Dietary interaction of high fat and marginal copper deficiency on cardiac contractile function.
OBJECTIVE
High-fat and marginally copper-deficient diets impair heart function, leading to cardiac hypertrophy, increased lipid droplet volume, and compromised contractile function, resembling lipotoxic cardiac dysfunction. However, the combined effect of the two on cardiac function is unknown. This study was designed to examine the interaction between high-fat and marginally copper-deficient diets on cardiomyocyte contractile function.


METHODS
Weanling male rats were fed diets incorporating a low- or high-fat diet (10% or 45% of kcal from fat, respectively) with adequate (6 mg/kg) or marginally deficient (1.5 mg/kg) copper content for 12 weeks. Contractile function was determined with an IonOptix system including peak shortening (PS), time-to-PS, time-to-90% relengthening, maximal velocity of shortening/relengthening, and intracellular Ca(2+) ([Ca(2+)](I)) rise and decay.


RESULTS
Neither dietary treatment affected blood pressure or glucose levels, although the high-fat diet elicited obesity and glucose intolerance. Both diets depressed PS, maximal velocity of shortening/relengthening, and intracellular Ca(2+) ([Ca(2+)](I)) rise and prolonged time-to-90% relengthening and Ca(2+) decay without an additive effect between the two. Ca(2+) sensitivity, apoptosis, lipid peroxidation, nitrosative damage, tissue ceramide, and triglyceride levels were unaffected by either diet or in combination. Phospholamban (PLB) but not sarco(endo)plasmic reticulum Ca(2+)-ATPase was increased by both diets. Endothelial NO synthase was depressed with concurrent treatments. The electron transport chain was unaffected, although mitochondrial aconitase activity was inhibited by the high-fat diet.


CONCLUSIONS
These data suggest that high-fat and marginally copper deficient diets impaired cardiomyocyte contractile function and [Ca(2+)](i) homeostasis, possibly through a similar mechanism, without obvious lipotoxicity, nitrosative damage, and apoptosis.
Relling
David P
DP
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine, Grand Forks, North Dakota, USA.
Esberg
Lucy B
LB
Johnson
W Thomas
WT
Murphy
Eric J
EJ
Carlson
Edward C
EC
Lukaski
Henry C
HC
Saari
Jack T
JT
Ren
Jun
J
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003300:Copper / Q000172:deficiency*; D004041:Dietary Fats / Q000494:pharmacology*; D006331:Heart Diseases / Q000209:etiology; D008275:Magnesium Deficiency; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D051381:Rats
D001786:Blood Glucose; D004041:Dietary Fats; D003300:Copper