👤 Quinten R Ducarmon

Lifestyle interventions, such as diet and exercise, are currently the main therapies against metabolic dysfunction-associated steatotic liver disease (MASLD). However, not much is known about the combined impact of fiber and exercise on the modulation of gut-liver axis and MASLD amelioration. Here, we studied the impact of the combination of exercise training and a fiber-rich diet on the amelioration of MASLD. Male APOE*3-Leiden.CETP mice were fed a high-fat high-cholesterol diet with or without the addition of fiber (10% inulin) and exercise trained on a treadmill, or remained sedentary. Exercise training and fiber supplementation reduced fat mass gain and lowered plasma glucose levels. Only the combination treatment, however, induced fat loss and decreased plasma triglyceride and cholesterol levels compared with sedentary control mice. Exercise training with and without the addition of fiber had a similar ameliorating effect on the MASLD score. Only exercise without fiber decreased the hepatic expression of inflammatory markers. Fiber diet was mainly responsible for remodeling the gut microbial composition, with an increase in the relative abundance of the short-chain fatty acid (SCFA)-producing genera Show less

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; L-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as Akkermansia, Lachnospiraceae, and Rikenella. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis. Show less