Decreased expression of the NLRP6 inflammasome is associated with increased intestinal permeability and inflammation in obesity with type 2 diabetes

• DOI: 10.1007/s00018-024-05124-3
• Publication Date: 2024-02-05T13:02:21Z
• Authors: Gema Frühbeck; Javier Gómez-Ambrosi; Beatriz Ramírez; Sara Becerril; Amaia Rodríguez; Amaia Mentxaka; Víctor Valentí; Rafael Moncada; Gabriel Reina; Jorge Baixauli; Marcos Casado; Camilo Silva; Javier Escalada; Victoria Catalán
• Keywords: Intestinal Permeability; Proinflammatory cytokine; Interleukin 18

Abstract Background Obesity-associated dysfunctional intestinal permeability contributes to systemic chronic inflammation leading the development of metabolic diseases. The inflammasomes constitute essential components in regulation homeostasis. We aimed determine impact gut barrier dysfunction and context obesity type 2 diabetes (T2D). Methods Blood samples obtained from 80 volunteers ( n = 20 normal weight, 21 OB without T2D, 39 with T2D) a subgroup jejunum were used case–control study. Circulating levels damage markers expression as well their main effectors (IL-1β IL-18) key inflammation-related genes analyzed. factors, different metabolites Akkermansia muciniphila integrity was evaluated. effect blocking NLRP6 by using siRNA also studied. Results Increased circulating P < 0.01) endotoxin, LBP, zonulin patients decreased 0.05) after weight loss. Patients T2D exhibited gene its effector IL18 together increased mRNA inflammatory markers. further showed that while primarily localized goblet cells, NLRP3 epithelial cells. Additionally, Nlrp1 , Nlrp3 Nlrp6 small tract rats diet-induced found. regulated taurine, parthenolide A. human enterocyte cell line CCL-241. Finally, significant decrease release MUC2 knockdown observed. Conclusions downregulation obesity-associated suggest defective inflammasome sensing, driving an impaired may regulate progression multiple comorbidities.