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

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White Adipose Tissue
Liver
Acetyl-CoA Carboxylase
Carnitine
Fats
Transferases
Adenoviridae
Messenger RNA
Adipose Tissue
Triglycerides
Up-Regulation
White Adipocytes
AMP-Activated Protein Kinases
Leptin
Fatty Acids
Down-Regulation
Eating
Weights and Measures

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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title = "PPARα is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue",
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.",
author = "Lee, {Young H} and X. Yu and F. Gonzales and Mangelsdorf, {David J} and May-Yun Wang and C. Richardson and Witters, {L. A.} and Unger, {Roger H}",
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T1 - PPARα is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue

AU - Lee, Young H

AU - Yu, X.

AU - Gonzales, F.

AU - Mangelsdorf, David J

AU - Wang, May-Yun

AU - Richardson, C.

AU - Witters, L. A.

AU - Unger, Roger H

PY - 2002/9/3

Y1 - 2002/9/3

N2 - 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.

AB - 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.

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