UC Riverside identified sex differences in adipose eosinophils in mice

Scientists from the University of California, Riverside, led by Meera Nair and Adam Godzik, have identified differences in how immune cell populations in fat tissue respond to obesity between male and female mice, news.ucr.edu reported ucr.edunews.ucr.edunews.ucr.eduOpen source ↗. Publishing their results in PNAS Nexus, the researchers used single-cell sequencing to analyze adipose tissue and discovered six distinct populations of eosinophils, each exhibiting unique gene expression patterns and functions.

Cellular heterogeneity and sex differences

Historically associated primarily with asthma and allergic responses, eosinophils in adipose tissue were previously regarded as relatively uniform cells. The team established that the response to obesity involves distinct functional subsets rather than overall cell abundance. In female mice, researchers detected a protective subset of eosinophils that engaged in active communication with adipose macrophages, helping to sustain metabolic health. In contrast, male mice maintained on a high-fat diet predominantly developed pro-inflammatory eosinophil populations displaying a less protective genetic profile.

Signaling pathways and organoid modeling

The study determined that RELM alpha, a protein secreted by macrophages, stabilizes the regulatory signaling network between macrophages and eosinophils in female mice. Prior laboratory tests revealed that introducing RELM alpha produced protective metabolic effects in animal models. Because identical therapies targeting the immune system may trigger distinct biological cascades depending on sex, the researchers stressed the need to study sex-specific immunology before designing targeted therapies.

To bridge the gap between rodent biology and human medicine, the researchers are constructing three-dimensional adipose organoids ucr.edunews.ucr.edunews.ucr.eduOpen source ↗. These in vitro human fat structures will serve as experimental platforms to examine interactions between eosinophils and adipose cells and test whether immune cell signaling can be directed to promote metabolic protection.