Female Mice Protected Against Obesity and Inflammation by RELMalpha

Although over 30% of American adults are classified as obese, males have been found to be more susceptible to obesity comorbidities and exacerbated inflammation.

Scientists from the University of California, Riverside, investigating the effects of a high-fat diet on mice discovered that, compared to males, female mice are protected against obesity and inflammation by higher levels of an immune protein called RELMalpha. According to their study, published in eLife, RELMalpha plays a crucial role in these sex-specific differences in the immune response to obesity.

The RELM family of proteins, including RELMalpha, is secreted by mammals and is highly expressed in infectious and inflammatory diseases. Following infection, RELMalpha is rapidly triggered in the mouse body to protect its tissues. The protein regulates two immune cell types: anti-inflammatory macrophages and eosinophils, both essential in fighting diseases. Male mice, on the other hand, expressed less RELMalpha, leading to a higher prevalence of inflammatory macrophages that promoted obesity.

By deleting RELMalpha in female mice, researchers observed that the mice lost their protection against obesity and exhibited fewer eosinophils and more inflammatory macrophages, similar to male mice. However, they were able to reduce obesity in female mice by treating them with eosinophils or RELMalpha, indicating promising therapeutic targets for obesity.

The study highlights a critical "RELMalpha-eosinophil-macrophage axis" in females that guards against diet-induced obesity and inflammation. Considering sex differences is essential in tackling metabolic diseases like obesity, and promoting these pathways could lead to novel therapies to combat obesity.