Intermittent Fasting Activates AMP-Kinase to Restructure Right Ventricular Lipid Metabolism and Microtubules

Felipe Kazmirczak, Lynn M Hartweck, Neal Vogel, Jenna B. Mendelson, Anna K. Park, Rashmi M. Raveendran, Jin O-Uchi, Bong Sook Jhun, Sasha Z Prisco, Kurt W Prins

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)239-254
Number of pages16
JournalJACC: Basic to Translational Science
Volume8
Issue number3
DOIs
StatePublished - Mar 2023

Bibliographical note

Funding Information:
The authors thank Drs LeeAnn Higgins and Todd Markowski of the University of Minnesota Center for Mass Spectrometry and Proteomics for assistance with our proteomics experiments, Dr Keita Uchida for sharing his antigen retrieval protocol for cardiomyocyte microtubule imaging, Trace Christensen and the Mayo Microscopy and Cell Analysis Core for experimental and technical support, Bridget Nieto and Dr Michael Cypress for experimental and technical support, and Dr Yasunori Shintani for generously sharing the phospho-CLIP170 antibody.

Publisher Copyright:
© 2023 The Authors

Keywords

  • fatty acid oxidation
  • ferroptosis
  • microtubules
  • mitochondria
  • peroxisomes
  • right ventricular function

PubMed: MeSH publication types

  • Journal Article

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