Peroxisome proliferator-activated receptor-alpha deficiency protects aged mice from insulin resistance induced by high-fat diet

Dae Ryong Cha, Jee Young Han, Dong Ming Su, Yahua Zhang, Xuefeng Fan, Matthew D. Breyer, Youfei Guan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background/Aims: Insulin resistance is a central feature of the metabolic syndrome and progressively increases with age, resulting in excessively high incidence of type II diabetes in the elderly population. Peroxisome proliferator-activated receptor-α (PPARα) is widely expressed in insulin target tissues, including those of the liver, kidney, and muscle, where it mediates expression of genes promoting fatty acid β-oxidation. The aim of this study was to evaluate the potential role of PPARα in insulin resistance in aging mice induced by a high-fat diet. Methods: We used male PPARα knockout (KO) mice and wild-type (WT) littermates that were 18 months old. Animals were fed with a high-fat diet (HFD) for 4 weeks, and metabolic parameters associated with insulin sensitivity were assessed. Results: Following HFD treatment, WT mice showed more severe insulin resistance than did mice lacking the PPARα gene, as assessed by both the glucose tolerance test (GTT) and insulin tolerance test (ITT). In addition, WT mice exhibited significantly higher HOMA-IR, plasma total cholesterol levels and urinary albumin-creatinine ratio but less liver weight than did PPARα KO mice. Conclusion: These data suggest that PPARα gene deficiency may protect aged mice from developing insulin resistance and albuminuria induced by a HFD.

Original languageEnglish
Pages (from-to)479-482
Number of pages4
JournalAmerican journal of nephrology
Volume27
Issue number5
DOIs
Publication statusPublished - 2007 Sep 1

Keywords

  • Aged mice
  • High-fat diet
  • Insulin resistance
  • Peroxisome proliferator-activated receptor-α

ASJC Scopus subject areas

  • Nephrology

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