MiR-155 Has a Protective Role in the Development of Non-Alcoholic Hepatosteatosis in MiceReportar como inadecuado

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Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs miRs are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL-6 wild-type WT and miR-155−-− mice were fed either normal chow or high fat diet HFD for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL-LDL cholesterol and alanine transaminase ALT levels, as well as increased hepatic expression of genes involved in glucose regulation Pck1, Cebpa, fatty acid uptake Cd36 and lipid metabolism Fasn, Fabp4, Lpl, Abcd2, Pla2g7. Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−-− livers, we identified and validated that Nr1h3 LXRα as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−-− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes.

Autor: Ashley M. Miller, Derek S. Gilchrist, Jagtar Nijjar, Elisa Araldi, Cristina M. Ramirez, Christopher A. Lavery, Carlos Fernández-

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


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