Molecular and Cellular Biochemistry

, Volume 368, Issue 1–2, pp 37–45 | Cite as

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

  • Barbara Huisamen
  • Daneel Dietrich
  • Nicole Bezuidenhout
  • John Lopes
  • Brian Flepisi
  • Dee Blackhurst
  • Amanda Lochner


The 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 RT-PCR. 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.


Heart Obesity Insulin resistance Ischaemia/reperfusion Insulin signalling 


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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Barbara Huisamen
    • 1
    • 2
  • Daneel Dietrich
    • 3
  • Nicole Bezuidenhout
    • 1
  • John Lopes
    • 1
  • Brian Flepisi
    • 1
  • Dee Blackhurst
    • 4
  • Amanda Lochner
    • 1
    • 2
  1. 1.Division Medical Physiology, Department of Biomedical SciencesFaculty of Health Sciences, University of StellenboschTygerbergSouth Africa
  2. 2.Cape Heart CentreUniversity of Cape TownCape TownSouth Africa
  3. 3.Department of Medical BiosciencesUniversity of Western CapeBellvilleSouth Africa
  4. 4.Cape Heart Centre Lipid ClinicUniversity of Cape TownCape TownSouth Africa

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