The polyphenol-rich plant extract Totum-448 decreases hepatic steatosis and inflammation in diet-induced MASLD mice

Abstract The increasing prevalence of obesity-driven metabolic dysfunction-associated steatotic liver disease (MASLD) urges the development of new therapeutic strategies. Totum-448 is a patented blend of polyphenol-rich plant extracts designed to reduce hepatic steatosis, a key risk factor for steatohepatitis and type 2 diabetes. In a mouse model of MASLD, Totum-448 (1.5% w/w) significantly improved metabolic homeostasis by lowering hyperinsulinemia and systemic glucose intolerance, without affecting body weight, fat mass, or calorie intake. It also reduced hepatic steatosis and plasma alanine aminotransferase levels, as assessed by histological/biochemical assays and MS-based lipidomics. RNA sequencing and spectral flow cytometry approaches revealed that liver inflammation and pro-fibrotic gene expression were decreased, along with preservation of tissue-resident Kupffer cells and reduced recruitment of pro-inflammatory macrophages. These combined effects suggest that Totum-448 ameliorates both steatosis and hepatic inflammation, contributing to improved whole-body metabolic health. Totum-448 may represent a promising nutritional intervention for MASLD management in humans.