Fructose induces hepatic steatosis in adolescent mice linked to the disorders of lipid metabolism, bile acid metabolism, and autophagy

Abstract

The effects of excessive fructose intake on the development and progression of metabolic disorders have received widespread attention. However, the deleterious effects of fructose on the development of hepatic metabolic disease in adolescents and its potential mechanisms are not fully understood. In this study, we investigated the effects of isocaloric fructose-rich diets on the liver of adolescent mice. The results showed that fructose-rich diets had no effect on the development of obesity in the adolescent mice, but did induce hepatic lipid accumulation. Besides, we found that fructose-rich diets promoted hepatic inflammatory responses and oxidative stress in adolescent mice, which may be associated with activation of the NLRP3 inflammasome and inhibition of the Nrf2 pathway. Furthermore, our results showed that fructose-rich diets caused disturbances in hepatic lipid metabolism and bile acid metabolism, as well as endoplasmic reticulum stress and autophagy dysfunction. Finally, we found that the intestinal barrier function was impaired in the mice fed fructose-rich diets. In conclusion, our study demonstrates that dietary high fructose induces hepatic metabolic disorders in adolescent mice. These findings provide a theoretical foundation for fully understanding the effects of high fructose intake on the development of hepatic metabolic diseases during adolescence.

Keywords: Adolescent mice; Autophagy; Bile acid metabolism; Fructose; Lipid metabolism; Non-alcoholic fatty liver disease.