FGF15/FGF19 is involved in the development of cardiac hypertrophy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Funded by MCIN/AEI/ 10.13039/501100011033 and, by “ERDF A way of making Europe”, by the “European Union” Introduction FGF15 (and its human orthologue, FGF19) are members of the endocrine...

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Published in:Cardiovascular research 2022-06, Vol.118 (Supplement_1)
Main Authors: Planavila, A, Moron-Ros, S, Villarroya, F, Gavalda-Navarro, A
Format: Article
Language:English
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Summary:Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Funded by MCIN/AEI/ 10.13039/501100011033 and, by “ERDF A way of making Europe”, by the “European Union” Introduction FGF15 (and its human orthologue, FGF19) are members of the endocrine FGF family. They are produced by ileal enterocytes in response to bile acids. The liver is its main target tissue but recent studies indicate that FGF19 also regulates skeletal muscle mass and adipose tissue plasticity. Objective To determine the role of the enterokine FGF15/19 during the development of cardiac hypertrophy Methods Circulating FGF19 levels were assessed in patients with heart failure (HF) and myocardial infarction. The hypertrophic response was characterized in Fgf15-null mice subjected to a high-fat diet for 16 weeks or isoproterenol infusion with osmotic minipumps for 7 days. Effects of experimentally increased FGF15 and FGF19 levels in vivo were determined in mice using adenoviral (Ad-Fgf15) and adeno-associated vectors (AAV8-Fgf19) for 1-week or 3-weeks injection, respectively. Results In humans, we found that the FGF19 levels were significantly reduced in patients suffering from heart failure or myocardial infarction, reciprocally to FGF21 levels. We found that mice lacking Fgf15 do not develop cardiac hypertrophy in response to high-fat diet or isoproterenol induced cardiac hypertrophy. Specifically, we found that the ratio heart weight/tibia length (HW/TL), the quantification of cardiomyocyte area and the hypertrophy marker gene atrial natriuretic factor (Anf) -as measures of cardiac hypertrophy development- were reduced in Fgf15-null mice subjected to hypertrophy compared to their corresponding wild-type mice. By contrast, we found that experimental increases in FGF15 or FGF19 induced cardiac hypertrophy development in vivo, characterized by an increase in the HW/TL ratio, area of the cardiomyocytes and hypertrophy marker genes. Conclusions We stablish a cross-talk between the intestine and the myocardium through the enterokine FGF15/19 which seems a key factor required for cardiac hypertrophy development.
ISSN:0008-6363
1755-3245
DOI:10.1093/cvr/cvac066.096