Acylated Ghrelin Activates PI3K/mTOR Signaling Pathway by Promoting ThPOK Acetylation to Promote Milk Fat Synthesis in Bovine Mammary Epithelial Cells

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 sec...

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Veröffentlicht in:Journal of agricultural and food chemistry 2024-01, Vol.72 (1), p.390-404
Hauptverfasser: Wang, Jiaxin, Cao, Yu, Long, Xiaoyu, Li, Feng, Jiang, Naiyuan, Sun, Mingyang, Xie, Yachun, Ge, Yusong, Guo, Wenjin, Liu, Juxiong, Fu, Shoupeng
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container_issue 1
container_start_page 390
container_title Journal of agricultural and food chemistry
container_volume 72
creator Wang, Jiaxin
Cao, Yu
Long, Xiaoyu
Li, Feng
Jiang, Naiyuan
Sun, Mingyang
Xie, Yachun
Ge, Yusong
Guo, Wenjin
Liu, Juxiong
Fu, Shoupeng
description 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.
doi_str_mv 10.1021/acs.jafc.3c06977
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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.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/acs.jafc.3c06977</identifier><identifier>PMID: 38154091</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Acetylation ; Animals ; Bioactive Constituents, Metabolites, and Functions ; Cattle ; Epithelial Cells - metabolism ; Ghrelin - metabolism ; Ghrelin - pharmacology ; Mammary Glands, Animal - metabolism ; Milk - metabolism ; Phosphatidylinositol 3-Kinases - genetics ; Phosphatidylinositol 3-Kinases - metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases - genetics ; TOR Serine-Threonine Kinases - metabolism</subject><ispartof>Journal of agricultural and food chemistry, 2024-01, Vol.72 (1), p.390-404</ispartof><rights>2023 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a336t-17329d749e576d4dbcc3d8b303b76532fc3d69eb08fc1bf836f78747d4bc74b83</citedby><cites>FETCH-LOGICAL-a336t-17329d749e576d4dbcc3d8b303b76532fc3d69eb08fc1bf836f78747d4bc74b83</cites><orcidid>0000-0002-2545-8929</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.jafc.3c06977$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.jafc.3c06977$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27055,27903,27904,56716,56766</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38154091$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Jiaxin</creatorcontrib><creatorcontrib>Cao, Yu</creatorcontrib><creatorcontrib>Long, Xiaoyu</creatorcontrib><creatorcontrib>Li, Feng</creatorcontrib><creatorcontrib>Jiang, Naiyuan</creatorcontrib><creatorcontrib>Sun, Mingyang</creatorcontrib><creatorcontrib>Xie, Yachun</creatorcontrib><creatorcontrib>Ge, Yusong</creatorcontrib><creatorcontrib>Guo, Wenjin</creatorcontrib><creatorcontrib>Liu, Juxiong</creatorcontrib><creatorcontrib>Fu, Shoupeng</creatorcontrib><title>Acylated Ghrelin Activates PI3K/mTOR Signaling Pathway by Promoting ThPOK Acetylation to Promote Milk Fat Synthesis in Bovine Mammary Epithelial Cells</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>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. 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Agric. Food Chem</addtitle><date>2024-01-10</date><risdate>2024</risdate><volume>72</volume><issue>1</issue><spage>390</spage><epage>404</epage><pages>390-404</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><abstract>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. 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subjects Acetylation
Animals
Bioactive Constituents, Metabolites, and Functions
Cattle
Epithelial Cells - metabolism
Ghrelin - metabolism
Ghrelin - pharmacology
Mammary Glands, Animal - metabolism
Milk - metabolism
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Signal Transduction
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - metabolism
title Acylated Ghrelin Activates PI3K/mTOR Signaling Pathway by Promoting ThPOK Acetylation to Promote Milk Fat Synthesis in Bovine Mammary Epithelial Cells
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