Mitofusin 2 in POMC Neurons Connects ER Stress with Leptin Resistance and Energy Imbalance
作者： Marc Schneeberger , Marcelo O. Dietrich , David Sebastián , Mónica Imbernón , Carlos Castaño
DOI: 10.1016/J.CELL.2013.09.003
关键词:
摘要: 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 development leptin resistance, but underlying mechanisms are largely unknown. Here, we show that mitochondria-ER contacts anorexigenic pro-opiomelanocortin (POMC) neurons hypothalamus decreased diet-induced obesity. POMC-specific ablation Mfn2 resulted in loss contacts, defective POMC processing, stress-induced hyperphagia, reduced energy expenditure, Pharmacological relieve hypothalamic reversed these metabolic alterations. Our data establish MFN2 an essential regulator systemic balance by fine-tuning mitochondrial-ER axis homeostasis function. This previously unrecognized role argues crucial involvement mediating resistance.
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