Note: This page contains sample records for the topic adipose tissue protein from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: November 12, 2013.
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

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

3

Fatty acid handling protein expression in adipose tissue, fatty acid composition of adipose tissue and serum, and markers of insulin resistance  

Microsoft Academic Search

Objective:Proteins involved in cellular fatty acid (FA) uptake and metabolism may be of relevance in the context of disturbed FA metabolism associated with insulin resistance. Therefore this study investigated relationships between FA handling protein mRNA expression in adipose tissue, FA composition of adipose tissue and serum, and markers of insulin resistance.Subjects:75 subjects with a range of insulin sensitivities recruited from

K Gertow; M Rosell; P Sjögren; P Eriksson; B Vessby; U de Faire; A Hamsten; M-L Hellenius; R M Fisher

2006-01-01

4

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

PubMed

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

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

2013-07-01

5

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

6

Oxidative stress and protein carbonylation in adipose tissue - Implications for insulin resistance and diabetes mellitus.  

PubMed

While historically considered simply as a depot for excess energy, white adipose tissue is a dynamically active endocrine organ capable of responding to a variety of efferent stimuli resulting in the synthesis and secretion of peptides, proteins and metabolites that serve as signal transducers to the peripheral and central circulation. Such regulation controls a variety of physiological processes including energy expenditure, food intake, reproductive capacity and responsiveness to insulin. Indeed, the accumulation of inflammatory cells in white adipose tissue is considered to be causative in the development of insulin resistance and eventually type 2 diabetes mellitus. A large body of evidence suggests that oxidative stress in adipose tissue not only correlates with insulin resistance but is also causative in its development. Moreover, using the available plasma oxidative stress biomarkers, many clinical studies have shown the presence of systemic oxidative stress in obese insulin resistant subjects, and its decrease after the successful treatment of obesity. In this review we emphasize the role of protein carbonylation in dysfunctional obese white adipose tissue and its metabolic implications. We focus on glutathione S-transferase A4 as the key enzyme for trans-4-hydroxy-2-nonenal and trans-4-oxo-2-nonenal removal from the cell, thus preventing protein carbonylation. This article is part of a Special Issue entitled: Protein Modifications. PMID:23584148

Ruskovska, Tatjana; Bernlohr, David A

2013-04-11

7

Effects of male hypogonadism on regional adipose tissue fatty acid storage and lipogenic proteins.  

PubMed

Testosterone has long been known to affect body fat distribution, although the underlying mechanisms remain elusive. We investigated the effects of chronic hypogonadism in men on adipose tissue fatty acid (FA) storage and FA storage factors. Twelve men with chronic hypogonadism and 13 control men matched for age and body composition: 1) underwent measures of body composition with dual energy x-ray absorptiometry and an abdominal CT scan; 2) consumed an experimental meal containing [(3)H]triolein to determine the fate of meal FA (biopsy-measured adipose storage vs. oxidation); 3) received infusions of [U-(13)C]palmitate and [1-(14)C]palmitate to measure rates of direct free (F)FA storage (adipose biopsies). Adipose tissue lipoprotein lipase, acyl-CoA synthetase (ACS), and diacylglycerol acetyl-transferase (DGAT) activities, as well as, CD36 content were measured to understand the mechanism by which alterations in fat storage occur in response to testosterone deficiency. Results of the study showed that hypogonadal men stored a greater proportion of both dietary FA and FFA in lower body subcutaneous fat than did eugonadal men (both p<0.05). Femoral adipose tissue ACS activity was significantly greater in hypogonadal than eugonadal men, whereas CD36 and DGAT were not different between the two groups. The relationships between these proteins and FA storage varied somewhat between the two groups. We conclude that chronic effects of testosterone deficiency has effects on leg adipose tissue ACS activity which may relate to greater lower body FA storage. These results provide further insight into the role of androgens in body fat distribution and adipose tissue metabolism in humans. PMID:22363653

Santosa, Sylvia; Jensen, Michael D

2012-02-20

8

Effects of Male Hypogonadism on Regional Adipose Tissue Fatty Acid Storage and Lipogenic Proteins  

PubMed Central

Testosterone has long been known to affect body fat distribution, although the underlying mechanisms remain elusive. We investigated the effects of chronic hypogonadism in men on adipose tissue fatty acid (FA) storage and FA storage factors. Twelve men with chronic hypogonadism and 13 control men matched for age and body composition: 1) underwent measures of body composition with dual energy x-ray absorptiometry and an abdominal CT scan; 2) consumed an experimental meal containing [3H]triolein to determine the fate of meal FA (biopsy-measured adipose storage vs. oxidation); 3) received infusions of [U-13C]palmitate and [1-14C]palmitate to measure rates of direct free (F)FA storage (adipose biopsies). Adipose tissue lipoprotein lipase, acyl-CoA synthetase (ACS), and diacylglycerol acetyl-transferase (DGAT) activities, as well as, CD36 content were measured to understand the mechanism by which alterations in fat storage occur in response to testosterone deficiency. Results of the study showed that hypogonadal men stored a greater proportion of both dietary FA and FFA in lower body subcutaneous fat than did eugonadal men (both p<0.05). Femoral adipose tissue ACS activity was significantly greater in hypogonadal than eugonadal men, whereas CD36 and DGAT were not different between the two groups. The relationships between these proteins and FA storage varied somewhat between the two groups. We conclude that chronic effects of testosterone deficiency has effects on leg adipose tissue ACS activity which may relate to greater lower body FA storage. These results provide further insight into the role of androgens in body fat distribution and adipose tissue metabolism in humans.

Santosa, Sylvia; Jensen, Michael D.

2012-01-01

9

Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation.  

PubMed

AMPK (AMP-activated protein kinase) is a key regulator of cellular and whole-body energy balance. AMPK phosphorylates and regulates many proteins concerned with nutrient metabolism, largely acting to suppress anabolic ATP-consuming pathways while stimulating catabolic ATP-generating pathways. This has led to considerable interest in AMPK as a therapeutic target for the metabolic dysfunction observed in obesity and insulin resistance. The role of AMPK in skeletal muscle and the liver has been extensively studied, such that AMPK has been demonstrated to inhibit synthesis of fatty acids, cholesterol and isoprenoids, hepatic gluconeogenesis and translation while increasing fatty acid oxidation, muscle glucose transport, mitochondrial biogenesis and caloric intake. The role of AMPK in the other principal metabolic and insulin-sensitive tissue, adipose, remains poorly characterized in comparison, yet increasing evidence supports an important role for AMPK in adipose tissue function. Obesity is characterized by hypertrophy of adipocytes and the development of a chronic sub-clinical pro-inflammatory environment in adipose tissue, leading to increased infiltration of immune cells. This combination of dysfunctional hypertrophic adipocytes and a pro-inflammatory environment contributes to insulin resistance and the development of Type 2 diabetes. Exciting recent studies indicate that AMPK may not only influence metabolism in adipocytes, but also act to suppress this pro-inflammatory environment, such that targeting AMPK in adipose tissue may be desirable to normalize adipose dysfunction and inflammation. In the present review, we discuss the role of AMPK in adipose tissue, focussing on the regulation of carbohydrate and lipid metabolism, adipogenesis and pro-inflammatory pathways in physiological and pathophysiological conditions. PMID:23298225

Bijland, Silvia; Mancini, Sarah J; Salt, Ian P

2013-04-01

10

Sympathetic activity in brown adipose tissue from rats adapted to a high protein, carbohydrate-free diet  

Microsoft Academic Search

Previous studies have shown that adaptation of rats to a high protein, carbohydrate-free (HP) diet results in a marked reduction in brown adipose tissue (BAT) thermogenic capacity. The present experiments were carried out to assess BAT sympathetic activity in HP diet-adapted rats. It was found that interscapular brown adipose tissue (IBAT) norepinephrine (NE) content, fractional turnover rate and calculated rate

Marcia N Brito; Nilton A Brito; Maria A. R Garófalo; Isis C Kettelhut; Renato H Migliorini

1998-01-01

11

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

12

Mesenteric Adipose Tissue-Derived Monocyte Chemoattractant Protein1 Plays a Crucial Role in Adipose Tissue Macrophage Migration and Activation in Obese Mice  

Microsoft Academic Search

Objective: To determine whether chemokines, which play a pivotal role in monocyte\\/macrophage trafficking, modulate macrophage infiltration into and activation in the adipose tissues.Research Methods and Procedures: Various types of adipose tissue were isolated from different fat depots (e.g., mesenteric, epididymal, renal, and subcutaneous adipose tissues) from obese mice fed a high-fat diet and from non-obese controls fed a standard diet.

Rina Yu; Chu-Sook Kim; Byung-Se Kwon; Teruo Kawada

2006-01-01

13

Adipose tissue and fetal programming.  

PubMed

Adipose tissue function changes with development. In the newborn, brown adipose tissue (BAT) is essential for ensuring effective adaptation to the extrauterine environment, and its growth during gestation is largely dependent on glucose supply from the mother to the fetus. The amount, location and type of adipose tissue deposited can also determine fetal glucose homeostasis. Adipose tissue first appears at around mid-gestation. Total adipose mass then increases through late gestation, when it comprises a mixture of white and brown adipocytes. BAT possesses a unique uncoupling protein, UCP1, which is responsible for the rapid generation of large amounts of heat at birth. Then, during postnatal life some, but not all, depots are replaced by white fat. This process can be utilised to investigate the physiological conversion of brown to white fat, and how it is re-programmed by nutritional changes in pre- and postnatal environments. A reduction in early BAT deposition may perpetuate through the life cycle, thereby suppressing energy expenditure and ultimately promoting obesity. Normal fat development profiles in the offspring are modified by changes in maternal diet at defined stages of pregnancy, ultimately leading to adverse long-term outcomes. For example, excess macrophage accumulation and the onset of insulin resistance occur in an adipose tissue depot-specific manner in offspring born to mothers fed a suboptimal diet from early to mid-gestation. In conclusion, the growth of the different fetal adipose tissue depots varies according to maternal diet and, if challenged in later life, this can contribute to insulin resistance and impaired glucose homeostasis. PMID:22402988

Symonds, M E; Pope, M; Sharkey, D; Budge, H

2012-03-09

14

Proteomic analysis of epicardial and subcutaneous adipose tissue reveals differences in proteins involved in oxidative stress.  

PubMed

Epicardial adipose tissue (EAT) is an endocrine organ adjacent to coronary arteries and myocardium without anatomy barriers. Locally produced adipokines may reflect or affect to cardiovascular physiology and pathology. Our aim was to study the protein expression profiles of EAT and subcutaneous adipose tissue (SAT) to identify local candidate molecules characterizing EAT in patients with cardiovascular disease. EAT and SAT samples were collected from 55 patients undergoing heart surgery. Proteins from these tissues were separated by two-dimensional (2D) gel electrophoresis, and differences between them were identified by MALDI-TOF/TOF spectra. Differences in protein levels were further investigated by real-time RT-PCR and Western blots, and production of reactive oxygen species (ROS) in EAT and SAT was evaluated by nitroblue tetrazolium chloride assays. ROS production was higher in EAT than SAT. We have found mRNA differences for catalase, glutathione S-transferase P, and protein disulfide isomerase, and 2D Western blots additionally showed post-translational differences for phosphoglycerate mutase 1; all four are related to oxidative stress pathways. EAT suffers greater oxidative stress than SAT in patients with cardiovascular diseases and exhibits associated proteomic differences that suggest the possibility of its association with myocardial stress in these patients. PMID:20435850

Salgado-Somoza, Antonio; Teijeira-Fernández, Elvis; Fernández, Angel Luis; González-Juanatey, José Ramón; Eiras, Sonia

2010-04-30

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

Targeting adipose tissue.  

PubMed

Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT) is generally known and stores excess energy in the form of triacylglycerol (TG), insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT) helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP). The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET), however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs), activators of peroxisome proliferator-activated receptor ? (PPAR?) a 'master' regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity. PMID:23102228

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

2012-10-27

17

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

PubMed Central

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

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

2003-01-01

18

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

SciTech Connect

Incubation in vitro of brown adipose tissue (BAT) mitochondria with divalent cations, spermine, or alkaline phosphatase led to a marked increase in the binding of ({sup 3}H)GDP. The effect of Mg{sup 2+} appeared to be the most specific and led to the largest increase in GDP binding. A simplified method was developed for measuring GDP binding to purified uncoupling protein from rat BAT mitochondria. Application of this method indicates that uncoupling protein from cold-acclimated rats binds twice as much GDP as uncoupling protein from cold-acclimated rats that were briefly returned to thermoneutrality, paralleling changes in GDP binding to the mitochondria. Incubation of BAT mitochondria with Mg{sup 2+} led to a smaller increase in GDP binding to the subsequently purified uncoupling protein, suggesting that divalent cations may somehow participate in the regulation of the activity of the uncoupling protein.

Swick, A.G.; Swick, R.W. (Univ. of Wisconsin, Madison (USA))

1988-12-01

19

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

PubMed

Much attention is currently focused on the role of perivascular adipose tissue in development of cardiovascular disease (CVD). Some researchers view it as promoting CVD through secretion of cytokines and growth factors called adipokines, while recent reports reveal that perivascular adipose tissue can exert a protective effect on CVD development. Furthermore, adiponectin, an anti-inflammatory adipokine, reportedly suppresses neointimal hyperplasia after endovascular injury, whereas such vascular remodeling is enhanced by pro-inflammatory adipokines secreted by perivascular adipose, such as tumor necrosis factor-? (TNF-?). These findings suggest that extent of vascular remodeling, a pathological process associated with CVD development, depends on the balance between pro- and anti-inflammatory adipokines secreted from perivascular adipose tissue. We previously demonstrated that angiopoietin-like protein 2 (Angptl2), a pro-inflammatory factor secreted by adipose tissue, promotes adipose tissue inflammation and subsequent systemic insulin resistance in obesity. Here, we examined whether Angptl2 secreted by perivascular adipose tissue contributes to vascular remodeling after endovascular injury in studies of transgenic mice expressing Angptl2 in adipose tissue (aP2-Angptl2 transgenic mice) and Angptl2 knockout mice (Angptl2(-/-) mice). To assess the role of Angptl2 secreted by perivascular adipose tissue on vascular remodeling after endovascular injury, we performed adipose tissue transplantation experiments using these mice. Wild-type mice with perivascular adipose tissue derived from aP2-Angptl2 mice exhibited accelerated neointimal hyperplasia after endovascular injury compared to wild-type mice transplanted with wild-type tissue. Conversely, vascular inflammation and neointimal hyperplasia after endovascular injury were significantly attenuated in wild-type mice transplanted with Angptl2(-/-) mouse-derived perivascular adipose tissue compared to wild-type mice transplanted with wild-type tissue. RT-PCR analysis revealed that mouse Angptl2 expression in perivascular adipose tissue was significantly increased by aging, hypercholesterolemia, and endovascular injury, all risk factors for coronary heart disease (CHD). Immunohistochemical and RT-PCR analysis of tissues from patients with CHD and from non-CHD patients indicated that ANGPTL2 expression in epicardial adipose tissue was unchanged. Interestingly, that analysis also revealed a positive correlation in ANGPTL2 and ADIPONECTIN expression in epicardial adipose tissue of non-CHD patients, a correlation not seen in CHD patients. However, in epicardial adipose tissue from CHD patients, ANGPTL2 expression was positively correlated with that of TNF-?, a correlation was not seen in non-CHD patients. These findings suggest that pro-inflammatory adipokines cooperatively accelerate CHD development and that maintaining a balance between pro- and anti-inflammatory adipokines likely protects non-CHD patients from developing CHD. Overall, our studies demonstrate that perivascular adipose tissue-secreted Angptl2 accelerates vascular inflammation and the subsequent CVD development. PMID:23333801

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

2013-01-16

20

Adipose Tissue as an Endocrine Organ  

Microsoft Academic Search

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

Rexford S Ahima; JEFFREY S. FLIER

2000-01-01

21

Concerted expression of the thermogenic and bioenergetic mitochondrial protein machinery in brown adipose tissue.  

PubMed

Brown adipose tissue (BAT) is specialized in non-shivering thermogenesis through the expression of the mitochondrial uncoupling protein-1 (UCP1). In this paper, we describe the relationship between UCP1 and proteins involved in ATP synthesis. By the use of BATIRKO mice, which have enhanced UCP1 expression in BAT, an increase in ATP synthase as well as in ubiquinol cytochrome c reductase levels was observed. Alterations in mitochondrial mass or variations in ATP levels were not observed in BAT of these mice. In addition, using a protocol of brown adipocyte differentiation, the concerted expression of UCP1 with ATP synthase was found. These two scenarios revealed that increases in the uncoupling machinery of brown adypocites must be concomitantly followed by an enhancement of proteins involved in ATP synthesis. These concerted changes reflect the need to maintain ATP production in an essentially uncoupling cell type. J. Cell. Biochem. 114: 2306-2313, 2013. © 2013 Wiley Periodicals, Inc. PMID:23606415

Guillen, Carlos; Bartolome, Alberto; Vila-Bedmar, Rocio; García-Aguilar, Ana; Gomez-Hernandez, Almudena; Benito, Manuel

2013-10-01

22

Adipose tissue macrophages.  

PubMed

It is now broadly accepted that low-grade chronic inflammation associated with obesity leads to the onset of insulin resistance and type 2 diabetes mellitus. Obesity-associated inflammation is characterized by an increased abundance of macrophages in adipose tissue along with production of inflammatory cytokines. Adipose tissue macrophages (ATMs) are suspected to be the major source of inflammatory mediators such as TNF-alpha and IL-6 that interfere with adipocyte function by inhibiting insulin action. However, ATMs phenotypically resemble alternatively activated (M2) macrophages and are capable of anti-inflammatory mediator production challenging the concept that ATMs are simply the "bad guys" in obese adipose tissue. Triggers promoting ATM recruitment, ATM functions and dysfunctions, and stimuli and molecular mechanisms that drive them into becoming detrimental to their environment are subject to current research. Strategies to interfere with ATM recruitment and adverse activation could give rise to novel options for treatment and prevention of insulin resistance and type 2 diabetes mellitus. PMID:17719095

Zeyda, Maximilian; Stulnig, Thomas M

2007-07-31

23

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

24

Adipose Tissue Engineering for Soft Tissue Regeneration  

PubMed Central

Current treatment modalities for soft tissue defects caused by various pathologies and trauma include autologous grafting and commercially available fillers. However, these treatment methods present a number of challenges and limitations, such as donor-site morbidity and volume loss over time. As such, improved therapeutic modalities need to be developed. Tissue engineering techniques offer novel solutions to these problems through development of bioactive tissue constructs that can regenerate adipose tissue in both structure and function. Recently, a number of studies have been designed to explore various methods to engineer human adipose tissue. This review will focus on these developments in the area of adipose tissue engineering for soft tissue replacement. The physiology of adipose tissue and current surgical therapies used to replace lost tissue volume, specifically in breast tissue, are introduced, and current biomaterials, cell sources, and tissue culture strategies are discussed. We discuss future areas of study in adipose tissue engineering.

Choi, Jennifer H.; Gimble, Jeffrey M.; Lee, Kyongbum; Marra, Kacey G.; Rubin, J. Peter; Yoo, James J.; Vunjak-Novakovic, Gordana

2010-01-01

25

Glucose uptake and glycolytic flux in adipose tissue from rats adapted to a high-protein, carbohydrate-free diet.  

PubMed

Rates of glucose uptake by epididymal and retroperitoneal adipose tissue in vivo, as well as rates of hexose uptake and glycolytic flux in isolated adipocytes, were determined in rats adapted to a high-protein, carbohydrate-free (HP) diet and in control rats fed a balanced (N) diet. Adaptation to the HP diet induced a significant reduction in rates of glucose uptake, estimated with 2-deoxy-[1-(3)H]-glucose, both by adipose tissue (epididymal and retroperitoneal) in vivo and by isolated adipocytes. Twelve hours after replacement of the HP diet with the balanced diet, rates of adipose tissue uptake in vivo in HP-adapted rats returned to levels that did not differ significantly from those in N-fed rats. The rate of flux in the glycolytic pathway, estimated with (3)H[5]-glucose, was also significantly reduced in adipocytes from HP-fed rats. In agreement with the above findings, the activities of hexokinase (HK), phosphofructo-1-kinase (PFK-1), and pyruvate kinase (PK) were markedly reduced in adipose tissue from HP-adapted rats. The activity of pyruvate kinase was partially reverted by diet replacement for 12 hours. The low-plasma insulin and high-glucagon levels in HP-fed rats may have played an important role in the reduction of adipose tissue glucose utilization in these animals. PMID:11586495

Brito, S R; Moura, M A; Kawashita, N H; Brito, M N; Kettelhut, I C; Migliorini, R H

2001-10-01

26

Glucose uptake and glycolytic flux in adipose tissue from rats adapted to a high-protein, carbohydrate-free diet  

Microsoft Academic Search

Rates of glucose uptake by epididymal and retroperitoneal adipose tissue in vivo, as well as rates of hexose uptake and glycolytic flux in isolated adipocytes, were determined in rats adapted to a high-protein, carbohydrate-free (HP) diet and in control rats fed a balanced (N) diet. Adaptation to the HP diet induced a significant reduction in rates of glucose uptake, estimated

S. R. C. Brito; M. A. F. Moura; N. H. Kawashita; M. N. Brito; I. C. Kettelhut; R. H. Migliorini

2001-01-01

27

Adipose tissue: friend or foe?  

PubMed

The perception of adipose tissue has changed considerably with the dramatic increase in the incidence of obesity and obesity-related comorbidities over the past 3 decades. Excess fat is no longer associated with wealth, but is instead recognized as a risk factor for many diseases. Adipose tissue is increasingly being identified as a vital, complex endocrine organ, and not simply as a fat store. Not all fat is created equal--regional, developmental, structural, and functional variations exist. Epicardial adipose tissue is a metabolically active organ producing a number of factors that modulate cardiac structure and function. The global epidemic of obesity and metabolic syndrome imposes a major disease burden, particularly of cardiovascular disease. In this Review, we describe the various types of adipose tissue--their developmental biology, differentiation, cell heterogeneity, and functional characteristics. We discuss the link between adipose tissue and inflammation, the signaling factors released by adipose tissue, as well as cardiac adiposity and its relevance to cardiovascular diseases. Finally, we review the myocardial regenerative potential of adipose-tissue-derived stem cells. We believe that a thorough understanding of adipose tissue is of great clinical value. PMID:23149834

Hassan, Mohamed; Latif, Najma; Yacoub, Magdi

2012-11-13

28

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

29

Biochemistry of adipose tissue: an endocrine organ.  

PubMed

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. PMID:23671428

Coelho, Marisa; Oliveira, Teresa; Fernandes, Ruben

2013-02-10

30

Cholesteryl ester transfer protein (CETP) mRNA abundance in human adipose tissue: relationship to cell size and membrane cholesterol content  

Microsoft Academic Search

Cholesteryl ester transfer protein (CETP) has a well-defined role in plasma neutral lipid transport. CETP synthesized by human adipose tissue may contribute to the plasma CETP pool. CETP mRNA abundance increases in subcutaneous adipose tissue in response to cholesterol feed- ing and we have hypothesized that CETP gene expression is regulated by a specific pool of cellular sterol. In the

Thierry Radeau; Paulina Lau; Malcolm Robb; Gerard Ailhaud; Ruth McPherson

31

Dietary proteins alter tissue-specific gene expression and adiposity in male Sprague-Dawley rats  

Technology Transfer Automated Retrieval System (TEKTRAN)

Dietary soy protein elicits anti-obesity effects in rodents. This study examined adiposity and gene expression in male Sprague-Dawley rats lifetime-fed diets containing casein (CAS), soy protein isolate (SPI), or casein supplemented with genistein (250 mg/kg diet; GEN). At 48 days of age, retroper...

32

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, A Y; Ledoux, S; Larger, E

2013-04-18

33

Expression of fatty-acid-handling proteins in human adipose tissue in relation to obesity and insulin resistance  

Microsoft Academic Search

Aims\\/hypothesis  Protein-mediated trans-membrane and intracellular fatty acid trafficking are becoming increasingly recognised as biochemically and physiologically important concepts. Obesity and insulin resistance are polygenic disorders, heavily influenced by environmental and life-style factors, and are virtually always associated with disturbed fatty acid metabolism in adipose and other tissues. The aim of this study was to investigate mRNA expression levels of fatty-acid-handling proteins

K. Gertow; K. H. Pietiläinen; H. Yki-Järvinen; J. Kaprio; A. Rissanen; P. Eriksson; A. Hamsten; R. M. Fisher

2004-01-01

34

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

35

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

PubMed

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

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

2013-03-28

36

Insulin effects in muscle and adipose tissue.  

PubMed

The major effects of insulin on muscle and adipose tissue are: (1) Carbohydrate metabolism: (a) it increases the rate of glucose transport across the cell membrane, (b) it increases the rate of glycolysis by increasing hexokinase and 6-phosphofructokinase activity, (c) it stimulates the rate of glycogen synthesis and decreases the rate of glycogen breakdown. (2) Lipid metabolism: (a) it decreases the rate of lipolysis in adipose tissue and hence lowers the plasma fatty acid level, (b) it stimulates fatty acid and triacylglycerol synthesis in tissues, (c) it increases the uptake of triglycerides from the blood into adipose tissue and muscle, (d) it decreases the rate of fatty acid oxidation in muscle and liver. (3) Protein metabolism: (a) it increases the rate of transport of some amino acids into tissues, (b) it increases the rate of protein synthesis in muscle, adipose tissue, liver, and other tissues, (c) it decreases the rate of protein degradation in muscle (and perhaps other tissues). These insulin effects serve to encourage the synthesis of carbohydrate, fat and protein, therefore, insulin can be considered to be an anabolic hormone. PMID:21864752

Dimitriadis, George; Mitrou, Panayota; Lambadiari, Vaia; Maratou, Eirini; Raptis, Sotirios A

2011-08-01

37

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

2013-08-14

38

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

PubMed Central

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

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

2012-01-01

39

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

PubMed

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

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

2013-06-14

40

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

PubMed Central

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

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

2012-01-01

41

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

PubMed

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

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

2011-05-20

42

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

2012-09-24

43

Engineering of volume-stable adipose tissues  

Microsoft Academic Search

Autologous adipose tissues have been clinically used for augmentation of soft tissues lost due to mastectomy or lumpectomy in plastic and reconstructive surgery. However, this therapy has problems of absorption and subsequent volume loss of the implanted adipose tissues. In this study, volume-stable adipose tissues were engineered in vivo using mechanical support structures fabricated from biodegradable synthetic polymers. Dome-shaped mechanical

Seung-Woo Cho; Sang-Soo Kim; Jong Won Rhie; Hyun Mi Cho; Cha Yong Choi; Byung-Soo Kim

2005-01-01

44

The developmental origins of adipose tissue.  

PubMed

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

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

2013-10-01

45

The dietary protein/carbohydrate ratio differentially modifies lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation.  

PubMed

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. PMID:23874950

Velázquez-Villegas, Laura A; Tovar, Armando R; López-Barradas, Adriana M; Torres, Nimbe

2013-07-16

46

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

47

Human collagen isolated from adipose tissue.  

PubMed

Collagen, the most abundant protein in vertebrates, is a useful biomaterial in pharmaceutical and medical industries. So far, most collagen has been extracted from animals and cadavers. Herein, we suggest human adipose tissue, which is routinely abandoned after liposuction, as a plentiful source of human collagen. In this study, human collagen was obtained from adipose tissue through two successive major steps: (i) extraction of the extracellular matrix (ECM) by pulverization, centrifugation, alkaline, and alcohol treatment; (ii) isolation of collagen from ECM by pepsin treatment in dilute acetic acid. The purified human adipose-derived collagen was characterized by Fourier transform infrared spectroscopy, polyacrylamide gel electrophoresis, amino acid analysis, and circular dichroism spectroscopy. The extracted collagen showed a typical triple helix structure, good thermal stability due to abundant imino acids, and high solubility at acidic pH. The collagen greatly facilitated the adhesion and proliferation of human adipose-derived stem cells and normal human dermal fibroblasts on polystyrene plates. These results suggest that human adipose tissue obtained by liposuction can provide human collagen for use in cosmetics, pharmaceutics, and medicine. PMID:22549937

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

2012-06-08

48

Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals  

PubMed Central

Background Excess adipose tissue and sarcopenia presents a multifaceted clinical challenge that promotes morbidity and mortality in the obese, elderly population. Unfortunately, the mortality risks of muscle loss may outweigh the potential benefits of weight loss in the elderly. We have previously demonstrated the effectiveness of whey protein and essential amino acids towards the preservation of lean tissue, even under the conditions of strict bedrest in the elderly. Methods In the context of caloric restriction-based weight loss, we hypothesized that a similar formulation given as a meal replacement (EAAMR) would foster the retention of lean tissue through an increase in the skeletal muscle fractional synthesis rate (FSR). We also proposed that EAAMR would promote the preferential loss of adipose tissue through the increased energy cost of skeletal muscle FSR. We recruited and randomized 12 elderly individuals to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (800 kcal/day): 1) EAAMR or a 2) competitive meal replacement (CMR) in conjunction with 400 kcal of solid food that totaled 1200 kcal/day designed to induce 7% weight loss. Combined with weekly measurements of total body weight and body composition, we also measured the acute change in the skeletal muscle FSR to EAAMR and CMR. Results By design, both groups lost ~7% of total body weight. While EAAMR did not promote a significant preservation of lean tissue, the reduction in adipose tissue was greater in EAAMR compared to CMR. Interestingly, these results corresponded to an increase in the acute skeletal muscle protein FSR. Conclusion The provision of EAAMR during caloric restriction-induced weight loss promotes the preferential reduction of adipose tissue and the modest loss of lean tissue in the elderly population.

2012-01-01

49

AcetylCoA carboxylase and fatty acid synthase activity and immunodetectable protein in adipose tissues of ruminants: Effect of temperature and feeding level1,2  

Microsoft Academic Search

To gain insights into the regulation of fat synthesis, we have investigated the effect of cold environmental exposure and feed restriction of sheep on activity and immunodetectable protein content of acetyl-CoA carboxylase (ACC) and fatty acid synthase in adipose tissue. Subcutaneous and mesenteric adi- pose tissues were collected at slaughter from sheep ex- posed to either cold (0 ± 2°C)

J. A. Moibi; E. D. Ekpe; R. J. Christopherson

50

Lean Phenotype and Resistance to Diet-Induced Obesity in Vitamin D Receptor Knockout Mice Correlates with Induction of Uncoupling Protein-1 in White Adipose Tissue  

PubMed Central

Increased adiposity is a feature of aging in both mice and humans, but the molecular mechanisms underlying age-related changes in adipose tissue stores remain unclear. In previous studies, we noted that 18-month-old normocalcemic vitamin D receptor (VDR) knockout (VDRKO) mice exhibited atrophy of the mammary adipose compartment relative to wild-type (WT) littermates, suggesting a role for VDR in adiposity. Here we monitored body fat depots, food intake, metabolic factors, and gene expression in WT and VDRKO mice on the C57BL6 and CD1 genetic backgrounds. Regardless of genetic background, both sc and visceral white adipose tissue depots were smaller in VDRKO mice than WT mice. The lean phenotype of VDRKO mice was associated with reduced serum leptin and compensatory increased food intake. Similar effects on adipose tissue, leptin and food intake were observed in mice lacking Cyp27b1, the 1?-hydroxylase enzyme that generates 1,25-dihydroxyvitamin D3, the VDR ligand. Although VDR ablation did not reduce expression of peroxisome proliferator-activated receptor-? or fatty acid synthase, PCR array screening identified several differentially expressed genes in white adipose tissue from WT and VDRKO mice. Uncoupling protein-1, which mediates dissociation of cellular respiration from energy production, was greater than 25-fold elevated in VDRKO white adipose tissue. Consistent with elevation in uncoupling protein-1, VDRKO mice were resistant to high-fat diet-induced weight gain. Collectively, these studies identify a novel role for 1,25-dihydroxyvitamin D3 and the VDR in the control of adipocyte metabolism and lipid storage in vivo.

Narvaez, Carmen J.; Matthews, Donald; Broun, Emily; Chan, Michelle; Welsh, JoEllen

2009-01-01

51

Lean phenotype and resistance to diet-induced obesity in vitamin D receptor knockout mice correlates with induction of uncoupling protein-1 in white adipose tissue.  

PubMed

Increased adiposity is a feature of aging in both mice and humans, but the molecular mechanisms underlying age-related changes in adipose tissue stores remain unclear. In previous studies, we noted that 18-month-old normocalcemic vitamin D receptor (VDR) knockout (VDRKO) mice exhibited atrophy of the mammary adipose compartment relative to wild-type (WT) littermates, suggesting a role for VDR in adiposity. Here we monitored body fat depots, food intake, metabolic factors, and gene expression in WT and VDRKO mice on the C57BL6 and CD1 genetic backgrounds. Regardless of genetic background, both sc and visceral white adipose tissue depots were smaller in VDRKO mice than WT mice. The lean phenotype of VDRKO mice was associated with reduced serum leptin and compensatory increased food intake. Similar effects on adipose tissue, leptin and food intake were observed in mice lacking Cyp27b1, the 1alpha-hydroxylase enzyme that generates 1,25-dihydroxyvitamin D(3), the VDR ligand. Although VDR ablation did not reduce expression of peroxisome proliferator-activated receptor-gamma or fatty acid synthase, PCR array screening identified several differentially expressed genes in white adipose tissue from WT and VDRKO mice. Uncoupling protein-1, which mediates dissociation of cellular respiration from energy production, was greater than 25-fold elevated in VDRKO white adipose tissue. Consistent with elevation in uncoupling protein-1, VDRKO mice were resistant to high-fat diet-induced weight gain. Collectively, these studies identify a novel role for 1,25-dihydroxyvitamin D(3) and the VDR in the control of adipocyte metabolism and lipid storage in vivo. PMID:18845643

Narvaez, Carmen J; Matthews, Donald; Broun, Emily; Chan, Michelle; Welsh, JoEllen

2008-10-09

52

Increased mitogen-activated protein kinase expression and activity in white adipose tissue of ventromedial hypothalamus-lesioned rats  

Microsoft Academic Search

Summary   Ventromedial hypothalamus lesions in rats induce hyperphagia and hyperinsulinaemia associated with a rapid growth of white\\u000a adipose tissue resulting in massive obesity. It has been shown previously that at an early stage after the lesion, during\\u000a the dynamic phase of obesity, the white adipose tissue is hyper-responsive to insulin. In the present work, we show that the\\u000a effects of

M. Combettes-Souverain; L. Pénicaud; P. Ferré; T. Issad

1997-01-01

53

Time course of high-fat diet-induced reductions in adipose tissue mitochondrial proteins: potential mechanisms and the relationship to glucose intolerance.  

PubMed

Increasing evidence suggests that reduced adipose tissue mitochondrial content is associated with the pathogenesis of type 2 diabetes. These investigations have utilized severely insulin-resistant rodent models. Thus, it is difficult to ascertain the potential mechanisms that initiate these changes and whether reductions in adipose mitochondria are an initiating event in the development of impaired glucose homeostasis. Thus, we sought to determine the time course of high-fat diet-induced reductions of mitochondrial content in epididymal adipose tissue in relation to changes in purported mediators of mitochondrial biogenesis and the development of impaired glucose homeostasis. Male Wistar rats were fed a high-fat diet ( approximately 59% of kcals from fat) for 2, 4, or 6 wk. Six weeks of high-fat feeding resulted in reductions in CORE I, COX IV, cytochrome c, HSP60, relative mtDNA copy number, and PGC-1alpha expression. These changes were not associated with decreases in eNOS and AMPK or increases in markers of oxidative stress. Interestingly, ex vivo treatment of adipose tissue cultures with palmitate led to decreases in PGC-1alpha expression and COX IV and CORE I protein content as observed in vivo. Thus, the high-fat diet-induced reductions in adipose tissue mitochondrial proteins may be mediated by increases in plasma fatty acids. Importantly, reductions in adipose tissue mitochondrial content occurred after the development of impaired glucose homeostasis. Thus, reductions in adipose tissue mitochondrial proteins are most likely not a causal event in the development of impaired glucose homeostasis. PMID:18780775

Sutherland, Lindsey N; Capozzi, Lauren C; Turchinsky, N Joan; Bell, Rhonda C; Wright, David C

2008-09-09

54

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

55

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

56

AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin: a randomised glycaemia-controlled crossover study  

Microsoft Academic Search

Aims\\/hypothesis  The hypoglycaemic actions of metformin have been proposed to be mediated by hepatic AMP-activated protein kinase (AMPK). As\\u000a the effects of metformin and the role of AMPK in adipose tissue remain poorly characterised, we examined the effect of metformin\\u000a on AMPK activity in adipose tissue of individuals with type 2 diabetes in a randomised glycaemia-controlled crossover study.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Twenty men with

J. G. Boyle; P. J. Logan; G. C. Jones; M. Small; N. Sattar; J. M. C. Connell; S. J. Cleland; I. P. Salt

2011-01-01

57

Gene expression in human brown adipose tissue.  

PubMed

Brown adipose tissue (BAT) has profound effects on body weight and metabolism in rodents. Recent reports show that human adults have significant amounts of BAT. Our aim was to study the gene expression profile of human BAT. Biopsies of adipose tissue with brown-red color and subcutaneous white adipose tissue (WAT) were obtained from 24 patients undergoing surgery in the thyroid region. Intrascapular BAT and epididymal WAT biopsies were obtained from 10 mice. Expression was analyzed by DNA microarray, real-time PCR and immunohistochemistry. Using the expression of the brown adipocyte-specific gene uncoupling protein 1 (UCP1) as a marker, approximately half of the human brown-red adipose tissue biopsies taken in the thyroid region contained BAT, and the presence of cells with brown adipocyte morphology was also verified by histology. Microarray analysis of 9 paired human BAT and WAT samples showed that 17 genes had at least a 4-fold higher expression in BAT compared to WAT and five of them (CKMT1, KCNK3, COBL, HMGCS2, TGM2) were verified using real-time PCR (P<0.05 for all). In addition, immunohistochemistry showed that the UCP1, KCNK3 and CKMT1 proteins are expressed in brown adipocytes. Except for UCP1 and KCNK3, the genes overexpressed in human BAT were not overexpressed in mouse BAT compared to mouse WAT. Our analysis identified genes that are differentially expressed in human BAT compared to WAT. The results also show that there are species-specific differences in BAT gene expression and this emphasizes the need for further molecular characterization of human BAT to clarify the mechanisms involved in regulated heat production in humans. PMID:21125211

Svensson, Per-Arne; Jernås, Margareta; Sjöholm, Kajsa; Hoffmann, Jenny M; Nilsson, Bengt E; Hansson, Magnus; Carlsson, Lena M S

2010-12-01

58

Linear viscoelastic behavior of subcutaneous adipose tissue  

Microsoft Academic Search

Subcutaneous adipose tissue contributes to the overall mechanical behavior of the skin. Until today, however, no thorough constitutive model is available for this layer of tissue. As a start to the development of such a model, the objective of this study was to measure and describe the linear viscoelastic behavior of subcutaneous adipose tissue. Although large strains occur in vivo,

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

2008-01-01

59

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

60

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

61

Vascular augmentation of free adipose tissue grafts  

Microsoft Academic Search

Summary  The effect of vascular implantation on the healing of free adipose tissue grafts was studied experimentally in rats. Adipose tissue resected from the parauterine pad was transplanted around the femoral vascular bundle. Two biological variants of the method were used: transplantation to (a) the freshly mobilized vascular bundle and (b) a bundle prepared three days previously. Implants made directly under

J. Šmahel; V. E. Meyer; K. Schütz

1990-01-01

62

Regulation of cholesterol storage in adipose tissue  

Microsoft Academic Search

Adipose tissue is a major site of cholesterol storage. In an attempt to define mechanisms controlling this process, a variety of nutritional and metabolic alterations were employed and their effects on adipose tissue cholesterol levels were deter- mined by direct chemical analysis. When rats were raised on Purina chow, a linear increase in the cholesterol\\/DNA ratio in relation to animal

A. Angel; J. Farkas

2009-01-01

63

Molecular links between aging and adipose tissue  

Microsoft Academic Search

White adipose tissue now emerges as a pivotal organ controlling lifespan. Calorie restriction, which so far extends lifespan in all organisms, primarily affects energy stores in adipose tissue. Genetic manipulations aiming at modifying fat mass also impact on the duration of life in several model organisms. We recently proposed that silent information regulator 2 (SIR2) ortholog, sirtuin 1 (SIRT1), the

F Picard; L Guarente

2005-01-01

64

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

PubMed

The intake of whey protein isolate (WPI) is known to reduce high-fat diet (HFD)-induced body-weight gain and adiposity. However, the molecular mechanisms are not fully understood. To this end, we fed C57BL/6J mice for 8 weeks with diets containing 10 % energy as fat (low-fat diet, LFD) or 45 % energy as fat (HFD) enriched with either 20 % energy as casein (LFD and HFD) or WPI (high-fat WPI). Metabolic parameters and the hypothalamic and epididymal adipose tissue expression of energy balance-related genes were investigated. The HFD increased fat mass and plasma leptin levels and decreased the dark-phase energy intake, meal number, RER, and metabolic (VO2 and heat) and locomotor activities compared with the LFD. The HFD increased the hypothalamic tissue mRNA expression of the leptin receptor, insulin receptor (INSR) and carnitine palmitoyltransferase 1b (CPT1b). The HFD also reduced the adipose tissue mRNA expression of GLUT4 and INSR. In contrast, WPI reduced fat mass, normalised dark-phase energy intake and increased meal size in HFD-fed mice. The dietary protein did not have an impact on plasma leptin, insulin, glucose or glucagon-like peptide 1 levels, but increased plasma TAG levels in HFD-fed mice. At a cellular level, WPI significantly reduced the HFD-associated increase in the hypothalamic tissue mRNA expression of the leptin receptor, INSR and CPT1b. Also, WPI prevented the HFD-induced reduction in the adipose tissue mRNA expression of INSR and GLUT4. In comparison with casein, the effects of WPI on energy intake and hypothalamic and adipose tissue gene expression may thus represent a state of reduced susceptibility to weight gain on a HFD. PMID:23731955

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

2013-06-01

65

Effect of cold acclimation on brown adipose tissue fatty acid synthesis in rats adapted to a high-protein, carbohydrate-free diet  

Microsoft Academic Search

The effect of cold acclimation on brown adipose tissue (BAT) fatty acid synthesis was investigated in rats adapted to a high-protein, carbohydrate-free diet. At an ambient temperature (25[deg ]C), rates of fatty acid synthesis in BAT from rats adapted to the high-protein diet were reduced to 27% of rats fed the balanced diet and increased markedly after cold acclimation (10

M. A. F. Moura; N. H. Kawashita; S. M. R. C. Brito; M. N. Brito; I. C. Kettelhut; R. H. Migliorini

2001-01-01

66

Activation of Cholesterol Synthesis in Preference to Fatty Acid Synthesis in Liver and Adipose Tissue of Transgenic Mice Overproducing Sterol Regulatory Element-binding Protein2  

Microsoft Academic Search

We produced transgenic mice that express a dominant-posi- tive truncated form of sterol regulatory element-binding protein-2 (SREBP-2) in liver and adipose tissue. The en- coded protein lacks the membrane-binding and COOH-ter- minal regulatory domains, and it is therefore not susceptible to negative regulation by cholesterol. Livers from the trans- genic mice showed increases in mRNAs encoding multi- ple enzymes of

Jay D. Horton; Iichiro Shimomura; Michael S. Brown; Robert E. Hammer; Joseph L. Goldstein; Hitoshi Shimano

1998-01-01

67

Resistance exercise did not alter intramuscular adipose tissue but reduced retinol-binding protein-4 concentration in individuals with type 2 diabetes mellitus.  

PubMed

Lipid accumulation in muscle is associated with diminished insulin sensitivity. It was hypothesized that resistance exercise decreases muscular adipose tissue and reduces the level of retinol-binding protein-4 (RBP4), which is linked to adipose tissue and insulin sensitivity in diabetics. Forty-four women with type 2 diabetes were randomly assigned to three groups for a period of 12 weeks: control (asked to maintain a sedentary lifestyle); resistance exercise (elastic band exercise at moderate intensity five times per week); and aerobic exercise (walking for 60 min at moderate intensity five times per week). Subcutaneous (SCAT), subfascial (SFAT) and intramuscular (IMAT) adipose tissues at mid-thigh level were assessed using computed tomography, and RBP4 level and insulin sensitivity (fractional disappearance rate of insulin, k(ITT)) were assessed before and after intervention. Changes in SCAT, SFAT, IMAT, RBP4 and k(ITT) were similar among the three groups. Within-group analysis revealed that body mass index and waist circumference decreased significantly in both exercise groups, but RBP4 decreased significantly only with resistance exercise. Resistance exercise did not alter muscular adipose tissue or improve insulin sensitivity. PMID:20819415

Ku, Y H; Han, K A; Ahn, H; Kwon, H; Koo, B K; Kim, H C; Min, K W

68

Mechanical homeostasis regulating adipose tissue volume  

PubMed Central

Background The total body adipose tissue volume is regulated by hormonal, nutritional, paracrine, neuronal and genetic control signals, as well as components of cell-cell or cell-matrix interactions. There are no known locally acting homeostatic mechanisms by which growing adipose tissue might adapt its volume. Presentation of the hypothesis Mechanosensitivity has been demonstrated by mesenchymal cells in tissue culture. Adipocyte differentiation has been shown to be inhibited by stretching in vitro, and a pathway for the response has been elucidated. In humans, intermittent stretching of skin for reconstructional purposes leads to thinning of adipose tissue and thickening of epidermis – findings matching those observed in vitro in response to mechanical stimuli. Furthermore, protracted suspension of one leg increases the intermuscular adipose tissue volume of the limb. These findings may indicate a local homeostatic adipose tissue volume-regulating mechanism based on movement-induced reduction of adipocyte differentiation. This function might, during evolution, have been of importance in confined spaces, where overgrowth of adipose tissue could lead to functional disturbance, as for instance in the turtle. In humans, adipose tissue near muscle might in particular be affected, for instance intermuscularly, extraperitoneally and epicardially. Mechanical homeostasis might also contribute to protracted maintainment of soft tissue shape in the face and neck region. Testing of the hypothesis Assessment of messenger RNA-expression of human adipocytes following activity in adjacent muscle is planned, and study of biochemical and volumetric adipose tissue changes in man are proposed. Implications of the hypothesis The interpretation of metabolic disturbances by means of adipose tissue might be influenced. Possible applications in the head and neck were discussed.

Svedman, Paul

2007-01-01

69

Engineering of volume-stable adipose tissues.  

PubMed

Autologous adipose tissues have been clinically used for augmentation of soft tissues lost due to mastectomy or lumpectomy in plastic and reconstructive surgery. However, this therapy has problems of absorption and subsequent volume loss of the implanted adipose tissues. In this study, volume-stable adipose tissues were engineered in vivo using mechanical support structures fabricated from biodegradable synthetic polymers. Dome-shaped mechanical support structures were fabricated by reinforcing poly(glycolic acid) fiber-based matrices with poly(L-lactic acid). The support structures were placed into subcutaneous pockets of athymic mice, and human preadipocytes suspended in fibrin matrix were injected into the space under the support structures (group I). Injection of either fibrin matrix without preadipocytes under the support structures (group II) or fibrin matrix containing preadipocytes into subcutaneous spaces with no support structures (group III) served as controls. Six weeks after implantation, the original implant volume was maintained approximately in groups I and II, whereas, group III showed significant implant shrinkage. The compressive modulus of the mechanical support structures did not change significantly over 6-week incubation in phosphate-buffered saline at 37 degrees C. Histological analyses of the implants showed regeneration of adipose tissues in group I. In contrast, groups II and III did not show extensive adipose tissue formation. This study demonstrates that volume-stable adipose tissues can be engineered in vivo using mechanical support structures. This technique offers the potential for augmentation of adipose tissues with volume conservation. PMID:15621248

Cho, Seung-Woo; Kim, Sang-Soo; Rhie, Jong Won; Cho, Hyun Mi; Choi, Cha Yong; Kim, Byung-Soo

2005-06-01

70

Differential scanning calorimetry of porcine adipose tissues  

Microsoft Academic Search

Differential scanning calorimetry (DSC) was used for the direct analysis of melting properties in porcine subcutaneous, intermuscular, and kidney leaf adipose tissue by heating at a constant ratio of +5°C\\/min from 4 to 90°C. Melting curves for adipose tissues as well as fat extracted from the associated tissues by chloroform–methanol were generated using DSC. Major peaks in DSC curves were

K. Sasaki; M. Mitsumoto; T. Nishioka; M. Irie

2006-01-01

71

Glucose uptake, glucose transporter GLUT4, and glycolytic enzymes in brown adipose tissue from rats adapted to a high-protein diet  

Microsoft Academic Search

In vivo rates of glucose uptake, insulin-responsive glucose transporter (GLUT4) content, and activities of glycolytic enzymes were determined in brown adipose tissue (BAT) from rats adapted to a high-protein, carbohydrate-free (HP) diet. Adaptation to the HP diet resulted in marked decreases in BAT glucose uptake and in GLUT4 content. Replacement of the HP diet by a balanced control diet for

N. H. Kawashita; M. N. Brito; S. R. C. Brito; M. A. F. Moura; W. T. L. Festuccia; M. A. R. Garofalo; U. F. Machado; I. C. Kettelhut; R. H. Migliorini

2002-01-01

72

Uncoupling Protein2 and -3 Messenger Ribonucleic Acids in Adipose Tissue and Skeletal Muscle of Healthy Males: Variability, Factors Affecting Expression, and Relation to Measures of Metabolic Rate  

Microsoft Academic Search

Mitochondrial uncoupling protein-2 and -3 (UCP2 and UCP3) may be involved in the modulation of resting metabolic rate and energy balance. To investigate their variability, the influence of this on the variability of energy expenditure, and potential regulatory factors of the expression of the corresponding genes, we measured their mes- senger ribonucleic acids (mRNAs) in muscle and white adipose tissue

MICHEL BOIVIN; ANNE CAMIRAND; FRANCESCO CARLI; L. JOHN HOFFER; J. ENRIQUE SILVA

2010-01-01

73

Infusion of a Lipid Emulsion Modulates AMPK and Related Proteins in Rat Liver, Muscle, and Adipose Tissues  

Microsoft Academic Search

The primary objective of this study was to investigate the impact of lipid oversupply on the AMPK pathway in skeletal muscle, liver, and adipose tissue. Male Wistar rats were infused with lipid emulsion (LE) or phosphate-buffered saline for 5 h\\/day for 6 days. Muscles exposed to LE for 6 days exhibited increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation, along with

Sarit Anavi; Erez Ilan; Oren Tirosh; Zecharia Madar

2010-01-01

74

Acute inflammation plays a limited role in the regulation of adipose tissue COL1A1 protein abundance  

Microsoft Academic Search

Obesity is an inflammatory condition that is also associated with increased extracellular matrix (ECM) gene expression. However, a direct link between adipose tissue inflammation and ECM gene expression has not been established. Therefore, we determined the effect of chronic inflammation induced by obesity and acute inflammation by lipopolysaccharide (LPS) challenge on ECM genes including biglycan (BGN), collagen 1A1 (COL1A1) and

Venkata J. Adapala; Sunday A. Adedokun; Robert V. Considine; Kolapo M. Ajuwon

75

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

Microsoft Academic Search

The study of thermoinduced changes of optical properties of adipose tissue is very actual problem. We made the optical model of thermo-sensitive heterophase medium (adipose tissue). Here the elementary adipose cell will consist of a cube which basic volume will contain a adipose ball, everything else- water. The adipose ball will contain liquid and crystal phases. Has been created the

A. V. Belikov; O. A. Smolyanskaya

2007-01-01

76

Serum angiopoietin-like 4 protein levels and expression in adipose tissue are inversely correlated with obesity in monozygotic twins.  

PubMed

Animal studies have suggested that angiopoietin-like 4 (Angptl4) regulates adiposity through central and peripheral mechanisms. The aim of this study was to investigate whether serum concentration and adipose tissue expression of Angptl4 are associated with obesity-related parameters in humans. Altogether, 75 dizygotic (DZ) and 46 monozygotic (MZ) twin pairs were studied, from the FinnTwin12 and FinnTwin16 cohorts. Among the MZ pairs, 21 were discordant for body mass index (BMI) (intra-pair BMI-difference >2.5 kg/m², age 23-33 years). Serum Angptl4 (s-Angptl4) levels were measured by ELISA, and adipose tissue gene expression was analyzed by genome-wide transcript profiling. In MZ twin pairs discordant for BMI, s-Angptl4 and adipose tissue ANGPTL4 mRNA (at-ANGPTL4) levels were significantly decreased (P = 0.04 and P = 0.03, respectively) in obese twins as compared with their nonobese cotwins. In all twins, intra-pair differences in s-Angptl4 levels were inversely correlated with intra-pair differences in BMI (r = -0.27, P = 0.003). In individual MZ twins, at-ANGPTL4 expression was inversely correlated with BMI (r = -0.44, P = 0.001) and positively correlated with at-LIPE (r = 0.24, P = 0.01) and at-ABHD5 (r = 0.41, P = 0.005) expression. Our results demonstrated that variation in Angptl4 concentration was only modestly accounted for by genetic factors and suggest a role for Angptl4 in acquired obesity in humans. PMID:21596930

Robciuc, Marius R; Naukkarinen, Jussi; Ortega-Alonso, Alfredo; Tyynismaa, Henna; Raivio, Taneli; Rissanen, Aila; Kaprio, Jaakko; Ehnholm, Christian; Jauhiainen, Matti; Pietiläinen, Kirsi H

2011-05-19

77

Serum angiopoietin-like 4 protein levels and expression in adipose tissue are inversely correlated with obesity in monozygotic twins  

PubMed Central

Animal studies have suggested that angiopoietin-like 4 (Angptl4) regulates adiposity through central and peripheral mechanisms. The aim of this study was to investigate whether serum concentration and adipose tissue expression of Angptl4 are associated with obesity-related parameters in humans. Altogether, 75 dizygotic (DZ) and 46 monozygotic (MZ) twin pairs were studied, from the FinnTwin12 and FinnTwin16 cohorts. Among the MZ pairs, 21 were discordant for body mass index (BMI) (intra-pair BMI-difference >2.5 kg/m2, age 23–33 years). Serum Angptl4 (s-Angptl4) levels were measured by ELISA, and adipose tissue gene expression was analyzed by genome-wide transcript profiling. In MZ twin pairs discordant for BMI, s-Angptl4 and adipose tissue ANGPTL4 mRNA (at-ANGPTL4) levels were significantly decreased (P = 0.04 and P = 0.03, respectively) in obese twins as compared with their nonobese cotwins. In all twins, intra-pair differences in s-Angptl4 levels were inversely correlated with intra-pair differences in BMI (r = ?0.27, P = 0.003). In individual MZ twins, at-ANGPTL4 expression was inversely correlated with BMI (r = ?0.44, P = 0.001) and positively correlated with at-LIPE (r = 0.24, P = 0.01) and at-ABHD5 (r = 0.41, P = 0.005) expression. Our results demonstrated that variation in Angptl4 concentration was only modestly accounted for by genetic factors and suggest a role for Angptl4 in acquired obesity in humans

Robciuc, Marius R.; Naukkarinen, Jussi; Ortega-Alonso, Alfredo; Tyynismaa, Henna; Raivio, Taneli; Rissanen, Aila; Kaprio, Jaakko; Ehnholm, Christian; Jauhiainen, Matti; Pietilainen, Kirsi H.

2011-01-01

78

Adipose Tissue Quantification by Imaging Methods: A Proposed Classification  

Microsoft Academic Search

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

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

2003-01-01

79

[Adipose tissue. Cellular and molecular principles].  

PubMed

For many decades, cutaneous biology research has primarily focused on the dermis and epidermis. In recent years the subcutaneous far has attracted the attention of basic science, cosmetology and industry. Numerous new approaches are in the process of development, enabling us to better understand assembly, differentiation and function of adipose tissue. To understand these developments a background in the cellular and molecular basics of adipose tissue is indispensable. This state-of the art article provides the needed information. PMID:20871971

Grether-Beck, S; Krutmann, J

2010-10-01

80

Hunting for human obesity genes? Look in the adipose tissue!  

PubMed

Over-eating and physical inactivity in combination with genetic factors play the most important roles in the development of over weight in humans. The common genetic components behind excess accumulation of body fat are so far unknown. Studies of candidate genes indicate that most of the genes that associate with obesity control important functions of adipose tissue as well. Furthermore, structural variations in these genes may alter adipose tissue function in a way that promotes obesity. The genes which both are functional in human adipose tissue and associate with obesity are: hormone sensitive lipase, beta2 and beta3-adrenoceptors, tumor necrosis factor alpha, low density lipoprotein receptor, uncoupling protein-1 and peroxisome proliferator activated receptor gamma-2. Other genes are mostly important for obesity among women (for example beta2 -and beta3-adrenoceptors, low density lipoprotein receptor and tumor necrosis factor alpha). Some of these genes may promote obesity by gene-gene interactions (for example beta3-adrenoceptors and uncoupling protein-1) or gene-environmental interactions (for example beta2-adrenoceptors and physical activity). Few genes with no known function in adipose tissue have shown a firm association with excess body fat. The latter suggests that the important human obesity genes also control adipose tissue function. Therefore it might be of value to focus the further hunt for obesity genes on the fat tissue. PMID:11126244

Arner, P

2000-11-01

81

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

PubMed Central

Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

Herman, Mark A.; She, Pengxiang; Peroni, Odile D.; Lynch, Christopher J.; Kahn, Barbara B.

2010-01-01

82

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

83

Elevated AT1 receptor protein but lower angiotensin II-binding in adipose tissue of rats with monosodium glutamate-induced obesity.  

PubMed

Age-related hypertrophy of adipose tissue has been associated with a significant decrease in the number of angiotensin II receptors. The aim of this study was to investigate the characteristics of angiotensin II receptors in hypertrophic adipose tissue in animal obesity model using rats postnatally treated with monosodium glutamate. Angiotensin II is known to induce hypertrophy in several tissues of the cardiovascular system and might do the same in fat tissue. The expression and binding properties of angiotensin II AT(1) receptors in epididymal fat tissue of adult rats were studied using membrane-binding, RT-PCR, and immunoblotting. The amount of AT(1) receptor mRNA did not differ significantly between obese and control rats. Despite that glutamate-treated rats displayed approximately 4-times more AT(1) receptor immunoreactive protein content in fat tissue cell membranes than the controls did. In contrast, binding experiments showed a significant (40.3 +/- 6.2 %) decrease of (125)I-Sar(1)-Ile(8)-angiotensin II-binding to fat tissue cell membranes in obese rats compared to controls. In conclusion, the present study provides evidence for the low binding properties associated with an accumulation of AT(1) receptor protein in cell membranes of the fat tissue of rats with glutamate-induced obesity. Discrepancies among angiotensin II-binding, AT(1) receptor protein, and AT(1) receptor mRNA levels indicate a possible defect in the receptor protein, which remains to be identified. The results obtained support a role of angiotensin II and AT(1) receptors in the pathogenesis of obesity. PMID:11753755

Pintérová, L; Zelezná, B; Ficková, M; Macho, L; Krizanová, O; Jezová, D; Zórad, S

2001-12-01

84

FAT/CD36 regulates PEPCK expression in adipose tissue.  

PubMed

Fatty acid translocase (FAT)/CD36 has been extensively studied for its role in facilitating fatty acid uptake. Recent findings have also demonstrated that this protein regulates adipocyte lipolysis and may modulate fatty acid reesterification. As FAT/CD36 has been shown to control the expression of genes involved in fatty acid oxidation in adipocytes, we reasoned that this protein might also control the expression of enzymes involved in fatty acid reesterification. In adipose tissue from FAT/CD36 knockout (KO) mice, we found that glycerol and fatty acid release were reduced and this was associated with reductions in adipose triglyceride lipase. Decreases in lipolysis were paralleled by increases in the free fatty acid-to-glycerol ratio and reductions in primary and fractional rates of fatty acid reesterfication in cultured adipose tissue from FAT/CD36 KO mice. Reductions in reesterfication were associated with decreases in the mRNA expression and protein content of phosphoenolpyruvate carboxykinase (PEPCK). To determine if reductions in lipolysis could lead to decreases in PEPCK mRNA expression, we treated cultured mouse adipose tissue with the lipase inhibitor CAY10499 (2 ?M) and found that this resulted in an ?50% reduction in PEPCK mRNA expression. Treatment with hexarelin (10 ?M, 12 h), a CD36 agonist, increased PEPCK mRNA expression independent of lipolysis. Collectively, our results provide novel evidence that FAT/CD36 regulates PEPCK in adipose tissue and that this could be secondary to reductions in lipolysis. PMID:23302781

Wan, Zhongxiao; Matravadia, Sarthak; Holloway, Graham P; Wright, David C

2013-01-09

85

Regional variation in plasminogen activator inhibitor-1 expression in adipose tissue from obese individuals.  

PubMed

High plasma plasminogen activator inhibitor-1 (PAI-1) activity is a frequent finding in obesity and adipose tissue has recently been suggested to be a source of circulating PAI-1 in humans. In the present study, differences in adipose tissue gene expression and protein secretion rate of PAI-1 between subcutaneous and visceral adipose tissue was analysed in specimens obtained from 22 obese individuals. The secretion rate of PAI-1 was two-fold higher in subcutaneous adipose tissue than in visceral adipose tissue (292 +/- 50 vs 138 +/- 24 ng PAI-1/10(7) cells, P <0.05). In accordance with the secretion data, subcutaneous adipose tissue contained about three-fold higher levels of PAI-1 mRNA than visceral adipose tissue (2.43 +/- 0.37 vs 0.81 +/- 0.12 attomole PAI-1 mRNA/microg total RNA, P <0.00 ). PAI-1 secretion from subcutaneous but not from visceral adipose tissue correlated significantly with cell size (r = 0.43, P<0.05). In summary, subcutaneous adipose tissue secreted greater amounts of PAI-1 and had a higher PAI-1 gene expression than visceral adipose tissue from the same obese individuals. Bearing in mind that subcutaneous adipose tissue is the largest fat depot these finding may be important for the coagulation abnormalities associated with obesity. PMID:10780314

Eriksson, P; Van Harmelen, V; Hoffstedt, J; Lundquist, P; Vidal, H; Stemme, V; Hamsten, A; Arner, P; Reynisdottir, S

2000-04-01

86

[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

2012-07-13

87

Vitamin D signalling in adipose tissue.  

PubMed

Vitamin D deficiency and the rapid increase in the prevalence of obesity are both considered important public health issues. The classical role of vitamin D is in Ca homoeostasis and bone metabolism. Growing evidence suggests that the vitamin D system has a range of physiological functions, with vitamin D deficiency contributing to the pathogenesis of several major diseases, including obesity and the metabolic syndrome. Clinical studies have shown that obese individuals tend to have a low vitamin D status, which may link to the dysregulation of white adipose tissue. Recent studies suggest that adipose tissue may be a direct target of vitamin D. The expression of both the vitamin D receptor and 25-hydroxyvitamin D 1?-hydroxylase (CYP27B1) genes has been shown in murine and human adipocytes. There is evidence that vitamin D affects body fat mass by inhibiting adipogenic transcription factors and lipid accumulation during adipocyte differentiation. Some recent studies demonstrate that vitamin D metabolites also influence adipokine production and the inflammatory response in adipose tissue. Therefore, vitamin D deficiency may compromise the normal metabolic functioning of adipose tissue. Given the importance of the tissue in energy balance, lipid metabolism and inflammation in obesity, understanding the mechanisms of vitamin D action in adipocytes may have a significant impact on the maintenance of metabolic health. In the present review, we focus on the signalling role of vitamin D in adipocytes, particularly the potential mechanisms through which vitamin D may influence adipose tissue development and function. PMID:23046765

Ding, Cherlyn; Gao, Dan; Wilding, John; Trayhurn, Paul; Bing, Chen

2012-10-09

88

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

89

Glycerokinase activity in human brown adipose tissue  

Microsoft Academic Search

Brown adipose tissue (BAT) is known to be respon- sible for heat production in newborn and adult hibernating mammals. In rats and mice, BAT has been demonstrated to possess a much higher glycerokinase activity than white adi- pose tissue (WAT). It has been speculated that this high activity may cause the futile cycle of triglyceride breakdown and re- synthesis to

Krishna Chakrabarty; Bina Chaudhuri; Henry Jeffay

90

Combining decellularized human adipose tissue extracellular matrix and adipose-derived stem cells for adipose tissue engineering.  

PubMed

Repair of soft tissue defects resulting from lumpectomy or mastectomy has become an important rehabilitation process for breast cancer patients. This study aimed to provide an adipose tissue engineering platform for soft tissue defect repair by combining decellularized human adipose tissue extracellular matrix (hDAM) and human adipose-derived stem cells (hASCs). To derive hDAM incised human adipose tissues underwent a decellularization process. Effective cell removal and lipid removal were proved by immunohistochemical analysis and DNA quantification. Scanning electron microscopic examination showed a three-dimensional nanofibrous architecture in hDAM. The hDAM included collagen, sulfated glycosaminoglycan, and vascular endothelial growth factor, but lacked major histocompatibility complex antigen I. hASC viability and proliferation on hDAM were proven in vitro. hDAM implanted subcutaneously in Fischer rats did not cause an immunogenic response, and it underwent remodeling, as indicated by host cell infiltration, neovascularization, and adipose tissue formation. Fresh fat grafts (Coleman technique) and engineered fat grafts (hDAM combined with hASCs) were implanted subcutaneously in nude rats. The implanted engineered fat grafts maintained their volume for 8weeks, and the hASCs contributed to adipose tissue formation. In summary, the combination of hDAM and hASCs provides not only a clinically translatable platform for adipose tissue engineering, but also a vehicle for elucidating fat grafting mechanisms. PMID:23816649

Wang, Lina; Johnson, Joshua A; Zhang, Qixu; Beahm, Elisabeth K

2013-06-29

91

Adipose tissue dysfunction in nascent metabolic syndrome.  

PubMed

The metabolic syndrome (MetS) confers an increased risk for both type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome's low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT) in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin) and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin), as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD. PMID:23653857

Bremer, Andrew A; Jialal, Ishwarlal

2013-04-04

92

Adipose Tissue Dysfunction in Nascent Metabolic Syndrome  

PubMed Central

The metabolic syndrome (MetS) confers an increased risk for both type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome's low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT) in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin) and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin), as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.

Bremer, Andrew A.

2013-01-01

93

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

94

Obestatin induction of early-response gene expression in gastrointestinal and adipose tissues and the mediatory role of G protein-coupled receptor, GPR39.  

PubMed

Obestatin was identified as a brain/gut peptide hormone encoded by the ghrelin gene and found to interact with the G protein-coupled receptor, GPR39. We investigated target cells for obestatin based on induction of an early-response gene c-fos in different tissues. After ip injection of obestatin, c-fos staining was found in the nuclei of gastric mucosa, intestinal villi, white adipose tissues, hepatic cords, and kidney tubules. Immunohistochemical analyses using GPR39 antibodies further revealed cytoplasmic staining in these tissues. In cultured 3T3-L1 cells, treatment with obestatin, but not motilin, induced c-fos expression. In these preadipocytes, treatment with obestatin also stimulated ERK1/2 phosphorylation. Because phenotypes of GPR39 null mice are partially consistent with a role of GPR39 in mediating obestatin actions, we hypothesized that inconsistencies on the binding of iodinated obestatin to GPR39 are due to variations in the bioactivity of iodinated obestatin. We obtained monoiodoobestatin after HPLC purification and demonstrated its binding to jejunum, stomach, ileum, pituitary, and white adipose tissue. Furthermore, human embryonic kidney 293T cells transfected with plasmids encoding human or mouse GPR39 or a human GPR39 isoform, but not the ghrelin receptor, exhibited high-affinity binding to monoiodoobestatin. Binding studies using jejunum homogenates and recombinant GPR39 revealed obestatin-specific displacement curves. Furthermore, treatment with obestatin induced c-fos expression in gastric mucosa of wild-type, but not GPR39 null, mice, underscoring a mediating role of this receptor in obestatin actions. The present findings indicate that obestatin is a metabolic hormone capable of binding to GPR39 to regulate the functions of diverse gastrointestinal and adipose tissues. PMID:18337590

Zhang, Jian V; Jahr, Holger; Luo, Chin-Wei; Klein, Cynthia; Van Kolen, Kristof; Ver Donck, Luc; De, Ananya; Baart, Esther; Li, Jing; Moechars, Dieder; Hsueh, Aaron J W

2008-03-12

95

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

96

Mitochondrial Dysfunction in White Adipose Tissue  

PubMed Central

While mitochondria in brown adipose tissue and their role in non-shivering thermogenesis have been widely studied, we have only a limited understanding of the relevance of mitochondria in white adipose tissue for cellular homeostasis of the adipocyte, and their impact on systemic energy homeostasis. A better understanding of the regulatory role that white adipocyte mitochondria play on whole body physiology becomes increasingly important. White adipose mitochondrial biogenesis can effectively be induced pharmacologically using a number of agents, including PPAR? agonists. Through their ability to influence key biochemical processes central to the adipocyte, such as fatty acid esterification and lipogenesis, as well as their impact on production and release of key adipokines, mitochondria exert a critical role on systemic insulin sensitivity.

Kusminski, Christine M.; Scherer, Philipp E.

2012-01-01

97

Polychlorinated Biphenyls in Human Adipose Tissue and Mother's Milk.  

National Technical Information Service (NTIS)

Statistical Analysis of trends of polychlorinated biphenyl levels in human adipose tissue specimens collected in the EPA National Human Adipose Tissue Survey and in milk specimens collected in an EPA human mother's milk study.

R. M. Lucas V. G. Iannacchione D. K. Melroy

1982-01-01

98

Seasonal Changes in Adipose Tissue Lipogenesis In the Hibernator.  

National Technical Information Service (NTIS)

Seasonal effects on lipogenesis from glucose or acetate by white and brown adipose tissue preparations from the ground squirrel were studied. Lipogenic capacity of white adipose tissue follows a yearly cycle, reaching a maximal rate in June, declining in ...

G. J. Klain G. B. Rogers

1969-01-01

99

Physiological Activity of the Brown Adipose Tissue.  

National Technical Information Service (NTIS)

Brown adipose tissue was recently found to be a major site of heat production in cold-adapted animals. It is also known that the increased secretion of thyroid hormone is responsible for the thermogenesis during cold exposure. Accordingly, the thyroid hor...

S. Itoh

1967-01-01

100

Brown Adipose Tissue in Morbidly Obese Subjects  

Microsoft Academic Search

BackgroundCold-stimulated adaptive thermogenesis in brown adipose tissue (BAT) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI) and body fat percentage (BF%), suggesting that obesity is associated with lower BAT activity. Here, we

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

2011-01-01

101

Novel measurements of periaortic adipose tissue in comparison to anthropometric measures of obesity, and abdominal adipose tissue  

Microsoft Academic Search

Background:Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue.Methods:Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study

C L Schlett; J M Massaro; S J Lehman; F Bamberg; C J O'Donnell; C S Fox; U Hoffmann

2009-01-01

102

Endurance training blocks uncoupling protein 1 up-regulation in brown adipose tissue while increasing uncoupling protein 3 in the muscle tissue of rats fed with a high-sugar diet.  

PubMed

The mitochondrial uncoupling proteins (UCPs) of interscapular brown adipose tissue (iBAT) and of muscles play important roles in energy balance. For instance, the expression of UCP1 and UCP3 are modulated by free fatty acid gradients induced by high-sugar diets and acute exercise that is dependent on sympathetic stimulation. However, the effects of endurance training in animals fed with high-sugar diets are unknown. This study aims to evaluate the long-term effects of diet and exercise on UCP1 and UCP3 levels and energy balance efficiency. Rats fed with standard or high-sugar (HSD) diets were simultaneously subjected to running training over an 8-week period. After the training period, the rats were decapitated, and the iBAT and gastrocnemius muscle tissues were removed for evaluation of the ??-receptor, Ucp1, and Ucp3 mRNA and protein expression, which were analyzed by quantitative reverse transcriptase polymerase chain reaction and Western blot, respectively. Groups fed with an HSD displayed a higher adiposity index and iBAT weight (P < .05), whereas exhibited an up-regulation of Ucp1 mRNA and protein levels (P < .05). Training increased ??-receptor mRNA in iBAT and reduced the Ucp3 mRNA in muscle tissues. In association with an HSD, training restored the increasing ??-receptor mRNA and greatly up-regulated the levels of Ucp3 mRNA. Therefore, training blocked the HSD-induced up-regulation of UCP1 expression in iBAT, whereas it up-regulated the expression of Ucp3 mRNA in muscle. These results suggest that training enhances the relationship between Ucp1/Ucp3 mRNA levels, which could result in higher energy efficiency, but not when HSD-induced elevated sympathetic activity is maintained. PMID:23084644

de Queiroz, Karina Barbosa; Rodovalho, Gisele Vieira; Guimarães, Juliana Bohnen; de Lima, Daniel Carvalho; Coimbra, Cândido Celso; Evangelista, Elísio Alberto; Guerra-Sá, Renata

2012-09-28

103

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

PubMed

The original concept of adipose tissue as an inert storage depot for the excess of energy has evolved over the last years and it is now considered as one of the most important organs regulating body homeostasis. This conceptual change has been supported by the demonstration that adipose tissue serves as a major endocrine organ, producing a wide variety of bioactive molecules, collectively termed adipokines, with endocrine, paracrine and autocrine activities. Adipose tissue is indeed a complex organ wherein mature adipocytes coexist with the various cell types comprising the stromal-vascular fraction (SVF), including preadipocytes, adipose-derived stem cells, perivascular cells, and blood cells. It is known that not only mature adipocytes but also the components of SVF produce adipokines. Furthermore, adipokine production, proliferative and metabolic activities and response to regulatory signals (i.e. insulin, catecholamines) differ between the different fat depots, which have been proposed to underlie their distinct association to specific diseases. Herein, we discuss the recent proteomic studies on adipose tissue focused on the analysis of the separate cellular components and their secretory products, with the aim of identifying the basic features and the contribution of each component to different adipose tissue-associated pathologies. PMID:22246603

Peinado, Juan R; Pardo, María; de la Rosa, Olga; Malagón, Maria M

2012-01-23

104

Urokinase Plasminogen Activator Receptor in Adipose Tissue Macrophages of Morbidly Obese Subjects  

Microsoft Academic Search

SummaryObjective: At present, circulating markers characterizing the inflammatory infiltration of white adipose tissue (WAT) in human obesity are not well known. We previously identified, by a pangenomic approach (microarrays), the urokinase plasminogen activator receptor (PLAUR or CD87) as a potential marker of subcutaneous adipose tissue macrophage infiltration (ATM). Method: We studied i) the presence of PLAUR protein in WAT; ii)

Raffaella Cancello; Christine Rouault; Gaël Guilhem; Jean-François Bedel; Christine Poitou; Anna Maria Di Blasio; Arnaud Basdevant; Joan Tordjman; Karine Clément

2011-01-01

105

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

106

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

PubMed Central

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

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

2012-01-01

107

High-mobility group protein HMGA2-derived fragments stimulate the proliferation of chondrocytes and adipose tissue-derived stem cells.  

PubMed

In previous research, it was shown that recombinant HMGA2 protein enhances the proliferation of porcine chondrocytes grown in vitro, opening up promising applications of this embryonic architectural transcription factor for tissue engineering, such as in cartilage repair. In this paper, we describe the development and analyses of two synthetic fragments comprising the functional AT-hook motifs of the HMGA2 protein, as well as the nuclear transport domain. They can be synthesised up to large scales, while eliminating some of the problems of recombinant protein production, including unwanted modification or contamination by the expression hosts, or of gene therapy approaches such as uncontrolled viral integration and transgene expression even after therapy. Application of one of these peptides onto porcine hyaline cartilage chondrocytes, grown in in vitro monolayer cell culture, showed a growth-promoting effect similar to that of the wild type HMGA2 protein. Furthermore, it also promoted cell growth of adult adipose tissue derived stem cells. Due to its proliferation inducing function and vast availability, this peptide is thus suitable for further application and investigation in various fields such as tissue engineering and stem cell research. PMID:21484705

Richter, A; Lübbing, M; Frank, H G; Nolte, I; Bullerdiek, J C; von Ahsen, I

2011-04-11

108

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

PubMed Central

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

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

2012-01-01

109

Adipose tissue-specific PPAR? gene targeting.  

PubMed

The nuclear receptor peroxisome proliferator activated receptor gamma (PPAR?) is most abundantly expressed in adipose tissue and has been shown to play imperative roles in controlling adipogenesis and lipogenesis in cultured cell systems in vitro as well as in mice and humans. However, it is unclear how important the role this receptor plays in regulating physiological functions of mature adipocytes in vivo. The Cre-loxP gene targeting strategy is employed to specifically disrupt PPAR? in mature adipocytes in mice. In this chapter, I will describe generation of "floxed" PPAR? mice, which bear loxP sequences in the introns of PPAR? gene locus flanking the coding exons 1 and 2 of PPAR? and creation of the aP2-Cre transgenic mice, which express Cre recombinase under the control of the promoter of adipocyte fatty acid binding protein (aP2). Crossing of the two mouse lines results in deletion of PPAR? gene only in differentiated adipocytes in Cre positive mice. PMID:23100228

He, Weimin

2013-01-01

110

Visceral adipose tissue and cardiovascular risk factors in obese children  

Microsoft Academic Search

Objective: In adults visceral adipose tissue (VAT) has been shown to be more highly correlated with cardiovascular (CV) risk factors than are other measures of adiposity such as subcutaneous abdominal adipose tissue (SAAT), percent body fat (%BF), or total body fat mass (TFM). We examined the relations between these measures of fatness and CV risk factors in obese children.Study design:

Scott Owens; Bernard Gutin; Michael Ferguson; Jerry Allison; Warren Karp; Ngoc-Anh Le

1998-01-01

111

Ovarian hormones influence brown adipose tissue.  

PubMed

Adult female rats were ovariectomized (OVX) or sham-operated and 4-5 weeks later OVX groups were treated with estradiol benzoate (EB), progesterone, both hormones, or the oil vehicle. All rats were sacrificed on the 4th day of hormone treatment following an overnight fast and a terminal meal. Interscapular brown adipose tissue (BAT) pads of EB-treated groups were heavier and contained more lipid than those of the other OVX groups. Lipid content of adipose tissue differed according to site (BAT less than inguinal less than parametrial = retroperitoneal), but only BAT exhibited differential responsiveness to hormonal treatments. There was also a trend for increased oxygen consumption by BAT from EB-treated rats. It is concluded that BAT may be involved in the process of increased energy expenditure by estrogen-treated rats. PMID:6867061

Kemnitz, J W; Glick, Z; Bray, G A

1983-04-01

112

The adipose tissue as an endocrine organ.  

PubMed

During the past 2 decades, results of both basic science and clinical studies have changed the physicians' views about adipocyte pathophysiology. Since leptin was discovered in 1994, white adipose tissue was recognized as an endocrine organ and an important source of biologically active substances with local and/or systemic action called adipokines. Inappropriate secretion of several adipokines by the excessive amount of white adipose tissue seems to participate in the pathogenesis of obesity-related pathologic processes including endothelial dysfunction, inflammation, atherosclerosis, diabetes mellitus, and chronic kidney disease. In this review endocrine action of selected adipokines (mainly leptin and adiponectin) in the context of kidney diseases is discussed. Specifically, the role of these adipokines in malnutrition, chronic kidney disease progression, and pathogenesis of cardiovascular complications is presented. PMID:23374889

Adamczak, Marcin; Wiecek, Andrzej

2013-01-01

113

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

Microsoft Academic Search

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

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

2000-01-01

114

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

2013-01-24

115

The development and endocrine functions of adipose tissue.  

PubMed

White adipose tissue is a mesenchymal tissue that begins developing in the fetus. Classically known for storing the body's fuel reserves, adipose tissue is now recognized as an endocrine organ. As such, the secretions from adipose tissue are known to affect several systems such as the vascular and immune systems and play major roles in metabolism. Numerous studies have shown nutrient or hormonal manipulations can greatly influence adipose tissue development. In addition, the associations between various disease states, such as insulin resistance and cardiovascular disease, and disregulation of adipose tissue seen in epidemiological and intervention studies are great. Evaluation of known adipokines suggests these factors secreted from adipose tissue play roles in several pathologies. As the identification of more adipokines and determination of their role in biological systems, and the interactions between adipocytes and other cells types continues, there is little doubt that we will gain a greater appreciation for a tissue once thought to simply store excess energy. PMID:20025936

Poulos, Sylvia P; Hausman, Dorothy B; Hausman, Gary J

2009-12-16

116

Pulsed electric breakdown in adipose tissue  

NASA Astrophysics Data System (ADS)

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

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

2011-08-01

117

Comparison of the Release of Adipokines by Adipose Tissue, Adipose Tissue Matrix, and Adipocytes from Visceral and Subcutaneous Abdominal Adipose Tissues of Obese Humans  

Microsoft Academic Search

The purpose of this study was to examine the source of adi- pokines released by the visceral and sc adipose tissues of obese humans. Human adipose tissue incubated in primary culture for 48 h released more prostaglandin E2, IL-8, and IL-6 than adiponectin, whereas the release of plasminogen acti- vator inhibitor 1 and hepatocyte growth factor was less than that

JOHN N. FAIN; ATUL K. MADAN; M. LLOYD HILER; PARAMJEET CHEEMA; SULEIMAN W. BAHOUTH

2004-01-01

118

Adipose tissue-specific CETP expression in mice: impact on plasma lipoprotein metabolism.  

PubMed

Adipose tissue appears to be a highly conserved site of cholesteryl ester transfer protein (CETP) expression across species. To investigate the impact of adipose CETP expression on lipid metabolism, we created adipose tissue-specific CETP transgenic (CETPTg) mice. CETP mRNA is predominantly expressed in adipose tissue. Plasma CETP mass and activity are readily detectable in CETPTg mice but not in controls. Plasma lipoprotein analysis shows marked reductions in HDL cholesterol and phospholipids, increases non-HDL lipids, decreases apolipoprotein A-I (apoA-I), and increases apoB. Unexpectedly, CETPTg adipocytes are significantly smaller than those in control mice (44%), triglyceride and cholesterol in adipose tissue were significantly decreased compared with controls (50% and 37%, respectively), and phospholipids showed no significant changes. To study the mechanism, we measured peroxisome proliferator-activated receptor gamma, sterol-regulatory element binding protein-1c, LPL, and hormone-sensitive lipase (HSL) in aP2-CETPTg adipose tissue and controls and found that, except for HSL, all mRNA levels are significantly decreased in the transgenic mice compared with controls (26, 33, and 22%). In conclusion, adipose tissue CETP makes a major contribution to CETP in the circulation, reduces HDL, and increases non-HDL cholesterol levels. Moreover, adipose tissue CETP expression changes triglyceride and cholesterol content and the size of adipocytes. PMID:16751623

Zhou, Hongwen; Li, Zhiqiang; Hojjati, Mohamad R; Jang, David; Beyer, Thomas P; Cao, Guoqing; Tall, Alan R; Jiang, Xian-Cheng

2006-06-02

119

Extracellular degradation of lipoprotein lipase in rat adipose tissue  

PubMed Central

Background Recent studies in vivo indicate that short-term regulation of lipoprotein lipase (LPL) in rat adipose tissue is post-translational and occurs by a shift of the lipase protein towards an inactive form under the influence of another gene with short-lived message and product. It has not been possible to reproduce this process with isolated adipocytes suggesting that other cells are needed, and perhaps mediate the regulation. The objective of the present study was, therefore, to explore if explants of adipose tissue could be used for studies of the regulatory process. Results When explants of rat epididymal adipose tissue were incubated, LPL mass and activity decreased rapidly. Mass and activity within adipocytes remained constant for at least six hours, demonstrating that it was the extracellular portion of the enzyme that decreased. Adipocytes isolated from the explants after three or six hours of incubation retained their ability to secrete LPL to the medium. Addition of a cocktail of protease inhibitors to the incubation medium slowed down the decrease of LPL mass. Chloroquine was without effect, indicating that the degradation was not lysosomal. 125I-labeled LPL added to the medium was degraded to acid soluble products, indicating that the degradation occurred extracellularly. Fragmentation of the labelled lipase occurred in conditioned medium and this process was virtually abolished by two MMP inhibitors. Conclusions The decrease of LPL mass and activity that occurs when explants of rat adipose tissue are incubated is due to proteolysis of extracellular LPL. The adipocytes continue to produce and secrete the enzyme. The effect of inhibitors indicates, but does not prove, that the degradation is mediated by MMPs. It appears that this process is accelerated in the tissue fragments compared to intact tissue.

Wu, Gengshu; Olivecrona, Gunilla; Olivecrona, Thomas

2005-01-01

120

Adipose tissue-derived cells: from physiology to regenerative medicine.  

PubMed

During the last past years, the importance and the role of adipose tissues have been greatly expanded. After finding that adipose tissues are metabolically very active, the discovery of leptin moved the status of adipose tissue towards an endocrine tissue able to interact with all major organs via secretion of adipokines. Some years ago, the presence of adipocyte precursors, termed preadipocytes, has been described in all adipose tissue depots from various species of different age. More recently, the discovery that different phenotypes can be obtained from stroma cells of adipose tissue has largely emphazised the concept of adipose tissue plasticity. Therefore, raising great hope in regenerative medicine as adipose tissue can be easily harvested in adults it could represent an abundant source of therapeutic cells. Thus, adipose tissue plays the dual role of Mr Obese Hyde as a main actor of obesity and of Dr Regenerative Jekyll as a source of therapeutic cells. Adipose tissue has not yet revealed all its mysteries although one facet could not be well understood without the other one. PMID:17110894

Casteilla, L; Dani, C

2006-11-01

121

A 1 adenosine receptor of human and mouse adipose tissues  

Microsoft Academic Search

The aberrant functioning of the A1 adenosine receptor of adipose tissue has been implicated as a factor in obesity. To begin to address questions concerning this relationship, the possibility of a unique A1 adenosine receptor in adipose tissue must be investigated. Therefore, cDNAs encoding the A1 adenosine receptors of adipose tissues of a mouse and an obese human were isolated,

Irene Tatsis-Kotsidis; Bernard F Erlanger

1999-01-01

122

Hormone-sensitive lipase protein expression and extent of phosphorylation in subcutaneous and retroperitoneal adipose tissues in the periparturient dairy cow.  

PubMed

Lipomobilization is essential for dairy cows to balance the energy requirement for milk production in early lactation. This study aimed to determine the role of hormone-sensitive lipase (HSL) and its activation by phosphorylation at Ser 660 (HSLp660) and 563 (HSLp563) in different adipose tissue depots as influenced by time and postpartum diet in dairy cows. Biopsy samples were obtained from s.c. (SCAT) and retroperitoneal (RPAT) adipose tissues of 20 Holstein cows 21 d prepartum, and 1 and 21 d postpartum. After d 1 postpartum, cows were randomly assigned to 2 groups (n=10). Groups received diets with either a concentrate-to-roughage ratio on a dry matter basis of 30:70% (low-concentrate, LC, group) or 60:40% (high-concentrate group), fed until the third biopsy sampling 21 d postpartum. Dry matter intake, milk yield, and milk composition were recorded. Blood samples were taken weekly, starting 21 d prepartum and analyzed for nonesterified fatty acids, ?-hydroxybutyrate (BHBA), glucose, and insulin. Protein expression of HSL and its extent of phosphorylation in adipose tissue were measured by semiquantitative Western blotting. Total HSL expression was lower in both adipose tissues 1 d after calving compared with prepartum sampling (SCAT: 4.10±0.5 vs. 2.4±0.3; RPAT: 11.1±1.3 vs. 6.6±1.1). Phosphorylation at Ser 660 was higher 21 d postpartum compared with 21 d prepartum in RPAT (2.9±0.3 vs. 4.6±0.6). Phosphorylation at Ser 563 was higher 21 d postpartum than 21 d prepartum in SCAT (0.6±0.1 vs. 3.9±1.1), and in RPAT a difference was observed between 21 d prepartum and 1 d postpartum (1.0±0.1 vs. 3.3. ± 0.6). On d 21 postpartum, the LC group showed a lower extent of Ser 563 phosphorylation in RPAT (3.9±0.8 vs.10.0±1.9) and a higher concentration of serum BHBA (0.77±0.05 vs. 0.47±0.11) than did the high-concentrate group. An inhibitory influence of higher BHBA concentrations on HSL phosphorylation in the LC group could be a possible explanation. On comparing RPAT to SCAT, HSL expression and the extent of Ser 660 and 563 phosphorylation was higher in RPAT at 21 d prepartum (HSL: 4.1±0.5 vs. 11.1±1.2; HSLp660 1.3±0.2 vs. 2.9±0.3; HSLp563: 0.6±0.1 vs. 1.0±0.1). In conclusion, the postpartum feeding regimen influenced the phosphorylation pattern, especially in RPAT, implying a regulatory role for different phosphorylation sites in adaptive lipolysis of dairy cows. It is suggested that RPAT is more sensitive to periparturient challenges than is SCAT. PMID:21854923

Locher, L F; Meyer, N; Weber, E-M; Rehage, J; Meyer, U; Dänicke, S; Huber, K

2011-09-01

123

Mammary hamartoma with brown adipose tissue.  

PubMed

This report documents a rare variant of mammary hamartoma with presence of lobules of brown adipose tissue. The lesion was discovered in a control mammogram performed in a 42-year-old woman 15 months after hormonal substitute therapy for radical hysterectomy with bilateral salpingo-oophorectomy. Complete excision is the adequate therapy. The presence of brown fat in the hamartoma should be considered in the differential diagnosis of the exceptional hibernoma of the breast and other tumors composed of large cells with granular or multilocular cytoplasm, such as lipoblastoma, sebaceous adenoma, granular cell tumor and histiocytoid or lipid rich carcinomas. PMID:9489958

Garijo, M F; Torío, B; Val-Bernal, J F

1997-12-01

124

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

2012-01-28

125

Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity.  

PubMed

When caloric intake exceeds caloric expenditure, the positive caloric balance and storage of energy in adipose tissue often causes adipocyte hypertrophy and visceral adipose tissue accumulation. These pathogenic anatomic abnormalities may incite metabolic and immune responses that promote Type 2 diabetes mellitus, hypertension and dyslipidemia. These are the most common metabolic diseases managed by clinicians and are all major cardiovascular disease risk factors. 'Disease' is traditionally characterized as anatomic and physiologic abnormalities of an organ or organ system that contributes to adverse health consequences. Using this definition, pathogenic adipose tissue is no less a disease than diseases of other body organs. This review describes the consequences of pathogenic fat cell hypertrophy and visceral adiposity, emphasizing the mechanistic contributions of genetic and environmental predispositions, adipogenesis, fat storage, free fatty acid metabolism, adipocyte factors and inflammation. Appreciating the full pathogenic potential of adipose tissue requires an integrated perspective, recognizing the importance of 'cross-talk' and interactions between adipose tissue and other body systems. Thus, the adverse metabolic consequences that accompany fat cell hypertrophy and visceral adiposity are best viewed as a pathologic partnership between the pathogenic potential adipose tissue and the inherited or acquired limitations and/or impairments of other body organs. A better understanding of the physiological and pathological interplay of pathogenic adipose tissue with other organs and organ systems may assist in developing better strategies in treating metabolic disease and reducing cardiovascular disease risk. PMID:18327995

Bays, Harold E; González-Campoy, J Michael; Bray, George A; Kitabchi, Abbas E; Bergman, Donald A; Schorr, Alan Bruce; Rodbard, Helena W; Henry, Robert R

2008-03-01

126

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

PubMed

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

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

2012-03-10

127

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

PubMed

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

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

2012-07-02

128

Induction of uncoupling protein-1 and -3 in brown adipose tissue by kaki-tannin in type 2 diabetic NSY/Hos mice.  

PubMed

Kaki-tannin, a highly polymerized-tannin from the young fruits of persimmon (Diospyros kaki 'Hachiya'), has been shown to have bile acid-binding activity. To verify the effect of kaki-tannin on the metabolism of lipid and glucose in type 2 diabetes, type 2 diabetic NSY/Hos mice were fed an AIN76-modified high fat diet supplemented with 1% (w/w) kaki-tannin for 8weeks. Kaki-tannin induced a 2-fold increase in fecal bile acid excretion and was significantly effective in the prevention of a rise in plasma cholesterol, triglyceride, and insulin levels. Kaki-tannin treatment also prevented fatty liver. To identify the molecular mechanism underlying these effects, gene expression analysis was performed on liver, brown adipose tissue (BAT), and skeletal muscle. The genes related to cholesterol metabolism, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein 2, were increased in the liver of the kaki-tannin group. Interestingly, the uncoupling protein-1 (UCP1) gene and the UCP3 gene were significantly increased in the BAT of the kaki-tannin group, which was also confirmed at the protein level. These findings indicated that induction of UCP1 and UCP3 in the BAT by kaki-tannin treatment might influence the energy metabolism, thus contributing beneficial effects to type 2 diabetic NSY/Hos mice. PMID:22079182

Matsumoto, Kenji; Yokoyama, Shin-Ichiro

2011-11-06

129

Assessment of biological characteristics of adipose tissue?derived stem cells co?labeled with Molday ION Rhodamine B™ and green fluorescent protein in vitro.  

PubMed

The current study aimed to investigate adipose tissue?derived stem cells (ADSCs) in vivo by multimodality imaging following implantation for cellular therapy. The biological characteristics of ADSCs co?labeled with Molday ION Rhodamine B™ (MIRB) and green fluorescent protein (GFP) were studied in vitro. Following rat ADSC isolation and culture, a combined labeling strategy for ADSCs based on genetic modification of the reporter gene GFP with lentiviral vector expression enhancement and physical MIRB labeling was performed. Cell viability, proliferation, membrane?bound antigens and multiple differentiation ability were compared between the labeled and unlabeled ADSCs. The ADSCs were successfully labeled with GFP and MIRB, showing various fluorescent colors for marker identification. The fluorescence emitted by the GFP protein was sustained and exhibited stable expression, while MIRB fluorescence decreased with time. Compared with the unlabeled ADSCs, no significant differences were detected in cell viability, proliferation, membrane?bound antigens and multiple differentiation ability in the co?labeled samples (P>0.05). No significant effects on the biophysical properties of ADSCs were observed following co?labeling with lentiviral vectors encoding the gene for emerald green fluorescent protein and MIRB. The ADSCs were able to be efficiently tracked in vitro and in vivo by multimodality imaging thus, the co?labeling approach provides a novel strategy for therapeutic gene studies. PMID:24065138

Nan, Hua; Huang, Jiacheng; Li, Hongmian; Li, Qiong; Liu, Dalie

2013-09-18

130

Seasonal regulations of energetics, serum concentrations of leptin, and uncoupling protein 1 content of brown adipose tissue in root voles (Microtus oeconomus) from the Qinghai-Tibetan plateau.  

PubMed

Survival of small mammals in winter requires proper adjustments in physiology, behavior and morphology. The present study was designed to examine the changes in serum leptin concentration and the molecular basis of thermogenesis in seasonally acclimatized root voles (Microtus oeconomus) from the Qinghai-Tibetan plateau. In January root voles had lower body mass and body fat mass coupled with higher nonshivering thermogenesis (NST) capacity. Consistently, cytochrome c oxidase activity and mitochondrial uncoupling protein-1 (UCP1) protein contents in brown adipose tissues were higher in January as compared to that in July. Circulating level of serum leptin was significantly lower in winter and higher in July. Correlation analysis showed that serum leptin levels were positively related with body mass and body fat mass while negatively correlated with UCP1 protein contents. Together, these data provided further evidence for our previous findings that root voles from the Qinghai-Tibetan plateau mainly depend on higher NST coupled with lower body mass to enhance winter survival. Further, fat deposition was significantly mobilized in cold winter and leptin was potentially involved in the regulation of body mass and thermogenesis in root voles. Serum leptin might act as a starvation signal in winter and satiety signal in summer. PMID:16786335

Wang, Jian-Mei; Zhang, Yan-Ming; Wang, De-Hua

2006-06-20

131

Adipose tissue as a medium for epidemiologic exposure assessment.  

PubMed Central

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

Kohlmeier, L; Kohlmeier, M

1995-01-01

132

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

133

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

Microsoft Academic Search

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

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

2012-01-01

134

Obesity--a genetic disease of adipose tissue?  

PubMed

Although the rapid increase in the prevalence of obesity in many countries suggests that environmental factors (mainly overeating and physical inactivity) play the most important role in the development of overweight, it is very likely that genetic factors also contribute. It appears that one major gene in combination with one or several minor genes constitute the genetic components behind excess accumulation of body fat in most obese individuals. However, monogenic obesity has been described in a few families due to changes in leptin, leptin receptor, prohormone convertase, pro-opiomelanocortin or melanocortin-4 receptor. None of the monogenic variants is of great importance for common human obesity; the latter genes are unknown so far. Results from genomic scans suggest that major obesity genes are located on chromosomes 2, 10, 11 and 20. Studies of candidate genes indicate that the minor obesity genes control important functions of adipose tissue, and that structural variance in these genes may alter adipose tissue function in a way that promotes obesity. Such genes are beta 2- and beta 3-adrenoceptors, hormone-sensitive lipase, tumour necrosis factor alpha, uncoupling protein-1, low-density lipoprotein receptor, and peroxisome proliferator activator receptor gamma-2. Some of these genes may promote obesity by gene-gene interactions (for example beta 3-adrenoceptors and uncoupling protein-1) or gene-environment interactions (for example beta 2-adrenoceptors and physical activity). Some are important for obesity only among women (for example beta 2- and beta 3-adrenoceptors, low-density lipoprotein receptor and tumour necrosis factor alpha). Few 'non-adipose' genes have so far shown a firm association to common human obesity, which could suggest that the important genes for the development of excess body fat also control adipose tissue function. PMID:10889786

Arner, P

2000-03-01

135

An endocrine role for brown adipose tissue?  

PubMed

White adipose tissue is recognized as both a site of energy storage and an endocrine organ that produces a myriad of endocrine factors called adipokines. Brown adipose tissue (BAT) is the main site of nonshivering thermogenesis in mammals. The amount and activity of brown adipocytes are associated with protection against obesity and associated metabolic alterations. These effects of BAT are traditionally attributed to its capacity for the oxidation of fatty acids and glucose to sustain thermogenesis. However, recent data suggest that the beneficial effects of BAT could involve a previously unrecognized endocrine role through the release of endocrine factors. Several signaling molecules with endocrine properties have been found to be released by brown fat, especially under conditions of thermogenic activation. Moreover, experimental BAT transplantation has been shown to improve glucose tolerance and insulin sensitivity mainly by influencing hepatic and cardiac function. It has been proposed that these effects are due to the release of endocrine factors by brown fat, such as insulin-like growth factor I, interleukin-6, or fibroblast growth factor-21. Further research is needed to determine whether brown fat plays an endocrine role and, if so, to comprehensively identify which endocrine factors are released by BAT. Such research may reveal novel clues for the observed association between brown adipocyte activity and a healthy metabolic profile, and it could also enlarge a current view of potential therapeutic tools for obesity and associated metabolic diseases. PMID:23839524

Villarroya, Joan; Cereijo, Rubén; Villarroya, Francesc

2013-07-09

136

Brown adipose tissue activity controls triglyceride clearance.  

PubMed

Brown adipose tissue (BAT) burns fatty acids for heat production to defend the body against cold and has recently been shown to be present in humans. Triglyceride-rich lipoproteins (TRLs) transport lipids in the bloodstream, where the fatty acid moieties are liberated by the action of lipoprotein lipase (LPL). Peripheral organs such as muscle and adipose tissue take up the fatty acids, whereas the remaining cholesterol-rich remnant particles are cleared by the liver. Elevated plasma triglyceride concentrations and prolonged circulation of cholesterol-rich remnants, especially in diabetic dyslipidemia, are risk factors for cardiovascular disease. However, the precise biological role of BAT for TRL clearance remains unclear. Here we show that increased BAT activity induced by short-term cold exposure controls TRL metabolism in mice. Cold exposure drastically accelerated plasma clearance of triglycerides as a result of increased uptake into BAT, a process crucially dependent on local LPL activity and transmembrane receptor CD36. In pathophysiological settings, cold exposure corrected hyperlipidemia and improved deleterious effects of insulin resistance. In conclusion, BAT activity controls vascular lipoprotein homeostasis by inducing a metabolic program that boosts TRL turnover and channels lipids into BAT. Activation of BAT might be a therapeutic approach to reduce elevated triglyceride concentrations and combat obesity in humans. PMID:21258337

Bartelt, Alexander; Bruns, Oliver T; Reimer, Rudolph; Hohenberg, Heinz; Ittrich, Harald; Peldschus, Kersten; Kaul, Michael G; Tromsdorf, Ulrich I; Weller, Horst; Waurisch, Christian; Eychmüller, Alexander; Gordts, Philip L S M; Rinninger, Franz; Bruegelmann, Karoline; Freund, Barbara; Nielsen, Peter; Merkel, Martin; Heeren, Joerg

2011-01-23

137

Expression and Regulation of Soluble Epoxide Hydrolase in Adipose Tissue  

PubMed Central

Obesity is an increasingly important public health issue reaching epidemic proportions. Visceral obesity has been defined as an important element of the metabolic syndrome and expansion of the visceral fat mass has been shown to contribute to the development of insulin resistance and cardiovascular disease. To identify novel contributors to cardiovascular and metabolic abnormalities in obesity, we analyzed the adipose proteome and identified soluble epoxide hydrolase (sEH) in the epididymal fat pad from C57BL/6J mice that received either a regular diet or a “western diet.” sEH was synthesized in adipocytes and expression levels increased upon differentiation of 3T3-L1 preadipocytes. Although normalized sEH mRNA and protein levels did not differ in the fat pads from mice receiving a regular or a “western diet,” total adipose sEH activity was higher in the obese mice, even after normalization for body weight. Furthermore, peroxisome proliferator–activated recetor ?(PPAR?) agonists increased the expression of sEH in mature 3T3-L1 adipocytes in vitro and in adipose tissue in vivo. Considering the established role for sEH in inflammation, cardiovascular diseases, and lipid metabolism, and the suggested involvement of sEH in the development of type 2 diabetes, our study has identified adipose sEH as a potential novel therapeutic target that might affect the development of metabolic and cardiovascular abnormalities in obesity.

De Taeye, Bart M.; Morisseau, Christophe; Coyle, Julie; Covington, Joseph W.; Luria, Ayala; Yang, Jun; Murphy, Sheila B.; Friedman, David B.; Hammock, Bruce B.; Vaughan, Douglas E.

2010-01-01

138

Expression and regulation of soluble epoxide hydrolase in adipose tissue.  

PubMed

Obesity is an increasingly important public health issue reaching epidemic proportions. Visceral obesity has been defined as an important element of the metabolic syndrome and expansion of the visceral fat mass has been shown to contribute to the development of insulin resistance and cardiovascular disease. To identify novel contributors to cardiovascular and metabolic abnormalities in obesity, we analyzed the adipose proteome and identified soluble epoxide hydrolase (sEH) in the epididymal fat pad from C57BL/6J mice that received either a regular diet or a "western diet." sEH was synthesized in adipocytes and expression levels increased upon differentiation of 3T3-L1 preadipocytes. Although normalized sEH mRNA and protein levels did not differ in the fat pads from mice receiving a regular or a "western diet," total adipose sEH activity was higher in the obese mice, even after normalization for body weight. Furthermore, peroxisome proliferator-activated receptor gamma (PPARgamma) agonists increased the expression of sEH in mature 3T3-L1 adipocytes in vitro and in adipose tissue in vivo. Considering the established role for sEH in inflammation, cardiovascular diseases, and lipid metabolism, and the suggested involvement of sEH in the development of type 2 diabetes, our study has identified adipose sEH as a potential novel therapeutic target that might affect the development of metabolic and cardiovascular abnormalities in obesity. PMID:19644452

De Taeye, Bart M; Morisseau, Christophe; Coyle, Julie; Covington, Joseph W; Luria, Ayala; Yang, Jun; Murphy, Sheila B; Friedman, David B; Hammock, Bruce B; Vaughan, Douglas E

2009-07-30

139

Endocrine and nutritional regulation of fetal adipose tissue development.  

PubMed

In the fetus, adipose tIssue comprises both brown and white adipocytes for which brown fat is characterised as possessing the unique uncoupling protein (UCP)1. The dual characteristics of fetal fat reflect its critical role at birth in providing lipid that is mobilised rapidly following activation of UCP1 upon cold exposure to the extra-uterine environment. A key stage in the maturation of fetal fat is the gradual rise in the abundance of UCP1. For species with a mature hypothalamic-pituitary axis at birth there is a gradual increase in the amount and activity of UCP1 during late gestation, in conjunction with an increase in the plasma concentrations of catecholamines, thyroid hormones, cortisol, leptin and prolactin. These may act individually, or in combination, to promote UCP1 expression and, following the post-partum surge in each hormone, UCP1 abundance attains maximal amounts. Adipose tIssue grows in the fetus at a much lower rate than in the postnatal period. However, its growth is under marked nutritional constraints and, in contrast to many other fetal organs that are unaffected by nutritional manipulation, fat mass can be significantly altered by changes in maternal and, therefore, fetal nutrition. Fat deposition in the fetus is enhanced during late gestation following a previous period of nutrient restriction up to mid gestation. This is accompanied by increased mRNA abundance for the receptors of IGF-I and IGF-II. In contrast, increasing maternal nutrition in late gestation results in less adipose tIssue deposition but enhanced UCP1 abundance. The pronounced nutritional sensitivity of fetal adipose tIssue to both increased and decreased maternal nutrition may explain why the consequences of an adverse nutritional environment persist into later life. PMID:14656200

Symonds, M E; Mostyn, A; Pearce, S; Budge, H; Stephenson, T

2003-12-01

140

Hypertrophy and\\/or Hyperplasia: Dynamics of Adipose Tissue Growth  

Microsoft Academic Search

Adipose tissue grows by two mechanisms: hyperplasia (cell number increase) and hypertrophy (cell size increase). Genetics and diet affect the relative contributions of these two mechanisms to the growth of adipose tissue in obesity. In this study, the size distributions of epididymal adipose cells from two mouse strains, obesity-resistant FVB\\/N and obesity-prone C57BL\\/6, were measured after 2, 4, and 12

Junghyo Jo; Oksana Gavrilova; Stephanie Pack; William Jou; Shawn Mullen; Anne E. Sumner; Samuel W. Cushman; Vipul Periwal

2009-01-01

141

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

Microsoft Academic Search

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

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

2005-01-01

142

Differential patterns of serum concentration and adipose tissue expression of chemerin in obesity: adipose depot specificity and gender dimorphism.  

PubMed

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

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

2012-04-27

143

Adipose tissue engineering with human adipose tissue-derived adult stem cells and a novel porous scaffold.  

PubMed

We investigated the effect of a novel porous scaffold composed with water-soluble poly(L-glutamic acid) (PLGA) and chitosan (CS) on the attachment, proliferation, and adipogenic differentiation of human adipose tissue-derived adult stem cells (ADSCs) in vitro and in vivo. Scanning electron microscope and fluorescent Dil labeling were used to reveal the attachment and growth of ADSCs on scaffolds; cell proliferation was detected by DNA assay. The adipogenic differentiation potential of ADSCs on the scaffolds was assayed by Oil-red O staining and further confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) for adipogenic gene markers (peroxisome proliferator-activated receptor ?2, lipoprotein lipase, fatty acid-binding protein, adiponectin). Cell-seeded constructs exposed to adipogenic medium for 2 weeks in vitro were implanted in severe combined immunodeficient (SCID) mice for 6 weeks. It was shown that ADSCs attached and spread well on scaffolds with good proliferation behaviors and abundance of extracellular matrix deposition. Oil-red O staining and RT-PCR showed adipogenic differentiation potential of ADSCs on scaffolds. Newly formed adipose-like tissue was confirmed in vivo in SCID mice by Oil-red O staining. PLGA/CS porous scaffolds exhibit good compatibility to ADSCs and can be promising biomaterials for adipose tissue engineering. PMID:23090921

Wang, Wei; Cao, Bin; Cui, Lei; Cai, Jinglong; Yin, Jingbo

2012-10-22

144

Predicting abdominal adipose tissue in overweight Latino youth  

Microsoft Academic Search

Objectives. 1) Examine associations between visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and anthropometric and demographic variables; 2) generate and cross-validate prediction equations for estimating VATand SAAT in overweight Latino children. Study design. Cross-sectional. Participants. 196 overweight 8! 13-year-old Latino youth. Two-thirds (n\\

Geoff D. C. Ball; Terry T-K Huang; Martha L. Cruz; Gabriel Q. Shaibi; Marc J. Weigensberg; Michael I. Goran

2006-01-01

145

Adipose tissue as an endocrine and paracrine organ  

Microsoft Academic Search

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

V Mohamed-Ali; JH Pinkney; SW Coppack

1998-01-01

146

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

147

Adiposity, adipose tissue distribution and mortality rates in the Canada Fitness Survey follow-up study  

Microsoft Academic Search

OBJECTIVE: To compare mortality rates across indicators of adiposity and relative adipose tissue distribution in the Canadian population.SUBJECTS: The sample included 10 323 adult participants 20–69 y of age from the Canada Fitness Survey who were monitored for all-cause mortality over 13 y.METHODS: BMI, waist circumference (WC) and the sum of five skinfolds (SF5) were indicators of adiposity, and the

PT Katzmarzyk; CL Craig; C Bouchard

2002-01-01

148

The interactions between rat-adipose-derived stromal cells, recombinant human bone morphogenetic protein-2, and beta-tricalcium phosphate play an important role in bone tissue engineering.  

PubMed

Cells, scaffolds, and growth factors are the three main factors for creating a stem-cell-based tissue-engineered construct, but the interactions between three factors are not very clear. We hereby explored the interactions between rat-adipose-derived stromal cells (rASCs), recombinant human bone morphogenetic protein-2 (rhBMP-2), and beta-tricalcium phosphate (beta-TCP) to provide evidence for their application in bone tissue engineering by evaluating the protein adsorption of beta-TCP, the cell attachment, alkaline phosphatase (ALP) activity/protein, osteocalcin (OCN) content, mineral formation, calcium content, phosphonium content, cell vitality, gene expression, and implantation in the backs of severe combined immunodeficient mice of rhBMP-2 preinducing rASCs seeded onto beta-TCP. The results showed that beta-TCP could adsorb the proteins from the media. The attachment, proliferation, and osteogenic properties of rASCs were supported by beta-TCP, as revealed using scanning electron microscopy. Compared with rASCs cultured on the culture plate, rASCs cultured on beta-TCP had significantly higher ALP activity/protein, OCN content, and mineral formation. These values for rASCs cultured on beta-TCP with rhBMP-2 increased most significantly. The rhBMP-2 significantly increased the calcium content, phosphonium content, and ALP, type I collagen, and OCN mRNA levels of rASCs cultured on beta-TCP. The methylthiazol tetrazolium method revealed that the vitality of rASCs cultured on beta-TCP with or without rhBMP-2 for 4, 7, and 28 days in vitro was insignificantly different. After 8 and 12 weeks of implantation, each group displayed increased bone formation over the 12-week period. The percentage of the new bone formed areas for beta-TCP/rhBMP-2 and beta-TCP was not significantly different. This value for rASCs/beta-TCP construct was significantly higher than that for beta-TCP group, but the maximal and robust bone formation was presented in rASCs/beta-TCP with rhBMP-2. The results implied that stem cells existed in adult rat adipose tissue. beta-TCP could adsorb rhBMP-2 from the media and had osteoinductivity when alone implanted in the back of severe combined immunodeficient mice. beta-TCP was also sufficient to trigger the differentiation of rASCs toward an osteoblastic phenotype without the addition of osteogenic factor. The rhBMP-2 could better sufficiently induce osteogenic differentiation of rASCs seeded onto beta-TCP. The rASCs and rhBMP-2 could promote the dissolution of beta-TCP to provide Ca2+ and PO4(3-) needed for bone formation. The interactions between the three factors could provide an optimizing microenvironment for osteogenic differentiation of rASCs, and this might be essential for sufficient and timely bone formation in vivo. This study may provide insight into the clinical repair of bone defect with ASCs+beta-TCP+rhBMP-2 construct. PMID:20486786

E, Ling-Ling; Xu, Lu-Lu; Wu, Xia; Wang, Dong-Sheng; Lv, Yan; Wang, Jia-Zhu; Liu, Hong-Chen

2010-09-01

149

Lipogenic enzyme activities and cellularity of porcine adipose tissue from various anatomical locations  

Microsoft Academic Search

The activities of acetyl CoA carboxylaqe, citrate cleavage enzyme, malic enzyme, glucose-6-phosphate dehy- drogenase, and 6-phosphogluconate dehydrogenase were de- termined in porcine adipose tissue samples taken from seven anatomical locations, including three layers of backfat, inter- muscular, perirenal, mesenteric, and leg subcutaneous adipose tissues. Adipocyte size and number, as well as lipid and soluble protein content, were also measured in

D. B. Anderson; R. G. Kauffman; L. L. Kastenschmidt

2009-01-01

150

Adipose tissue as regulator of vascular tone.  

PubMed

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

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

2012-06-01

151

Triglyceride Synthesis in Epididymal Adipose Tissue  

PubMed Central

The obesity epidemic has generated interest in determining the contribution of various pathways to triglyceride synthesis, including an elucidation of the origin of triglyceride fatty acids and triglyceride glycerol. We hypothesized that a dietary intervention would demonstrate the importance of using glucose versus non-glucose carbon sources to synthesize triglycerides in white adipose tissue. C57BL/6J mice were fed either a low fat, high carbohydrate (HC) diet or a high fat, carbohydrate-free (CF) diet and maintained on 2H2O (to determine total triglyceride dynamics) or infused with [6,6-2H]glucose (to quantify the contribution of glucose to triglyceride glycerol). The 2H2O labeling data demonstrate that although de novo lipogenesis contributed ?80% versus ?5% to the pool of triglyceride palmitate in HC- versus CF-fed mice, the epididymal adipose tissue synthesized ?1.5-fold more triglyceride in CF- versus HC-fed mice, i.e. 37 ± 5 versus 25 ± 3 ?mol × day–1. The [6,6-2H]glucose labeling data demonstrate that ?69 and ?28% of triglyceride glycerol is synthesized from glucose in HC- versus CF-fed mice, respectively. Although these data are consistent with the notion that non-glucose carbon sources (e.g. glyceroneogenesis) can make substantial contributions to the synthesis of triglyceride glycerol (i.e. the absolute synthesis of triglyceride glycerol from non-glucose substrates increased from ?8 to ?26 ?mol × day–1 in HC- versus CF-fed mice), these observations suggest (i) the importance of nutritional status in affecting flux rates and (ii) the operation of a glycerol-glucose cycle.

Bederman, Ilya R.; Foy, Steven; Chandramouli, Visvanathan; Alexander, James C.; Previs, Stephen F.

2009-01-01

152

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

PubMed

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

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

2012-03-06

153

Overproduction of Angiotensinogen from Adipose Tissue Induces Adipose Inflammation, Glucose Intolerance, and Insulin Resistance  

Microsoft Academic Search

Although obesity is associated with overactivation of the white adipose tissue (WAT) renin–angiotensin system (RAS), a causal link between the latter and systemic insulin resistance is not established. We tested the hypothesis that overexpression of angiotensinogen (Agt) from WAT causes systemic insulin resistance via modulation of adipose inflammation. Glucose tolerance, systemic insulin sensitivity, and WAT inflammatory markers were analyzed in

Nishan S. Kalupahana; Florence Massiera; Annie Quignard-Boulange; Gérard Ailhaud; Brynn H. Voy; David H. Wasserman; Naima Moustaid-Moussa

2012-01-01

154

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

NASA Astrophysics Data System (ADS)

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

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

2007-06-01

155

Proteome of Human Subcutaneous Adipose Tissue Stromal Vascular Fraction Cells vs. Mature Adipocytes Based on DIGE  

PubMed Central

Adipose tissue contains a heterogeneous population of mature adipocytes, endothelial cells, immune cells, pericytes, and pre-adipocytic stromal/stem cells. To date, the majority of proteomic analyses have focused on intact adipose tissue or isolated adipose stromal/stem cells in vitro. In this study, human subcutaneous adipose tissue from multiple depots (arm and abdomen) obtained from female donors was separated into populations of stromal vascular fraction cells and mature adipocytes. Out of 960 features detected by 2-D gel electrophoresis, a total of 200 features displayed a 2-fold up- or down-regulation relative to each cell population. The protein identity of 136 features was determined. Immunoblot analyses comparing SVF relative to adipocytes confirmed that carbonic anhydrase II was up-regulated in both adipose depots while catalase was up-regulated in the arm only. Bioinformatic analyses of the dataset determined that cytoskeletal, glycogenic, glycolytic, lipid metabolic, and oxidative stress related pathways were highly represented as differentially regulated between the mature adipocytes and stromal vascular fraction cells. These findings extend previous reports in the literature with respect to the adipose tissue proteome and the consequences of adipogenesis. The proteins identified may have value as biomarkers for monitoring the physiology and pathology of cell populations within subcutaneous adipose depots.

Kheterpal, Indu; Ku, Ginger; Coleman, Liana; Yu, Gang; Ptitsyn, Andrey A.; Floyd, Z. Elizabeth; Gimble, Jeffrey M.

2011-01-01

156

Adipose tissue and skeletal muscle blood flow during mental stress  

SciTech Connect

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

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

1989-01-01

157

Does adipose tissue thermogenesis play a role in metabolic health?  

PubMed

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

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

2013-04-17

158

Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Deficiency Reduces Leukocyte Infiltration into Adipose Tissue and Favors Fat Deposition  

PubMed Central

Obesity is associated with low-grade inflammation and leukocyte infiltration in white adipose tissue (WAT) and is linked to diabetic complications. Semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1 (SSAO/VAP-1), is a membrane protein that is highly expressed in adipocytes and is also present on the endothelial cell surface where it is involved in leukocyte extravasation. We studied fat deposition and leukocyte infiltration in WAT of mice with a null mutation in the amine oxidase copper-containing-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-month-old AOC3-KO males than in age-matched wild-type controls. However, WAT from AOC3-KO mice contained lower CD45 mRNA levels and fewer CD45+ leukocytes. Subpopulation analyses revealed a diminished infiltration of WAT by T cells, macrophages, natural killer, and natural killer T cells. A decrease in leukocyte content in WAT was also detected in female AOC3-KO mice as early as 2 months of age, whereas increased fat mass was evident by 6 months of age. Reduced CD45+ populations in WAT of AOC3-KO mice was not rescued by human SSAO/VAP-1 expression on adipocytes under the control of aP2, suggesting the importance of vascular AOC3 in leukocyte entrance into fat. Our results indicate that SSAO/VAP-1 is instrumental for the presence of leukocytes in WAT. Therefore, AOC3-KO mice present a unique model of mild obesity, characterized by increased WAT devoid of low-grade inflammation.

Bour, Sandy; Caspar-Bauguil, Sylvie; Iffiu-Soltesz, Zsuzsa; Nibbelink, Maryse; Cousin, Beatrice; Miiluniemi, Mari; Salmi, Marko; Stolen, Craig; Jalkanen, Sirpa; Casteilla, Louis; Penicaud, Luc; Valet, Philippe; Carpene, Christian

2009-01-01

159

Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 deficiency reduces leukocyte infiltration into adipose tissue and favors fat deposition.  

PubMed

Obesity is associated with low-grade inflammation and leukocyte infiltration in white adipose tissue (WAT) and is linked to diabetic complications. Semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1 (SSAO/VAP-1), is a membrane protein that is highly expressed in adipocytes and is also present on the endothelial cell surface where it is involved in leukocyte extravasation. We studied fat deposition and leukocyte infiltration in WAT of mice with a null mutation in the amine oxidase copper-containing-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-month-old AOC3-KO males than in age-matched wild-type controls. However, WAT from AOC3-KO mice contained lower CD45 mRNA levels and fewer CD45(+) leukocytes. Subpopulation analyses revealed a diminished infiltration of WAT by T cells, macrophages, natural killer, and natural killer T cells. A decrease in leukocyte content in WAT was also detected in female AOC3-KO mice as early as 2 months of age, whereas increased fat mass was evident by 6 months of age. Reduced CD45(+) populations in WAT of AOC3-KO mice was not rescued by human SSAO/VAP-1 expression on adipocytes under the control of aP2, suggesting the importance of vascular AOC3 in leukocyte entrance into fat. Our results indicate that SSAO/VAP-1 is instrumental for the presence of leukocytes in WAT. Therefore, AOC3-KO mice present a unique model of mild obesity, characterized by increased WAT devoid of low-grade inflammation. PMID:19218346

Bour, Sandy; Caspar-Bauguil, Sylvie; Iffiú-Soltész, Zsuzsa; Nibbelink, Maryse; Cousin, Béatrice; Miiluniemi, Mari; Salmi, Marko; Stolen, Craig; Jalkanen, Sirpa; Casteilla, Louis; Pénicaud, Luc; Valet, Philippe; Carpéné, Christian

2009-02-13

160

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

PubMed Central

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

Salas, Anna; Noe, Veronique; Ciudad, Carlos J; Romero, M Mar; Remesar, Xavier; Esteve, Montserrat

2007-01-01

161

Immunological goings-on in visceral adipose tissue.  

PubMed

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

Mathis, Diane

2013-06-01

162

Total DDT and dieldrin content of human adipose tissue  

SciTech Connect

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

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

1988-12-01

163

AN INJECTABLE ADIPOSE MATRIX FOR SOFT TISSUE RECONSTRUCTION  

PubMed Central

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

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

2012-01-01

164

Effects of limited and excess protein intakes of pregnant gilts on carcass quality and cellular properties of skeletal muscle and subcutaneous adipose tissue in fattening pigs.  

PubMed

The aim of this study was to investigate whether dietary protein intake of gilts during gestation below (50%) or above (250%) recommendations affects body composition, carcass and meat quality, and properties of skeletal muscle and subcutaneous adipose tissue (SCAT) in offspring at d 83 and 188 of age. German Landrace gilts were fed isoenergetic gestation diets (~13.7 MJ of ME/kg) containing a low (LP, 6.5%; n = 18), an adequate (AP, 12.1%; n = 20), or a high (HP, 30%; n = 16) protein content from mating until farrowing. Within 48 h of birth, offspring were cross-fostered to sows fed a standard diet. On d 83 of age, no effects of the LP diet on BW and body composition were detected, whereas HP pigs showed a slight growth delay (P = 0.06) associated with increased relative weights of small intestine (P < 0.01) and brain (P = 0.08), and reduced relative thymus weight (P < 0.01). On d 188 of age, BW was not different among the dietary groups. However, the carcass of LP pigs contained less (P = 0.01) lean and more (P = 0.07) fat compared with AP and HP pigs, which was only pronounced in pigs originating from large litters (P < 0.05). Like skeletal muscles (P = 0.06), the heart muscle weighed less (P = 0.02) in LP than AP pigs. Compared with AP pigs, LP pigs exhibited a fewer (P = 0.09) total number of myofibers in semitendinosus muscle plus LM both at d 83 and 188 of age, whereas total muscular DNA was less (P = 0.02) at d 188 only. The mRNA abundance of IGF2 measured on d 188 was reduced in SCAT (P = 0.03) and LM (P = 0.07) of LP compared with AP pigs. No changes in muscular fiber type frequency, capillary density, or creatine kinase activity, as well as SCAT adipocyte size and number, were observed at either stages of age. Meat quality characteristics remained unchanged at d 83, whereas Warner-Bratzler shear force value in LM was decreased (P = 0.03) in LP compared with AP pigs on d 188 of age. The results suggest that the maternal LP diet impairs prenatal myofiber formation, reduces the potential of postnatal lean growth related to reduced IGF2 mRNA expression and myonuclear accumulation, and consequently changes carcass quality toward reduced lean proportion and improved tenderness at market weight. In contrast, except for a slight transient growth delay, excess dietary protein during gestation seems to have little effect on the fetal programming of postnatal muscle and adipose tissue phenotype of the progeny. PMID:21890499

Rehfeldt, C; Stabenow, B; Pfuhl, R; Block, J; Nürnberg, G; Otten, W; Metges, C C; Kalbe, C

2011-09-02

165

The role of androgen in the adipose tissue of males.  

PubMed

Adipose tissue, where various metabolic hormones are secreted, plays a role in metabolizing different substances including androgen. Within fat tissue, enzymes such as aromatase and aldo-keto reductase 1C are responsible for metabolizing testosterone into estrogen and 5-dihydrotestosterone into inactive metabolites. Adipose tissue can also affect the secretion of gonadotropin, which influences the formation of androgen in the testes. At the same time, androgen has an impact on the distribution and proliferation of adipose tissue. The adrenoreceptors for catecholamines, which have been proven to play an essential role in controlling lipolysis, function by being up-regulated by androgens. Furthermore, androgens regulate the activity of lipoprotein lipase, a key enzyme involved in intracellular esterification of adipose tissue. PMID:24044108

Lee, Hyun-Ki; Lee, Joo Kyung; Cho, Belong

2013-08-31

166

The Role of Androgen in the Adipose Tissue of Males  

PubMed Central

Adipose tissue, where various metabolic hormones are secreted, plays a role in metabolizing different substances including androgen. Within fat tissue, enzymes such as aromatase and aldo-keto reductase 1C are responsible for metabolizing testosterone into estrogen and 5-dihydrotestosterone into inactive metabolites. Adipose tissue can also affect the secretion of gonadotropin, which influences the formation of androgen in the testes. At the same time, androgen has an impact on the distribution and proliferation of adipose tissue. The adrenoreceptors for catecholamines, which have been proven to play an essential role in controlling lipolysis, function by being up-regulated by androgens. Furthermore, androgens regulate the activity of lipoprotein lipase, a key enzyme involved in intracellular esterification of adipose tissue.

Lee, Hyun-Ki; Lee, Joo Kyung

2013-01-01

167

UCP3: An Uncoupling Protein Homologue Expressed Preferentially and Abundantly in Skeletal Muscle and Brown Adipose Tissue  

Microsoft Academic Search

Uncoupling proteins (UCPs) are inner mitochondrial membrane transporters which dissipate the proton gradient, releasing stored energy as heat. UCP1 is expressed exclusively in brown adipocytes while UCP2 is expressed widely. We now report the molecular cloning of a third uncoupling protein homologue, designated UCP3. At the amino acid level, hUCP3 is 71% identical to hUCP2 and 57% identical to hUCP1.

Antonio Vidal-Puig; Gemma Solanes; Danica Grujic; Jeffrey S. Flier; Bradford B. Lowell

1997-01-01

168

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

PubMed

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 over-express 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. PMID:22614697

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

2012-05-22

169

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

170

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

Microsoft Academic Search

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

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

2008-01-01

171

Adipose tissue cholesteryl ester transfer protein mRNA in response to probucol treatment: cholesterol and species dependence  

Microsoft Academic Search

Probucol treatment results in an increase in plasma concentrations of cholesteryl ester transfer protein (CETP) which may account, in part, for the effects of this agent on plasma concentrations of HDL cholesterol. We have examined the mechanism by which probucol increases plasma CETP and have determined the associated changes in the plasma distribu- tion of high density lipoprotein (HDL) particles.

Elaine M. Quinet; Patricia Huerta; Dipchan Nancoo; Alan R. Tall; Yves L. Marcel; Ruth McPherson

172

Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin.  

PubMed

Adiponutrin is a newly described white adipose tissue (WAT)-derived protein whose function and regulation remain widely unclear in humans though it is suggested to be related to insulin sensitivity. Recently, we found that adiponutrin expression is reduced in type 2 diabetic subjects in basal and insulin-stimulated states. To examine adiponutrin regulation by the insulin pathway in relation to other WAT-related proteins with well-known relation to insulin signaling and action, we examined in healthy young men (1) the association of adiponutrin with p85alpha PI3K and HKII, leptin, adiponectin, and acylation-stimulating protein (ASP) and (2) the regulation of adiponutrin and WAT-derived proteins by 3-h hyperinsulinemic euglycemic clamp (HIEG). At baseline (N = 20), adiponutrin expressions were positively correlated with those of p85alpha PI3K (R = 0.54, P = 0.017), HKII (R = 0.58, P = 0.010), and serum leptin (R = 0.51, P = 0.036), but not with any other parameter measured including insulin sensitivity. Hyperinsulinemia (N = 10, +2365% above baseline) significantly increased the expression of adiponutrin (+770%, P = 0.002), p85alpha PI3K (+150%, P = 0.033), HKII (+147%, P = 0.007), and serum leptin (+11%, P = 0.031), while it decreased serum adiponectin (-15%, P = 0.001). In the insulin-stimulated state, adiponutrin mRNA expression levels correlated with basal p85alpha PI3K (R = 0.76, P = 0.018) and HKII (R = 0.86, P = 0.003) expression levels, with percentage increase in insulin (R = 0.73, P = 0.040), and with insulin-stimulated state HKII (R = 0.82, P = 0.007), leptin (R = 0.84, P = 0.005), and adiponectin (R = 0.85, P = 0.004) mRNA levels. In healthy young men, adiponutrin expression is upregulated [corrected] by hyperinsulinemia and is related to basal and/or insulin-stimulated p85alpha PI3K, HKII, adiponectin, and leptin expression levels. We hypothesize that insulin-mediated regulation of adiponutrin expression is under the PI3K pathway. The relevance of the present findings to reduced adiponutrin expression in type 2 diabetes is discussed. PMID:17088412

Faraj, May; Beauregard, Genevieve; Loizon, Emmanuelle; Moldes, Marthe; Clément, Karine; Tahiri, Youssef; Cianflone, Katherine; Vidal, Hubert; Rabasa-Lhoret, Rémi

2006-11-01

173

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

PubMed

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

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

2013-07-21

174

The Determination of Pentachlorophenol and Hexachlorophene in Human Adipose Tissue.  

National Technical Information Service (NTIS)

The identification and quantitation of potential chemical pollutants and their metabolites in human adipose tissue are of great importance for monitoring human exposure to these environmental compounds. The two highly chlorinated phenols, pentachloropheno...

T. M. Shafik

1973-01-01

175

[Epicardial adipose tissue: more than a simple fat deposit?].  

PubMed

Obesity increases the risk of development of atherosclerosis. However, this risk significantly depends on adipose tissue distribution in the body and ectopic accumulation of visceral adipose tissue (VAT). Recent evidence suggests that each visceral fat deposit is anatomically and functionally different. Due to proximity to the organ, each visceral fat deposit exerts a local modulation rather than a systemic effect. Because of its unique location and biomolecular properties, a "non-traditional" fat depot - the epicardial adipose tissue - has been considered to play a causative role in atherosclerosis. Epicardial adipose tissue may be measured with imaging techniques and is clinically related to left ventricular mass, coronary artery disease, and metabolic syndrome. Therefore, epicardial fat measurement may play a role in stratification of cardiometabolic risk and may serve as a therapeutic target. PMID:23117053

Lima-Martínez, Marcos M; Blandenier, Claudia; Iacobellis, Gianluca

2012-10-30

176

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

PubMed

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

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

2012-05-29

177

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

178

Metabolic and Vascular Consequences of Adipose Tissue Dysfunction  

Microsoft Academic Search

Adipose Tissue Dysfunction (ATD) has been proposed as the pathophysiological route by which obesity confers its associated increased risk for cardiovascular disease and is characterized by an increased secretion of pro-inflammatory cytokines and adipokines and reduced secretion of anti-inflammatory adipokines such as adiponectin from adipose tissue. A review of literature shows that a range of currently available (non-)pharmacological interventions such

J. Westerink

2012-01-01

179

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

180

Automatic Segmentation of Abdominal Adipose Tissue in MRI  

Microsoft Academic Search

\\u000a This paper presents a method for automatically segmenting abdominal adipose tissue from 3-dimensional magnetic resonance images.\\u000a We distinguish between three types of adipose tissue; visceral, deep subcutaneous and superficial subcutaneous. Images are\\u000a pre-processed to remove the bias field effect of intensity in-homogeneities. This effect is estimated by a thin plate spline\\u000a extended to fit two classes of automatically sampled intensity

Thomas Hammershaimb Mosbech; Kasper Pilgaard; Allan Vaag; Rasmus Larsen

2011-01-01

181

Tissue inhibitor of metalloproteinase-1 predicts adiposity in humans  

Microsoft Academic Search

Objective: Tissue inhibitor of metalloproteinase (TIMP)-1 is upregulated in fat of obese rodents and promotes adipose tissue development in these animals. However, it is unclear whether TIMP-1 independently predicts adiposity in humans and whether serum levels are increased in s.c. and visceral obesity. Design: Twenty-four lean, 16 s.c. obese, and 20 visceral obese subjects were studied. Methods: Plasma TIMP-1 concentrations

Susan Kralisch; Matthias Bluher; Anke Tonjes; Ulrike Lossner; Ralf Paschke; Michael Stumvoll; Mathias Fasshauer

2007-01-01

182

Gene expression profile of omental adipose tissue in human obesity  

Microsoft Academic Search

The aim of the present study was to gain insight into the pathophysiology of obesity by comparing the pattern of gene expression of omental adipose tissue of obese and lean volunteers using DNA microarrays. Omental adipose tissue biopsies were obtained by laparoscopic surgery from six male patients (44.2±6.3 yr). RNA was extracted and pooled for the obese (BMI: 37.3±2.5 kg\\/m2)

J. Gomez-Ambrosi; Victoria Catalán; Alberto Diez-Caballero; L. Alfonso Martínez-Cruz; María J. Gil; Jesús García-Foncillas; Javier A. Cienfuegos; Javier Salvador; José M. Mato; Gema Frühbeck

2003-01-01

183

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

184

Perivascular adipose tissue in the pathogenesis of cardiovascular disease.  

PubMed

Adipose tissue, which has been considered mainly as a site of energy storage and mobilization, is found in many depots throughout the body. Adipose depots may have structural properties such as, for instance, the fat pads located in the hands and feet and the periorbital fat supporting the eyes. Adipose tissue also shows remarkable regional heterogeneity. For instance, substantial differences have been reported in the metabolic properties of visceral (intra-abdominal) vs. subcutaneous adipose depots. Visceral adipose tissue (VAT) has active endocrine and paracrine functions with the secretion of various pro-inflammatory chemokines potentially contributing to the progression of atherosclerosis related with obesity. In addition, adipose depots surrounding the heart, such as epicardial (EAT) and perivascular adipose tissues (PAT) may also exert important roles in the pathogenesis of cardiovascular disease beyond the contribution of VAT due to their close anatomic relationships with vascular structures and myocardium. The purpose of the present review is to outline the current understanding of the pathophysiological links between EAT, PAT and atherosclerotic cardiovascular disease. Also, we discuss the current investigative methods for PAT quantification and discuss the potential impact of PAT on cardiovascular risk prediction. Finally, potential clinical implications of these notions are discussed. PMID:24075741

Lee, Hae-Young; Després, Jean-Pierre; Koh, Kwang Kon

2013-07-27

185

Reducing Glycosphingolipid Content in Adipose Tissue of Obese Mice Restores Insulin Sensitivity, Adipogenesis and Reduces Inflammation  

PubMed Central

Adipose tissue is a critical mediator in obesity-induced insulin resistance. Previously we have demonstrated that pharmacological lowering of glycosphingolipids and subsequently GM3 by using the iminosugar AMP-DNM, strikingly improves glycemic control. Here we studied the effects of AMP-DNM on adipose tissue function and inflammation in detail to provide an explanation for the observed improved glucose homeostasis. Leptin-deficient obese (LepOb) mice were fed AMP-DNM and its effects on insulin signalling, adipogenesis and inflammation were monitored in fat tissue. We show that reduction of glycosphingolipid biosynthesis in adipose tissue of LepOb mice restores insulin signalling in isolated ex vivo insulin-stimulated adipocytes. We observed improved adipogenesis as the number of larger adipocytes was reduced and expression of genes like peroxisome proliferator-activated receptor (PPAR) ?, insulin responsive glucose transporter (GLUT)-4 and adipsin increased. In addition, we found that adiponectin gene expression and protein were increased by AMP-DNM. As a consequence of this improved function of fat tissue we observed less inflammation, which was characterized by reduced numbers of adipose tissue macrophages (crown-like structures) and reduced levels of the macrophage chemo attractants monocyte-chemoattractant protein-1 (Mcp-1/Ccl2) and osteopontin (OPN). In conclusion, pharmacological lowering of glycosphingolipids by inhibition of glucosylceramide biosynthesis improves adipocyte function and as a consequence reduces inflammation in adipose tissue of obese animals.

van Eijk, Marco; Aten, Jan; Bijl, Nora; Ottenhoff, Roelof; van Roomen, Cindy P. A. A.; Dubbelhuis, Peter F.; Seeman, Ingar; Ghauharali-van der Vlugt, Karen; Overkleeft, Hermen S.; Arbeeny, Cynthia; Groen, Albert K.; Aerts, Johannes M. F. G.

2009-01-01

186

Organotypic culture of human bone marrow adipose tissue.  

PubMed

The precise role of bone marrow adipose tissue (BMAT) in the marrow remains unknown. The purpose of the present study was therefore to describe a novel method for studying BMAT using 3-D collagen gel culture of BMAT fragments, immunohistochemistry, ELISA and real-time reverse transcription-polymerase chain reaction. Mature adipocytes and CD45+ leukocytes were retained for >3 weeks. Bone marrow stromal cells (BMSC) including a small number of lipid-laden preadipocytes and CD44+/CD105+ mesenchymal stem cell (MSC)-like cells, developed from BMAT. Dexamethasone (10 micromol/L), but not insulin (20 mU/mL), significantly increased the number of preadipocytes. Dexamethasone and insulin also promoted leptin production and gene expression in BMAT. Adiponectin production by BMAT was <0.8 ng/mL under all culture conditions. Dexamethasone promoted adiponectin gene expression, while insulin inhibited it. This finding suggests that dexamethasone, but not insulin, may serve as a powerful adipogenic factor for BMAT, in which adiponectin protein secretion is normally very low, and that BMAT may exhibit a different phenotype from that of the visceral and subcutaneous adipose tissues. BMAT-osteoblast interactions were also examined, and it was found that osteoblasts inhibited the development of BMSC and reduced leptin production, while BMAT inhibited the growth and differentiation of osteoblasts. The present novel method proved to be useful for the study of BMAT biology. PMID:20403027

Uchihashi, Kazuyoshi; Aoki, Shigehisa; Shigematsu, Masamori; Kamochi, Noriyuki; Sonoda, Emiko; Soejima, Hidenobu; Fukudome, Kenji; Sugihara, Hajime; Hotokebuchi, Takao; Toda, Shuji

2010-04-01

187

The effects of glucocorticoids on adipose tissue lipid metabolism.  

PubMed

Glucocorticoids (GCs) have long been accepted as being catabolic in nature, liberating energy substrates during times of stress to supply the increased metabolic demand of the body. The effects of GCs on adipose tissue metabolism are conflicting, however, because patients with elevated GCs present with central adiposity. We performed an extensive literature review of the effects of GCs on adipose tissue metabolism. The contradictory effects of GCs on lipid metabolism occur through a number of different mechanisms, some of which are well defined and others remain to be elucidated. Firstly, through increases in caloric and dietary fat intake, along with increased hydrolysis of circulating triglycerides (chylomicrons, very low-density lipoproteins) by lipoprotein lipase activity, GCs increase the amount of fatty acids in circulation, which are then available for ectopic fat distribution (liver, muscle, and central adipocytes). Glucocorticoids also increase de novo lipid production in hepatocytes through increased expression of fatty acid synthase. There is some controversy as to whether these same mechanisms occur in adipocytes, thereby contributing to adipose hypertrophy. Glucocorticoids promote preadipocyte conversion to mature adipocytes, causing hyperplasia of the adipose tissue. Glucocorticoids also have acute antilipolytic effect on adipocytes, whereas their genomic actions facilitate increased lipolysis after about 48 hours of exposure. The acute and long-term effects of GCs on adipose tissue lipolysis remain unclear. Although considerable evidence supports the notion that GCs increase lipolysis through glucocorticoid-induced increases of lipase expression, they clearly have antilipolytic effects within these same tissues and cell line models. PMID:21864867

Peckett, Ashley J; Wright, David C; Riddell, Michael C

2011-08-23

188

Inflammation and adipose tissue macrophages in lipodystrophic mice.  

PubMed

Lipodystrophy and obesity are opposites in terms of a deficiency versus excess of adipose tissue mass, yet these conditions are accompanied by similar metabolic consequences, including insulin resistance, dyslipidemia, hepatic steatosis, and increased risk for diabetes and atherosclerosis. Hepatic and myocellular steatosis likely contribute to metabolic dysregulation in both states. Inflammation and macrophage infiltration into adipose tissue also appear to participate in the pathogenesis of obesity-induced insulin resistance, but their contributions to lipodystrophy-induced insulin resistance have not been evaluated. We used aP2-nSREBP-1c transgenic (Tg) mice, an established model of lipodystrophy, to ask this question. Circulating cytokine elevations suggested systemic inflammation but even more dramatic was the number of infiltrating macrophages in all white and brown adipose tissue depots of the Tg mice; in contrast, there was no evidence of inflammatory infiltrates or responses in any other tissue including liver. Despite there being overt evidence of adipose tissue inflammation, antiinflammatory strategies including salicylate treatment and genetic suppression of myeloid NF-kappaB signaling that correct insulin resistance in obesity were ineffective in the lipodystrophic mice. We further showed that adipose tissue macrophages (ATMs) in lipodystrophy and obesity are very different in terms of activation state, gene expression patterns, and response to lipopolysaccharide. Although ATMs are even more abundant in lipodystrophy than in obesity, they have distinct phenotypes and likely roles in tissue remodeling, but do not appear to be involved in the pathogenesis of insulin resistance. PMID:20007767

Herrero, Laura; Shapiro, Hagit; Nayer, Ali; Lee, Jongsoon; Shoelson, Steven E

2009-12-10

189

Regulation of Microvascular Function by Adipose Tissue in Obesity and Type 2 Diabetes: Evidence of an Adipose-Vascular Loop  

PubMed Central

In recent years, the general concept has emerged that chronic low-grade inflammation is the condition linking excessive development of adipose tissue and obesity-associated pathologies such as type 2 diabetes and cardiovascular diseases. Obesity and type 2 diabetes are characterized by a diminished production of protective factors such as adiponectin and increased detrimental adipocytokines such as leptin, resistin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF?), and monocyte chemoattractant protein-1 (MCP-1) by adipose tissue. Moreover, the evidence that the growth of the fat mass is associated with an accumulation of adipose tissue macrophages and T-lymphocytes has raised the hypothesis that the development of an inflammatory process within the growing fat mass is a primary event involved in the genesis of systemic metabolic and vascular alterations. This crosstalk of adipocyte, macrophage, lymphocyte, endothelial cells, and vascular smooth muscle cells contribute to the production of various cytokines, chemokines, and hormone-like factors, which actively participate in the regulation of vascular function by an endocrine and/or paracrine pattern. Thus, the signaling from perivascular adipose to the blood vessels is emerging as a potential therapeutic target for obesity and diabetes-associated vascular dysfunction.

Zhang, Hanrui; Zhang, Cuihua

2009-01-01

190

Dexamethasone and the inflammatory response in explants of human omental adipose tissue.  

PubMed

Dexamethasone is a synthetic glucocorticoid that is a potent anti-inflammatory agent. The present studies examined the changes in gene expression of 64 proteins in human omental adipose tissue explants incubated for 48h both in the absence and presence of dexamethasone as well as the release of 8 of these proteins that are putative adipokines. The proteins were chosen because they are inflammatory response proteins in other cells, are key regulatory proteins or are proteins with known functions. About 50% were significantly up-regulated while about 10% were unchanged and the remaining 40% were down-regulated. Dexamethasone significantly up-regulated the expression of about 33% of the proteins but down-regulated the expression of about 12% of the proteins. We conclude that dexamethasone is a selective anti-inflammatory agent since it inhibits only about one-fourth of the proteins up-regulated during in vitro incubation of human omental adipose tissue. PMID:19853017

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

2009-10-21

191

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

192

[Brown adipose tissue: the body's own weapon against obesity?].  

PubMed

Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP1. It has recently been discovered that BAT is present and active in adults. BAT is situated predominantly around the aorta and in the supraclavicular area. BAT volume and activity are lower in individuals who are obese. This suggests that BAT significantly contributes to total energy expenditure. Several pathological conditions that are accompanied by activation of BAT, such as hyperthyroidism and phaeochromocytoma, result in the increased expenditure of energy and in weight loss. Various ways in which BAT can be manipulated to increase the expenditure of energy have been identified, e.g. exposure to cold, the use of so-called uncoupling agents or the administration of the hormone irisin. The activation of BAT could potentially be used to induce weight loss. PMID:23676126

Boon, Mariëtte R; Bakker, Leontine E H; Meinders, A Edo; van Marken Lichtenbelt, Wouter; Rensen, Patrick C N; Jazet, Ingrid M

2013-01-01

193

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

2012-08-31

194

Brown Adipose Tissue in Morbidly Obese Subjects  

PubMed Central

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

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

2011-01-01

195

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

196

Natural killer T cells in adipose tissue prevent insulin resistance  

PubMed Central

Lipid overload and adipocyte dysfunction are key to the development of insulin resistance and can be induced by a high-fat diet. CD1d-restricted invariant natural killer T (iNKT) cells have been proposed as mediators between lipid overload and insulin resistance, but recent studies found decreased iNKT cell numbers and marginal effects of iNKT cell depletion on insulin resistance under high-fat diet conditions. Here, we focused on the role of iNKT cells under normal conditions. We showed that iNKT cell–deficient mice on a low-fat diet, considered a normal diet for mice, displayed a distinctive insulin resistance phenotype without overt adipose tissue inflammation. Insulin resistance was characterized by adipocyte dysfunction, including adipocyte hypertrophy, increased leptin, and decreased adiponectin levels. The lack of liver abnormalities in CD1d-null mice together with the enrichment of CD1d-restricted iNKT cells in both mouse and human adipose tissue indicated a specific role for adipose tissue–resident iNKT cells in the development of insulin resistance. Strikingly, iNKT cell function was directly modulated by adipocytes, which acted as lipid antigen-presenting cells in a CD1d-mediated fashion. Based on these findings, we propose that, especially under low-fat diet conditions, adipose tissue–resident iNKT cells maintain healthy adipose tissue through direct interplay with adipocytes and prevent insulin resistance.

Schipper, Henk S.; Rakhshandehroo, Maryam; van de Graaf, Stan F.J.; Venken, Koen; Koppen, Arjen; Stienstra, Rinke; Prop, Serge; Meerding, Jenny; Hamers, Nicole; Besra, Gurdyal; Boon, Louis; Nieuwenhuis, Edward E.S.; Elewaut, Dirk; Prakken, Berent; Kersten, Sander; Boes, Marianne; Kalkhoven, Eric

2012-01-01

197

Secretome analysis of rat adipose tissues shows location-specific roles for each depot type.  

PubMed

Obesity prevalence is reaching pandemic proportions becoming a major public health threat for many industrialized nations. It is especially worrying as it causes a higher risk of premature death due to associated diseases such as type 2 diabetes, cardiovascular disease, and some cancers. Current evidence shows biological and genetic differences between adipose tissues depending on its anatomical location. Particularly, upper body/visceral fat distribution in obesity is closely linked to metabolic complications. In this report, we characterize for the first time the secretome of rat adipose tissue explants from different anatomical localizations and its differential analysis. Visceral, subcutaneous, and gonadal fat specific secretomes and differentially secreted proteins among the three fat depots were analyzed by 2-DE and MS. Reference maps for location-specific adipose tissue secretomes are shown and the 45 most significant differences are listed. Identified proteins include classical adipokines and novel secreted proteins. Interestingly, our results show that the type of proteins and their role in different biological processes diverge significantly when comparing the set of proteins identified from visceral, subcutaneous and gonadal fat explants. This study emphasizes and supports the differential role of adipose tissue in accordance to its anatomical localization. PMID:21439414

Roca-Rivada, Arturo; Alonso, Jana; Al-Massadi, Omar; Castelao, Cecilia; Peinado, Juan Ramón; Seoane, Luisa María; Casanueva, Felipe F; Pardo, María

2011-03-23

198

Concentration of sex steroids in adipose tissue after menopause.  

PubMed

Adipose tissue is a site of uptake, storage, action, and metabolism of sex steroids. After menopause aromatization of androgens to estrogens in adipose tissue is one of the most important sources of estrogen in the circulation and for peripheral tissues. The aim of this study was to estimate local sex steroid concentrations in breast and abdominal subcutaneous (s.c.) adipose tissue, to compare them with plasma concentrations and to investigate possible correlations with body mass index (BMI). The patients were postmenopausal women undergoing surgery for non-oncological reasons (Group A; n = 35) and breast cancer patients (group B; n = 19). The concentrations of estrone, 17 beta-estradiol, estrone sulfate, 17 beta-estradiol sulfate, androstenedione, androstenediol (androst-5-ene-3 beta, 17 beta-diol), testosterone and dehydroepiandrosterone were measured. The method was based on frozen tissue homogenization, extraction with ethanol: acetone, delipidation, extraction of estrogens with ether, and of androgens with iso-octane in toluene, followed by RIA. The mean levels of steroids were higher in fat than in plasma, apart from testosterone. Levels of sulfates of estrogens and androstenediol were higher in breast than abdominal adipose tissue, and levels of estradiol lower. Positive correlations were found between BMI and tissue and plasma concentration of both estrone and androstenedione. PMID:9618794

Szymczak, J; Milewicz, A; Thijssen, J H; Blankenstein, M A; Daroszewski, J

199

Extended longevity and insulin signaling in adipose tissue.  

PubMed

Caloric restriction and leanness have been shown to increase longevity in organisms ranging from yeast to mammals. Adipose tissue seems to be a pivotal organ in the aging process and in determination of lifespan. We have recently shown that fat-specific disruption of the insulin receptor gene is sufficient to increase lifespan in FIRKO mice, suggesting that reduced adiposity, even in the presence of normal or increased food intake, can extend lifespan. The model also suggests a special role for the insulin-signaling pathway in adipose tissue in the longevity process. Reduced fat mass has an impact on the duration of life in several other model organisms. In Drosophila, a specific reduction in the fat body through overexpression of forkhead type transcription factor (dFOXO) extends lifespan. Furthermore, sirtuin1 (SIRT1), the mammalian ortholog of the life-extending yeast gene silent information regulator 2 (SIR2), was proposed to be involved in the molecular mechanisms linking lifespan to adipose tissue. In the control of human aging and longevity, one of the striking physiological characteristics identified in centenarians is their greatly increased insulin sensitivity even compared with younger individuals. The effect of reduced adipose tissue mass on lifespan could be due to the prevention of obesity-related metabolic disorders including type 2 diabetes and atherosclerosis. PMID:16125891

Klöting, Nora; Blüher, Matthias

2005-08-25

200

Adipocyte fetuin-a contributes to macrophage migration into adipose tissue and polarization of macrophages.  

PubMed

Macrophage infiltration into adipose tissue during obesity and their phenotypic conversion from anti-inflammatory M2 to proinflammatory M1 subtype significantly contributes to develop a link between inflammation and insulin resistance; signaling molecule(s) for these events, however, remains poorly understood. We demonstrate here that excess lipid in the adipose tissue environment may trigger one such signal. Adipose tissue from obese diabetic db/db mice, high fat diet-fed mice, and obese diabetic patients showed significantly elevated fetuin-A (FetA) levels in respect to their controls; partially hepatectomized high fat diet mice did not show noticeable alteration, indicating adipose tissue to be the source of this alteration. In adipocytes, fatty acid induces FetA gene and protein expressions, resulting in its copious release. We found that FetA could act as a chemoattractant for macrophages. To simulate lipid-induced inflammatory conditions when proinflammatory adipose tissue and macrophages create a niche of an altered microenvironment, we set up a transculture system of macrophages and adipocytes; the addition of fatty acid to adipocytes released FetA into the medium, which polarized M2 macrophages to M1. This was further confirmed by direct FetA addition to macrophages. Taken together, lipid-induced FetA from adipocytes is an efficient chemokine for macrophage migration and polarization. These findings open a new dimension for understanding obesity-induced inflammation. PMID:23943623

Chatterjee, Priyajit; Seal, Soma; Mukherjee, Sandip; Kundu, Rakesh; Mukherjee, Sutapa; Ray, Sukanta; Mukhopadhyay, Satinath; Majumdar, Subeer S; Bhattacharya, Samir

2013-08-13

201

Liver fat content is linked to inflammatory changes in subcutaneous adipose tissue in type 2 diabetes patients.  

PubMed

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are typically overweight and have an increased liver fat content (LFAT). High LFAT may be explained by an increased efflux of free fatty acids from the adipose tissue, which is partly instigated by inflammatory changes. This would imply an association between inflammatory features of the adipose tissue and liver fat content. OBJECTIVE: To analyse associations between inflammatory features of the adipose tissue and liver fat content. DESIGN: A cross-sectional study. PATIENTS: Twenty-seven obese patients with insulin-treated T2DM were studied. MEASUREMENTS: LFAT content was measured by proton magnetic resonance spectroscopy. A subcutaneous (sc) fat biopsy was obtained to determine morphology and protein levels within adipose tissue. In addition to fat cell size, the percentage of macrophages and the presence of crown-like structures (CLSs) within sc fat were assessed by CD68-immunohistochemical staining. RESULTS: Mean LFAT percentage was 11·1 ± 1·7% (range: 0·75-32·9%); 63% of the patients were diagnosed with an elevated LFAT (upper range of normal ?5·5%). Whereas adipocyte size did not correlate with LFAT, 3 of 4 subjects with CLSs in sc fat had elevated LFAT and the percentage of macrophages present in sc adipose tissue was positively associated with LFAT. Protein concentrations of adiponectin within adipose tissue negatively correlated with LFAT. Adipose tissue protein levels of the key inflammatory adipokine plasminogen activator inhibitor-1 (PAI-1) were positively associated with LFAT. CONCLUSIONS: Several pro-inflammatory changes in sc adipose tissue associate with increased LFAT content in obese insulin-treated patients with T2DM. These findings suggest that inflammatory changes at the level of the adipose tissue may drive liver fat accumulation. PMID:23167778

Jansen, Henry J; Vervoort, Gerald M; van der Graaf, Marinette; Stienstra, Rinke; Tack, Cees J

2012-11-20

202

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

PubMed

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

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

2013-02-11

203

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

PubMed Central

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

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

2012-01-01

204

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

PubMed

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

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

2011-09-21

205

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

2013-06-04

206

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

PubMed Central

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.

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

207

Effect of Dietary Canola on Fatty Acid Composition of Bovine Adipose Tissue, Muscle, Kidney, and Liver  

Microsoft Academic Search

The purpose of this study was to determine effects of feeding canola and soybean products as protein supplements on fatty acid composi- tion of adipose tissue and muscle of slaughter bulls and steers and on fatty acid composition of kidney and liver total lipids of bulls. Products included canola meal (CM), extruded canola (EC, full-fat), ground canola (GC, full-fat), soybean

J. R. Busboom; C. J. Kercher

2010-01-01

208

Regional Differences in Subcutaneous Adipose Tissue Gene Expression  

PubMed Central

Adipose tissue located in the viscera is considered to be functionally and metabolically different from that found in the subcutaneous depot. However, subcutaneous adipose tissue in generalized regions is considered to be homogeneous in nature. Affymetrix GeneChip Human Exon 1.0 ST Arrays were used to determine differential gene expression in four subcutaneous adipose depots (upper abdomen, lower abdomen, flank and hip) in normal weight women. A total of 2890/24,409 transcripts were differentially expressed between all sites. When comparing the hip and flank to the lower abdomen, 248 and 83 genes were differentially expressed, respectively. When comparing the hip and flank to the upper abdomen, 2480 and 79 genes were differentially expressed, respectively. No genes were significantly different when the lower abdomen was compared to the upper abdomen and the hip to the flank. Genes involved in the complement and coagulation cascades and immune responses showed increased expression in the lower abdomen compared to the flank. In addition, two genes involved in the complement and coagulation cascade, CR1 and C7, were expressed more highly in the lower abdomen compared to the hip. Genes involved in basic biochemical metabolism including insulin signaling, the urea cycle, glutamate metabolism, arginine and proline metabolism and aminosugar metabolism had higher expression in the lower abdomen compared to the hip. These results in normal weight healthy women provide a new perspective on regional differences in subcutaneous adipose tissue biology that may have pathophysiologic implications when adiposity increases.

Rehrer, Charles W.; Karimpour-Fard, Anis; Hernandez, Teri L.; Law, Christopher K.; Stob, Nichole; Hunter, Lawrence; Eckel, Robert H.

2012-01-01

209

Biglycan Deletion Alters Adiponectin Expression in Murine Adipose Tissue and 3T3-L1 Adipocytes  

PubMed Central

Obesity promotes increased secretion of a number of inflammatory factors from adipose tissue. These factors include cytokines and very lately, extracellular matrix components (ECM). Biglycan, a small leucine rich proteoglycan ECM protein, is up-regulated in obesity and has recently been recognized as a pro-inflammatory molecule. However, it is unknown whether biglycan contributes to adipose tissue dysfunction. In the present study, we characterized biglycan expression in various adipose depots in wild-type mice fed a low fat diet (LFD) or obesity-inducing high fat diet (HFD). High fat feeding induced biglycan mRNA expression in multiple adipose depots. Adiponectin is an adipokine with anti-inflammatory and insulin sensitizing effects. Due to the importance of adiponectin, we examined the effect of biglycan on adiponectin expression. Comparison of adiponectin expression in biglycan knockout (bgn?/0) and wild-type (bgn+/0) reveals higher adiponectin mRNA and protein in epididymal white adipose tissue in bgn?/0 mice, as well higher serum concentration of adiponectin, and lower serum insulin concentration. On the contrary, knockdown of biglycan in 3T3-L1 adipocytes led to decreased expression and secretion of adiponectin. Furthermore, treatment of 3T3-L1 adipocytes with conditioned medium from biglycan treated macrophages resulted in an increase in adiponectin mRNA expression. These data suggest a link between biglycan and adiponectin expression. However, the difference in the pattern of regulation between in vivo and in vitro settings reveals the complexity of this relationship.

Ward, Meliza G.; Ajuwon, Kolapo M.

2012-01-01

210

Growth hormone regulates leptin gene expression in bovine adipose tissue: correlation with adipose IGF-1 expression  

Microsoft Academic Search

Leptin, the product of the ob gene, is secreted from white adipocytes and regulates food intake and whole-body energy metabolism. In rodents and humans, leptin gene expression is under complex endocrine and metabolic control, and is strongly influenced by energy balance. Growth hormone (GH) has myriad effects on adipose tissue metabolism. The primary aim of this study was to determine

K L Houseknecht; C P Portocarrero; R Lemenager; M E Spurlock

2000-01-01

211

Increased Macrophage Migration Into Adipose Tissue in Obese Mice  

PubMed Central

Macrophage-mediated inflammation is a key component of insulin resistance; however, the initial events of monocyte migration to become tissue macrophages remain poorly understood. We report a new method to quantitate in vivo macrophage tracking (i.e., blood monocytes from donor mice) labeled ex vivo with fluorescent PKH26 dye and injected into recipient mice. Labeled monocytes appear as adipose, liver, and splenic macrophages, peaking in 1–2 days. When CCR2 KO monocytes are injected into wild-type (WT) recipients, or WT monocytes given to MCP-1 KO recipients, adipose tissue macrophage (ATM) accumulation is reduced by ~40%, whereas hepatic macrophage content is decreased by ~80%. Using WT donor cells, ATM accumulation is several-fold greater in obese recipient mice compared with lean mice, regardless of the source of donor monocytes. After their appearance in adipose tissue, ATMs progressively polarize from the M2- to the M1-like state in obesity. In summary, the CCR2/MCP-1 system is a contributory factor to monocyte migration into adipose tissue and is the dominant signal controlling the appearance of recruited macrophages in the liver. Monocytes from obese mice are not programmed to become inflammatory ATMs but rather the increased proinflammatory ATM accumulation in obesity is in response to tissue signals.

Oh, Da Young; Morinaga, Hidetaka; Talukdar, Saswata; Bae, Eun Ju; Olefsky, Jerrold M.

2012-01-01

212

Increased macrophage migration into adipose tissue in obese mice.  

PubMed

Macrophage-mediated inflammation is a key component of insulin resistance; however, the initial events of monocyte migration to become tissue macrophages remain poorly understood. We report a new method to quantitate in vivo macrophage tracking (i.e., blood monocytes from donor mice) labeled ex vivo with fluorescent PKH26 dye and injected into recipient mice. Labeled monocytes appear as adipose, liver, and splenic macrophages, peaking in 1-2 days. When CCR2 KO monocytes are injected into wild-type (WT) recipients, or WT monocytes given to MCP-1 KO recipients, adipose tissue macrophage (ATM) accumulation is reduced by ~40%, whereas hepatic macrophage content is decreased by ~80%. Using WT donor cells, ATM accumulation is several-fold greater in obese recipient mice compared with lean mice, regardless of the source of donor monocytes. After their appearance in adipose tissue, ATMs progressively polarize from the M2- to the M1-like state in obesity. In summary, the CCR2/MCP-1 system is a contributory factor to monocyte migration into adipose tissue and is the dominant signal controlling the appearance of recruited macrophages in the liver. Monocytes from obese mice are not programmed to become inflammatory ATMs but rather the increased proinflammatory ATM accumulation in obesity is in response to tissue signals. PMID:22190646

Oh, Da Young; Morinaga, Hidetaka; Talukdar, Saswata; Bae, Eun Ju; Olefsky, Jerrold M

2011-12-21

213

Epinephrine induces PDK4 mRNA expression in adipose tissue from obese, insulin resistant rats.  

PubMed

Thiazolidinediones (TZDs) are a commonly prescribed class of insulin sensitizing drugs that increase fatty acid re-esterification, in part through the induction of pyruvate dehydrogenase kinase 4 (PDK4). Owing to the deleterious side effects of TZDs the identification of alternative approaches with which to increase PDK4 is essential. We recently demonstrated that epinephrine increases PDK4 expression through p38 and peroxisome proliferator-activated receptor ? (PPAR?) dependent pathways in cultured adipose tissue from lean rats. The purpose of this study was to determine whether acute epinephrine treatment, in vivo, can induce PDK4 mRNA expression in adipose tissue from obese, insulin resistant rats and if the reputed signaling pathways mediating this effect are intact. To this end we fed male Wistar rats a chow or high-fat diet (HFD, 60% kcals from fat) for 6 weeks. Rats were then injected with a weight-adjusted bolus of epinephrine and tissue harvested. Despite a blunted activation of p38 epinephrine increased PDK4 mRNA expression to a similar extent in adipose tissue from chow and HFD rats. 5'AMP-activated protein kinase (AMPK) signaling was not altered by the HFD. Similar to epinephrine, 2 h of swim exercise, an intervention that increases plasma catecholamines, also increased PDK4 mRNA levels to a similar extent in adipose tissue from both lean and HFD rats. Collectively these findings demonstrate, for the first time, that acute elevations in catecholamines induce PDK4 in adipose tissue from HFD rats, that this effect is likely independent of p38, a reputed mediator of PDK4 expression and that exercise, similar to TZDs can induce PDK4 in adipose tissue from obese, insulin resistant rats. PMID:21818153

Wan, Zhongxiao; Frier, Bruce C; Williams, Deon B; Wright, David C

2011-08-04

214

[Adipose tissue renin-angiotensin system in obese].  

PubMed

Activation of the renin-angiotensin system (RAS) is commonly observed in patients with obesity. Adipose tissue expresses all components of RAS, implicating adipose renin-angiotensin system (A-RAS) in the pathophysiology of obesity. Angiotensin-converting enzyme(ACE) inhibitors and angiotensin II type 1 receptor (AT1R) blockers ameliorate obesity-related metabolic derangement. Of note, CASE-J trial demonstrated that a systemic blockade of RAS significantly reduced the incidence of newly occurring type 2 diabetes, notably in obese patients with hypertension. We reported that adipose tissue-derived AGT is substantially augmented in obesity and may contribute to hypertension in humans, thereby highlighting a pivotal role of A-RAS in systemic RAS activation and resultant metabolic derangement. PMID:23012802

Yasue, Shintaro; Ebihara, Ken; Nakao, Kazuwa

2012-09-01

215

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

PubMed

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

Peschechera, Alessandro; Eckel, Juergen

2013-05-30

216

Low Number of Insulin Receptors but High Receptor Protein Content in Adipose Tissue of Rats with Monosodium Glutamate-Induced Obesity  

Microsoft Academic Search

In order to better understand the mechanisms leading to insulin resis- tance, the number of fat tissue insulin receptors, their anity and insulin receptor protein in rats with monosodium glutamate-induced obesity were studied. Obese rats displayed signicantly lower number of insulin receptors with high anity. Sur- prisingly, the amount of insulin receptor protein was signicantly elevated in these animals. The

S. Zora; D. Jezova; L. Szabova; L. Macho; K. Tybitanclova

2003-01-01

217

The Fatty Acid Composition of Subcutaneous, Omental and Inguinal Adipose Tissue in the Arctic Fox.  

National Technical Information Service (NTIS)

Fatty acid composition was investigated in the subcutaneous, omental and inguinal adipose tissue by means of flame detection gas chromatography. The monounsaturated and polyunsaturated fatty acids predominated in the subcutaneous adipose tissue, whereas t...

T. D. Shultz J. H. Ferguson

1973-01-01

218

Endurance exercise training increases adipose tissue glucocorticoid exposure: adaptations that facilitate lipolysis.  

PubMed

Glucocorticoids (GCs) have long been thought to be lipolytic in nature. Recently, however, increased exposure to GCs in insulin-sensitive tissues has been associated with lipid accumulation and metabolic complications, regardless of plasma concentrations. Intracellular GC action is determined by both 11-beta hydroxysteroid dehydrogenase type 1 (11betaHSD1) and the GC receptor (GR). We hypothesized that exercise training would increase 11betaHSD1 and GR protein in adipose tissue, resulting in increased lipolysis. To test the effects of exercise on adipose tissue GR and 11betaHSD1 protein, 2 sets of hamsters were trained for 6 weeks: young, diet-induced obese animals and older, overweight animals. Young (6 week old) hamsters, fructose-fed to induce an obese phenotype, and older (6 month old) hamsters were randomly divided into exercising and sedentary groups. Exercise training decreased adipose tissue mass in both fructose-fed and older hamsters. In addition, exercise training increased 11betaHSD1 (31.5% +/- 15% and 20.0% +/- 7%, fructose-fed and older, respectively) and GR (45.6% +/- 14% and 61.1% +/- 27%, fructose-fed and older, respectively) protein expression in the perirenal adipose depot and increased 11betaHSD1 (16.7% +/- 7%, P = .09) and GR (47.4% +/- 19%, P < .05) in the subcutaneous adipose depot of the older hamsters. To determine the metabolic effect of increased GC exposure in adipocytes, 3T3-L1 adipocytes were treated with corticosterone for 24 hours; and measures of lipolytic rates were conducted. Low concentrations of GCs (0.01-0.1 micromol/L) increased GR (44.1% +/- 18%, P < .05) and 11betaHSD1 (95.3% +/- 24%) protein expression, as well as lipolytic rates (34.6% +/- 6%) as measured by glycerol release. The increased lipolysis was blocked by RU486, a GR antagonist, suggesting that the elevated lipolysis was a direct result of GC action. These results suggest that exercise training amplifies the activity of GCs in adipose tissue of overweight animals through alterations in 11betaHSD1 and GR despite differences in age and amounts of adiposity. In vitro, GCs are capable of increasing lipolysis, but depend upon the presence of GR. We propose that GCs play a significant role in changing the phenotype of adipose tissue during exercise training, resulting in decreased fat mass. PMID:19375588

Campbell, Jonathan E; Fediuc, Sergiu; Hawke, Thomas J; Riddell, Michael C

2009-05-01

219

Epinephrine-mediated regulation of PDK4 mRNA in rat adipose tissue.  

PubMed

Fatty acid reesterification in adipose tissue is dependent on the generation of glycerol 3-phosphate, and, at least in rodent adipose tissue, this appears to occur primarily through glyceroneogenesis. A key enzyme in this process is pyruvate dehydrogenase kinase 4 (PDK4). PDK4 is induced in white adipose tissue by thiazolidinediones (TZDs) and the inhibition or knockdown of PDK4 inhibits TZD-induced increases in glyceroneogenesis. Since TZDs have many unwanted side effects, we were interested in identifying alternative mechanisms that could regulate PDK4 mRNA expression in white adipose tissue. In this regard we hypothesized that exercise, fasting, and epinephrine would increase PDK4 mRNA levels in rat epididymal adipose tissue. We further postulated that the p38 mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase (AMPK) signaling pathways would control PDK4 mRNA expression in cultured adipose tissue. Exercise, fasting, and in or ex vivo epinephrine treatment increased PDK4 mRNA levels. These perturbations did not increase the expression of PDK1, -2, or -3. Pyruvate dehydrogenase phosphorylation was increased after an overnight fast and 4 h after the cessation of exercise. In cultured adipose tissue, epinephrine increased p38 and AMPK signaling; however, the direct activation of AMPK by AICAR or metformin led to reductions in PDK4 mRNA levels. The p38 inhibitor SB202190 reduced epinephrine-mediated increases in p38 MAPK activation without altering hormone-sensitive lipase or AMPK phosphorylation or attenuating epinephrine-induced increases in lipolysis. Reductions in p38 MAPK signaling were associated with decreases in PDK4 mRNA expression. The inhibition of peroxisome proliferator-activated receptor-? (PPAR?) also attenuated the induction of PDK4. Our results are the very first to demonstrate an epinephrine-mediated regulation of PDK4 mRNA levels in white adipose tissue and suggest that p38 MAPK and PPAR? could be involved in this pathway. PMID:20739620

Wan, Zhongxiao; Thrush, A Brianne; Legare, Melanie; Frier, Bruce C; Sutherland, Lindsey N; Williams, Deon B; Wright, David C

2010-08-25

220

Angiogenesis in an in vivo model of adipose tissue development  

Microsoft Academic Search

Obesity is associated with an increased risk for cardiovascular disease and cancer. Angiogenesis is a critical component of these pathological processes, and expanding adipose tissue represents one of the few sites of active angiogenesis in the adult. Despite the potential importance of angiogenesis in obesity, little is known about underlying mechanisms. This problem is magnified by the absence of useful

Jaap G. Neels; Terri Thinnes; David J. Loskutoff

2004-01-01

221

Dichotomous effects of VEGF-A on adipose tissue dysfunction.  

PubMed

Obese fat pads are frequently undervascularized and hypoxic, leading to increased fibrosis, inflammation, and ultimately insulin resistance. We hypothesized that VEGF-A-induced stimulation of angiogenesis enables sustained and sufficient oxygen and nutrient exchange during fat mass expansion, thereby improving adipose tissue function. Using a doxycycline (Dox)-inducible adipocyte-specific VEGF-A overexpression model, we demonstrate that the local up-regulation of VEGF-A in adipocytes improves vascularization and causes a "browning" of white adipose tissue (AT), with massive up-regulation of UCP1 and PGC1?. This is associated with an increase in energy expenditure and resistance to high fat diet-mediated metabolic insults. Similarly, inhibition of VEGF-A-induced activation of VEGFR2 during the early phase of high fat diet-induced weight gain, causes aggravated systemic insulin resistance. However, the same VEGF-A-VEGFR2 blockade in ob/ob mice leads to a reduced body-weight gain, an improvement in insulin sensitivity, a decrease in inflammatory factors, and increased incidence of adipocyte death. The consequences of modulation of angiogenic activity are therefore context dependent. Proangiogenic activity during adipose tissue expansion is beneficial, associated with potent protective effects on metabolism, whereas antiangiogenic action in the context of preexisting adipose tissue dysfunction leads to improvements in metabolism, an effect likely mediated by the ablation of dysfunctional proinflammatory adipocytes. PMID:22451920

Sun, Kai; Wernstedt Asterholm, Ingrid; Kusminski, Christine M; Bueno, Ana Carolina; Wang, Zhao V; Pollard, Jeffrey W; Brekken, Rolf A; Scherer, Philipp E

2012-03-26

222

Angiogenic Role of LYVE-1Positive Macrophages in Adipose Tissue  

Microsoft Academic Search

Here we report the discovery of a characteristic dense vascular network (DVN) in the tip portion of epididymal adipose tissue in adult mice. The DVN is formed by angiogenesis rather than by vasculogenesis, and has functional blood circulation. This DVN and its subsequent branching may provide a new functional route for adipogenesis. The recruitment, infiltration, and accumulation of bone marrow-derived

Chung-Hyun Cho; Jun Koh; Jinah Han; Hoon-Ki Sung; Hyuek Jong Lee; Tohru Morisada; Reto A. Schwendener; Rolf A. Brekken; Guson Kang; Yuichi Oike; Tae-Saeng Choi; Toshio Suda; Ook-Joon Yoo; Gou Young Koh

2008-01-01

223

Adipocyte Death, Adipose Tissue Remodeling and Obesity Complications  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

224

Larger Amounts of Visceral Adipose Tissue in Asian Americans  

Microsoft Academic Search

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

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

2001-01-01

225

The occurrence of brown adipose tissue in outdoor workers  

Microsoft Academic Search

Summary  Histochemical reactions and activities of mitochondrial enzymes in adipose tissue around the neck arteries and in pericardium were studied in men who had been outdoor workers in northern Finland. The purpose was to study the occurrence of brown fat in workers having been exposed to cool or cold ambient temperature. Indoor workers of the same age were used as controls.Histochemically,

Pirkko Huttunen; J. Hirvonen; V. Kinnula

1981-01-01

226

Metabolic syndrome pathophysiology: The role of adipose tissue  

Microsoft Academic Search

Several pathophysiological explanations for the metabolic syndrome have been proposed involving insulin resistance, chronic inflammation and ectopic fat accumulation following adipose tissue saturation. However, current concepts create several paradoxes, including limited cardiovascular risk reduction with intensive glucose control in diabetics, therapies that result in weight gain (PPAR agonists), and presence of some of the metabolic traits among some lipodystro- phies.

Martin Laclaustra; Dolores Corella

2007-01-01

227

Metabolic syndrome pathophysiology: The role of adipose tissue  

Microsoft Academic Search

Several pathophysiological explanations for the metabolic syndrome have been proposed involving insulin resistance, chronic inflammation and ectopic fat accumulation following adipose tissue saturation. However, current concepts create several paradoxes, including limited cardiovascular risk reduction with intensive glucose control in diabetics, therapies that result in weight gain (PPAR agonists), and presence of some of the metabolic traits among some lipodystrophies. We

Martin Laclaustra; Dolores Corella; José M. Ordovas

2007-01-01

228

The Inhibition of Ureteral Motility by Periureteral Adipose Tissue  

PubMed Central

Perivascular adipose tissue exerts an anticontractile influence on vascular smooth muscle. This study was conducted to determine whether periureteral adipose tissue (PUAT) could exert a similar influence upon ureteral smooth muscle. Acetylcholine-stimulated (10?7?M–10?4?M) contractile responses of ureteral segments obtained from male Wistar rats were recorded in the presence and absence of PUAT. Ureters with PUAT generated phasic contractile responses with significantly lower frequencies (P < 0.001) and magnitudes (P < 0.001) compared with ureters cleared of their periureteral adipose tissue. Removal of PUAT significantly increased the frequency (P < 0.01) and magnitude (P < 0.01) of the contractile responses. Bioassay experiments demonstrated that ureters with PUAT released a transferable factor that significantly reduced frequencies (P < 0.05), but not magnitudes, of the contractile responses of ureters cleared of PUAT. The nitric oxide synthase inhibitor L-NNA (10?4?M) did not significantly influence the anticontractile effect exerted by ureters with PUAT. This is the first study to demonstrate that ureteral motility is influenced by its surrounding adipose tissue. The PUAT has an anticontractile effect which is mediated by a transferable factor released from the PUAT. The identity of the factor is unknown but does not exert its effect through nitric oxide.

Killian, Lyndsey M.; Bund, Stuart J.

2012-01-01

229

Obesity induces a phenotypic switch in adipose tissue macrophage polarization.  

PubMed

Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance. PMID:17200717

Lumeng, Carey N; Bodzin, Jennifer L; Saltiel, Alan R

2007-01-01

230

Reversal of obesity by targeted ablation of adipose tissue  

Microsoft Academic Search

Obesity is an increasingly prevalent human condition in developed societies. Despite major progress in the understanding of the molecular mechanisms leading to obesity, no safe and effective treatment has yet been found. Here, we report an antiobesity therapy based on targeted induction of apoptosis in the vasculature of adipose tissue. We used in vivo phage display to isolate a peptide

Mikhail G Kolonin; Pradip K Saha; Lawrence Chan; Renata Pasqualini; Wadih Arap

2004-01-01

231

Sleep deprivation affects inflammatory marker expression in adipose tissue  

Microsoft Academic Search

: Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels

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

2010-01-01

232

Exercise and adrenaline increase PGC-1{alpha} mRNA expression in rat adipose tissue.  

PubMed

The purpose of the present investigation was to explore the effects of exercise and adrenaline on the mRNA expression of PGC-1alpha, a master regulator of mitochondrial biogenesis, in rat abdominal adipose tissue. We hypothesized that (1) exercise training would increase PGC-1alpha mRNA expression in association with increases in mitochondrial marker enzymes, (2) adrenaline would increase PGC-1alpha mRNA expression and (3) the effect of exercise on PGC-1alpha mRNA expression in white adipose tissue would be attenuated by a beta-blocker. Two hours of daily swim training for 4 weeks led to increases in mitochondrial marker proteins and PGC-1alpha mRNA expression in epididymal and retroperitoneal fat depots. Additionally, a single 2 h bout of exercise led to increases in PGC-1alpha mRNA expression immediately following exercise cessation. Adrenaline treatment of adipose tissue organ cultures led to dose-dependent increases in PGC-1alpha mRNA expression. A supra-physiological concentration of adrenaline increased PGC-1alpha mRNA expression in epididymal but not retroperitoneal adipose tissue. beta-Blockade attenuated the effects of an acute bout of exercise on PGC-1alpha mRNA expression in epididymal but not retroperitoneal fat pads. In summary, this is the first investigation to demonstrate that exercise training, an acute bout of exercise and adrenaline all increase PGC-1alpha mRNA expression in rat white adipose tissue. Furthermore it would appear that increases in circulating catecholamine levels may be one potential mechanism mediating exercise induced increases in PGC-1alpha mRNA expression in rat abdominal adipose tissue. PMID:19221126

Sutherland, Lindsey N; Bomhof, Marc R; Capozzi, Lauren C; Basaraba, Susan A U; Wright, David C

2009-02-16

233

Lessons on conditional gene targeting in mouse adipose tissue.  

PubMed

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. PMID:23321074

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

2013-01-15

234

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

235

Multiple Symmetric Lipomatosis: Substantial Subcutaneous Adipose Tissue Accumulation Did Not Induce Glucose and Lipid Metabolism Dysfunction  

Microsoft Academic Search

Objective: To study whether substantial subcutaneous adipose tissue (SCAT) can induce glucose and lipid metabolism dysfunction and possible underlying mechanisms. Methods: We report a male patient with multiple symmetrical lipomatosis (MSL) suffering from increased adipose tissue accumulation in abdomen and back for 7 years, accompanied by the gradual expansion of excess adipose tissue to the nuchal region, upper thorax, upper

Ke Chen; Yanhong Xie; Pinan Hu; Shaoli Zhao; Zhaohui Mo

2010-01-01

236

Telomere length of subcutaneous adipose tissue cells is shorter in obese and formerly obese subjects  

Microsoft Academic Search

Obesity and increased fat mass are associated with increased adipocyte proliferation. Telomere length can serve as a biomarker of a cell's biological (vs chronological) age. To gain insight in the physiology of adipose tissue, we aimed to investigate telomere length in subcutaneous adipose tissue in relation to age and obesity. Telomere length was measured in 72 subcutaneous adipose tissue samples

J M Moreno-Navarrete; F Ortega; M Sabater; W Ricart; J M Fernández-Real

2010-01-01

237

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

238

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

239

Transforming Growth Factor ?1 release by human adipose tissue is enhanced in obesity  

Microsoft Academic Search

The present studies examined the effect of obesity in humans on the release of transforming growth factor ?1 (TGF-?1) by human adipose tissue. The regulation of TGF-?1 release by adipose tissue as well as the question of whether its release is due to the adipocytes or the nonfat cells in adipose tissue was also examined. There was a statistically significant

John N. Fain; David S. Tichansky; Atul K. Madan

2005-01-01

240

A computational model of adipose tissue metabolism: Evidence for intracellular compartmentation and differential activation of lipases  

Microsoft Academic Search

Regulation of lipolysis in adipose tissue is critical to whole body fuel homeostasis and to the development of insulin resistance. Due to the challenging nature of laboratory investigations of regulatory mechanisms in adipose tissue, mathematical models could provide a valuable adjunct to such experimental work. We have developed a computational model to analyze key components of adipose tissue metabolism in

Jaeyeon Kim; Gerald M. Saidel; Satish C. Kalhan

2008-01-01

241

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

Microsoft Academic Search

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

Christine M. Williams; Rodney Ellis

1985-01-01

242

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

PubMed

Examination of adipose tissue biology may provide important insight into mechanistic links for the observed association between higher body fat and risk of several types of cancer, in particular colorectal and breast cancer. We tested two different methods of obtaining adipose tissue from healthy individuals. Ten overweight or obese (body mass index, 25-40 kg/m(2)), postmenopausal women were recruited. Two subcutaneous abdominal adipose tissue samples were obtained per individual (i.e., right and left lower abdominal regions) using two distinct methods (method A: 14-gauge needle with incision, versus method B: 16-gauge needle without incision). Gene expression was examined at the mRNA level for leptin, adiponectin, aromatase, interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in flash-frozen tissue, and at the protein level for leptin, adiponectin, IL-6, and TNF-alpha following short-term culture. Participants preferred biopsy method A and few participants reported any of the usual minor side effects. Gene expression was detectable for leptin, adiponectin, and aromatase, but was below detectable limits for IL-6 and TNF-alpha. For detectable genes, relative gene expression in adipose tissue obtained by methods A and B was similar for adiponectin (r = 0.64, P = 0.06) and leptin (r = 0.80, P = 0.01), but not for aromatase (r = 0.37,P = 0.34). Protein levels in tissue culture supernatant exhibited good intra-assay agreement [coefficient of variation (CV), 1-10%], with less agreement for intraindividual agreement (CV, 17-29%) and reproducibility, following one freeze-thaw cycle (CV, >14%). Subcutaneous adipose tissue biopsies from healthy, overweight individuals provide adequate amounts for RNA extraction, gene expression, and other assays of relevance to cancer prevention research. PMID:19139016

Campbell, Kristin L; Makar, Karen W; Kratz, Mario; Foster-Schubert, Karen E; McTiernan, Anne; Ulrich, Cornelia M

2009-01-01

243

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

Microsoft Academic Search

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

Hyun Jung Chung; Jin Sup Jung; Tae Gwan Park

2011-01-01

244

Loss of PPAR gamma in immune cells impairs the ability of abscisic acid to improve insulin sensitivity by suppressing monocyte chemoattractant protein-1 expression and macrophage infiltration into white adipose tissue.  

PubMed

Abscisic acid (ABA) is a natural phytohormone and peroxisome proliferator-activated receptor gamma (PPARgamma) agonist that significantly improves insulin sensitivity in db/db mice. Although it has become clear that obesity is associated with macrophage infiltration into white adipose tissue (WAT), the phenotype of adipose tissue macrophages (ATMs) and the mechanisms by which insulin-sensitizing compounds modulate their infiltration remain unknown. We used a loss-of-function approach to investigate whether ABA ameliorates insulin resistance through a mechanism dependent on immune cell PPARgamma. We characterized two phenotypically distinct ATM subsets in db/db mice based on their surface expression of F4/80. F4/80(hi) ATMs were more abundant and expressed greater concentrations of chemokine receptor (CCR) 2 and CCR5 when compared to F4/80(lo) ATMs. ABA significantly decreased CCR2(+) F4/80(hi) infiltration into WAT and suppressed monocyte chemoattractant protein-1 (MCP-1) expression in WAT and plasma. Furthermore, the deficiency of PPARgamma in immune cells, including macrophages, impaired the ability of ABA to suppress the infiltration of F4/80(hi) ATMs into WAT, to repress WAT MCP-1 expression and to improve glucose tolerance. We provide molecular evidence in vivo demonstrating that ABA improves insulin sensitivity and obesity-related inflammation by inhibiting MCP-1 expression and F4/80(hi) ATM infiltration through a PPARgamma-dependent mechanism. PMID:17618105

Guri, Amir J; Hontecillas, Raquel; Ferrer, Gerardo; Casagran, Oriol; Wankhade, Umesh; Noble, Alexis M; Eizirik, Decio L; Ortis, Fernanda; Cnop, Miriam; Liu, Dongmin; Si, Hongwei; Bassaganya-Riera, Josep

2007-07-06

245

In vitro neovasculogenic potential of resident adipose tissue precursors.  

PubMed

Adipose tissue development is associated with neovascularization, which might be exploited therapeutically. We investigated the neovasculogenesis antigenic profile and kinetics in adipose tissue-derived stromal cells (ADSCs) to understand the potential of ADSCs to generate new vessels. Murine and human visceral adipose tissues were processed with collagenase to obtain ADSCs from the stromal vascular fraction. Freshly isolated murine and human ADSCs featured the expression of early markers of endothelial differentiation [uptake of DiI-labeled acetylated LDL, CD133, CD34, kinase insert domain receptor (KDR)], but not markers for more mature endothelial cells (CD31 and von Willebrand factor). In methylcellulose medium, multilocular cells positive for Oil Red O staining appeared after 6 days. After 10 days, clusters of ADSCs spontaneously formed branched tubelike structures, which were strongly positive for CD34 and CD31, while losing their ability to undergo adipocyte differentiation. In Matrigel, in the presence of endothelial growth factors ADSCs formed branched tubelike structures. By clonal assays in methylcellulose we also determined the frequency of granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) colony-forming units from ADSCs, compared with bone marrow-derived stromal cells (BMSCs) used as a positive control. After 4-14 days, BMSCs formed 8 +/- 3 BFU-E and 40 +/- 10 CFU-GM, while ADSCs never produced colonies of myeloid progenitors. The developing adipose tissue has neovasculogenic potential, based on the recruitment of local rather than circulating progenitors. Adipose tissue might therefore be a viable autonomous source of cells for postnatal neovascularization. PMID:18787077

Madonna, Rosalinda; De Caterina, Raffaele

2008-09-11

246

Isolation and culture of preadipocytes from rodent white adipose tissue.  

PubMed

Much of the research devoted to understanding adipose tissue development is currently performed in vitro. Several cell culture models, including preadipocyte cell lines and primary culture of adipose-derived stromal vascular precursor cells, are commonly used to study molecular and cellular events and regulatory influences on preadipocyte proliferation and differentiation. Primary preadipocyte culture systems have several distinct advantages over preadipose cell lines. Because they have not been passaged continuously in culture, primary cultures of adipose derived stromal-vascular (SV) cells more closely reflect the in vivo characteristics of the tissue from which they are derived. In addition, primary cells can be obtained from various adipose tissue depots and from animals at different stages of development, from early postnatal life through advanced age. Cells can also be obtained from genetic rodent models of obesity or from rats and/or mice subjected to nutritional or hormonal manipulation. In each case, specific adipose tissue depots are dissected and the SV cells obtained after collagenase digestion. To examine the effect of tissue source or in vivo or in vitro treatment on preadipocyte proliferation, SV cells are labeled by thymidine incorporation during the exponential growth phase and maintained in culture until sufficiently lipid-filled to allow separation by density. Regulatory influences on various stages of preadipocyte differentiation can be examined in rat SV cultures in a controlled environment featuring chemically defined serum-free medium; whereas, more temperamental mouse SV cultures require the presence of serum for optimal differentiation. Alternatively, preadipocytes differentiated in vitro may be used for examining adipocyte metabolic or secretory responses. PMID:18516563

Hausman, Dorothy B; Park, Hea Jin; Hausman, Gary J

2008-01-01

247

Low number of insulin receptors but high receptor protein content in adipose tissue of rats with monosodium glutamate-induced obesity.  

PubMed

In order to better understand the mechanisms leading to insulin resistance, the number of fat tissue insulin receptors, their affinity and insulin receptor protein in rats with monosodium glutamate-induced obesity were studied. Obese rats displayed significantly lower number of insulin receptors with high affinity. Surprisingly, the amount of insulin receptor protein was significantly elevated in these animals. The same relations have been already reported for angiotensin II binding and AT1 receptor protein in the same model of obesity. Therefore we suggest an existence of general defect of adipocyte cell membrane in monosodium glutamate-induced obesity characterized by the presence of high quantity of impaired receptor protein. PMID:15113127

Zorad, S; Jezova, D; Szabova, L; Macho, L; Tybitanclova, K

2003-12-01

248

Epicardial adipose tissue and relationship with coronary artery disease  

Microsoft Academic Search

Epicardial adipose tissue (EAT) is metabolically active tissue that accumulates around the coronary arteries. Epicardial fat\\u000a is a rich source of free fatty acids and may contribute to local inflammatory load by increased synthesis of inflammatory\\u000a cytokines. Direct passage of bioactive molecules into the coronary arteries due to close contact with the vascular wall and\\u000a the lack of fascia may

Alina Cristina Silaghi; Raluca Pais; Ana Valea; Aurel Ion Mironiuc; Horatiu Silaghi

2011-01-01

249

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

PubMed

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

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

2012-07-26

250

Subcutaneous adipose tissue fatty acid desaturation in adults with and without rare adipose disorders  

PubMed Central

Background Elevated stearoyl-CoA desaturase activity has been described in obese states, with an increased desaturation index (DI) suggesting enhanced lipogenesis. Differences in the DI among various phenotypes of abnormal adiposity have not been studied. Abnormal accumulation of subcutaneous adipose tissue occurs in rare adipose disorders (RADs) including Dercum's disease (DD), multiple symmetric lipomatosis (MSL), and familial multiple lipomatosis (FML). Examining the DI in subcutaneous fat of people with DD, MSL and FML may provide information on adipose tissue fatty acid metabolism in these disorders. The aims of this pilot study were: 1) to determine if differences in adipose tissue DIs are present among RADs, and 2) to determine if the DIs correlate to clinical or biochemical parameters. Methods Subcutaneous adipose tissue was obtained from human participants with DD (n = 6), MSL (n = 5), FML (n = 8) and obese Controls (n = 6). Fatty acid composition was determined by gas chromatography/mass spectrometry. The DIs (palmitoleic/palmitic, oleic/stearic, vaccenic/stearic ratios) were calculated from the gas chromatogram peak intensities. SCD1 gene expression was determined. Spearman's correlations between the DIs and available clinical or biochemical data were performed. Results In DD subjects, the vaccenic/stearic index was lower (p < 0.05) in comparison to Controls. Percent of total of the saturated fatty acid myristic acid was higher in DD compared with Controls and FML. Percent of monounsaturated vaccenic acid in DD trended lower when compared with Controls, and was decreased in comparison to FML. In MSL, total percent of the polyunsaturated fatty acids was significantly lower than in the Control group (p < 0.05). In the total cohort of subjects, the palmitoleic/palmitic and oleic/stearic DIs positively correlated with age, BMI, and percent body fat. Conclusions The positive associations between the DIs and measures of adiposity (BMI and percent body fat) support increased desaturase activity in obesity. The lower vaccenic/stearic DI in DD SAT compared with Controls suggests presence of other factors involved in fat accumulation in addition to lifestyle. Other mechanisms driving fat accumulation in DD such as inflammation or lymphatic dysfunction should be investigated.

2012-01-01

251

Brown adipose tissue mitochondria oxidizing fatty acids generate high levels of reactive oxygen species irrespective of the uncoupling protein-1 activity state.  

PubMed

Mitochondria from brown adipose tissue (BATM) have a high enzymatic capacity for fatty acid oxidation and therefore are an ideal model to examine the sites of reactive oxygen species (ROS) generation during fatty acid oxidation. ROS generation by BATM (isolated from 3-week-old rats) was measured during acylcarnitine oxidation as release of H(2)O(2) into the medium and as inactivation of the matrix enzyme aconitase. The following results were obtained: (1) BATM release large amounts of H(2)O(2) in the coupled as well as in the uncoupled states, several times more than skeletal muscle mitochondria. (2) H(2)O(2) release is especially large with acylcarnitines of medium-chain fatty acids (e.g. octanoylcarnitine). (3) Reverse electron transport does not contribute in a significant extent to the overall ROS generation. (4) Despite the large release of H(2)O(2), the ROS-sensitive matrix enzyme aconitase is not inactivated during acylcarnitine oxidation. (5) In contrast to acylcarnitines, oxidation of ?-glycerophosphate by BATM is characterized by large H(2)O(2) release and a pronounced aconitase inactivation. We hypothesize that acylcarnitine-supported ROS generation in BATM may be mainly associated with acyl-CoA dehydrogenase and electron transferring flavoprotein-ubiquinone reductase rather than with complexes of the respiratory chain. PMID:22226918

Schönfeld, Peter; Wojtczak, Lech

2011-12-27

252

? 9 desaturase activity in bovine subcutaneous adipose tissue of different fatty acid compositiondesaturase activity in bovine subcutaneous adipose tissue of different fatty acid composition  

Microsoft Academic Search

Two experiments were conducted to investigate the relationship between ?9 desaturase (stearoyl-coenzyme A desaturase) activity and fatty acid composition in subcutaneous adipose tissue from cattle\\u000a of different backgrounds. In Experiment 1, subcutaneous adipose tissue samples were taken from carcasses of pasture-fed cattle\\u000a and feedlot cattle fed for 100, 200, or 300 d. Adipose tissue from pasture-fed cattle had significantly lower

A. Yang; T. W. Larsen; S. B. Smith; R. K. Tume

1999-01-01

253

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

2013-08-02

254

Free Fatty Acid Storage in Human Visceral and Subcutaneous Adipose Tissue  

PubMed Central

OBJECTIVE Because direct adipose tissue free fatty acid (FFA) storage may contribute to body fat distribution, we measured FFA (palmitate) storage rates and fatty acid (FA) storage enzymes/proteins in omental and abdominal subcutaneous fat. RESEARCH DESIGN AND METHODS Elective surgery patients received a bolus of [1-14C]palmitate followed by omental and abdominal subcutaneous fat biopsies to measure direct FFA storage. Long chain acyl-CoA synthetase (ACS) and diacylglycerol acyltransferase activities, CD36, fatty acid-binding protein, and fatty acid transport protein 1 were measured. RESULTS Palmitate tracer storage (dpm/g adipose lipid) and calculated palmitate storage rates were greater in omental than abdominal subcutaneous fat in women (1.2 ± 0.8 vs. 0.7 ± 0.4 ?mol ? kg adipose lipid?1 ? min?1, P = 0.005) and men (0.7 ± 0.2 vs. 0.2 ± 0.1, P < 0.001), and both were greater in women than men (P < 0.0001). Abdominal subcutaneous adipose tissue palmitate storage rates correlated with ACS activity (women: r = 0.66, P = 0.001; men: r = 0.70, P = 0.007); in men, CD36 was also independently related to palmitate storage rates. The content/activity of FA storage enzymes/proteins in omental fat was dramatically lower in those with more visceral fat. In women, only omental palmitate storage rates were correlated (r = 0.54, P = 0.03) with ACS activity. CONCLUSIONS Some adipocyte FA storage factors correlate with direct FFA storage, but sex differences in this process in visceral fat do not account for sex differences in visceral fatness. The reduced storage proteins in those with greater visceral fat suggest that the storage factors we measured are not a predominant cause of visceral adipose tissue accumulation.

Ali, Asem H.; Koutsari, Christina; Mundi, Manpreet; Stegall, Mark D.; Heimbach, Julie K.; Taler, Sandra J.; Nygren, Jonas; Thorell, Anders; Bogachus, Lindsey D.; Turcotte, Lorraine P.; Bernlohr, David; Jensen, Michael D.

2011-01-01

255

Paradoxical roles of perivascular adipose tissue in atherosclerosis and hypertension.  

PubMed

Perivascular adipose tissue (PVAT) is the fat tissue surrounding most of the vasculature and it has long been considered solely as vessel-supporting connective tissue. There are 2 major types of adipose tissue widely distributed throughout the body: white (WAT) and brown (BAT). PVAT is similar to BAT in rodents, but it was believed that only WAT existed in adult humans and BAT was present only in infants. However, the presence of functional BAT in adult humans is now accepted. The main function of BAT is to generate heat, and it is essential for adaptive thermogenesis and energy expenditure, whereas the main function of WAT is to store lipids. Besides the different functions of WAT and BAT, growing evidence suggests that different depots of adipose tissue have different functions. Similar to other fat depots, PVAT produces various adipokines, growth factors and inhibitors that affect functions of adjacent layers of the vasculature. Pathophysiological conditions such as obesity, vascular injury, aging and infection could cause PVAT dysfunction, leading to vascular endothelial and smooth muscle cell dysfunctions. In this review, we discuss the function and dysfunction of PVAT on atherosclerosis and hypertension. PMID:23207957

Chang, Lin; Milton, Hamblin; Eitzman, Daniel T; Chen, Y Eugene

2012-12-01

256

Determination of PPAR? Activity in Adipose Tissue and Spleen  

PubMed Central

Peroxisome proliferator-activated receptor-gamma (PPAR?) is a nuclear transcription factor that regulates many genes and is involved in extensive biological functions. Accurately determining PPAR? activity in various tissues is important to understanding mechanisms of human physiology and pathophysiology. Thus, we evaluated a PPAR? DNA binding immunoassay using nuclear extracts of spleen and adipose tissue from rats treated with rosiglitazone (20 mg/kg in food, 7 days, n=6) or vehicle (n=6) and compared results to mRNA expression of PPAR? target genes, a well-established method to investigate PPAR? activity. In adipose tissue, the PPAR? immunoassay showed that rosiglitazone did not change PPAR? binding, but qPCR analysis showed that expression of two PPAR? target genes, CD36 and liver X receptor-?, were significantly increased. In spleen, the PPAR? immunoassay showed that rosiglitazone decreased PPAR? binding, but qPCR analysis showed no significant change. The different results obtained between PPAR? binding immunoassay and target gene expression suggest that PPAR? immunoassays may not be suitable when used with fresh homogenates of spleen and adipose tissue. Validation of the assay with each individual tissue is recommended.

Chan, Siu-Lung; Cipolla, Marilyn J.

2011-01-01

257

Antioxidative defense and mitochondrial thermogenic response in brown adipose tissue  

PubMed Central

Cold-exposure activates interscapular brown adipose tissue (IBAT) non-shivering thermogenesis that relies primarily on intensification of metabolic rate and uncoupling. During cold-acclimation, uncoupling in IBAT decreases superoxide (O2·?) production and as an adaptive response the activities of manganese and copper, zinc superoxide dismutase (Mn- and CuZn-SOD, respectively) are decreased, as well. However, molecular mechanisms governing this SODs adaptive response are still unsolved. Besides, knowing that NO reinforces IBAT uncoupling, we wondered whether nitric oxide (NO) is taking part in SODs regulation? Mn- and CuZn-SOD mRNA and protein expression, uncoupling protein 1 (UCP1), nitrotyrosine and nuclear factor-kappa B (NF-?B) immunolabeling, as well as total SOD (tSOD) activity in IBAT of rats subjected to cold (4 ± 1°C) for 1, 3, 7, 12, 21 and 45 days and treated by l-arginine or N?-nitro-l-arginine-methyl ester (l-NAME) were examined. Cold increased UCP1 immunopositivity and decreased tSOD activity during entire cold-acclimation and transiently, (day 3), activated NF-?B and increased Mn and CuZn-SOD mRNA expression and nitrotyrosine labeling, suggesting NO involvement in this signaling. However, SODs mRNA expression was decreasing from day 12 till the end of cold-acclimation. l-arginine augmented and prolonged cold-induced UCP1 and nitrotyrosine immunopositivity, NF-?B activation and SODs mRNA expression increase, while l-NAME expressed an opposite effect. Related to cold, l-arginine decreased, while l-NAME increased Mn-SOD protein expression. In contrast, neither low temperature nor both treatments applied affected CuZn-SOD protein expression. The results showed that adaptive decrease in SODs activity on uncoupling-decreased O2·? production was achieved already at the level of gene transcription and that NO takes part in the regulation of IBAT SOD isoforms.

Petrovic, Vesna; Buzadzic, Biljana; Korac, Aleksandra

2009-01-01

258

Isolation and culture of porcine adipose tissue-derived somatic stem cells.  

PubMed

Adipose tissue-derived stem cells (ASCs) have been described for a number of laboratory animals and humans. Improved culture conditions and cellular characteristics of ASCs have been identified. ASCs can self-renew and differentiate into multiple tissue lineages. Further characterization of ASCs in this manner could enhance the isolation and purification of a population of mesenchymal stem cells (MSCs) from easily obtainable adipose tissue. These stem cell populations from domestic animals, which make attractive models for transplantation studies, will be valuable for the evaluation of their efficacy in tissue regeneration applications in the future. These cells may also represent a population more easily reprogrammable during somatic cell nuclear transfer and thus expedite the development of transgenic animals for models and production of valuable pharmaceutical proteins. PMID:21082396

Williams, Kellie J; Godke, Robert A; Bondioli, Kenneth R

2011-01-01

259

What distinguishes adipose tissue of severely obese humans who are insulin sensitive and resistant?  

PubMed Central

Purpose of review Despite a strong correlation between obesity and insulin resistance, 25% of severely obese (BMI >40) individuals are insulin sensitive. In this review, we will examine the factors in adipose tissue that distinguish the two groups, as well as reasons for believing the insulin-sensitive group will be less disease prone. Recent findings Obesity has been linked to the metabolic syndrome with an increase in visceral (intra-abdominal) compared to subcutaneous fat. Recent studies in which adipose tissue of insulin-sensitive and insulin-resistant patients with severe obesity were compared indicate that the insulin-resistant group is also distinguished by increases in oxidative stress and decreases in AMP-activated protein kinase (AMPK) activity. In contrast, changes in the expression of genes for SIRT1, inflammatory cytokines, mitochondrial biogenesis and function, and the two ?-isoforms of AMPK showed more depot variation. Studies of how these and other changes in adipose tissue respond to bariatric surgery are still in their infancy. Summary Available data suggest that increases in oxidative stress, decreases in AMPK activity and SIRT1 gene expression, depot-specific changes in inflammatory, mitochondrial and other genes distinguish adipose tissue of insulin resistant from insulin-sensitive individuals with severe obesity.

Xu, X. Julia; Pories, Walter J.; Dohm, Lynis G.; Ruderman, Neil B.

2013-01-01

260

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

PubMed

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. PMID:23362435

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

2013-01-26

261

Adipose tissue development in extramuscular and intramuscular depots in meat animals  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

262

Predicting abdominal adipose tissue among women with familial partial lipodystrophy.  

PubMed

The objective of the study was to determine correlations between magnetic resonance imaging (MRI) measures of truncal adiposity (trunk fat percentage [TrF %(MRI)], visceral adipose tissue [VAT], and subcutaneous abdominal adipose tissue [SAT]), simple clinical measures (body mass index [BMI], waist circumference [WC], and waist-to-hip ratio [WHR]), and bioelectrical impedance analysis (BIA)-derived measures (total fat percentage [TF %] and TrF %(BIA)) in female patients with familial partial lipodystrophy (FPLD). Our secondary aim was to generate and cross-validate predictive equations for VAT and SAT using these simple clinical and BIA-derived variables. Measures of truncal adiposity were measured using 1.5-T MRI (VAT, SAT, and TrF %(MRI)) and Tanita (Tokyo, Japan) 8-electrode body composition analyzer BC-418 (TrF %(BIA)) in 13 female FPLD patients. Pearson correlation coefficients were determined among the various adiposity parameters (BMI, WC, WHR, SAT, VAT, TrF %(MRI), TrF %(BIA), and TF %). Equations to estimate VAT and SAT were determined among 6 of the 13 FPLD subjects using multilinear regression analysis, and the best equations were then cross-validated in the remaining 7 subjects. Variables entered into the model included age, BMI, WC, WHR, TrF %(BIA), and TF %. The TrF %(MRI) showed moderate correlation (r = 0.647, P = .02) with the TrF %(BIA), but the discrepancy between the 2 variables increased with increasing truncal adiposity. The strongest correlate for TrF %(MRI) was BMI (r = 0.886, P < .0001). Visceral adipose tissue was poorly associated with simple clinical measures of BMI, WC, and WHR, but was inversely correlated with TF %, TrF %(BIA), and SAT. The TF % was the strongest correlate for both SAT and VAT. Thus, the best regression equation for VAT included age, BMI, WC, and TF % (R(2) = 1.0), whereas that for SAT only included TF % (R(2) = 0.75). The corresponding standard error of the estimate for the predictive equations was approximately 0.03 % and 18.5 % of the mean value of VAT and SAT, respectively. In the cross-validation study, differences between predicted and observed values of SAT were larger than those of VAT. We conclude that, among female FPLD patients, (1) no simple clinical anthropometric measure correlates well with VAT, whereas BMI correlates well with SAT; (2) BIA measure of TF % most strongly correlated with both VAT and SAT; and (3) based on the cross-validation study, VAT but not SAT could be more reliably estimated using the regression equations derived. PMID:19375764

Joy, Tisha; Kennedy, Brooke A; Al-Attar, Salam; Rutt, Brian K; Hegele, Robert A

2009-06-01

263

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

PubMed Central

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

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

2008-01-01

264

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

SciTech Connect

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

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

1991-08-01

265

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

266

Insulin activates protein kinase B, inhibits glycogen synthase kinase-3 and activates glycogen synthase by rapamycin-insensitive pathways in skeletal muscle and adipose tissue  

Microsoft Academic Search

Insulin stimulated protein kinase B? (PKB?) more than 10-fold and decreased glycogen synthase kinase-3 (GSK3) activity by 50±10% in skeletal muscle and adipocytes. Rapamycin did not prevent the activation of PKB, inhibition of GSK3 or stimulation of glycogen synthase up to 5 min. Thus rapamycin-insensitive pathways mediate the acute effect of insulin on glycogen synthase in the major insulin-responsive tissues.

Darren A. E. Cross; Peter W. Watt; Morag Shaw; Jeroen van der Kaay; C. Peter Downes; Julie C. Holder; Philip Cohen

1997-01-01

267

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

PubMed

One of the 'side effects' of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain's survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure. Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders. PMID:22915019

Yi, Chun-Xia; Tschöp, Matthias H

2012-09-01

268

Brain-gut-adipose-tissue communication pathways at a glance  

PubMed Central

One of the ‘side effects’ of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain’s survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure. Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders.

Yi, Chun-Xia; Tschop, Matthias H.

2012-01-01

269

Central nervous system regulation of liver and adipose tissue metabolism  

Microsoft Academic Search

Summary  Hypothalamic and autonomic nervous regulation of carbohydrate and amino acid metabolism in the liver and of lipid metabolism\\u000a in adipose tissues is described. The direct neural mechanism underlying this regulation has been evaluated. Electrical stimulation\\u000a of the ventromedial hypothalamic nucleus (VMH)-splanchnic nerve system causes glycogenolysis in the liver by rapid activation\\u000a of glycogen phosphorylase, whereas electrical stimulation of the lateral

T. Shimazu

1981-01-01

270

Measuring Abdominal Adipose Tissue: Comparison of Simpler Methods with MRI  

Microsoft Academic Search

SummaryObjective: This cross-sectional study compares the relationship of visceral and total abdominal adipose tissue (VAT and TAAT) measurements obtained with magnetic resonance imaging (MRI) and a range of ‘simpler’ techniques suitable for field or bedside use: BMI, waist circumference (WC), bioelectrical impedance (BIA) devices and dual X-ray absorptiometry (DXA). Method: 120 participants were recruited, stratified by gender and BMI (20

Lucy M. Browning; Owen Mugridge; Adrian K. Dixon; Sri W. Aitken; Andrew M. Prentice; Susan A. Jebb

2011-01-01

271

Glucocorticoids and 11beta-Hydroxysteroid Dehydrogenase in Adipose Tissue  

Microsoft Academic Search

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

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

2010-01-01

272

Anger, hostility, and vesceral adipose tissue in healthy postmenopausal women  

Microsoft Academic Search

Central Obesity is an important risk factor for chronic disease. Its etiology remains unclear. We examined whether anger and hostility, ie, psychological attributes that influence cardiovascular morbidity and mortality, prospectively predict central visceral obesity across 13 years. Visceral adipose tissue (VAT) was determined by X-ray computed tomography (CT) at the L4-–L5 disc space in a population-based sample of 157 postmenopausal

Katri Räikkönen; Karen A. Matthews; Lewis H. Kuller; Chris Reiber; Clareann H. Bunker

1999-01-01

273

Polybrominated Diphenyl Ethers in Swedish Human Liver and Adipose Tissue  

Microsoft Academic Search

Paired samples of human liver and adipose tissue were analyzed for polybrominated diphenyl ethers (PBDEs) containing 3–6 bromine\\u000a atoms. The samples were obtained at autopsy from one woman and four men at the age of 47 and 66–83 years, respectively. PBDEs\\u000a were found in all samples. The sum of nine PBDE congeners ranged 5–18 ng\\/g lipids and 4–8 ng\\/g lipids

D. Meironyté Guvenius; Å. Bergman; K. Norén

2001-01-01

274

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

PubMed

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

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

2013-07-18

275

Food consumption and adipose tissue DDT levels in Mexican women.  

PubMed

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

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

276

Brominated dioxins and dibenzofurans in human adipose tissue. Final report  

SciTech Connect

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

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

1990-04-11

277

Relationship between human adipose tissue agouti and fatty acid synthase (FAS).  

PubMed

The human homologue of the murine obesity gene, agouti, is expressed in adipose tissue. We have shown that recombinant agouti protein regulates adipocyte lipogenesis and lipolysis coordinately and promotes lipid storage via a Ca(2+)-dependent mechanism in vitro, which may contribute to agouti-induced obesity. However, little is known about agouti's physiologic function in humans. We first studied the agouti content in human mature adipocytes vs. preadipocytes. The agouti content of human mature adipocytes was five times as abundant as in preadipocytes (19.18 +/- 2.46 vs. 4.07 +/- 0.51 pg/microg protein, P: < 0.005), suggesting that agouti is up-regulated during adipocyte differentiation. We next studied the relationship of agouti mRNA and protein to fatty acid synthase (FAS) mRNA and activity in adipose tissue obtained from nonobese and mildly obese patients (body mass index range, 21-31 kg/m(2)). Agouti protein was correlated with FAS activity (r = 0.782, P: < 0.005). Similarly, human adipose tissue agouti mRNA level was also correlated with FAS mRNA level (r = 0.846, P: < 0.001). These data suggest that agouti may be another adipocyte-produced factor that modulates adipocyte lipid metabolism via a paracrine/autocrine mechanism. PMID:11015476

Xue, B; Zemel, M B

2000-10-01

278

Thermogenesis in brown adipose tissue with age: post-receptor activation by forskolin  

Microsoft Academic Search

š-Adrenergic-stimulated thermogenesis in brown adipose tissue (BAT) is diminished with age. š-Adrenergic receptors are positively coupled to adenylyl cyclase in BAT. To determine whether thermo- genesis, in response to direct activation of adenylyl cyclase, is also impaired with age, we examined whole body oxygen consumption, mitochondrial guanosine diphosphate (GDP) binding and BAT mitochondrial uncoupling protein (UPC) mRNA levels in 4-

Philip J. Scarpace; Michael Matheny

1996-01-01

279

Thermogenesis in brown adipose tissue with age: Post-receptor activation by forskolin  

Microsoft Academic Search

?3-Adrenergic-stimulated thermogenesis in brown adipose tissue (BAT) is diminished with age.?3-Adrenergic receptors are positively coupled to adenylyl cyclase in BAT. To determine whether thermogenesis, in response to direct activation of adenylyl cyclase, is also impaired with age, we examined whole body oxygen consumption, mitochondrial guanosine diphosphate (GDP) binding and BAT mitochondrial uncoupling protein (UPC) mRNA levels in 4- and 24-month-old

Philip J. Scarpace; Michael Matheny

1996-01-01

280

Weight Loss Reduces Adipose Tissue Cathepsin S and Its Circulating Levels in Morbidly Obese Women  

Microsoft Academic Search

Context:Humanadiposetissueproducesseveraladipokines,includingthe newlyidentifiedproteincathepsinS(CTSS),acysteineproteaseinvolvedin the pathogenesis of atherosclerosis. Obesity is characterized by high levels of CTSS in the circulation and in sc white adipose tissue (scWAT). Objective: We investigated the effect of surgery-induced weight loss on circulating CTSS and its protein expression in scWAT. Design: Fifty morbidly obese women before and 3 months after sur- gery and 10 healthy lean women were

Soraya Taleb; Raffaella Cancello; Christine Poitou; Christine Rouault; Philippe Sellam; Patrick Levy; Jean-Luc Bouillot; Christiane Coussieu; Arnaud Basdevant; Michele Guerre-Millo; Daniele Lacasa; Karine Clement

281

Intracerebroventricular administration of neuropeptide Y to normal rats increases obese gene expression in white adipose tissue  

Microsoft Academic Search

Summary  The aim of this work was to determine the possible inter-relationship between neuropeptide Y (NPY, a hypothalamic stimulator of feeding) and adipose tissue expression of the ob protein (a novel potent inhibitor of feeding). Such a relationship could be of importance in the maintenance of normal body weight. To this end, normal rats were intracerebro-ventricularly (i.c.v.) infused for 6 days

A. Sainsbury; I. Cusin; P. Doyle; F. Rohner-Jeanrenaud; B. Jeanrenaud

1996-01-01

282

Regulation of gene expression by FSP27 in white and brown adipose tissue  

Microsoft Academic Search

BACKGROUND: Brown and white adipose tissues (BAT and WAT) play critical roles in controlling energy homeostasis and in the development of obesity and diabetes. The mouse Fat-Specific protein 27 (FSP27), a member of the cell death-inducing DFF45-like effector (CIDE) family, is expressed in both BAT and WAT and is associated with lipid droplets. Over-expression of FSP27 promotes lipid storage, whereas

De Li; Yinxin Zhang; Li Xu; Linkang Zhou; Yue Wang; Bofu Xue; Zilong Wen; Peng Li; Jianli Sang

2010-01-01

283

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

PubMed

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

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

2013-01-02

284

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

PubMed Central

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

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

2012-01-01

285

Unequivocal identification of brown adipose tissue in a human infant.  

PubMed

We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties. PMID:22180228

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

2011-12-16

286

METABOLIC AND ULTRASTRUCTURAL CHANGES INDUCED IN ADIPOSE TISSUE BY INSULIN  

PubMed Central

The addition in vitro of insulin to rat adipose tissue (epididymal) produces marked metabolic changes which may be followed by measurement of the net gas exchange of the tissue. Using this method to monitor the metabolic action of insulin, concomitant observations with the electron microscope on the tissue have been made. These reveal that pronounced morphological changes are induced by insulin. The plasma membranes of the adipose cells become invaginated at many sites to form minute finger-like indentations. Numerous tiny, membrane-bounded vesicles are also present and arranged in relationship to the plasma membrane in such a way as to suggest that their formation occurred when a recessed fold was pinched off. Deeper in the cytoplasm, especially in specimens that had been incubated a longer time, numerous large, smooth, membrane-limited vesicles are seen. Finally, in these incubated specimens the cytoplasmic matrix has lost much of its granular nature, small lipid droplets are frequently found in the cytoplasm and suggestive changes have occurred in mitochondria. In control specimens, incubated without insulin for identical periods of time, indentations and vesicles in the plasma membrane are sparse at best and no vesicles or membrane-bound spaces appear deeper in the cytoplasm. The metabolic and morphologic changes induced by insulin seem to be interdependent events. Both changes appear to be initiated rapidly and concomitantly in the tissue. Both processes are initiated by insulin at concentrations considered to be physiological, 0.004 µg. (100 µunits) per ml. Insulin treated with alkali fails to initiate either process. It is concluded that insulin initiates pinocytosis in rat adipose tissue and the possible significance of this process in the mode of action of insulin is discussed.

Barrnett, Russell J.; Ball, Eric G.

1960-01-01

287

Detecting Brown Adipose Tissue Activity with BOLD MRI in Mice  

PubMed Central

The recent discovery of active brown adipose tissue (BAT) in adult humans and the correlation found between the activity of this tissue and resting metabolic rate strongly suggest that this tissue may be implicated in the development of obesity in humans, as it is in rodents. Despite the possible physiological role of this tissue in the onset of human obesity, few non-invasive imaging techniques to detect BAT activity in humans exist. The scope of this work is to investigate the possibility of detecting BAT activity using BOLD MRI. Our results show that the strong increase in oxygen consumption and consequent increase in blood deoxyhemoglobin levels following BAT activation lead to a well-localized signal drop in BAT. This strongly suggests the possibility to use BOLD MRI for the non invasive detection of BAT activity.

Khanna, Arjun; Branca, Rosa T.

2011-01-01

288

Detecting brown adipose tissue activity with BOLD MRI in mice.  

PubMed

The recent discovery of active brown adipose tissue (BAT) in adult humans and the correlation found between the activity of this tissue and resting metabolic rate strongly suggest that this tissue may be implicated in the development of obesity in humans, as it is in rodents. Despite the possible physiological role of this tissue in the onset of human obesity, few noninvasive imaging techniques to detect BAT activity in humans exist. The scope of this work is to investigate the possibility of detecting BAT activity using blood-oxygen-level-dependent MRI. Our results show that the strong increase in oxygen consumption and consequent increase in blood deoxyhemoglobin levels following BAT activation lead to a well-localized signal drop in BAT. This strongly suggests the possibility to use blood-oxygen-level-dependent MRI for the noninvasive detection of BAT activity. PMID:22231619

Khanna, Arjun; Branca, Rosa T

2012-01-09

289

Obesity after genetic ablation of brown adipose tissue.  

PubMed

Brown adipose tissue (BAT) has been proposed to play an important role in the regulation of energy balance. The unique presence of uncoupling protein (UCP) permits BAT to expend calories unrelated to the performance of work with the net result being the generation of heat. The role of BAT in mediating diet-induced thermogenesis had led to the suggestion that BAT activity contributes to metabolic inefficiency and, as such, might provide a cellular and molecular explanation for protection from obesity. In order to directly test this hypothesis, we recently created mice with isolated BAT deficiency by using a suicide DNA transgenic vector in which regulatory elements of the UCP gene were used to drive brown fat specific expression of diptheria toxin A-chain (DTA). Transgenic mice are characterized by reduced energy expenditure and marked obesity, associated with insulin resistance and NIDDM with both receptor and post-receptor components. Feeding of a "Western diet" which derives 41% of its calories from fat leads to a synergistic effect on the development of obesity and its accompanying disorders in transgenics. The results of our studies support a critical role for BAT in the nutritional homeostasis of mice and suggest that the intact thermogenic function of BAT is required for protection from diet induced obesity. Obese UCP-DTA mice have many features in common with obesity as it appears in most humans, and should therefore be a useful model that may aid studies of the pathogenesis and treatment of human obesity, NIDDM and their complications. PMID:9558722

Hamann, A; Flier, J S; Lowell, B B

1998-01-01

290

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

PubMed Central

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

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

2012-01-01

291

Diversity of lipid mediators in human adipose tissue depots.  

PubMed

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

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

2013-01-30

292

Mutant Amyloid Precursor Protein Differentially Alters Adipose Biology under Obesogenic and Non-Obesogenic Conditions  

PubMed Central

Mutations in amyloid precursor protein (APP) have been most intensely studied in brain tissue for their link to Alzheimer’s disease (AD) pathology. However, APP is highly expressed in a variety of tissues including adipose tissue, where APP is also known to exhibit increased expression in response to obesity. In our current study, we analyzed the effects of mutant APP (E693Q, D694N, K670N/M671L) expression toward multiple aspects of adipose tissue homeostasis. These data reveal significant hypoleptinemia, decreased adiposity, and reduced adipocyte size in response to mutant APP, and this was fully reversed upon high fat diet administration. Additionally, mutant APP was observed to significantly exacerbate insulin resistance, triglyceride elevations, and macrophage infiltration of adipose tissue in response to a high fat diet. Taken together, these data have significant implications for linking mutant APP expression to adipose tissue dysfunction and global changes in endocrine and metabolic function under both obesogenic and non-obesogenic conditions.

Freeman, Linnea R.; Zhang, Le; Dasuri, Kalavathi; Fernandez-Kim, Sun-Ok; Bruce-Keller, Annadora J.; Keller, Jeffrey N.

2012-01-01

293

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

Microsoft Academic Search

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

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

2011-01-01

294

Adipose Tissue Resting Energy Expenditure and Expression of Genes Involved in Mitochondrial Function Are Higher in Women than in Men  

PubMed Central

Context: Men and women differ in body fat distribution and adipose tissue metabolism as well as in obesity comorbidities and their response to obesity treatment. Objective: The objective of the study was a search for sex differences in adipose tissue function. Design and Setting: This was an exploratory study performed at a university hospital. Participants and Main Outcome Measures: Resting metabolic rate (RMR), body composition, and sc adipose tissue genome-wide expression were measured in the SOS Sib Pair study (n = 732). Results: The relative contribution of fat mass to RMR and the metabolic rate per kilogram adipose tissue was higher in women than in men (P value for sex by fat mass interaction = .0019). Women had increased expression of genes involved in mitochondrial function, here referred to as a mitochondrial gene signature. Analysis of liver, muscle, and blood showed that the pronounced mitochondrial gene signature in women was specific for adipose tissue. Brown adipocytes are dense in mitochondria, and the expression of the brown adipocyte marker uncoupling protein 1 was 5-fold higher in women compared with men in the SOS Sib Pair Study (P = 7.43 × 10?7), and this was confirmed in a cross-sectional, population-based study (n = 83, 6-fold higher in women, P = .00256). Conclusions: The increased expression of the brown adipocyte marker uncoupling protein 1 in women indicates that the higher relative contribution of the fat mass to RMR in women is in part explained by an increased number of brown adipocytes.

Nookaew, Intawat; Jacobson, Peter; Jernas, Margareta; Taube, Magdalena; Larsson, Ingrid; Andersson-Assarsson, Johanna C.; Sjostrom, Lars; Froguel, Philippe; Walley, Andrew; Nielsen, Jens; Carlsson, Lena M. S.

2013-01-01

295

Diabetes as a complication of adipose tissue dysfunction. Is there a role for potential new biomarkers?  

PubMed

Increasing incidence of type 2 diabetes is a major health problem of the modern world and requires new diagnostic tools to assess early metabolic disorders, particularly insulin resistance. The link between obesity, inflammation and insulin resistance indicates the important secretory role of adipose tissue. Proinflammatory factors (cytokines, adipokines) produced by enlarged adipose tissue are related to impaired glucose metabolism. Adipokines act as paracrine factors in adipose tissue and as endocrine hormones in the liver, muscles and central nervous system. Novel adipokines secreted from adipocytes such as retinol binding protein-4 (RBP-4), vaspin, omentin, chemerin, fibroblast growth factor 21 (FGF21), adipocyte fatty acid-binding protein (A-FABP) and dipeptidyl peptidase 4 (DPP4) demonstrate pleiotropic activity and their insulin-sensitizing or enhancing insulin resistance properties have not been clearly confirmed yet. In spite of the lack of standardized automated assay methods currently available for these novel biomarkers, promising results from several studies emphasize that they might potentially be useful prognostic factors for diabetes and its complications, especially in individuals without the typical symptoms of metabolic syndrome. PMID:23241684

Bergmann, Katarzyna; Sypniewska, Grazyna

2013-01-01

296

FGF21 regulates PGC-1? and browning of white adipose tissues in adaptive thermogenesis  

PubMed Central

Certain white adipose tissue (WAT) depots are readily able to convert to a “brown-like” state with prolonged cold exposure or exposure to ?-adrenergic compounds. This process is characterized by the appearance of pockets of uncoupling protein 1 (UCP1)-positive, multilocular adipocytes and serves to increase the thermogenic capacity of the organism. We show here that fibroblast growth factor 21 (FGF21) plays a physiologic role in this thermogenic recruitment of WATs. In fact, mice deficient in FGF21 display an impaired ability to adapt to chronic cold exposure, with diminished browning of WAT. Adipose-derived FGF21 acts in an autocrine/paracrine manner to increase expression of UCP1 and other thermogenic genes in fat tissues. FGF21 regulates this process, at least in part, by enhancing adipose tissue PGC-1? protein levels independently of mRNA expression. We conclude that FGF21 acts to activate and expand the thermogenic machinery in vivo to provide a robust defense against hypothermia.

Fisher, ffolliott M.; Kleiner, Sandra; Douris, Nicholas; Fox, Elliott C.; Mepani, Rina J.; Verdeguer, Francisco; Wu, Jun; Kharitonenkov, Alexei; Flier, Jeffrey S.; Maratos-Flier, Eleftheria; Spiegelman, Bruce M.

2012-01-01

297

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

2013-07-24

298

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

299

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

PubMed

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

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

2013-06-18

300

Improvement of liquid fructose-induced adipose tissue insulin resistance by ginger treatment in rats is associated with suppression of adipose macrophage-related proinflammatory cytokines.  

PubMed

Adipose tissue insulin resistance (Adipo-IR) results in excessive release of free fatty acids from adipose tissue, which plays a key role in the development of "lipotoxicity." Therefore, amelioration of Adipo-IR may benefit the treatment of other metabolic abnormalities. Here we found that treatment with the alcoholic extract of ginger (50?mg/kg/day, by oral gavage) for five weeks attenuated liquid fructose-induced hyperinsulinemia and an increase in the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. More importantly, ginger reversed the increases in the Adipo-IR index and plasma nonesterified fatty acid concentrations during the oral glucose tolerance test assessment. Adipose gene/protein expression profiles revealed that ginger treatment suppressed CD68 and F4/80, two important macrophage accumulation markers. Consistently, the macrophage-associated cytokines tissue necrosis factor alpha and interleukin-6 were also downregulated. In contrast, insulin receptor substrate (IRS)-1, but not IRS-2, was upregulated. Moreover, monocyte chemotactic protein (MCP)-1 and its receptor chemokine (C-C motif) receptor-2 were also suppressed. Thus these results suggest that amelioration of fructose-induced Adipo-IR by ginger treatment in rats is associated with suppression of adipose macrophage-related proinflammatory cytokines. PMID:23533500

Wang, Jianwei; Gao, Huanqing; Ke, Dazhi; Zuo, Guowei; Yang, Yifan; Yamahara, Johji; Li, Yuhao

2013-02-21

301

Epicardial adipose tissue thickness in type 1 diabetic patients.  

PubMed

Insulin resistance is getting important in the course of type 1 diabetes mellitus. Visceral fat depot is associated with insulin resistance and assessment of epicardial fat thickness is a way of measuring visceral fat. The aim of the study was to measure epicardial adipose tissue (EAT) thickness and to determine its relationship with waist-hip-ratio (WHR) and estimated glucose disposal rate (eGDR) in adult type 1 diabetic patients. Thirty-six type 1 diabetic patients (aged 31±8 years; Female/Male: 22/14) and 43 age, gender and BMI matched healthy controls were included. Fasting blood glucose (FBG), hemoglobin A1c, and lipid profiles were measured. Waist-hip-ratio (WHR) was calculated. Daily insulin dose/kg of patients were recorded and eGDR of all subjects was calculated. Epicardial adipose tissue (EAT) thickness was evaluated by echocardiography. EAT thickness of the type 1 diabetic patients was significantly higher than controls (3.30±1.06 vs. 2.30±0.34 mm, P<0.0001). EAT thickness was correlated with age (P=0.05; r=0.35), WHR (P=0.003; r=0.67), daily insulin dose/kg (r=0.45, P=0.005), and eGDR (r=-0.55, P=0.0004). Multivariate analysis revealed WHR and eGDR to be related to EAT among age, WHR, daily insulin dose/kg, eGDR, FBG, and hemoglobin A1c (r2 of the model=0.64). Epicardial adipose tissue thickness is increased in type 1 diabetic patients compared to controls and is related to WHR and eGDR in this group of patients. This measurement may point to the presence of insulin resistance in type 1 diabetic patients. PMID:21553302

Yaz?c?, Dilek; Özben, Beste; Yavuz, Dilek; Deyneli, O?uzhan; Ayd?n, Hasan; Tarcin, Özlem; Akal?n, Sema

2011-05-08

302

Divergent phenotype of rat thoracic and abdominal perivascular adipose tissues.  

PubMed

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

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

2013-02-06

303

Hypoxia-Inducible Factor 1  Induces Fibrosis and Insulin Resistance in White Adipose Tissue  

Microsoft Academic Search

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 1 (HIF1) expression. Using a transgenic

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

2009-01-01

304

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

305

Chondrogenic Potential of Adipose Tissue-Derived Stromal Cells in Vitro and in Vivo  

Microsoft Academic Search

Articular cartilage exhibits little intrinsic repair capacity, and new tissue engineering approaches are being developed to promote cartilage regeneration using cellular therapies. The goal of this study was to examine the chondrogenic potential of adipose tissue-derived stromal cells. Stromal cells were isolated from human subcutaneous adipose tissue obtained by liposuction and were expanded and grown in vitro with or without

Geoffrey R. Erickson; Jeffrey M. Gimble; Dawn M. Franklin; Henry E. Rice; Hani Awad; Farshid Guilak

2002-01-01

306

Analysis of an expression profile of genes in the human adipose tissue  

Microsoft Academic Search

Increasing evidence suggests that in addition to storing excess energy as fat, adipose tissue acts as an endocrine organ secreting various factors into the blood stream. Every time a new factor is found in adipose tissue, however, its implication is discussed independently, and a systematic analyses based upon a global view of gene expression of this tissue has not been

Kazuhisa Maeda; Kousaku Okubo; Iichiro Shimomura; Katsuya Mizuno; Yuji Matsuzawa; Kenichi Matsubara

1997-01-01

307

Caveolin-1 Expression Is Essential for Proper Nonshivering Thermogenesis in Brown Adipose Tissue  

Microsoft Academic Search

Recently, we have shown that loss of caveolin-1 leads to marked alterations in insulin signaling and lipolysis in white adipose tissue. However, little is known about the role of caveolin-1 in brown adipose tissue (BAT), a tissue responsible for nonshivering thermogenesis. Here, we show that caveolin-1 null mice have a mildly, yet significantly, decreased resting core body tempera- ture. To

Alex W. Cohen; William Schubert; Dawn L. Brasaemle; Philipp E. Scherer; Michael P. Lisanti

308

From the epicardial adipose tissue to vulnerable coronary plaques.  

PubMed

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. PMID:23675552

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

2013-04-26

309

Adipose tissue as a stem cell source for musculoskeletal regeneration.  

PubMed

Adipose tissue is an abundant, easily accessible, and reproducible cell source for musculo-skeletal regenerative medicine applications. Initial derivation steps yield a heterogeneous population of cells of stromal vascular fraction (SVF) cells. Subsequent adherent selection of the SVF results in a relatively homogeneous population of adipose-derived stromal/stem cells (ASCs) capable of adipogenic, chondrogenic, myogenic, and osteogenic differentiation in vitro on scaffolds in bioreactors and in vivo in pre-clinical animal models. Unlike hematopoietic cells, ASCs do not elicit a robust lymphocyte reaction and instead release immunosuppressive factors, such as prostaglandin E2. These immunomodulatory features suggest that allogeneic and autologous ASCs will engraft successfully for tissue regeneration purposes. The differentiation and expansion potential of ASCs can be modified by growth factors, bio-inductive scaffolds, and bioreactors providing environmental control and biophysical stimulation. Gene therapy approaches using lentiviral transduction can be used to direct differentiation of ASCs to particular lineages. We discuss the utility of ASCs for musculo-skeletal tissue repair and some of the technologies that can be implemented to unlock the full regenerative potential of these highly valuable cells. PMID:21196358

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

2011-01-01

310

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

PubMed

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

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

2013-04-28

311

MicroRNA Transcriptomes Relate Intermuscular Adipose Tissue to Metabolic Risk.  

PubMed

Intermuscular adipose tissue is located between the muscle fiber bundles in skeletal muscles, and has similar metabolic features to visceral adipose tissue, which has been found to be related to a number of obesity-related diseases. Although various miRNAs are known to play crucial roles in adipose deposition and adipogenesis, the microRNA transcriptome of intermuscular adipose tissue has not, until now, been studied. Here, we sequenced the miRNA transcriptomes of porcine intermuscular adipose tissue by small RNA-sequencing and compared it to a representative subcutaneous adipose tissue. We found that the inflammation- and diabetes-related miRNAs were significantly enriched in the intermuscular rather than in the subcutaneous adipose tissue. A functional enrichment analysis of the genes predicted to be targeted by the enriched miRNAs also indicated that intermuscular adipose tissue was associated mainly with immune and inflammation responses. Our results suggest that the intermuscular adipose tissue should be recognized as a potential metabolic risk factor of obesity. PMID:23609494

Ma, Jideng; Yu, Shuzhen; Wang, Fengjiao; Bai, Lin; Xiao, Jian; Jiang, Yanzhi; Chen, Lei; Wang, Jinyong; Jiang, Anan; Li, Mingzhou; Li, Xuewei

2013-04-22

312

Epicardial perivascular adipose tissue as a therapeutic target in obesity-related coronary artery disease  

PubMed Central

Adipose tissue is an active endocrine and paracrine organ that may influence the development of atherosclerosis and vascular disease. In the setting of obesity, adipose tissue produces a variety of inflammatory cytokines (or adipokines) that are known to modulate key mechanisms of atherogenesis. In particular, adipose tissue located on the surface of the heart surrounding large coronary arteries (i.e. epicardial perivascular adipose tissue) has been implicated in the pathogenesis of coronary artery disease. The present review outlines our current understanding of the cellular and molecular links between perivascular adipose tissue and atherosclerosis with a focus on potential mechanisms by which epicardial perivascular adipose tissue contributes to obesity-related coronary disease. The pathophysiology of perivascular adipose tissue in obesity and its influence on oxidative stress, inflammation, endothelial dysfunction and vascular reactivity is addressed. In addition, the contribution of specific epicardial perivascular adipose-derived adipokines (e.g. leptin, adiponectin) to the initiation and expansion of coronary disease is also highlighted. Finally, future investigative goals are discussed with an emphasis on indentifying novel therapeutic targets and disease markers within perivascular adipose tissue. 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

Payne, Gregory A; Kohr, Meredith C; Tune, Johnathan D

2012-01-01

313

Differential effects of reduced protein diets on fatty acid composition and gene expression in muscle and subcutaneous adipose tissue of Alentejana purebred and Large White × Landrace × Pietrain crossbred pigs.  

PubMed

The present study assessed the effect of pig genotype (fatty v. lean) and dietary protein and lysine (Lys) levels (normal v. reduced) on intramuscular fat (IMF) content, subcutaneous adipose tissue (SAT) deposition, fatty acid composition and mRNA levels of genes controlling lipid metabolism. The experiment was conducted on sixty intact male pigs (thirty Alentejana purebred and thirty Large White × Landrace × Pietrain crossbred), from 60 to 93 kg of live weight. Animals were divided into three groups fed with the following diets: control diet equilibrated for Lys (17·5 % crude protein (CP) and 0·7 % Lys), reduced protein diet (RPD) equilibrated for Lys (13·2 % CP and 0·6 % Lys) and RPD not equilibrated for Lys (13·1 % CP and 0·4 % Lys). It was shown that the RPD increased fat deposition in the longissimus lumborum muscle in the lean but not in the fatty pig genotype. It is strongly suggested that the effect of RPD on the longissimus lumborum muscle of crossbred pigs is mediated via Lys restriction. The increase in IMF content under the RPD was accompanied by increased stearoyl-CoA desaturase (SCD) and PPARG mRNA levels. RPD did not alter backfat thickness, but increased the total fatty acid content in both lean and fatty pig genotype. The higher amount of SAT in fatty pigs, when compared with the lean ones, was associated with the higher expression levels of ACACA, CEBPA, FASN and SCD genes. Taken together, the data indicate that the mechanisms regulating fat deposition in pigs are genotype and tissue specific, and are associated with the expression regulation of the key lipogenic genes. PMID:23286604

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

2013-01-04

314

[Application of human adipose-derived stromal cells in bone tissue engineering].  

PubMed

Human adipose-derived stromal cells (hASCs) can be obtained from adipose tissues that offer an abundant and easily accessible pool of stem cells. Thus, hASCs have become a highly attractive source of seed cells in bone tissue engineering and have promising prospects in bone regeneration. Since 2002, our research group has performed a series of experiments on hASCs and its application in bone tissue engineering, including: to substitute dexamethasone by 1,25 (OH)? vitamin D? to induce osteogenic differentiation of hASCs; to explore the effect of epigenetic regulation and to inflammation on the osteogenic differentiation of hASCs; to construct a novel and simple tissue engineered bone system by hASCs and human platelet-rich plasma (hPRP) and to investigate the bone formation capability of this tissue engineered bone and the stimulatory effect of simvastatin. Our results suggested that 1,25 (OH)? vitamin D? could replace dexamethasone to induce the osteogenic differentiation of hASCs; retinoblastoma binding protein 2 (RBP2), as one of histone demethylases, could regulate the osteogenic differentiation of hASCs epigenetically while tumor necrosis factor ? (TNF?), as a inflammatory factor, could also influence the osteogenic differentiation of hASCs. Moreover, we found that in vivo bone formation could be detected by our novel tissue engineered bone composed with hASCs and hPRP; simvastatin could enhance the bone formation capability of this tissue-engineered structure. PMID:22353921

Zhou, Yong-sheng; Liu, Yun-song; Ge, Wen-shu; Zhang, Xiao; Ma, Gui-e; Zeng, Bai-jin; Ni, Yong-wei

2012-02-18

315

The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase.  

PubMed Central

A previous study reported the increased expression of the cytokine TNF in the adipose tissue of genetically obese rodents. To examine this paradigm in humans, we studied TNF expression in lean, obese, and reduced-obese human subjects. TNF mRNA was demonstrated in human adipocytes and adipose tissue by Northern blotting and PCR. TNF protein was quantitated by Western blotting and ELISA in both adipose tissue and the medium surrounding adipose tissue. Using quantitative reverse transcriptase PCR (RT-PCR), TNF mRNA levels were examined in the adipose tissue of 39 nondiabetic subjects, spanning a broad range of body mass index (BMI). There was a significant increase in adipose TNF mRNA levels with increasing adiposity. There was a significant correlation between TNF mRNA and percent body fat (r = 0.46, P < 0.05, n = 23). TNF mRNA tended to decrease in very obese subjects, but when subjects with a BMI > 45 kg/m2 were excluded, there was a significant correlation between TNF mRNA and BMI (r = 0.37, P < 0.05, n = 32). In addition, there was a significant decrease in adipose TNF with weight loss. In 11 obese subjects who lost between 14 and 66 kg (mean 34.7 kg, or 26.6% of initial weight), TNF mRNA levels decreased to 58% of initial levels after weight loss (P < 0.005), and TNF protein decreased to 46% of initial levels (P < 0.02). TNF is known to inhibit LPL activity. When fasting adipose LPL activity was measured in these subjects, there was a significant inverse relationship between TNF expression and LPL activity (r = -0.39, P < 0.02, n = 39). With weight loss, LPL activity increased to 411% of initial levels. However, the magnitude of the increase in LPL did not correlate with the decrease in TNF. Thus, TNF is expressed in human adipocytes. TNF is elevated in most obese subjects and is decreased by weight loss. In addition, there is an inverse relationship between TNF and LPL expression. These data suggest that endogenous TNF expression in adipose tissue may help limit obesity in some subjects, perhaps by increasing insulin resistance and decreasing LPL. Images

Kern, P A; Saghizadeh, M; Ong, J M; Bosch, R J; Deem, R; Simsolo, R B

1995-01-01

316

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

PubMed Central

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

2011-01-01

317

Regulation of the Fibrosis and Angiogenesis Promoter SPARC/Osteonectin in Human Adipose Tissue by Weight Change, Leptin, Insulin, and Glucose  

PubMed Central

OBJECTIVE Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 ± 3.7 kg). Another six lean subjects underwent fast-food–based hyperalimentation for 4 weeks (weight gain: 7.2 ± 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. RESULTS SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment–insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. CONCLUSIONS Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.

Kos, Katrina; Wong, Steve; Tan, Bee; Gummesson, Anders; Jernas, Margareta; Franck, Niclas; Kerrigan, David; Nystrom, Fredrik H.; Carlsson, Lena M.S.; Randeva, Harpal S.; Pinkney, Jonathan H.; Wilding, John P.H.

2009-01-01

318

Relationship between serum amyloid A level and Tanis/SelS mRNA expression in skeletal muscle and adipose tissue from healthy and type 2 diabetic subjects.  

PubMed

Tanis is a recently described protein reported to be a putative receptor for serum amyloid A and found to be dysregulated with diabetes in the Israeli sand rat Psamommys obesus. Tanis has also been identified as a selenoprotein, one of the first two identified membrane selenoproteins. We determined mRNA expression of the human homologue of Tanis, SelS/AD-015, in skeletal muscle and adipose tissue biopsies obtained from 10 type 2 diabetic patients and 11 age- and weight-matched healthy subjects. Expression of Tanis/SelS mRNA in skeletal muscle and adipose tissue biopsies was similar between diabetic and control subjects. A subset of subjects underwent a euglycemic-hyperinsulinemic clamp, and adipose tissue expression of Tanis/SelS was determined after in vivo insulin stimulation. Adipose tissue Tanis/SelS mRNA expression was unchanged after insulin infusion in control subjects, whereas Tanis/SelS mRNA increased in seven of eight subjects following insulin stimulation in diabetic subjects. Skeletal muscle and adipose tissue Tanis/SelS mRNA expression were positively correlated with plasma serum amyloid A. In conclusion, there is a strong trend toward upregulation of Tanis/SelS following insulin infusion in adipose tissue from type 2 diabetic subjects. Moreover, the positive relationship between Tanis mRNA and the acute-phase protein serum amyloid A suggests an interaction between innate immune system responses and Tanis expression in muscle and adipose tissue. PMID:15161744

Karlsson, Håkan K R; Tsuchida, Hiroki; Lake, Staffan; Koistinen, Heikki A; Krook, Anna

2004-06-01

319

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

PubMed Central

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.

Boscaro, Marco; Giacchetti, Gilberta; Ronconi, Vanessa

2012-01-01

320

Visceral adipose tissue in children and adolescents: a review.  

PubMed

Research conducted among adults has mainly shown that visceral adipose tissue (VAT) is strongly linked to insulin resistance, type 2 diabetes, hypertension and dyslipidaemia, leading to increased risk of CVD or the metabolic syndrome. However, little is known about the aetiology, determinants and consequences of VAT in children. The present article reviews the current literature relating to the factors influencing visceral fat accumulation in children and adolescents. The literature used in the present study was collected by searching a PubMed database, in which studies up to 2008 exploring the factors influencing accumulation of visceral fat among children and youth were found on the basis of appropriate keywords. Further studies concerning different factors influencing deposition of VAT among children and youth should first of all concentrate on: carrying out long-term analyses among children of different ethnical groups, which should begin in the period of prepuberty and which should cover the whole period of puberty till adulthood; drawing up norms specifying the amount of VAT among healthy children; identification of anthropometric indicators which will help to determine the VAT:subcutaneous adipose tissue ratio in the most precise way; broader studies of the influence of eating habits on developing VAT deposit among children and youth. PMID:19737436

Suliga, Edyta

2009-12-01

321

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

2012-12-10

322

Seeking the source of adipocytes in adult white adipose tissues  

PubMed Central

Adipocyte progenitors are thought to play a fundamental role in white adipose tissue (WAT) plasticity, which enables dynamic modulation of WAT metabolic and cellular characteristics in response to various stimuli. In general, two main strategies have been used to identify adipocyte progenitor cells: fluorescence-activated cell sorting (FACS)-based prospective analysis and lineage tracing. Although FACS-isolation is highly useful in defining multipotential stem cell populations for in vitro analysis and transplantation, lineage tracing is essential to identify endogenous progenitors that do, in fact, differentiate into adipocytes in vivo. Our recent lineage tracing studies have shown that cells expressing the surface marker platelet-derived growth factor receptor ? (PDGFR?) give rise to white and brown adipocytes in adult WAT, depending on inductive cues. PDGFR?+ cells are a subpopulation of those expressing CD34 and Sca1, and have unique morphology whereby long dendritic processes contact numerous cell types in the microenvironment. The significant contribution of PDGFR?+ cells to browning and hyperplastic expansion of WAT leads us to propose that PDGFR?+ cells are remodeling stem cells in adult WAT. Application of advanced imaging technology and genetic tools to this progenitor population will allow greater understanding of cellular plasticity in adipose tissue.

Lee, Yun-Hee; Granneman, James G.

2012-01-01

323

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

Microsoft Academic Search

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

Ali Sajjadian; Keshav Tandav Magge

2007-01-01

324

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

PubMed Central

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

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

2012-01-01

325

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

326

Liver kinase b1 is required for white adipose tissue growth and differentiation.  

PubMed

White adipose tissue (WAT) is not only a lipogenic and fat storage tissue but also an important endocrine organ that regulates energy homeostasis, lipid metabolism, appetite, fertility, and immune and stress responses. Liver kinase B1 (LKB1), a tumor suppressor, is a key regulator in energy metabolism. However, the role of LKB1 in adipogenesis is unknown. The current study aimed to determine the contributions of LKB1 to adipogenesis in vivo. Using the Fabp4-Cre/loxP system, we generated adipose tissue-specific LKB1 knockout (LKB1(ad-/-)) mice. LKB1(ad-/-) mice exhibited a reduced amount of WAT, postnatal growth retardation, and early death before weaning. Further, LKB1 deletion markedly reduced the levels of insulin receptor substrate 1 (IRS1), peroxisome proliferator-activated receptor ?, CCAAT/enhancer-binding protein ?, and phosphorylated AMP-activated protein kinase (AMPK). Consistent with these results, overexpression of constitutively active AMPK partially ablated IRS1 degradation in LKB1-deficient cells. LKB1 deletion increased the levels of F-box/WD repeat-containing protein (Fbw) 8, the IRS1 ubiquitination E3 ligase. Silencing of Fbw8 increased IRS1 levels. Finally, promoter analysis and DNA chromatin immunoprecipitation analysis identified three sterol regulatory element (SRE) sites in the Fbw8 promoter, where SRE-binding protein 1c binds and induces the expression of Fbw8. Taken together, these data indicate that LKB1 controls IRS1-dependent adipogenesis via AMPK in WAT. PMID:23396401

Zhang, Wencheng; Wang, Qilong; Song, Ping; Zou, Ming-Hui

2013-02-08

327

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. [(14)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

2013-07-03

328

Forms of lipoprotein lipase in rat tissues: in adipose tissue the proportion of inactive lipase increases on fasting.  

PubMed Central

Previous studies have shown that the ratio of lipoprotein lipase (LPL) catalytic activity to LPL mass in tissues differs in different conditions, but it is not clear whether this occurs by a change in the catalytic efficiency of the LPL molecules, or because of a shift in the relation between active and inactive forms of the enzyme. To explore this, we have measured LPL activity and mass in detergent extracts of rat tissues. LPL specific activity was high and similar in heart, skeletal muscle, lung and brain. The liver had significantly lower specific activity, which is in accord with previous findings that the liver takes up and catabolizes LPL. The specific activity was also low in adipose tissue from fasted rats. When tissue extracts were applied to columns of heparin-agarose and eluted by a gradient of NaCl, a peak of active LPL was eluted at 1.0 M NaCl, but there was also a peak of inactive LPL protein, which was eluted at 0.6 M NaCl. In adipose tissue, LPL activity decreased by 70-80% during an overnight fast, whereas LPL mass decreased by only 20-40%. The mass ratio between inactive and active LPL, as separated by heparin-agarose chromatography, increased from 0.5 to over 2 during the fast. In hearts there was no significant difference between fed and fasted rats in total LPL activity, LPL mass or in the distribution between inactive and active forms. The results indicate that the relation between inactive (probably monomeric) and active (dimeric) forms of LPL is a target for post-translational regulation in adipose tissue.

Bergo, M; Olivecrona, G; Olivecrona, T

1996-01-01

329

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

PubMed Central

Extracellular matrix (ECM) secreted from the resident cell of tissue is an ideal biomaterial evolved by nature. Cartilage is also built from well-organized ECM components in a gel-like structure with a high collagen and proteoglycan content. Here, we explored cartilage tissue engineering using ECM scaffolds seeded with stem cells. Both scaffolds and stem cells were isolated from human adipose tissue, which is abundant and easily harvested in the human body. The human ECM scaffolds contained various endogenous bioactive factors, including transforming growth factor-beta1 (TGF-?1, 8782±4989?pg/g, dry ECM), insulin growth factor-1 (13319±1388?pg/g, dry ECM), basic fibroblast growth factor (82373±9572?pg/g, dry ECM), and vascular endothelial growth factor (25647±2749?pg/g, dry ECM). A composite of ECM and stem cells was prepared and cultured in chondrogenic medium (with 10?ng/mL TGF-?1 or not) for 45 days. The volumes and weights of the composites increased during culture and the surface gradually became smooth. Cell viability remained high throughout the 45 days of in vitro culture. Composites showed the formation of cartilage-like tissue with the synthesis of cartilage-specific proteins such as collagen and glycosaminoglycan. Important chondrogenic markers were expressed including Sox-9, aggrecan, and collagen type II and XI. These results demonstrate that a cell/ECM composite containing endogenous bioactive factors could provide biochemical cues for the promotion of cartilage formation.

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

2012-01-01

330

Isolation and immunophenotypic characterization of mesenchymal stem cells derived from equine species adipose tissue  

Microsoft Academic Search

The purpose of this work was to isolate and cultivate mesenchymal stem cells (MSC) derived from equine adipose tissue and conduct cellular characterization with the following markers: CD90, CD44 and CD13. Adipose tissue collection was performed at the base of the horses’ tails, followed by immediate isolation and cultivation of the MSC and posterior characterization by flow cytometry for the

Armando de Mattos Carvalho; Ana Liz Garcia Alves; Marjorie Assis Golim; Andrei Moroz; Carlos Alberto Hussni; Patrícia Galvão Gomes de Oliveira; Elenice Deffune

2009-01-01

331

Stranger in a strange land: Roles of glycogen turnover in adipose tissue metabolism  

Microsoft Academic Search

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

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

2010-01-01

332

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

Microsoft Academic Search

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

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

2005-01-01

333

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

334

NEW PERSPECTIVES ON ENDOCRINE SIGNALLING Tumour necrosis factor : a key regulator of adipose tissue mass  

Microsoft Academic Search

In addition to its established role in the immune system, tumour necrosis factor (TNF) exerts complex regulat- ory actions on adipose tissue. TNF is produced in and secreted by the adipocyte and thus is in a position to exert a paracrine and\\/or autocrine role within adipose tissue. TNF affects many aspects of adipocyte function, from adipocyte development to lipid metabolism.

J P Warne

335

Human mesenchymal stem cells from adipose tissue: Differentiation into hepatic lineage  

Microsoft Academic Search

Adipose tissue represents an accessible source of mesenchymal stem cells (ADSCs), with similar characteristics to bone marrow-derived stem cells. The aim of this work was to investigate the transdifferentiation of ADSCs into hepatic lineage cells in vitro. ADSCs were obtained from human adipose tissue from lipectomy. Cells were grown in medium containing 15% AB human serum. Cultures were serum deprived

R. Taléns-Visconti; A. Bonora; R. Jover; V. Mirabet; F. Carbonell; J. V. Castell; M. J. Gómez-Lechón

2007-01-01

336

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

Microsoft Academic Search

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

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

2007-01-01

337

Severe Hypoinsulinaemic Hypoglycaemia in a Premature Infant Associated with Poor Weight Gain and Reduced Adipose Tissue  

Microsoft Academic Search

Background: Hypoglycaemia is common in preterm and intrauterine growth retarded (IUGR) newborns. Although preterm and IUGR infants have limited adipose tissue stores, the role of adipose tissue and the associated adipocytokines in glucose physiology is not known. Aim: We report the case of a premature intrauterine growth retarded infant who had poor weight gain for the first 6 weeks of

Raquel Coelho; Jonathan Wells; John Symth; Robert Semple; Stephen O’Rahilly; Simon Eaton; Khalid Hussain

2007-01-01

338

Lipoprotein Lipase Activity in Heart, Diaphragm and Adipose Tissue in Rats Fed Various Carbohydrates  

Microsoft Academic Search

The lipoprotein lipase activities in the heart, diaphragm and adipose tissue were investigated in rats fed high-carbohydrate diets containing various carbohydrates. The ingestion of sucrose or fructose, as compared with ingestion of starch or glucose, increased significantly the lipoprotein lipase activity in the heart and diaphragm and slightly decreased the activity in adipose tissue. The relations of these changes with

A. Vrána; P. Fábry; L. Kazdová

1974-01-01

339

Insulin sensitivity of adipose tissue and of diaphragm in rats adapted to periodic hyperphagia  

Microsoft Academic Search

Summary  In the present paper the authors have investigated the sensitivity of adipose tissue and diaphragm to insulin in rats adapted to periodic hyperphagia. Insulin was administered by the intraperitoneal route in amounts that did not affect the blood sugar level. The incorporation of labelled glucose, administered simultaneously with insulin, into lipids of parametrial adipose tissue and into glycogen of the

A. Vrána; P. Fábry; T. Braun

1969-01-01

340

Progenitor-Enriched Adipose Tissue Transplantation as Rescue for Breast Implant Complications  

Microsoft Academic Search

n Abstract: Breast enhancement with artificial implants is one of the most frequently performed cosmetic surgeries but is associated with various complications, such as capsular contracture, that lead to implant removal or replacement at a relatively high rate. For replacement, we used transplantation of progenitor-supplemented adipose tissue (cell-assisted lipotransfer; CAL) in 15 patients. The stromal vascular fraction containing adipose tissue

Kotaro Yoshimura; Yuko Asano; Noriyuki Aoi; Masakazu Kurita; Yoshio Oshima; Katsujiro Sato; Keita Inoue; Hirotaka Suga; Hitomi Eto; Harunosuke Kato; Kiyonori Harii

2009-01-01

341

Acute exercise increases adipose tissue interstitial adiponectin concentration in healthy overweight and lean subjects  

Microsoft Academic Search

Objective: We studied how an acute bout of exercise influences expression and concentration of adiponectin and regulators of adiponectin in adipose tissue and plasma. Design and methods: Eight overweight and eight lean males were examined by large-pore microdialysis in s.c. abdominal adipose tissue (SCAAT) and had arterialized blood sampled. On one day subjects rested for 3 h, exercised for 1

L. Hojbjerre; Mary Rosenzweig; Flemming Dela; Jens M Bruun; Bente Stallknecht

2007-01-01

342

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

343

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

PubMed

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

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

2000-09-01

344

Adipose-specific deletion of stearoyl-CoA desaturase 1 up-regulates the glucose transporter GLUT1 in adipose tissue  

PubMed Central

Stearoyl-CoA desaturase 1 (SCD1) deficiency protects mice from diet-induced obesity and insulin resistance. To understand the tissue-specific role of SCD1 in energy homeostasis, we have generated mice with an adipose-specific knockout of Scd1 (AKO), and report here that SCD1 deficiency increases GLUT1 expression in adipose tissue of AKO mice, but not global SCD1 knockout (GKO) mice. In 3T3-L1 adipocytes treated with a SCD inhibitor, basal glucose uptake and the cellular expression of GLUT1 were significantly increased while GLUT4 expression remained unchanged. Consistently, adipose-specific SCD1 knockout (AKO) mice had significantly elevated GLUT1 expression, but not GLUT4, in white adipose tissue compared to Lox counterparts. Concurrently, adiponectin expression was significantly diminished, whereas TNF-? expression was elevated. In contrast, in adipose tissue of GKO mice, GLUT4 and adiponectin expression were significantly elevated with lowered TNF-? expression and little change in GLUT1 expression, suggesting a differential responsiveness of adipose tissue to global- or adipose-specific SCD1 deletion. Taken together, these results indicate that adipose-specific deletion of SCD1 induces GLUT1 up-regulation in adipose tissue, associated with decreased adiponectin and increased TNF-? production, and suggest that GLUT1 may play a critical role in controlling glucose homeostasis of adipose tissue in adipose-specific SCD1-deficient conditions.

Hyun, Chang-Kee; Kim, Eun-Do; Flowers, Matthew T.; Liu, Xueqing; Kim, Eunha; Strable, Maggie; Ntambi, James M.

2010-01-01

345

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

346

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

PubMed

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

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

2008-02-19

347

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

PubMed

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

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

2009-05-28

348

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

349

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

2009-10-15

350

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

PubMed

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

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

2010-06-11

351

Therapeutic Prospects of Metabolically Active Brown Adipose Tissue in Humans  

PubMed Central

The world-wide obesity epidemic constitutes a severe threat to human health and wellbeing and poses a major challenge to health-care systems. Current therapeutic approaches, relying mainly on reduced energy intake and/or increased exercise energy expenditure, are generally of limited effectiveness. Previously believed to be present only in children, the existence of metabolically active brown adipose tissue (BAT) was recently demonstrated also in healthy human adults. The physiological role of BAT is to dissipate chemical energy, mainly from fatty acids, as heat to maintain body temperature in cold environments. Recent studies indicate that the activity of BAT is negatively correlated with overweight and obesity, findings that raise the exciting possibility of new and effective weight reduction therapies based on increased BAT energy expenditure, a process likely to be amenable to pharmacological intervention.

Betz, Matthias J.; Enerback, Sven

2011-01-01

352

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

PubMed

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

Carey, Andrew L; Kingwell, Bronwyn A

2013-05-26

353

Crosstalk Between Perivascular Adipose Tissue and Blood Vessels  

PubMed Central

Crosstalk between cells in the blood vessel wall is vital to normal vascular function and is perturbed in diseases such as atherosclerosis and hypertension. Perivascular adipocytes reside at the adventitial border of blood vessels but until recently were virtually ignored in studies of vascular function. However, perivascular adipocytes have been demonstrated to be powerful endocrine cells capable of responding to metabolic cues and transducing signals to adjacent blood vessels. Accordingly, crosstalk between perivascular adipose tissue (PVAT) and blood vessels is now being intensely examined. Emerging evidence suggests that PVAT regulates vascular function through numerous mechanisms, but evidence to date suggests modulation of three key aspects that are the focus of this review: inflammation, vasoreactivity, and smooth muscle cell proliferation.

Rajsheker, Srinivas; Manka, David; Blomkalns, Andra L.; Chatterjee, Tapan K.; Stoll, Lynn L.; Weintraub, Neal L.

2009-01-01

354

Perilipin Overexpression in White Adipose Tissue Induces a Brown Fat-Like Phenotype  

PubMed Central

Background Perilipin A (PeriA) exclusively locates on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Previously, we reported that adipocyte specific overexpression of PeriA caused resistance to diet-induced obesity and resulted in improved insulin sensitivity. In order to better understand the biological basis for this observed phenotype, we performed additional studies in this transgenic mouse model. Methodology and Principal Findings When compared to control animals, whole body energy expenditure was increased in the transgenic mice. Subsequently, we performed DNA microarray analysis and real-time PCR on white adipose tissue. Consistent with the metabolic chamber data, we observed increased expression of genes associated with fatty acid ?-oxidation and heat production, and a decrease in the genes associated with lipid synthesis. Gene expression of Pgc1a, a regulator of fatty acid oxidation and Ucp1, a brown adipocyte specific protein, was increased in the white adipose tissue of the transgenic mice. This observation was subsequently verified by both Western blotting and histological examination. Expression of RIP140, a regulator of white adipocyte differentiation, and the lipid droplet protein FSP27 was decreased in the transgenic mice. Importantly, FSP27 has been shown to control gene expression of these crucial metabolic regulators. Overexpression of PeriA in 3T3-L1 adipocytes also reduced FSP27 expression and diminished lipid droplet size. Conclusions These findings demonstrate that overexpression of PeriA in white adipocytes reduces lipid droplet size by decreasing FSP27 expression and thereby inducing a brown adipose tissue-like phenotype. Our data suggest that modulation of lipid droplet proteins in white adipocytes is a potential therapeutic strategy for the treatment of obesity and its related disorders.

Sawada, Takashi; Miyoshi, Hideaki; Shimada, Kohei; Suzuki, Akira; Okamatsu-Ogura, Yuko; Perfield, James W.; Kondo, Takuma; Nagai, So; Shimizu, Chikara; Yoshioka, Narihito; Greenberg, Andrew S.; Kimura, Kazuhiro; Koike, Takao

2010-01-01

355

Increased Expression of Macrophage-Inducible C-type Lectin in Adipose Tissue of Obese Mice and Humans  

PubMed Central

OBJECTIVE We have provided evidence that saturated fatty acids, which are released from adipocytes via macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for the Toll-like receptor (TLR) 4 complex in macrophages, thereby aggravating obesity-induced adipose tissue inflammation. The aim of this study was to identify the molecule(s) activated in adipose tissue macrophages in obesity. RESEARCH DESIGN AND METHODS We performed a cDNA microarray analysis of coculture of 3T3-L1 adipocytes and RAW264 macrophages. Cultured adipocytes and macrophages and the adipose tissue of obese mice and humans were used to examine mRNA and protein expression. RESULTS We found that macrophage-inducible C-type lectin (Mincle; also called Clec4e and Clecsf9), a type II transmembrane C-type lectin, is induced selectively in macrophages during the interaction between adipocytes and macrophages. Treatment with palmitate, a major saturated fatty acid released from 3T3-L1 adipocytes, induced Mincle mRNA expression in macrophages at least partly through the TLR4/nuclear factor (NF)-?B pathway. Mincle mRNA expression was increased in parallel with macrophage markers in the adipose tissue of obese mice and humans. The obesity-induced increase in Mincle mRNA expression was markedly attenuated in C3H/HeJ mice with defective TLR4 signaling relative to control C3H/HeN mice. Notably, Mincle mRNA was expressed in bone-marrow cell (BMC)-derived proinflammatory M1 macrophages rather than in BMC-derived anti-inflammatory M2 macrophages in vitro. CONCLUSIONS Our data suggest that Mincle is induced in adipose tissue macrophages in obesity at least partly through the saturated fatty acid/TLR4/NF-?B pathway, thereby suggesting its pathophysiologic role in obesity-induced adipose tissue inflammation.

Ichioka, Masayuki; Suganami, Takayoshi; Tsuda, Naoto; Shirakawa, Ibuki; Hirata, Yoichiro; Satoh-Asahara, Noriko; Shimoda, Yuri; Tanaka, Miyako; Kim-Saijo, Misa; Miyamoto, Yoshihiro; Kamei, Yasutomi; Sata, Masataka; Ogawa, Yoshihiro

2011-01-01

356

Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice  

PubMed Central

The white adipose organ is composed of both subcutaneous and several intra-abdominal depots. Excess abdominal adiposity is a major risk factor for metabolic disease in rodents and humans, while expansion of subcutaneous fat does not carry the same risks. Brown adipose produces heat as a defense against hypothermia and obesity, and the appearance of brown-like adipocytes within white adipose tissue depots is associated with improved metabolic phenotypes. Thus, understanding the differences in cell biology and function of these different adipose cell types and depots may be critical to the development of new therapies for metabolic disease. Here, we found that Prdm16, a brown adipose determination factor, is selectively expressed in subcutaneous white adipocytes relative to other white fat depots in mice. Transgenic expression of Prdm16 in fat tissue robustly induced the development of brown-like adipocytes in subcutaneous, but not epididymal, adipose depots. Prdm16 transgenic mice displayed increased energy expenditure, limited weight gain, and improved glucose tolerance in response to a high-fat diet. shRNA-mediated depletion of Prdm16 in isolated subcutaneous adipocytes caused a sharp decrease in the expression of thermogenic genes and a reduction in uncoupled cellular respiration. Finally, Prdm16 haploinsufficiency reduced the brown fat phenotype in white adipose tissue stimulated by ?-adrenergic agonists. These results demonstrate that Prdm16 is a cell-autonomous determinant of a brown fat–like gene program and thermogenesis in subcutaneous adipose tissues.

Seale, Patrick; Conroe, Heather M.; Estall, Jennifer; Kajimura, Shingo; Frontini, Andrea; Ishibashi, Jeff; Cohen, Paul; Cinti, Saverio; Spiegelman, Bruce M.

2010-01-01

357

Insulin action in adipose tissue in type 1 diabetes  

PubMed Central

Background: Insulin action has been reported to be normal in type 1 diabetic patients. However, some studies have reported an insulin resistance state in these patients. The aim of this study was to investigate insulin resistance in a group of type 1 diabetic patients. We studied the insulin action in adipose tissue and analyzed the effects of duration of disease, body mass index (BMI), and glycosylated hemoglobin on insulin action at the receptor and postreceptor levels in adipocytes. Methods: Nine female type 1 diabetic patients with different durations of disease and eight nondiabetic female patients of comparable age and BMI were studied. 125I-insulin binding and U-[14C]-D-glucose transport was measured in a sample of subcutaneous gluteus adipose tissue obtained by open surgical biopsy from each subject. Results: The duration of disease was negatively correlated with both 125I-insulin binding capacity (r = ?0.70, P < 0.05) and basal and maximum insulin-stimulated glucose transport (r = ?0.87, P < 0.01, and r = ?0.88, P < 0.01, respectively). Maximum specific 125I-insulin binding to the receptors in adipocytes was higher in the group of patients with a shorter duration of disease (P < 0.01). Basal and maximum insulin-stimulated glucose transport was significantly higher in the group with less than 5 years of disease (P < 0.01). No correlation was found between BMI and insulin action. Conclusion: Female type 1 diabetic patients have normal insulin action. There is a high glucose uptake in the early phase of the disease, although a longer duration of disease appears to be a contributing factor to a decrease in insulin action in these patients, and involving both receptor and postreceptor mechanisms.

Arrieta-Blanco, Francisco; Botella-Carretero, Jose Ignacio; Iglesias, Pedro; Balsa, Jose Antonio; Zamarron, Isabel; De la Puerta, Cristina; Arrieta, Juan Jose; Ramos, Francisco; Vazquez, Clotilde; Rovira, Adela

2011-01-01

358

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

359

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

360

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

Microsoft Academic Search

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

F. J. Bavelaar; A. C. Beynen

2003-01-01

361

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

Microsoft Academic Search

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

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

2009-01-01

362

Combined Gene and Protein Expression of Hormone-Sensitive Lipase and Adipose Triglyceride Lipase, Mitochondrial Content, and Adipocyte Size in Subcutaneous and Visceral Adipose Tissue of Morbidly Obese Men  

Microsoft Academic Search

SummaryAims: Lipotoxicity in obesity might be a failure of adipocytes to respond sufficiently adequate to persistent energy surplus. To evaluate the role of lipolytic enzymes or mitochondria in lipotoxicity, we studied expression levels of genes and proteins involved in lipolysis and mitochondrial DNA (mtDNA) content. Methods: As differences in lipid metabolism between men and women are extremely complex, we recruited

Hélène De Naeyer; D. Margriet Ouwens; Yves Van Nieuwenhove; Piet Pattyn; Leen M. ‘t Hart; Jean-Marc Kaufman; Henrike Sell; Juergen Eckel; Claude Cuvelier; Youri E. Taes; Johannes B. Ruige

2011-01-01

363

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

2009-06-22

364

Hypoxia-Inducible Factor 1? Induces Fibrosis and Insulin Resistance in White Adipose Tissue ? §  

PubMed Central

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 1? (HIF1?) expression. Using a transgenic model of overexpression of a constitutively active form of HIF1?, we determined that HIF1? fails to induce the expected proangiogenic response. In contrast, we observed that HIF1? 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 HIF1? and acts by cross-linking collagen I and III to form the fibrillar collagen fibers. Inhibition of LOX activity by ?-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.

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.

2009-01-01

365

Effect of age on brown adipose tissue activity in the obese (ob/ob) mouse.  

PubMed

Brown adipose tissue (BAT), a highly thermogenic tissue in young animals, is relatively atrophied and thermogenetically quiescent (e.g. as measured by colonic temperature) in mice that are obese or old. The aim of the current study was to investigate the effect of aging (3.1 (young) versus 14.6 (old) months old) on BAT activity in lean and obese (ob/ob) mice. In young but not in old mice, BAT mass in terms of weight per unit body weight was significantly lower in obese mice than in lean mice. A significant increase in BAT mass of obese mice with age was noted in terms of weight or weight per unit body weight, probably because of a tendency to become white adipose tissue and the deposit of fat, accompanied by the lowest levels of total protein, guanosine 5'-diphosphate binding, and uncoupling protein (UCP) antigen in the mitochondria of BAT, as well as the lowest colonic temperature among the groups examined. Unlike old lean animals, the old obese (ob/ob) animals did not increase but rather decreased the expression of mRNA for UCP in the mitochondria of BAT. These findings suggest that a marked decrease in BAT thermogenic capacity and activity is noted in old obese mice, probably due to synergism of aging and obesity. PMID:9509396

Ueno, N; Oh-ishi, S; Segawa, M; Nishida, M; Fukuwatari, Y; Kizaki, T; Ookawara, T; Ohno, H

1998-01-12

366

Cellularity and Adipogenic Profile of the Abdominal Subcutaneous Adipose Tissue From Obese Adolescents: Association With Insulin Resistance and Hepatic Steatosis  

PubMed Central

OBJECTIVE We explored whether the distribution of adipose cell size, the estimated total number of adipose cells, and the expression of adipogenic genes in subcutaneous adipose tissue are linked to the phenotype of high visceral and low subcutaneous fat depots in obese adolescents. RESEARCH DESIGN AND METHODS A total of 38 adolescents with similar degrees of obesity agreed to have a subcutaneous periumbilical adipose tissue biopsy, in addition to metabolic (oral glucose tolerance test and hyperinsulinemic euglycemic clamp) and imaging studies (MRI, DEXA, 1H-NMR). Subcutaneous periumbilical adipose cell-size distribution and the estimated total number of subcutaneous adipose cells were obtained from tissue biopsy samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. The adipogenic capacity was measured by Affymetrix GeneChip and quantitative RT-PCR. RESULTS Subjects were divided into two groups: high versus low ratio of visceral to visceral + subcutaneous fat (VAT/[VAT+SAT]). The cell-size distribution curves were significantly different between the high and low VAT/(VAT+SAT) groups, even after adjusting for age, sex, and ethnicity (MANOVA P = 0.035). Surprisingly, the fraction of large adipocytes was significantly lower (P < 0.01) in the group with high VAT/(VAT+SAT), along with the estimated total number of large adipose cells (P < 0.05), while the mean diameter was increased (P < 0.01). From the microarray analyses emerged a lower expression of lipogenesis/adipogenesis markers (sterol regulatory element binding protein-1, acetyl-CoA carboxylase, fatty acid synthase) in the group with high VAT/(VAT+SAT), which was confirmed by RT-PCR. CONCLUSIONS A reduced lipo-/adipogenic capacity, fraction, and estimated number of large subcutaneous adipocytes may contribute to the abnormal distribution of abdominal fat and hepatic steatosis, as well as to insulin resistance in obese adolescents.

Kursawe, Romy; Eszlinger, Markus; Narayan, Deepak; Liu, Teresa; Bazuine, Merlijn; Cali, Anna M.G.; D'Adamo, Ebe; Shaw, Melissa; Pierpont, Bridget; Shulman, Gerald I.; Cushman, Samuel W.; Sherman, Arthur; Caprio, Sonia

2010-01-01

367

In vivo manipulation of stem cells for adipose tissue repair/reconstruction.  

PubMed

Many features of adipose stem/progenitor cells, including their physiological functions and localization, have been clarified in the past decade. Adipose tissue turns over very slowly, with perivascular progenitor cells differentiating into new adipocytes to replace dead adipocytes. A number of clinical trials using freshly isolated or cultured adipose-derived stromal cells containing adipose progenitor/stem cells are ongoing. Therapeutic use of adipose stem/progenitor cells has been shown to promote angiogenesis and adipose tissue regeneration. Identification of adipocyte-releasing factors upon apoptosis/necrosis would be a breakthrough and could lead to the next stage for adipose tissue regeneration. Activation of precursors in perichondrium and periosteum shows a dramatic neogenesis by simple injection and is an ideal example of in situ tissue engineering. The 'hit and catch' strategy using a mobilizer of bone-marrow stem/progenitor cells (hit) and attractants to lead the cells to proper homing into the target tissue (catch) may be the future of stem cell manipulation. Careful design of the microenvironment, cell delivery protocol to avoid unexpected behavior and induce maximal potential, and selection of target diseases, will be critical to the success of clinical applications of adipose-derived stromal cells. PMID:21999260

Yoshimura, Kotaro; Eto, Hitomi; Kato, Harunosuke; Doi, Kentaro; Aoi, Noriyuki

2011-11-01

368

Feedback looping between ChREBP and PPAR? in the regulation of lipid metabolism in brown adipose tissues.  

PubMed

Carbohydrate response element binding protein (ChREBP) and peroxisome proliferator-activated receptor alpha (PPAR?) play an important role in the regulation of lipid metabolism in the liver. Chrebp and Ppara mRNA levels are equally abundant in brown adipose tissue and liver. However, their functions in brown adipose tissues are unclear. In this study, we attempted to clarify the role of ChREBP and PPAR? using brown adipose HB2 cell lines and tissues from wild type and Chrebp(-/-) C57BL/6J mice. In liver and brown adipose tissues, Chrebpb mRNA levels in the fasting state were much lower than those fed ad libitum, while Ppara mRNA levels in the fasting state were much higher than in the fed state. In differentiated brown adipose HB2 cell lines, glucose increased mRNA levels of ChREBP target genes such as Chrebpb, Fasn, and Glut4 in a dose dependent manner, while glucose decreased both Chrebpa and Ppara mRNA levels. Accordingly, adenoviral overexpression of ChREBP and a reporter assay demonstrated that ChREBP partially suppressed Ppara and Acox mRNA expression. Moreover, in brown adipose tissues from Chrebp(-/-) mice, Chrebpb and Fasn mRNA levels in the ad libitum fed state were much lower than those in the fasting state, while Ppara and Acox mRNA levels were not. Finally, using Wy14,643, a selective PPAR? agonist, and overexpression of PPAR? partially suppressed glucose induction of Chrebpb and Fasn mRNA in HB2 cells. In conclusion, the feedback loop between ChREBP and PPAR? plays an important role in the regulation of lipogenesis in brown adipocytes. PMID:23831548

Iizuka, Katsumi; Wu, Wudelehu; Horikawa, Yukio; Saito, Masayuki; Takeda, Jun

2013-07-05

369

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

2013-01-09

370

Transillumination of subcutaneous adipose tissues using near-infrared hyperspectral imaging in the 1100-1800 nm wavelength range  

NASA Astrophysics Data System (ADS)

Hyperspectral imaging (HSI) is a chemical imaging modality with spectroscopic information. This technique was often used in agricultural or pharmaceutical industries. But there have been a few reports for clinical medical applications. In near-infrared (NIR) wavelength region, the significant absorption peaks are often observed by the overtone of midinfrared molecular vibration. In addition, NIR light has a high penetration because of low scattering and less absorption by water or protein. In this study, we constructed the NIR-HSI system and the high-contrast subcutaneous adipose tissue imaging was conducted in-vitro. In the absorption spectra which are obtained by our NIR-HSI system, the characteristic absorption bands were observed around 1200 nm and 1700 nm. In the processed images using these wavelength bands, subcutaneous adipose tissue was observed through a skin. In a hyperspectral image by another processing using all wavelengths, a high-contrast image of subcutaneous adipose tissue is also obtained. NIR-HSI system is a powerful diagnostic technique for adipose tissues distribution and their morphological change on/inside a tissue.

Ishii, K.; Kitayabu, A.; Kobayashi, Y.; Honda, N.; Awazu, K.

2011-02-01

371

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

PubMed Central

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

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

2011-01-01

372

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

PubMed

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

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

2013-08-15

373

Reduced expression of PGC1 and insulin-signaling molecules in adipose tissue is associated with insulin resistance  

Microsoft Academic Search

Peroxisome proliferator-activated receptor ? (PPAR?) co-activator 1 (PGC-1) regulates glucose metabolism and energy expenditure and, thus, potentially insulin sensitivity. We examined the expression of PGC-1, PPAR?, insulin receptor substrate-1 (IRS-1), glucose transporter isoform-4 (GLUT-4), and mitochondrial uncoupling protein-1 (UCP-1) in adipose tissue and skeletal muscle from non-obese, non-diabetic insulin-resistant, and insulin-sensitive individuals. PGC-1, both mRNA and protein, was expressed in

A. Hammarstedt; P.-A. Jansson; C. Wesslau; X. Yang; U. Smith

2003-01-01

374

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

375

Brown adipose tissue. VI. Amount, location, extent, and correlation with nutritional status in adult humans  

Microsoft Academic Search

Multilocular brown adipose tissue (BAT) is a versatile endocrine tissue involved in non-shivering thermogenesis, mitochondrial\\u000a biogenesis, extracellular matrix homeostasis and signalling, and hibernation in hibernating animals. This study investigated\\u000a the correlations between the amount and extent of BAT and nutritional status in adult humans. Samples of adipose tissue from\\u000a nine body locations were taken from 107 consecutive autopsies in males

Jozef Šidlo; Peter Kvasni?ka; Henrieta Šidlová; Milan Zavia?i?

2010-01-01

376

Evidence for selective effects of vanadium on adipose cell metabolism involving actions on cAMP-dependent protein kinase  

Microsoft Academic Search

The insulin-like effects of vanadiumin vivo are likely to be achieved at micromolar concentrations. Demonstrated effects of vanadium on adipose tissue of streptozotocin-diabetic rats include inhibition of basal and stimulated rates of lipolysis and effects on fat cell protein phosphorylation. The studies described below examined the effects of vanadium (to a maximum concentration of 0.5 mM) on adipose cells or

Roger W. Brownsey; Gordon W. Dong

1995-01-01

377

FATTY ACID COMPOSITION OF MUSCLE AND ADIPOSE TISSUE FROM CROSSBRED BULLS AND STEERS 1  

Microsoft Academic Search

Fatty acid composition of total lipid extracts of muscle and adipose samples from crossbred bulls (N = 34) and steers (N = 35) was determined by gas-liquid chromatography. Samples of semitendinosus, triceps brachii and longissimus muscle and of subcutaneous and perinephric adipose tissue were excised from the right side of each carcass. In addition, thin-layer chroma- tography was utilized to

Jeffrey M. Eichhorn; Curtiss M. Bailey; Gary J. Blomquist

2010-01-01

378

Regulation of adipose tissue leptin secretion by alpha-melanocyte-stimulating hormone and agouti-related protein: further evidence of an interaction between leptin and the melanocortin signalling system.  

PubMed

The central role of the melanocortin system in the regulation of energy balance has been studied in great detail. However, the functions of circulating melanocortins and the roles of their peripheral receptors remain to be elucidated. There is increasing evidence of a peripheral action of melanocortins in the regulation of leptin production by adipocytes. Here we investigate the interaction of alpha-melanocyte stimulating hormone (alpha-MSH) and agouti-related protein (AgRP) in the regulation of leptin secretion from cultured rat adipocytes and examine the changes in circulating alpha-MSH and AgRP in lean and obese rodents after hormonal and energetic challenge. Leptin secretion (measured by ELISA) and gene expression (by real-time quantitative PCR) of differentiated rat adipocytes cultured in vitro were inhibited by the administration of alpha-MSH (EC50=0.24 nM), and this effect was antagonised by antagonists of the melanocortin receptors MC4R and MC3R (AgRP and SHU9119). The presence of MC4R in rat adipocytes (RT-PCR and restriction digest) supports the involvement of this receptor subtype in this interaction. Leptin administered to ob/ob mice in turn increases the release of alpha-MSH into the circulation, suggesting a possible feedback loop between the site of alpha-MSH release and the release of leptin from the adipose tissue. However, the physiological significance of this putative feedback probably depends upon the underlying state of energy balance, since in the fasting state low plasma alpha-MSH is paralleled by low plasma leptin. PMID:14765998

Hoggard, N; Hunter, L; Duncan, J S; Rayner, D V

2004-02-01

379

Toxicological Function of Adipose Tissue: Focus on Persistent Organic Pollutants  

PubMed Central

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

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

2012-01-01

380

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

SciTech Connect

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

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

1987-11-01