CSF1R blockade improves prediabetic symptoms in fructose-fed rhesus macaques 4223

Abstract Description We previously found that depletion of CSF1Rhi macrophages (Mθ) using a rhesus IgG1 recombinant antibody against CSF1R (α-CSF1R) reduced cholesterol and improved insulin sensitivity in naturally prediabetic rhesus macaques (RM). High fructose diet (HFrD)-fed RMs have been established as a model of metabolic syndrome (MetS), with increased insulin resistance and increased monocyte chemoattractant protein 1 (MCP-1). We hypothesized that depletion of CSF1Rhi tissue Mθ using a monoclonal α-CSF1R and replacement with freshly differentiated Mθ could alleviate inflammation in tissues and ameliorate prediabetic disease in HFrD-fed RMs. We induced MetS in 8 Indian RMs (aged 13-27) through a HFrD for 3-13 months. RMs were treated with either α-CSF1R or an IgG1 control administered intravenously (15 mg/kg) once every 2 weeks for 6 weeks. Clinical parameters such as serum triglycerides (TG), glucose, insulin, adiponectin, CSF1, IL1β, and MCP-1 were monitored during treatment (Tx) and 8 weeks after the Tx. Mθ subsets and circulating immune cell subsets were quantified by immunofluorescent staining and flow cytometry. HFrD resulted in increased TG, fasting insulin levels, and myelopoiesis in all animals, and type 2 diabetes in 2 animals. Tx with α-CSF1R resulted in decreased TG, glucose, fructose consumption, and insulin and increased adiponectin, CSF1, serum globulin and transitional B cells. In conclusion, Tx with α-CSF1R improved multiple clinical parameters associated with MetS. Funding Sources Supported by American Heart Association Predoctoral Fellowship 24PRE1188080, American Heart Association Predoctoral Fellowship Natalie Stahr (PI), 01/01/2024-12/31/2025. CSF1R Blockade in Prediabetic Rhesus Monkeys. Topic Categories Immune Mechanisms of Human Disease (HUM)