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

Obesity is characterized by whole-body insulin resistance, yet the expression of many insulinstimulated 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 im...

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Bibliographic Details
Published in:The Journal of nutrition 2004-05, Vol.134 (5), p.1045
Main Authors: Mizuno, Tooru M, Funabashi, Toshiya, Kleopoulos, Steven P, Mobbs, Charles V
Format: Article
Language:English
Subjects:
Body fat
Genes
Insulin
Obesity
Rodents
Tissues
Online Access:Get full text
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Summary:Obesity is characterized by whole-body insulin resistance, yet the expression of many insulinstimulated 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^sup 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^sup 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 insulinresistant 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. J. Nutr. 134: 1045-1050, 2004. [PUBLICATION ABSTRACT] KEY WORDS: . insulin resistance . jun-B . c-fos . leptin
ISSN:0022-3166
1541-6100