Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21
| Autor: | Iordanes Karagiannides, Konstantinos Drosatos, Ira J. Goldberg, Brett R. Brown, Michael J. Jurczak, Christine J. Pol, Effimia Zacharia, Nina M. Pollak, Panagiotis Ntziachristos, Diego Scerbo, Iannis Aifantis, Ioannis D. Kyriazis, Gerald I. Shulman |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Leptin Male medicine.medical_specialty FGF21 Adipose Tissue White Kruppel-Like Transcription Factors White adipose tissue Diet High-Fat Article 03 medical and health sciences Mice 0302 clinical medicine Internal medicine Diabetes mellitus Gene expression medicine Animals Humans Myocytes Cardiac Obesity Molecular Biology chemistry.chemical_classification Mice Knockout Mediator Complex Myocardium Cardiac myocyte Body Weight Fatty acid medicine.disease Fibroblast Growth Factors MicroRNAs 030104 developmental biology Endocrinology chemistry Knockout mouse Molecular Medicine Female 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Biochim Biophys Acta Mol Basis Dis |
| ISSN: | 1879-260X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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