title: MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.
abstract: 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.
authors.affiliation: Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Miller
authors.forename: Derek S
authors.initials: DS
authors.lastname: Gilchrist
authors.forename: Jagtar
authors.initials: J
authors.lastname: Nijjar
authors.forename: Elisa
authors.initials: E
authors.lastname: Araldi
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Ramirez
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lavery
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Hernando
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Mariola
authors.initials: M
authors.lastname: Kurowska-Stolarska
mesh_terms: D000821:Animal Feed; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000378:metabolism / Q000517:prevention & control*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000502:physiology*; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse