Leucine and arginine enhance milk fat and milk protein synthesis via the CaSR/Gi/mTORC1 and CaSR/Gq/mTORC1 pathways.
Background and aims: Amino acids (AAs) not only constitute milk protein but also stimulate milk synthesis through the activation of mTORC1 signaling, but which amino acids that have the greatest impact on milk fat and protein synthesis is still very limited. In this study, we aimed to identify the m...
| Publicado en: | European Journal of Nutrition Vol. 62; no. 7; pp. 2873 - 2891 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Oct2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=171101886&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 171101886 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14366207 CR0 jtl: European Journal of Nutrition issn: 14366207 maglogo: N pubinfo: dt: Oct2023 vid: 62 iid: 7 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 171101886 164608245 171101886 171101886 10.1007/s00394-023-03197-7 171101886 ppf: 2873 ppct: 18 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Leucine and arginine enhance milk fat and milk protein synthesis via the CaSR/Gi/mTORC1 and CaSR/Gq/mTORC1 pathways. aug: au: Li, Qihui Chen, Jiaming Liu, Jiaxin Lin, Tongbin Liu, Xinghong Zhang, Shuchang Yue, Xianhuai Zhang, Xiaoli Zeng, Xiangfang Ren, Man Guan, Wutai Zhang, Shihai affil: Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, 510642, Guangzhou, China sug: subj: Leucine Pharmacodynamics Arginine Pharmacodynamics Dietary Fats Metabolism Milk Proteins Metabolism Receptors, G-Protein-Coupled Drug Effects Intracellular Signaling Peptides and Proteins Drug Effects Membrane Proteins Drug Effects Calcium Binding Proteins Drug Effects Signal Transduction Drug Effects In Vitro Studies Animal Studies Mice Swine Epithelial Cells Drug Effects Cell Line Drug Effects Epithelial Cells Metabolism Cell Line Metabolism Lactation Gene Expression Drug Effects Fatty Acid-Binding Proteins Drug Effects Acyltransferases Drug Effects Transcription Factors Drug Effects Caseins Drug Effects Polymerase Chain Reaction Blotting, Western Descriptive Statistics Funding Source ab: Background and aims: Amino acids (AAs) not only constitute milk protein but also stimulate milk synthesis through the activation of mTORC1 signaling, but which amino acids that have the greatest impact on milk fat and protein synthesis is still very limited. In this study, we aimed to identify the most critical AAs involved in the regulation of milk synthesis and clarify how these AAs regulate milk synthesis through the G-protein-coupled receptors (GPCRs) signaling pathway. Methods: In this study, a mouse mammary epithelial cell line (HC11) and porcine mammary epithelial cells (PMECs) were selected as study subjects. After treatment with different AAs, the amount of milk protein and milk fat synthesis were detected. Activation of mTORC1 and GPCRs signaling induced by AAs was also investigated. Results: In this study, we demonstrate that essential amino acids (EAAs) are crucial to promote lactation by increasing the expression of genes and proteins related to milk synthesis, such as ACACA, FABP4, DGAT1, SREBP1, α-casein, β-casein, and WAP in HC11 cells and PMECs. In addition to activating mTORC1, EAAs uniquely regulate the expression of calcium-sensing receptor (CaSR) among all amino-acid-responsive GPCRs, which indicates a potential link between CaSR and the mTORC1 pathway in mammary gland epithelial cells. Compared with other EAAs, leucine and arginine had the greatest capacity to trigger GPCRs (p-ERK) and mTORC1 (p-S6K1) signaling in HC11 cells. In addition, CaSR and its downstream G proteins Gi, Gq, and Gβγ are involved in the regulation of leucine- and arginine-induced milk synthesis and mTORC1 activation. Taken together, our data suggest that leucine and arginine can efficiently trigger milk synthesis through the CaSR/Gi/mTORC1 and CaSR/Gq/mTORC1 pathways. Conclusion: We found that the G-protein-coupled receptor CaSR is an important amino acid sensor in mammary epithelial cells. Leucine and arginine promote milk synthesis partially through the CaSR/Gi/mTORC1 and CaSR/Gq/mTORC1 signaling systems in mammary gland epithelial cells. Although this mechanism needs further verification, it is foreseeable that this mechanism may provide new insights into the regulation of milk synthesis. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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