Open AccessHepatokine Pregnancy Zone Protein Governs the Diet‐Induced Thermogenesis Through Activating Brown Adipose Tissue
Author(s) -
Lin Jun,
Jiang Xiaoxiao,
Dong Meng,
Liu Xiaomeng,
Shen Qiwei,
Huang Yuanyuan,
Zhang Hanlin,
Ye Rongcai,
Zhou Huiqiao,
Yan Chunlong,
Yuan Shouli,
Wu Xiangnan,
Chen Li,
Wang Yanfang,
He Min,
Tao Yi,
Zhang Zhaoyun,
Jin Wanzhu
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202101991
Subject(s) - thermogenesis , brown adipose tissue , thermogenin , endocrinology , medicine , adipose tissue , biology , uncoupling protein , weight loss , pregnancy , obesity , microbiology and biotechnology , genetics
Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter‐organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant induction during the refeeding stage of IF. Further, loss of function studies and protein therapeutic experiment in mice revealed that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT). Mechanistically, circulating PZP can bind to cell surface glucose‐regulated protein of 78 kDa (GRP78) to promote uncoupling protein 1 (UCP1) expression via a p38 MAPK‐ATF2 signaling pathway in BAT. These studies illuminate a systemic regulation in which the IF promotes BAT thermogenesis through the endocrinal system and provide a novel potential target for treating obesity and related disorders.