A Combined Transcriptomics and Lipidomics Analysis of Subcutaneous, Epididymal and Mesenteric Adipose Tissue Reveals Marked Functional Differences

Depot-dependent differences in adipose tissue physiology may reflect specialized functions and local interactions between adipocytes and surrounding tissues. We combined time-resolved microarray analyses of mesenteric- (MWAT), subcutaneous- (SWAT) and epididymal adipose tissue (EWAT) during high-fat feeding of male transgenic ApoE3Leiden mice with histology, targeted lipidomics and biochemical analyses of metabolic pathways to identify differentially regulated processes and site-specific functions. EWAT was found to exhibit physiological zonation. De novo lipogenesis in fat proximal to epididymis was stably low, whereas de novo lipogenesis distal to epididymis and at other locations was down-regulated in response to high-fat diet. The contents of linoleic acid and α-linolenic acid in EWAT were increased compared to other depots. Expression of the androgen receptor (Ar) was higher in EWAT than in MWAT and SWAT. We suggest that Ar may mediate depot-dependent differences in de novo lipogenesis rate and propose that accumulation of linoleic acid and α-linolenic acid in EWAT is favored by testosterone-mediated inhibition of de novo lipogenesis and may promote further elongation and desaturation of these polyunsaturated fatty acids during spermatogenesis

Progression of atherosclerosis in ApoE-deficient mice that express distinct molecular forms of TNF-alpha

TNFalpha (TNF) critically regulates inflammation-driven atherosclerosis. Because the transmembrane (tmTNF) and soluble (sTNF) forms of TNF possess distinct immuno-modulatory properties, we hypothesized that they might differentially regulate atherosclerosis progression. Three groups of male ApoE(-/-) mice were studied: one expressing wild-type TNF (WT-TNF); one expressing exclusively a mutated non-cleavable form of TNF (KI-TNF); and one deficient in TNF (KO-TNF). Mice aged 5 weeks were fed the high-fat diet for 5 (T5) and 15 weeks (T15) or a standard chow diet for 15 weeks. At T5, in mice fed the high-fat diet, no significant differences in lesion area were observed among the three groups, either in valves or in aortas. At T15, lesion areas in valves were significantly lower in KO-TNF mice compared with those in WT-TNF mice, whereas in KI-TNF mice, they were intermediate between KO- and WT-TNF mice but not significantly different from these two groups. In aortas, lesions in KI-TNF were comparable to those of KO-TNF, both being significantly lower than those in WT-TNF. Theses differences were not linked to circulating lipids, or to macrophage, actin, and collagen contents of lesions. At T15, in mice fed the chow diet, lesion areas in valves and the aortic arch were not significantly different between the three groups. Levels of IL-6, IFNgamma, IL-10, and Foxp3 mRNAs in spleens and production of IL-6, IL-10, MCP-1, RANTES, and TNFR-2 by peritoneal macrophages at T15 of the high-fat diet showed a decrease in pro-inflammatory status, more marked in KO-TNF than in KI-TNF mice. Apoptosis was reduced only in KO-TNF mice. In conclusion, these data show that TNF effects on atherosclerosis development are detectable at stages succeeding fatty streaks and that wild-type TNF is superior to tmTNF alone in promoting atherosclerosis. TNF-dependent progression of atherosclerosis is probably linked to the differential production of pro-inflammatory mediators whether tmTNF is preponderant or essentially cleaved. Copyright (c) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley ; Sons, Ltd

CD28 deletion improves obesity-induced liver steatosis but increases adiposity in mice

International audienceLymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown.During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions.Cd28 deficiency decreased pathogenic T cells and Treg content within AT without changing the macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and failed to improve liver fat accumulation.Deletion of CD28 creates a new pro/anti-inflammatory balance in epiAT and liver and exerts a protective effect against hepatic steatosis

CD28 deletion improves obesity-induced liver steatosis but increases adiposity in mice

International audienceLymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown.During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions.Cd28 deficiency decreased pathogenic T cells and Treg content within AT without changing the macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and failed to improve liver fat accumulation.Deletion of CD28 creates a new pro/anti-inflammatory balance in epiAT and liver and exerts a protective effect against hepatic steatosis

Alteration of CD28 T cell costimulatory pathway protects against obesity-induced inflammation and metabolic disorders

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Usage des ouvrages de correction torrentielle et plages de dépôt : origine, état des lieux, perspectives

International audienceLarge operations of torrent control works in the most active catchments have been launched in France by the 1882’s mountain areas restoration policy, based on older pioneer works. It first implemented headwater soil and erosion control structures and plantations, although protection structures closer from assets were built on alluvial fans to trap sediment and channelize flows. Soil erosion and the related torrential hazard mitigation continue to be financed by public grants to maintain existing systems and, if necessary, build new ones. The environmental, socio-economic and technical contexts of risk management have changed. The current use of check dams and open check dams in protection strategies may consequently need an update. This paper firstly reviews the historical emergence of check dams and open check dams. It secondly lists their function, i.e., the qualitative effect we can expect they have on hazards in the light of 150 years of tests and trials. The last section gives some perspectives on the use of these structures: why, although complicated and expensive, it worth maintaining some headwater structures? When is it justified to abandon or even dismantled some structures? And finally what seems to be the future way of designing and planning these structures, especially the open check dams?La correction torrentielle des torrents les plus actifs a été lancée en France par la politique de restauration des terrains en montagne de 1882 sur la base de travaux pionniers plus anciens. Elle a d'abord mis à profit la correction active des hauts bassins par la lutte contre l'érosion à la source mais a aussi accompagné le développement de la protection passive des enjeux par le piégeage et la canalisation des écoulements dans les zones aval. Cette lutte contre l'érosion et les risques torrentiels induits fait toujours l'objet d'investissements publics pour entretenir les systèmes de protection existants et, si nécessaire, en construire de nouveaux. Les contextes environnementaux, socio-économiques et techniques d'implantation et de gestion de ces systèmes de protection ont évolué. Il y a donc matière à s'interroger sur l'usage actuel qui est fait des ouvrages de correction torrentielle et des plages de dépôts, ouvrages spécifiques au contexte torrentiel. Cet article rappelle en premier lieu un historique de leur émergence. La seconde partie liste les fonctions de ces ouvrages : quels effets qualitatifs pouvons-nous espérer de ces structures à la lumière de plus de 150 ans d'expérience ? La dernière partie donne quelques perspectives concernant l'usage de ces ouvrages : pourquoi faut-il maintenir un part de correction active malgré les difficultés associées ? Qu'est-ce qui peut justifier d'abandonner ou de détruire certains ouvrages ? Quelles nouvelles approches semblent émerger dans la conception de ces ouvrages, et plus particulièrement des plages de dépôt modernes