NDUFAB1 protects against obesity and insulin resistance by enhancing mitochondrial metabolism
NDUFAB1 protects against obesity and insulin resistance by enhancing mitochondrial metabolism
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DOI：
10.1096/fj.201901117rr
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发表时间：
2019-11
期刊：
影响因子：
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通讯作者：
Rufeng Zhang;Tingting Hou;Heping Cheng;Xianhua Wang
中科院分区：
文献类型：
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作者：
Rufeng Zhang;Tingting Hou;Heping Cheng;Xianhua Wang
线粒体是细胞和全身代谢的基本细胞器，其功能障碍与多种代谢疾病的发生有关。增强线粒体代谢可能能够保护免受代谢应激和预防代谢紊乱。在这里，我们表明，NADH：泛醌氧化还原酶（NDU）-FAB 1，也被称为线粒体酰基载体蛋白，作为一种新的线粒体代谢增强剂，并防止肥胖和胰岛素抵抗。在机制上，NDUFAB 1协同增强由线粒体脂肪酸合成途径介导的丙酮酸脱氢酶的脂酰化和活化，并增加呼吸复合物和超复合物的组装。骨骼肌特异性消融NDUFAB 1会导致葡萄糖稳态的全身性破坏和胰岛素信号传导缺陷，导致生长停滞和出生后5天内的早期死亡。相比之下，NDUFAB 1过表达有效地保护小鼠免受肥胖和胰岛素抵抗，当动物受到高脂肪饮食的挑战时。我们的研究结果表明，NDUFAB 1可能是一种新的线粒体靶点，通过增强线粒体代谢来预防肥胖和胰岛素抵抗。张，R. Hou，T.，郑洪，Wang，X. NDUFAB 1通过增强线粒体代谢来防止肥胖和胰岛素抵抗。FASEB J. 33，13310-13322（2019）。www.fasebj.org
Mitochondria are fundamental organelles for cellular and systemic metabolism, and their dysfunction has been implicated in the development of diverse metabolic diseases. Boosted mitochondrial metabolism might be able to protect against metabolic stress and prevent metabolic disorders. Here we show that NADH:ubiquinone oxidoreductase (NDU)‐FAB1, also known as mitochondrial acyl carrier protein, acts as a novel enhancer of mitochondrial metabolism and protects against obesity and insulin resistance. Mechanistically, NDUFAB1 coordinately enhances lipoylation and activation of pyruvate dehydrogenase mediated by the mitochondrial fatty acid synthesis pathway and increases the assembly of respiratory complexes and supercomplexes. Skeletal muscle‐specific ablation of NDUFAB1 causes systemic disruption of glucose homeostasis and defective insulin signaling, leading to growth arrest and early death within 5 postnatal days. In contrast, NDUFAB1 overexpression effectively protects mice against obesity and insulin resistance when the animals are challenged with a high‐fat diet. Our findings indicate that NDUFAB1 could be a novel mitochondrial target to prevent obesity and insulin resistance by enhancing mitochondrial metabolism.—Zhang, R., Hou, T., Cheng, H., Wang, X. NDUFAB1 protects against obesity and insulin resistance by enhancing mitochondrial metabolism. FASEB J. 33, 13310–13322 (2019). www.fasebj.org