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Abrogation of Hepatic ATP-Citrate Lyase Protects Against Fatty Liver and Ameliorates Hyperglycemia in Leptin Receptor-Deficient Mice
文献类型：期刊论文
| 作者 | Wang, Qiong; Jiang, Lei; Wang, Jue; Li, Shoufeng; Yu, Yue; You, Jia; Zeng, Rong; Gao, Xiang; Rui, Liangyou; Li, Wenjun |
| 刊名 | HEPATOLOGY
 |
| 出版日期 | 2009 |
| 卷号 | 49期号:4页码:1166-1175 |
| 通讯作者 | Liu, Y (reprint author), Chinese Acad Sci, Inst Nutr Sci, Grad Sch, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China. |
| 英文摘要 | Hepatic steatosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and a key component of obesity-associated metabolic dysfunctions featuring dyslipidemia, insulin resistance, and loss of glycemic control. It has yet to be completely understood how much dysregulated de novo lipogenesis contributes to the pathogenic development of hepatic steatosis and insulin resistance. ATP-citrate lyase (ACL) is a lipogenic enzyme that catalyzes the critical reaction linking cellular glucose catabolism and lipogenesis, converting cytosolic citrate to acetyl-coenzyme A (CoA). Acetyl-CoA is further converted to malonyl-CoA, the essential precursor for fatty acid biosynthesis. We investigated whether dysregulation of hepatic ACL is metabolically connected to hepatic steatosis, insulin resistance, and hyperglycemia. We found that in leptin receptor-deficient db/db mice, the expression of ACL was selectively elevated in the liver but not in the white adipose tissue. Liver-specific ACL abrogation via adenovirus-mediated RNA interference prominently reduced the hepatic contents of both acetyl-CoA and malonyl-CoA, markedly inhibited hepatic de novo lipogenesis, and protected against hepatic steatosis in db/db mice. Surprisingly, liver-specific ACL abrogation markedly inhibited the expression of peroxisome proliferator-activated receptor-gamma and the entire lipogenic program in the liver. Moreover, hepatic ACL deficiency resulted in significantly down-regulated expression of gluconeogenic genes in the liver as well as enhanced insulin sensitivity in the muscle, leading to substantially improved systemic glucose metabolism. Conclusion: These findings establish a crucial role of hepatic ACL in lipid and glucose metabolism; therefore, hepatic ACL may serve as a potential target to treat NAFLD and type 2 diabetes. (HEPATOLOGY 2009;49:1166-1175.) |
| 类目[WOS] | Gastroenterology & Hepatology |
| 研究领域[WOS] | Gastroenterology & Hepatology |
| 关键词[WOS] | INDUCED INSULIN-RESISTANCE ; ACETYL-COA CARBOXYLASE-1 ; PPAR-ALPHA ; METABOLIC SYNDROME ; ACID SYNTHESIS ; NONALCOHOLIC STEATOHEPATITIS ; TRANSCRIPTION FACTOR ; MOUSE-LIVER ; MALONYL-COA ; STEATOSIS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000264862100014 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/298]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 |
| 推荐引用方式 GB/T 7714 | Wang, Qiong,Jiang, Lei,Wang, Jue,et al. Abrogation of Hepatic ATP-Citrate Lyase Protects Against Fatty Liver and Ameliorates Hyperglycemia in Leptin Receptor-Deficient Mice[J]. HEPATOLOGY,2009,49(4):1166-1175. |
| APA | Wang, Qiong.,Jiang, Lei.,Wang, Jue.,Li, Shoufeng.,Yu, Yue.,...&Liu, Yong.(2009).Abrogation of Hepatic ATP-Citrate Lyase Protects Against Fatty Liver and Ameliorates Hyperglycemia in Leptin Receptor-Deficient Mice.HEPATOLOGY,49(4),1166-1175. |
| MLA | Wang, Qiong,et al."Abrogation of Hepatic ATP-Citrate Lyase Protects Against Fatty Liver and Ameliorates Hyperglycemia in Leptin Receptor-Deficient Mice".HEPATOLOGY 49.4(2009):1166-1175. |
入库方式： OAI收割
来源：上海营养与健康研究所
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