A study led by the CIBER Diabetes and Associated Metabolic Diseases Area (CIBERDEM), in collaboration with the Institute for Bioengineering of Catalonia (IBEC), has shown that high-fat diets alter gene expression in key tissues for metabolic control in different ways depending on sex. These results provide a new perspective on how obesity affects people differently depending on their sex.
Researchers from the CIBER Diabetes and Associated Metabolic Diseases Area (CIBERDEM) have demonstrated in mouse models that high-fat diets can profoundly alter the expression of genes in tissues that are key to metabolic control. The genes that typically mark differences between the sexes are particularly sensitive to the effects of obesity.
This study was recently published in the American Journal of Physiology – Cell Physiology and involved researchers from the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and the Institute for Bioengineering of Catalonia (IBEC).
The researchers observed that males showed more severe metabolic deterioration than females when fed a high-fat diet, despite both sexes developing a similar amount of body fat. By analysing changes in gene expression in the liver and adipose tissue, the researchers found that obesity altered gene expression very differently depending on sex. “The most surprising finding was that the genes that mark differences between the sexes under normal conditions — called ‘sexually dimorphic’ genes — are precisely the most sensitive to ‘obesogenic’ diets,” says Joan-Marc Servitja, a CIBERDEM researcher and co-leader of the study. Consequently, natural differences in gene expression between the sexes are lost, indicating that obesity can erase sex-specific patterns that are fundamental to metabolic balance.
These results provide ‘a new perspective on how obesity impacts differently depending on sex, highlighting that differences in gene expression between the sexes play a key role in metabolic health’, concludes Vicent Ribas, a CIBERDEM researcher and co-leader of the study. The study highlights the importance of analysing both sexes in metabolic disease research, as this can be crucial in developing more effective prevention and treatment strategies.
Reference article:
Vicent Ribas, Samantha Morón-Ros, Helena Mari, Albert Gracia-Batllori, Laura Brugnara, Alba Herrero-Gomez, Elena Eyre, Marc Claret, Irene Marco-Rius, Anna Novials, Joan-Marc Servitja. Diet-Induced Obesity Disrupts Sexually Dimorphic Gene Expression in Mice. Am J Physiol Cell Physiol. (2025). DOI: 10.1152/ajpcell.00098.2025.
