The Role of NLRP3 Inflammasome in Obesity and PCOS—A Systematic Review and Meta-Analysis

Abstract

Inflammasomes have recently been implicated in the pathogenesis of several chronic inflammatory disorders, such as diabetes and obesity. The aim of this meta-analysis was to investigate the possible role of the NLRP3 inflammasome in obesity and polycystic ovarian syndrome (PCOS). A comprehensive search of electronic databases was conducted to identify studies investigating NLRP3 its related components (Caspase 1, ASC and IL-1β) in adipose tissue and/or blood from obese individuals compared to non-obese controls. Another search was conducted for studies investigating NLRP3 in PCOS women and animal models. The ssearched databases included Medline, EMBASE, Cochrane Library, PubMed, Clinicaltrials.gov, the EU Clinical Trials Register and the WHO International Clinical Trials Register. The quality and risk of bias for the included articles were assessed using the modified Newcastle–Ottawa scale. Data were extracted and pooled using RevMan software for the calculation of the standardized mean difference (SMD) and 95% confidence interval (CI). Twelve eligible studies were included in the obesity systematic review and nine in the PCOS review. Of the obesity studies, nine (n = 270) were included in the meta-analysis, which showed a significantly higher adipose tissue NLRP3 gene expression in obese (n = 186) versus non-obese (n = 84) participants (SMD 1.07; 95% CI, 0.27, 1.87). Pooled analysis of adipose tissue IL-1β data from four studies showed significantly higher IL-1β gene expression levels in adipose tissue from 88 obese participants versus 39 non-obese controls (SMD 0.56; 95% CI, 0.13, 0.99). Meta-analysis of adipose tissue ASC data from four studies showed a significantly higher level in obese (n = 109) versus non-obese (n = 42) individuals (SMD 0.91, 95% CI, 0.30, 1.52). Of the nine PCOS articles, three were human (n = 185) and six were animal studies utilizing PCOS rat/mouse models. All studies apart from one article consistently showed upregulated NLRP3 and its components in PCOS women and animal models. In conclusion, obesity and PCOS seem to be associated with upregulated expression of NLRP3 inflammasome components. Further research is required to validate these findings and to elucidate the role of NLRP3 in obesity and PCOS.

Inhibition of NLRP3 inflammasome—A potential mechanistic therapeutic for treatment of polycystic ovary syndrome?

“…This suggests that this inflammasome may have a role in the development of PCOS. [22] Therefore, these results highlight the potential significance of targeting the NLRP3 inflammasome and related molecular pathways as a potential approach for this condition.…”

The Impact of High BMI on Pregnancy Outcomes and Complications in Women with PCOS Undergoing IVF—A Systematic Review and Meta-Analysis

“…Polycystic ovary syndrome (PCOS) is a very prevalent and intricate endocrine disorder in women which represents a major concern in public health [ 1 ]. Throughout their lifespan, women with PCOS encounter various health challenges including anxiety, depression, insulin resistance, hypertension, metabolic disorders, and obesity-related chronic inflammation [ 2 , 3 ]. Moreover, PCOS emerges as a significant contributor to infertility among women in their reproductive years due to the associated anovulation [ 4 ].…”