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High Fat Diet Consumption and its Association with Parenchymal Arteriole Structure and Cognition

Obesity has been identified as a major risk factor for the development of vascular cognitive impairment with dementia, which is a form of dementia with a vascular origin. Early onset obesity increases the risk of cognitive impairment and sets individuals on a path of cognitive decline that is associated with cerebral hypoperfusion. The parenchymal arterioles (PAs) link the pial arteries to the microcirculation and they form a bottleneck in the perfusion of the microcirculation. Alterations in the structure of PAs could reduce cerebral blood flow and lead to cognitive decline. In this study, we hypothesized that a high fat (HF) diet would lead to a decline in cognition and inward remodeling of PAs. 3‐week‐old male and female Sprague Dawley rats were fed a HF or control diet for 21 weeks. Data are presented as the mean ± SEM, HF vs Control, n=3–4 in each group. At euthanasia, the HF groups weighed more than the controls (Male: 577 ± 68.9vs 450.8 ±18.8g, p=0.0637, Female: 301.3 ±12.0vs 257.3 ± 15.9g, p=0.0351). The HF fed rats had significantly higher abdominal fat weight in both males and females (Male: 20.3± 4.79 vs 7.02 ±1.32g, p<0.05, Females: 11.5 ± 2.02vs 4.05±1.31g, p<0.05). The HF males had significantly elevated fasting blood glucose of 188± 10.8 vs 150.3 ± 8.8mmol/l, p=0.0348while blood glucose was unchanged in the females; 134.5 ± 11.87 vs 129.5 ± 14.5mmol/l, p=0.750. PAs were collected and their structure was assessed using pressure myography under Ca+2free conditions and zero flow. The change in outer, lumen diameter and wall thickness of PAs from HF rats was expressed as a % of the control. In males, a decrease of 35.3± 5.1% in the outer diameter, a decrease of 24 ± 10.3% in the lumen diameter, and a decrease of 58.5 ± 5.9% in the wall thickness was observed. In the females, a decrease of 26.4 ± 8.1% in the outer diameter, a decrease of 36.2 ± 7.8% in the lumen diameter, and an increase of 25± 20% in wall thickness was observed. Cognitive function was assessed using the novel object recognition test. There was no significant difference observed in the % novel object exploration in either group (Male: 36.7 ± 6.34 vs 32.4 ± 1.63%, p=0.0792, Females: 44.8 ± 4.28 vs 45.4 ± 4.35%, p=0.968). Preliminary studies suggest that HF diet alters PA structure without affecting cognition. Interestingly, a sex difference was observed in the effects of HF feeding on wall thickness which was reduced in males and increased in females. This suggests the mechanisms responsible for artery remodeling may differ between sexes.