QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mizuno, T. M. Articles by Mobbs, C. V. Search for Related Content PubMed PubMed Citation Articles by Mizuno, T. M. Articles by Mobbs, C. V.

---

Nutrient-Gene Interactions

Specific Preservation of Biosynthetic Responses to Insulin in Adipose Tissue May Contribute to Hyperleptinemia in Insulin-Resistant Obese Mice¹

Fishberg Center for Neurobiology, Neurobiology of Aging Laboratories and Department of Geriatrics, Mount Sinai School of Medicine, New York, NY 10029 and ^* Department of Physiology, Yokohama City University School of Medicine, Yokohama, 236-0004, Japan

³To whom correspondence should be addressed. E-mail: Charles.Mobbs{at}mssm.edu.

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 A^y/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 A^y/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.

KEY WORDS: • insulin resistance • jun-B • c-fos • leptin

This article has been cited by other articles:

				E. Isganaitis and R. H. Lustig Fast Food, Central Nervous System Insulin Resistance, and Obesity Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2451 - 2462. [Abstract] [Full Text] [PDF]