oa Impact Of Metabolic Health On Microvascular Endothelial Function In Morbidly Obese Qataris

Background & objectives: Vascular complications account for much of the morbidity of obesity. The proportion of Qatari population that is overweight or obese is one of the highest in the world. With this comes the increased risk of blood vessel dysfunction and predisposition to type 2 diabetes and hypertension. The vascular endothelium is often the first target of the negative impact of obesity. It is however unclear how the heterogeneity in the metabolic status of obese individuals (ie metabolically healthy [MHO] vs. Pathologically obese [PO]) will impact on endothelial function, particularly in a relatively young obese population, as in Qatar. This study investigated endothelium-dependent relaxation of small arteries embedded in the visceral (omental) and subcutaneous adipose tissues in morbid obesity with varying metabolic status. Methods: Arteries were isolated from abdominal omental (OM) and subcutaneous (SC) fat collected from consented Qatari patients undergoing bariatric surgery for weight reduction. The arteries (normalized luminal diameter ~250 µm for SC and ~ 240 µm for OM) were cut into segments (~2 mm) and mounted on a dual wire Myograph (510A) for measurement of isometric tension. Cumulative concentration-response curves were constructed for acetylcholine (1- 30000 nM, the classical endothelium-dependent relaxant) in the absence or presence of Nω-Nitro-L-arginine methyl ester (L-NAME,100 µM, nitric oxide [NO] synthase inhibitor) on initial tone generated with noradrenaline (5 µM). Relaxation to sodium nitroprusside (SNP, an NO donor) was also recorded. Results: There were no differences in age (~32 years), blood glucose (~5.6 mmol/L) and body mass index (BMI , ~ 43.4 Kg.m-2) between the MHO and PO patients . Insulin levels were 3 vs 19 µU/ml for MHO vs PO patients and their indices of insulin resistance (HOMA) were 1 vs 5 respectively. In general, relaxation to Ach was significantly attenuated in OM vessels (Emax 44±8 %) compared with SC vessels (Emax 78±4 %, p<0.01) from same patients. In contrast, relaxation to SNP was greater in the OM compared with the SC vessels. When Ach relaxation of the OM vessels were separated according to the patients' metabolic status, the MHO patients had significantly improved result compared with PO patients. On the other hand, relaxation of SC vessels from both groups of patients were comparable. In both vessel types, L-NAME caused a right-ward shift in the Ach curves. Conclusions: These results suggest that the metabolic status of obese Qatari patients has bearing on the physiology of their microvascular endothelium. The data also demonstrate that early changes in endothelial vasomotor function are depot-specific, being more marked in OM compared with SC vessels of pathologically obese patients.