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The prevalence of the metabolic syndrome (MetS) is increasing worldwide due in part to the increased consumption of a Western diet. MetS is associated with peripheral neuropathy (PN). PN develops in a cell non-autonomous manner with involvement of axons, Schwann cells (SC) and nerve tissue-infiltrating macrophages (TIM). SC are divided into subtypes with different roles in nerve injury. Our aim in the current study was to determine how gene expression of different types of SC and macrophages are affected in MetS and how these cells communicate with one another. C57BL6/j male mice (6-weeks old) were fed either a standard diet (SD, 10% fat) or high fat diet (HFD, 60%) for 17 weeks. Metabolic and PN phenotyping were performed for all mice and SC were extracted from sciatic nerves for single cell RNA sequencing (scRNA-seq). Cellular communication was determined using the CellChat tool. Mice on …