PPARα is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue

• DOI: 10.1073/pnas.182420899
• Publication Date: 2002-09-03T19:58:55Z
• Authors: Y. Lee; X. Yu; F. Gonzales; D. J. Mangelsdorf; May-Yun Wang; C. Richardson; L. A. Witters; R. H. Unger
• Keywords: Leptin; Mice, Knockout; 0301 basic medicine; Base Sequence; Lipolysis; Receptors, Cytoplasmic and Nuclear; AMP-Activated Protein Kinases; Protein Serine-Threonine Kinases; Polymerase Chain Reaction; Gene Expression Regulation, Enzymologic; 3. Good health; Mice; 03 medical and health sciences; Adipose Tissue; Liver; Multienzyme Complexes; Animals; Phosphorylation; Oxidation-Reduction; Triglycerides; DNA Primers; Transcription Factors

Adenovirus-induced hyperleptinemia causes rapid disappearance of body fat in normal rats, presumably by up-regulating fatty acid oxidation within white adipocytes. To determine the role of peroxisomal proliferation-activated receptor (PPAR)α expression, which was increased during the rapid loss of fat, we infused adenovirus–leptin into PPARα −/− and PPARα +/+ mice. Despite similar degrees of hyperleptinemia and reduction in food intake, epididymal fat pad weight declined 55% in wild-type but only 6% in PPARα −/− mice; liver triacylglycerol fell 39% in the wild-type group but was unchanged in PPAR −/− mice. Carnitine palmitoyl transferase-1 mRNA rose 52% in the wild-type mice but did not increase in PPARα −/− mice. PPARγ coactivator-1α rose 3-fold in the fat and 46% in the liver of wild-type mice but was unchanged in PPARα −/− mice. Although AMP-activated protein kinase could not be implicated in the lipopenic actions of hyperleptinemia, acetyl CoA carboxylase protein was reduced in the liver of wild-type but not in PPARα −/− mice. Thus, in PPARα −/− mice, up-regulation of carnitine palmitoyl transferase-1 mRNA in fat, down-regulation of acetyl CoA carboxylase in liver, and up-regulation of PPARγ coactivator-1α mRNA in both tissues are abolished, as is the reduction in their triacylglycerol content.