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

Young H Lee, X. Yu, F. Gonzales, David J Mangelsdorf, May-Yun Wang, C. Richardson, L. A. Witters, Roger H Unger

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Abstract

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 PPARα-/- 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.

Original languageEnglish (US)
Pages (from-to)11848-11853
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number18
DOIs
StatePublished - Sep 3 2002

ASJC Scopus subject areas

  • General

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