PMID- 37841648 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231020 IS - 2405-6383 (Electronic) IS - 2405-6545 (Print) IS - 2405-6383 (Linking) VI - 15 DP - 2023 Dec TI - Propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin (mTOR) pathway in calf hepatocytes. PG - 88-98 LID - 10.1016/j.aninu.2023.07.001 [doi] AB - Enhancing hepatic gluconeogenesis is one of the main modes of meeting the glucose requirement of dairy cows. This study attempted to determine whether the gluconeogenesis precursor propionate had an effect on the expression of the main genes involved in gluconeogenesis in calf hepatocytes and elucidate the associated mechanisms. Calf hepatocytes were obtained from 5 healthy calves (1 d old; 30 to 40 kg) and exposed to 0-, 1-, 2.5-, or 5-mM sodium propionate (NaP), which is known to promote the expression of genes involved in the gluconeogenesis pathway, including fructose 1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase. With regard to the underlying mechanism, propionate promoted the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, hepatocyte nuclear factor 4, and forkhead box O1 (transcription factors that regulate the expression of hepatic gluconeogenic genes) by promoting mammalian target of rapamycin complex 1 (mTORC1), but inhibiting mTORC2 activity (P < 0.01). We also established a model of palmitic acid (PA)-induced hepatic injury in calf hepatocytes and found that PA could inhibit the gluconeogenic capacity of calf hepatocytes by suppressing the expression of gluconeogenic genes, inhibiting mTORC1, and promoting the activity of mTORC2 (P < 0.01). In contrast, NaP provided protection to calf hepatocytes by counteracting the inhibitory effect of PA on the gluconeogenic capacity of calf hepatocytes (P < 0.05). Collectively, these findings indicate that NaP enhances the gluconeogenic capacity of calf hepatocytes by regulating the mTOR pathway activity. Thus, in addition to improving the glucose production potential, propionate may have therapeutic potential for the treatment of hepatic injury in dairy cows. CI - (c) 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. FAU - Wang, Guo Yan AU - Wang GY AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. FAU - Qin, Sen Lin AU - Qin SL AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. FAU - Zheng, Yi Ning AU - Zheng YN AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. FAU - Geng, Hui Jun AU - Geng HJ AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. FAU - Chen, Lei AU - Chen L AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. FAU - Yao, Jun Hu AU - Yao JH AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. FAU - Deng, Lu AU - Deng L AD - College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. LA - eng PT - Journal Article DEP - 20230722 PL - China TA - Anim Nutr JT - Animal nutrition (Zhongguo xu mu shou yi xue hui) JID - 101717655 PMC - PMC10568569 OTO - NOTNLM OT - Gluconeogenesis OT - Mechanistic target of rapamycin OT - Palmitic acid OT - Propionate COIS- We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper. EDAT- 2023/10/16 06:48 MHDA- 2023/10/16 06:49 PMCR- 2023/07/22 CRDT- 2023/10/16 04:38 PHST- 2022/11/01 00:00 [received] PHST- 2023/06/13 00:00 [revised] PHST- 2023/07/18 00:00 [accepted] PHST- 2023/10/16 06:49 [medline] PHST- 2023/10/16 06:48 [pubmed] PHST- 2023/10/16 04:38 [entrez] PHST- 2023/07/22 00:00 [pmc-release] AID - S2405-6545(23)00090-2 [pii] AID - 10.1016/j.aninu.2023.07.001 [doi] PST - epublish SO - Anim Nutr. 2023 Jul 22;15:88-98. doi: 10.1016/j.aninu.2023.07.001. eCollection 2023 Dec.