增加活化的棕色脂肪组织可以提高机体能耗，进而抑制肥胖，而提高内源性棕脂的含量是最安全有效的方法。体内棕脂主要来源于Myf5阳性祖细胞（与骨骼肌同源），分化密切相关，但其分化机制尚不明确。本课题组前期发现呼吸链甘油磷酸穿梭关键组分——线粒体甘油磷酸脱氢酶（mGPDH）参与骨骼肌分化的调控，同时参与棕脂分化的调控。提示：mGPDH可双向调控骨骼肌和棕脂分化，其下调可能是促进棕脂分化进而抵制高脂导致的肥胖的重要因素。故项目拟在肌母细胞成脂分化模型中，阐述mGPDH对棕脂分化的调控，寻找其下游信号传递途径（前期已发现可能与BMP/PRDM16相关）；进而经已有的mGPDH-/-鼠及高脂喂养的mGPDH-/-鼠探讨其在抵制肥胖中的作用。从棕脂来源的角度揭示mGPDH与棕脂细胞功能的维持关联，解析其信号级联机制，旨在深入理解棕脂抵制肥胖的发生机理，为其干预提供新的策略与依据。

Brown fat dissipates energy as heat and protects against obesity. The body's brown fat is mainly derived from Myf5+ progenitor cells (homologous to skeletal muscle). brown fat differentiation maybe is closely related to skeletal muscle differentiation but its mechanism remains unclear.In our study,we found that introduction of mitochondrial glycerol phosphate dehydrogenase (mGPDH) into myoblasts results in skeletal muscle differentiation. Conversely, the brown fat of mGPDH-knockout mice displays impaired expression of the muscle genes and reciprocal elevation of brown-fat-specific genes. Our finding indicated that : mGPDH may play an important role in differentiation of both skeletal muscle and brown fat , and its knockout may be an important factor in resisting obesity caused by high fat. To illustrate the mechanism of mGPDH to regulation on brown fat differentiation we analyzed the downstream pathway; The project intends to study the resisting obesity within the high-fat-fed mGPDH-/- mice and to find its downstream signaling pathway (previously found to be related to BMP/PRDM16); and then through the existing mGPDH-/- mice The high-fat-fed mGPDH-/- mice explored their role in resisting obesity. From the perspective of brown fat source, it reveals the maintenance relationship between mGPDH and brown cell function, and analyzes its signal cascade mechanism. It aims to understand the mechanism of brown fat resistance to obesity and provide new strategies and evidence for its intervention. in the further step, the Brown fat specific knockout mGPDHflog/flog mice will be used to explore the role of mGPDH in the formation of brown fat differentiation, and the possibility of becoming an effective target of obesity intervention. Thus to reveal the relationship between mGPDH and the brown fat differentiation function, and to analyze the cascade signal system, in order to understand the mechanism of resisting obesity and provide new strategies for the intervention.