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Yu, A; Zheng, Y; Zhang, R; Huang, J; Zhu, Z; Zhou, R; Jin, D; Yang, Z.
Resistin impairs SIRT1 function and induces senescence-associated phenotype in hepatocytes.
Mol Cell Endocrinol. 2013; 377(1-2):23-32 Doi: 10.1016/j.mce.2013.06.028
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Co-Autor*innen der Med Uni Graz
Huang Jianfeng
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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.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Cell Aging - drug effects
DNA - metabolism
Gene Expression Regulation - drug effects
Hep G2 Cells -
Hepatocytes - cytology
Humans -
Male -
Mice -
Mice, Inbred C57BL -
MicroRNAs - genetics
Phenotype -
Protein Binding - drug effects
Resistin - pharmacology
Sirtuin 1 - genetics
Transcription, Genetic - drug effects
beta-Galactosidase - metabolism

Find related publications in this database (Keywords)
Resistin
SIRT1
Hepatocytes
PPAR alpha
PGC-1 alpha
Senescence-associated beta-galactosidase activity
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