Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21

Christine J Pol; Nina M Pollak; Michael J Jurczak; Effimia Zacharia; Iordanes Karagiannides; Ioannis D Kyriazis; Panagiotis Ntziachristos; Diego A Scerbo; Brett R Brown; Iannis Aifantis; Gerald I Shulman; Ira J Goldberg; Konstantinos Drosatos

doi:10.1016/j.bbadis.2019.04.010

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Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21

Journal article

Peer reviewed

Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21

Christine J Pol, Nina M Pollak, Michael J Jurczak, Effimia Zacharia, Iordanes Karagiannides, Ioannis D Kyriazis, Panagiotis Ntziachristos, Diego A Scerbo, Brett R Brown, Iannis Aifantis, …

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol.1865(9), pp.2125-2137

2019

DOI: https://doi.org/10.1016/j.bbadis.2019.04.010

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Abstract

Biochemistry and Cell Biology

Medical Biochemistry and Metabolomics

Clinical Sciences

Krüppel-like factor

FGF21

heart

obesity

high fat diet

Cardiac metabolism affects systemic energetic balance. Previously, we showed that Krüppel-like factor (KLF)-5 regulates cardiomyocyte PPARα and fatty acid oxidation-related gene expression in diabetes. We surprisingly found that cardiomyocyte-specific KLF5 knockout mice (αMHC-KLF5−/−) have accelerated diet-induced obesity, associated with increased white adipose tissue (WAT). Alterations in cardiac expression of the mediator complex subunit 13 (Med13) modulates obesity. αMHC-KLF5−/− mice had reduced cardiac Med13 expression likely because KLF5 upregulates Med13 expression in cardiomyocytes. We then investigated potential mechanisms that mediate cross-talk between cardiomyocytes and WAT. High fat diet-fed αMHC-KLF5−/− mice had increased levels of cardiac and plasma FGF21, while food intake, activity, plasma leptin, and natriuretic peptides expression were unchanged. Consistent with studies reporting that FGF21 signaling in WAT decreases sumoylation-driven PPARγ inactivation, αMHC-KLF5−/− mice had less SUMO-PPARγ in WAT. Increased diet-induced obesity found in αMHC-KLF5−/− mice was absent in αMHC-[KLF5−/−;FGF21−/−] double knockout mice, as well as in αMHC-FGF21−/− mice that we generated. Thus, cardiomyocyte-derived FGF21 is a component of pro-adipogenic crosstalk between heart and WAT.

Details

Title: Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21
Authors: Christine J Pol (Author) - Temple University, United States
Nina M Pollak (Author) - University of Graz, Austria
Michael J Jurczak (Author) - Yale University School of Medicine, United States
Effimia Zacharia (Author) - Temple University, United States
Iordanes Karagiannides (Author) - David Geffen School of Medicine at UCLA, United States
Ioannis D Kyriazis (Author) - Temple University, United States
Panagiotis Ntziachristos (Author) - NYU School of Medicine, United States
Diego A Scerbo (Author) - Columbia University, United States
Brett R Brown (Author) - Temple University, United States
Iannis Aifantis (Author) - NYU School of Medicine, United States
Gerald I Shulman (Author) - Yale University School of Medicine, United States
Ira J Goldberg (Author) - Columbia University, United States
Konstantinos Drosatos (Author) - Temple University, United States
Publication details: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol.1865(9), pp.2125-2137
Publisher: Elsevier BV
Date published: 2019
DOI: 10.1016/j.bbadis.2019.04.010
ISSN: 0925-4439
Organisation Unit: School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99450794302621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Biochemistry & Molecular Biology; Biophysics; Cell Biology

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