Fig. 4: Hyperlipidemia and cardiometabolic syndrome exacerbates myelopoiesis, increases immune cell infiltration of the spinal cord, and worsens clinical scoring in P-EAE.

a Measurement of total and free cholesterol in the plasma of WT, WT + HFD, Apoe^−/−, and Apoe^−/−+HFD mice (n = 8 WT, n = 10 WT + HFD, n = 5 Apoe^−/−, n = 7 Apoe^−/−+HFD). b Quantification of circulating Ly6C^hi monocytes and neutrophils (n = 20 WT, n = 10 WT + HFD, n = 8 Apoe^−/−, n = 16 Apoe^−/−+HFD). c Quantification of LSK and MPP3 hematopoietic progenitors in the femur bone marrow of WT and Apoe^−/−+HFD mice (n = 7 WT, n = 8 Apoe^−/−+HFD). d Measurement of M-CSF in femur bone marrow fluid by ELISA (n = 14 WT, n = 8 Apoe^−/−+HFD, student’s unpaired t-test). e Quantification of LSKs and MPP3s in the vertebral bone marrow (n = 8/group). f Quantification of LSKs and MPP3s in the spleen (n = 4 WT, n = 5 Apoe^−/−+HFD). g Progressive EAE (MOG_35-55/CFA) was induced in WT, WT + HFD, Apoe^−/−, and Apoe^−/−+HFD. Mean clinical disease scores of diseased mice over the course of 21 days (n = 15 WT, n = 4 WT + HFD, n = 7 Apoe^−/−, n = 15 Apoe^−/−+HFD). h Representative images of fluoromyelin-stained diseased spinal cords and quantification of demyelination of white matter in WT and Apoe^−/−+HFD mice at peak EAE (n = 6 WT, n = 5 Apoe^−/−+HFD). i Quantification of CD45⁺ cells in the spinal cord at peak EAE (n = 8 WT, n = 5 Apoe^−/−+HFD). j Quantification of LSKs and MPP3 hematopoietic progenitors in the femur bone marrow, 21 days dpi (n = 6 WT, n = 7 Apoe^−/−+HFD). k Measurement of growth factors in femur bone marrow fluid, 21 days dpi, by ELISA (n = 4 WT, n = 6 Apoe^−/−+HFD). l Correlation of blood monocytes and neutrophils, prior to EAE induction, with subsequent clinical disease score (n = 26). m Circulating blood leukocytes in individuals with MS and a BMI of 18–25 (n = 329), 25–30 (n = 329), or 30+ (n = 222), from the UK Biobank. Data presented as mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. a-g are a combination of 2–3 experiments, h–k are from a representative experiment. a, b one-way ANOVA, c–f, h–k, m two sided Mann Whitney U tests, g two sided ANOVA, l Pearson’s Correlation. Created in BioRender. McAlpine, C. (2025) https://BioRender.com/kvggmpp. EAE experimental autoimmune encephalomyelitis WT wild-type, HFD high-fat diet, Apoe^−/− Apolipoprotein E knockout, LSK Lin^-Sca1⁺cKit⁺, MPP3 myeloid-biased multipotent progenitor 3, GM-CSF granulocyte-macrophage colony stimulating factor, IL-3 interleukin-3, M-CSF macrophage colony stimulating factor, ELISA enzyme-linked immunosorbent assay, AUC area under the curve, dpi days post-immunization, MS multiple sclerosis, BMI body mass index.