Androgen deprivation in men leads to increased adiposity,but the mechanisms underlying androgen regulation of fat mass have not been fully defined.Androgen receptor (AR) is expressed in monocytes/macrophages,which are resident in key metabolic tissues and influence energy metabolism in surrounding cells.Male mice bearing a cell-specific knockout of the AR in monocytes/macrophages (M-ARKO) were generated to determine whether selective loss of androgen signaling in these cells would lead to altered body composition.Wild-type (WT) and M-ARKO mice (12-22 weeks of age,n =12 per group) were maintained on a regular chow diet for 8 weeks and then switched to a high-fat diet for 8 additional weeks.At baseline and on both the regular chow and high-fat diets,no differences in lean mass or fat mass were observed between groups.Consistent with the absence of differential body weight or adiposity,no differences in food intake (3.0 + 0.5 g per day for WT mice vs 2.8 ± 0.4 g per day for M-ARKO mice) or total energy expenditure (0.6 + 0.1 Kcal h-1 for WT mice vs 0.5 ± 0.1 Kcal h-1 for M-ARKO mice) were evident between groups during high-fat feeding.Liver weight was greater in M-ARKO than that in WT mice (1.5 ± 0.1 g vs 1.3 ± 0.0 g,respectively,P =0.02).Finally,M-ARKO mice did not exhibit impairments in glucose tolerance or insulin sensitivity relative to WT mice at any study time point.In aggregate,these findings suggest that AR signaling specifically in monocytes/macrophages does not contribute to the regulation of systemic energy balance,adiposity,or insulin sensitivity in male mice.