Environmental estrogen exposure converts lipid metabolism in male fish to a female pattern mediated by AMPK and mTOR signaling pathways.

Environmental estrogens, including bisphenol A (BPA) and 17ß-estradiol (E2), which are widely used in industries and medicine, pose a severe ecological threat to fish due to feminization induction. However, the related metabolic basis for reproductive feminization in male fish has not been well addressed. We first found that female zebrafish exhibited higher lipid accumulation and lipogenesis activity than males. Next, we exposed male and female zebrafish to E2 (200 ng/L) or BPA (100 µg/L) for six weeks, and observed an early-phase reproductive feminization in males, accompanied with reduced spermatids, significant fat deposition and lipogenic gene expressions that mimicked female patterns. Cellular signaling assays revealed that, E2 or BPA modulated lipid metabolism in males mainly through lowering 5' AMP-activated protein kinase (AMPK) and upregulating the lipogenic mechanistic target of rapamycin (mTOR) pathways. For the first time, we show that environmental estrogens could alter lipid metabolism in male fish to a female pattern (metabolic feminization) prior to gonad feminization in male fish, to allows males to accumulate efficiently lipids to harmonize with the feminized gonads. This study suggests that negative effects of environmental estrogens, as hazardous materials, on vertebrate health are more complicated than originally thought.

Concentration-dependent effects of 17ß-estradiol and bisphenol A on lipid deposition, inflammation and antioxidant response in male zebrafish (Danio rerio).

Environmental estrogenic compounds are important pollutants, which are widely distributed in natural water bodies. They produce various adverse effects on fish, but their concentration-dependent toxicities in fish metabolism and health are not fully understood. This study investigated the effects of 17ß-estradiol (E2) and bisphenol A (BPA) at low and high concentrations on lipid deposition, inflammation and antioxidant response in male zebrafish. We measured fish growth parameters, gonad development, lipid contents and the activities of inflammatory and antioxidant enzymes, as well as their mRNA expressions. All E2 and BPA concentrations used increased body weight, damaged gonad structure and induced feminization in male zebrafish. The exposure of zebrafish to E2 and BPA promoted lipid accumulation by increasing total fat, liver triglycerides and free fatty acid contents, and also upregulated lipogenic genes expression, although they decreased total cholesterol content. Notably, zebrafish exposed to low concentrations of E2 (200 ng/L) and BPA (100 µg/L) had higher lipid synthesis and deposition compared to high concentrations (2000 ng/L and 2000 µg/L, respectively). However, the high concentrations of E2 and BPA increased inflammation and antioxidant response. Furthermore, BPA caused greater damage to fish gonad development and more severe lipid peroxidation compared to E2. Overall, the results suggest that the toxic effects of E2 and BPA on zebrafish are concentration-dependent such that, the relative low concentrations used induced lipid deposition, whereas the high ones caused adverse effects on inflammation and antioxidant response.

Reduced oxidative stress increases acute cold stress tolerance in zebrafish.

Cold stress is a major threat to fish in both nature and aquaculture, and can induce oxidative stress in various fish. While the exact role of oxidative stress in cold-caused mortality is still unknown. The purpose of the present study was to evaluate the effects of oxidative stress on cold tolerance in fish and verify whether changing oxidative status could affect cold tolerance. We firstly demonstrated that acute cold exposure induced high oxidative stress in zebrafish liver, which may lead to mortality. Then we performed in vivo and in vitro experiments to determine the effects of the altered oxidative status on cold tolerance in zebrafish and zebrafish liver cell line (ZFL), respectively. In the in vivo study, the zebrafish which were fed with α-lipoic acid or reduced glutathione had lower cold-caused oxidative stress and tissues damage, and showed higher cold tolerance. In the experiment using zebrafish cells, increasing oxidative stress by H2O2 decreased the cellular cold tolerance, and the cold tolerance was partly recovered when oxidative stress was reduced by the addition of Vitamin C (VC). Taken together, we conclude that the reduction of oxidative stress increases cold tolerance in fish.

Tracking pollutants in dietary fish oil: From ocean to table.

Dietary fish oil used in aquafeed transfers marine pollutants to farmed fish. However, the entire transfer route of marine pollutants in dietary fish oil from ocean to table fish has not been tracked quantitatively. To track the entire transfer route of marine pollutants from wild fish to farmed fish through dietary fish oil and evaluate the related human health risks, we obtained crude and refined fish oils originating from the same batch of wild ocean anchovy and prepared fish oil-containing purified aquafeeds to feed omnivorous lean Nile tilapia and carnivorous fatty yellow catfish for eight weeks. The potential human health risk of consumption of these fish was evaluated. Marine persistent organic pollutants (POPs) were concentrated in fish oil, but were largely removed by the refining process, particularly dioxins and polychlorinated biphenyls (PCBs). The differences in the POP concentrations between crude and refined fish oils were retained in the fillets of the farmed fish. Fillets fat content and fish growth were positively and negatively correlated to the final POPs deposition in fillets, respectively. The retention rates of marine POPs in the final fillets through fish oil-contained aquafeeds were 1.3%-5.2%, and were correlated with the POPs concentrations in feeds and fillets, feed utilization and carcass ratios. The dietary crude fish oil-contained aquafeeds are a higher hazard ratio to consumers. Prohibiting the use of crude fish oil in aquafeed and improving growth and feed efficiency in farmed fish are promising strategies to reduce health risks originating from marine POPs.