Title: Early microcystin-LR exposure-linked inflammasome activation in mice causes development of fatty liver disease and insulin resistance.

Authors: Al-Badrani, Muayad; Saha, Punnag; Mondal, Ayan; Seth, Ratanesh K; Sarkar, Sutapa; Kimono, Diana; Bose, Dipro; Porter, Dwayne E; Scott, Geoff I; Brooks, Bryan; Raychoudhury, Samir; Nagarkatti, Mitzi; Nagarkatti, Prakash; Chatterjee, Saurabh

Published In Environ Toxicol Pharmacol, (2020 Nov)

Abstract: Evidence from pediatric studies show that infants and children are at risk for early exposure to microcystin. The present report tests the hypothesis that early life exposure to microcystin (MC), a principal component of harmful algal blooms followed by a juvenile exposure to high-fat diet feeding potentiate the development of nonalcoholic fatty liver disease phenotype in adulthood. Results showed classical symptoms of early NAFLD linked inflammation. Cytokines and chemokines such as CD68, IL-1β, MCP-1, and TNF-α, as well as α-SMA were increased in the groups that were exposed to MC-LR with the high-fat diet compared to the vehicle group. Also, mechanistically, NLRP3 KO mice showed a significant decrease in the inflammation and NAFLD phenotype and resisted the metabolic changes such as insulin resistance and glucose metabolism in the liver. The data suggested that MC-LR exposure and subsequent NLRP3 inflammasome activation in childhood could impact liver health in juveniles.

PubMed ID: 32687983

MeSH Terms: Animals; Diet, High-Fat/adverse effects; Inflammasomes/metabolism*; Insulin Resistance*; Liver/drug effects; Liver/immunology; Male; Marine Toxins/toxicity*; Mice; Mice, Inbred C57BL; Microcystins/toxicity*; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism; Non-alcoholic Fatty Liver Disease/chemically induced*; Non-alcoholic Fatty Liver Disease/immunology; Non-alcoholic Fatty Liver Disease/metabolism; Water Pollutants, Chemical/toxicity*