Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice.
Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice.
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分泌的 EMC10 在人类肥胖中表达上调，其中和抗体可预防小鼠饮食诱发的肥胖
DOI：
10.1038/s41467-022-34259-9
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发表时间：
2022-11-28
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
分泌型内质网膜复合体10亚基(ScEMC10)是一种功能不明的分泌型蛋白。在这里，我们证明了SCEMC10在肥胖者中表达上调，并与胰岛素抵抗呈正相关。与scEMC10在肥胖中的因果作用一致，Emc10-/-小鼠对饮食诱导的肥胖具有抵抗力，因为能量消耗增加，而scEMC10过表达减少能量消耗，从而促进小鼠肥胖。此外，使用单抗中和循环中的scEMC10可减轻肥胖小鼠的体重并增强其对胰岛素的敏感性。从机制上讲，我们提供的证据表明，scEMC10可以被转运到细胞内，在那里它可以与PKA的催化亚单位结合并抑制其对CREB的刺激作用，而消融EMC10则通过激活PKA信号通路及其下游靶点促进脂肪细胞的产热。综上所述，我们的数据证实scEMC10是一种循环产热抑制因子，是肥胖及其心脏代谢并发症的潜在治疗靶点。分泌型内质网膜复合体10亚基(ScEMC10)是一种分泌型蛋白，其生理功能尚不完全清楚。在这里，作者证明了scEMC10在肥胖者中上调，并且EMC10的基因缺失或基于抗体的中和可以防止饮食诱导的小鼠肥胖。
Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterized secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in people with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10-/- mice are resistant to diet-induced obesity due to an increase in energy expenditure, while scEMC10 overexpression decreases energy expenditure, thus promoting obesity in mouse. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 can be transported into cells where it binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications. Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a secreted protein of incompletely understood physiological function. Here the authors show that scEMC10 is upregulated in people with obesity, and that that genetic EMC10 deletion or antibody-based neutralization of EMC10 prevents diet-induced obesity in mice.
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影响因子：
15.9
作者：
Kahn, BB;Flier, JS
通讯作者：
Flier, JS
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
8.7
作者：
Hotta, K;Funahashi, T;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
82.9
作者：
Jun H;Yu H;Gong J;Jiang J;Qiao X;Perkey E;Kim DI;Emont MP;Zestos AG;Cho JS;Liu J;Kennedy RT;Maillard I;Xu XZS;Wu J
通讯作者：
Wu J
影响因子：
15.9
作者：
Liew, Chong Wee;Bochenski, Jacek;Kulkarni, Rohit N.
通讯作者：
Kulkarni, Rohit N.