Aged garlic extract ameliorates fatty liver and insulin resistance and improves the gut microbiota profile in a mouse model of insulin resistance

Aged garlic extract (AGE) produced by the aging process has various beneficial pharmacological effects. In this study, the effects of AGE on fatty liver, insulin resistance and intestinal microbiota were compared between ddYH mice, an insulin resistance mouse, and ddYL mice, normal mice. Mice were fed an AGEsupplemented diet (4% w/w) for 7 weeks. The administration of AGE had no effect on the body weight and dietary intake of both types of mice. In the ddYH mice, the serum levels of glucose and insulin were increased and glucose tolerance was impaired; however, the administration of AGE ameliorated these abnormal conditions. AGE did not have these effects in ddYL mice. Triglyceride (TG) accumulation in the liver and fat absorption from the digestive tract were increased in the ddYH mice; however, the administration of AGE reduced this increase. On the other hand, AGE exerted no such effects in the ddYL mice. In addition, the gut microbiota has been shown to be closely associated with obesity, diabetes, dyslipidemia and nonalcoholic fatty liver disease in human and animal models. The bacterial composition of the gut microbiota in the feces of the ddYH mice did not differ from that of the ddYL mice at 5 weeks of age; however, it was altered in the mice at 9 and 12 weeks of age even when the mice were fed a standard diet. In the ddYH mice, the relative presence of Lactobacillales was increased, while that of Bifidobacterium, Clostridium cluster XVIII and Prevotella was decreased. The alteration of the bacterial composition in the ddYH mice was reversed by the administration of AGE; however, this effect of AGE was not observed in the ddYL mice. On the whole, the findings of this study indicate that AGE improves abnormal fat accumulation and insulin resistance, and also alters the intestinal flora in ddYH mice, suggesting the possibility that these effects of AGE may be related.