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

16 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/j.jacbts.2022.12.001

Find It

Find It at U of M Libraries

Cite this

@article{c88c4e1fbf0047e29e9b85db32156280,

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",

year = "2023",

month = mar,

doi = "10.1016/j.jacbts.2022.12.001",

language = "English (US)",

volume = "8",

pages = "239--254",

journal = "JACC: Basic to Translational Science",

issn = "2452-302X",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - Intermittent Fasting Activates AMP-Kinase to Restructure Right Ventricular Lipid Metabolism and Microtubules

AU - Kazmirczak, Felipe

AU - Hartweck, Lynn M

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

Y1 - 2023/3

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.

KW - fatty acid oxidation

KW - ferroptosis

KW - microtubules

KW - mitochondria

KW - peroxisomes

KW - right ventricular function

UR - http://www.scopus.com/inward/record.url?scp=85150386223&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85150386223&partnerID=8YFLogxK

U2 - 10.1016/j.jacbts.2022.12.001

DO - 10.1016/j.jacbts.2022.12.001

M3 - Article

C2 - 37034280

AN - SCOPUS:85150386223

SN - 2452-302X

VL - 8

SP - 239

EP - 254

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this