Abstract 1090: Bariatric Surgery Treats Morbid Obesity and Type 2 Diabetes: Mechanisms of Improved Endothelial Function
Morbid obesity and type 2 diabetes are closely associated with various complications of cardiovascular disease. Bariatric surgery is a relatively new and more aggressive therapy for these individuals. Despite these links, little has been known of the relationships between bariatric surgery and improved vascular endothelial function in severe obesity and type 2 diabetes. Accordingly, we hypothesized that bariatric surgery would ameliorate impaired endothelial function in severe obesity and type 2 diabetes and designed this study to elucidate the mechanisms that are responsible for this improved vascular function. To test this, we used wild type (WT) control mice (n=6) and type 2 diabetic db/db mice, which were divided into 5 groups, db/db-sham (n=6), −db/db-5days (n=6), −10days (n=5), −20days (n=6) and −30days (n=5) recovery after gastrojejunal bypass surgery (GJBS). Surgery significantly reduced body weight in db/db mice by ~20% (p<0.01), and lean mass remained unchanged after surgery. Fasting glucose levels in db/db mice were 462~517 mg/dl before surgery and 133~215 mg/dl after surgery (significantly different at p<0.01). We assessed endothelium dependent-(acetylcholine, ACh- and flow-induced) and independent -(sodium nitroprusside, SNP) dilation from isolated and pressurized (60 cmH2O) coronary arterioles (40 –100 μm). Although SNP-induced dilation was not altered after surgery, both ACh- and flow-mediated dilation were significantly improved in db/db-5days, −10days and −30days after surgery (p<0.05) and indistinguishable from the WT at db/db-20days surgery (p<0.01). Protein expression of eNOS was increased after surgery (p<0.05), but not in db/db-30days. Surgery reduced circulating level of interleukin 6 (IL-6) (p<0.05), but not in db/db-5days. Superoxide production was significantly reduced in all surgically treated db/db mice (p<0.05). Our results suggest that bariatric surgery in diabetic mice
reduces fat mass and blood glucose level, and
improves coronary endothelial function through increased eNOS protein expression, diminished proinflammatory cytokine, and decreased reactive oxidative stress.