The Effects of Sex Differences and Diet on the Development of Non‐Alcoholic Fatty Liver Disease in SAMP8 Mice

Abstract

Non‐alcoholic fatty liver disease (NAFLD) has become the leading form of chronic liver disease and has been associated with increased risk for non‐alcoholic steatohepatitis (NASH) and hepatocellular carcinoma. Western diets, high in both saturated fats and fructose, have been associated with hepatic lipotoxicity, however, little is known about sex‐related differences in the progression of NAFLD. Therefore, the purpose of this study was to determine the effects of sex‐ and diet‐related differences on the development of NAFLD in a senescence‐accelerated mouse model. At 12 weeks of age, Senescence Accelerated Mouse‐Prone 8 (SAMP8) mice were divided by sex and randomly assigned to either a standard diet (SD; 10% kcal fat) or a Western diet (WD; 45% kcal fat and 24% kcal fructose) for 9 months. Hepatic tissue was analyzed for total lipid, triglyceride, and cholesterol levels. A two‐way (sex × diet) ANOVA was used to identify sex‐ and diet‐differences with statistical significance set at p<0.05. A diet effect was observed where the consumption of a WD resulted in elevated total lipid (9.25 ± 3.4% vs. 4.03 ± 1.0%), hepatic triglyceride (24.8 ± 13.9 μg/mg vs. 1.2 ± 0.9 μg/mg), and hepatic cholesterol (2.6 ± 1.7 μg/mg vs. 0.5 ± 0.1 μg/mg) when compared to SD. A sex effect was observed with male mice having higher total lipid (7.70 ± 0.4% vs. 5.98 ± 0.4%), hepatic triglyceride (16.1 ± 1.9 μg/mg vs. 10.9 ± 1.8 μg/mg), and hepatic cholesterol (2.0 ± 0.2 μg/mg vs. 1.2 ± 0.2 μg/mg) than the female mice. The interaction between sex and diet revealed no difference between male and female mice for SD, however, male mice displayed greater hepatic total lipid, triglyceride, and cholesterol levels than female mice fed the WD. In summary, consumption of a Western diet in male mice resulted in a greater progression of fatty liver disease than female mice in a senescence‐accelerated mouse model.Support or Funding InformationSupported by NIH R21NS090282‐01.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.