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Adipocyte and Cell Biology

Adipokines disrupt cardiac differentiation and cardiomyocyte survival

Abstract

Background

The role of adipose tissue in the pathophysiology of cardiovascular disease remains a major subject of research. The objective of the present study was to dissect the molecular mechanisms that regulate the survival and differentiation of cardiac cells in an obese environment.

Material and methods

We isolated murine/human cardiac cells from adult hearts of control and obese mice/subjects and analyzed the communication between cardiac cells and adipocytes in vitro, as well as the effects on their main functions such as survival and differentiation.

Results

We found that the presence of visceral or subcutaneous adipocytes in the environment of cardiomyocytes or cardiac precursors provoked apoptosis or blocked differentiation, respectively, and these effects were mediated by secreted adipokines. Remarkably, cardiac precursors changed their fate and differentiated into mature adipocytes, contributing to the overall increase in adipose cell content. Inhibiting the adipokines TNF-α, visfatin, or HMGB1 could block the deleterious effects of adipokines on cardiac cells.

Conclusions

Our findings demonstrate that mouse and human visceral adipose tissue contributes negatively to the homeostasis and regeneration of the heart. Moreover, our results suggest that blocking the action of certain adipokines might enhance cardiac differentiation and survival.

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Acknowledgements

This study was supported by funding from the Spanish Ministry of Science and Innovation (SAF2015-67911-R) to BGG. BdL is supported by an FPU fellowship from the Spanish Ministry of Science and Innovation. We would like to thank Dr Kenneth McCreath for critically reviewing the paper.

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LMP, BdL, and AB carried out the experiments. All authors contributed to drafting and reviewing the paper. LMP and BGG wrote the paper and discussed data.

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Correspondence to Laura M. Pérez.

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Pérez, L.M., de Lucas, B., Bernal, A. et al. Adipokines disrupt cardiac differentiation and cardiomyocyte survival. Int J Obes 44, 908–919 (2020). https://doi.org/10.1038/s41366-019-0455-4

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