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

doi:10.1016/j.jacbts.2022.12.001

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 journal › Article › peer-review

3 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 language	English (US)
Pages (from-to)	239-254
Number of pages	16
Journal	JACC: Basic to Translational Science
Volume	8
Issue number	3
DOIs	https://doi.org/10.1016/j.jacbts.2022.12.001
State	Published - 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

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10.1016/j.jacbts.2022.12.001

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title = "Intermittent Fasting Activates AMP-Kinase to Restructure Right Ventricular Lipid Metabolism and Microtubules",

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.",

keywords = "fatty acid oxidation, ferroptosis, microtubules, mitochondria, peroxisomes, right ventricular function",

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

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: {\textcopyright} 2023 The Authors",

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AU - Vogel, Neal

AU - Mendelson, Jenna B.

AU - Park, Anna K.

AU - Raveendran, Rashmi M.

AU - O-Uchi, Jin

AU - Jhun, Bong Sook

AU - Prisco, Sasha Z

AU - Prins, Kurt W

N1 - 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

PY - 2023/3

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N2 - 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.

AB - 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.

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KW - microtubules

KW - mitochondria

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

Abstract

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Keywords

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