Hepatokine Pregnancy Zone Protein Governs the Diet-Induced Thermogenesis Through Activating Brown Adipose Tissue,Advanced Science

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Hepatokine Pregnancy Zone Protein Governs the Diet-Induced Thermogenesis Through Activating Brown Adipose Tissue
Advanced Science ( IF 14.3 ) Pub Date : 2021-09-13 , DOI: 10.1002/advs.202101991
Jun Lin ₁ , Xiaoxiao Jiang _{1,

2} , Meng Dong ₁ , Xiaomeng Liu ₃ , Qiwei Shen ₄ , Yuanyuan Huang _{1,

2} , Hanlin Zhang _{1,

2} , Rongcai Ye _{1,

2} , Huiqiao Zhou _{1,

2} , Chunlong Yan ₅ , Shouli Yuan _{1,

2} , Xiangnan Wu _{1,

2} , Li Chen _{1,

2} , Yanfang Wang ₆ , Min He ₇ , Yi Tao ₁ , Zhaoyun Zhang ₇ , Wanzhu Jin _{1,

2}

Affiliation

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.

中文翻译：

肝因子孕区蛋白通过激活棕色脂肪组织来控制饮食诱导的生热作用

间歇性禁食（IF）作为减肥的饮食干预措施，主要通过增加能量消耗来发挥作用。然而，器官间系统是否在 IF 中发挥关键作用仍不清楚。在这里，鉴定出一种新的肝因子，即妊娠区蛋白 (PZP)，它在 IF 的再喂养阶段具有显着的诱导作用。此外，小鼠功能丧失研究和蛋白质治疗实验表明，PZP 通过激活棕色脂肪组织 (BAT) 促进饮食诱导的生热作用。从机制上讲，循环中的 PZP 可以与细胞表面 78 kDa 的葡萄糖调节蛋白 (GRP78) 结合，通过 BAT 中的 p38 MAPK-ATF2 信号通路促进解偶联蛋白 1 (UCP1) 的表达。这些研究阐明了 IF 通过内分泌系统促进 BAT 产热的系统性调节，并为治疗肥胖和相关疾病提供了新的潜在靶点。

更新日期：2021-11-04

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