Docosahexaenoic acid attenuates Western diet-induced hepatic fibrosis in Ldlr-/- mice by targeting the TGFβ-Smad3 pathway.

ABSTRACT: DHA (22:6,ω3), but not EPA (20:5,ω3), attenuates Western diet (WD)-induced hepatic fibrosis in a Ldlr(-/-) mouse model of nonalcoholic steatohepatitis. We examined the molecular basis for the differential effect of dietary EPA and DHA on WD-induced hepatic fibrosis. DHA was more effective than EPA at preventing WD-induced effects on hepatic transcripts linked to fibrosis, including collagen 1A1 (Col1A1), transforming growth factor-β (TGFβ) signaling and proteins involved in remodeling the extracellular matrix, including metalloproteases, tissue inhibitors of metalloproteases, and lysyl oxidase subtypes. Examination of the TGFβ pathway showed that mice fed the WD supplemented with either olive oil or EPA had a significant (≥2.5-fold) increase in hepatic nuclear abundance of phospho-mothers

SUBMITTER: Lytle KA 

PROVIDER: S-EPMC4583081 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature