Short-term dietary intervention improves endothelial dysfunction induced by high-fat feeding in mice through upregulation of the AMPK-CREB signaling pathway

AimIn addition to functioning as an energy sensor switch, AMPK plays a key role in the maintenance of cardiovascular homeostasis. However, obesity disrupts AMPK signaling, contributing to endothelial dysfunction and cardiovascular disease. This study aimed to elucidate if a short-term dietary intervention consisting in replacing the high-fat diet with a standard diet for 2 weeks could reverse obesity-induced endothelial dysfunction via AMPK-CREB activation. MethodsFor this, 5-week-old male C57BL6J mice were fed a standard (Chow) or a high-fat (HF) diet for 8 weeks. The HF diet was replaced by the chow diet for the last 2 weeks in half of HF mice, generating 3 groups: Chow, HF and HF-Chow. Vascular reactivity and western-blot assays were performed in the thoracic aorta. ResultsReturning to a chow diet significantly reduced body weight and glucose intolerance. Relaxant responses to acetylcholine and the AMPK activator (AICAR) were significantly impaired in HF mice but improved in HF-Chow mice. The protein levels of AMPK & alpha;, p-CREB and antioxidant systems (heme oxygenase-1 (HO-1) and catalase) were significantly reduced in HF but normalized in HF-Chow mice. ConclusionImproving dietary intake by replacing a HF diet with a standard diet improves AMPK-mediated responses due to the upregulation of the AMPK/CREB/HO-1 signaling pathway.

Automated summary

This study aimed to investigate if replacing a high-fat diet with a standard diet for a short period could reverse obesity-induced endothelial dysfunction through AMPK-CREB activation. The results showed that improving dietary intake significantly improved vascular function and the antioxidant system mediated by the AMPK/CREB signaling pathway.