obELVs were intravenously injected into TLR4 knockout B6 mice, the levels of glucose intolerance and insulin resistance were much lower. RBP4 is enriched in the obELVs. Bone marrow–derived macrophages preincubated with recombinant RBP4 led to attenuation of obELV-mediated induction of IL-6 and TNF-?. CONCLUSIONS ELVs released by adipose tissue can act as a mode of communication between adipose tissues and macrophages. The obELV-mediated induction of TNF-? and IL-6 in macrophages and insulin resistance requires the TLR4/TRIF pathway.

Deng, Zhong-bin; Poliakov, Anton; Hardy, Robert W.; Clements, Ronald; Liu, Cunren; Liu, Yuelong; Wang, Jianhua; Xiang, Xiaoyu; Zhang, Shuangqin; Zhuang, Xiaoying; Shah, Spandan V.; Sun, Dongmei; Michalek, Sue; Grizzle, William E.; Garvey, Timothy; Mobley, Jim; Zhang, Huang-Ge

2009-01-01

294

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

295

The role of adenosine monophosphate kinase in remodeling white adipose tissue metabolism.  

PubMed

Recent evidence indicates that the enzyme adenosine monophosphate (AMP) kinase exerts important fat-reducing effects in the adipose tissue, which has created great interest in this enzyme as a potential target for obesity treatment. This review summarizes our findings that chronic AMP kinase activation remodels adipocyte glucose and lipid metabolism and enhances the ability of adipose tissue to dissipate energy within itself and reduce adiposity. PMID:21206283

Gaidhu, Mandeep Pinky; Ceddia, Rolando Bacis

2011-04-01

296

Adipose Stem Cell Engineering: Characterization and Current Application in Neurological Tissue Repair  

Microsoft Academic Search

\\u000a Adipose stem cells (ASCs) are one of heterogeneous mixed populations in the stromal vascular fraction of adipose tissue. Recently,\\u000a ASCs become attractive alternative for autologous neural cells due to its abundance, easy accessibility, and several successful\\u000a inductions to neural and glial cells. In this review, we summarized recent progresses in identification of primary cell types\\u000a in adipose tissue and their

Guangfan Chi; Youngsook Son

297

Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue  

PubMed Central

Aims/hypothesis Increasing the expression of the brown adipose tissue-specific gene uncoupling protein-1 (Ucp1) is a potential target for treating obesity. We investigated the role of DNA methylation and histone modification in Ucp1 expression in adipose cell lines and ex vivo murine adipose tissues. Methods Methylation state of the Ucp1 enhancer was studied using bisulphite mapping in murine adipose cell lines, and tissue taken from cold-stressed mice, coupled with functional assays of the effects of methylation and demethylation of the Ucp1 promoter on gene expression and nuclear protein binding. Results We show that demethylation of the Ucp1 promoter by 5-aza-deoxycytidine increases Ucp1 expression while methylation of Ucp1 promoter–reporter constructs decreases expression. Brown adipose tissue-specific Ucp1 expression is associated with decreased CpG dinucleotide methylation of the Ucp1 enhancer. The lowest CpG dinucleotide methylation state was found in two cyclic AMP response elements (CRE3, CRE2) in the Ucp1 promoter and methylation of the CpG in CRE2, but not CRE3 decreased nuclear protein binding. Chromatin immunoprecipitation assays revealed the presence of the silencing DiMethH3K9 modification on the Ucp1 enhancer in white adipose tissue and the appearance of the active TriMethH3K4 mark at the Ucp1 promoter in brown adipose tissue in response to a cold environment. Conclusions/interpretation The results demonstrate that CpG dinucleotide methylation of the Ucp1 enhancer exhibits tissue-specific patterns in murine tissue and cell lines and suggest that adipose tissue-specific Ucp1 expression involves demethylation of CpG dinucleotides found in regulatory CREs in the Ucp1 enhancer, as well as modification of histone tails. Electronic supplementary material The online version of this article (doi:10.1007/s00125-010-1701-4) contains supplementary material, which is available to authorised users.

Shore, A.; Karamitri, A.; Kemp, P.; Speakman, J. R.

2010-01-01

298

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

PubMed Central

Clustering of insulin resistance and dysmetabolism with obesity is attributed to pathologic adipose tissue. The morphologic hallmarks of this pathology are adipocye hypertrophy and heightened inflammation. However, it's underlying molecular mechanisms remains unknown. Study of gene function in metabolically active tissues like adipose tissue, skeletal muscle and liver is a promising strategy. Microarray is a powerful technique of assessment of gene function by measuring transcription of large number of genes in an array. This technique has several potential applications in understanding pathologic adipose tissue. They are: (1) transcriptomic differences between various depots of adipose tissue, adipose tissue from obese versus lean individuals, high insulin resistant versus low insulin resistance, brown versus white adipose tissue, (2) transcriptomic profiles of various stages of adipogenesis, (3) effect of diet, cytokines, adipokines, hormones, environmental toxins and drugs on transcriptomic profiles, (4) influence of adipokines on transcriptomic profiles in skeletal muscle, hepatocyte, adipose tissue etc., and (5) genetics of gene expression. The microarray evidences of molecular basis of obesity and insulin resistance are presented here. Despite the limitations, microarray has potential clinical applications in finding new molecular targets for treatment of insulin resistance and classification of adipose tissue based on future risk of insulin resistance syndrome.

Mathur, Sandeep Kumar; Jain, Priyanka; Mathur, Prashant

2011-01-01

299

Androgen Effects on Adipose Tissue Architecture and Function in Nonhuman Primates  

PubMed Central

The differential association of hypoandrogenism in men and hyperandrogenism in women with insulin resistance and obesity suggests that androgens may exert sex-specific effects on adipose and other tissues, although the underlying mechanisms remain poorly understood. Moreover, recent studies also suggest that rodents and humans may respond differently to androgen imbalance. To achieve better insight into clinically relevant sex-specific mechanisms of androgen action, we used nonhuman primates to investigate the direct effects of gonadectomy and hormone replacement on white adipose tissue. We also employed a novel ex vivo approach that provides a convenient framework for understanding of adipose tissue physiology under a controlled tissue culture environment. In vivo androgen deprivation of males did not result in overt obesity or insulin resistance but did induce the appearance of very small, multilocular white adipocytes. Testosterone replacement restored normal cell size and a unilocular phenotype and stimulated adipogenic gene transcription and improved insulin sensitivity of male adipose tissue. Ex vivo studies demonstrated sex-specific effects of androgens on adipocyte function. Female adipose tissue treated with androgens displayed elevated basal but reduced insulin-dependent fatty acid uptake. Androgen-stimulated basal uptake was greater in adipose tissue of ovariectomized females than in adipose tissue of intact females and ovariectomized females replaced with estrogen and progesterone in vivo. Collectively, these data demonstrate that androgens are essential for normal adipogenesis in males and can impair essential adipocyte functions in females, thus strengthening the experimental basis for sex-specific effects of androgens in adipose tissue.

Varlamov, Oleg; White, Ashley E.; Carroll, Julie M.; Bethea, Cynthia L.; Reddy, Arubala; Slayden, Ov; O'Rourke, Robert W.

2012-01-01

300

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

301

Resveratrol supplementation improves white adipose tissue function in a depot-specific manner in Zucker diabetic fatty rats.  

PubMed

Resveratrol (RSV) is a polyphenolic compound suggested to have anti-diabetic properties. Surprisingly, little is known regarding the effects of RSV supplementation on adipose tissue (AT) metabolism in vivo. The purpose of this study was to assess the effects of RSV on mitochondrial content and respiration, glyceroneogenesis (GNG), and adiponectin secretion in adipose tissue from Zucker diabetic fatty (ZDF) rats. Five-week-old ZDF rats were fed a chow diet with (ZDF RSV) or without (ZDF chow) RSV (200 mg/kg body wt) for 6 wk. Changes in adipose tissue metabolism were assessed in subcutaneous (scAT) and intra-abdominal [retroperitoneal (rpWAT), epididymal (eWAT)] adipose tissue depots. ZDF RSV rats showed lower fasting glucose and higher circulating adiponectin, as well as lower glucose area under the curve during intraperitoneal glucose and insulin tolerance tests than ZDF chow. [¹?C]pyruvate incorporation into triglycerides and adiponectin secretion were higher in scAT from ZDF RSV rats, concurrent with increases in adipose tissue triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and the phosphorylation of pyruvate dehydrogenase-E1? (PDH) (Ser293) protein content in this depot. Moreover, uncoupled mitochondrial respiration and complex I and II-supported respiration were increased in both scAT and rpWAT, which correlated with increases in cytochrome c oxidase subunit IV (COX4) protein content. In vitro treatment of scAT with RSV (50 ?mol/l; 24 h) induced pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator-activated receptor (PPAR)-? coactivator-1? (PGC-1?) mRNA expression. Collectively, these data demonstrate that RSV can induce adipose tissue mitochondrial biogenesis in parallel with increases in GNG and adiponectin secretion. PMID:23824959

Beaudoin, Marie-Soleil; Snook, Laelie A; Arkell, Alicia M; Simpson, Jeremy A; Holloway, Graham P; Wright, David C

2013-09-01

302

Comparison of the expression and activity of the lipogenic pathway in human and rat adipose tissue  

Microsoft Academic Search

Lipogenesis is considered less active in human than in rat adipose tissue. This could be explained by differ- ent nutritional conditions, namely high-carbohydrate (HCHO) diet in rats and high-fat (HF) diet in humans. Adipose tissue was sampled (postabsorptive state) in rats and humans re- ceiving HCHO or HF diets, ad libitum fed humans, and obese subjects. We measured 1 )

Dominique Letexier; Claudie Pinteur; Valérie Large; Vincent Fréring; Michel Beylot

2003-01-01

303

Diabetic and nondiabetic patients express similar adipose tissue adiponectin and leptin levels  

Microsoft Academic Search

Objective:Epicardial adipose tissue (EAT) is an interesting visceral fat pad with a particular location. EAT and subcutaneous adipose tissue (SAT) produce a wide range of adipokines. Some of them, including adiponectin and leptin, can influence the risk of development of diabetes and other associated metabolic and cardiovascular conditions. We sought to assess whether EAT and SAT adiponectin and leptin expression

E Teijeira-Fernandez; S Eiras; L Grigorian-Shamagian; A Salgado-Somoza; J M Martinez-Comendador; J R Gonzalez-Juanatey

2010-01-01

304

GDP binding to brown-adipose-tissue mitochondria of mice treated chronically with corticosterone.  

PubMed Central

Cytochrome oxidase activity and mitochondrial GDP binding were decreased in brown adipose tissue of mice treated chronically with corticosterone. These changes occurred both in corticosterone-treated mice fed ad libitum and in treated mice pair-fed to control animals. Although the dietary stimulation of brown-adipose-tissue thermogenesis was suppressed by corticosterone, the acute response to cold was not affected.

Galpin, K S; Henderson, R G; James, W P; Trayhurn, P

1983-01-01

305

Vaspin gene expression in human adipose tissue: Association with obesity and type 2 diabetes  

Microsoft Academic Search

Recently, vaspin was identified as an adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes. In this study, we examined whether vaspin mRNA expression is a marker of visceral obesity and correlates with anthropometric and metabolic parameters in paired samples of visceral and subcutaneous adipose tissue from 196 subjects

Nora Klöting; Janin Berndt; Susan Kralisch; Peter Kovacs; Mathias Fasshauer; Michael R. Schön; Michael Stumvoll; Matthias Blüher

2006-01-01

306

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

PubMed

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

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

2014-05-31

307

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.

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

2014-01-01

308

Emerging role of adipose tissue hypoxia in obesity and insulin resistance  

Microsoft Academic Search

Recent studies consistently support a hypoxia response in the adipose tissue in obese animals. The observations have led to the formation of an exciting concept, adipose tissue hypoxia (ATH), in the understanding of major disorders associated with obesity. ATH may provide cellular mechanisms for chronic inflammation, macrophage infiltration, adiponectin reduction, leptin elevation, adipocyte death, endoplasmic reticulum stress and mitochondrial dysfunction

J Ye

2009-01-01

309

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.

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

2013-01-01

310

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

PubMed Central

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

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

2012-01-01

311

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

312

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

313

Perivascular adipose tissue and its role in type 2 diabetes and cardiovascular disease.  

PubMed

Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity. Adipose tissue-derived substances (adipokines) and especially inflammatory products of adipose tissue control insulin sensitivity and vascular function. In the past years, adipose tissue associated with the vasculature, or perivascular adipose tissue (PAT), has been shown to produce a variety of adipokines that contribute to regulation of vascular tone and local inflammation. This review describes our current understanding of the mechanisms linking perivascular adipose tissue to vascular function, inflammation, and insulin resistance. Furthermore, we will discuss mechanisms controlling the quantity and adipokines secretion by PAT. PMID:21461998

Meijer, Rick I; Serne, Erik H; Smulders, Yvo M; van Hinsbergh, Victor W M; Yudkin, John S; Eringa, Etto C

2011-06-01

314

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

PubMed Central

The fibroblast growth factor (FGF)–FGF receptor (FGFR) system plays a role in angiogenesis and maintenance of vascular integrity, but its potential role in adipose tissue related angiogenesis and development is still unknown. Administration of SSR, a low molecular weight inhibitor of multiple FGFRs, did not significantly affect body weight nor weight of subcutaneous or gonadal (GON) fat, as compared with pair-fed control mice. Adipocyte hypertrophy and reduced adipocyte density were only observed in GON adipose tissues of treated mice. Adipose tissue angiogenesis was not affected by SSR treatment, as normalized blood vessel density was comparable in adipose tissues of both groups. Blocking the FGF–FGFR system in vivo does not markedly affect adipose tissue development in mice with nutritionally induced obesity.

Scroyen, Ilse; Vranckx, Christine; Lijnen, Henri Roger

2014-01-01

315

The local corticotropin-releasing hormone receptor 2 signalling pathway partly mediates hypoxia-induced increases in lipolysis via the cAMP-protein kinase A signalling pathway in white adipose tissue.  

PubMed

Our objective was to investigate the mechanisms by which the endogenous CRHR2 in white adipose tissue (WAT) regulates metabolic activities associated with lipogenesis and lipolysis under continuous exposure to hypoxia. We found that hypobaric hypoxia at a simulated altitude of 5000m significantly reduced the body weight, food intake, and WAT mass of rats. Hypoxia also accelerated lipolysis and suppressed lipogenesis in WAT. Pretreatment with astressin 2B, a selective CRHR2 antagonist, partly but significantly attenuated the hypoxia-induced reductions in body weight and WAT mass by blocking the cAMP-protein kinase A (PKA)-hormone-sensitive lipase (HSL)/perilipin signalling pathway. Astressin 2B treatment failed to attenuate hypoxia induced lipogenic inhibition. In conclusion, activation of endogenous WAT Ucn2/3 autocrine/paracrine pathway was involved in hypoxia induced lipolysis via CRHR2 - cAMP-PKA signalling pathway. This study provides the novel understanding of local CRHR2 signaling pathway playing important role in WAT loss and lipid metabolism under hypoxia. PMID:24859650

Xiong, Yanlei; Qu, Zhuan; Chen, Nan; Gong, Hui; Song, Mintao; Chen, Xuequn; Du, Jizeng; Xu, Chengli

2014-07-01

316

The blood flow and oxygen consumption of brown adipose tissue in the new-born rabbit  

PubMed Central

1. A direct method for measuring venous outflow from brown adipose tissue in anaesthetized new-born rabbits is described. 2. During noradrenaline infusion the mean blood flow through brown adipose tissue increased from 87 to 360 ml./100 g tissue (wet wt.).min, and the mean rate of oxygen consumption of brown adipose tissue rose from 9·3 to 60 ml. O2/100 g tissue.min. 3. During cold exposure the mean blood flow through brown adipose tissue increased from 90 to 304 ml./100 g tissue.min. 4. The mean cardiac output was 266 ml./kg body weight.min; during noradrenaline infusion it was 405 ml./kg body weight.min. At rest about one tenth, and during noradrenaline infusion about one quarter of the cardiac output went to brown adipose tissue. 5. It was calculated that most of the extra oxygen consumed during the metabolic response of the anaesthetized new-born rabbit to noradrenaline infusion or cold exposure was consumed by brown adipose tissue. 6. Hypoxia (breathing 10% O2 in N2) greatly reduced the increase in oxygen consumption but not the increase in blood flow in brown adipose tissue caused by noradrenaline infusion.

Heim, T.; Hull, D.

1966-01-01

317

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

318

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

ERIC Educational Resources Information Center

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

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

1975-01-01

319

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.

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

320

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

PubMed Central

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

2014-01-01

321

Release of 12 adipokines by adipose tissue, nonfat cells, and fat cells from obese women.  

PubMed

The relative release in vitro of endothelin-1, zinc-alpha2-glycoprotein (ZAG), lipocalin-2, CD14, RANTES (regulated on activation, normal T cell expressed and secreted protein), lipoprotein lipase (LPL), osteoprotegerin (OPG), fatty acid-binding protein 4 (FABP-4), visfatin/PBEF/Nampt, glutathione peroxidase-3 (GPX-3), intracellular cell adhesion molecule 1 (ICAM-1), and amyloid A was examined using explants of human adipose tissue as well as the nonfat cell fractions and adipocytes from obese women. Over a 48-h incubation the majority of the release of LPL was by fat cells whereas that of lipocalin-2, RANTES, and ICAM-1 was by the nonfat cells present in human adipose tissue. In contrast appreciable amounts of OPG, amyloid A, ZAG, FABP-4, GPX-3, CD14, and visfatin/PBEF/Nampt were released by both fat cells and nonfat cells. There was an excellent correlation (r = 0.75) between the ratios of adipokine release by fat cells to nonfat cells over 48 h and the ratio of their mRNAs in fat cells to nonfat cells at the start of the incubation. The total release of ZAG, OPG, RANTES, and amyloid A by incubated adipose tissue explants from women with a fat mass of 65 kg was not different from that by women with a fat mass of 29 kg. In contrast that of ICAM-1, FABP-4, GPX-3, visfatin/PBEF/Nampt, CD14, lipocalin-2, LP, and endothelin-1 was significantly greater in tissue from women with a total fat mass of 65 kg. PMID:19834460

Fain, John N; Tagele, Balkachew M; Cheema, Paramjeet; Madan, Atul K; Tichansky, David S

2010-05-01

322

Implication of Low Level Inflammation in the Insulin Resistance of Adipose Tissue at Late Pregnancy  

PubMed Central

Insulin resistance is a characteristic of late pregnancy, and adipose tissue is one of the tissues that most actively contributes to the reduced maternal insulin sensitivity. There is evidence that pregnancy is a condition of moderate inflammation, although the physiological role of this low-grade inflammation remains unclear. The present study was designed to validate whether low-grade inflammation plays a role in the development of insulin resistance in adipose tissue during late pregnancy. To this end, we analyzed proinflammatory adipokines and kinases in lumbar adipose tissue of nonpregnant and late pregnant rats at d 18 and 20 of gestation. We found that circulating and tissue levels of adipokines, such as IL-1?, plasminogen activator inhibitor-1, and TNF-?, were increased at late pregnancy, which correlated with insulin resistance. The observed increase in adipokines coincided with an enhanced activation of p38 MAPK in adipose tissue. Treatment of pregnant rats with the p38 MAPK inhibitor SB 202190 increased insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate-1 in adipose tissue, which was paralleled by a reduction of IR substrate-1 serine phosphorylation and an enhancement of the metabolic actions of insulin. These results indicate that activation of p38 MAPK in adipose tissue contributes to adipose tissue insulin resistance at late pregnancy. Furthermore, the results of the present study support the hypothesis that physiological low-grade inflammation in the maternal organism is relevant to the development of pregnancy-associated insulin resistance.

de Castro, J.; Sevillano, J.; Marciniak, J.; Rodriguez, R.; Gonzalez-Martin, C.; Viana, M.; Eun-suk, O. H.; de Mouzon, S. Hauguel; Herrera, E.

2011-01-01

323

Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering  

PubMed Central

A series of thermosensitive copolymer hydrogels, aminated hyaluronic acid-g-poly(N-isopropylacrylamide) (AHA-g-PNIPAAm), were synthesized by coupling carboxylic end-capped PNIPAAm (PNIPAAm-COOH) to AHA through amide bond linkages. AHA was prepared by grafting adipic dihydrazide to the HA backbone and PNIPAAm-COOH copolymer was synthesized via a facile thermo-radical polymerization technique by polymerization of NIPAAm using 4,4?-azobis(4-cyanovaleric acid) as an initiator, respectively. The structure of AHA and AHA-g-PNIPAAm copolymer was determined by 1H NMR. Two AHA-g-PNIPAAm copolymers with different weight ratios of PNIPAAm on the applicability of injectable hydrogels were characterized. The lower critical solution temperature (LCST) of AHA-g-PNIPAAm copolymers in PBS were measured as ~30°C by rheological analysis, regardless of the grafting degrees. Enzymatic resistance of AHA-g-PNIPAAm hydrogels with 28% and 53% of PNIPAAm in 100U/mL hyaluronidase/PBS at 37°C was 12.3% and 37.6% over 28 days, respectively. Equilibrium swelling ratios of AHA-g-PNIPAAm hydrogels with 28% of PNIPAAm were 21.5, and significantly decreased to 13.3 with 53% of PNIPAAm in PBS at 37°C. Results from SEM observations confirm a porous 3D AHA-g-PNIPAAm hydrogel structure with interconnected pores after freeze-drying and the pore diameter depends on the weight ratios of PNIPAAm. Encapsulation of human adipose-derived stem cells (ASCs) within hydrogels showed the AHA-g-PNIPAAm copolymers were noncytotoxic and preserved the viability of the entrapped cells. A preliminary in vivo study demonstrated the usefulness of the AHA-g-PNIPAAm copolymer as an injectable hydrogel for adipose tissue engineering. This newly described thermoresponsive AHA-g-PNIPAAm copolymer demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications.

Tan, Huaping; Ramirez, Christina M.; Miljkovic, Natasa; Li, Han; Rubin, J. Peter; Marra, Kacey G.

2009-01-01

324

Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering.  

PubMed

A series of thermosensitive copolymer hydrogels, aminated hyaluronic acid-g-poly(N-isopropylacrylamide) (AHA-g-PNIPAAm), were synthesized by coupling carboxylic end-capped PNIPAAm (PNIPAAm-COOH) to AHA through amide bond linkages. AHA was prepared by grafting adipic dihydrazide to the HA backbone and PNIPAAm-COOH copolymer was synthesized via a facile thermo-radical polymerization technique by polymerization of NIPAAm using 4,4'-azobis(4-cyanovaleric acid) as an initiator, respectively. The structure of AHA and AHA-g-PNIPAAm copolymer was determined by (1)H NMR. Two AHA-g-PNIPAAm copolymers with different weight ratios of PNIPAAm on the applicability of injectable hydrogels were characterized. The lower critical solution temperature (LCST) of AHA-g-PNIPAAm copolymers in PBS were measured as approximately 30 degrees C by rheological analysis, regardless of the grafting degrees. Enzymatic resistance of AHA-g-PNIPAAm hydrogels with 28% and 53% of PNIPAAm in 100U/mL hyaluronidase/PBS at 37 degrees C was 12.3% and 37.6% over 28 days, respectively. Equilibrium swelling ratios of AHA-g-PNIPAAm hydrogels with 28% of PNIPAAm were 21.5, and significantly decreased to 13.3 with 53% of PNIPAAm in PBS at 37 degrees C. Results from SEM observations confirm a porous 3D AHA-g-PNIPAAm hydrogel structure with interconnected pores after freeze-drying and the pore diameter depends on the weight ratios of PNIPAAm. Encapsulation of human adipose-derived stem cells (ASCs) within hydrogels showed the AHA-g-PNIPAAm copolymers were noncytotoxic and preserved the viability of the entrapped cells. A preliminary in vivo study demonstrated the usefulness of the AHA-g-PNIPAAm copolymer as an injectable hydrogel for adipose tissue engineering. This newly described thermoresponsive AHA-g-PNIPAAm copolymer demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications. PMID:19783043

Tan, Huaping; Ramirez, Christina M; Miljkovic, Natasa; Li, Han; Rubin, J Peter; Marra, Kacey G

2009-12-01

325

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

PubMed Central

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

2012-01-01

326

Fyn deficiency promotes a preferential increase in subcutaneous adipose tissue mass and decreased visceral adipose tissue inflammation.  

PubMed

Previous studies have demonstrated that Fyn knockout (FynKO) mice on a standard chow diet display increased glucose clearance and whole-body insulin sensitivity associated with decreased adiposity resulting from increased fatty acid use and energy expenditure. Surprisingly, however, despite a similar extent of adipose tissue (AT) mass accumulation on a high-fat diet, the FynKO mice remained fully glucose tolerant and insulin sensitive. Physiologic analyses demonstrated that the FynKO mice had a combination of skewed AT expansion into the subcutaneous compartment rather than to the visceral depot, reduced AT inflammation associated with reduced T-cell and macrophage infiltration, and increased proportion of anti-inflammatory M2 macrophages. These data demonstrate that Fyn is an important regulator of whole-body integrative metabolism that coordinates AT expansion, inflammation, and insulin sensitivity in states of nutrient excess. These data further suggest that inhibition of Fyn function may provide a novel target to prevent AT inflammation, insulin resistance, and the dyslipidemia components of the metabolic syndrome. PMID:23321073

Lee, Ting-Wen A; Kwon, Hyokjoon; Zong, Haihong; Yamada, Eijiro; Vatish, Manu; Pessin, Jeffrey E; Bastie, Claire C

2013-05-01

327

Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast cancer.  

PubMed

Among the many different cell types surrounding breast cancer cells, the most abundant are those that compose mammary adipose tissue, mainly mature adipocytes and progenitors. New accumulating recent evidences bring the tumor-surrounding adipose tissue into the light as a key component of breast cancer progression. The purpose of this review is to emphasize the role that adipose tissue might play by locally affecting breast cancer cell behavior and subsequent clinical consequences arising from this dialog. Two particular clinical aspects are addressed: obesity that was identified as an independent negative prognostic factor in breast cancer and the oncological safety of autologous fat transfer used in reconstructive surgery for breast cancer patients. This is preceded by the overall description of adipose tissue composition and function with special emphasis on the specificity of adipose depots and the species differences, key experimental aspects that need to be taken in account when cancer is considered. PMID:22643115

Wang, Yuan-Yuan; Lehuédé, Camille; Laurent, Victor; Dirat, Béatrice; Dauvillier, Stéphanie; Bochet, Ludivine; Le Gonidec, Sophie; Escourrou, Ghislaine; Valet, Philippe; Muller, Catherine

2012-11-28

328

Interactive in vitro effect of prolactin, growth hormone and season on leptin secretion by ovine adipose tissue  

Microsoft Academic Search

White adipose tissue is an important endocrine organ. Receptors for several hormones are found in the adipocytes, suggesting that these hormones may directly regulate the activity of the fat cells. The effects of prolactin (PRL), growth hormone (GH), melatonin, insulin and their interaction on the regulation of leptin secretion from ovine peri-renal adipose tissue samples were evaluated. Adipose tissue isolated

M. Szczesna; D. A. Zieba; B. Klocek-Gorka; D. H. Keisler

2011-01-01

329

Changes in the transcriptome of abdominal subcutaneous adipose tissue in response to short-term overfeeding in lean and obese  

Microsoft Academic Search

Background: Obesity is caused by the excessive accumulation of adipose tissue as a result of a chronic energy surplus. Little is known regarding the molecular mechanisms involved in the re- sponse to an energy surplus in human adipose tissue at the genomic level. Objective: The objective was to investigate changes in the tran- scriptome of abdominal subcutaneous adipose tissue after

Jennifer Shea; Curtis R French; Jessica Bishop; Glynn Martin; Barbara Roebothan; David Pace; Donald Fitzpatrick; Guang Sun

330

Liver Attenuation, Pericardial Adipose Tissue, Obesity, and Insulin Resistance: The MultiEthnic Study of Atherosclerosis (MESA)  

Microsoft Academic Search

Insulin resistance is linked to general and abdominal obesity, but its relation to hepatic lipid content and pericardial adipose tissue is less clear. The purpose of this study was to examine cross-sectional associations of liver attenuation, pericardial adipose tissue, BMI, and waist circumference with insulin resistance. We measured liver attenuation and pericardial adipose tissue using the existing cardiac computed tomography

Paul A. McAuley; Fang-Chi Hsu; Kurt K. Loman; J. Jeffrey Carr; Matthew J. Budoff; Moyses Szklo; A. Richey Sharrett; Jingzhong Ding

2011-01-01

331

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

PubMed Central

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

Ma, Tao; Liaset, Bj?rn; Hao, Qin; Petersen, Rasmus Koefoed; Fjaere, Even; Ngo, Ha Thi; Lillefosse, Haldis Haukas; Ringholm, Stine; Sonne, Si Brask; Treebak, Jonas Thue; Pilegaard, Henriette; Fr?yland, Livar; Kristiansen, Karsten; Madsen, Lise

2011-01-01

332

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

333

Metabolic Signatures of Human Adipose Tissue Hypoxia in Obesity  

PubMed Central

Adipose tissue (AT) hypoxia has been proposed as the cause of obesity-related AT dysfunction, moving the tissue toward a proinflammatory phenotype. In humans, AT oxygenation has been assessed by expression of hypoxia-sensitive genes or direct assessment of O2 tension; the obvious read out of hypoxia, effects on intermediary metabolism, has not been investigated. We used tissue-specific venous catheterization of subcutaneous abdominal AT in humans to investigate oxygen-related metabolic processes, searching for metabolic signatures relating to hypoxia in obesity. O2 delivery to AT was reduced in obesity (P < 0.05). However, O2 consumption was low (<30% of resting forearm skeletal muscle [SM], P < 0.001); this was not related to obesity. AT primarily oxidized glucose, as demonstrated by a respiratory quotient close to 1.0 (higher than SM, P < 0.05). AT was a net producer of lactate, but there was an inverse relationship in venous outflow between lactate-to-pyruvate ratio (a marker of cytosolic redox state) and BMI, suggesting that AT is glycolytic but obese AT is not hypoxic. Although delivery of O2 to the obese AT is reduced, O2 consumption is low, and metabolic signatures of human AT do not support the notion of a hypoxic state in obesity.

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

2013-01-01

334

Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue.  

PubMed

Adipose tissue can undergo rapid expansion during times of excess caloric intake. Like a rapidly expanding tumor mass, obese adipose tissue becomes hypoxic due to the inability of the vasculature to keep pace with tissue growth. Consequently, during the early stages of obesity, hypoxic conditions cause an increase in the level of hypoxia-inducible factor 1alpha (HIF1alpha) expression. Using a transgenic model of overexpression of a constitutively active form of HIF1alpha, we determined that HIF1alpha fails to induce the expected proangiogenic response. In contrast, we observed that HIF1alpha initiates adipose tissue fibrosis, with an associated increase in local inflammation. "Trichrome- and picrosirius red-positive streaks," enriched in fibrillar collagens, are a hallmark of adipose tissue suffering from the early stages of hypoxia-induced fibrosis. Lysyl oxidase (LOX) is a transcriptional target of HIF1alpha and acts by cross-linking collagen I and III to form the fibrillar collagen fibers. Inhibition of LOX activity by beta-aminoproprionitrile treatment results in a significant improvement in several metabolic parameters and further reduces local adipose tissue inflammation. Collectively, our observations are consistent with a model in which adipose tissue hypoxia serves as an early upstream initiator for adipose tissue dysfunction by inducing a local state of fibrosis. PMID:19546236

Halberg, Nils; Khan, Tayeba; Trujillo, Maria E; Wernstedt-Asterholm, Ingrid; Attie, Alan D; Sherwani, Shariq; Wang, Zhao V; Landskroner-Eiger, Shira; Dineen, Sean; Magalang, Ulysses J; Brekken, Rolf A; Scherer, Philipp E

2009-08-01

335

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

Microsoft Academic Search

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

Hiroyuki Nobusue; Tsuyoshi Endo; Koichiro Kano

2008-01-01

336

Decreased Transcription of ChREBP-?/? Isoforms in Abdominal Subcutaneous Adipose Tissue of Obese Adolescents With Prediabetes or Early Type 2 Diabetes  

PubMed Central

Insulin resistance associated with altered fat partitioning in liver and adipose tissues is a prediabetic condition in obese adolescents. We investigated interactions between glucose tolerance, insulin sensitivity, and the expression of lipogenic genes in abdominal subcutaneous adipose and liver tissue in 53 obese adolescents. Based on their 2-h glucose tests they were stratified in the following groups: group 1, 2-h glucose level <120 mg/dL; group 2, 2-h glucose level between 120 and 140 mg/dL; and group 3, 2-h glucose level >140 mg/dL. Liver and adipose tissue insulin sensitivity were greater in group 1 than in group 2 and group 3, and muscle insulin sensitivity progressively decreased from group 1 to group 3. The expression of the carbohydrate-responsive element-binding protein (ChREBP) was decreased in adipose tissue but increased in the liver (eight subjects) in adolescents with impaired glucose tolerance or type 2 diabetes. The expression of adipose ChREBP? and ChREBP? was inversely related to 2-h glucose level and positively correlated to insulin sensitivity. Improvement of glucose tolerance in four subjects was associated with an increase of ChREBP/GLUT4 expression in the adipose tissue. In conclusion, early in the development of prediabetes/type 2 diabetes in youth, ChREBP? expression in adipose tissue predicts insulin resistance and, therefore, might play a role in the regulation of glucose tolerance.

Kursawe, Romy; Caprio, Sonia; Giannini, Cosimo; Narayan, Deepak; Lin, Aiping; D'Adamo, Ebe; Shaw, Melissa; Pierpont, Bridget; Cushman, Samuel W.; Shulman, Gerald I.

2013-01-01

337

Peptide Nucleic Acids Conjugated to Short Basic Peptides Show Improved Pharmacokinetics and Antisense Activity in Adipose Tissue  

PubMed Central

A peptide nucleic acid (PNA) targeting a splice junction of the murine PTEN primary transcript was covalently conjugated to various basic peptides. When systemically administered to healthy mice, the conjugates displayed sequence-specific alteration of PTEN mRNA splicing as well as inhibition of full length PTEN protein expression. Correlating activity with drug concentration in various tissues indicated strong tissue-dependence with highest levels of activity observed in adipose tissue. While the presence of a peptide carrier was found to be crucial for efficient delivery to tissue, little difference was observed between the various peptides evaluated. A second PNA-conjugate targeting the murine insulin receptor primary transcript showed a similar activity profile suggesting that short basic peptides can generally be used to effectively deliver peptide nucleic acids to adipose tissue.

Wancewicz, Edward V.; Maier, Martin A.; Siwkowski, Andrew M.; Albertshofer, Klaus; Winger, Theodore M.; Berdeja, Andres; Gaus, Hans; Vickers, Timothy A.; Bennett, C. Frank; Monia, Brett P.; Griffey, Richard H.; Nulf, Christopher J.; Hu, Jiaxin; Corey, David R.; Swayze, Eric E.; Kinberger, Garth A.

2010-01-01

338

Cellular and molecular mechanisms of adipose tissue plasticity in muscle insulin receptor knockout mice.  

PubMed

White adipose tissue (WAT) plays a critical role in the development of insulin resistance via secretion of free fatty acids (FFA) and adipocytokines. Muscle-specific insulin receptor knockout (MIRKO) mice do not develop insulin resistance or diabetes under physiological conditions despite a marked increase in adiposity and plasma FFA. On the contrary, WAT of MIRKO is sensitized to insulin action during a euglycemic clamp, and WAT glucose utilization is dramatically increased. To get insight into the potential antidiabetic role of MIRKO adiposity, we have studied insulin action in WAT during a euglycemic, hyperinsulinemic clamp, and we have characterized the morphology and biology of WAT. During the clamp, there is no alteration in the expression or activation in the insulin signaling molecules involved in glucose transport through the phosphoinositide 3-kinase/Akt and CAP/Cbl pathways in WAT from MIRKO. The 53% increase in WAT mass results from a 48% increase in adipocyte number (P < 0.05) without alteration in cell size and contemporary to a 300% increase in mRNA levels of the adipogenic transcription factor CCAAT enhancer binding protein-alpha (C/EBP-alpha) (P < 0.05). There is a 39.5% increase in serum adiponectin (P < 0.01) without modification in serum leptin, resistin, and TNF-alpha. In conclusion, the MIRKO mouse displays muscle insulin resistance, visceral obesity, and dyslipidemia but does not develop hyperinsulinemia or diabetes. There is an accelerated differentiation of small insulin sensitive adipocytes, an increased secretion of the insulin sensitizer adiponectin, and maintenance of leptin sensitivity. The MIRKO mouse confirms the importance of WAT plasticity in the maintenance of whole body insulin sensitivity and represents an interesting model to search for new secreted molecules that positively alter adipose tissue biology. PMID:14684612

Cariou, Bertrand; Postic, Catherine; Boudou, Philippe; Burcelin, Rémy; Kahn, C Ronald; Girard, Jean; Burnol, Anne-Françoise; Mauvais-Jarvis, Franck

2004-04-01

339

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

340

Isolation, characterization, and mesodermic differentiation of stem cells from adipose tissue of camel (Camelus dromedarius).  

PubMed

Adipose-derived stem cells are an attractive alternative as a source of stem cells that can easily be extracted from adipose tissue. Isolation, characterization, and multi-lineage differentiation of adipose-derived stem cells have been described for human and a number of other species. Here we aimed to isolate and characterize camel adipose-derived stromal cell frequency and growth characteristics and assess their adipogenic, osteogenic, and chondrogenic differentiation potential. Samples were obtained from five adult dromedary camels. Fat from abdominal deposits were obtained from each camel and adipose-derived stem cells were isolated by enzymatic digestion as previously reported elsewhere for adipose tissue. Cultures were kept until confluency and subsequently were subjected to differentiation protocols to evaluate adipogenic, osteogenic, and chondrogenic potential. The morphology of resultant camel adipose-derived stem cells appeared to be spindle-shaped fibroblastic morphology, and these cells retained their biological properties during in vitro expansion with no sign of abnormality in karyotype. Under inductive conditions, primary adipose-derived stem cells maintained their lineage differentiation potential into adipogenic, osteogenic, and chondrogenic lineages during subsequent passages. Our observation showed that like human lipoaspirate, camel adipose tissue also contain multi-potent cells and may represent an important stem cell source both for veterinary cell therapy and preclinical studies as well. PMID:23299319

Mohammadi-Sangcheshmeh, Abdollah; Shafiee, Abbas; Seyedjafari, Ehsan; Dinarvand, Peyman; Toghdory, Abdolhakim; Bagherizadeh, Iman; Schellander, Karl; Cinar, Mehmet Ulas; Soleimani, Masoud

2013-02-01

341

Effect of selenium on selenoprotein expression in the adipose tissue of chickens.  

PubMed

This study describes the effects of selenium (Se) deficiency on the messenger ribonucleic acid (mRNA) expression of 25 selenoproteins (Sels) (including glutathione peroxidases (GPx1-GPx4), thioredoxin reductases (TrxR1-TrxR3), iodothyronine deiodinases (ID1-ID3), selenophosphate synthetase 2 (SPS2), 15-kDa Sel (Sel15), SelH, SelI, SelK, SelM, Sepn1, SelO, Sepx, Selpb, SelS, SelT, SelW, Sepp1, and SelU in the adipose tissues (subcutaneous adipose, visceral adipose, and articular adipose) of chickens. One hundred and fifty 1-day-old chickens were randomly assigned to two groups of 75 each and were fed a low-Se diet (0.032 mg/kg Se) or a control diet (0.282 mg/kg Se). The expression levels of 25 Sel mRNAs were determined on days 35, 45, and 55 from three parts (subcutaneous adipose, visceral adipose, and articular adipose) of the chicken adipose tissues. The results showed that the expression levels of the 25 Sel mRNAs were significantly lower (P?adipose tissues were observed to decrease in a time-dependent manner with increasing feeding time. PMID:24894829

Liang, Yang; Lin, Shi-Lei; Wang, Cong-Wu; Yao, Hai-Dong; Zhang, Zi-Wei; Xu, Shi-Wen

2014-07-01

342

Establishment of a Transgenic Mouse Model Specifically Expressing Human Serum Amyloid A in Adipose Tissue  

PubMed Central

Obesity and obesity co-morbidities are associated with a low grade inflammation and elevated serum levels of acute phase proteins, including serum amyloid A (SAA). In the non-acute phase in humans, adipocytes are major producers of SAA but the function of adipocyte-derived SAA is unknown. To clarify the role of adipocyte-derived SAA, a transgenic mouse model expressing human SAA1 (hSAA) in adipocytes was established. hSAA expression was analysed using real-time PCR analysis. Male animals were challenged with a high fat (HF) diet. Plasma samples were subjected to fast protein liquid chromatography (FPLC) separation. hSAA, cholesterol and triglyceride content were measured in plasma and in FPLC fractions. Real-time PCR analysis confirmed an adipose tissue-specific hSAA gene expression. Moreover, the hSAA gene expression was not influenced by HF diet. However, hSAA plasma levels in HF fed animals (37.7±4.0 µg/mL, n?=?7) were increased compared to those in normal chow fed animals (4.8±0.5 µg/mL, n?=?10; p<0.001), and plasma levels in the two groups were in the same ranges as in obese and lean human subjects, respectively. In FPLC separated plasma samples, the concentration of hSAA peaked in high-density lipoprotein (HDL) containing fractions. In addition, cholesterol distribution over the different lipoprotein subfractions as assessed by FPLC analysis was similar within the two experimental groups. The established transgenic mouse model demonstrates that adipose tissue produced hSAA enters the circulation, resulting in elevated plasma levels of hSAA. This new model will enable further studies of metabolic effects of adipose tissue-derived SAA.

Olsson, Maja; Ahlin, Sofie; Olsson, Bob; Svensson, Per-Arne; Stahlman, Marcus; Boren, Jan; Carlsson, Lena M. S.; Sjoholm, Kajsa

2011-01-01

343

The role of adipose tissue in mediating the beneficial effects of dietary fish oil  

PubMed Central

Fish oil improves several features of metabolic syndrome such as dyslipidemia, insulin resistance and hepatic steatosis. Fish oil may mediate some of its beneficial effects by modulating the storage and/or secretory functions of adipose tissue. The storage of triglycerides in adipose tissue is regulated by the availability of free fatty acids as well as the degree of lipolysis in adipose tissue. Fish oil has been shown to reduce lipolysis in several studies indicating improved triglyceride storage. Importantly, adipose tissue secretes a variety of adipokines and fish oil feeding is associated with remarkable changes in the plasma levels of two key adipokines, adiponectin and leptin. Much attention has been focused on the contribution of adiponectin in fish oil mediated improvements in metabolic syndrome. However, emerging evidence also indicates a role of leptin in modulating the components of the metabolic syndrome upon fish oil feeding. In addition to improving the storage and secretory functions of adipose tissue, fish oil, and the n-3 fatty acids found in fish oil, has been shown to reduce inflammation in adipose tissue. These effects may be in part a result of activation of peroxisome proliferator-activated receptor ? or inhibition of toll-like receptor 4. Thus, there is compelling evidence that fish oil mediates its beneficial effects on metabolic syndrome by improving adipose tissue storage and secretory functions and by reducing inflammation.

Puglisi, Michael J.; Hasty, Alyssa H.; Saraswathi, Viswanathan

2010-01-01

344

The adipose tissue to serum dichlorodiphenyldichloroethane (DDE) ratio: Some methodological considerations  

SciTech Connect

Dichlorodiphenyldichloroethane (DDE) adipose tissue level has been regarded as a preferred indicator of accumulated human exposure to DDT; however, blood sera are more feasible to obtain and analyze than adipose tissue samples. Inconsistent and scarce information exists in relation to the adipose tissue/serum DDE ratio. As a part of a hospital-based case-control study performed in Mexico City from 1994 to 1996, 198 paired serum and adipose tissue samples were obtained from 72 women with histologically confirmed breast cancer and 126 women with benign breast disease. Both adipose tissue and serum DDE levels were determined by gas-liquid chromatography and reported as ppb lipid weight (ng/g) as well as wet basis (ng/ml). Results showed that the adipose tissue/serum DDE ratio (ADSE) varies according to the type of information (lipid vs wet basis, arithmetic vs geometric means) used for its estimation. ADSE gets a value near 1 (1.1) only when the geometric DDE levels in lipid basis are used for its estimation. The correlation between DDE serum and adipose tissue levels was found (r = 0.364, P < 0.001). The ADSE did not vary by disease status, nor was it altered by parity, history of breast-feeding, and other reproductive characteristics. The authors endorse the use of venipuncture instead of biopsy as a way to estimate DDT body burden levels in further research.

Lopez-Carrillo, L. (Mexico Secretariat of Health, Cuernavaca (Mexico). National Inst. of Public Health John D. and Catherine T. MacArthur Foundation (United States)); Torres-Sanchez, L.; Lopez-Cervantes, M. (Mexico Secretariat of Health, Cuernavaca (Mexico). National Inst. of Public Health); Blair, A. (National Cancer Inst., Bethesda, MD (United States)); Cebrian, M.E.; Uribe, M. (National Polytechnic Inst. (United States). Center for Research and Advanced Studies)

1999-08-01

345

Gene expression profiling reveals distinct features of various porcine adipose tissues  

PubMed Central

Background The excessive accumulation of body fat is a major risk factor to develop a variety of metabolic diseases. To investigate the systematic association between the differences in gene expression profiling and adipose deposition, we used pig as a model, and measured the gene expression profiling of six variant adipose tissues in male and females from three pig breeds which display distinct fat level. Results We identified various differential expressed genes among breeds, tissues and between sexes, and further used a clustering method to identify sets of functionally co-expression genes linked to different obesity-related phenotypes. Our results reveal that the subcutaneous adipose tissues mainly modulate metabolic indicators, nonetheless, the visceral adipose tissues as well as the intermuscular adipose tissue were mainly associated with the impaired inflammatory and immune response. Conclusions The present study provided the evidence of gene expression profiling that the subcutaneous adipose tissues are mainly affected the metabolism process, whereas the visceral and intermuscular adipose tissues should been term as the metabolic risk factors of obesity.

2013-01-01

346

Development of obesity in transgenic mice after genetic ablation of brown adipose tissue  

Microsoft Academic Search

BROWN adipose tissue, because of its capacity for uncoupled mitochondria! respiration1,2, has been implicated as an important site of facultative energy expenditure3-5. This has led to speculation that this tissue normally functions to prevent obesity3-5. Attempts to ablate or denervate brown adipose tissue surgically have been uninformative because it exists in diffuse depots and has substantial capacity for regeneration and

Bradford B. Lowell; Vedrana S-Susulic; Andreas Hamann; Joel A. Lawitts; Jean Himms-Hagen; Bert B. Boyer; Leslie P. Kozak; Jeffrey S. Flier

1993-01-01

347

The Expression of SPARC in Adipose Tissue and Its Increased Plasma Concentration in Patients with Coronary Artery Disease  

Microsoft Academic Search

Objective: Adipocytes secrete various cytokines and matrix proteins. Several of them precipitate in obesity-associated diseases, including atherosclerosis. In the current study, we have examined the expression of secreted protein, acidic and rich in cysteine (SPARC) in adipose tissue and its significance in obesity and coronary artery disease (CAD).Research Methods and Procedures: The SPARC mRNA expressions both in vivo and in

Masahiko Takahashi; Hiroyuki Nagaretani; Tohru Funahashi; Hitoshi Nishizawa; Norikazu Maeda; Ken Kishida; Hiroshi Kuriyama; Iichiro Shimomura; Kazuhisa Maeda; Kikuko Hotta; Noriyuki Ouchi; Shinji Kihara; Tadashi Nakamura; Shizuya Yamashita; Yuji Matsuzawa

2001-01-01

348

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

PubMed

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

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

2014-01-01

349

Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance  

PubMed Central

Although insulin regulates metabolism in both brown and white adipocytes, the role of these tissues in energy storage and utilization is quite different. Recombination technology using the Cre-loxP approach allows inactivation of the insulin receptor in a tissue-specific manner. Mice lacking insulin receptors in brown adipocytes show an age-dependent loss of interscapular brown fat but increased expression of uncoupling protein-1 and -2. In parallel, these mice develop an insulin-secretion defect resulting in a progressive glucose intolerance, without insulin resistance. This model provides direct evidence for not only a role for the insulin receptors in brown fat adipogenesis, the data also suggest a novel role of brown adipose tissue in the regulation of insulin secretion and glucose homeostasis.

Guerra, Carmen; Navarro, Paloma; Valverde, Angela M.; Arribas, Monica; Bruning, Jens; Kozak, Leslie P.; Kahn, C. Ronald; Benito, Manuel

2001-01-01

350

Increased apoptosis of periprostatic adipose tissue in VDR null mice.  

PubMed

The vitamin D receptor (VDR) is a member of the steroid/retinoid receptor superfamily of nuclear receptors that controls mineral ion homeostatis and has potential tumor-suppressive functions for various cancer types, specifically prostate cancer. A VDR ablated transgenic animal model (VDDRII, vitamin D-dependent rickets type II) has been developed and the animals typically have various diseases including, hypocalcemia, hyperparathyroidism, rickets, osteomalacia, and alopecia. This transgenic mouse system provides us with a model to decipher the influences of the VDR on prostatic growth and function. VDRs are abundant both in prostatic epithelial and stromal cells, and vitamin D signaling can be studied in this model. Although, there were no gross differences between the prostate tissue of the experimental and control groups, VDR null mice showed fat necrosis and individual cell apoptosis in the periprostatic adipose tissue. This indicates a possible role of VDR in the signaling pathways resulting the prostate. This may be particularly attractive for VDR targets for the inhibition of cancer progression using VD(3) and its analogs as potential chemo-preventive agents. PMID:15352170

Guzey, Meral; Jukic, Drazen; Arlotti, Julie; Acquafondata, Marie; Dhir, Rajiv; Getzenberg, Robert H

2004-09-01

351

Association between serum vaspin concentrations and visceral adipose tissue in Korean subjects  

Microsoft Academic Search

Adipokines modulate multiple signaling pathways of insulin resistance via endocrine, paracrine, or autocrine mechanisms. Visceral adipose tissue (VAT)–derived serpin (vaspin) is a novel adipokine with potential insulin-sensitizing effects. We investigated the association between serum vaspin concentrations and abdominal adiposity. We recruited subjects (N = 150) aged 20 to 69 years who visited our hospital for regular health examinations. Abdominal VAT

Hye Mi Chang; Hye Soon Park; Cheol-Young Park; Young Sook Song; Yeon Jin Jang

2010-01-01

352

Myostatin Inhibition in Muscle, but Not Adipose Tissue, Decreases Fat Mass and Improves Insulin Sensitivity  

Microsoft Academic Search

Myostatin (Mstn) is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn?\\/? mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in

Tingqing Guo; William Jou; Tatyana Chanturiya; Jennifer Portas; Oksana Gavrilova; Alexandra C. McPherron; Jose A. L. Calbet

2009-01-01

353

Cellular and Molecular Mechanisms of Adipose Tissue Plasticity in Muscle Insulin Receptor Knockout Mice  

Microsoft Academic Search

White adipose tissue (WAT) plays a critical role in the devel- opment of insulin resistance via secretion of free fatty acids (FFA) and adipocytokines. Muscle-specific insulin receptor knockout (MIRKO) mice do not develop insulin resistance or diabetes under physiological conditions despite a marked in- crease in adiposity and plasma FFA. On the contrary, WAT of MIRKO is sensitized to insulin

BERTRAND CARIOU; CATHERINE POSTIC; PHILIPPE BOUDOU; REMY BURCELIN; C. RONALD KAHN; JEAN GIRARD; ANNE-FRANCOISE BURNOL; FRANCK MAUVAIS-JARVIS

2003-01-01

354

Proteomic profiling of tissue-engineered blood vessel walls constructed by adipose-derived stem cells.  

PubMed

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 1701±15 and 1265±26 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; Cui, Lei

2013-02-01

355

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 1701±15 and 1265±26 protein spots fro