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Introduction: There is growing interest in the benefits of intermittent fasting for weight loss, glucose control, vascular protection, and mitigating chronic inflammation. Nonetheless, it remains unclear whether the metabolic and endothelial protective benefits depend on weight loss or anti-inflammatory effects. Objective: Using type 2 diabetic (db/db) mice and the respective heterozygote controls, we aimed to determine whether alternate day fasting (ADF) provides metabolic benefits and endothelial protection, partially independent of its effects on weight control and adipose inflammation. Methods: Mice were either allowed to eat ad libitum or placed on an ADF diet regimen for 12 weeks. Results: In control mice, ADF led to significant reductions in body weight and insulin levels. There was a modest, though not statistically significant, decrease in blood glucose and HOMA-IR. In db/db mice, ADF significantly reduced blood glucose and HOMA-IR while not affecting body weight or insulin levels. This underscores the effects of ADF on improving glucose metabolism despite the absence of weight loss in diabetic mice. ADF improved endothelium-dependent vasorelaxation in small mesenteric arteries of db/db mice without altering endothelium-independent vasorelaxation or phenylephrine-induced vasoconstriction. In control mice, ADF exhibited a trend toward enhancing the maximal relaxation at 10-7 mol/L acetylcholine while not affecting endothelium-independent vasorelaxation or vasoconstriction. Despite the significant metabolic and endothelial protective benefits, ADF did not mitigate adipose inflammation in either control or db/db mice. Conclusions: ADF's weight control, metabolic, endothelial protective, and anti-inflammatory benefits can manifest independently in diabetic and control mice. The results also imply the potential to explore ADF benefits in non-obese, healthy individuals. Disclosure H. Zhang: None.
HANRUI ZHANG (Fri,) studied this question.