Specific Preservation of Biosynthetic Responses to Insulin in Adipose Tissue May Contribute to Hyperleptinemia in Insulin-Resistant Obese Mice

Tooru M. Mizuno, Toshiya Funabashi, Steven P. Kleopoulos, Charles V. Mobbs

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Obesity is characterized by whole-body insulin resistance, yet the expression of many insulin-stimulated genes, including leptin, is elevated in obesity. These observations suggest that insulin resistance may depend on tissue type and gene. To address this hypothesis, we examined the regulation of immediate-early gene expression in liver and adipose tissue after injection of insulin and glucose, in lean insulin-sensitive, and in Ay/a obese insulin-sensitive and obese insulin-resistant mice. Expression of hepatic jun-B mRNA was robustly increased after insulin injection in lean insulin-sensitive a/a mice and insulin-sensitive Ay/a mice. In contrast, induction of hepatic jun-B and c-fos gene expression by insulin was markedly attenuated in obese insulin-resistant mice. Surprisingly, induction of adipose jun-B and c-fos gene expression by insulin was markedly enhanced in obese insulin-resistant mice. Furthermore, the expressions of jun-B and leptin were also enhanced in insulin-resistant mice after injection of glucose. Leptin mRNA was positively correlated with blood glucose levels and jun-B mRNA in lean but not insulin-resistant mice. Multiple regression analysis indicated that the correlation between leptin mRNA and jun-B mRNA was significant even after removing the effect of blood glucose, but the correlation between leptin mRNA and glucose was no longer significant after removing the effect of jun-B mRNA. These data suggest that some impairments in biosynthetic responses to insulin are manifest primarily in the liver, leading to hyperinsulinemia and stimulating the expression of some adipose insulin-stimulated genes, including leptin. These studies demonstrate the utility of immediate-early gene expression in the analysis of biosynthetic mechanisms of insulin resistance.

Original languageEnglish
Pages (from-to)1045-1050
Number of pages6
JournalJournal of Nutrition
Volume134
Issue number5
DOIs
StatePublished - May 2004
Externally publishedYes

Keywords

  • Insulin resistance
  • Leptin
  • c-fos
  • jun-B

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