Gender differences in Western-type diet-induced alterations of lipid metabolisms in the liver and adipose tissue of mice

It is increasingly recognized that beyond alterations in hepatic lipid metabolisms, the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is closely related to insulin resistance and dysfunctionality of adipose tissue.

The aim of this study was to assess gender differences within these complex disturbances of components of the metabolic syndrome in an experimental mouse model.

Methods and results A Western-type diet (WTD; 38 % fat, 30 % sucrose and 0.2 % cholesterol) supplemented with 30 % fructose in drinking water [CH1] was applied to 8 week-old male and female mice for 20 weeks. Littermate controls were fed with standard chow. WTD-induced weight gain and visceral adipose tissue (VAT) mass was significantly higher in male than in female mice, and only WTD-fed male mice showed pathological glucose tolerance. Furthermore, expression of pro-inflammatory factors IL-6 and MCP-1 was significantly higher in VAT of male mice. In contrast, liver/body weight ratio und hepatic triglyceride content did not significantly differ between sexes, although female mice showed significantly higher hepatic expression of the fatty acid transporter CD36, fatty acid synthase and nicotinamide phosphoribosyl transferase (NAMPT), an enzyme involved in the development of hepatic steatosis. Moreover, female mice had significantly higher hepatic HMG-CoA reductase (HMGCR) and ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression levels, and fitting to this, significantly higher hepatic cholesterol as well as primary and secondary bile acid levels. Furthermore, induction of oxidative stress and pro-inflammatory gene expression were higher in WTD-fed female mice.

Conclusion Our study reveals significant gender-specific differences in fatty acid accumulation and pro-inflammatory gene expression in VAT on the one side and hepatic lipid, cholesterol and bile-acid metabolisms on the other side. Future studies are needed to verify these mechanisms in men. Potentially, this could lead to the identification of new sex-specific therapeutic targets to prevent NAFLD development and its progression.

Publication History

Article published online:
04 January 2021