title: Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice.
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.
authors.affiliation: Department of Neuroscience, University of Parma, Parma, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Carnevali
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Gallia
authors.initials: G
authors.lastname: Graiani
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Preclinical Phenotyping Facility, CSF-Campus Science Support Facilities GmbH, Vienna, Austria; European Molecular Biology Laboratory (EMBL) Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Mumna
authors.initials: M
authors.lastname: Al Banchaabouchi
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Macchi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Quaini
authors.affiliation: Australian Regenerative Medicine Institute/EMBL Australia, Monash University, Melbourne, Victoria, Australia; European Molecular Biology Laboratory (EMBL) Mouse Biology Unit, Monterotondo, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosenthal
authors.affiliation: Department of Neuroscience, University of Parma, Parma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sgoifo
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D001341:Autonomic Nervous System / Q000378:metabolism / Q000502:physiology*; D001831:Body Temperature; D006339:Heart Rate / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D011506:Proteins; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO
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