| First Author | Pol CJ | Year | 2019 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1865 |
| Issue | 9 | Pages | 2125-2137 |
| PubMed ID | 31029826 | Mgi Jnum | J:278433 |
| Mgi Id | MGI:6323739 | Doi | 10.1016/j.bbadis.2019.04.010 |
| Citation | Pol CJ, et al. (2019) Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21. Biochim Biophys Acta Mol Basis Dis 1865(9):2125-2137 |
| abstractText | Cardiac metabolism affects systemic energetic balance. Previously, we showed that Kruppel-like factor (KLF)-5 regulates cardiomyocyte PPARalpha and fatty acid oxidation-related gene expression in diabetes. We surprisingly found that cardiomyocyte-specific KLF5 knockout mice (alphaMHC-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. alphaMHC-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 alphaMHC-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 PPARgamma inactivation, alphaMHC-KLF5(-/-) mice had less SUMO-PPARgamma in WAT. Increased diet-induced obesity found in alphaMHC-KLF5(-/-) mice was absent in alphaMHC-[KLF5(-/-);FGF21(-/-)] double knockout mice, as well as in alphaMHC-FGF21(-/-) mice that we generated. Thus, cardiomyocyte-derived FGF21 is a component of pro-adipogenic crosstalk between heart and WAT. |
