Compared with their male counterparts, female mice are protected against obesity and inflammation by secreting an immune protein called RELMalpha, according to a team of scientists at the University of California, who used a mouse model of high fat diet-induced obesity.
"Our study identifies immune cells and RELMalpha in causing these sex-specific differences in the immune response to obesity," said Dr Meera G Nair, an associate Professor of Biomedical Sciences in the School of Medicine, who co-led the study with Dr Djurdjica Coss, a Professor of Biomedical Sciences.
RELM or resistin-like molecules, constitute a family of proteins secreted by mammals that are highly expressed in infectious and inflammatory diseases. One of these proteins, RELMalpha, is quickly triggered in the mouse body following infection and serves to protect the body's tissues. It has a sequence and function similar to resistin in humans.
"RELMalpha regulates two immune cell types: the anti-inflammatory macrophage and the eosinophil," explained Nair. Macrophages and eosinophils are types of disease-fighting white blood cells but can be damaging to the body in the absence of infection. "In contrast, males expressed less RELMalpha, had less eosinophils, and had inflammatory macrophages that promoted obesity."
When the researchers deleted RELMalpha in female mice, they found the mice were no longer protected from obesity, had fewer eosinophils and had inflammatory macrophages - similar to male mice.
"However, we were able to reduce obesity in these female mice by treating them with eosinophils or with RELMalpha, suggesting promising therapeutic targets. We are the first to map this pathway in females that protects against obesity."
The research team found RELMalpha deficiency had significant effects in males also, but to a lesser extent than females.
"In our experiments, female mice had higher levels of RELMalpha than males, which likely explains why RELMalpha deficiency affected females more than males," added Coss. "The implications of our study are that consideration of sex differences is critical to tackle metabolic diseases such as obesity."
According to Nair, the study is novel in showing a previously unrecognized role for RELMalpha in modulating metabolic and inflammatory responses during diet-induced obesity that is sex dependent.
"Our results highlight a critical 'RELMalpha–eosinophil–macrophage axis' that functions in females to protect from diet-induced obesity and inflammation," she said. "Promoting these pathways could, therefore, provide novel therapies for combating obesity."
The outcomes were featured in the paper, 'Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils', published in eLife. To access this paper, please click here