Early cardiovascular changes occurring in diet-induced, obese insulin-resistant rats

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dc.contributor.authorHuisamen B.
dc.contributor.authorDietrich D.
dc.contributor.authorBezuidenhout N.
dc.contributor.authorLopes J.
dc.contributor.authorFlepisi B.
dc.contributor.authorBlackhurst D.
dc.contributor.authorLochner A.
dc.date.accessioned2012-08-17T12:26:49Z
dc.date.available2012-08-17T12:26:49Z
dc.date.issued2012
dc.descriptionArticle
dc.description.abstractThe metabolic syndrome is recognized as a cluster of disturbances associated with obesity, type 2 diabetes and hypertension. Over the past two decades, the number of people with the metabolic syndrome has increased at an alarming rate. This increase is associated with the global epidemic of both obesity and diabetes. Cardiovascular mortality is increased among diabetics and obesity-related insulin-resistant patients, and obesity is currently recognized as independent risk factor for cardiovascular disease. We aimed to establish the effects of a short period of an altered diet on the heart using a rat model of hyperphagia-induced obesity (diet supplemented with sucrose and condensed milk for 8 weeks = DIO) compared to age-matched controls. Isolated, perfused hearts were subjected to global or regional ischaemia/reperfusion. Function on reperfusion was recorded and infarct size determined. A plasma lipid profile was established via HPLC-based methods and proteins involved in metabolic signalling determined either by western blotting or RTPCR. 8 weeks of diet resulted in whole-body but not myocardial insulin resistance, increased plasma triglyceride and phospholipid levels as well as increased lipid peroxidation. Despite the similar baseline function, hearts from DIO animals showed significantly poorer postischaemic recovery than controls (41.9 % RPP recovery vs 57.9 %, P\0.05, n = 7-11/group) but surprisingly, smaller infarct size (24.95 ± 1.97 vs 47.26 ± 4.05 % of the area at risk, P\0.005, n = 8/group). Basal phosphorylation of PKB/Akt was elevated but IRS-1 and SERCA-2 expression severely downregulated. In conclusion, after only 8 weeks of a slight change in diet, the rat heart shows signs of metabolic remodelling. Some of these changes may be protective but others may be detrimental and eventually lead to maladaptation. © 2012 Springer Science+Business Media, LLC.
dc.identifier.citationMolecular and Cellular Biochemistry
dc.identifier.citation368
dc.identifier.citation02-Jan
dc.identifier.citation37
dc.identifier.citation45
dc.identifier.issn3008177
dc.identifier.other10.1007/s11010-012-1340-9
dc.identifier.urihttp://hdl.handle.net/10019.1/49258
dc.subjectHeart
dc.subjectInsulin resistance
dc.subjectInsulin signalling
dc.subjectIschaemia/reperfusion
dc.subjectObesity
dc.titleEarly cardiovascular changes occurring in diet-induced, obese insulin-resistant rats
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