| Autor: |
Xuanchun Wang, Guifen Qiang, YANLIANG LI, Kaihua Wang, Jiarong Dai, Maximilian McCann, Victoria Gil, Yifei Yu, Shengxian Li, Zhihong Yang, Shanshan XU, Jose Cordoba-Chacon, Dario F De Jesus, Bei Sun, Kuangyang Chen, Xiaoxia Liu, Qing Miao, Linuo Zhou, Renming Hu, Qiang Ding, Rohit Kulkarni, Daming Gao, Matthias Blüher, Chong Wee Liew |
| Rok vydání: |
2021 |
| DOI: |
10.21203/rs.3.rs-869957/v1 |
| Popis: |
Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterised secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in humans 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. 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 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 novel circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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