(P15-023-24) Jackfruit Flour Fortified Diet Prevents Obesity and Metabolic Dysfunction-Associated Steatohepatitis via the Gut-Liver Axis

Objectives: The escalating prevalence of metabolic dysfunction-associated steatohepatitis (MASH) is a global health burden attributed to the surging rates of obesity and sedentary lifestyles. The use of green jackfruit flour (Jackfruit365™) fortified diet has been shown to achieve optimal glycemic control in patients with type 2 diabetes. Here, we evaluated the efficacy of green jackfruit flour (JF-5 kcal%) as a dietary intervention for the prevention of obesity and MASH and its underlying mechanisms.

Methods: A preclinical model that closely mimics human MASH was employed, subjecting the C57Bl/6 mice to either chow diet normal water (CDNW) or western diet sugar water (WDSW). Following 12 weeks, mice were randomized to receive (i) CDNW+placebo (wheat flour), (ii) CDNW+JF, (iii) WDSW+placebo, or (iv) WDSW+JF for an additional 12 weeks. Food intake and body weight were measured weekly. Histological, biochemical, and molecular analyses were performed to evaluate liver injury, inflammation, and fibrosis. Experiments were also carried out in the in vitro MASH model using the human hepatoma cell line, HepG2 cells.

Results: JF significantly prevented the increase in body weight in WDSW fed mice, reduced liver weight, and also improved insulin sensitivity compared to placebo. WDSW+JF mice showed positive outcomes in liver function tests, histopathological evaluation, and improved MASH scoring and fibrosis. Inflammatory and lipogenesis markers were significantly downregulated in the WDSW+JF mice. Furthermore, the liver tissues of WDSW+JF mice showed increased levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK), which inhibits hepatic lipogenesis. In line with these findings, AMPK signaling was similarly activated in HepG2 cells loaded with oleate or palmitate and treated with propionate, a short-chain fatty acid resulting from the microbial fermentation of soluble fibers in JF.

Conclusions: Our study provides the first evidence that 5% calorie replacement with jackfruit flour improves metabolic health in WDSW mice via the gut-liver axis, underscoring its therapeutic significance in preventing obesity and MASH.

Funding Sources: Department of Biotechnology (DBT), Science and Engineering Research Board (SERB), and God’s Own Food Solutions Pvt. Ltd