IRW prevents diet-induced non-alcoholic fatty liver disease by preserving mitochondrial content and enhancing hepatic fatty acid oxidation capacity

Abstract

Abstract Non-alcoholic fatty liver disease (NAFLD) the hepatic manifestation of the metabolic syndrome, remains without approved pharmacological treatment, with lifestyle modifications being the first line of therapy. Alternative approaches, including food-derived bioactive peptides can aid in the management of metabolic conditions including hypertension, obesity and insulin resistance. IRW is a tripeptide produced from the egg white protein ovotransferrin with angiotensin converting enzyme-inhibitory properties. Previous studies reveal that IRW supplementation elicits antihypertensive effects, improves skeletal muscle insulin signaling and glucose tolerance, while reducing BW gain. In this study, we hypothesized that IRW45 supplementation would prevent high-fat diet-induced NAFLD by modulating hepatic lipid metabolism and preserving mitochondrial content. We found that IRW45 prevents diet-induced NAFLD, while rosiglitazone (ROSI) treatment worsens it. IRW45 decreases hepatic triglyceride content and lipid droplet size compared to HFD and ROSI. This is accompanied by a trend to increase hepatic Ppargc1a gene expression and increase Cd36 compared to HFD. Moreover, IRW45 increases the hepatic mitochondrial complexes, p-AMPKα and has a trend to increase p-ACC abundance compared to HFD. Therefore, IRW45 prevents diet-induced NAFLD, in part by preserving mitochondrial content and increasing hepatic lipid oxidation capacity.