Kazmirczak Felipe, Hartweck Lynn M, Vogel Neal T, Mendelson Jenna B, Park Anna K, Raveendran Rashmi M, O-Uchi Jin, Jhun Bong Sook, Prisco Sasha Z, Prins Kurt W
Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
JACC Basic Transl Sci. 2023 Feb 20;8(3):239-254. doi: 10.1016/j.jacbts.2022.12.001. eCollection 2023 Mar.
Intermittent fasting (IF) extends life span via pleotropic mechanisms, but one important molecular mediator is adenosine monophosphate-activated protein kinase (AMPK). AMPK enhances lipid metabolism and modulates microtubule dynamics. Dysregulation of these molecular pathways causes right ventricular (RV) failure in patients with pulmonary arterial hypertension. In rodent pulmonary arterial hypertension, IF activates RV AMPK, which restores mitochondrial and peroxisomal morphology and restructures mitochondrial and peroxisomal lipid metabolism protein regulation. In addition, IF increases electron transport chain protein abundance and activity in the right ventricle. Echocardiographic and hemodynamic measures of RV function are positively associated with fatty acid oxidation and electron transport chain protein levels. IF also combats heightened microtubule density, which normalizes transverse tubule structure.
间歇性禁食（IF）通过多效性机制延长寿命，而一种重要的分子介质是腺苷单磷酸激活蛋白激酶（AMPK）。AMPK增强脂质代谢并调节微管动力学。这些分子途径的失调会导致肺动脉高压患者出现右心室（RV）衰竭。在啮齿动物肺动脉高压模型中，IF激活右心室AMPK，恢复线粒体和过氧化物酶体形态，并重组线粒体和过氧化物酶体脂质代谢蛋白调控。此外，IF增加右心室中电子传递链蛋白的丰度和活性。右心室功能的超声心动图和血流动力学测量与脂肪酸氧化和电子传递链蛋白水平呈正相关。IF还能对抗微管密度升高，使横管结构正常化。
