González Blázquez, RaquelSomoza Hernández, BeatrizViana Arribas, MartaGonzález Moreno, DanielChowen King, Julie AnnSanz-Gómez, MartaFernández Alfonso, María SoledadGil Ortega, MartaAlcalá Díaz-Mor, MartínUniversidad San Pablo-CEU. Facultad de FarmaciaGrupo de Metabolismo y Función Vascular (MET-VASC)2023-12-042023-12-042023-08-08González-Blázquez, R, Gil-Ortega, M, Alcalá, M, et al. Short-term dietary intervention improves endothelial dysfunction induced by high-fat feeding in mice through upregulation of the AMPK-CREB signaling pathway. Acta Physiol. 2023; 239:e14023. doi:10.1111/apha.140231748-1716http://hdl.handle.net/10637/14696Aim: In 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. Methods: For 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. Results: Returning 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 AMPKα, p-CREB and antioxidant systems (heme oxygenase-1 (HO-1) and catalase) were significantly reduced in HF but normalized in HF-Chow mice. Conclusion: Improving 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.application/pdfenopen accessAMPKCREBDietary interventionEndothelial dysfunctionHeme oxygenase-1Artículohttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es