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Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice.
Carnevali, Luca; Graiani, Gallia; Rossi, Stefano; Al Banchaabouchi, Mumna; Macchi, Emilio; Quaini, Federico; Rosenthal, Nadia; Sgoifo, Andrea.
Afiliação
  • Carnevali L; Department of Neuroscience, University of Parma, Parma, Italy.
  • Graiani G; Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
  • Rossi S; Department of Life Sciences, University of Parma, Parma, Italy.
  • Al Banchaabouchi M; Preclinical Phenotyping Facility, CSF-Campus Science Support Facilities GmbH, Vienna, Austria; European Molecular Biology Laboratory (EMBL) Mouse Biology Unit, Monterotondo, Italy.
  • Macchi E; Department of Life Sciences, University of Parma, Parma, Italy.
  • Quaini F; Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
  • Rosenthal N; Australian Regenerative Medicine Institute/EMBL Australia, Monash University, Melbourne, Victoria, Australia; European Molecular Biology Laboratory (EMBL) Mouse Biology Unit, Monterotondo, Italy.
  • Sgoifo A; Department of Neuroscience, University of Parma, Parma, Italy.
PLoS One ; 9(4): e95499, 2014.
Article em En | MEDLINE | ID: mdl-24743632
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sistema Nervoso Autônomo / Proteínas / Frequência Cardíaca Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sistema Nervoso Autônomo / Proteínas / Frequência Cardíaca Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article