Background— Adipose tissue development and remodeling are closely associated with the growth of vascular network. We hypothesized that adipose tissue may contain progenitor cells with angiogenic potential and that therapy based on adipose tissue-derived progenitor cells administration may constitute a promising cell therapy in patients with ischemic disease. Methods and Results— In mice, cultured stromal-vascular fraction (SVF) cells from adipose tissue have a great proangiogenic potential, comparable to that of bone marrow mononuclear cells in the mouse ischemic hindlimb model. Similarly, cultured human SVF cells differentiate into endothelial cells, incorporate into vessels, and promote both postischemic neovascularization in nude mice and vessel-like structure formation in Matrigel plug. In vitro, these cells represent a homogeneous population of CD34- and CD13-positive cells, which can spontaneously express the endothelial cell markers CD31 and von Willebrand factor when cultured in semisolid medium. Interestingly, dedifferentiated mature human adipocytes have the potential to rapidly acquire the endothelial phenotype in vitro and to promote neovascularization in ischemic tissue and vessel-like structure formation in Matrigel plug, suggesting that cells of endothelial and adipocyte phenotypes may have a common precursor. Conclusions— This study demonstrates, for the first time, that adipocytes and endothelial cells have a common progenitor. Such adipose lineage cells participate in vascular-like structure formation in Matrigel plug and enhance the neovascularization reaction in ischemic tissue. These results also highlight the concept that adipose lineage cells represent a suitable new cell source for therapeutic angiogenesis in ischemic disease.
Close relationships have been demonstrated between adipose tissue and the inflammatory/immune system. Furthermore, obesity is increasingly considered as a state of chronic inflammation. Cytofluorometric analysis reveals the presence of significant levels of lymphocytes in the stroma-vascular fraction of white adipose tissues. In epididymal (EPI) fat, lymphocytes display an ''ancestral'' immune system phenotype (up to 70% of natural killer (NK), cd + T and NKT cells among all lymphocytes) whereas the inguinal (ING) immune system presents more adaptive characteristics (high levels of ab + T and B cells). The percentage of NK cells in EPI fat was decreased in obese mice fed with a high-fat diet, whereas cd positive cells were significantly increased in ING fat. These data support the notion that adipose tissue may elaborate immunological mechanisms to regulate its functions which might be altered in obesity.
OBJECTIVE:To examine the possible involvement of an increase in diet-induced thermogenesis from brown adipose tissue (BAT) in the n-3 polyunsaturated fatty acids (n-3 PUFA) induced limitation of the development of white fat pads during high-fat feeding. DESIGN: Rats fed for four weeks on a low-fat/high-carbohydrate diet (C group) or high-fat diet without n-3 PUFA (REF group), with eicosapentaenoic acid (EPA group), with docosahexaenoic acid (DHA group) or with a mixture of these two fatty acids (MIX group). MEASUREMENTS: Epididymal and retroperitoneal fat pad mass, BAT composition, Guanosine 5'-diphosphate (GDP) binding and uncoupling protein (UCP) content were measured in the ®ve groups of rats. RESULTS: The masses of retroperitoneal and epididymal white fat pads were lower in the groups fed n-3 PUFA than in the C and REF groups. The total BAT GDP binding was 1.6 times higher in the MIX and EPA groups than in the REF group. The BAT from the EPA group presented an enrichment in mitochondria compared to the C and REF groups whereas the BAT from the DHA and REF groups presented a hyperplasia and an increase in thermogenic activity of the mitochondria compared to the C group. The higher thermogenic activity of BAT was observed in the MIX group and is due to hyperplasia and to an increase in thermogenic activity of mitochondria. CONCLUSIONS: n-3 PUFA induce a marked stimulation of BAT thermogenic activity without changes in the UCP content compared to a high-fat diet without n-3 PUFA. The mixture of EPA and DHA has the more pronounced effect while EPA and DHA seem to act in synergy on BAT thermogenesis via different mechanisms.
AIMS/HYPOTHESIS:Fibrates and thiazolidinediones are commonly used for the treatment of dyslipidemia and type 2 diabetes, respectively. The aim of this study was to investigate the effects on body weight as well as on glucose and lipid homeostasis of ligands for PPARa and PPARg, Fenofibrate and Rosiglitazone, alone or in association. METHODS: Ob/ob mice were divided into four groups: control, and mice daily injected (intraperitoneally), either with 10 mg/kg Rosiglitazone, 100 mg/kg Fenofibrate or both molecules. Body weight and food intake were monitored daily. After 13 days of treatment, mice were killed, and blood samples were collected for posterior metabolite quantification. The liver and adipose tissues were dissected and weighed. RESULTS: Body weight was significantly reduced or increased by Fenofibrate and Rosiglitazone, respectively. The effect of Rosiglitazone was prevented by coadministration of Fenofibrate. This was accompanied by a normalization of the daily food efficiency. Compared to those treated with Rosiglitazone, animals treated with Fenofibrate alone or in combination presented a decreased white adipose tissue mass. Fenofibrate or Rosiglitazone alone significantly reduced the levels of plasma lipid parameters. Surprisingly, Fenofibrate also decreased blood glucose levels in ob/ob mice, despite having no effect on insulin levels. By contrast, both glucose and insulin levels were decreased by Rosiglitazone treatment. Coadministration of both drugs improved all parameters as with Rosiglitazone. Fenofibrate restored almost normal hepatocyte morphology and significantly reduced the triglyceride content of the liver. This was accompanied by an increase in fatty acid oxidation in the liver in all groups receiving Fenofibrate. CONCLUSION/INTERPRETATION: These biological effects suggest that combined therapy with a PPARa and a PPARg ligand is more effective in ameliorating, specifically, lipid homeostasis than in activating any of this receptor separately. Furthermore, Fenofibrate prevents one of the most undesirable effects of Rosiglitazone, namely increased adiposity and body weight gain.
Until now, uncoupling protein 1 (UCP1) was considered as unique to brown adipocytes. It supports a highly regulated uncoupling of oxidative phosphorylation that is associated with diet as well as with non-shivering thermogenesis. Here we report that UCP1 is not specific to brown adipocytes and can be expressed in longitudinal smooth muscle layers. In the uterus, this conclusion was drawn from different convergent data. A specific antibody against mouse UCP1 revealed, in mitochondrial fractions, a protein with the same molecular weight as brown fat UCP1. Sensitive and specific reverse transcriptase-polymerase chain reaction detected a mRNA whose sequence was totally homologous to that of brown fat UCP1 mRNA. Antibody against UCP1 as well as a UCP1 antisense probe specifically stained uterine longitudinal smooth muscles. UCP1 was also expressed in longitudinal smooth muscle of digestive and male reproductive tracts but was never expressed in other types of smooth muscle, including those of arterial vessels. In uterine tract, UCP1 content was increased after cold exposure or -adrenergic agonist treatment. It was also up-regulated during the postovulatory period after sexual cycle synchronization. Its content transiently increased during gestation and decreased markedly after birth. These regulations strongly argue about a role for UCP1 in thermogenesis as well as in relaxation of longitudinal smooth muscle layers.The primary function of mitochondria is to supply the cell with energy as ATP. They are also involved in heat production and have other functions that are not directly related to energy transduction, such as redox state control and Ca 2ϩ homeostasis. (1, 2). In all the functions, membrane potential and permeability play key roles. In specialized thermogenic cells, such as the brown adipocyte, increased proton conductance across the mitochondrial inner membrane was first postulated by Nicholls and Locke (3). The protein supporting this activity was later purified, named uncoupling protein (UCP), 1 and cloned. This protein belongs to the mitochondrial anion carrier family. Its insertion into the mitochondrial inner membrane allows dissipation of the proton electrochemical gradient across this membrane with associated heat production and decreased ATP synthesis. Its ectopic expression in any eukaryotic cell is sufficient to reproduce similar uncoupled mitochondrial phenotypes (4, 5). Until now, its expression was only detected in mitochondria from brown adipocytes. The recent cloning and expression studies of other UCPs, such as UCP2 and UCP3, suggest that similar mechanisms may exist in numerous cells. New perspectives with regard to UCPs and particularly UCP1 are now being revealed with the discoveries that UCPs are modulators of mitochondrial reactive oxygen species generation and that coenzyme Q is an obligatory partner for their uncoupling activity (6, 7).The function of the different UCPs in the maintenance of body temperature has been debated (8). Until now, only UCP1 has been clearly linked to thermo...
To assess the putative role of mitochondrial uncoupling protein 2 (UCP2) during perinatal development, its expression was analysed in mice and rats. Expression was detected in a large range of foetal tissues. A unique developmental pattern of UCP2 expression was found in liver, where the level of UCP2 mRNA was about 30-fold higher in foetuses than in adults (mice data), and started to decline immediately after birth. Neither UCP1 nor UCP3 mRNA was expressed in foetal liver. As in adult liver, immunohistochemical analysis suggested exclusive localisation of UCP2 in the monocyte/macrophage cells. Our results indicate a role of UCP2 in haematopoietic system development.z 1998 Federation of European Biochemical Societies.
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