Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity.
Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity.
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DOI：
10.1016/j.molmet.2014.06.001
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发表时间：
2014-09
影响因子：
8.1
通讯作者：
Donato J Jr
中科院分区：
文献类型：
--
作者：
Pedroso JA;Buonfiglio DC;Cardinali LI;Furigo IC;Ramos-Lobo AM;Tirapegui J;Elias CF;Donato J Jr
改善瘦素敏感性的疗法有可能作为治疗肥胖和相关合并症的替代治疗方法。我们研究了SOCS 3基因切除在不同小鼠模型中的作用，以了解SOCS 3在调节瘦素敏感性、饮食诱导的肥胖（DIO）和葡萄糖稳态中的作用。SOCS 3的神经元缺失部分防止DIO和改善葡萄糖稳态。仅在表达LepR的细胞中失活SOCS 3可保护HFD诱导的瘦素抵抗，但不能防止DIO。然而，LepR表达细胞中SOCS 3的失活通过增加下丘脑Katp通道亚基的表达和POMC神经元中c-Fos的表达来保护小鼠免受饮食诱导的胰岛素抵抗。总之，SOCS 3对瘦素信号传导的调节协调了饮食诱导的血糖控制变化。这些发现有助于了解肥胖和2型糖尿病之间的分子机制，并强调SOCS 3抑制剂作为糖尿病治疗的一种有前途的治疗方法的潜力。
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.
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影响因子：
7.7
作者：
Briancon N;McNay DE;Maratos-Flier E;Flier JS
通讯作者：
Flier JS
DOI：
10.1016/j.bbrc.2008.09.158
发表时间：
2008-12-12
影响因子：
3.1
作者：
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影响因子：
15.9
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通讯作者：
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DOI：
10.1073/pnas.95.11.6061
发表时间：
1998-05-26
影响因子：
11.1
作者：
Carpenter, LR;Farruggella, TJ;Stahl, N
通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
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