Intermittent Fasting with a High Fat Diet Reveals the Contribution of Mitochondrial Free Radicals to the Endothelium-Dependent Relaxation of Mouse AortaAbstract+ Author Affiliations
- 1Research Center Montreal Heart Institute MONTREAL QC Canada
Obesity leads to endothelial dysfunction, promoting age-related cardiovascular diseases. In mice, a high fat diet (HFD) impairs endothelial function, while caloric restriction slows age-dependent endothelial dysfunction and increases lifespan. Whether intermittent fasting (IF) influences endothelial function is unknown. Three-month old C57BL6 mice were fed ad libitum (AL) or every other day (IF) either a regular diet (RD) or a HFD for 16 weeks. Caloric intake was similar in mice fed a RD either AL or in IF; however, RD-IF prevented body weight gain (p<.05), improved glucose tolerance and insulin sensitivity (p<.05). As expected, HFD-AL increased caloric intake (+27 %), body weight (+7 g), adipose tissue and liver weight (2 fold), glucose intolerance and insulin resistance (p<.05). Combining HFD and IF reduced by 50 % the rise in caloric intake compared to HFD-AL (p<.05), fully prevented HFD-induced gain in body weight, kept optimal (equal to RD-IF) glucose tolerance, and normalized insulin sensitivity (p<.05). Acetylcholine (Ach)-induced relaxation was measured in isolated aortic rings. Ach-induced maximal relaxation (Emax, see Table) was increased in HDF-AL mice (p<.05) due to a compensatory increase in eNOS activity. IF tended to ameliorate Emax (p=.06), irrespectively of the diet and without changing eNOS activity. In the 4 groups, TEMPOL (SOD mimetic) led to higher (p<.05) vascular sensitivity and Emax to Ach. Interestingly, mitoTEMPO targeting mitochondria, reduced (p<.05) endothelium-dependent relaxation in HFD-IF fed mice only, revealing the contribution of mitochondrial free radicals to the endothelium-dependent relaxation of mouse aorta.
(Edit: Or did mitotempol make it worse? I'm about to go to sleep right now so I can't think straight)
Edited by Cosmicalstorm, 09 August 2015 - 07:03 PM.