PPAR alpha is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue.
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)alpha expression, which was increased during the rapid loss of fat, we infused adenovirus-leptin into PPAR alpha(-/-) and PPAR alpha(+/+) mice. Despite similar degrees of hyperleptinemia and reduction in food intake, epididymal fat pad weight declined 55% in wild-type but only 6% in PPAR alpha(-/-) 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 PPAR alpha(-/-) mice. PPAR gamma coactivator-1 alpha rose 3-fold in the fat and 46% in the liver of wild-type mice but was unchanged in PPAR alpha(-/-) 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 PPAR alpha(-/-) mice. Thus, in PPAR alpha(-/-) mice, up-regulation of carnitine palmitoyl transferase-1 mRNA in fat, down-regulation of acetyl CoA carboxylase in liver, and up-regulation of PPAR gamma coactivator-1 alpha mRNA in both tissues are abolished, as is the reduction in their triacylglycerol content.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Y
Y
Lee
X
X
Yu
F
F
Gonzales
D J
DJ
Mangelsdorf
May-Yun
MY
Wang
C
C
Richardson
L A
LA
Witters
R H
RH
Unger
D055372:AMP-Activated Protein Kinases; D000273:Adipose Tissue / Q000201:enzymology / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D020738:Leptin / Q000097:blood / Q000502:physiology*; D008066:Lipolysis; D008099:Liver / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism
D017931:DNA Primers; D020738:Leptin; D009097:Multienzyme Complexes; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases