Hepatocyte retinoid X receptor-α-deficient mice have reduced food intake, increased body weight, and improved glucose tolerance

Yu-Jui Yvonne Wan, Guang Han, Yan Cai, Tiane Dai, Tamiko Konishi, Ai She Leng

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Hepatocyte retinoid X receptor (RXR)α-deficient mice and wild-type mice were fed either a regular or a high-saturated-fat diet for 12 wk to study the functional role of hepatocyte RXRα in fatty acid and carbohydrate metabolism. Food intake was significantly reduced in hepatocyte RXRα-deficient mice when either diet was used. The amount of food intake was negatively associated with serum leptin level. Although mutant mice ate less, body weight and fat content were significantly higher in mutant than wild-type mice. Examination of the expression of peroxisome proliferator-activated receptor-α target genes indicated that the peroxisome proliferator-activated receptor-α-mediated pathway was compromised in the mutant mice, which, in turn, might affect fatty-acid metabolism and result in increased body weight and fat content. Although mutant mice were obese, they demonstrated the same degree of insulin sensitivity and the same level of serum insulin as the wild-type mice. However, these mutant mice have improved glucose tolerance. To explore a mechanism that may be responsible for the improved glucose tolerance, serum IGF-I level was examined. Serum IGF-1 level was significantly increased in mutant mice compared with wild-type mice. Taken together, hepatocyte RXRα deficiency increases leptin level and reduces food intake. Those mice also develop obesity, with an unexpected improvement of glucose tolerance. The result also suggests that an increase in serum IGF-I level might be one of the mechanisms leading to improved glucose tolerance in hepatocyte RXRα-deficient mice.

Original languageEnglish (US)
Pages (from-to)605-611
Number of pages7
JournalEndocrinology
Volume144
Issue number2
DOIs
StatePublished - Feb 1 2003

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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