Aging is Associated with Increased Susceptibility to Western Diet‐Induced Glucose Intolerance and Endothelial Dysfunction in Mice

Abstract

Western diets (WD) are associated with impaired glucose tolerance (GT) and vascular endothelial dysfunction, but it is unknown if these deleterious effects are exacerbated in older age. To explore this, GT and endothelium dependent dilation (EDD) were measured in older (O: 29–34 mo) and young (Y: 4–7 mo) B6D2F1 mice (N= 4–5/group) fed WD (40% fat, 6–8 wk) or normal chow (NC). Body mass was greater in O (+3%) and Y (+6%) WD vs. NC (Y vs. O, ns). However, epididymal fat mass was ∼350% greater in O, but only 97% greater in Y (WD vs. NC, P<0.01). The area under the curve for glucose during a GT test (GTAUC) was greater in O WD vs. NC (1.63±0.13 vs. 1.27±0.05 (X 104) mg*min/ml, P=0.02), but not in Y (WD: 1.23±0.04 vs. NC:1.22±0.05). EDD (maximal carotid artery dilation to acetylcholine) was lower in O WD vs. NC (66±6 vs. 80±3%, P=0.03) but not in Y (WD: 91±8 vs. NC: 98±2%, P=0.43). Nitrotyrosine abundance, a marker of oxidative stress, was greater in the aortas of O vs. Y NC (1.8±0.4 vs. 1.0±0.2 AUs, P=0.02), but was increased in WD vs. NC only in O (+45%, 4.0±0.4 AUs, P<0.01). These preliminary observations suggest that aging is associated with impaired resistance to the potentially adverse effects of WD on glucose tolerance and vascular endothelial function in B6D2F1 mice, possibly via exacerbation of oxidative stress. This could contribute to the increased risk of cardiovascular diseases with aging. NIH AG015897, AG006537, AG013038, AG022241