Perchlorate exposure does not induce obesity or non-alcoholic fatty liver disease in zebrafish

Abstract

Perchlorate is a water-soluble contaminant found throughout the United States and many other countries. Perchlorate competitively inhibits iodide uptake at the sodium/iodide symporter, reducing thyroid hormone synthesis, which can lead to hypothyroidism and metabolic syndromes. Chronic perchlorate exposure induces hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) in developing threespine stickleback (Gasterosteus aculeatus). We hypothesized that perchlorate would also induce zebrafish (Danio rerio) to develop phenotypes consistent with NAFLD and to accumulate lipids throughout the body. We exposed zebrafish embryos to four concentrations of perchlorate treated water (10μg/L, 10mg/L, 30mg/L, and 100mg/L) and a control (0mg/L) over the course of 133 days. Adult zebrafish were euthanized, sectioned, H&E and Oil Red-O stained, and analyzed for liver morphology and whole body lipid accumulation. In a representative section of the liver, we counted the number of lipid droplets and measured the area of each droplet and the total lipid area. For whole body analysis, we calculated the ratio of lipid area to body area within a section. We found that zebrafish exposed to perchlorate did not differ in any measured liver variables or whole body lipid area when compared to controls. In comparison to stickleback, we see a trend that control stickleback accumulate more lipids in their liver than do control zebrafish. Differences between the species indicate that obesogenic effects due to perchlorate exposure are not uniform across fish species, and likely are mediated by evolutionary differences related to geographic location. For example, high latitude fishes such as stickleback evolved to deposit lipid stores for over-winter survival, which may lead to more pronounced obesogenic effects than seen in tropical fish such as zebrafish.