Adenosine is an endogenous signaling molecule upregulated during inflammatory conditions. Acting through the A2b receptor (A2bR), the predominant adenosine receptor in human colonic epithelia, adenosine has been directly implicated in immune and inflammatory responses in the intestine. Little is known about expression and regulation of A2bR during inflammation. Tumor necrosis factor alpha (TNF-alpha) is highly upregulated during chronic and acute inflammatory diseases. This study examined the expression of A2bR during colitis and studied effects of TNF-alpha on A2bR expression, signaling and function. Results demonstrated that A2bR expression increases during active colitis. TNF-alpha pretreatment of intestinal epithelial cells increased A2bR messenger RNA and protein expression. TNF-alpha significantly increased adenosine-induced membrane recruitment of A2bR and cyclic adenosine monophosphate downstream signaling. Further, TNF-alpha potentiated adenosine-induced shortcircuit current and fibronectin secretion. In conclusion, we demonstrated that TNF-alpha is an important regulator of A2bR, and during inflammation, upregulation of TNF-alpha may potentiate adenosine-mediated responses.

Introduction Micronutrient deficiencies are key concerns after bariatric surgery. We describe the prevalence of perioperative testing and diagnosis of micronutrient deficiencies among a cohort of insured bariatric surgery patients. Methods We used claims data from seven health insurers to identify bariatric surgery patients from 2002–2008. Our outcomes were perioperative claims for vitamin D, B12, folate, and iron testing and diagnosed deficiencies. We analyzed results by bariatric surgery type: Roux-en-Y gastric bypass (RYGB), restrictive, and malabsorptive. We calculated the prevalence of testing and deficiency diagnosis, and performed multivariate logistic regression to determine the association with surgery type. Results Of 21,345 eligible patients, 84% underwent RYGB. The pre-surgical testing prevalence for all micronutrients was <25%. The testing prevalence during the first 12 months after surgery varied: vitamin D (12%), vitamin B12 (60%), folate (47%) and iron (49%), and declined during 13–24 and 25–36 months. The deficiency prevalence during 0–12 months post-survey varied: vitamin D (34%), vitamin B12 (20%), folate (13%), and iron (10%). The odds of vitamin B12, folate, and iron deficiency during 0–12 months were significantly lower for restrictive as compared to RYGB, but were not different during 13–24 and 25–36 months post-surgery. The odds of vitamin D deficiency were significantly greater for malabsorptive as compared to RYGB during all post-surgical periods. Conclusion Many patients did not receive micronutrient testing pre- or post-surgery, yet deficiencies were relatively common among those tested. These results highlight the need for surgeons and primary care providers to test all bariatric surgery patients for micronutrient deficiencies.

Adenosine is an endogenous signaling molecule that is highly up-regulated in inflammatory states. Adenosine acts through the A2b receptor, a G protein-coupled receptor that couples positively to G␣ s and activates ad-

Background Recent studies describe a unique subset of obese individuals with normal metabolic profiles despite having excess weight called “metabolically healthy but obese (MHO)”. Objective Our aim was to determine the prevalence of individuals without diabetes and hypertension and risk factors associated with the MHO phenotype among bariatric surgery patients. Methods We conducted a retrospective study of 710 adults who underwent bariatric surgery at Johns Hopkins between 2008 and 2010. In the first analysis of 523 individuals, we identified 150 individuals without diabetes and hypertension; in the second analysis of 260 individuals, we identified 44 individuals without diabetes, hypertension and hypertriglyceridemia. We used multivariable logistic regression to examine the association between each group and potential risk factors including age, sex, race, BMI (body mass index) and presence of liver disease on liver biopsy. Results The prevalence of individuals without diabetes and hypertension was 28.7%; among these individuals 88.7% had liver steatosis, 7.3% nonalcoholic steatohepatitis (NASH), and 19.3% liver fibrosis. These individuals were significantly more likely to be White OR=1.9 (95% CI: 1.1–3.1), younger OR= 4.1 (95% CI=2.6–6.3), and female OR=2.1, (95% CI=1.2–3.6) and less likely to have liver steatosis OR=0.4 (95% CI=0.2–0.9) or NASH OR=0.3 (95% CI=0.2–0.6). Conclusion Among bariatric surgery patients, almost a third of patients do not have diabetes and hypertension and could be probably considered “MHO” and were more likely to be white, young, female and have less liver injury. The high prevalence of liver steatosis in MHO individuals among bariatric surgery patients challenges the notion of MHO as a truly metabolically healthy entity.