Dietary Saturated and Unsaturated Fat and Fructose Induce Distinct Patterns of Hepatic Steatosis in Male Mice

Objective Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease, with a global prevalence of 25.24%. The etiology of NAFLD is complex, and dietary nutrients and their interactions play a critical role. The aim of this study was to determine the effect of different types of dietary fat‐fructose interactions on the pathogenesis of NAFLD and to explore the potential underlying mechanism(s). Methods Male adult C57BL/6J mice were assigned to six groups and fed with diets (AIN‐93G based) enriched with different types of fat (with or without fructose added in the water), such as saturated fat (SF‐‐beef tallow), n−6 polyunsaturated fat (n6USF‐‐corn oil), or n−3 polyunsaturated fat (n3USF‐‐menhaden fish oil), respectively, for 20 weeks. 42% of calories was derived from the fat. Tap water or tap water containing 10% fructose (w/v) was given ad lib during the entire experiment. Body weight and energy efficiency ratio were monitored. Liver histology, fat accumulation, and liver enzymes, as well as glucose tolerance test were evaluated. Results Both SF and n6USF fed mice developed obesity and hepatic steatosis, but with distinct phenotypes. n3USF fed mice with or without fructose exhibited a lean shape with normal liver histology and liver enzymes. There was no difference between SF and n6USF fed mice in terms of body weight (BW). Mice fed with SF displayed more severe hepatic steatosis and liver injury as well as hepatic fibrosis compared to n6USF fed mice. Fructose feeding led to significantly increased liver weight and liver weight:body weight ratio in SF fed mice, but not in the n6USF or n3USF fed mice. While the energy efficiency ratio was the highest in n6USF fed mice, the hepatic triglyceride content in n6USF fed mice was significantly lower than that of SF fed mice. Interestingly, n6USF fed mice displayed marked glucose intolerance which was worsened by fructose feeding, and this effect was not obvious in SF fed mice. Conclusion Our data demonstrated that dietary SF‐fructose and n6USF‐fructose interactions differentially contribute to the development of obesity and hepatic steatosis. n3USF plays a beneficial role in the prevention of obesity and fatty liver, even with the consumption of excess fructose. The underlying mechanism(s) are currently under investigation. Support or Funding Information Supported by grants from NIH and Veterans Administration This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .