Does endothelial peroxisome proliferator‐activated receptor gamma (ePPAR‐γ) protect baroreflex function during obesity?

Abstract

We tested the hypothesis that ePPAR‐γ protects baroreflex function during obesity by determining whether a long term (10–12 weeks, LT) or short term (1–2 weeks, ST) high fat diet (HFD, 45% kcal fat) impairs baroreflex gain (BRG) in mice with a dominant‐negative mutation of ePPAR‐γ (E‐V290M) more than wild‐type mice (WT). Arterial pressure and HR were measured by telemetry for 24hrs in mice on a 12:12 dark (D): light (L) cycle. Spontaneous BRG (sBRG; msec/mmHg) was derived using the sequence method. sBRG was lower in lean E‐V290M compared to WT during L, but not D. The LT‐HFD attenuated sBRG in WT and E‐V290M during both L and D, with no difference between groups. During L, the ST‐HFD also blunted sBRG in WT, and sBRG remained lower in E‐V290M mice. During D, ST‐HFD only lowered sBRG in E‐V290M. However, the ST‐HFD‐induced decreases in sBRG were not greater in E‐V290M compared to WT mice during L (WT: −0.30±0.05 vs E‐V290M: −0.17±0.04) or D (WT: −0.06±0.05 vs E‐V290M: −0.17±0.04), indicating that there was not an interactive effect between obesity and the ePPAR‐γ mutation on sBRG. These data suggest that while ePPAR‐γ supports BRG in lean mice, it does not protect the baroreflex during obesity. sBRG (msec/mmHg) Lean L D WT (n=11) 1.63 ± 0.08 1.18 ± 0.06 E‐V290M (n=11) 1.28 ± 0.07† 1.08 ± 0.07 LT‐HFD WT (n=5) 0.96 ± 0.18 # 0.84± 0.10 # E‐V290M (n=3) 0.88 ± 0.19 # 0.69 ± 0.08 # ST‐HFD WT HFD (n=5) 1.36 ± 0.05# 1.10 ± 0.06 E‐V290M HFD (n=7) 1.12 ± 0.05† 0.89 ± 0.06†# Data are mean ± SE. P<0.05 group within diet, P<0.05 diet within group