The role of sex-specific mitochondrial changes in the pathogenesis of fatty liver disease

Mitochondria are more than merely the primary source of cellular energy. Their physiological functionality exerts a pivotal influence on energy metabolism, which in turn affects the overall function of the cell. Mitochondrial dysfunction has been identified as a significant contributing factor in the progression of fatty liver disease. However, there is a lack of knowledge regarding the differences between males and females.

To investigate sex-specific changes in mitochondrial functions, an animal study was performed, whereby a western diet (WD) was administered for several time points (13, 26 and 32 weeks) to induce fatty liver disease. A control group of mice was given a standard diet (SD). Liver samples from the mice were processed for proteomic analysis and also underwent measurement of mitochondrial respiration via Seahorse analysis. Proteomics was utilized for a comprehensive core network analysis using Ingenuity Pathway Analysis (IPA) software.

The data of the IPA analysis indicate an inverse effect between the sexes in the WD groups, characterized by up-regulation of essential mitochondrial pathways in females. Unexpectedly, no notable differences are observed between the WD and SD groups over time when considering only mice of the same sex. However, in this context, there is a greater degree of mitochondrial down-regulation in male WD mice.

The results suggest a notable discrepancy between males and females in the progression of fatty liver disease related to mitochondrial functionality, a subject that requires further investigation.

Publication History

Article published online:
20 January 2025