Sirt1 and Sirt6 Mediate Beneficial Effects of Rosiglitazone on Hepatic Lipid AccumulationReportar como inadecuado




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Background

Sirtuin Sirt, a sensor of the cell metabolic state, regulates glucose and lipid metabolism. The aim of this study was to address whether rosiglitazone RGZ alters hepatic Sirt1 and whether Sirt1 and-or Sirt6 have a regulatory role in the protective effects of RGZ on hepatocyte steatosis.

Methods

To investigate the effect of RGZ on hepatic Sirt1, rats were administered with RGZ for 6 weeks. The involvement of Sirt1-6 in the RGZ-mediated effect against hepatic steatosis was evaluated by single or double knockdown of Sirt1 and Sirt6 in a hepatocyte steatosis model.

Results

RGZ in vivo increased Sirt1 expression and its activity in rat livers. In a hepatocyte steatosis model, RGZ significantly reduced lipid accumulation and activated the Sirt1-6-LKB1-AMPK pathway. Sirt1 knockdown abolished the effects of RGZ with regard to hepatocyte fat accumulation and the Sirt1-6-LKB1-AMPK pathway, suggesting that Sirt1 is a key regulator of RGZ-mediated metabolic processes. Sirt6 knockdown inhibited the protective effects of RGZ to a lesser extent than Sirt1, and double knockdown of Sirt1-6 showed no synergistic effects.

Conclusion

Our results demonstrate that Sirt1-6 are involved in the RGZ-mediated effects on hepatocyte steatosis, and the regulatory effects of Sirt1 and Sirt6 are not synergistic but compensatory for improving hepatocyte steatosis.



Autor: Soo Jin Yang, Jung Mook Choi, Eugene Chang, Sung Woo Park, Cheol-Young Park

Fuente: http://plos.srce.hr/



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