title: High carbohydrate and high fat diets protect the heart against ischaemia/reperfusion injury.
abstract: BACKGROUND
  Although obesity is still considered a risk factor in the development of cardiovascular disorders, recent studies suggested that it may also be associated with reduced morbidity and mortality, the so-called "obesity paradox". Experimental data on the impact of diabetes, obesity and insulin resistance on myocardial ischaemia/reperfusion injury are controversial. Similar conflicting data have been reported regarding the effects of ischaemic preconditioning on ischaemia/reperfusion injury in hearts from such animals. The aim of the present study was to evaluate the susceptibility to myocardial ischaemia/reperfusion damage in two models of diet-induced obesity as well as the effect of ischaemic and pharmacological preconditioning on such hearts.
  
  
  METHODS
  Three groups of rats were fed with: (i) normal rat chow (controls) (ii) a sucrose-supplemented diet (DIO) (iii) a high fat diet (HFD). After 16 weeks, rats were sacrificed and isolated hearts perfused in the working mode and subjected to 35 min regional ischaemia/60 min reperfusion. Endpoints were infarct size and functional recovery. Infarct size was determined, using tetrazolium staining. Activation of PKB/Akt and ERKp44/p42 (RISK pathway) during early reperfusion was determined using Western blot. Statistical evaluation was done using ANOVA and the Bonferroni correction.
  
  
  RESULTS
  Infarct sizes of non-preconditioned hearts from the two obese groups were significantly smaller than those of the age-matched controls. Ischaemic as well as pharmacological (beta-adrenergic) preconditioning with a beta2-adrenergic receptor agonist, formoterol, caused a significant reduction in infarct size of the controls, but were without effect on infarct size of hearts from the obese groups. However, ischaemic as well as beta-preconditioning caused an improvement in functional performance during reperfusion in all three groups. A clear-cut correlation between the reduction in infarct size and activation of ERKp44/p42 and PKB/Akt was not observed: The reduction in infarct size observed in the non-preconditioned hearts from the obese groups was not associated with activation of the RISK pathway. However, beta-adrenergic preconditioning caused a significant activation of ERKp44/p42, but not PKB/Akt, in all three groups.
  
  
  CONCLUSIONS
  Relatively long-term administration of the two obesity-inducing diets resulted in cardioprotection against ischaemia/reperfusion damage. Further protection by preconditioning was, however, without effect on infarct size, while an improvement in functional recovery was observed.
authors.forename: Ruduwaan
authors.initials: R
authors.lastname: Salie
authors.forename: Barbara
authors.initials: B
authors.lastname: Huisamen
authors.forename: Amanda
authors.initials: A
authors.lastname: Lochner
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000379:methods*; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000178:diet therapy* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004040:Dietary Carbohydrates