Adipose tissue growth and regression are regulated by angiopoietin-1

Adipose tissue is unique in its plasticity, capacity for vascular remodeling, and susceptibility to angiogenesis inhibitors. We hypothesize that these characteristics are enabled by maintaining relatively immature adipose vessels to facilitate vascular/tissue remodeling. We examined the vascular maturation regulators, angiopoietin-1, angiopoietin-2, and tie2 receptor, under different weight-modifying conditions. Adipocytes expressed angiopoietin-1, while adipose endothelial cells expressed angiopoietin-2 and tie2. Adipose tissue growth/regression were associated with decreased angiopoietin-1 mRNA and protein, and tie2 phosphorylation. Angiopoietin-2 and tie2 mRNA levels were stable. Angiopoietin-1 mRNA levels inversely correlated with the rates of change in body weight, independent of the direction (weight gain, loss) or etiology (TNP-470, leptin, and diet restriction) of the weight shift. Obese mice injected with ang1/pcDNA had reduced rates of weight gain and fat pad weights, regardless of the route of plasmid administration (subcutaneous, intramuscular, and intravenous). Thus, angiopoietin-1 may regulate adipose tissue growth, suggesting that vascular maturation alters tissue plasticity.     

Rapid Postnatal Weight Gain and Visceral Adiposity in Adulthood: The Fels Longitudinal Study

Rapid infant weight gain is associated with increased abdominal adiposity, but there is no published report of the relationship of early infant growth to differences in specific adipose tissue depots in the abdomen, including visceral adipose tissue (VAT). In this study, we tested the associations of birth weight, infant weight gain, and other early life traits with VAT, abdominal subcutaneous adipose tissue (ASAT), and other body composition measures using magnetic resonance imaging (MRI) and dual‐energy X‐ray absorptiometry in middle adulthood (mean age = 46.5 years). The sample included 233 appropriate for gestational age singleton white children (114 males) enrolled in the Fels Longitudinal Study. Multivariate‐adjusted general linear models were used to test the association of infant weight gain (from 0 to 2 years), maternal BMI, gestational age, parity, maternal age, and other covariates with adulthood body composition. Compared to infants with slow weight gain, rapid weight gain was associated with elevated risk of obesity (adjusted odds ratio = 4.1, 95% confidence interval = 1.4, 11.1), higher total body fat (+7 kg, P = 0.0002), percent body fat (+5%, P = 0.0006), logVAT mass (+0.43 kg, P = 0.02), logASAT mass (+0.47 kg, P = 0.001), and percent abdominal fat (+5%, P = 0.03). There was no evidence that the increased abdominal adipose tissue was due to a preferential deposition of VAT. In conclusion, rapid infant weight gain is associated with increases in both VAT and ASAT, as well as total adiposity and the risk of obesity in middle adulthood.     

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

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

Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth

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 weeks under regular and high-fat feeding conditions. The total cell number in the epididymal fat pad was estimated from the fat pad mass and the normalized cell-size distribution. The cell number and volume-weighted mean cell size increase as a function of fat pad mass. To address adipose tissue growth precisely, we developed a mathematical model describing the evolution of the adipose cell-size distributions as a function of the increasing fat pad mass, instead of the increasing chronological time. Our model describes the recruitment of new adipose cells and their subsequent development in different strains, and with different diet regimens, with common mechanisms, but with diet- and genetics-dependent model parameters. Compared to the FVB/N strain, the C57BL/6 strain has greater recruitment of small adipose cells. Hyperplasia is enhanced by high-fat diet in a strain-dependent way, suggesting a synergistic interaction between genetics and diet. Moreover, high-fat feeding increases the rate of adipose cell size growth, independent of strain, reflecting the increase in calories requiring storage. Additionally, high-fat diet leads to a dramatic spreading of the size distribution of adipose cells in both strains; this implies an increase in size fluctuations of adipose cells through lipid turnover.     

New scanning electron microscopic method for determination of adipocyte size in humans and mice

Objective: To evaluate a new scanning electronic microscopic (EM) method for assessing fat cell sizes and compare fat cell size distribution in human adipose tissue from different fat depots before and after weight loss. Research Methods and Procedures: Identical human fat tissue biopsies were separated into two fractions: one used to prepare a fat cell suspension by collagenase digestion followed by photomicrography (collagenase method) and the other fixed in formalin for EM analysis. The EM method was evaluated further by determining fat cell sizes from lean and ob/ob mice. Finally, the EM method was used to assess fat cell sizes in biopsies of different human depots from before and after weight loss. Results: Fat cell size distributions measured by the two methods were not identical, but differences were generally small. The EM method reproduced the well‐documented fat cell size difference between lean and ob/ob mice. Large variation was detected in fat cell distributions among three depots in humans. Weight loss reduced fat cell sizes in subjects with large baseline fat cells but had no effect in subjects with small baseline fat cell sizes. Discussion: Our results suggest that the EM method may be a useful alternative for fat cell size analysis of clinical samples.     

Moderate doses of conjugated linoleic acid isomers mix contribute to lowering body fat content maintaining insulin sensitivity and a noninflammatory pattern in adipose tissue in mice

Conjugated linoleic acid (CLA) modulates body composition, especially by reducing adipose tissue. However, despite the increasing knowledge about CLA's beneficial effects on obesity management, the mechanism of action is not yet fully understood. Furthermore, in some human studies fat loss is accompanied by impairment in insulin sensitivity, especially when using the trans-10,cis-12 isomer. The aim of this work was to study the effects of moderate doses of CLA on body fat deposition, cytokine profile and inflammatory markers in mice. Mice were orally treated with a mixture of CLA isomers, cis-9,trans-11 and trans-10,cis-12 (50:50), for 35 days with doses of CLA1 (0.15 g CLA/kg body weight) and CLA2 (0.5 g CLA/kg body weight). CLA had discrete effects on body weight but caused a clear reduction in fat mass (retroperitoneal and mesenteric as the most sensitive depots), although no other tissue weights were affected. Glucose and insulin were not altered by CLA treatment, and maintenance of glucose homeostasis was observed even under insulin overload. The study of gene expression (Emr1, MCP-1, IL-6, TNFα, PPARγ2 and iNOS) either in adipocytes and/or in the stromal vascular fraction indicated that CLA does not lead to the infiltration of macrophages in adipose tissue or to the induction of expression of pro-inflammatory cytokines. The use of a mixture of both isomers, as well as moderate doses of CLA, is able to induce a reduction of fat gain without an impairment of adipose tissue function while preserving insulin sensitivity.     

Adipocyte cellularity in different adipose depots in bulls of seven Spanish breeds slaughtered at two body weights

The influence of body weight (BW) at slaughter and genotype on adipocyte size and number in the omental (OM), perirenal (PR), subcutaneous (SC) and intermuscular (IM) adipose tissues was studied in 168 bulls of Spain's local Asturiana, Avileña, Morucha, Parda Alpina, Pirenaica, Retinta, and Rubia Gallega cattle breeds. The young bulls were slaughtered at two BWs, 320 and 540 kg. The results obtained showed the higher amounts of lipids that accumulated between 320 and 540 kg BW (P < 0.001) to be ascribable primarily to adipose cell hypertrophy, i.e. larger adipocyte size, in the OM and PR depots (P < 0.001). In addition to hypertrophy, there was also an increase (P < 0.001) in the number of adipose cells, i.e. hyperplasia, in the SC and IM adipose depots. Significant differences were observed when comparing the different genotypes, with the Morucha, Retinta and Avileña breeds having the highest amount of adipose tissue and the largest adipocytes. The Asturiana and Rubia Gallega breeds had the lowest amount of adipose tissue and the smallest adipocytes. The Pirenaica and Parda Alpina breeds had intermediate values in between the two groups identified above. In short, the results were indicative of different lipid deposition patterns in the different breeds depending on the individual growth and maturation rates in each. Similar findings were made when comparing the different adipose tissue depots, with adipocyte hypertrophy being the main factor responsible for lipid accumulation in the OM and PR depots, as opposed to adipocyte hyperplasia in the SC and IM depots.     

Pharmacological and nutritional agents promoting browning of white adipose tissue

The role of brown adipose tissue in the regulation of energy balance and maintenance of body weight is well known in rodents. Recently, interest in this tissue has re-emerged due to the realization of active brown-like adipose tissue in adult humans and inducible brown-like adipocytes in white adipose tissue depots in response to appropriate stimuli (“browning process”). Brown-like adipocytes that appear in white fat depots have been called “brite” (from brown-in-white) or “beige” adipocytes and have characteristics similar to brown adipocytes, in particular the capacity for uncoupled respiration. There is controversy as to the origin of these brite/beige adipocytes, but regardless of this, induction of the browning of white fat represents an attractive potential strategy for the management and treatment of obesity and related complications. Here, the different physiological, pharmacological and dietary determinants that have been linked to white-to-brown fat remodeling and the molecular mechanisms involved are reviewed in detail. In the light of available data, interesting therapeutic perspectives can be expected from the use of specific drugs or food compounds able to induce a program of brown fat differentiation including uncoupling protein 1 expression and enhancing oxidative metabolism in white adipose cells. However, additional research is needed, mainly focused on the physiological relevance of browning and its dietary control, where the use of ferrets and other non-rodent animal models with a more similar adipose tissue organization and metabolism to humans could be of much help. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.     

Helminth infection modulates number and function of adipose tissue Tregs in high fat diet-induced obesity

BackgroundEpidemiological and experimental studies have shown a protective effect of helminth infections in weight gain and against the development of metabolic dysfunctions in the host. However, the mechanisms Treg cells exert in the helminth-obesity interface has been poorly investigated. The present study aimed to verify the influence of Heligmosomoides polygyrus infection in early stages of high fat diet-induced obesity.Principal findingsThe presence of infection was able to prevent exacerbated weight gain in mice fed with high fat diet when compared to non-infected controls. In addition, infected animals displayed improved insulin sensitivity and decreased fat accumulation in the liver. Obesity-associated inflammation was reduced in the presence of infection, demonstrated by lower levels of leptin and resistin, lower infiltration of Th1 and Th17 cells in adipose tissue, higher expression of IL10 and adiponectin, increased infiltration of Th2 and eosinophils in adipose tissue of infected animals. Of note, the parasite infection was associated with increased Treg frequency in adipose tissue which showed higher expression of cell surface markers of function and activation, like LAP and CD134. The infection could also increase adipose Treg suppressor function in animals on high fat diet.ConclusionThese data suggest that H. polygyrus modulates adipose tissue Treg cells with implication for weight gain and metabolic syndrome.     

Fat depot-specific gene signature and ECM remodeling of Sca1high adipose-derived stem cells

Stem cell antigen-1 (Sca1 or Ly6A/E) is a cell surface marker that is widely expressed in mesenchymal stem cells, including adipose-derived stem cells (ASCs). We hypothesized that the fat depot-specific gene signature of Sca1^high ASCs may play the major role in defining adipose tissue function and extracellular matrix (ECM) remodeling in a depot-specific manner. Herein we aimed to characterize the unique gene signature and ECM remodeling of Sca1^high ASCs isolated from subcutaneous (inguinal) and visceral (epididymal) adipose tissues. Sca1^high ASCs are found in the adventitia and perivascular areas of adipose tissues. Sca1^high ASCs purified with magnetic-activated cell sorting (MACS) demonstrate dendrite or round shape with the higher expression of cytokines and chemokines (e.g., Il6, Cxcl1) and the lower expression of a glucose transporter (Glut1). Subcutaneous and visceral fat-derived Sca1^high ASCs particularly differ in the gene expressions of adhesion and ECM molecules. While the expression of the major membrane-type collagenase (MMP14) is comparable between the groups, the expressions of secreted collagenases (MMP8 and MMP13) are higher in visceral Sca1^high ASCs than in subcutaneous ASCs. Consistently, slow but focal MMP-dependent collagenolysis was observed with subcutaneous adipose tissue-derived vascular stromal cells, whereas rapid and bulk collagenolysis was observed with visceral adipose tissue-derived cells in MMP-dependent and -independent manners. These results suggest that the fat depot-specific gene signatures of ASCs may contribute to the distinct patterns of ECM remodeling and adipose function in different fat depots.     

Changes of Adipose Tissue Morphology and Composition during Late Pregnancy and Early Lactation in Dairy Cows

Dairy cows mobilize large amounts of body fat during early lactation to overcome negative energy balance which typically arises in this period. As an adaptation process, adipose tissues of cows undergo extensive remodeling during late pregnancy and early lactation. The objective of the present study was to characterize this remodeling to get a better understanding of adaptation processes in adipose tissues, affected by changing metabolic conditions including lipid mobilization and refilling as a function of energy status. This was done by determining adipocyte size in histological sections of subcutaneous and retroperitoneal adipose tissue biopsy samples collected from German Holstein cows at 42 days prepartum, and 1, 21, and 100 days postpartum. Characterization of cell size changes was extended by the analysis of DNA, triacylglycerol, and protein content per gram tissue, and β-actin protein expression in the same samples. In both adipose tissue depots cell size was becoming smaller during the course of the study, suggesting a decrease in cellular triacylglycerol content. Results of DNA, triacylglycerol, and protein content, and β-actin protein expression could only partially explain the observed differences in cell size. The retroperitoneal adipose tissue exhibited a greater extent of time-related differences in cell size, DNA, and protein content, suggesting greater dynamics and metabolic flexibility for this abdominal depot compared to the investigated subcutaneous depot.     

Dietary calcium attenuation of body fat gain during high-fat feeding in mice

Human epidemiological studies have supported the hypothesis that a dairy food-rich diet is associated with lower fat accumulation, although prospective studies and intervention trials are not so conclusive and contradictory data exist in animal models. The purpose of this study was to assess the effects on body weight and fat depots of dairy calcium (12 g/kg diet) in wild-type mice under ad libitum high-fat (43%) and normal-fat (12%) diets and to gain comprehension on the underlying mechanism of dairy calcium effects. Our results show that calcium intake decreases body weight and body fat depot gain under high-fat diet and accelerates weight loss under normal-fat diet, without differences in food intake. No differences in gene or protein expression of UCP1 in brown adipose tissue or UCP2 in white adipose tissue were found that could be related with calcium feeding, suggesting that calcium intake contributed to modulate body weight in wild-type mice by a mechanism that is not associated with activation of brown adipose tissue thermogenesis. UCP3 protein but not gene expression increased in muscle due to calcium feeding. In white adipose tissue there were effects of calcium intake decreasing the expression of proteins related to calcium signalling, in particular of stanniocalcin 2. CaSR levels could play a role in decreasing cytosolic calcium in adipocytes and, therefore, contribute to the diminution of fat accretion. Results support the anti-obesity effect of dietary calcium in male mice and indicate that, at least at the time-point studied, activation of thermogenesis is not involved.     

Characterization and comparison of adipose tissue‐derived cells from human subcutaneous and omental adipose tissues

Different fat depots contribute differently to disease and function. These differences may be due to the regional variation in cell types and inherent properties of fat cell progenitors. To address the differences of cell types in the adipose tissue from different depots, the phenotypes of freshly isolated adipose tissue‐derived cells (ATDCs) from subcutaneous (SC) and omental (OM) adipose tissues were compared using flow cytometry. Our results showed that CD31^?CD34⁺CD45^?CD90^‐CD105^?CD146⁺ population, containing vascular smooth muscle cells and pericytes, was specifically defined in the SC adipose tissue while no such population was observed in OM adipose tissue. On the other hand, CD31^?CD34⁺CD45^?CD90^?CD105^?CD146^? population, which is an undefined cell population, were found solely in OM adipose tissue. Overall, the SC adipose tissue contained more ATDCs than OM adipose tissue, while OM adipose tissue contained more blood‐derived cells. Regarding to the inherent properties of fat cell progenitors from the two depots, adipose‐derived stem cells (ADSCs) from SC had higher capacity to differentiate into both adipogenic and osteogenic lineages than those from OM, regardless of that the proliferation rates of ADSCs from both depots were similar. The higher differentiation capacity of ADSCs from SC adipose tissue suggests that SC tissue is more suitable cell source for regenerative medicine than OM adipose tissue. Copyright © 2009 John Wiley & Sons, Ltd.     

Exploring the activated adipogenic niche: Interactions of macrophages and adipocyte progenitors

Adult adipose tissue contains a large supply of progenitors that can renew fat cells for homeostatic tissue maintenance and adaptive growth or regeneration in response to external challenges. However, the in vivo mechanisms that control adipocyte progenitor behavior are poorly characterized. We recently demonstrated that recruitment of adipocyte progenitors by macrophages is a central feature of adipose tissue remodeling under various adipogenic conditions. Catabolic remodeling of white adipose tissue by β3-adrenergic receptor stimulation requires anti-inflammatory M2-polarized macrophages to clear dying adipocytes and to recruit new brown adipocytes from progenitors. In this Extra Views article, we discuss in greater detail the cellular elements of adipogenic niches and report a strategy to isolate and characterize the subpopulations of macrophages and adipocyte progenitors that actively participate in adrenergic tissue remodeling. Further characterization of these subpopulations may facilitate identification of new cellular targets to improve metabolic and immune function of adipose tissue.     

Level of Preadipocyte Growth Factor in Rat Adipose Tissue which Specifically Permits the Proliferation of Preadipocytes Is Affected by Restricted Energy Intake

We previously reported the presence of a protein growth factor in rat adipose tissue which specifically permits the proliferation of 3T3-L1 and Obl771 preadipocytes [Biochem. Biophys. Res. Commun. 1990;171:905–912, ref. 1] and which is hereinafter referred to as PAGF (preadipocyte growth factor). In this study, the effects of long-term restricted energy intake on the PAGF activity in rat epididymal and perirenal adipose tissue toward 3T3-L1 preadipocytes were investigated. When rats were subjected to restricted energy intake for three weeks, PAGF activity increased with energy intake. The body weight, epididymal and perirenal fat depot weights and glycerol 3-phosphate dehydrogenase activity also increased with the energy intake, whereas the lactate dehydrogenase activity remained almost constant in all energy intake groups. These results suggest that the PAGF in fat depots functions in response to energy intake and contributes to the de novo formation of adipocytes and the growth of adipose tissue. This factor may provide a useful tool for further elucidation of the relationship between energy storage in adipose tissue and adipose tissue development.     

Plasminogen activator inhibitor-1, adipose tissue and insulin resistance

PURPOSE OF REVIEW: Plasminogen activator inhibitor (PAI)-1 is a physiological inhibitor of plasminogen activators (urokinase and tissue types) and vitronectin. It is synthesized by adipose tissue, and its levels in plasma are increased in obesity and reduced with weight loss. Circulating PAI-1 level predicts development of type 2 diabetes, suggesting that it may be causally related to development of obesity. A role for PAI-1 in development of obesity has only partially been established, however. This review summarizes current knowledge, gives context to developments thus far and discusses controversies. RECENT FINDINGS: In addition to its role in atherothrombosis, PAI-1 might be involved in adipose tissue development. PAI-1 is produced by ectopic fat depots under the influence of inducers. Among the most recently described inducers are inflammation, oxidative stress and circadian clock protein. PAI-1 may play several roles in contributing to obesity: through indirect effects on insulin signalling, by influencing adipocyte differentiation and by regulating recruitment of inflammatory cells within adipose tissue. SUMMARY: These recent findings emphasize the involvement of PAI-1 in controlling the biology of adipose tissue; PAI-1 is an attractive new therapeutic target to retard the metabolic complications that accompany obesity.     

Childbearing may increase visceral adipose tissue independent of overall increase in body fat

Objective: To examine whether childbearing is associated with increased visceral adiposity and whether the increase is proportionally larger than other depots. Methods and Procedures: This prospective study examined changes in adiposity assessed via computed tomography (CT) and dual‐energy X‐ray absorptiometry among 122 premenopausal women (50 black, 72 white) examined in 1995–1996 and again in 2000–2001. During the 5‐year interval, 14 women had one interim birth and 108 had no interim births. Multiple linear regression models estimated mean (95% confidence interval (CI)) 5‐year changes in anthropometric and adiposity measures by interim births adjusted for age, race, and changes in total and subcutaneous adiposity. Results: We found no significant differences between one interim birth and no interim births for 5‐year changes in weight, BMI, total body fat, subcutaneous adipose tissue, or total abdominal adipose tissue. Visceral adipose tissue increased by 40 and 14% above initial levels for 1 birth and 0 birth groups, respectively. Having 1 birth vs. 0 births was associated with a greater increase in visceral adipose tissue of 18.0 cm² (4.8, 31.2), P < 0.01; gain of 27.1 cm² (14.5, 39.7) vs. 9.2 cm² (4.8, 13.6), and a borderline greater increase in waist girth of 2.3 cm (0, 4.5), P = 0.05; gain of 6.3 cm (4.1, 8.5) vs. 4.0 cm (3.2, 4.8), controlling for gain in total body fat and covariates. Discussion: Pregnancy may be associated with preferential accumulation of adipose tissue in the visceral compartment for similar gains in total body fat. Further investigation is needed to confirm these findings and determine whether excess visceral fat deposition with pregnancy adversely affects metabolic risk profiles among women.     

Differences in Hematopoietic Stem Cells Contribute to Sexually Dimorphic Inflammatory Responses to High Fat Diet-induced Obesity

Women of reproductive age are protected from metabolic disease relative to postmenopausal women and men. Most preclinical rodent studies are skewed toward the use of male mice to study obesity-induced metabolic dysfunction because of a similar protection observed in female mice. How sex differences in obesity-induced inflammatory responses contribute to these observations is unknown. We have compared and contrasted the effects of high fat diet-induced obesity on glucose metabolism and leukocyte activation in multiple depots in male and female C57Bl/6 mice. With both short term and long term high fat diet, male mice demonstrated increased weight gain and CD11c⁺ adipose tissue macrophage content compared with female mice despite similar degrees of adipocyte hypertrophy. Competitive bone marrow transplant studies demonstrated that obesity induced a preferential contribution of male hematopoietic cells to circulating leukocytes and adipose tissue macrophages compared with female cells independent of the sex of the recipient. Sex differences in macrophage and hematopoietic cell in vitro activation in response to obesogenic cues were observed to explain these results. In summary, this report demonstrates that male and female leukocytes and hematopoietic stem cells have cell-autonomous differences in their response to obesity that contribute to an amplified response in males compared with females.     

Recruitment of brown fat and conversion of white into brown adipocytes: Strategies to fight the metabolic complications of obesity?

The role of white and brown adipose tissues in energy metabolism is well established. However, the existence of brown fat in adult humans was until very recently a matter of debate, and the molecular mechanisms underlying brown adipocyte development remained largely unknown. In 2009, several studies brought direct evidence for functional brown adipose tissue in adults. New factors involved in brown fat cell differentiation have been identified. Moreover, work on the origin of fat cells took an unexpected path with the recognition of different populations of brown fat cell precursors according to the anatomical location of the fat depots: a precursor common to skeletal muscle cells and brown adipocytes from brown fat depots, and a progenitor cell common to white adipocytes and brown adipocytes that appear in certain conditions in white fat depots. There is also mounting evidence that mature white adipocytes, including human fat cells, can be converted into brown fat-like adipocytes, and that the typical fatty acid storage phenotype of white adipocyte can be altered towards a fat utilization phenotype. These data open up new opportunities for the development of drugs for obesity and its metabolic and cardiovascular complications.