Upregulated NLRP3 inflammasome activation is attenuated by anthocyanins in patients with nonalcoholic fatty liver disease: A case-control and an intervention study

• NLRP3 inflammasome is activated in mononuclear blood cells from NAFLD patients. • Plasma levels of interleukin (IL)−1β and IL-18 are increased in NAFLD patients. • Anthocyanins interrupt NLRP3 inflammasome activation in NAFLD patients. • Anthocyanins inhibit IL-1β and IL-18 expression in NAFLD patients. Despite the recent attention focused on the roles of the NLRP3 inflammasome in the pathogenesis of metabolic and inflammatory diseases, little is known about the activation status of NLRP3 inflammasome in patients with nonalcoholic fatty liver disease (NAFLD). The present study aimed to investigate whether inflammasomes activation is upregulated in patients with NAFLD and the upregulation can be attenuated by anthocyanins, which are polyphenols with known anti-inflammatory activities. This study included a case-control study and a randomized controlled intervention trial. In the first part, NAFLD patients and healthy controls were recruited from a cohort of railroad workers. In the second part, NAFLD patients were randomly assigned to receive either capsules of anthocyanins (320 mg daily) or placebo for 12 weeks. A series of genes and factors associated with activation of NLRP3 inflammasome in subjects’ plasma and peripheral blood mononuclear cells (PBMCs) were analyzed. Compared with healthy controls, the mRNA levels of NLRP3 inflammasome components (NLRP3, caspase-1, interleukin (IL)-1β, and IL-18) were significantly upregulated in the PBMCs of NAFLD patients. Consistently, plasma levels of mature IL-1β and IL-18 in NAFLD patients were significantly higher than in controls. After anthocyanin administration, both mRNA expression of NLRP3 inflammasome components (caspase-1, IL-1β, and IL-18) in PBMCs and plasma levels of IL-1β and IL-18 decreased dramatically in NAFLD patients compared with controls. This study has demonstrated that the activation of NLRP3 inflammasome is highly increased in NAFLD patients, but it can be markedly suppressed by anthocyanins, which provides a rationale for the development of anti-inflammatory therapies in NAFLD.