Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance.
Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance.
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DOI：
10.1016/j.cell.2013.09.003
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发表时间：
2013-09-26
期刊：
影响因子：
64.5
通讯作者：
Claret M
中科院分区：
文献类型：
--
作者：
Schneeberger M;Dietrich MO;Sebastián D;Imbernón M;Castaño C;Garcia A;Esteban Y;Gonzalez-Franquesa A;Rodríguez IC;Bortolozzi A;Garcia-Roves PM;Gomis R;Nogueiras R;Horvath TL;Zorzano A;Claret M
Mitofusin 2 (Mfn2) plays critical roles in both mitochondrial fusion and the establishment of mitochondria-endoplasmic reticulum (ER) interactions. Hypothalamic ER stress has emerged as a causative factor for the development of leptin resistance, but the underlying mechanisms are largely unknown. Here we show that mitochondria-ER contacts in anorexigenic pro-opiomelanocortin (POMC) neurons in the hypothalamus are decreased in diet-induced obesity. POMC-specific ablation of Mfn2 resulted in loss of mitochondria-ER contacts, defective POMC processing, ER stress-induced leptin resistance, hyperphagia, reduced energy expenditure and obesity. Pharmacological relieve of hypothalamic ER stress reversed these metabolic alterations. Our data establishes Mfn2 in POMC neurons as an essential regulator of systemic energy balance by fine-tuning the mitochondrial-ER axis homeostasis and function. This previously unrecognized role for Mfn2 argues for a crucial involvement in mediating ER stress-induced leptin resistance.
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影响因子：
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影响因子：
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Zorzano, A
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
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Chan DC
DOI：
10.1523/jneurosci.6338-11.2012
发表时间：
2012-03-21
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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