Lack of liver steatosis in germ-free mice following hypercaloric diets

Purpose Experimental liver steatosis induced by overfeeding is associated with enhanced gut permeability and endotoxin translocation to the liver. We examined the role of the gut microbiota for steatosis formation by performing the feeding experiments in mice raised under conventional and germ-free (GF) housing. Methods Adult wild-type and GF mice were fed a Western-style diet (WSD) or a control diet (CD), the latter combined with liquid fructose supplementation (F) or not, for 8 weeks. Markers of liver steatosis and gut permeability were measured after intervention. Results Mice fed a WSD increased body weight compared to those fed a CD (p<0.01) under conventional, but not under GF conditions. Increased liver weight, liver-to-body-weight ratio and hepatic triglycerides observed in both the WSD and the CD+F groups, when compared with the CD group, were not apparent under GF conditions, whereas elevated plasma triglycerides were visible (p<0.05). Wild-type mice fed a WSD or a CD+F, respectively, had thinner adherent mucus layer compared to those fed a CD (p<0.01), whereas GF mice had always a thin mucus layer independently of the diet. GF mice fed a CD showed increased plasma levels of FITC-dextran 4000 (1.9-fold, p<0.05) and intestinal fatty acid-binding protein-2 (2.4-fold, p<0.05) compared with wild-type mice. Conclusions GF housing results in an impaired weight gain and a lack of steatosis following a WSD. Also the fructose-induced steatosis, which is unrelated to body weight changes, is absent in GF mice. Thus, diet-induced experimental liver steatosis depends in multiple ways on intestinal bacteria.