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Animal Models

Murine model of left ventricular diastolic dysfunction and electro-mechanical uncoupling following high-fat diet

International Journal of Obesity volume 44, pages 1428–1439 (2020)Cite this article

Subjects

Abstract

Background/Objectives

It is well established that obesity is an independent risk factor for cardiac death. In particular various cardiac alterations have been described in obese patients such as long QT on ECG, impaired diastolic filling of the left ventricle (LV), and all-type arrhythmias. In the present study, the above alterations were all reproduced in a mouse model of fat diet-induced obesity.

Animals/Methods

In C57BL6 mice fed on a high fat (n = 20, HF-group) or standard diet (n = 20, C-group) for 13 weeks, balanced by sex and age, we examined heart morphology and function by high-frequency ultrasounds and electric activity by surface ECG. Besides, the autonomic sympathovagal balance (heart-rate variability) and the arrhythmogenic susceptibility to adrenergic challenge (i.p. isoproterenol) were compared in the two groups, as well as glucose tolerance (i.p. glucose test) and liver steatosis (ultrasounds).

Results

Body weight in HF-group exceeded C-group at the end of the experiment (+28% p < 0.01). An abnormal ventricular repolarization (long QTc on ECG) together with impaired LV filling rate and increased LV mass was found in HF-group as compared to C. Moreover, HF-group showed higher heart rate, unbalanced autonomic control with adrenergic prevalence and a greater susceptibility to develop rhythm disturbances under adrenergic challenge (i.p. isoprenaline). Impaired glucose tolerance and higher liver fat accumulation were also found in HF mice compared to C.

Conclusions

The described murine model of 13 weeks on HF diet, well reproduced the cardiovascular and metabolic disorders reported in clinical obesity, suggesting its potential utility as translational mean suitable for testing new pharmaco-therapeutic approaches to the treatment of obesity and its comorbidity.

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Acknowledgements

We wish to express their gratitude to Prof. A. L’Abbate for his helpful criticism and valuable suggestions, and thank Mrs. Cecilia Ciampi and Mrs. Sara Ciampi for their assistance in animal care and Mrs. Sabrina Marchetti for her assistance in setting up histological samples. This study was supported by the Consiglio Nazionale delle Ricerche, Italy, (Grant GAE P0001865, Principal Investigator: C. Kusmic).

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  1. CNR Institute of Clinical Physiology, Pisa, Italy

    Serena L’Abbate, Nicole Di Lascio, Giuseppina Nicolini, Francesca Forini, Francesco Faita & Claudia Kusmic

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Correspondence to Claudia Kusmic.

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L’Abbate, S., Di Lascio, N., Nicolini, G. et al. Murine model of left ventricular diastolic dysfunction and electro-mechanical uncoupling following high-fat diet. Int J Obes 44, 1428–1439 (2020). https://doi.org/10.1038/s41366-019-0500-3

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