Single cell transcriptomic profiling of RELMα-regulated adipose macrophage and eosinophil subsets in diet-induced obesity 3281

Abstract Description Obesity is a global health crisis, increasing the risk of infections and chronic diseases like cardiovascular disease and type 2 diabetes. Chronic inflammation in adipose tissue impacts obesity outcomes, with sex differences influencing disease severity. We recently showed that resistin-like molecule-alpha (RELMα) protects females from high-fat diet (HFD)-induced obesity by affecting adipose macrophages and eosinophils. This study explores adipose eosinophil and macrophage subsets using single-cell transcriptomic profiling and examines the effects of helminth infection, sex, and RELMα. Male and female C57BL6/J or RELMα-deficient mice were fed HFD for 6 weeks, with or without infection with helminth Nippostrongylus brasiliensis. Single-cell suspensions of visceral adipose tissue were enriched for SiglecF+ macrophages and eosinophils and analyzed using 10x Genomics Fixed RNA Profiling. We identified unique eosinophil and SiglecF+ macrophage subsets. Eosinophil clustering revealed seven clusters influenced by sex, infection, and RELMα status. Gene ontology (GO) analysis highlighted sex-specific pathways, including leukocyte immunity and cell adhesion, and RELMα-driven pathways in wound healing and adaptive immune response. Infection impacted metabolic processes like phosphorus and amide metabolism. This study uncovers eosinophil heterogeneity and macrophage-eosinophil interactions in adipose tissue, suggesting these mechanisms may protect against diet-induced obesity. Funding Sources Supported by NIH R01AI153195; NIH R21AI180561. Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)