Fructooligosaccharides ameliorate hepatic and renal lipid accumulation and intestinal barrier dysfunctions in a pre-diabetic rat model.

Abstract

Consumption of a high-fat diet (HFD) diet is a factor associated with several diseases including obesity and its associated complications, especially liver and kidney dysfunction via promoting derangement of lipid metabolism. It has been reported that fructooligosaccharides (FOS) improve insulin sensitivity and ectopic lipid accumulation. The aim of this study was to investigate the effects of FOS on insulin resistance, liver and renal lipid accumulation, inflammasome formation, oxidative stress and intestinal barrier integrity in an obese rat model. Male Wistar rats were fed a normal (ND) or HFD for 16 weeks. The rats given a HFD were then given FOS at 1 or 2 g/day and metformin at 30 mg/kg/day daily for 8 weeks by oral gavage. The results demonstrated that FOS and metformin improved insulin resistance. FOS showed greater efficacy than metformin in attenuating intestinal barrier leakage. FOS and metformin decreased liver lipid synthesis as evidenced by the downregulation of SREBP1c, FAS and perilipin2. Renal lipid accumulation was restored concomitant with the reduction in renal lipid content and lipotoxicity. Liver and renal inflammation and organ injury were restored to within normal limits. However, FOS had no effect on the antioxidant enzymes via KEAP1/NRF2. Metformin attenuated renal oxidative stress via the suppression of PKCα and the FOXO1 signaling pathway. These suggest that FOS and metformin have the potential to improve gut health and prevent liver and renal complications and could be used as a useful supplement in the obese condition.