A high-fat diet increases risk of ventricular arrhythmia in female rats: enhanced arrhythmic risk in the absence of obesity or hyperlipidemia.
Obesity increases the incidence of cardiac arrhythmias and impairs wound healing. However, it is presently unknown whether a high-fat diet affects arrhythmic risk or wound healing before the onset of overt obesity or hyperlipidemia. After 8 wk of feeding a high-fat diet to adult female rats, a nonsignificant increase in body weight was observed and associated with a normal plasma lipid profile. Following ischemia/reperfusion injury, scar length (standard diet 0.29 +/- 0.09 vs. high-fat 0.32 +/- 0.13 cm), thickness (standard diet 0.047 +/- 0.02 vs. high-fat 0.059 +/- 0.01 cm), and collagen alpha(1) type 1 content (standard diet 0.21 +/- 0.04 vs. high-fat 0.20 +/- 0.04 arbitrary units/mm(2)) of infarcted hearts were not altered by the high-fat diet. However, the mortality rate was greatly increased 24 h postinfarction (from 5% to 46%, P < 0.01 for ischemia/reperfusion rats; from 20% to 89%, P < 0.0001, in complete-occlusion rats) in high-fat fed rats, in association with a higher prevalence of ventricular arrhythmias. Ventricular arrhythmia inducibility was also significantly increased in noninfarcted rats fed a high-fat diet. In the hearts of rats fed a high-fat diet, connexin-40 expression was absent, connexin-43 was hypophosphorylated and lateralized, and neurofilament-M immunoreactive fiber density (standard diet 2,020 +/- 260 vs. high-fat diet 2,830 +/- 250 microm(2)/mm(2)) and tyrosine hydroxylase protein expression were increased (P < 0.05). Thus, in the absence of overt obesity and hyperlipidemia, sympathetic hyperinnervation and an aberrant pattern of gap junctional protein expression and regulation in the heart of female rats fed a high-fat diet may have contributed in part to the higher incidence of inducible cardiac arrhythmias.
Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada.
Marie-Claude
MC
Aubin
Sophie
S
Cardin
Philippe
P
Comtois
Robert
R
Clément
Hugues
H
Gosselin
Marc-Antoine
MA
Gillis
Khaï
K
Le Quang
Stanley
S
Nattel
Louis P
LP
Perrault
Angelino
A
Calderone
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D017630:Connexins / Q000187:drug effects / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics; D006949:Hyperlipidemias / Q000150:complications* / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008136:Longevity / Q000187:drug effects; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D017180:Tachycardia, Ventricular / Q000139:chemically induced* / Q000503:physiopathology; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects
D017630:Connexins; D004041:Dietary Fats; D008055:Lipids