Bergamot Polyphenols Reduce Hepatic Lipogenesis While Boosting Autophagy and Short-Chain Fatty Acid Production in a Murine "Cafeteria" Model of MASLD.

backgroundNon-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western countries, characterized by excessive fat storage in the form of lipid droplets (LDs) in hepatocytes; it is also called Metabolic-Associated Steatotic Liver Disease (MASLD), if coexisting with at least one cardiometabolic risk factor. Bergamot polyphenols (BPF) have been shown to counteract hepatic LD accumulation through potent lipogenesis suppression and associated metabolic benefits in Wistar rats, but their liver-specific anti-lipogenic effects may be species- and strain-dependent. RESULTS AND

methodsTo address this issue we examined the effect of a cafeteria diet (CAF) and BPF in C3H/HeOuJ mice, which are considered resistant to diet-induced MASLD and fibrosis. Interestingly, a 15-week CAF diet led to a robust LD accumulation, weak portal and focal inflammation, and induced a higher expression of lipogenesis (

conclusionsIn conclusion, while CAF diet supplementation in C3H/HeOuJ mice proves to be a suitable model of MASLD with deficient SCFA production, BPF confirms its potency to prevent murine MASLD by pleiotropic mechanisms, including beneficial effects on SCFA content, hepatic autophagy, and lipogenesis.