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PPARγ-AGPAT6 signaling mediates acetate-induced mTORC1 activation and milk fat synthesis in mammary epithelial cells of dairy cows

Published online by Cambridge University Press:  18 November 2022

Can Liu ,
Chuanping Liu ,
Xiaoqing Gong ,
Yi Jiang ,
Yang Yang ,
Jinyou Zhang ,
Xiaoming Hou  and
Ye Lin
Can Liu
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Chuanping Liu
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Xiaoqing Gong
Affiliation:
Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University, Harbin 150030, China
Yi Jiang
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Yang Yang
Affiliation:
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, China
Jinyou Zhang
Affiliation:
Institute of Animal Husbandry and Veterinary of Heilongjiang Academy of Land Reclamation Science, Harbin 150038, China
Xiaoming Hou
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
*
Author for correspondence: Ye Lin, Email: linlu516@163.com
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Abstract

This research communication investigated the role and the underlying mechanism of sn-1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT6) in acetate-induced mTORC1 signaling activation and milk fat synthesis in dairy cow mammary epithelial cells. The data showed AGPAT6 knockdown significantly decreased acetate-induced phosphorylation of mTORC1 signaling molecules and intracellular triacylglycerol (TAG) content, whereas this inhibition effect was reversed after the addition of 16:0,18:1 phosphatidic acid (PA), suggesting that AGPAT6 could generate PA in response to acetate simulation, that in turn activates mTORC1 signaling. PPARγ is the upstream regulator of AGPAT6 upon acetate stimulation. Luciferase assay with clones containing various deletions and mutation in AGPAT6 promoter showed that there is a RXRα binding sequence located at −96 bp of AGPAT6 promoter. Acetate stimulation significantly increased the interaction between PPARγ and AGPAT6 via this RXRα binding site. Taken together, our data indicated that AGPAT6 could activate mTORC1 signaling by producing PA during acetate-induced milk fat synthesis, and PPARγ acts as a transcription factor to mediate the effect of acetate on AGPAT6 via RXRα.

Keywords

Acetatemammary epithelial cellmilk fatmTORC1PPARγ-AGPAT6
Type
Research Article
Information
Journal of Dairy Research , Volume 89 , Issue 4 , November 2022 , pp. 410 - 412
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press on behalf of Hannah Dairy Research Foundation

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References

Beigneux, AP, Vergnes, L, Qiao, X, Quatela, S, Davis, R, Watkins, SM, Coleman, RA, Walzem, RL, Philips, M, Reue, K and Young, SG (2006) Agpat6 – a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium. Journal of Lipid Research 47, 734–744.CrossRefGoogle ScholarPubMed
Donkor, J, Sariahmetoglu, M, Dewald, J, Brindley, DN and Reue, K (2007) Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns. Journal of Biological Chemistry 282, 3450–3457.CrossRefGoogle ScholarPubMed
Fang, Y, Vilella-Bach, M, Bachmann, R, Flanigan, A and Chen, J (2001) Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science (New York, N.Y.) 294, 1942–1945.CrossRefGoogle ScholarPubMed
Frohman, MA, Sung, TC and Morris, AJ (1999) Mammalian phospholipase D structure and regulation. Biochimica et Biophysica Acta 1439, 175–186.CrossRefGoogle ScholarPubMed
Lv, H, Meng, Q, Wang, N, Duan, X, Hou, X and Lin, Y (2021) Cell death-inducing DNA fragmentation factor-alpha-like effector C (CIDEC) regulates acetate- and beta-hydroxybutyrate-induced milk fat synthesis by increasing FASN expression in mammary epithelial cells of dairy cows. Journal of Dairy Science 104, 6212–6221.CrossRefGoogle ScholarPubMed
Nagle, CA, Vergnes, L, Dejong, H, Wang, S, Lewin, TM, Reue, K and Coleman, RA (2008) Identification of a novel sn-glycerol-3-phosphate acyltransferase isoform, GPAT4, as the enzyme deficient in Agpat6-/- mice. Journal of Lipid Research 49, 823–831.CrossRefGoogle ScholarPubMed
Shi, HB, Zhao, WS, Luo, J, Yao, DW, Sun, YT, Li, J, Shi, HP and Loor, JJ (2014) Peroxisome proliferator-activated receptor gamma1 and gamma2 isoforms alter lipogenic gene networks in goat mammary epithelial cells to different extents. Journal of Dairy Science 97, 5437–5447.CrossRefGoogle ScholarPubMed
Toschi, A, Lee, E, Xu, L, Garcia, A, Gadir, N and Foster, DA (2009) Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid: competition with rapamycin. Molecular and Cellular Biology 29, 1411–1420.CrossRefGoogle ScholarPubMed
Urrutia, N, Bomberger, R, Matamoros, C and Harvatine, KJ (2019) Effect of dietary supplementation of sodium acetate and calcium butyrate on milk fat synthesis in lactating dairy cows. Journal of Dairy Science 102, 5172–5181.CrossRefGoogle ScholarPubMed
Yoon, MS, Sun, Y, Arauz, E, Jiang, Y and Chen, J (2011) Phosphatidic acid activates mammalian target of rapamycin complex 1 (mTORC1) kinase by displacing FK506 binding protein 38 (FKBP38) and exerting an allosteric effect. Journal of Biological Chemistry 286, 29568–29574.CrossRefGoogle ScholarPubMed
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