MiR-205 Mediated Cu-Induced Lipid Accumulation in Yellow Catfish Pelteobagrus fulvidraco

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.

Zn Induces Lipophagy via the Deacetylation of Beclin1 and Alleviates Cu-Induced Lipotoxicity at Their Environmentally Relevant Concentrations

“…3,16 Studies pointed out that single Cu and Zn exposure influenced lipid deposition and metabolism in mammals 17,18 and fish. 1,19,20 The dysfunction of lipid metabolism adversely affects growth performance, reproduction, movement, and migration of aquatic organisms. 21 However, Cu and Zn coexist in the waters, which leads to combined exposure and joint toxicity.…”

miR-101b Regulates Lipid Deposition and Metabolism of Primary Hepatocytes in Teleost Yellow Catfish Pelteobagrus fulvidraco

“…Accumulating evidences have shown that miRNAs are implicated in the lipid metabolism [ 14 , 15 , 24 ], suggesting that miRNAs may be a novel therapeutic target to fatty livers. Thus, it is rather crucial to identify novel miRNAs that target key nodes of lipid metabolism and explore their regulatory mechanisms.…”

“…MiRNAs inhibit translation or degradation of target genes by base-pairing to the 3′-UTR of target mRNAs [ 11 , 12 ]. Evidences show that miRNAs are implicated in many physiological and pathological processes of fatty liver diseases [ 12 ] and act as key regulators in lipid metabolism [ 13 , 14 , 15 ]. Thus, miRNAs may be a novel therapeutic target to ameliorate fatty liver diseases.…”

Novel insights for SREBP-1 as a key transcription factor in regulating lipogenesis in a freshwater teleost, grass carp Ctenopharyngodon idella

“…We speculated that it may be because increased SREBP-1 protein expression was not enough to up-regulate mRNA expression of its target genes fas and scd1. It is well reported that some miR regulate the expression of target genes involved in lipid metabolism (15) . Recently, in mammals, Ru et al reported that SREBP-1 transcriptionally activated specific SRE motifs on the promoter of miR-29, and then miR-29 inversely suppressed SREBP-1 expression by binding to their 3 0 UTR region (16) .…”

“…MicroRNA (miR) are a class of small non-coding RNAs that regulate gene expression post-transcriptionally by binding to the complementary regions in the 3 0 UTR of target mRNAs, resulting in mRNA degradation or attenuated translation (14) . Studies have shown that miR play a role in TAG homeostasis (15) . Recently, Ru et al reported that SREBP-1 can activate miR-29 expression and in turn miR-29 inhibited srebp-1 expression, which unravelled a negative feedback loop mediated by miR-29 in SREBP-1 signalling (16) .…”