The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α
Cattle can efficiently perform de novo generation of glucose through hepatic gluconeogenesis to meet post-weaning glucose demand. Substantial evidence points to cattle and non-ruminant animals being characterized by phylogenetic features in terms of their differing capacity for hepatic gluconeogenes...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2022-12-01
|
| Series: | Animal Nutrition |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405654522000968 |
| _version_ | 1797975179607932928 |
|---|---|
| author | Guoyan Wang Jun Zhang Shengru Wu Senlin Qin Yining Zheng Chao Xia Huijun Geng Junhu Yao Lu Deng |
| author_facet | Guoyan Wang Jun Zhang Shengru Wu Senlin Qin Yining Zheng Chao Xia Huijun Geng Junhu Yao Lu Deng |
| author_sort | Guoyan Wang |
| collection | DOAJ |
| description | Cattle can efficiently perform de novo generation of glucose through hepatic gluconeogenesis to meet post-weaning glucose demand. Substantial evidence points to cattle and non-ruminant animals being characterized by phylogenetic features in terms of their differing capacity for hepatic gluconeogenesis, a process that is highly efficient in cattle yet the underlying mechanism remains unclear. Here we used a variety of transcriptome data, as well as tissue and cell-based methods to uncover the mechanisms of high-efficiency hepatic gluconeogenesis in cattle. We showed that cattle can efficiently convert propionate into pyruvate, at least partly, via high expression of acyl-CoA synthetase short-chain family member 1 (ACSS1), propionyl-CoA carboxylase alpha chain (PCCA), methylmalonyl-CoA epimerase (MCEE), methylmalonyl-CoA mutase (MMUT), and succinate-CoA ligase (SUCLG2) genes in the liver (P < 0.01). Moreover, higher expression of the rate-limiting enzymes of gluconeogenesis, such as phosphoenolpyruvate carboxykinase (PCK) and fructose 1,6-bisphosphatase (FBP), ensures the efficient operation of hepatic gluconeogenesis in cattle (P < 0.01). Mechanistically, we found that cattle liver exhibits highly active mechanistic target of rapamycin complex 1 (mTORC1), and the expressions of PCCA, MMUT, SUCLG2, PCK, and FBP genes are regulated by the activation of mTORC1 (P < 0.001). Finally, our results showed that mTORC1 promotes hepatic gluconeogenesis in a peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) dependent manner. Collectively, our results not only revealed an important mechanism responsible for the quantitative differences in the efficiency of hepatic gluconeogenesis in cattle versus non-ruminant animals, but also established that mTORC1 is indeed involved in the regulation of hepatic gluconeogenesis through PGC-1α. These results provide a novel potential insight into promoting hepatic gluconeogenesis through activated mTORC1 in both ruminants and mammals. |
| first_indexed | 2024-04-11T04:31:28Z |
| format | Article |
| id | doaj.art-72bd791be9cb48de97e5d8b327467934 |
| institution | Directory Open Access Journal |
| issn | 2405-6545 |
| language | English |
| last_indexed | 2024-04-11T04:31:28Z |
| publishDate | 2022-12-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Animal Nutrition |
| spelling | doaj.art-72bd791be9cb48de97e5d8b3274679342022-12-29T04:13:28ZengKeAi Communications Co., Ltd.Animal Nutrition2405-65452022-12-0111121131The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1αGuoyan Wang0Jun Zhang1Shengru Wu2Senlin Qin3Yining Zheng4Chao Xia5Huijun Geng6Junhu Yao7Lu Deng8College 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, 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, ChinaCattle can efficiently perform de novo generation of glucose through hepatic gluconeogenesis to meet post-weaning glucose demand. Substantial evidence points to cattle and non-ruminant animals being characterized by phylogenetic features in terms of their differing capacity for hepatic gluconeogenesis, a process that is highly efficient in cattle yet the underlying mechanism remains unclear. Here we used a variety of transcriptome data, as well as tissue and cell-based methods to uncover the mechanisms of high-efficiency hepatic gluconeogenesis in cattle. We showed that cattle can efficiently convert propionate into pyruvate, at least partly, via high expression of acyl-CoA synthetase short-chain family member 1 (ACSS1), propionyl-CoA carboxylase alpha chain (PCCA), methylmalonyl-CoA epimerase (MCEE), methylmalonyl-CoA mutase (MMUT), and succinate-CoA ligase (SUCLG2) genes in the liver (P < 0.01). Moreover, higher expression of the rate-limiting enzymes of gluconeogenesis, such as phosphoenolpyruvate carboxykinase (PCK) and fructose 1,6-bisphosphatase (FBP), ensures the efficient operation of hepatic gluconeogenesis in cattle (P < 0.01). Mechanistically, we found that cattle liver exhibits highly active mechanistic target of rapamycin complex 1 (mTORC1), and the expressions of PCCA, MMUT, SUCLG2, PCK, and FBP genes are regulated by the activation of mTORC1 (P < 0.001). Finally, our results showed that mTORC1 promotes hepatic gluconeogenesis in a peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) dependent manner. Collectively, our results not only revealed an important mechanism responsible for the quantitative differences in the efficiency of hepatic gluconeogenesis in cattle versus non-ruminant animals, but also established that mTORC1 is indeed involved in the regulation of hepatic gluconeogenesis through PGC-1α. These results provide a novel potential insight into promoting hepatic gluconeogenesis through activated mTORC1 in both ruminants and mammals.http://www.sciencedirect.com/science/article/pii/S2405654522000968Hepatic gluconeogenesisCattlemTORC1Peroxisome-proliferator-activated receptor γ coactivator-1α |
| spellingShingle | Guoyan Wang Jun Zhang Shengru Wu Senlin Qin Yining Zheng Chao Xia Huijun Geng Junhu Yao Lu Deng The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α Animal Nutrition Hepatic gluconeogenesis Cattle mTORC1 Peroxisome-proliferator-activated receptor γ coactivator-1α |
| title | The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α |
| title_full | The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α |
| title_fullStr | The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α |
| title_full_unstemmed | The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α |
| title_short | The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α |
| title_sort | mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome proliferator activated receptor γ coactivator 1α |
| topic | Hepatic gluconeogenesis Cattle mTORC1 Peroxisome-proliferator-activated receptor γ coactivator-1α |
| url | http://www.sciencedirect.com/science/article/pii/S2405654522000968 |
| work_keys_str_mv | AT guoyanwang themechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT junzhang themechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT shengruwu themechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT senlinqin themechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT yiningzheng themechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT chaoxia themechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT huijungeng themechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT junhuyao themechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT ludeng themechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT guoyanwang mechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT junzhang mechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT shengruwu mechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT senlinqin mechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT yiningzheng mechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT chaoxia mechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT huijungeng mechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT junhuyao mechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a AT ludeng mechanistictargetofrapamycincomplex1pathwayinvolvedinhepaticgluconeogenesisthroughperoxisomeproliferatoractivatedreceptorgcoactivator1a |