High-fructose diet elevates myocardial superoxide generation in mice in the absence of cardiac hypertrophy.
OBJECTIVE
Dietary fructose intake has increased considerably in recent decades and this has been paralleled by an increase in the incidence of insulin resistance, especially in children and adolescents. The impact of a high-fructose diet on the myocardium is not fully understood. The aims of this study were to characterize the murine metabolic and cardiac phenotypes associated with a high-fructose diet and to determine whether this diet imparts differential effects with age.


METHODS
Juvenile (4 wk) and adult (14 wk) C57Bl/6 mice were fed a 60% fructose diet or isoenergetic control (starch) diet for 6 wk.


RESULTS
At completion of the dietary intervention (at ages 10 and 20 wk), fructose-fed mice were normotensive; hyperinsulinemia and cardiac hypertrophy were not evident. Interestingly, fructose-fed mice exhibited lower blood glucose levels (10 wk: 4.81+/-0.28 versus 5.42+/-0.31 mmol/L; 20 wk: 4.88+/-0.30 versus 5.96+/-0.42 mmol/L, P<0.05) compared with controls. Nicotinamide adenosine dinucleotide phosphate-driven myocardial superoxide production was significantly increased in fructose-fed mice at both ages (by approximately 29% of control at 10 wk of age and 16% at 20 wk, P<0.01). No increase in aortic superoxide production was observed. Fructose feeding did not alter gene expression of the antioxidant thioredoxin-2, suggesting an imbalance between myocardial reactive oxygen species generation and antioxidant induction.


CONCLUSIONS
These findings indicate that increased myocardial superoxide production may represent an early and primary cardiac pathologic response to the metabolic challenge of excess dietary fructose in juveniles and adults that can be detected in the absence of cardiac hypertrophy and hypertension.
Mellor
Kimberley
K
Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia.
Ritchie
Rebecca H
RH
Meredith
Greta
G
Woodman
Owen L
OL
Morris
Margaret J
MJ
Delbridge
Lea M D
LM
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly; D019422:Dietary Sucrose / Q000008:administration & dosage*; D005632:Fructose / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007328:Insulin / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009249:NADP / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
D001786:Blood Glucose; D019422:Dietary Sucrose; D007328:Insulin; D013481:Superoxides; D005632:Fructose; D013879:Thioredoxins; D009249:NADP