oa Insulin resistance alters noradrenergic sensitivity of omental vessels from morbidly obese Qataris

Background: Expanding adipose tissue in obesity requires effective angiogenesis and vasoreactivity to combat hypoxia and its consequences, such as insulin resistance and type-2 diabetes. While recent evidence suggests that the adipose tissue is highly angiogenic and inflammed, the tissue arteriolar vasoreactivity has been less investigated. As a consequence of the inflammation the omental adipose tissue (OAT) also synthesizes greater levels of vasoconstrictive molecules, such as cytokines and catecholamines, compared to the sub-cutaneous (SAT) depot, and these are likely to impact on the maintenance of vascular tone leading to greater susceptibility to hypoxia. This study compared the contractile responses of OAT and SAT arterioles from insulin-resistant (IR) and insulin-sensitive (IS) morbidly obese non-diabetic Qatari patients. Methods: Segments of arterioles (ID ~240-250 µm) isolated from SAT and OAT obtained from obese non-diabetic Qatari patients (age ~29 years, BMI ~40kg.m-2), undergoing bariatric weight reduction surgery, were mounted on a dual wire myograph (510A) and investigated for noradrenergic responsiveness. Cumulative concentration-response curves were constructed for noradrenaline (10-9 -10-5 M). Curves were also constructed for potassium chloride (KCl, 1-70 mM). Results: OM arterioles from IR patients were significantly less sensitive to NA compared with SAT arterioles from same patients (log EC50 -5.9±0.2 vs. -6.5±0.1, p<0.05). Maximum NA contractile response was also attenuated in OAT compared with SAT vessels (p<0.05) from these patients. On the other hand, KCl curves were comparable for OAT and SAT vessels from the same patients. In addition, no differences in noradrenergic sensitivity were observed between OAT and SAT vessels from IS patients. Conclusions: The data suggest that insulin resistance selectively alters noradrenergic responsiveness of OAT arterioles compared with SAT vessels from morbidly obese non-diabetic Qataris. Differences in adrenoceptor density/function may underlie these depot-specific responses. Studies on the disease specific differences need further investigation.