P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage.

Purpose: Low-grade inflammation contributes to heart failure in obesity or type 2 diabetes mellitus. The P2X7 receptor (P2X7R) is a key regulator of several pro-inflammatory responses in multiple tissues and organs; however, its involvement in the onset of heart dysfunction remains unclear. The study evaluated the role of P2X7R as a cardiac function regulator in C57BL/6J wild-type (WT) and P2X7R knockout (KO) mice by inducing systemic inflammation with high fat diet (HFD). Methods: Specific parameters of systolic and diastolic function and heart morphology were measured in vivo before animal sacrifice by high-frequency ultrasonographic analysis. Gene and protein expression of cardiac biomarkers associated with inflammatory-oxidative pathways were evaluated by real-time PCR and Western Blotting. Results: P2X7R-mediated up-regulation of the NLRP3-caspase-1 complex, increased expression of key oxidative stress (NOS-2, TNFα), and chemotactic (MCP-1) mediators were revealed in WT-HFD animals. In KO-HFD mice, such inflammatory-oxidative pathway was silent. Nevertheless, HFD induced in vivo a clear alteration of diastolic pattern (E/A: p < 0.03 vs WT-HFD) and a cardiac morphologic remodelling (left ventricular mass: p < 0.05 vs WT-HFD) only in P2X7R KO animals. Surprisingly, the transcriptional and protein expression of IL-1β and IL-6, usually regulated through P2X7R activation, were significantly higher in KO-HFD than in WT-HFD mice (both p < 0.05). Furthermore, an up-regulation of miR-214 and a down-regulation of miR-126 in heart of HFD-KO mice were observed, suggesting a link between such epigenetic dysregulation and cytokine overexpression as a potential pathophysiologic mechanism concurring to the progressive cardiac dysfunction. Conclusion: These findings seem to suggest a cardioprotective role of P2X7R toward this tissue-specific inflammatory damage, likely through tissue homeostasis and organ functionality preservation.

Nutritional science is gaining increasing attention due to the implicit potential to prevent cardio-metabolic diseases. It is also becoming clear that food-making process might influence the metabolic response to the meal. We have conducted a proof-of-concept study to investigate whether slowly processed pasta might positively impact glucose homeostasis. A total of 14 healthy male volunteers underwent two different mixed-meal tests in a randomized order. One meal was composed of 100 g of normally processed pasta and the other 100 g of slowly processed pasta. Each meal was completed with 10 g of olive oil and 10 g of parmesan cheese. Glucose, insulin, and incretin post-prandial responses were assessed at 15, 30, 60, 90, 120, 150, and 180 min. Glucose tolerance, insulin, and incretin response were unaffected by the two different pasta types. However, a slight difference was evident in the shape of the curve of post-prandial insulin (i.e., mildly delayed with the slowly processed pasta). Despite the common belief of a different impact of normally processed and slowly processed pasta on glucose metabolism, they show a superimposable post-prandial metabolic response after a single meal in male healthy individuals. Further studies are required to confirm these results also in chronic, real-life settings and then to translate them to metabolically impaired individuals.