Feeding-induced hepatokine, Manf, ameliorates diet-induced obesity by promoting adipose browning via p38 MAPK pathway

• DOI: 10.1084/jem.20201203
• Publication Date: 2021-04-17T01:37:16Z
• Authors: Tong Wu; Qinhui Liu; Yanping Li; Hong Li; Lei Chen; Xuping Yang; Qin Tang; Shiyun Pu; Jiangying Kuang; Rui Li; Ya Huang; Jinhang Zhang; Zijing Zhang; Jian Zhou; Cuiyuan Huang; Guorong Zhang; Yingnan Zhao; Min Zou; Wei Jiang; Li Mo; Jinhan He
• Keywords: Browning

Activating beige adipocytes in white adipose tissue (WAT) to increase energy expenditure is a promising strategy combat obesity. We identified that mesencephalic astrocyte-derived neurotrophic factor (Manf) feeding-induced hepatokine. Liver-specific Manf overexpression protected mice against high-fat diet-induced obesity and promoted browning of inguinal subcutaneous WAT (iWAT). liver was also associated with decreased inflammation improved insulin sensitivity hepatic steatosis. Mechanistically, could directly promote via the p38 MAPK pathway. Blockade abolished Manf-induced browning. Consistently, liver-specific knockout showed impaired iWAT exacerbated obesity, resistance, Recombinant reduced resistance both genetic obese mouse models. Finally, we circulating level positively correlated BMI humans. This study reveals crucial role regulating thermogenesis tissue, representing potential therapeutic target for related metabolic disorders.