Peroxisome proliferator-activated receptor-α regulates lipid homeostasis, but is not associated with obesity. Studies with congenic mouse lines

Taro E. Akiyama, Christopher J. Nicol, Catherine Fievet, Bart Staels, Jerrold M. Ward, Johan Auwerx, Susanna S.T. Lee, Frank J. Gonzalez, Jeffrey M. Peters

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Considerable controversy exists in determining the role of peroxisome proliferator-activated receptor-α (PPARα) in obesity. Two purebred congenic strains of PPARα-null mice were developed to study the role of this receptor in modulating lipid transport and storage. Weight gain and average body weight in wild-type and PPARα-null mice on either an Sv/129 or a C57BL/6N background were not markedly different between genotypes from 3 to 9 months of age. However, gonadal adipose stores were significantly greater in both strains of male and female PPARα-null mice. Hepatic accumulation of lipids was greater in both strains and sexes of PPARα-null mice compared with wild-type controls. Administration of the peroxisome proliferator WY-14643 caused hepatomegaly, alterations in mRNAs encoding proteins that regulate lipid metabolism, and reduced serum triglycerides in a PPARα-dependent mechanism. Constitutive differences in serum cholesterol and triglycerides in PPARα-null mice were found between genetic backgrounds. Results from this work establish that PPARα is a critical modulator of lipid homeostasis in two congenic mouse lines. This study demonstrates that disruption of the murine gene encoding PPARα results in significant alterations in constitutive serum, hepatic, and adipose tissue lipid metabolism. However, an overt, obese phenotype in either of the two congenic strains was not observed. In contrast to earlier published work, this study establishes that PPARα is not associated with obesity in mice.

Original languageEnglish (US)
Pages (from-to)39088-39093
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number42
DOIs
StatePublished - Oct 19 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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