Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice

Luca Carnevali, Gallia Graiani, Stefano Rossi, Mumna Al Banchaabouchi, Emilio Macchi, Federico Quaini, Nadia Alicia Rosenthal, Andrea Sgoifo

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

In humans, variants of the fat mass and obesity associated (FTO) gene have recently been associated with obesity. However, the physiological function of FTO is not well defined. Previous investigations in mice have linked FTO deficiency to growth retardation, loss of white adipose tissue, increased energy metabolism and enhanced systemic sympathetic activation. In this study we investigated for the first time the effects of global knockout of the mouse FTO gene on cardiac function and its autonomic neural regulation. ECG recordings were acquired via radiotelemetry in homozygous knockout (n = 12) and wild-type (n = 8) mice during resting and stress conditions, and analyzed by means of time- and frequency-domain indexes of heart rate variability. In the same animals, cardiac electrophysiological properties (assessed by epicardial mapping) and structural characteristics were investigated. Our data indicate that FTO knockout mice were characterized by (i) higher heart rate values during resting and stress conditions, (ii) heart rate variability changes (increased LF to HF ratio), (iii) larger vulnerability to stress-induced tachyarrhythmias, (iv) altered ventricular repolarization, and (v) cardiac hypertrophy compared to wild-type counterparts. We conclude that FTO deficiency in mice leads to an imbalance of the autonomic neural modulation of cardiac function in the sympathetic direction and to a potentially proarrhythmic remodeling of electrical and structural properties of the heart.
Original languageEnglish
Pages (from-to)1 - 10
Number of pages10
JournalPLoS ONE
Volume9
Issue number4 (Art. No.: e95499)
DOIs
Publication statusPublished - 2014

Cite this

Carnevali, L., Graiani, G., Rossi, S., Banchaabouchi, M. A., Macchi, E., Quaini, F., ... Sgoifo, A. (2014). Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice. PLoS ONE, 9(4 (Art. No.: e95499)), 1 - 10. https://doi.org/10.1371/journal.pone.0095499
Carnevali, Luca ; Graiani, Gallia ; Rossi, Stefano ; Banchaabouchi, Mumna Al ; Macchi, Emilio ; Quaini, Federico ; Rosenthal, Nadia Alicia ; Sgoifo, Andrea. / Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice. In: PLoS ONE. 2014 ; Vol. 9, No. 4 (Art. No.: e95499). pp. 1 - 10.
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abstract = "In humans, variants of the fat mass and obesity associated (FTO) gene have recently been associated with obesity. However, the physiological function of FTO is not well defined. Previous investigations in mice have linked FTO deficiency to growth retardation, loss of white adipose tissue, increased energy metabolism and enhanced systemic sympathetic activation. In this study we investigated for the first time the effects of global knockout of the mouse FTO gene on cardiac function and its autonomic neural regulation. ECG recordings were acquired via radiotelemetry in homozygous knockout (n = 12) and wild-type (n = 8) mice during resting and stress conditions, and analyzed by means of time- and frequency-domain indexes of heart rate variability. In the same animals, cardiac electrophysiological properties (assessed by epicardial mapping) and structural characteristics were investigated. Our data indicate that FTO knockout mice were characterized by (i) higher heart rate values during resting and stress conditions, (ii) heart rate variability changes (increased LF to HF ratio), (iii) larger vulnerability to stress-induced tachyarrhythmias, (iv) altered ventricular repolarization, and (v) cardiac hypertrophy compared to wild-type counterparts. We conclude that FTO deficiency in mice leads to an imbalance of the autonomic neural modulation of cardiac function in the sympathetic direction and to a potentially proarrhythmic remodeling of electrical and structural properties of the heart.",
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Carnevali, L, Graiani, G, Rossi, S, Banchaabouchi, MA, Macchi, E, Quaini, F, Rosenthal, NA & Sgoifo, A 2014, 'Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice', PLoS ONE, vol. 9, no. 4 (Art. No.: e95499), pp. 1 - 10. https://doi.org/10.1371/journal.pone.0095499

Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice. / Carnevali, Luca; Graiani, Gallia; Rossi, Stefano; Banchaabouchi, Mumna Al; Macchi, Emilio; Quaini, Federico; Rosenthal, Nadia Alicia; Sgoifo, Andrea.

In: PLoS ONE, Vol. 9, No. 4 (Art. No.: e95499), 2014, p. 1 - 10.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice

AU - Carnevali, Luca

AU - Graiani, Gallia

AU - Rossi, Stefano

AU - Banchaabouchi, Mumna Al

AU - Macchi, Emilio

AU - Quaini, Federico

AU - Rosenthal, Nadia Alicia

AU - Sgoifo, Andrea

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N2 - In humans, variants of the fat mass and obesity associated (FTO) gene have recently been associated with obesity. However, the physiological function of FTO is not well defined. Previous investigations in mice have linked FTO deficiency to growth retardation, loss of white adipose tissue, increased energy metabolism and enhanced systemic sympathetic activation. In this study we investigated for the first time the effects of global knockout of the mouse FTO gene on cardiac function and its autonomic neural regulation. ECG recordings were acquired via radiotelemetry in homozygous knockout (n = 12) and wild-type (n = 8) mice during resting and stress conditions, and analyzed by means of time- and frequency-domain indexes of heart rate variability. In the same animals, cardiac electrophysiological properties (assessed by epicardial mapping) and structural characteristics were investigated. Our data indicate that FTO knockout mice were characterized by (i) higher heart rate values during resting and stress conditions, (ii) heart rate variability changes (increased LF to HF ratio), (iii) larger vulnerability to stress-induced tachyarrhythmias, (iv) altered ventricular repolarization, and (v) cardiac hypertrophy compared to wild-type counterparts. We conclude that FTO deficiency in mice leads to an imbalance of the autonomic neural modulation of cardiac function in the sympathetic direction and to a potentially proarrhythmic remodeling of electrical and structural properties of the heart.

AB - In humans, variants of the fat mass and obesity associated (FTO) gene have recently been associated with obesity. However, the physiological function of FTO is not well defined. Previous investigations in mice have linked FTO deficiency to growth retardation, loss of white adipose tissue, increased energy metabolism and enhanced systemic sympathetic activation. In this study we investigated for the first time the effects of global knockout of the mouse FTO gene on cardiac function and its autonomic neural regulation. ECG recordings were acquired via radiotelemetry in homozygous knockout (n = 12) and wild-type (n = 8) mice during resting and stress conditions, and analyzed by means of time- and frequency-domain indexes of heart rate variability. In the same animals, cardiac electrophysiological properties (assessed by epicardial mapping) and structural characteristics were investigated. Our data indicate that FTO knockout mice were characterized by (i) higher heart rate values during resting and stress conditions, (ii) heart rate variability changes (increased LF to HF ratio), (iii) larger vulnerability to stress-induced tachyarrhythmias, (iv) altered ventricular repolarization, and (v) cardiac hypertrophy compared to wild-type counterparts. We conclude that FTO deficiency in mice leads to an imbalance of the autonomic neural modulation of cardiac function in the sympathetic direction and to a potentially proarrhythmic remodeling of electrical and structural properties of the heart.

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JF - PLoS ONE

SN - 1932-6203

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Carnevali L, Graiani G, Rossi S, Banchaabouchi MA, Macchi E, Quaini F et al. Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice. PLoS ONE. 2014;9(4 (Art. No.: e95499)):1 - 10. https://doi.org/10.1371/journal.pone.0095499