Gut microbiota composition combined with reduced intestinal fatty acid uptake prevents hepatic steatosis in obesity-resistant mice fed a high-fat diet

Abstract The metabolic response to excessive caloric intake varies and some individuals remain resistant to obesity with different tendencies to develop hepatic steatosis. Gut microbiota may play a crucial role in these differences by influencing energy utilization. The aim of this study was to investigate gut microbiota composition that may underlie variations in the occurrence of hepatic steatosis between obese and obesity-resistant mice. After 14 weeks on a high-fat diet (60 kcal% fat), the male C57BL/6J mice with the highest body mass were categorized as obese, while the animals without weight gain were selected as obesity-resistant. Despite similar caloric intake, obesity-resistant mice had lower liver mass and serum triglyceride levels compared to obese animals. The gut microbiota profile of the obesity-resistant mice was characterized by an increased abundance of RF39 and Lactobacillus, which was negatively correlated with triglyceride levels, and a lower abundance of Helicobacter and Rothia. These changes paralleled the improved gut morphology and decreased protein levels of free fatty acid transporters in the small intestine and liver of the obesity-resistant mice. In summary, gut microbiota composition of obesity-resistant animals in combination with the reduced intestinal capacity for fatty acid uptake can influence the lipid influx into the liver and ultimately prevent ectopic fat accumulation.