In vivo leptin infusion impairs insulin and leptin signalling in liver and hypothalamus

被引：38

作者：

Benomar, Y

Wetzler, S

Larue-Achagiotis, C

Djiane, J

Tomé, D

Taouis, M

机构：

[1] Univ Paris 11, CNRS, Neuroendocrinol Mol Prise Alimentaire INRA, IBAIC, F-91405 Orsay, France

[2] INRA, UMR 914, F-75231 Paris, France

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2005年 / 242卷 / 1-2期

关键词：

leptin and insulin resistance; signal transduction; hypothalamus; liver;

D O I：

10.1016/j.mce.2005.07.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Leptin resistance contributes to the pathogenesis of common obesity related metabolic diseases, including insulin resistance. However, the relationship between leptin and insulin resistance is not clearly established. Here, we show that induced hyperleptinemia by leptin infusion alters insulin signalling in rat liver. Leptin infusion clearly reduced the insulin or leptin dependent IRS-I/IRS-2 association to p85 regulatory subunit of PI 3-kinase. Leptin infusion also abolished STAT-3 phosphorylation in response to insulin or leptin and similar results were obtained for MAP-kinase phosphorylation. Hypothalamic leptin resistance was also induced by leptin infusion since leptin was unable to induce STAT-3 phosphorylation. These results provide evidence that induced hyperleptinemia can contribute to the onset of insulin resistance at least at the hepatic level. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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页码：59 / 66

页数：8

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