Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARalpha, activated by polyunsaturated fatty acids and fibrates, is implicated in regulation of lipid metabolism, lipoprotein synthesis and metabolism and inflammatory response in liver and other tissues. PPARgamma plays important roles in regulation of proliferation and differentiation of several cell types, including adipose cells. Its activation by thiazolidinediones results in insulin sensibilization and antidiabetic action. Until recently, the physiological functions of PPARdelta remain elusive. The utilization of specific agonists and of appropriate cellular and animal models revealed that PPARdelta has an important role in metabolic adaptation of several tissues to environmental changes. Treatment of obese animals by specific PPARdelta agonists results in normalization of metabolic parameters and reduction of adiposity. The nuclear receptor appeared to be implicated in the regulation of fatty acid burning capacities of skeletal muscle and adipose tissue by controlling the expression of genes involved in fatty acid uptake, beta-oxidation and energy uncoupling. PPARdelta is also implicated in the adaptive metabolic response of skeletal muscle to endurance exercise by controlling the number of oxidative myofibers. Given the results obtained with animal models, PPARdelta agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue.

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Our data suggest PPARbeta pharmacological activation as a novel approach to increase cardiac vascularization and cardiac muscle mass.

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The CD36 scavenger receptor is involved in the uptake and transport of fatty acids, as well as the phagocytosis process in macrophages. We show here that the CD36 protein is expressed by Sertoli cells in the seminiferous epithelium, mainly during the stages where phagocytosis takes place. Using a Sertoli-derived cell line, we show that addition of germ cells and residual bodies triggers a re-localization of CD36 from the cytoplasm to the plasma membrane of the cells, while latex beads do not. Moreover, Sertoli cell phagocytosis of germ cells, but not of latex beads, is reduced by the presence of fatty acids in the culture medium. In the testis, CD36 plays a key role in both phagocytosis and lipid recycling, for constant production of mature spermatozoa.

We reported recently that peroxisome proliferatoractivated receptor β (PPARβ) activation promotes a calcineurin-dependent exercise-like remodelling characterised by increased numbers of oxidative fibres and capillaries. As physical exercise also induces myonuclear accretion, we investigated whether PPARβ activation alters myonuclear density. Transgenic muscle-specific PPARβ over-expression induced 14% increase of myonuclear density. Pharmacological PPARβ activation promoted rapid and massive myonuclear accretion (20% increase after 48 h), which is dependent upon calcineurin/nuclear factor of activated T cells signalling pathway. In vivo bromodeoxyuridine labelling and proliferating cell nuclear antigen immunodetection revealed that PPARβ activation did not promote cell proliferation, suggesting that the PPARβ-promoted myonuclear accretion involves fusion of pre-existing muscle precursor cells to myofibres rather than cell division. Finally, we showed that in skeletal muscle, ageing led to a down-regulation of PPARβ accompanied by decrease of both oxidative fibre number and myonuclear density. PPARβ pharmacological activation counteracts, at least in part, the ageing-driven muscle remodelling.

Aims/hypothesis Due to their ability to regulate various signalling pathways (cytokines, hormones, growth factors), the suppressor of cytokine signalling (SOCS) proteins are thought to be promising therapeutic targets for metabolic and inflammatory disorders. Hence, their role in vivo has to be precisely determined. Methods We generated transgenic mice constitutively producing SOCS-3 in skeletal muscle to define whether the sole abundance of SOCS-3 is sufficient to induce metabolic disorders and whether SOCS-3 is implicated in physiological roles distinct from metabolism. Results We demonstrate here that chronic expression of SOCS-3 in skeletal muscle leads to overweight in mice and worsening of high-fat diet-induced systemic insulin resistance. Counter-intuitively, insulin sensitivity in muscle of transgenic mice appears to be unaltered. However, following constitutive SOCS-3 production, several genes had deregu-P. Lebrun and E. Cognard contributed equally to this work. Electronic supplementary materialThe online version of this article