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

Abstract

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.

Obesity induced by high fat diet attenuates postinfarct myocardial remodeling and dysfunction in adult B6D2F1 mice

“…Since hyperglycemia activates the cardiac intracellular renin-angiotensin system, which increases oxidative stress and cardiac fibrosis [36], the absence of hyperglycemia in our model could explain the preservation of function and heart morphology. Different experimental studies have previously shown that obese, dyslipidemic and insulin resistant mice are more prone to acute ischemia/reperfusion injury [13][14][15][16]37]. However, our results reveal that HFD-induced obesity paradoxically reduces ventricular dilatation, dysfunction and infarct size after transient coronary occlusion.…”

Increased Abdominal Adiposity Exacerbates Ex-Vivo Cardiac Reperfusion Injury through Augmented Mitochondrial Oxidative Stress

“…This agrees well with results obtained ex-vivo [5][6][7] and in-vivo [4,8,9] in rats fed a HF diet. However, this is in total opposition with the results from ZDF rats [13,14] and SMC-fed animals [2,3]. Yet, the two last situations are associated with increased blood glucose, whereas the increased chow intake was not in our study.…”

“…Thirdly, IAA is associated with low-grade inflammation [49], which could also have played a role. In spite of these environmental differences, several studies [2][3][4][5][6][7][8][9] have shown that the response to ischemia/reperfusion was similar in both in-vivo and exvivo contexts.…”

“…Sweetened condensed milk (SCM) and high-fat (HF) diets are the main energy-dense food diets tested. With SCM, CSI decreases [2,3] whereas, with HF diets, similar to so-called Western diets rich in saturated fats, CSI increases [4][5][6][7][8][9].…”

Myocardial susceptibility to ischaemia/reperfusion in obesity: a re-evaluation of the effects of age

“…This difference was still present after 17 months, although aging per se also caused a significant increase in intraperitoneal fat in the age-matched controls. We have previously demonstrated that the diet induced insulin resistance associated with a significant rise in serum insulin but not glucose levels [38]. …”