Propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin (mTOR) pathway in calf hepatocytes
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 elucid...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-12-01
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| Series: | Animal Nutrition |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405654523000902 |
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| author | Guo Yan Wang Sen Lin Qin Yi Ning Zheng Hui Jun Geng Lei Chen Jun Hu Yao Lu Deng |
| author_facet | Guo Yan Wang Sen Lin Qin Yi Ning Zheng Hui Jun Geng Lei Chen Jun Hu Yao Lu Deng |
| author_sort | Guo Yan Wang |
| collection | DOAJ |
| description | 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. |
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| issn | 2405-6545 |
| language | English |
| last_indexed | 2024-03-08T21:29:37Z |
| publishDate | 2023-12-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Animal Nutrition |
| spelling | doaj.art-df87a45ca32044feb93686c672c8a2802023-12-21T07:32:58ZengKeAi Communications Co., Ltd.Animal Nutrition2405-65452023-12-01158898Propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin (mTOR) pathway in calf hepatocytesGuo Yan Wang0Sen Lin Qin1Yi Ning Zheng2Hui Jun Geng3Lei Chen4Jun Hu Yao5Lu Deng6College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, ChinaCollege of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, ChinaCollege of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, ChinaCollege of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, ChinaCollege of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, ChinaCorresponding authors.; College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, ChinaCorresponding authors.; College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, ChinaEnhancing 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.http://www.sciencedirect.com/science/article/pii/S2405654523000902PropionateGluconeogenesisMechanistic target of rapamycinPalmitic acid |
| spellingShingle | Guo Yan Wang Sen Lin Qin Yi Ning Zheng Hui Jun Geng Lei Chen Jun Hu Yao Lu Deng Propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin (mTOR) pathway in calf hepatocytes Animal Nutrition Propionate Gluconeogenesis Mechanistic target of rapamycin Palmitic acid |
| title | Propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin (mTOR) pathway in calf hepatocytes |
| title_full | Propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin (mTOR) pathway in calf hepatocytes |
| title_fullStr | Propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin (mTOR) pathway in calf hepatocytes |
| title_full_unstemmed | Propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin (mTOR) pathway in calf hepatocytes |
| title_short | Propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin (mTOR) pathway in calf hepatocytes |
| title_sort | propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin mtor pathway in calf hepatocytes |
| topic | Propionate Gluconeogenesis Mechanistic target of rapamycin Palmitic acid |
| url | http://www.sciencedirect.com/science/article/pii/S2405654523000902 |
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