title: Protein phosphatase 4 promotes hepatic lipogenesis through dephosphorylating acetyl‑CoA carboxylase 1 on serine 79.
abstract: Reversible phosphorylation has a critical role in the regulation of the activity of acetyl‑CoA carboxylase 1 (ACC1), which is associated with de novo lipogenesis. It has been shown that AMP‑activated protein kinase (AMPK) phosphorylates ACC1 on serine 79 and inhibits its activity; however, the mechanism of ACC1 dephosphorylation remains elusive. Protein phosphatase 4 (PP4), a ubiquitous serine/threonine phosphatase, regulates a variety of cellular functions; however, whether PP4 is involved in lipid metabolism has yet to be elucidated. In the present study, PP4 was identified as a novel regulator of ACC1, which is also involved in hepatic lipogenesis. The expression of PP4 was found to be significantly increased in the livers of db/db mice. Furthermore, pACC1‑Ser79/ACC1 levels were observed to be decreased and high triglyceride accumulation was found in the livers of db/db mice. Moreover, PP4 overexpression was observed to lead to a decreased pACC1‑Ser79/ACC1 ratio and subsequently an increased intracellular triglyceride content in mouse primary hepatocytes. PP4 was also found to directly interact with pACC1‑Ser79 in human HepG2 cells. In conclusion, the present study showed that PP4 may be a novel regulator in hepatic lipogenesis through dephosphorylating ACC1 on serine 79, suggesting that PP4 may be a promising therapeutic target in lipid metabolism disorders.
authors: Peking University Fifth School of Clinical Medicine, Beijing Hospital, Ministry of Health, Beijing 100730, P.R. China.
authors: Xiangyu
authors: X
authors: Meng
authors: Peking University Fifth School of Clinical Medicine, Beijing Hospital, Ministry of Health, Beijing 100730, P.R. China.
authors: Meng
authors: M
authors: Li
authors: Peking University Fifth School of Clinical Medicine, Beijing Hospital, Ministry of Health, Beijing 100730, P.R. China.
authors: Jun
authors: J
authors: Guo
authors: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, P.R. China.
authors: Weiqing
authors: W
authors: Tang
authors: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, P.R. China.
authors: Shu
authors: S
authors: Wang
authors: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, P.R. China.
authors: Yong
authors: Y
authors: Man
authors: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, P.R. China.
authors: Xiuqing
authors: X
authors: Huang
authors: Peking University Fifth School of Clinical Medicine, Beijing Hospital, Ministry of Health, Beijing 100730, P.R. China.
authors: Jian
authors: J
authors: Li
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000737:chemistry / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014280:Triglycerides; D012694:Serine; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4; D000103:Acetyl-CoA Carboxylase