Schematic illustration depicting the effects of chronic intermittent hypoxia (IH) or room air (RA) with and without physical activity in mice. (a) IH induces fecal microbiota alterations that increase colonic epithelial permeability in vivo and in vitro, and elicit changes in functional properties of circulating exosomes that induce insulin resistance. Fecal microbiota transfer of experimental groups recapitulates such findings including the beneficial effects of PA y. (b) Average body weight of mice exposed to RA, RA+EX, IH, and IH+PA for 6 weeks with and without exercise (EX) (n = 12; * - p<0.01). * Indicates between IH vs. IH+PA or RA vs. RA+PA. (c) ITT reveals that IH exposures induce insulin resistance compared to RA, and that such effects are improved by PA. (d) Illustrative western blots of vWAT proteins from all 4 experimental groups for CD11c (M1 macrophage), CD146 (integral membrane glycoprotein), CD31 (cell adhesion molecule), and TIE2 (TEK tyrosine kinase). The findings are representative of 8 different experiments. (e) Summary of densitometry signal intensities across experimental groups after normalization to β-actin as the loading control. Significant increases in CD11c protein expression occurred in IH compared to both RA and IH+PA (p = 0.01). Results are expressed as fold change and represent mean ± SD, n = 8/ group, *p = 0.01. Two-way of variance (ANOVA) for repeated measures for body weight and ITT: ** - p<0.01, n = 12/group. Data are presented as mean ± SD. * Indicates statistical significance between IH vs. HI+PA, and IH vs. RA.