Short‐term intermittent hypoxia induces simultaneous systemic insulin resistance and higher cardiac contractility in lean mice

FIGURE 1. Experimental groups (a) and study design (b)

FIGURE 2. Impact of 20 weeks high‐fat diet (HFD) on body weight (a) and heart weight‐to‐tibia length ratio (HW/TL) (b). Fasted blood glucose (c) and plasma insulin (d) levels were monitored after 19 weeks diet and insulin tolerance test was performed (e). Data are expressed as means ± SEM (n = 7). The protein expression of IRβ, Akt, and phosphorylation states on Tyr1150IRβ and Ser473Akt was determined by Western blot (f and g) and quantified by densitometric analysis. The phospho‐to‐total ratios were calculated and expressed as fold change relative to LFD control mice. Data are expressed as means ± SEM (n = 3). *p < 0.05 compared to LFD

FIGURE 3. Impact of 6 weeks IH on metabolic parameters in LFD mice. Body weight (a) and heart weight‐to‐tibia length ratio (HW/TL) (b) were monitored after 20 weeks diet and 6 weeks IH exposure. Fasted blood glucose (c) and plasma insulin (d) levels were monitored after 19 weeks LFD and insulin tolerance test was performed (e). Data are expressed as means ± SEM (n = 7). The protein expression of IRβ, Akt and phosphorylation states on Tyr1150IRβ and Ser473Akt were determined under basal conditions or 15 min after insulin injection by Western blot (f and g) and quantified by densitometric analysis. The phospho‐to‐total ratios were calculated and expressed as fold change relative to LFD‐N‐NaCl condition. Data are expressed as means ± SEM (n = 3). *p < 0.05, compared to LFD‐N

FIGURE 4. Impact of 6 weeks IH on cardiac remodeling and function in LFD mice. Quantification of cardiac interstitial fibrosis expressed as percentage of tissue area (10–12 images analyzed per mice; 3 mice per group) (a). Representative images of interstitial fibrosis in N and IH mice (b). mRNA expression of fibrosis markers Col1a1, Col3a1, Ctgf and Tgfβ (n = 3) (c). Cardiomyocyte cross‐sectional (CSA) area quantification (around 500 cardiomyocytes analyzed; 3 mice per group) (d) and representative WGA stainings (e). Quantification of mRNA expression of markers of cardiac hypertrophy, Acta1, Nppa, and Nppb (n = 3) (f). Echocardiographic assessment of ejection fraction in LFD mice (n = 7) (g). Data are expressed as means ± SEM, *p < 0.05

FIGURE 5. Impact of 6 weeks IH on metabolic parameters in HFD mice. Body weight (a) and heart weight‐to‐tibia length ratio (HW/TL) (b) were monitored after 20 weeks diet and 6 weeks IH exposure. Fasted blood glucose (c) and plasma insulin (d) levels were monitored after 19 weeks HFD and insulin tolerance test was performed (e). Data are expressed as means ± SEM (n = 7). The protein expression of IRβ, Akt and phosphorylation states on Tyr1150IRβ and Ser473Akt were determined under basal conditions or 15 min after insulin injection by Western blot (f and g) and quantified by densitometric analysis. The phospho‐to‐total ratios were calculated and expressed as fold change relative to HFD‐N‐NaCl condition. Data are expressed as means ± SEM (n = 3). *p < 0.05 compared to HFD‐N

FIGURE 6. Impact of 6 weeks IH on cardiac remodeling and function in HFD mice. Quantification of cardiac interstitial fibrosis expressed as percentage of tissue area (10–12 images analyzed per mice; 3 mice per group) (a). Representative images of interstitial fibrosis in N and IH mice (b). mRNA expression of fibrosis markers Col1a1, Col3a1, Ctgf and Tgfβ (n = 3) (c). Cardiomyocyte cross‐sectional area (CSA) quantification (around 500 cardiomyocytes analyzed; 3 mice per group) (d) and representative WGA stainings (e). Quantification of mRNA expression of markers of cardiac hypertrophy, Acta1, Nppa, and Nppb (n = 3) (f). Echocardiographic assessment of ejection fraction in HFD mice (n = 7) (g). Data are expressed as means ± SEM