Abstract
The present working hypothesis is that the Cu-induced changes in lipid metabolism may be mediated by miRNAs. Here, we describe the miRNA profile of the liver tissues of yellow catfish exposed to waterborne Cu, based on larger-scale sequencing of small RNA libraries. We identified a total of 172 distinct miRNAs. Among these miRNAs, compared to the control, mRNA expression levels of 16 miRNAs (miR-203a, 205, 1788-3p, 375, 31, 196a, 203b-3p, 2187-5p, 196d, 459-3p, 153a and miR-725, and two novel-miRNAs: chr4-1432, chr-7684) were down-regulated, and mRNA levels of miR-212 and chr20-5274 were up-regulated in Cu-exposed group. The functions of their target genes mainly involved ether lipid metabolism, glycerophospholipid metabolism, linoleic acid metabolism and α-linolenic acid metabolism. Cu exposure inhibited the expression of miR-205, whose predicted target genes were enriched in the pathway of lipid metabolism, including fas, lxrα, ddit3, lamp2, casp3a and baxa. These potential target genes were further verified by Dual-luciferase reporter gene assay. Using primary hepatocytes of yellow catfish, Cu incubation down-regulated miR-205 expression, and increased TG contents and FAS activity. LXR antagonist effectively ameliorate the Cu-induced change of TG content and FAS activity. These data suggest that down-regulation of the miRNA-205 may be an important step in Cu-induced changes in lipid metabolism in yellow catfish.
Highlights
During environmental stress, maintenance of homeostasis requires constant metabolic adjustment, which is achieved partly through the fine-tuning of gene expression
The present study indicated that Cu incubation increased the TG contents of the hepatocytes, in agreement with our previous studies [20]
In Expt. 3, primary hepatocytes of P. fulvidraco were used to examine the effects of the target gene lxra on miR-205 mediating Cu-induced changes in hepatic lipid metabolism
Summary
Maintenance of homeostasis requires constant metabolic adjustment, which is achieved partly through the fine-tuning of gene expression. MiRNAs, along with their associated target genes, are involved in various physiological processes including development, growth and stress response [8,9,10] Their role in lipid metabolism has been studied in several fish species, including zebrafish (Danio rerio) [11], rainbow trout (Oncorhynchus mykiss) [12] and blunt snout bream (Megalobrama amblycephala) [13]. Our studies have pointed out that waterborne Cu exposure could influence lipid metabolism in yellow catfish Pelteobagrus fulvidraco, a widely cultured freshwater teleost [18,19,20] Environmental chemicals such as heavy metals can interfere with the biogenesis and expression of miRNAs, leading to toxicological consequences [21]. Our findings provide a better understanding for the role of miR-205 in yellow catfish lipid metabolism and may help to identify novel targets for interventions to reduce the occurrence of fatty liver disease in yellow catfish farming
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