A study led by researchers from Australia finds crucial differences in the way the immune system acting in the body fat of male and female mice operates. Studying the visceral adipose tissue (VAT) in the mice, they find key differences. Visceral adipose tissue is fat tissue that is found in the abdominal region, surrounding various organs. This includes perigonadal VAT which surrounds the ovaries in females and testes in males, which is what the researchers studied.
Controlling immune response
The perigonadal VAT taken from male mice had many more regulatory T cells (Treg) than that of female mice. These cells play a role in controlling immune response to the self and external cells, thereby protecting the body from autoimmune diseases such as rheumatoid arthritis or lupus. The Treg cells in the male VAT also showed a distinct phenotype, functional parameters and gene expression pattern compared to Treg cells in female VAT. “We found elevated expression of inflammatory genes in male VAT. A special population of stromal cells that made the cytokine IL-33 was exclusive to male VAT,” says Ajith Vasanthakumar, from Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Australia. He is the first author of the paper published in Nature. “Historically, visceral adipose tissue was simply regarded as an energy storage [organ]. Many studies, however, have highlighted its endocrine function. Visceral adipose tissue has an endocrine function, meaning it secretes adipokines and hormones that play key roles in energy balance and metabolism,” says Dr. Vasanthakumar.
It is known that men (in a similar manner to male mice) are more susceptible to metabolic diseases such as type 2 diabetes. “This is linked to higher adipose tissue inflammation in men compared to women, again similar to mice,” says Dr Vasanthakumar. “Finally, we have previously shown that human adipose tissue (omental) harbours Treg cells of a phenotype similar to the one found in mice.” Thus, it is likely that the difference in Treg cell distribution seen in the visceral adipose tissue of male and female mice would hold true in humans.
The study has implications for the way trials are conducted with animal models when carrying out research on diseases. For instance when studying metabolic disease, mostly male mice are used. This study implies that findings of such a test will not hold equally good for males and females.
“Until the recent past, for clinical trials mostly men were recruited although it is clear that disease susceptibility and response to drugs are different,” he says. “In this context tailoring drugs to gender is a possibility in the future. We will continue to explore the role of sex hormones in metabolism and other inflammatory and autoimmune diseases.”
