INDUCTION BY LEPTIN OF UNCOUPLING PROTEIN-2 AND ENZYMES OF FATTY-ACIDOXIDATION

We have studied mechanisms by which leptin overexpression, which reduc es body weight via anorexic and thermogenic actions, induces triglycer ide depletion in adipocytes and nonadipocytes, Here we show that lepti n alters in pancreatic islets the mRNA of the gents Encoding enzymes o f free fatty acid metabolism and uncoupling protein-2 (UCP-2). In anim als infused with a recombinant adenovirus containing the leptin cDNA, the levels of mRNAs encoding enzymes of mitochondrial and peroxisomal oxidation rose 2- to 3-fold, whereas mRNA encoding an enzyme of esteri fication declined in islets from hyperleptinemic rats, Islet UCP-2 mRN A rose 6-fold. All iii vitro changes occurred Bz vitro in normal islet s cultured with recombinant leptin, indicating direct extraneural effe cts, Leptin overexpression increased UCP-2 mRNA by more than 10-fold i n epididymal, retroperitoneal, and subcutaneous fat tissue of normal, but not of leptin-receptor-defective obese rats, By directly regulatin g the expression of enzymes of free fatty acid metabolism and of UCP-2 , leptin controls intracellular triglyceride content of certain nonadi pocytes, as well as adipocytes.