Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity.

Molecular metabolism ·第 3 卷 ·第 6 期 ·2014-08-27

Pedroso João A B, Buonfiglio Daniella C, Cardinali Lais I, Furigo Isadora C, Ramos-Lobo Angela M, Tirapegui Julio, Elias Carol F, Donato Jose

摘要

Therapies that improve leptin sensitivity have potential as an alternative treatment approach against obesity and related comorbidities. We investigated the effects of Socs3 gene ablation in different mouse models to understand the role of SOCS3 in the regulation of leptin sensitivity, diet-induced obesity (DIO) and glucose homeostasis. Neuronal deletion of SOCS3 partially prevented DIO and improved glucose homeostasis. Inactivation of SOCS3 only in LepR-expressing cells protected against leptin resistance induced by HFD, but did not prevent DIO. However, inactivation of SOCS3 in LepR-expressing cells protected mice from diet-induced insulin resistance by increasing hypothalamic expression of Katp channel subunits and c-Fos expression in POMC neurons. In summary, the regulation of leptin signaling by SOCS3 orchestrates diet-induced changes on glycemic control. These findings help to understand the molecular mechanisms linking obesity and type 2 diabetes, and highlight the potential of SOCS3 inhibitors as a promising therapeutic approach for the treatment of diabetes.

关键词

AP area postrema ARH arcuate nucleus of the hypothalamus DIO diet-induced obesity DMV dorsal motor nucleus of the vagus GTT glucose tolerance test HFD high-fat diet High-fat diet Hypothalamus ITT insulin tolerance test KO knockout LepR leptin receptor Leptin resistance NTS nucleus of the solitary tract PI3K phosphatidylinositol 3-kinase PKC protein kinase C POMC POMC proopiomelanocortin PTPs protein-tyrosine phosphatases SOCS3 suppressor of cytokine signaling-3 Suppressor of cytokine signaling-3 T2DM type 2 diabetes mellitus Type 2 diabetes mellitus VMH ventromedial nucleus of the hypothalamus

文献信息

期刊

Molecular metabolism

期刊简称

Mol Metab

ISSN

2212-8778

发表日期

2014-08-27

收录日期

2014-08-27

更新日期

2016-10-25

语言

英语

国家/地区

Germany

NLM ID

101605730

外部链接

PubMed 原文查看期刊详情

分析服务

Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity.

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