Most cells in the human body carry the genome, but not all cells express all genes. The genes that a cell expresses determine its identity and variations in gene sequences or how they are expressed may have a big impact on a cell's function. Scientists have now examined how the physiology of fat cells carried by men and women lead to differences in gene expression that affect people's risk of disease. The findings have been reported in Genome Sciences.
Sex-dependent differences in the distribution and physiology of fat have been connected to sex-dependent differences in cardiometabolic diseases. In this work, the scientists examined the expression of genes in fat cells from men and women. The work revealed 162 genes that have significant sex-dependent differences in how they are expressed in fat tissue. There are common variants in the sequences of thirteen of these genes that lead to different health outcomes in men and women, and some of these genes have already been linked to metabolic or cardiovascular disorders. The work may help explain why men and women are at risk for different diseases and often respond to different treatments.
"Obesity is associated with a number of health risks, and how men and women store excess calories as fat makes a difference in how they have different susceptibilities to common diseases," said Mete Civelek, Ph.D., of the University of Virginia's Department of Biomedical Engineering. "We studied people of different ethnicities and health conditions, and we found a group of genes that are different in their abundance between men and women independent of ethnicity or health status."
Scientists are already aware of thousands of genes in fat cells that seem to have different effects depending on sex. This work, which used a diverse set of 3,000 human samples, identified "robust" sex-dependent changes in only 162.
"By combining a variety of data resources, we were able to identify specific genes that could be targeted to elicit distinct therapeutic outcomes in men and women," said Warren Anderson, Ph.D., a researcher in Civelek's lab.
More work showed that there are six specific genes that have an especially significant effect on the regulation of fat cells. "We can now focus on these six genes as potential therapeutic targets," Civelek said.
"We believe our findings will be beneficial in precision medicine efforts to find drug targets that can help with specific problems that men and women face," Civelek said. "For example, men are more prone to cardiovascular disorders and women to obesity. The fat genes we identified could contribute to the severity of those illnesses and how men and women respond to treatment differently."