6533b873fe1ef96bd12d5305

RESEARCH PRODUCT

Effects of modulation of body fat in production of adiponectin in mice : consequences on hepatic metabolism of lipids

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Adiponectin (ApN), a 30-kDa adipokine abundantly produced by adipose tissue has been described for the first time in 1995. Early findings demonstrating serum adiponectin levels are inversely correlated with obesity initiated intense investigation of the relationship between adiponectin and all symptoms of the metabolic syndrome. Of these studies, strong evidence suggests that a weight loss induced by medication or hypocaloric diet led to increased circulating ApN levels and improvement of biochemical parameters. Thus, high levels of ApN have been correlated with an improvement of insulin sensitivity and lipid parameters reducing cardiovascular risk. However mechanisms involved in the improvement of glucose and lipid metabolism are not fully understood. In this study, we wanted to determine whether variations of plasma ApN levels are associated with alterations of liver lipid metabolism in mice. For this, we used different nutritional and pharmacological strategies to induce fat mass variations and measured corresponding ApN production and lipid parameters. First, results suggested that production of ApN is not dependent on the size of adipocytes, but rather to their inflammatory state. The effect of ApN of liver metabolism was further studied using an in vitro model of liver explants in culture. A first approach consists of testing the long-term effects of ApN on liver incubating the slices for 21h in the presence or not of insulin. Biochemical and molecular data suggested that ApN accentuates the effects of insulin, resulting in improvement of glucose utilization associated with a stimulation of lipogenesis and a reduction in β-oxidation in the presence of insulin. In addition, ApN appears to affect HDL catabolism pathways. In a second approach, we tested the short-term effects of ApN on β-oxidative capacity treating the slices for 45 min. Under these conditions more appropriated to highlight the activation of fast regulatory pathways, ApN induced a stimulation of ß-oxidation which was accompanied by an increase in p-AMPK. In conclusion, data suggested that ApN has direct effects on hepatic glucose metabolism consistent with the insulin-sensitizer effect demonstrated in vivo. However, at this stage, these results did not give evidence of a relationship between induction of liver fatty acid β- oxidation by ApN and its beneficial effects on lipid parameters.