Acrolein-induced atherosclerosis <i>via</i> AMPK/SIRT1-CLOCK/BMAL1 pathway and the protection from intermittent fasting

作者：Qianfeng Chen, Yuxia Zhong, Bohan Li, Yucong Feng, Yuandie Zhang, Tao Wei, Margaret Zaitoun, Shuang Rong, Hua Wan, Qing Feng · 发表于：Journal of Biomedical Research · 年份：2024 · DOI：10.7555/jbr.38.20240025 · 被引用次数：7 · 研究领域：Dietary Effects on Health、Circadian rhythm and melatonin、Diet and metabolism studies

Circadian clock plays a vital role in the pathological progression of cardiovascular disease (CVD). Our previous studies showed that acrolein, an environmental pollutant, promoted atherosclerosis by reducing CLOCK/BMAL1 and disturbing circadian rhythm. Whereas, intermittent fasting (IF), a diet pattern, was able to ameliorate acrolein-induced atherosclerosis. In vivo , mice were fed acrolein 3 mg/kg/day via drinking water and IF for 18h (0:00-18:00). We observed that IF decreased acrolein-accelerated the formation of aortic lesion in ApoE −/− mice. Up-regulation of NF-κB, IL-1β and TNF-α levels were found in liver and heart tissue upon acrolein exposure, while was down-regulated by IF. Interestingly, IF treatment exhibited higher AMPK, p-AMPK and SIRT1and lower MAPK expression which was caused by acrolein. Besides, circadian genes Clock/ Bmal1 expression were suppressed and disturbed treated with acrolein, while were reversed by IF. Furthermore, consistent with that in vivo , short-term starvation as a fasting cell model in vitro could improve the disorders of CLOCK/BMAL1 and raised SIRT1 via regulating AMPK, as well as ROS-MAPK induced by acrolein. In conclusion, we demonstrated that IF repressed ROS-MAPK while activated AMPK to elevate the expression of circadian clock genes to ameliorate acrolein-induced atherogenesis, which shed a novel light to prevent cardiovascular diseases.