High-Fat Diets Increase Myeloid Cell Formation During Steady State Hematopoiesis

Exercise (EX) and high-fat diets (HFDs) incur differential effects on hematopoietic stem cell (HSC) differentiation via altered intercellular signaling. HFDs promote inflammatory myeloid cell formation while EX prevents it. Previous studies involving stress hematopoiesis suggest EX and HFDs may impose these effects through altered miR-193 and miR-331-5p expression in bone marrow. miR-193 and miR-331-5p may derive from mesenchymal stromal cells (MSCs). However, whether similar impacts occur with EX and HFDs during steady state hematopoiesis due to alterations in miR-193 and miR-331-5p expression from bone marrow MSCs remains unknown. PURPOSE: The purpose of the study was to investigate the effects of EX and HFD on bone marrow cell composition, HSC differentiation patterns, and whether miR-193 and miR-331-5p expression is altered in MSCs during steady state hematopoiesis. METHODS: Male CBA mice (n = 40) were placed on either HFD or control (CON) diet for 8 weeks, with the final 4 weeks involving EX or sedentary (SED) conditions. HSC myeloid differentiation potential was measured using a colony forming unit assay. Bone marrow cell populations were measured via flow cytometry. miR-193 and miR-331-5p expression was measured via RT-qPCR after 10 minutes of in vitro C3H10T1/2 cell straining to mimic EX with early adipogenic media addition to mimic HFD. RESULTS: HFDs induced higher HSC (0.80 ± 0.04 vs. 0.60 ± 0.04, p < 0.05, mean ± SEM) and myeloid progenitor cell (36.31 ± 2.62 vs. 25.64 ± 1.41, p < 0.05) concentrations without impacting lymphoid progenitor cells. EX had lower myeloid colony formation (240.80 ± 4.25 vs. 287.65 ± 8.13, p < 0.0001) compared to SED. MSC concentrations were lower with EX (0.48 ± 0.02 vs. 0.58 ± 0.04, p < 0.05). In vitro, adipogenic media induced lower miR-193 expression compared to control media (0.87 ± 0.08 vs. 1.77 ± 0.44, p < 0.05). CONCLUSIONS: EX discourages inflammatory conditions by inhibiting myeloid cell formation while HFDs oppose these effects. Adipogenic conditions may promote HSC expansion by reducing MSC-derived miR-193. National Sciences and Engineering Research Council (RGPIN-2017-04320)