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An excess of fat mass excess predisposes to multiple complications such as type 2 diabetes, cardiovascular diseases or cancer. A dysregulation of lipid metabolism contributes to the development of obesity and the metabolic syndrome. Recent data on lipid mobilization in adipose tissue have revealed a complex pathway involving a human specific hormonal control of lipolysis via the natriuretic peptides and a new triglyceride lipase, ATGL. Activation of fatty acid reesterification and oxidation can lead to an increase in fatty acid utilization. Targeting these key steps of lipid metabolism (adipose tissue lipolysis and fatty acid oxidation) constitutes a potential strategy for the treatment of obesity and associated metabolic disorders.

Transcriptional coactivators can be important targets for physiologic regulation. PPARgamma coactivator-1alpha (PGC-1alpha), in cooperation with several transcription factors, has emerged as a key regulator of several aspects of mammalian energy metabolism including mitochondrial biogenesis, adaptive thermogenesis in brown adipose tissue, glucose uptake, fiber type-switching in skeletal muscle, gluconeogenesis in liver and insulin secretion from pancreas. Recent studies have shown a reduced expression of PGC-1alpha in skeletal muscle of diabetic and prediabetic humans. Moreover, expression of PGC-1alpha in white fat cells activates a broad program of adaptive thermogenesis characteristic of brown fat cells. PGC-1alpha could be a target for antiobesity or diabetes drugs. The aim of this article was to summarize the molecular mechanisms and biological programs controlled by the transcriptional coactivator PGC-1alpha.

The mechanisms involved in the nutritional regulation of genes encoding lipogenic (lipoprotein lipase (LPL) and fatty acid synthase (FAS)) and lipolytic (hormone-sensitive lipase (HSL)) enzymes were investigated by comparing the levels of the corresponding mRNAs in the adipose tissue (AT) of underfed or underfed-refed ewes and cows. Refeeding sharply increased LPL and FAS activities (19-25- and 6-8-fold, respectively) and moderately increased (2-4 fold) the activities of glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME) and glyce- rol-3-phosphate dehydrogenase (G3PDH). Northern blot analysis revealed three LPL transcripts and a single FAS transcript in cow and ewe AT. A single HSL mRNA was detected in cow AT and two transcripts in ewe AT. Refeeding sharply increased LPL and FAS mRNA levels, while restriction slightly increased (cows) or had no effect (ewes) on the HSL mRNA levels. This sug- gests that nutritional factors regulate sharply the expression of LPL and FAS genes by pretrans- lational mechanisms, but less clearly that of HSL gene. @ Inra/Elsevier, Paris

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Carbonyl compound toxicity is known in several species but no study has been carried out with ruminants. Such volatile compounds exist in silages. After condensation of aldehydes and ketones with 2,4-dinitrophenylhydrazine, quantitative analysis was performed with 37 silages. It was found that quantities of carbonyl compounds varied from 36 mg/kg of dry matter (DM) to 1,535 mg/kg DM with a mean value of 642 mg/kg DM. Ethanal was 63% of the total amount of carbonyl compounds (mol/kg DM). Other molecules were propanal, propanone, butanal (n- and iso-), butanone and n- and iso- pentanal. The total amount of carbonyl compounds correlated positively with the dry matter percentage and negatively with the pH, crude fiber, ash content and volatile fatty acids. Thus, carbonyl compounds seem to be dependent up on silage storage conditions. Lactic flora could be involved in the synthesis of these compounds.

Les corégulateurs de transcription sont des protéines essentielles à l’activation de l’expression des gènes. Ces corégulateurs ne se lient pas à l’ADN ; associés aux facteurs de transcription, ils servent de pont avec la machinerie basale de transcription ou sont impliqués dans le remodelage de la chromatine. PGC-1α est le premier co-activateur à présenter une relative spécificité tissulaire d’expression. Exprimé dans le tissu adipeux brun, le muscle squelettique, le foie et le pancréas, il joue un rôle majeur dans le contrôle des métabolismes énergétique et glucidique. Sur le plan moléculaire, PGC-1α présente également la particularité de coupler la transcription des gènes à l’épissage des pré-ARNm., Transcriptional coactivators can be important targets for physiologic regulation. PPARγ coactivator-1α (PGC-1α), in cooperation with several transcription factors, has emerged as a key regulator of several aspects of mammalian energy metabolism including mitochondrial biogenesis, adaptive thermogenesis in brown adipose tissue, glucose uptake, fiber type-switching in skeletal muscle, gluconeogenesis in liver and insulin secretion from pancreas. Recent studies have shown a reduced expression of PGC-1α in skeletal muscle of diabetic and prediabetic humans. Moreover, expression of PGC-1α in white fat cells activates a broad program of adaptive thermogenesis characteristic of brown fat cells. PGC-1α could be a target for antiobesity or diabetes drugs. The aim of this article was to summarize the molecular mechanisms and biological programs controlled by the transcriptional coactivator PGC-1α.