PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α
PGC-1α plays a central role in hepatic gluconeogenesis and has been implicated in the onset of type 2 diabetes. Acetylation is an important posttranslational modification for regulating the transcriptional activity of PGC-1α. Here, we show that PCAF is a pivotal acetyltransferase for acetylating PGC...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714009954 |
| _version_ | 1811294847837929472 |
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| author | Cheng Sun Meihong Wang Xiaoyu Liu Lan Luo Kaixuan Li Shuqiang Zhang Yongjun Wang Yumin Yang Fei Ding Xiaosong Gu |
| author_facet | Cheng Sun Meihong Wang Xiaoyu Liu Lan Luo Kaixuan Li Shuqiang Zhang Yongjun Wang Yumin Yang Fei Ding Xiaosong Gu |
| author_sort | Cheng Sun |
| collection | DOAJ |
| description | PGC-1α plays a central role in hepatic gluconeogenesis and has been implicated in the onset of type 2 diabetes. Acetylation is an important posttranslational modification for regulating the transcriptional activity of PGC-1α. Here, we show that PCAF is a pivotal acetyltransferase for acetylating PGC-1α in both fasted and diabetic states. PCAF acetylates two lysine residues K328 and K450 in PGC-1α, which subsequently triggers its proteasomal degradation and suppresses its transcriptional activity. Adenoviral-mediated expression of PCAF in the obese mouse liver greatly represses gluconeogenic enzyme activation and glucose production and improves glucose homeostasis and insulin sensitivity. Moreover, liver-specific knockdown of PCAF stimulates PGC-1α activity, resulting in an increase in blood glucose and hepatic glucose output. Our results suggest that PCAF might be a potential pharmacological target for developing agents against metabolic disorders associated with hyperglycemia, such as obesity and diabetes. |
| first_indexed | 2024-04-13T05:23:39Z |
| format | Article |
| id | doaj.art-15ad1a4e123b4512a30c882c001a8bb8 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T05:23:39Z |
| publishDate | 2014-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-15ad1a4e123b4512a30c882c001a8bb82022-12-22T03:00:40ZengElsevierCell Reports2211-12472014-12-01962250226210.1016/j.celrep.2014.11.029PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1αCheng Sun0Meihong Wang1Xiaoyu Liu2Lan Luo3Kaixuan Li4Shuqiang Zhang5Yongjun Wang6Yumin Yang7Fei Ding8Xiaosong Gu9Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PRCJiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PRCJiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PRCDepartment of Geratology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PRCDepartment of Geratology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PRCJiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PRCJiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PRCJiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PRCJiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PRCJiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PRCPGC-1α plays a central role in hepatic gluconeogenesis and has been implicated in the onset of type 2 diabetes. Acetylation is an important posttranslational modification for regulating the transcriptional activity of PGC-1α. Here, we show that PCAF is a pivotal acetyltransferase for acetylating PGC-1α in both fasted and diabetic states. PCAF acetylates two lysine residues K328 and K450 in PGC-1α, which subsequently triggers its proteasomal degradation and suppresses its transcriptional activity. Adenoviral-mediated expression of PCAF in the obese mouse liver greatly represses gluconeogenic enzyme activation and glucose production and improves glucose homeostasis and insulin sensitivity. Moreover, liver-specific knockdown of PCAF stimulates PGC-1α activity, resulting in an increase in blood glucose and hepatic glucose output. Our results suggest that PCAF might be a potential pharmacological target for developing agents against metabolic disorders associated with hyperglycemia, such as obesity and diabetes.http://www.sciencedirect.com/science/article/pii/S2211124714009954 |
| spellingShingle | Cheng Sun Meihong Wang Xiaoyu Liu Lan Luo Kaixuan Li Shuqiang Zhang Yongjun Wang Yumin Yang Fei Ding Xiaosong Gu PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α Cell Reports |
| title | PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α |
| title_full | PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α |
| title_fullStr | PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α |
| title_full_unstemmed | PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α |
| title_short | PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α |
| title_sort | pcaf improves glucose homeostasis by suppressing the gluconeogenic activity of pgc 1α |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714009954 |
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