Effect of long-term ketogenic diet on mouse body weight, adipose tissue, and gut microbiota

Gut microbiota is commonly considered a key mediator between nutrition and metabolic health, but little is known about sex differences in this connection. Ketogenic diet (KD) is a widely used nutritional intervention for body weight management and obesity treatment, but very few studies investigated the effect of long-term diet. Here we used 4-month KD in male and female C57Bl/6J mice to describe sex-specific changes in body weight, fat mass, liver metabolism, and gut microbiota composition. We found that in both sexes KD accelerated liver steatohepatitis and reshaped gut microbiota, which stays stable over 4 months. On a contrary, body weight and fat mass showed sex-specific changes: short-term KD reduced them only in males, while long-term KD only in females. This shows that sex differences in metabolic effects of KD are not connected with gut microbiota, reflecting that gut microbiota contributes only partially to the nutritional changes in body weight and fat mass.