Wang Jiaxin, Cao Yu, Long Xiaoyu, Li Feng, Jiang Naiyuan, Sun Mingyang, Xie Yachun, Ge Yusong, Guo Wenjin, Liu Juxiong, Fu Shoupeng
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China.
College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.
J Agric Food Chem. 2024 Jan 10;72(1):390-404. doi: 10.1021/acs.jafc.3c06977. Epub 2023 Dec 28.
Ghrelin regulates diverse physiological activities. However, the effects of this hormone on the milk fat synthesis remain unknown. This study aimed to investigate the effect of acylated ghrelin (AG) on milk fat synthesis by modifying the expression (knockdown or overexpression) of growth hormone secretagogue receptor 1a (GHSR1a) and Th-inducing POK (ThPOK) in primary bovine mammary epithelial cells (BMECs). The results showed that AG significantly increased the triglyceride relative content from 260.83 ± 9.87 to 541.67 ± 8.38 in BMECs via GHSR1a. ThPOK functions as a key regulatory target downstream of AG, activating the PI3K and mTOR signaling pathways to promote milk fat synthesis in BMECs. Moreover, AG-regulated ThPOK by increasing the EP300 activity, which promoted ThPOK acetylation to protect it from proteasomal degradation. In conclusion, AG increases ThPOK acetylation and stabilizes ThPOK through GHSR1a, thereby activating the PI3K/mTOR signaling pathway and ultimately promoting the milk fat synthesis in BMECs.
胃饥饿素调节多种生理活动。然而，这种激素对乳脂肪合成的影响尚不清楚。本研究旨在通过改变原代牛乳腺上皮细胞（BMECs）中生长激素促分泌素受体1a（GHSR1a）和Th诱导POK（ThPOK）的表达（敲低或过表达），来研究酰化胃饥饿素（AG）对乳脂肪合成的影响。结果表明，AG通过GHSR1a显著提高了BMECs中甘油三酯的相对含量，从260.83±9.87提高到541.67±8.38。ThPOK作为AG下游的关键调控靶点，激活PI3K和mTOR信号通路，促进BMECs中的乳脂肪合成。此外，AG通过增加EP300活性来调节ThPOK，从而促进ThPOK乙酰化，保护其免受蛋白酶体降解。总之，AG通过GHSR1a增加ThPOK乙酰化并稳定ThPOK，从而激活PI3K/mTOR信号通路，最终促进BMECs中的乳脂肪合成。
