The research team observed that in mice fed high-fat diets, the males showed more severe metabolic impairments, despite the fact that both sexes developed a similar amount of body fat. By analysing the changes in gene expression in liver and adipose tissue, it was found that obesity altered gene expression in very different ways according to sex.
“The most surprising finding was that the genes that differentiate between the sexes under normal conditions, called ‘sex-dimorphic’ genes, are precisely those that are most sensitive to high-fat diets,” says Joan-Marc Servitja, CIBERDEM researcher. As a result, there is a loss of the natural differences in gene expression between sexes, indicating that obesity can erase sex-specific patterns.
These results provide “a new perspective on how obesity impacts differently according to sex, and highlight that sex differences in gene expression play a key role in metabolic health,” concludes Vicent Ribas, IDIBAPS and CIBERDEM researcher and co-leader of the study. The study underlines the importance of analysing both sexes in research on metabolic diseases, as this approach can be decisive in designing more effective prevention and treatment strategies.
The study also involved the teams led by Anna Novials, head of the IDIBAPS research group, Marc Claret, head of the Neuronal Control of Metabolism research group, also at IDIBAPS, and Irene Marco-Rius from IBEC. This study was funded by the European Federation for the Study of Diabetes (EFSD)/Boehringer Ingelheim European Research Programme, by the Carlos III Health Institute (ISCIII, PI20-00658, co-funded by the European Union) and by the European Union’s Horizon 2020 programme (863037).
Study reference:
Vicent Ribas, Samantha Morón-Ros, Helena Mari, Albert Gracia-Batllori, Laura Brugnara, Alba Herrero-Gómez, 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 Aug 4. doi: 10.1152/ajpcell.00098.2025. Online ahead of print.
