Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systems

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious public health concern. Given the paucity of approved therapeutic strategies for this lifestyle disorder, dietary interventions may prove effective. We evaluated the mechanisms of how green jackfruit flour (JF) ameliorates metabolic-dysfunction-associated steatohepatitis (MASH) and halts the progression to hepatocellular carcinoma (HCC). The study used murine models of MASH and MASH-HCC that closely mimic human MASLD. C57Bl/6 male mice were fed with chow or western diet with normal or sugar water for 12 weeks, then randomized to receive either 5 kcal% green jackfruit flour (JF) or an equal volume of placebo flour (PB). JF significantly reduced body weight, liver injury, and insulin resistance, and alleviated obesity, steatosis, inflammation, fibrosis, and tumor development in WDSW or WDSW/CCl₄ mice compared to placebo. Furthermore, JF activated AMPK (AMP-activated protein kinase) and inhibited MAPK (mitogen-activated protein kinase) signaling pathways in MASH and MASH-HCC models, respectively. Sodium propionate treatment, the primary short-chain fatty acid entering the liver from JF's soluble fiber microbial fermentation, further supported these mechanistic insights. Hence, our findings present strong evidence of JF's therapeutic potential in attenuating MASH and MASH-HCC, warranting further investigation of JF's efficacy as a dietary intervention in clinical trials.