SIRT1 overexpression protects against high fat diet‐induced cerebral artery endothelial dysfunction (1070.10)

High fat (HF) diet is associated with increased cerebrovascular disease risk, but interventional targets to protect cerebral artery function with HF diet have not been elucidated. Sirtuins control cellular energy metabolism and SIRT1 transgenic overexpressing (SIRT‐TG) mice are protected against some of the negative consequences of HF diet, such as glucose intolerance. However, the effect of SIRT1‐TG on cerebral artery function after HF diet is unknown. We measured middle cerebral artery (MCA) endothelium‐dependent dilation to acetylcholine (ACh) in normal chow (NC) and HF diet fed SIRT‐TG and wildtype (WT) mice (6 mo, n=6‐8/group). In NC mice, MCA dilation to ACh did not differ between SIRT1‐TG and WT (max: 66±13% vs. 67±14%, P=0.90). HF WT mice had impaired MCA dilation to ACh (46±11%, P<0.01 vs. NC WT). However, MCA dilation to ACh for HF SIRT‐TG mice was greater than HF WT mice (63±10%, P=0.01) and not different from NC groups (P>0.05). There were no group differences after nitric oxide (NO) synthase inhibition with L‐NAME (P>0.05), indicating that the impaired dilation to ACh in HF WT mice resulted from reduced NO bioavailability. Endothelium‐independent dilation did not differ between groups (P>0.05). In conclusion, HF diet induced cerebral artery endothelial dysfunction by reducing NO bioavailability in WT mice. SIRT1‐TG mice are protected against cerebral artery endothelial dysfunction induced by HF diet. Grant Funding Source : AG029337, AG040297, AG033196, HL007576