title: Apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ.
abstract: Apelin, a novel adipokine, is the specific endogenous ligand of G protein-coupled receptor APJ. Consistent with its putative role as an adipokine, apelin has been linked to states of insulin resistance. However, the function of apelin in hepatic insulin resistance, a vital part of insulin resistance, and its underlying mechanisms still remains unclear. Here we define the impacts of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes. Our studies indicate that apelin reversed TNF-α-induced reduction of glycogen synthesis in HepG2 cells, mouse primary hepatocytes and liver tissues of C57BL/6J mice by improving JNK-IRS1-AKT-GSK pathway. Moreover, Western blot revealed that APJ, but not apelin, expressed in the hepatocytes and liver tissues of mice. We found that F13A, a competitive antagonist for G protein-coupled receptor APJ, suppressed the effects of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes, suggesting APJ is involved in the function of apelin. In conclusion, we show novel evidence suggesting that apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ. Apelin appears as a beneficial adipokine with anti-insulin resistance properties, and thus as a promising therapeutic target in metabolic disorders.
authors: Key Laboratory of Geriatrics, Beijing Institute of Geriatrics & Beijing Hospital, Ministry of Health, Beijing, China.
authors: Jiaojiao
authors: J
authors: Chu
authors: Hangxiang
authors: H
authors: Zhang
authors: Xiuqing
authors: X
authors: Huang
authors: Yajun
authors: Y
authors: Lin
authors: Tao
authors: T
authors: Shen
authors: Beidong
authors: B
authors: Chen
authors: Yong
authors: Y
authors: Man
authors: Shu
authors: S
authors: Wang
authors: Jian
authors: J
authors: Li
mesh_terms: D054392:Adipokines; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D005786:Gene Expression Regulation / Q000187:drug effects; D006003:Glycogen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D061251:Primary Cell Culture; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C532492:apelin-13, Ala(13)-; D006003:Glycogen