title: Hepatoprotective effects of AdipoRon against d-galactosamine-induced liver injury in mice.
abstract: Adiponectin is an antidiabetic and antiatherogenic adipokine, which plays distinct roles in the balance of energy homoeostasis. As an insulin sensitizing hormone, adiponectin exerts multiple biological effects by the specific receptors (AdipoR1 and AdipoR2), through activation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)α pathways. AdipoRon, an orally active synthetic small-molecule AdipoR agonist, shows very similar effects to adiponectin in vitro and in vivo, which could be a promising therapeutic approach for obesity-related disorders. In view of the regulatory effects of adiponectin or AdipoRon on inflammatory response and energy metabolism, they might be endowed a curative potential for tissue damage. Hence, its effects and possible mechanism were investigated. In vitro studies on hepatocytes (L02) and macrophages (RAW264.7) suggested a protective and anti-inflammatory potential of AdipoRon. The effects were verified in acute hepatic injury mice induced by d-galactosamine (D-GalN): hepatic lesions were restored by AdipoRon or bicyclol (positive reference drug) pretreatment, which were characterized by a significant increase in serological and hepatic biomarkers (AST, ALT, MDA and NOSs). Besides, AdipoRon attenuated the inflammation in the liver, characterized by the dwindling proinflammatory macrophage infiltration, as well as the shrinkage of tumor necrosis factor-α (TNF-α), transforming growth factor beta 1 (TGF-β1), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6); meanwhile conversely promoted AMPK activation by phosphorylation. Combined with liver histopathology, these results demonstrated the hepatoprotective effects of AdipoRon against D-GalN-induced damage, which might be ascribed to the attenuation of inflammation, inhibition of free radical reactions, as well as enhancement of liver energy metabolism.
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Ying
authors: Y
authors: Wang
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Yumeng
authors: Y
authors: Wan
authors: High School Affiliated To Nanjing Normal University, Nanjing 210003, PR China.
authors: Guihong
authors: G
authors: Ye
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Pu
authors: P
authors: Wang
authors: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Xiaowen
authors: X
authors: Xue
authors: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Guanzhong
authors: G
authors: Wu
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: yebp@cpu.edu.cn.
authors: Boping
authors: B
authors: Ye
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D005688:Galactosamine / Q000009:adverse effects*; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000494:pharmacology*
chemical_list: C585113:AdipoRon; D010880:Piperidines; D005688:Galactosamine
keywords: AdipoR agonist; AdipoRon; Hepatic injury; Hepatoprotective effects; Inflammation; d-Galactosamine (D-GalN)