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Leptin signaling promotes milk fat synthesis via PI3K/AKT/mTOR/SREBP1 in mammary gland of dairy cow

Published online by Cambridge University Press:  05 March 2025

Yang Yang ,
Zhihui Wang ,
Huiju Ge ,
Bo Wang ,
Pengfei Xing ,
Nan Wang ,
Zhiyi Song ,
Ye Lin  and
Xiaoming Hou
Yang Yang
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Zhihui Wang
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Huiju Ge
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Bo Wang
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Pengfei Xing
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Nan Wang
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Zhiyi Song
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Ye Lin
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University, Harbin 150030, China
Xiaoming Hou*
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
*
Corresponding author: Xiaoming Hou; Email: xiaominghou@126.com
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Abstract

Milk fat synthesis is tightly regulated by hormones and growth factors. Leptin is a versatile peptide hormone that exerts pleiotropic effects on metabolic pathways. In this study, we evaluated the expression and function of leptin and its long form receptor OB-Rb in dairy cow mammary tissues from different physiological stages and in cultured mammary epithelial cells. The results showed that the expression of leptin and OB-Rb were significantly higher in the mammary tissues of lactating cows as compared with dry cows, suggesting that they are related to milk component synthesis. In cultured dairy cow mammary epithelial cells, leptin treatment significantly increased OB-Rb expression and intracellular triacylglycerol content. Transcriptome analysis identified the difference in gene expression between leptin treated cells and control cells, and 317 differentially expressed genes were identified. Gene ontology and pathway mapping showed that lipid metabolism-related gene expression increased and signal transduction pathway-related genes were the most significantly enriched. Mechanistic studies showed that leptin stimulation enhanced sterol regulatory element-binding protein 1 expression via activating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway, which in turn up-regulated the expression of genes related to milk fat synthesis. Moreover, we found that fatty acid synthesis precursors, acetate and β-hydroxybutyrate, could positively regulate the expression of leptin and OB-Rb in bovine mammary epithelial cells, thereby potentially increasing milk fat synthesis. Our study provided novel evidence in the regulation of leptin on milk fat production in mammary glands of dairy cows, as well as experimental basis for artificial regulation of milk fat

Keywords

Leptinmammary glandmilk fatOB-RbPI3K/AKT/mTOR/SREBP 1 signaling
Type
Research Article
Information
Journal of Dairy Research , First View , pp. 1 - 12
Copyright
Copyright © The Author(s), 2025. Published by Cambridge University Press on behalf of Hannah Dairy Research Foundation

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