Objective: To evaluate the early effect of Roux-en-Y (RYGB) gastric bypass on hormones involved in body weight regulation and glucose metabolism. Significant Background Data: The RYGB is an effective bariatric procedure for which the mechanism of action has not been elucidated yet. Reports of hormonal changes after RYGB suggest a possible endocrine effect of the operation; however, it is unknown whether these changes are the cause or rather the effect of surgically induced weight loss. We speculated that if the mechanism of action of the RYGB involves an endocrine effect, then hormonal changes should occur early after surgery, prior to substantial body weight changes. Methods: Ten patients with a mean preoperative body mass index (BMI) of 46.2 kg/m 2 (40 -53 kg/m 2 ) underwent laparoscopic RYGB. Six patients had type 2 diabetes treated by oral hypoglycemic agents. Preoperatively and 3 weeks following surgery, all patients were tested for fasting glucose, insulin, glucagon, insulinlike growth factor 1 (IGF-1), leptin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), corticosterone, and neuropeptide Y (NPY). Results: Changes in mean BMI were rather minimal (43.2 kg/m 2 ; P ϭ not significant), but there was a significant decrease in blood glucose (P ϭ 0.005), insulin (P ϭ 0.02), IGF-1 (P Ͻ 0.05), leptin (P ϭ 0.001), and an increase in ACTH levels (P ϭ 0.01). The other hormones were not significantly changed by surgery. All the 6 diabetic patients had normal glucose and insulin levels and did not require medications after surgery. The RYGB reduced GIP levels in diabetic patients (P Ͻ 0.01), whereas no changes in GIP levels were found in nondiabetics. Conclusions: Roux-en-Y gastric bypass determines considerable hormonal changes before significant BMI changes take place. These results support the hypothesis of an endocrine effect as the possible mechanism of action of RYGB. S urgery represents the most effective therapeutic modality for morbid obesity.1,2 Interestingly, the Roux-en-Y gastric bypass (RYGB), a procedure that includes the creation of a small proximal gastric pouch and the bypass of the duodenum and proximal jejunum from the transit of food, not only determines permanent reduction of excess body weight, but also induces resolution of type 2 diabetes mellitus in more than 80% of morbidly obese patients. 3Body weight is the result of complex physiologic mechanisms that control food intake and energy expenditure. Regulation of body weight involves several systems such as the adipose tissue, 4 the hypothalamus, 5 and the adrenal glands, 6 which are linked by neural and hormonal signals. Recent investigations have identified several key molecules that regulate food intake, including ghrelin, neuropeptide Y (NPY), 7 and melanocortins 8 and have focused on the relationship between obesity and leptin levels. The effectiveness of gastric bypass in inducing remarkable weight loss and control of diabetes represents an "experimental mod...

We hypothesized that tissue hyperoxia would enhance and hypoxia inhibit neovascularization in a wound model. Therefore, we used female Swiss-Webster mice to examine the influence of differential oxygen treatment on angiogenesis. One milliliter plugs of Matrigel, a mixture of matrix proteins that supports but does not itself elicit angiogenesis, were injected subcutaneously into the mice. Matrigel was used without additive or with added vascular endothelial growth factor (VEGF) or anti-VEGF antibody. Animals were maintained in hypoxic, normoxic, or one of four hyperoxic environments: hypoxia -- 13 percent oxygen at 1 atmosphere absolute (ATA); normoxia -- 21 percent oxygen at 1 ATA; hyperoxia -- (groups a-d) 100 percent oxygen for 90 minutes twice daily at the following pressures: Group a, 1 ATA; Group b, 2 ATA; Group c, 2.5 ATA; Group d, 3.0 ATA. Subcutaneous oxygen tension was measured in all groups. The Matrigel was removed 7 days after implantation. Sections were graded microscopically for the extent of neovascularization. Angiogenesis was significantly greater in all hyperoxic groups and significantly less in the hypoxic group compared with room air-exposed controls. Anti-VEGF antibody abrogated the angiogenic effect of both VEGF and increased oxygen tension. We conclude that angiogenesis is proportional to ambient pO(2) over a wide range. This confirms the clinical impression that angiogenesis requires oxygen. Intermittent oxygen exposure can satisfy the need for oxygen in ischemic tissue.

Macrophages respond to various stimuli to produce angiogenic factors but few mechanistic details are known. We examined the effects of hypoxia, lactate and nicotinamide on the expression of vascular endothelial growth factor by cultured macrophages. These agents were chosen because they down-regulate polyadenosine diphosphoribose levels. Following exposure, conditioned media were analyzed for vascular endothelial growth factor protein. Nicotinamide adenine dinucleotide, polyadenosine diphosphoribose, and vascular endothelial growth factor mRNA were measured in the cellular fraction. Angiogenic capacity of the conditioned media was tested in rabbit corneas and Matrigel implants. All three agents, hypoxia, lactate and nicotinamide, elicited significantly increased levels of vascular endothelial growth factor mRNA and vascular endothelial growth factor in the conditioned media, and these levels were paralleled by their angiogenic activity. Polyadenosine diphosphoribose in the cellular fraction was correspondingly depressed. Anti-vascular endothelial growth factor antibody inhibited most of the angiogenic response whereas anti-basic fibroblast growth factor antibody had little effect. We propose that redox changes associated with the alteration of cellular nicotinamide adenine dinucleotide and polyadenosine diphosphoribose are involved in lactate-mediated VEGF expression.

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In this series, no difference in weight loss outcome variables were observed up to 1 year after laparoscopic RYGB. Thus, extending Roux limb length from < or =100 cm to 150 cm did not significantly improve weight loss outcome in patients with a BMI < 50 kg/m2.