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 |
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container_title | Journal of agricultural and food chemistry |
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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. 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><subject>Acetylation</subject><subject>Animals</subject><subject>Bioactive Constituents, Metabolites, and Functions</subject><subject>Cattle</subject><subject>Epithelial Cells - metabolism</subject><subject>Ghrelin - metabolism</subject><subject>Ghrelin - pharmacology</subject><subject>Mammary Glands, Animal - metabolism</subject><subject>Milk - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - genetics</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Signal Transduction</subject><subject>TOR Serine-Threonine Kinases - genetics</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1UTtPwzAQthAISmFnQh4ZSLHjOHbGUvGoALWCMke241BDEpfYBeWP8HtxaGFjOt19jzvdB8AJRiOMYnwhlBu9ilKNiEJpxtgOGGAao4hizHfBAAVOxGmKD8Chc68IIU4Z2gcHhGOaoAwPwNdYdZXwuoA3y1ZXpoFj5c1HmDg4n5K7i3oxe4RP5qURAXyBc-GXn6KDsoPz1tbW98PFcj67C0Ltey9jG-jtFtbwwVRv8Fp4-NQ1fqmdcTBsubQfpgmgqGvRdvBqZQJWGVHBia4qdwT2SlE5fbytQ_B8fbWY3Eb3s5vpZHwfCUJSH2FG4qxgSaYpS4ukkEqRgkuCiGQpJXEZ2jTTEvFSYVlykpaMs4QViVQskZwMwdnGd9Xa97V2Pq-NU-EC0Wi7dnmcIY5jQjkNVLShqtY61-oyX7WmPz7HKO_TyEMaeZ9Gvk0jSE637mtZ6-JP8Pv-QDjfEH6kdt2GL7v__b4BYUuXMg</recordid><startdate>20240110</startdate><enddate>20240110</enddate><creator>Wang, Jiaxin</creator><creator>Cao, Yu</creator><creator>Long, Xiaoyu</creator><creator>Li, Feng</creator><creator>Jiang, Naiyuan</creator><creator>Sun, Mingyang</creator><creator>Xie, Yachun</creator><creator>Ge, Yusong</creator><creator>Guo, Wenjin</creator><creator>Liu, Juxiong</creator><creator>Fu, Shoupeng</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2545-8929</orcidid></search><sort><creationdate>20240110</creationdate><title>Acylated Ghrelin Activates PI3K/mTOR Signaling Pathway by Promoting ThPOK Acetylation to Promote Milk Fat Synthesis in Bovine Mammary Epithelial Cells</title><author>Wang, Jiaxin ; Cao, Yu ; Long, Xiaoyu ; Li, Feng ; Jiang, Naiyuan ; Sun, Mingyang ; Xie, Yachun ; Ge, Yusong ; Guo, Wenjin ; Liu, Juxiong ; Fu, Shoupeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a336t-17329d749e576d4dbcc3d8b303b76532fc3d69eb08fc1bf836f78747d4bc74b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acetylation</topic><topic>Animals</topic><topic>Bioactive Constituents, Metabolites, and Functions</topic><topic>Cattle</topic><topic>Epithelial Cells - metabolism</topic><topic>Ghrelin - metabolism</topic><topic>Ghrelin - pharmacology</topic><topic>Mammary Glands, Animal - metabolism</topic><topic>Milk - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Signal Transduction</topic><topic>TOR Serine-Threonine Kinases - genetics</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><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><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Jiaxin</au><au>Cao, Yu</au><au>Long, Xiaoyu</au><au>Li, Feng</au><au>Jiang, Naiyuan</au><au>Sun, Mingyang</au><au>Xie, Yachun</au><au>Ge, Yusong</au><au>Guo, Wenjin</au><au>Liu, Juxiong</au><au>Fu, Shoupeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acylated Ghrelin Activates PI3K/mTOR Signaling Pathway by Promoting ThPOK Acetylation to Promote Milk Fat Synthesis in Bovine Mammary Epithelial Cells</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. 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. 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.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>38154091</pmid><doi>10.1021/acs.jafc.3c06977</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-2545-8929</orcidid></addata></record> |
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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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