Molecular and Pharmacological Evidence for the Expression of Multiple Functional P2 Purinergic Receptors in Human Adipocytes.

Extracellular ATP exerts important functions as an extracellular signaling molecule via the activation of specific P2 purinergic receptors (P2X and P2Y). We investigated the expression of the different P2 receptors and their possible functional activation in human adipocytes in primary culture. We performed molecular expression analysis of the P2 receptors in human mature adipocytes; examined their functional activation by different nucleotides evaluating [Ca2+]i modifications and IL-6 secretion, and determined the ability of adipocytes to release ATP in the extracellular medium. Human adipocytes express different P2X and P2Y receptors. Extracellular ATP elicited a rise in [Ca2+]i via the activation of P2X and P2Y receptor subtypes. Human adipocytes spontaneously released ATP in the extracellular medium and secreted IL-6 both at rest and after stimulation with ATP. This stimulatory effect of ATP on IL-6 secretion was inhibited by pre-incubation with apyrase, an ATP metabolizing enzyme. These results demonstrate that human adipocytes express different P2X and P2Y receptors that are functionally activated by extracellular nucleotides. Furthermore, human adipocytes spontaneously release ATP, which can act in an autocrine/paracrine fashion on adipocytes, possibly participating in the regulation of inflammatory cytokine release. Thus, P2 purinergic receptors could be a potential therapeutic target to contrast the inflammatory and metabolic complications characterizing obesity.

Improvement of Lipid Profile after One-Anastomosis Gastric Bypass Compared to Sleeve Gastrectomy.

Fewer studies compared the improvement of plasma lipid levels after different types of surgery, in particular compared to one-anastomosis gastric bypass (OAGB). The aim of our study was to investigate how laparoscopic sleeve gastrectomy (LSG) and OAGB impact on weight loss and lipid profile 18 months after surgery, in patients with severe obesity. Forty-six patients treated with OAGB were matched to eighty-eight patients submitted to LSG. Weight loss after OAGB (33.2%) was more evident than after LSG (29.6%) (p = 0.024). The difference in the prevalence of dyslipidemia showed a statistically significant reduction only after OAGB (61% versus 22%, p < 0.001). After adjustment for delta body mass index (BMI), age and sex, we demonstrated a statistically significant decrease of the differences between the changes before and after (delta Δ) the two surgery procedures: Δ total cholesterol values (p < 0.001), Δ low density lipoprotein-cholesterol values (p < 0.001) and Δ triglycerides values (p = 0.007). Patients with severe obesity undergoing to OAGB presented a better improvement of lipid plasma values than LSG patients. The reduction of lipid plasma levels was independent of the significant decrease of BMI after surgery, of age and of sex.

Prevalence of different subtypes of serrated polyps and risk of synchronous advanced colorectal neoplasia in average-risk population undergoing first-time colonoscopy.

OBJECTIVES: A growing body of evidence indicates that patients with sessile serrated adenoma/polyp (SSA/P) and traditional serrated adenoma (TSA) are at risk for subsequent malignancy. Despite increasing knowledge on histological categorization of serrated polyps (SPs) data are lacking on the actual prevalence and the association of each SP subtype with advanced colorectal neoplasia. METHODS: We prospectively determined the prevalence of different SP subtypes and evaluate the association with synchronous advanced neoplasia in asymptomatic average-risk subjects undergoing first-time colonoscopy. All retrieved polyps were examined by two independent pathologists. Serrated lesions were classified into hyperplastic polyps (HP), SSA/P (without and with cytological dysplasia, SSA/P/DIS), and TSA, and were screened for BRAF and K-ras mutations. RESULTS: Among 258 polyps detected in 985 subjects, the proportion of SSA/P and TSA was 8.9% and 1.9% with an overall prevalence of 2.3% and 0.6%, respectively. SSA/Ps were small without significant difference in their location between proximal and distal colon; TSA were predominantly left-sided. BRAF mutation was common in SSA/Ps and K-ras mutation was present in all TSA. Independent predictors of advanced neoplasia were male sex (odds ratio (OR)=2.0, 95% confidence interval (CI) 1.0-4.0), increasing age (OR=4.5, 95% CI 1.5-13.4 for 50-69 years and OR=9.9, 95% CI 3.1-31.5 for >70 years), current smoking (OR=2.0, 95% CI 1.3-6.8), >3 tubular adenoma (OR=3.6, 95% CI 1.9-6.4), and SSA/P (OR=6.0, 95% CI 1.9-19.5). CONCLUSIONS: The substantial prevalence of BRAF-mutated SSA/P and the independent association with synchronous advanced colorectal neoplasia in asymptomatic average-risk subjects support the overall impact of the serrated pathway on colorectal cancer (CRC) risk in general population. The endoscopic characteristics of SSA/P emphasize the need of high-quality colonoscopy as a key factor for an effective CRC screening program.