oa Endothelial dysfunction in morbidily obese young Qataris

Background & objectives: The prevalence of metabolic syndrome (MetS), including obesity, dyslipidemia, hyperglycemia and hypertension, associated with an increased predisposition to cardiovascular disease (CVD), is especially high in the Middle East, primarily amongst young Qataris. Both insulin resistance and endothelial dysfunction have been proposed to contribute to the pathogenesis of CVD in obese patients. Recent reports have shown that abdominal adipose tissue depot-specific differences impact on endothelial vasomotor function, with the visceral/omental environment considered more pathogenic. It is, however, unclear how severe the effect would be on a relatively young obese population. This study investigated endothelium-dependent relaxation of small arteries embedded in two adipose tissue depots, the sub-cutaneous and the omental. Methods: Arteries were isolated from omental (OM) and subcutaneous (SC) adipose tissues collected from consented Qatari patients undergoing bariatric surgery for weight reduction. The arteries (ID ~251 µM for SC and ~ 262 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- 10000 nM, the classical endothelium-dependent relaxant) in the absence or presence of Nω-Nitro-L-arginine methyl ester (L-NAME,100 µM, nitric oxide synthase inhibitor) on initial tone generated with noradrenaline (5 µM). Relaxation to sodium nitroprusside (SNP) and prostaglandin E2 were also recorded. Results: The mean age of the patients was 32 years, their blood glucose 5.6 mmol/L, Insulin 19.3 µU/ml , the index of insulin sensitivity/resistance (HOMA) 5.5 and body mass index 43.4 Kg/m2. Relaxation to Ach was significantly attenuated in OM vessels (Emax 51±9 %) compared with SC vessels (Emax 79±6 %, p<0.05) from same patients. The Ach response was further reduced in the presence of L-NAME. In contrast, the relaxation to SNP and PGE2 were greater in OM vessels compared with the SC vessels. Conclusions: These results demonstrate adipose tissue depot-specific differences in the impact of obesity on endothelial function in morbidly obese, insulin resistant, young Qataris, with a marked reduction in endothelium NO-dependent relaxation in the OM compared with SC vessels. The reversibility of this lesion by weight loss are yet to be ascertained.