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Aims: Studies demonstrated that oxidized fish oil (OFO) promoted oxidative stress and induced mitochondrial dysfunction and lipotoxicity, which attenuated beneficial effects of fish oil supplements in the treatment of nonalcoholic fatty liver disease (NAFLD). The current study was performed on yellow catfish, a good model to study NAFLD, and its hepatocytes to explore whether selenium (Se) could alleviate OFO-induced lipotoxicity via the inhibition of oxidative stress and determine its potential mechanism. Results: The analysis of triglycerides content, oxidative stress parameters, and histological and transmission electronic microscopy observation showed that high dietary Se supplementation alleviated OFO-induced lipotoxicity, oxidative stress, and mitochondrial injury and dysfunction. RNA-sequencing and immunoblotting analysis indicated that high dietary Se reduced OFO-induced decline of peroxisome-proliferator-activated receptor alpha (Pparα) and ubiquitin-specific protease 4 (Usp4) protein expression. High Se supplementation also alleviated OFO-induced reduction of thioredoxin reductase 2 (txnrd2) messenger RNA (mRNA) expression level and activity. The txnrd2 knockdown experiments revealed that txnrd2 mediated Se- and oxidized eicosapentaenoic acid (oxEPA)-induced changes of mitochondrial reactive oxygen species (mtROS) and further altered Usp4 mediated-deubiquitination and stabilization of Pparα, which, in turn, modulated mitochondrial fatty acid β-oxidation and metabolism. Mechanistically, Usp4 deubiquitinated Pparα and ubiquitin-proteasome-mediated Pparα degradation contributed to oxidative stress-induced mitochondrial dysfunction. Innovation: These findings uncovered a previously unknown mechanism by which Se and OFO interacted to affect lipid metabolism via the Txnrd2-mtROS-Usp4-Pparα pathway, which provides the new target for NAFLD prevention and treatment. Conclusion: Se ameliorated OFO-induced lipotoxicity via the inhibition of mitochondrial oxidative stress, remodeling of Usp4-mediated deubiquitination, and stabilization of Pparα. Antioxid. Redox Signal. 40, 433–452. [ABSTRACT FROM AUTHOR]

The current study is conducted to determine the influences of dietary selenium (Se) and oxidized fish oil (OFO) on growth, nutritional composition, muscle development, antioxidant responses and selenoprotein expression in the muscle of yellow catfish. We used the 2 × 2 factorial experimental design, which included two dietary Se levels at 0.25 (adequate) and 0.5 (high) mg Se/kg diets, and each Se level had fresh fish oil (FFO) and OFO, respectively. The experiment continued for 10 weeks. Compared to FFO group, dietary OFO reduced final body weight (FBW), specific growth rate (SGR) and weight gain (WG), and the contents of n-6 polyunsaturated fatty acid (PUFA), 18: 2n-6, 20: 4n-6, n-3 PUFA, 20: 5n-3, 22: 6n-3 and total PUFA, the diameters of muscle fibers >80 μm, mRNA expression of mef2d , myf5 , myod , s6kb and mTOR, and the ratio of p-mTOR to mTOR protein expression, but increased feed conversion rate (FCR), muscle lipid content, malic enzyme (ME) and isocitrate dehydrogenase (ICDH) activities, the number of the muscle fiber with the diameter lower than 50 μm; high dietary Se addition alleviated OFO- induced variations of these indices mentioned above. Dietary OFO also reduced muscle catalase (CAT) and glutathione peroxidase (GPX) activities and total antioxidant capacity (AOC), and mRNA expression of gpx1 , gpx2 , gpx3 , selenoe , selenok and selenos , but increased total superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and NRF2 protein expression, and high dietary Se addition alleviated OFO-induced changes of these parameters involved in antioxidant responses and selenoprotein expression in the muscle of yellow catfish. Based on these observations above, dietary Se addition alleviated OFO-induced lipogenesis, and reversed the OFO-induced inhibition of muscle growth and development, and oxidative damage of muscle. Our study provides new mechanistic insights into the Se and OFO interaction in fish. The biological basis through which dietary OFO and Se diets interacted to affect muscle metabolism and physiology is scarce. Our study indicated that dietary Se could alleviate OFO-induced negative effects on muscle metabolism and physiology, which will be helpful to the feed formulation and fish farm. • Se alleviated dietary OFO-induced reduction of growth performance. • Se alleviated dietary OFO-induced reduction of muscle PUFA content. • Se alleviated dietary OFO-induced reduction of muscle growth and development. • Se alleviated dietary OFO-induced increase of lipogenesis and lipid deposition. • Se reversed dietary OFO-induced oxidative stress and selenoprotein expression. [ABSTRACT FROM AUTHOR]

• We obtained the 1993-bp, 2000-bp and 1959-bp promoters of three selenoproteins. • Se increase the activities of the selenok , selenot and selenop promoters. • Functional FoxO4, Nrf2, KLF4 and ATF4 sites were identified on their promoters. • Se promoted FoxO4, Nrf2, KLF4 and ATF4 binding ability to their promoters. The selenok , selenot and selenop are three key selenoproteins involved in stress response. Our study, using the yellow catfish Pelteobagrus fulvidraco as the experimental animal, obtained the 1993-bp, 2000-bp and 1959-bp sequences of selenok , selenot and selenop promoters, respectively, and predicted the binding sites of several transcriptional factors on their promoters, such as Forkhead box O 4 (FoxO4), activating transcription factor 4 (ATF4), Kruppel-like factor 4 (KLF4) and nuclear factor erythroid 2-related factor 2 (NRF2). Selenium (Se) increased the activities of the selenok , selenot and selenop promoters. FoxO4 and Nrf2 can directly bind with selenok promoter and controlled selenok promoter activities positively; KLF4 and Nrf2 can directly bind with selenot promoter and controlled selenot promoter activities positively; FoxO4 and ATF4 can directly bind to selenop promoter and regulated selenop promoter activities positively. Se promoted FoxO4 and Nrf2 binding to selenok promoter, KLF4 and Nrf2 binding to selenot promoter, and FoxO4 and ATF4 binding to selenop promoter. Thus, we provide the first evidence for FoxO4 and Nrf2 bindnig elements in selenok promoter, KLF4 and Nrf2 binding elements in selenot promoter, and FoxO4 and ATF4 binding elements in selenop promoter, and offer novel insight into regulatory mechanism of these selenoproteins induced by Se. [ABSTRACT FROM AUTHOR]

• Oxidized fish oil increased lipid content by ROS-induced mitochondria dysfunction. • OxEPA-activated lipophagy was via inhibiting the CREB-1-Bcl-2-Beclin1 pathway. • Our study demonstrated the mechanisms of oxidized fish oils increasing lipid deposition. • Fish oils supplements after oxidization is harmful for obese and NAFLD patients. At present, the harmful effects and relevant mechanism of oxidized fish oils on fish and fish cells remain unknown. Our study found that oxidized fish oils increased lipogenesis, and reduced lipolysis, activated oxidative stress by decreasing glutathione peroxidase (GPX) activity, increasing malondialdhyde (MDA) content and damaging mitochondrial structure, and activated autophagy in the liver of yellow catfish; oxidized eicosapentaenoic acid (oxEPA) induced oxidative stress in yellow catfish hepatocytes. Oxidative stress, mitochondrial dysfunction and lipophagy mediated oxEPA induced-variations in lipid metabolism. Our further investigation indicated that oxEPA-activated lipophagy was via inhibiting the DNA binding capacity of the cAMP-response element binding protein (CREB)-1 to the region of Bcl-2 promoter, which in turn suppressed the binding activity of Bcl-2 to Beclin1 and promoted autophagosome formation. For the first time, our study elucidated the mechanisms of oxidized fish oils-induced lipid deposition by the oxidative stress, mitochondrial dysfunction and CREB1-Bcl-2-Beclin1 pathway in fish. [ABSTRACT FROM AUTHOR]

Background: The intestine is the main organ for absorbing dietary fat. High dietary lipid intake leads to fat deposition in the intestine and adversely influences fat absorption and health, but the underlying mechanism is unknown.Objectives: We used yellow catfish and their isolated intestinal epithelial cells to test the hypothesis that endoplasmic reticulum (ER) stress, autophagy, and apoptosis mediate fat-induced changes in lipid metabolism.Methods: Male and female yellow catfish (weight: 3.79 ± 0.16 g; age: 3 mo) were fed diets containing lipid at 6.98% (low-fat diet; LFD), 11.3% (middle-fat diet; MFD), or 15.4% (high-fat diet; HFD) (by weight) for 8 wk. Each dietary group had 3 replicates, 30 fish per replicate. Their intestinal epithelial cells were isolated and incubated for 24 h in control solution or various concentrations of fatty acids (FAs) with or without 2-h pretreatment with an inhibitor [3-methyladenine (3-MA), 4-phenyl butyric acid (4-PBA), or Ac-DVED-CHO (AC)]. Triglyceride (TG) contents, genes, and enzymes involved in lipid metabolism, ER stress, autophagy, and apoptosis were determined in intestinal tissue and cells; immunoblotting, BODIPY 493/503 staining, ultrastructural observation, and the detection of autophagic and apoptotic vesicles were performed on intestinal cells.Results: Compared with the LFD and MFD, the HFD increased intestinal TG content by 120-226%, activities of lipogenic enzymes by 19.0-245%, expression of genes related to lipogenesis (0.77-8.4-fold), lipolysis (0.36-6.0-fold), FA transport proteins (0.79-1.7-fold), ER stress (0.55-7.5-fold), autophagy (0.56-4.2-fold), and apoptosis (0.80-5.2-fold). Using isolated intestinal epithelial cells and inhibitors (4-PBA, 3-MA, and AC), we found that ER stress mediated FA-induced activation of autophagy (11.0-50.1%) and apoptosis (10.4-32.0%), and lipophagy and apoptosis mediated FA-induced lipolysis (3.40-41.6%).Conclusions: An HFD upregulated lipogenesis, lipolysis, and FA transport, induced ER stress, and activated autophagy and apoptosis. ER stress, autophagy, and apoptosis play important regulatory roles in fat-induced changes in lipid metabolism in the intestine and intestinal epithelial cells of yellow catfish. [ABSTRACT FROM AUTHOR]

Aims: Excessive manganese (Mn) exposure is toxic, and induces lipid deposition, but the underlying mechanisms remain elusive. Herein, we explored how dietary Mn supplementation affects lipid deposition and metabolism in the intestine of vertebrates using the yellow catfish Pelteobagrus fulvidraco as the model. Results: High-Mn (H-Mn) diet increased intestinal Mn content, promoted lipid accumulation and lipogenesis, and inhibited lipolysis. In addition, it induced oxidative stress, upregulated metal-response element-binding transcription factor-1 (MTF-1), and peroxisome proliferator-activated receptor gamma (PPARγ) protein expression in the nucleus, induced PPARγ acetylation, and the interaction between PPARγ and retinoid X receptor alpha (RXRα), while it downregulated sirtuin 1 (SIRT1) expression and activity. Mechanistically, Mn activated the MTF-1/divalent metal transporter 1 (DMT1) pathway, increased Mn accumulation in the mitochondria, and induced oxidative stress. This in turn promoted lipid deposition via deacetylation of PPARγ at K339 by SIRT1. Subsequently, PPARγ mediated Mn-induced lipid accumulation through transcriptionally activating fatty acid translocase, stearoyl-CoA desaturase 1, and perilipin 2 promoters. Innovation: These studies uncover a previously unknown mechanism by which Mn induces lipid deposition in the intestine via the oxidative stress–SIRT1–PPARγ pathway. Conclusion: High dietary Mn intake activates MTF-1/DMT1 and oxidative stress pathways. Oxidative stress-mediated PPARγ deacetylation at K339 site contributes to increased lipid accumulation. Our results provided a direct link between Mn and lipid metabolism via the oxidative stress–SIRT1–PPARγ axis. Antioxid. Redox Signal. 37, 417–436. [ABSTRACT FROM AUTHOR]

Zip family proteins are involved in the control of zinc (Zn) ion homeostasis. The present study cloned the promoters and investigated the transcription responses and protein subcellular localizations of three LIV-1 subfamily members (zip10, zip13, and zip14) from common freshwater teleost yellow catfish, Pelteobagrus fulvidraco, using in vitro cultured HEK293T model cells. The 2278 bp, 1917 bp, and 1989 bp sequences of zip10, zip13, and zip14 promoters, respectively, were subcloned into pGL3-Basic plasmid for promoter activity analysis. The pcDNA3.1 plasmid coding EGFP tagged pfZip10, pfZip13, and pfZip14 were generated for subsequent confocal microscope analysis. Several potential transcription factors' binding sites were predicted within the promoters. In vitro promoter analysis in the HEK293T cells showed that high Zn administration significantly reduced the transcriptional activities of the zip10, zip13, and zip14 promoters. The −2017 bp/−2004 bp MRE in the zip10 promoter, the −360 bp/−345 bp MRE in the zip13 promoter, and the −1457 bp/−1442 bp MRE in the zip14 promoter were functional loci that were involved in the regulation of the three zips. The −606 bp/−594 bp KLF4 binding site in the zip13 promoter was a functional locus responsible for zinc-responsive regulation of zip13. The −1383 bp/−1375 bp STAT3 binding site in the zip14 promoter was a functional locus responsible for zinc-responsive regulation of zip14. Moreover, confocal microscope analysis indicated that zinc incubation significantly reduced the fluorescence intensity of pfZip10-EGFP and pfZip14-EGFP but had no significant influence on pfZip13-EGFP fluorescence intensity. Further investigation found that pfZip10 localizes on cell membranes, pfZip14 colocalized with both cell membranes and lysosome, and pfZip13 colocalized with intracellular ER and Golgi. Our research illustrated the transcription regulation of zip10, zip13, and zip14 from P. fulvidraco under zinc administration, which provided a reference value for the mechanisms involved in Zip-family-mediated control of zinc homeostasis in vertebrates. [ABSTRACT FROM AUTHOR]

Iron is an essential micro-element, involved in multiple biological activities in vertebrates. Excess iron accumulation has been identified as an important mediator of lipid deposition. However, the underlying mechanisms remain unknown. In the present study, we found that a high-iron diet significantly increased intestinal iron content and upregulated the mRNA expression of two iron transporters (zip14 and fpn1). Intestinal iron overload increased lipogenesis, reduced lipolysis and promoted oxidative stress and mitochondrial dysfunction. Iron-induced lipid accumulation was mediated by hypoxia-inducible factor-1 α (HIF1α), which was induced in response to mitochondrial oxidative stress following inhibition of prolyl hydroxylase 2 (PHD2). Mechanistically, iron promoted lipid deposition by enhancing the DNA binding capacity of HIF1α to the pparγ and fas promoters. Our results provide experimental evidence that oxidative stress, mitochondrial dysfunction and the HIF1α-PPARγ pathway are critical mediators of iron-induced lipid deposition. [ABSTRACT FROM AUTHOR]

The positive impacts of dietary citric acid (CA) on aquaculture species have been studied. However, the wide application of CA in aquatic-feed requires a comprehensive understanding of its nutritional functions. Here, an 8- week feeding trial was performed to determine whether dietary CA supplementation could improve manganese (Mn) utilization and thus reduce Mn excretion by investigating the effect of dietary CA on growth performance, mineral statues, body and muscle composition, muscle growth and mTOR signaling of yellow catfish Pelteobagrus fulvidraco fed with low-manganese (L-Mn) diets. Four isonitrogenous and isolipidic diets were formulated and fed to triplicated groups of fish. A suitable Mn diet containing 5.7 mg kg−1 Mn was set as the control, while the diets without extra Mn addition was regarded as L-Mn group. The other two diets were supplemented with 30 g kg−1 CA into the control and L-Mn diet, respectively. The results showed that the weight gain, specific growth rate, feed efficiency, protein content in muscle, iron concentration in serum, and Mn content in whole body and muscle were significantly decreased after L-Mn diet and resumed by dietary CA addition (P < 0.05). Dietary low-Mn markedly decreased the diameters of muscle fibers, which was alleviated by CA supplementation. Dietary Mn and CA interacted to affect the density of the muscle fiber density, the mRNA expression of muscle development-, myocyte myogenic and myocyte enhancer factors-related genes (P -interaction <0.05). Besides, expression of genes in muscle involved in mTOR signaling including mtor , s6 and eif4e were significantly down-regulated in fish fed L-Mn diet compared to the control. CA supplementation reversed the L-Mn diet induced decrease of their mRNA levels. Furthermore, the protein expression of p-mTOR, S6 and p-S6 were significantly decreased after L-Mn diet, and were upregulated by CA supplementation in the muscle (P < 0.05). Taken together, this study revealed that CA as a feed additive could improve growth performance, mineral bioavailability, muscle growth and protein synthesis in yellow catfish under the condition of Mn deficiency. These positive effects may be partially attributed to dietary CA supplementation improving Mn absorption and bioavailability. This study also has a significance for the development of environmentally friendly feeds for the aquatic species. • L-Mn diet reduced growth performance and feed efficiency, whch was resumed by CA. • Low-Mn decreased the diameters of muscle fibers, which was alleviated by CA. • Dietary Mn and CA interacted to affect expression of genes of muscle development. • L-Mn diet inhibited mTOR signaling in the muscle, and CA reversed the effects. [ABSTRACT FROM AUTHOR]

Enrofloxacin (ENR) is a kind of widespread hazardous pollutant on aquatic ecosystems and causes toxic effects, such as disorders of metabolism, on aquatic animals. However, its potential mechanisms at an environmental concentration on metabolic disorders of aquatic organisms remain unclear. Herin, we found that hepatic lipotoxicity was induced by ENR exposure, which led to ENR accumulation, oxidative stress, mitochondrial fragmentation, and fatty acid transfer blockage from lipid droplets into fragmented mitochondria. ENR-induced lipotoxicity and mitochondrial β-oxidation down-regulation were mediated by reactive oxygen species (ROS). Moreover, dynamin-like protein 1 (DRP1) mediated ENR-induced mitochondrial fragmentation and changes of lipid metabolism. Mechanistically, ENR induced increment of DRP1 mitochondrial localization via dephosphorylating DRP1 at S627 and promoted its interaction with mitochondrial fission factor (MFF), leading to mitochondria fragmentation. For the first time, our study provides an innovative mechanistic link between hepatic lipotoxicity and mitochondrial fragmentation under ENR exposure, and thus identifies previously unknown mechanisms for the direct relationship between environmental ENR concentration and lipotoxicity in aquatic animals. Our study provides innovative insights for toxicological mechanisms and environmental risk assessments of antibiotics in aquatic environment. [Display omitted] • Enrofloxacin (ENR) induced lipotoxicity and promoted mitochondrial fragmentation. • ENR blocked fatty acids transfer from lipid droplets into mitochondria. • Reactive oxygen species mediated ENR-induced lipotoxicity. • Dynamin-like protein 1 (DRP1) mediated ENR-induced mitochondrial fragmentation. • ENR induced mitochondria fragmentation via dephosphorylating DRP1 at S627. [ABSTRACT FROM AUTHOR]

The present study was conducted to explore the mechanism of nano-Zn absorption and its influence on lipid metabolism in the intestine of yellow catfish Pelteobagrus fulvidraco. Compared to ZnSO4, dietary nano-Zn addition increased the triglyceride (TG) content, enzymatic activities of malic enzyme (ME) and fatty acid synthase (FAS), and up-regulated mRNA levels of 6pgd, fas, acca, dgat1, pparγ, and fatp4. Using primary intestinal epithelial cells of yellow catfish, compared to the ZnSO4 group, nano-Zn incubation increased the contents of TG and free fatty acids (FFA), the activities of glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6GPD), ME, and FAS, up-regulated mRNA levels of lipogenic genes (6pgd, g6pd, fas, dgat1, and pparγ), genes of lipid transport (fatp4 and ifabp), and Zn transport genes (znt5, znt7, mt, and mtf1), and increased the protein expression of fatty acid transport protein 4 (FATP4) and peroxisome proliferator activated receptor gamma (PPARγ). Further studies found that nano-Zn absorption was via the clathrin-dependent endocytic mechanism. PPARγ mediated the nano-Zn-induced increase in TG, and nano-Zn increased Zn accumulation and induced TG accumulation by activating the PPARγ pathway and up-regulating lipogenesis. [ABSTRACT FROM AUTHOR]

The goal of this study was to clone and characterize complete cDNA sequences of three important development-relevant genes of yellow catfish Pelteobagrus fulvidraco , including lrp6 , sox9a1 and fgfr2c , and explore their transcriptional responses in several tissues of P . fulvidraco to high fat diet. The predicted amino acid sequences of P . fulvidraco Lrp6, Sox9a1 and Fgfr2c contained all of the conserved structural features that were characteristic of these genes in other species, including YWTD domains, EGF-like repeats, LDLR ligand binding repeats, PPSP repeats motifs, HMG box, TA-binding functional domain, Ig I-III and PTK I-II. The mRNAs of the three genes were expressed in various tissues, but their mRNA levels varied among tissues. Compared to the control, high fat diet tended to down-regulate the mRNA expression of sox9a1 and fgfr2c in mesenteric fat, liver and ovary, and up-regulate their mRNA levels in muscle and kidney; in contrast, high fat diet down-regulated lrp6 mRNA levels in the ovary and muscle, but had no significant effects on lrp6 mRNA expression in mesenteric fat, liver and kidney. Our findings provide the first data about their expression responses to dietary lipid in teleosts and reinforce the multiple functions at the molecular level. [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate the influences of five dietary manganese (Mn) sources on growth, feed utilization, lipid metabolism, antioxidant capacity, inflammatory response and endoplasmic reticulum stress in intestinal tissues of yellow catfish Pelteobagrus fulvidraco. Five Mn sources include Mn sulfate monohydrate (MnSO 4 ·H 2 O), Mn dioxide (MnO 2), Mn dioxide nanoparticles (MnO 2 NPs), Mn glycine chelate (Mn-Gly) and hydroxymethionine-chelated Mn (Mn-MHA). Yellow catfish (initial body weight: 2.69 ± 0.01 g/fish) were fed five experimental diets for 10 weeks. Dietary Mn sources significantly affected intestinal Mn content and metabolism. Compared to other Mn sources, yellow catfish fed organic Mn sources (Mn-Gly and Mn-MHA) tended to improve growth, feed utilization, intestinal histology, up-regulated mRNA abundance of tight junction-relevant genes, increased intestinal fatty acid uptake and transport and triglyceride deposition, and reduced inflammatory responses. These dietary organic Mn supplements also increased intestinal antioxidant capacity by up-regulating antioxidant gene expression and enzymatic activities. Yellow catfish fed two organic Mn diets had the lower mRNA expressions of endoplasmic reticulum stress-relevant gene and protein expression. Based on these observations above, dietary organic supplements (Mn-Gly and Mn-MHA) improved the growth and feed utilization, and promoted intestinal health of yellow catfish, and accordingly seems to be optimal Mn sources for yellow catfish. Our results provided the innovative insights into dietary Mn sources influencing tight junction, antioxidant capacity and inflammatory responses, endoplasmic reticulum stress and fatty acid uptake and uptake in the fish intestine, and found that organic Mn sources were more suitable as the Mn supplements in yellow catfish feeds, and also possibly in other aquatic feed. • Two organic Mn sources in yellow catfish diet positively affect growth performance. • Two organic Mn sources in yellow catfish diet improved intestinal tight junction. • Two organic Mn in yellow catfish diet increased fatty acid uptake and TG deposition. • Two organic Mn reduced intestinal inflammation and increased antioxidant capacity. • Two organic Mn sources in yellow catfish diet improved the ER function. [ABSTRACT FROM AUTHOR]

Enrofloxacin (ENR), one representative of fluoroquinolones widely used in husbandry, poses potential threats to aquatic organisms. However, its toxicological effect remained largely unknown. Here, we explored the influences of environmentally relevant concentration of ENR exposure on the gills of yellow catfish Pelteobagrus fulvidraco , a well-known freshwater teleost. After 10-weeks of waterborne ENR exposure at environmentally relevant concentrations, the gill tissues were collected and subsequently used for histopathology, enzyme activity, protein and mRNA expression analysis in yellow catfish. Our study revealed that waterborne ENR exposure reduced Na+/K+-ATPase activity, tight junction genes' expression and cytokines secretion, activated oxidative stress and induced apoptosis in gills. ENR exposure also activated MAPK signaling in a concentration-dependent manner. Thus, we demonstrated that environmentally relevant concentration of ENR exposure activated oxidative stress and MAPK pathway, resulted in immune dysfunction and induced intrinsic apoptosis. These results elucidated that ENR, as an environmental pollutant, had more complex toxicological effects on gills of fish than previously assessed, which provided novel insight into ENR toxicology and the assessment of its environmental risks. [Display omitted] • ENR exposure reduced Na+/K+-ATPase activity and tight junction genes' expression. • ENR exposure reduced cytokines secretion, activated oxidative stress and induced apoptosis. • ENR exposure also activated MAPK signaling in a concentration-dependent manner. • ENR hindered the functions of gills via complex toxicological mechanism. [ABSTRACT FROM AUTHOR]

Excessive fat deposition in the hepatocytes, associated with excess dietary fat intake, was related to the occurrence of fatty livers in fish. miR-101b plays the important roles in controlling lipid metabolism, but the underlying mechanism at the post-transcriptional level remains unclear. The purpose of this study is to explore the roles and mechanism of miR-101b-mediating lipid deposition and metabolism in yellow catfish Pelteobagrus fulvidraco. We found that miR-101b directly targeted fatty acid translocase (cd36), caspase9 (casp9) and autophagy-related gene 4A (atg4a). Furthermore, using palmitic acid (PA) or oleic acid (OA) to incubate the primary hepatocytes of yellow catfish, we demonstrated that miR-101b inversely regulated cd36, casp9, and atg4a expression at the transcriptional level; the inhibition of miR-101b aggravated fatty acids (FAs, PA or OA)-induced lipid accumulation, indicating that miR-101b mediated FAs-induced variations of lipid metabolism in yellow catfish. Taken together, our study gave novel insight into the regulatory mechanism of lipid deposition and metabolism and might provide potential targets for the prevention and treatment of fatty livers in fish. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]