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Leucine and arginine enhance milk fat and milk protein synthesis via the CaSR/Gi/mTORC1 and CaSR/Gq/mTORC1 pathways

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

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.

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Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Kim SW, Wu G (2009) Regulatory role for amino acids in mammary gland growth and milk synthesis. Amino Acids 37(1):89–95

    CAS  PubMed  Google Scholar 

  2. Wu G, Bazer FW, Dai Z, Li D, Wang J, Wu Z (2014) Amino acid nutrition in animals: protein synthesis and beyond. Annu Rev Anim Biosci 2(1):387–417

    CAS  PubMed  Google Scholar 

  3. Zhang S, Chen F, Zhang Y, Lv Y, Heng J, Min T, Li L, Guan W (2018) Recent progress of porcine milk components and mammary gland function. J Anim Sci Biotechnol 9(1):1–13

    Google Scholar 

  4. Lei J, Feng D, Zhang Y, Zhao F-Q, Wu Z, San Gabriel A, Fujishima Y, Uneyama H, Wu G (2012) Nutritional and regulatory role of branched-chain amino acids in lactation. Front Biosci 17(725):722

    Google Scholar 

  5. Manjarin R, Bequette BJ, Wu G, Trottier NL (2014) Linking our understanding of mammary gland metabolism to amino acid nutrition. Amino Acids 46(11):2447–2462

    CAS  PubMed  Google Scholar 

  6. Lei J, Feng D, Zhang Y, Dahanayaka S, Li X, Yao K, Wang J, Wu Z, Dai Z, Wu G (2012) Regulation of leucine catabolism by metabolic fuels in mammary epithelial cells. Amino Acids 43(5):2179–2189

    CAS  PubMed  Google Scholar 

  7. Zhang S, Zeng X, Ren M, Mao X, Qiao S (2017) Novel metabolic and physiological functions of branched chain amino acids: a review. J Anim Sci Biotechnol 8(1):1–12

    Google Scholar 

  8. Zhang S, Heng J, Song H, Zhang Y, Lin X, Tian M, Chen F, Guan W (2019) Role of maternal dietary protein and amino acids on fetal programming, early neonatal development, and lactation in swine. Animals 9(1):19

    PubMed  PubMed Central  Google Scholar 

  9. Ge Y, Li F, He Y, Cao Y, Guo W, Hu G, Liu J, Fu SJJoAP, Nutrition A (2022) L‐arginine stimulates the proliferation of mouse mammary epithelial cells and the development of mammary gland in pubertal mice by activating the GPRC6A/PI3K/AKT/mTOR signalling pathway. 106(6):1383–1395

  10. Kim SW, Wu GJAa (2009) Regulatory role for amino acids in mammary gland growth and milk synthesis. 37:89–95

  11. Appuhamy JRN, Knoebel NA, Nayananjalie WD, Escobar J, Hanigan MDJTJon (2012) Isoleucine and leucine independently regulate mTOR signaling and protein synthesis in MAC-T cells and bovine mammary tissue slices. 142(3):484–491

  12. Lei J, Feng D, Zhang Y, Zhao F-Q, Wu Z, San Gabriel A, Fujishima Y, Uneyama H, Wu GJFiB-L (2012) Nutritional and regulatory role of branched-chain amino acids in lactation. 17 (7):2725–2739

  13. Innis SM (2011) Dietary triacylglycerol structure and its role in infant nutrition. Adv Nutr 2(3):275–283

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Wu Z, Tian M, Heng J, Chen J, Chen F, Guan W, Zhang S (2020) Current evidences and future perspectives for AMPK in the regulation of milk production and mammary gland biology. Front Cell Dev Biol 8:530

    PubMed  PubMed Central  Google Scholar 

  15. Abu-Elheiga L, Brinkley WR, Zhong L, Chirala SS, Woldegiorgis G, Wakil SJ (2000) The subcellular localization of acetyl-CoA carboxylase 2. Proc Natl Acad Sci 97(4):1444–1449

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Li N, Zhao F, Wei C, Liang M, Zhang N, Wang C, Li Q-Z, Gao X-J (2014) Function of SREBP1 in the milk fat synthesis of dairy cow mammary epithelial cells. Int J Mol Sci 15(9):16998–17013

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Che L, Xu M, Gao K, Zhu C, Wang L, Yang X, Wen X, Xiao H, Jiang Z, Wu D (2019) Valine increases milk fat synthesis in mammary gland of gilts through stimulating AKT/MTOR/SREBP1 pathway. Biol Reprod 101(1):126–137

    PubMed  Google Scholar 

  18. Yang D, Jiang T, Liu J, Hong J, Lin P, Chen H, Zhou D, Tang K, Wang A, Jin Y (2018) Hormone regulates endometrial function via cooperation of endoplasmic reticulum stress and mTOR-autophagy. J Cell Physiol 233(9):6644–6659

    CAS  PubMed  Google Scholar 

  19. Burgos S, Kim J, Dai M, Cant J (2013) Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses protein synthesis through inhibition of mTORC1 signaling. Horm Metab Res 45(03):183–189

    CAS  PubMed  Google Scholar 

  20. Jiang W, Zhu Z, Thompson HJ (2008) Dietary energy restriction modulates the activity of AMP-activated protein kinase, Akt, and mammalian target of rapamycin in mammary carcinomas, mammary gland, and liver. Can Res 68(13):5492–5499

    CAS  Google Scholar 

  21. Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DMJC (2010) Ragulator-rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. 141(2):290–303

  22. Morton R (1962) Biochemistry and nutrition. Nature 193(4810):15–17

    Google Scholar 

  23. Dong X, Zhou Z, Saremi B, Helmbrecht A, Wang Z, Loor J (2018) Varying the ratio of Lys: Met while maintaining the ratios of Thr: Phe, Lys: Thr, Lys: His, and Lys: Val alters mammary cellular metabolites, mammalian target of rapamycin signaling, and gene transcription. J Dairy Sci 101(2):1708–1718

    CAS  PubMed  Google Scholar 

  24. Gao H, Zhao S, Zheng N, Zhang Y, Wang S, Zhou X, Wang J (2017) Combination of histidine, lysine, methionine, and leucine promotes β-casein synthesis via the mechanistic target of rapamycin signaling pathway in bovine mammary epithelial cells. J Dairy Sci 100(9):7696–7709

    CAS  PubMed  Google Scholar 

  25. Li S, Hosseini A, Danes M, Jacometo C, Liu J, Loor JJ (2016) Essential amino acid ratios and mTOR affect lipogenic gene networks and miRNA expression in bovine mammary epithelial cells. J Anim Sci Biotechnol 7(1):1–11

    Google Scholar 

  26. Zhang Y, Wang P, Lin S, Mercier Y, Yin H, Song Y, Zhang X, Che L, Lin Y, Xu S (2018) mTORC1 signaling-associated protein synthesis in porcine mammary glands was regulated by the local available methionine depending on methionine sources. Amino Acids 50(1):105–115

    CAS  PubMed  Google Scholar 

  27. Che L, Xu M, Gao K, Wang L, Yang X, Wen X, Xiao H, Jiang Z, Wu D (2019) Valine supplementation during late pregnancy in gilts increases colostral protein synthesis through stimulating mTOR signaling pathway in mammary cells. Amino Acids 51(10):1547–1559

    CAS  PubMed  Google Scholar 

  28. Wu Z, Heng J, Tian M, Song H, Chen F, Guan W, Zhang S (2020) Amino acid transportation, sensing and signal transduction in the mammary gland: key molecular signalling pathways in the regulation of milk synthesis. Nutr Res Rev 33(2):287–297

    CAS  PubMed  Google Scholar 

  29. Zheng L, Zhang W, Zhou Y, Li F, Wei H, Peng JJIJoMS (2016) Recent advances in understanding amino acid sensing mechanisms that regulate mTORC1. 17(10):1636

  30. Shigemura N, Shirosaki S, Sanematsu K, Yoshida R, Ninomiya Y (2009) Genetic and molecular basis of individual differences in human umami taste perception. PLoS One 4(8):e6717

    PubMed  PubMed Central  Google Scholar 

  31. Wang J, Hua T, Liu Z-J (2020) Structural features of activated GPCR signaling complexes. Curr Opin Struct Biol 63:82–89

    CAS  PubMed  Google Scholar 

  32. Jain R, Watson U, Vasudevan L, Saini DK (2018) ERK activation pathways downstream of GPCRs. Int Rev Cell Mol Biol 338:79–109

    CAS  PubMed  Google Scholar 

  33. Conigrave AD, Hampson DRJP, therapeutics (2010) Broad-spectrum amino acid-sensing class C G-protein coupled receptors: molecular mechanisms, physiological significance and options for drug development. 127(3):252–260

  34. Li X, Li P, Wang L, Zhang M, Gao X (2019) Lysine enhances the stimulation of fatty acids on milk fat synthesis via the GPRC6A-PI3K-FABP5 signaling in bovine mammary epithelial cells. J Agric Food Chem 67(25):7005–7015

    CAS  PubMed  Google Scholar 

  35. Liu J, Wang Y, Li D, Wang Y, Li M, Chen C, Fang X, Chen H, Zhang C (2017) Milk protein synthesis is regulated by T1R1/T1R3, a G protein-coupled taste receptor, through the mTOR pathway in the mouse mammary gland. Mol Nutr Food Res 61(9):1601017

    Google Scholar 

  36. Wang Y, Liu J, Wu H, Fang X, Chen H, Zhang C (2017) Amino acids regulate mTOR pathway and milk protein synthesis in a mouse mammary epithelial cell line is partly mediated by T1R1/T1R3. Eur J Nutr 56(8):2467–2474

    CAS  PubMed  Google Scholar 

  37. Ma Q, Hu S, Bannai M, Wu G (2018) l-Arginine regulates protein turnover in porcine mammary epithelial cells to enhance milk protein synthesis. Amino Acids 50(5):621–628

    CAS  PubMed  Google Scholar 

  38. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(7):1–12

    Google Scholar 

  39. Wang F, Shi H, Wang S, Wang Y, Cao Z, Li S (2019) Amino acid metabolism in dairy cows and their regulation in milk synthesis. Curr Drug Metab 20(1):36–45

    CAS  PubMed  Google Scholar 

  40. Wu G (2017) Principles of animal nutrition. CRC Press

  41. Brown EM, MacLeod RJ (2001) Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 81(1):239–297

    CAS  PubMed  Google Scholar 

  42. Mamillapalli R, VanHouten J, Dann P, Bikle D, Chang W, Brown E, Wysolmerski J (2013) Mammary-specific ablation of the calcium-sensing receptor during lactation alters maternal calcium metabolism, milk calcium transport, and neonatal calcium accrual. Endocrinology 154(9):3031

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Laporta J, Keil KP, Vezina CM, Hernandez LL (2014) Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice. PLoS One 9(10):e110190

    PubMed  PubMed Central  Google Scholar 

  44. Kong X, Tan B, Yin Y, Gao H, Li X, Jaeger LA, Bazer FW, Wu G (2012) l-Arginine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells. J Nutr Biochem 23(9):1178–1183

    CAS  PubMed  Google Scholar 

  45. Hu L, Chen Y, Cortes IM, Coleman DN, Dai H, Liang Y, Parys C, Fernandez C, Wang M, Loor JJ (2020) Supply of methionine and arginine alters phosphorylation of mechanistic target of rapamycin (mTOR), circadian clock proteins, and α-s1-casein abundance in bovine mammary epithelial cells. Food Funct 11(1):883–894

    CAS  PubMed  Google Scholar 

  46. Gao H-n, Hu H, Zheng N, Wang J-q (2015) Leucine and histidine independently regulate milk protein synthesis in bovine mammary epithelial cells via mTOR signaling pathway. J Zhejiang Univ Sci B 16(6):560–572

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Soliman GA (2013) The role of mechanistic target of rapamycin (mTOR) complexes signaling in the immune responses. Nutrients 5(6):2231–2257

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Saxton RA, Knockenhauer KE, Wolfson RL, Chantranupong L, Pacold ME, Wang T, Schwartz TU, Sabatini DM (2016) Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science 351(6268):53–58

    CAS  PubMed  Google Scholar 

  49. Appuhamy JRN, Knoebel NA, Nayananjalie WD, Escobar J, Hanigan MD (2012) Isoleucine and leucine independently regulate mTOR signaling and protein synthesis in MAC-T cells and bovine mammary tissue slices. J Nutr 142(3):484–491

    CAS  PubMed  Google Scholar 

  50. Maxin G, Glasser F, Hurtaud C, Peyraud J-L, Rulquin H (2011) Combined effects of trans-10, cis-12 conjugated linoleic acid, propionate, and acetate on milk fat yield and composition in dairy cows. J Dairy Sci 94(4):2051–2059

    CAS  PubMed  Google Scholar 

  51. Nafikov R, Schoonmaker J, Korn K, Noack K, Garrick D, Koehler K, Minick-Bormann J, Reecy J, Spurlock D, Beitz D (2013) Association of polymorphisms in solute carrier family 27, isoform A6 (SLC27A6) and fatty acid-binding protein-3 and fatty acid-binding protein-4 (FABP3 and FABP4) with fatty acid composition of bovine milk. J Dairy Sci 96(9):6007–6021

    CAS  PubMed  Google Scholar 

  52. Schennink A, Heck JM, Bovenhuis H, Visker MH, van Valenberg HJ, van Arendonk JA (2008) Milk fatty acid unsaturation: genetic parameters and effects of stearoyl-CoA desaturase (SCD1) and acyl CoA: diacylglycerol acyltransferase 1 (DGAT1). J Dairy Sci 91(5):2135–2143

    CAS  PubMed  Google Scholar 

  53. Qi H, Meng C, Jin X, Li X, Li P, Gao X (2018) Methionine promotes milk protein and fat synthesis and cell proliferation via the SNAT2-PI3K signaling pathway in bovine mammary epithelial cells. J Agric Food Chem 66(42):11027–11033

    CAS  PubMed  Google Scholar 

  54. Qiu Y, Qu B, Zhen Z, Yuan X, Zhang L, Zhang M (2019) Leucine promotes milk synthesis in bovine mammary epithelial cells via the PI3K-DDX59 signaling. J Agric Food Chem 67(32):8884–8895

    CAS  PubMed  Google Scholar 

  55. Li P, Zhou C, Li X, Yu M, Li M, Gao X (2019) CRTC2 is a key mediator of amino acid-induced milk fat synthesis in mammary epithelial cells. J Agric Food Chem 67(37):10513–10520

    CAS  PubMed  Google Scholar 

  56. Velázquez-Villegas LA, López-Barradas AM, Torres N, Hernández-Pando R, León-Contreras JC, Granados O, Ortíz V, Tovar AR (2015) Prolactin and the dietary protein/carbohydrate ratio regulate the expression of SNAT2 amino acid transporter in the mammary gland during lactation. Biochimica et Biophysica Acta (BBA)-Biomembranes 1848(5):1157–1164

  57. Zhou J, Jiang M, Shi Y, Song S, Hou X, Lin Y (2020) Prolactin regulates LAT1 expression via STAT5 (signal transducer and activator of transcription 5) signaling in mammary epithelial cells of dairy cows. J Dairy Sci 103(7):6627–6634

    CAS  PubMed  Google Scholar 

  58. Pauloin A, Chanat E (2012) Prolactin and epidermal growth factor stimulate adipophilin synthesis in HC11 mouse mammary epithelial cells via the PI3-kinase/Akt/mTOR pathway. Biochimica et Biophysica Acta (BBA)-Mol Cell Res 1823(5):987–996

  59. Mun H-C, Franks AH, Culverston EL, Krapcho K, Nemeth EF, Conigrave AD (2004) The Venus fly trap domain of the extracellular Ca2+-sensing receptor is required for l-amino acid sensing. J Biol Chem 279(50):51739–51744

    CAS  PubMed  Google Scholar 

  60. Mine Y, Zhang H (2015) Calcium-sensing receptor (CaSR)-mediated anti-inflammatory effects of l-amino acids in intestinal epithelial cells. J Agric Food Chem 63(45):9987–9995

    CAS  PubMed  Google Scholar 

  61. Mun H-c, Leach KM, Conigrave AD (2019) l-amino acids promote calcitonin release via a calcium-sensing receptor: Gq/11-mediated pathway in human C-cells. Endocrinology 160(7):1590–1599

    CAS  PubMed  Google Scholar 

  62. Wang Y, Chandra R, Samsa LA, Gooch B, Fee BE, Cook JM, Vigna SR, Grant AO, Liddle RA (2011) Amino acids stimulate cholecystokinin release through the Ca2+-sensing receptor. Am J Physiol Gastroint Liver Physiol 300(4):G528-G537

  63. VanHouten J, Dann P, McGeoch G, Brown EM, Krapcho K, Neville M, Wysolmerski JJ (2004) The calcium-sensing receptor regulates mammary gland parathyroid hormone–related protein production and calcium transport. J Clin Investig 113(4):598–608

    CAS  PubMed  PubMed Central  Google Scholar 

  64. VanHouten JN, Neville MC, Wysolmerski JJ (2007) The calcium-sensing receptor regulates plasma membrane calcium adenosine triphosphatase isoform 2 activity in mammary epithelial cells: a mechanism for calcium-regulated calcium transport into milk. Endocrinology 148(12):5943–5954

    CAS  PubMed  Google Scholar 

  65. Di Mise A, Tamma G, Ranieri M, Centrone M, van den Heuvel L, Mekahli D, Levtchenko EN, Valenti G (2018) Activation of calcium-sensing receptor increases intracellular calcium and decreases cAMP and mTOR in PKD1 deficient cells. Sci Rep 8(1):1–14

    Google Scholar 

  66. Hernández-Bedolla MA, González-Domínguez E, Zavala-Barrera C, Gutiérrez-López TY, Hidalgo-Moyle JJ, Vázquez-Prado J, Sánchez-Torres C, Reyes-Cruz G (2016) Calcium-sensing-receptor (CaSR) controls IL-6 secretion in metastatic breast cancer MDA-MB-231 cells by a dual mechanism revealed by agonist and inverse-agonist modulators. Mol Cell Endocrinol 436:159–168

    PubMed  Google Scholar 

  67. Hernández-Bedolla MA, Carretero-Ortega J, Valadez-Sánchez M, Vázquez-Prado J, Reyes-Cruz G (2015) Chemotactic and proangiogenic role of calcium sensing receptor is linked to secretion of multiple cytokines and growth factors in breast cancer MDA-MB-231 cells. Biochimica et Biophysica Acta (BBA)-Mol Cell Res 1853(1):166–182

  68. Jin L, Qian Y, Zhou J, Dai L, Cao C, Zhu C, Li S (2019) Activated CRH receptors inhibit autophagy by repressing conversion of LC3BI to LC3BII. Cell Signal 58:119–130

    CAS  PubMed  Google Scholar 

  69. Gong Y, Zhang D-D, Tang Z, Coate K, Siv W, Yin L, Covington B, Patel R, Yang B, Yang L (2021) Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between mTORC1 and CaSR-Gq signaling pathways

  70. Wang Q, Chen J, Zhang M, Wang H, Zeng Y, Huang Y, Xu C (2022) Autophagy induced by muscarinic acetylcholine receptor 1 mediates migration and invasion targeting Atg5 via AMPK/mTOR pathway in prostate cancer. J Oncol 2022

  71. Gulati P, Gaspers LD, Dann SG, Joaquin M, Nobukuni T, Natt F, Kozma SC, Thomas AP, Thomas G (2008) Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34. Cell Metab 7(5):456–465

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Decuypere J-P, Kindt D, Luyten T, Welkenhuyzen K, Missiaen L, De Smedt H, Bultynck G, Parys JB (2013) mTOR-controlled autophagy requires intracellular Ca2+ signaling. PLoS One 8(4):e61020

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Conigrave AD, Ward DT (2013) Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways. Best Pract Res Clin Endocrinol Metab 27(3):315–331

    CAS  PubMed  Google Scholar 

  74. Alhosaini K, Azhar A, Alonazi A, Al-Zoghaibi F (2021) GPCRs: the most promiscuous druggable receptor of the mankind. Saudi Pharmaceut J 29(6):539–551

    CAS  Google Scholar 

  75. Lizarzaburu M, Turcotte S, Du X, Duquette J, Fu A, Houze J, Li L, Liu J, Murakoshi M, Oda K (2012) Discovery and optimization of a novel series of GPR142 agonists for the treatment of type 2 diabetes mellitus. Bioorg Med Chem Lett 22(18):5942–5947

    CAS  PubMed  Google Scholar 

  76. Wang T, Li Z, Cvijic ME, Zhang L, Sum CS (2017) Measurement of cAMP for Gαs-and Gαi protein-coupled receptors (GPCRs).

  77. Xie J, Ponuwei GA, Moore CE, Willars GB, Tee AR, Herbert TP (2011) cAMP inhibits mammalian target of rapamycin complex-1 and-2 (mTORC1 and 2) by promoting complex dissociation and inhibiting mTOR kinase activity. Cell Signal 23(12):1927–1935

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Zhang S, Wang H, Melick CH, Jeong M-H, Curukovic A, Tiwary S, Lama-Sherpa TD, Meng D, Servage KA, James NG (2021) AKAP13 couples GPCR signaling to mTORC1 inhibition. PLoS Genet 17(10):e1009832

    CAS  PubMed  PubMed Central  Google Scholar 

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Funding

The research was funded by the following funds: National Key R&D Program of China (No. 2021YFD1300700), the Guangdong Basic and Applied Basic Research Foundation (No. 2021A1515010440 and 2023A1515012098), the Science and Technology Program of Guangzhou (No. 202102020056), the National Natural Science Foundation of China (No. 31802067 and 31872364), and the Anhui Province Key Laboratory of Animal Nutrition Regulation and Health (No. APKLANRH202105).

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Authors and Affiliations

  1. Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China

    Qihui Li, Jiaming Chen, Jiaxin Liu, Tongbin Lin, Xinghong Liu, Shuchang Zhang, Xianhuai Yue, Xiaoli Zhang, Wutai Guan & Shihai Zhang

  2. College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, 510642, China

    Wutai Guan & Shihai Zhang

  3. Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China

    Wutai Guan & Shihai Zhang

  4. State Key Laboratory of Animal Nutrition, Ministry of Agriculture and Rural Affairs Feed Industry Center, China Agricultural University, Beijing, China

    Xiangfang Zeng

  5. Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang, China

    Man Ren

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  1. Qihui Li
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Li, Q., Chen, J., Liu, J. et al. Leucine and arginine enhance milk fat and milk protein synthesis via the CaSR/Gi/mTORC1 and CaSR/Gq/mTORC1 pathways. Eur J Nutr 62, 2873–2890 (2023). https://doi.org/10.1007/s00394-023-03197-7

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