Totum-448, a polyphenol-rich plant extract, decreases hepatic steatosis and inflammation in diet-induced MASLD mice
bioRxiv – March 24, 2025
Source: medRxiv/bioRxiv/arXiv
Summary
Obesity-related liver disease is on the rise, highlighting the need for effective treatments. A study found that Totum-448, a plant extract rich in polyphenols, significantly reduced liver fat and inflammation in mice with diet-induced metabolic issues. This suggests it could be a promising nutritional strategy for improving liver health in affected individuals.
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 unique patented combination of polyphenol-rich plant extracts designed to reduce hepatic steatosis, a risk factor for steatohepatitis and type 2 diabetes. In this study, we investigated the effects of Totum-448 on metabolic homeostasis and steatohepatitis in diet-induced MASLD mice. For this purpose, male C57Bl6/J mice were fed a high-fat diet in combination with sucrose-containing drinking water for 12 weeks, followed by diet supplementation with or without Totum-448 for 4 weeks. Body weight/composition, caloric intake, plasma parameters and whole-body glucose tolerance were measured throughout the study and fecal microbiota composition was determined by 16S sequencing. Hepatic steatosis, transcriptomic/lipidomic profiles and immune cell composition were assessed by histological/biochemical assays, RNA sequencing, MS-based lipidomics, and spectral flow cytometry. We found that Totum-448 significantly lowered hyperinsulinemia and systemic glucose intolerance in MASLD mice without affecting body weight, fat mass, calorie intake, feces production or fecal microbiota composition. Furthermore, a decrease in liver MASLD activity score and macrovesicular steatosis, hepatic triglycerides and cholesterol contents, and plasma alanine aminotransferase levels were observed. Totum-448 also reduced the liver inflammatory and pro-fibrotic transcriptomic signatures and decreased both MASLD-induced loss in tissue-resident Kupffer cells and recruitment of monocyte-derived pro-inflammatory macrophages. Altogether, Totum-448 reduces hepatic steatosis and inflammation in insulin-resistant, steatotic, obese mice, a dual effect that likely contributes to improved whole-body metabolic homeostasis. Supplementation with Totum-448 may therefore constitute a promising novel nutritional approach for MASLD patients.