Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21

Publication date: Available online 26 April 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): 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 DrosatosAbstractCardiac 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-KLF5âˆ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research