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Publication : Resistin impairs SIRT1 function and induces senescence-associated phenotype in hepatocytes.

First Author  Yu A Year  2013
Journal  Mol Cell Endocrinol Volume  377
Issue  1-2 Pages  23-32
PubMed ID  23827175 Mgi Jnum  J:210783
Mgi Id  MGI:5571824 Doi  10.1016/j.mce.2013.06.028
Citation  Yu A, et al. (2013) Resistin impairs SIRT1 function and induces senescence-associated phenotype in hepatocytes. Mol Cell Endocrinol 377(1-2):23-32
abstractText  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 PPARalpha as well as PGC-1alpha, and increases PGC-1alpha 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 beta-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.
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