| Literature DB >> 33856409 |
Tong Wu1,2, Qinhui Liu2, Yanping Li2, Hong Li1,2, Lei Chen1,2, Xuping Yang1,2, Qin Tang1,2, Shiyun Pu1,2, Jiangying Kuang1,2, Rui Li1,2, Ya Huang1,2, Jinhang Zhang1,2, Zijing Zhang1,2, Jian Zhou1,2, Cuiyuan Huang1,2, Guorong Zhang1,2, Yingnan Zhao1,2, Min Zou1, Wei Jiang3, Li Mo4, Jinhan He1,2.
Abstract
Activating beige adipocytes in white adipose tissue (WAT) to increase energy expenditure is a promising strategy to combat obesity. We identified that mesencephalic astrocyte-derived neurotrophic factor (Manf) is a feeding-induced hepatokine. Liver-specific Manf overexpression protected mice against high-fat diet-induced obesity and promoted browning of inguinal subcutaneous WAT (iWAT). Manf overexpression in liver was also associated with decreased adipose inflammation and improved insulin sensitivity and hepatic steatosis. Mechanistically, Manf could directly promote browning of white adipocytes via the p38 MAPK pathway. Blockade of p38 MAPK abolished Manf-induced browning. Consistently, liver-specific Manf knockout mice showed impaired iWAT browning and exacerbated diet-induced obesity, insulin resistance, and hepatic steatosis. Recombinant Manf reduced obesity and improved insulin resistance in both diet-induced and genetic obese mouse models. Finally, we showed that circulating Manf level was positively correlated with BMI in humans. This study reveals the crucial role of Manf in regulating thermogenesis in adipose tissue, representing a potential therapeutic target for obesity and related metabolic disorders.Entities:
Year: 2021 PMID： 33856409 DOI： 10.1084/jem.20201203
Source DB: PubMed Journal: J Exp Med ISSN： 0022-1007 Impact factor: 14.307