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Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice
Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 4, p e95499 (2014), PLoS ONE; Vol 9
- Publication Year :
- 2014
-
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.
- Subjects :
- STIMULATION
Male
Physiology
lcsh:Medicine
White adipose tissue
FTO gene
Nervous System
Body Temperature
Mice
Heart Rate
Heart rate variability
lcsh:Science
SOCIAL STRESS
Mice, Knockout
HEART-RATE-VARIABILITY
Multidisciplinary
PURKINJE-FIBERS
Animal Models
Cardiovascular physiology
Multidisciplinary Sciences
Electrophysiology
OBESITY
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Knockout mouse
Science & Technology - Other Topics
Anatomy
Research Article
Cardiac function curve
medicine.medical_specialty
General Science & Technology
DURATION
Mouse Models
Motor Activity
Autonomic Nervous System
Research and Analysis Methods
Model Organisms
Internal medicine
Heart rate
medicine
Genetics
Animals
ARRHYTHMIAS
Science & Technology
business.industry
lcsh:R
Proteins
Biology and Life Sciences
GENE
NERVOUS-SYSTEM
Endocrinology
QT INTERVAL PROLONGATION
Cardiovascular Anatomy
lcsh:Q
Gene Function
business
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....c744e4878c73926fc68c4689467571dc