Obesity is associated with metabolic and vascular dysfunction. Many models have shown insulin resistance reduces endothelium-dependent vasodilation but this is also seen in obese subjects with normal glucose tolerance. There is also evidence of increased response to vascular injury in obese animals, although the mechanisms underpinning this are not fully understood. This study used a mouse model of diet-induced obesity (DIO) to address the hypothesis that obesity causes metabolic dysfunction, inhibition of endothelium-dependent relaxation and increased neointimal proliferation following wire-induced injury.
Male C57Bl/6 mice (5 weeks old) were fed obesogenic or control diets (8 weeks) and then underwent metabolic testing, including blood pressure measurement by tail cuff plethysmography. They were then either killed and femoral arteries collected for function analysis (n=7/group), or subjected to femoral artery luminal wire injury surgery (N=5 CON 7 DIO/group) and killed 4 weeks post injury. Injured vessels were excised and lesion volume assessed using 3-dimensional optical projection tomography (OPT) and histology.
DIO mice were heavier than controls (P<0.01), had higher circulating cholesterol and triglyceride levels and were hyperglycaemic and hyperinsulinaemic (DIO 1.39±0.16 versus CON 0.52±0.08 ng/ml P<0.001) on fasting and following a glucose load (repeated measures ANOVA; glucose P<0.001, insulin P<0.05). Development of obesity did not alter blood pressure (DIO 119±4 versus CON 121±3 mmHg), agonist-mediated contraction or endothelium-dependent or -independent relaxation of isolated femoral arteries. Similarly, DIO had no effect on the size of neointimal lesions following femoral artery injury whether analysed using OPT (Lesion volume; DIO 29.9±9.0 versus CON 38.2±7.1%), or histology (maximum cross sectional area; CON 58.3±7.9 vesus DIO 53.8±11.5%).
Thus, in young mice, obesity-induced alterations in glucose/insulin and lipid metabolism occur in the absence of vascular dysfunction. More prolonged exposure to diet-induced obesity or metabolic abnormalities may induce vascular changes, though this remains to be explored.