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http://ntour.ntou.edu.tw:8080/ir/handle/987654321/45549
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| Title: | Glucagon regulates ACC activity in adipocytes through the CAMKKβ/AMPK pathway. |
| Authors: | I-Chen Peng;Zhen Chen;Wei Sun;Ying-Shiuan Li;Traci LaNai Marin;Pang-Hung Hsu;Mei-I Su;Xiaopei Cui;Songqin Pan;Christian Y. Lytle;David A. Johnson;Frank Blaeser;Talal Chatila;John Y-J. Shyy |
| Contributors: | 國立臺灣海洋大學：生命科學系 |
| Date: | 2012
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| Issue Date: | 2018-03-26T06:10:07Z
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| Publisher: | American Physiological Society |
| Abstract: | Abstract: Glucagon is important for regulating lipid metabolism in part through its inhibition of fatty acid synthesis in adipocytes. Acetyl-CoA carboxylase 1 (ACC1) is the rate-limiting enzyme for fatty acid synthesis. Glucagon has been proposed to activate cAMP-dependent protein kinase A (PKA), which phosphorylates ACC1 to attenuate the lipogenic activity of ACC1. Because AMP-activated protein kinase (AMPK) also inhibits fatty acid synthesis by phosphorylation of ACC1, we examined the involvement of AMPK and its upstream kinase in the glucagon-elicited signaling in adipocytes in vitro and in vivo. LC-MS-MS analysis suggested that ACC1 was phosphorylated only at Ser79, an AMPK-specific site, in glucagon-treated adipocytes. Pharmacological inhibitors and siRNA knockdown of AMPK or PKA in adipocytes demonstrate that glucagon regulates ACC1 and ACC2 activity through AMPK but not PKA. By using Ca2+/calmodulin-dependent protein kinase kinase-β knockout (CaMKKβ−/−) mice and cultured adipocytes, we further show that glucagon activates the CaMKKβ/AMPK/ACC cascade. Additionally, fasting increases the phosphorylation of AMPK and ACC in CaMKKβ+/+ but not CaMKKβ−/− mice. These results indicate that CaMKKβ/AMPK signaling is an important molecular component in regulating lipid metabolism in adipocytes responding to glucagon and could be a therapeutic target for the dysregulation of energy storage. |
| Relation: | 302(12) |
| URI: | http://ntour.ntou.edu.tw:8080/ir/handle/987654321/45549 |
| Appears in Collections: | [生命科學系] 期刊論文
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