cyanoginosin-lr and Insulin-Resistance

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.

Topics: Animals; Diet, High-Fat; Inflammasomes; Insulin Resistance; Liver; Male; Marine Toxins; Mice; Mice, Inbred C57BL; Microcystins; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease; Water Pollutants, Chemical

Epidemiological data from Lake Taihu showed significantly higher incidences of type 2 diabetes mellitus (T2DM) than in other areas of China. This may be related to the occurrence of a Microcystis bloom in Lake Taihu in the summer and autumn every year. The objective of this study is to investigate whether the contaminated water from the Microcystis bloom and the derivative pollutant microcystin-LR (MC-LR) can explain the higher incidences of T2DM. Healthy male mice were fed with water from different regions of Lake Taihu, and were either acutely or chronically exposed to MC-LR through oral administration or intraperitoneal injection. Serum lipid profiles were determined, and the effects on T2DM-related gene expression and insulin receptor signaling pathway were investigated. Intraperitoneal glucose tolerance (IPGTT) and insulin resistance (IRT) tests were implemented, and the functions of pancreatic islet and β-cell were also evaluated. The results showed that both water sampled from the region with a Microcysis bloom and those containing MC-LR altered the serum glucide and lipid profiles in mice after exposure. The exposure to a Microcysis bloom water affected the expression T2DM-related genes: up-regulated the mRNA levels of FASn, ACACA, G6pc, LPL, and Insig2, and down-regulated the mRNA level of PEPCK and Gsk-3β. Both acute and chronic exposure of MC-LR, even at very low concentrations (1 μg/L), impaired the insulin receptor signalling pathway and induced hyperinsulinemia and insulin resistance in mice. In this study, the most important intracellular target of MC-LR was found to be hetapocellular mitochondria. Thus, exposure to Microcystis bloom water containing microcystin-LR can induce the incidence of T2DM, by impairing the function of mitochondria by microcystin-LR. The study suggests a review of the risk assessment concerning 1 μg/L MC-LR as the reference dose in surface water.

Topics: Administration, Oral; Animals; China; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Environmental Monitoring; Gene Expression Regulation; Harmful Algal Bloom; Health Transition; Humans; Incidence; Injections, Intraperitoneal; Insulin Receptor Substrate Proteins; Insulin Resistance; Insulin-Secreting Cells; Lakes; Male; Marine Toxins; Mice; Microcystins; Microcystis; Mitochondria, Liver; Tissue Distribution; Toxicokinetics; Water Pollutants, Chemical