title: Resistin impairs SIRT1 function and induces senescence-associated phenotype in hepatocytes.
abstract: Resistin is a cysteine-rich secreted protein which significantly inhibits phosphorylation of AMP-activated protein kinase in both human and mouse hepatocytes. It has been demonstrated that resistin plays an important role in inducing hepatic insulin resistance. However, whether resistin has other unknown influences on hepatocytes still remains poorly studied. Here, we show that recombinant resistin protein significantly reduces expression of SIRT1, attenuates the interaction between SIRT1 and PPARα as well as PGC-1α, and increases PGC-1α acetyl-lysine levels in HepG2 cells. In line with this, resistin treatment weakens the association between SIRT1 and major satellite repeats and alters the transcription level of SIRT1 target genes in mouse primary hepatocytes. Resistin treatment also significantly increases senescence-associated β-galactosidase activity in mouse primary hepatocytes and this effect can be eliminated by co-treatment with the SIRT1 agonists resveratrol and nicotinamide mononucleotide. Our findings suggest that resistin is a negative regulator of SIRT1 in both human hepatoma cell line HepG2 and mouse hepatocytes and that it might also play an important role in the development of senescence-associated liver diseases.
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, HuaZhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: An
authors.initials: A
authors.lastname: Yu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zhang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Huang
authors.forename: Zhoujie
authors.initials: Z
authors.lastname: Zhu
authors.forename: Ronghua
authors.initials: R
authors.lastname: Zhou
authors.forename: Dan
authors.initials: D
authors.lastname: Jin
authors.forename: Zaiqing
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D052243:Resistin / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D052243:Resistin; D004247:DNA; D001616:beta-Galactosidase; D056564:Sirtuin 1
keywords: Hepatocytes; PGC-1α; PPARα; Resistin; SIRT1; Senescence-associated β-galactosidase activity