FREE RADICAL BIOLOGY AND MEDICINE
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2025
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IF 8.2
Peng-Cheng Xu,Yu-Chen Zhou,Kostas Pantopoulos,Xiao-Lei Wei,Hong Yang,An-Gen Yu,Zhi Luo
Despite the widespread use of iron oxide nanoparticles (Fe 2 O 3 NPs) in various applications, their differential effects on iron metabolism and iron form-dependent toxicity relative to ferrous sulphate (FeSO 4 ) remain unclear. In this study, we demonstrate that, Fe 2 O 3 NPs, in contrast to FeSO 4 , cause liver structural damage, promote hepatic iron accumulation, impair iron-sulfur cluster (ISC) biogenesis and induce mitochondrial dysfunction in yellow catfish Pelteobagrus fulvidraco . Mechanistically, Fe 2 O 3 NPs-induced oxidative stress suppresses NRF2 expression, thereby reducing transcription of frataxin (FXN), a crucial ISC biogenesis factor. This leads to impaired ISC biogenesis and downstream disruption of iron homeostasis. Notably, ISC-dependent F-box and leucine rich repeat protein 5 (FBXL5), which mediates ubiquitination and degradation of iron regulatory protein 2 (IRP2), exhibits reduced interaction with IRP2 following Fe 2 O 3 NPs exposure. As a result, stabilized IRP2 activates the IRP/IRE system and eventually increases the labile iron pool (LIP), which further contributes to mitochondrial dysfunction. Our findings demonstrate that FeSO 4 and Fe 2 O 3 NPs elicit distinct hepatic antioxidant metabolic responses in yellow catfish, offering critical insights into the molecular mechanisms underlying nanoparticle-induced hepatotoxicity compared with inorganic salts.
研究领域:
毒理学
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环境科学
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纳米医学
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分子生物学
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水生毒理学
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产品关联
DOI
PubMed
高影响因子
Water Biology and Security
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2025
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IF 4.4
Xuebo Liu,Xianda He,Haoyu Tian,Wuxiao Zhang,Wenwei Chen,Aolin Xie,Wenwei Ouyang,Xiaobo Wen,Guanghui Chen,Kun Wu
High-fat diets (HFDs) are frequently used in aquaculture to enhance feed efficiency, yet they often induce hepatic steatosis by disrupting the balance between lipogenesis and lipolysis. In mammals, activation of the farnesoid X receptor (Fxr) alleviates hepatic lipid accumulation by modulating fibroblast growth factor 19 (Fgf19) expression, which in turn regulates lipid homeostasis. However, the molecular characteristics and regulatory mechanisms of Fgf19 in fishes remains poorly defined. In this study, we investigated the role of Fxr in hepatic lipid metabolism in yellow catfish ( Pelteobagrus fulvidraco ) fed a HFD, using the Fxr agonist GW4064. Our in vivo experiments demonstrated that while the HFD reduced growth and increased hepatic fat deposition, GW4064 supplementation reduced liver triglyceride and non-esterified fatty acid levels, restored the balance between lipogenesis and lipolysis, and alleviated oxidative stress. In vitro assays with primary hepatocytes confirmed these results, showing that Fxr activation via GW4064 lowered lipid accumulation and improved cellular redox status. Furthermore, the GW4064 treatment elevated the fgf19 and fgfr4 genes expression levels, and Fgf19 content. We also cloned the yellow catfish fgf19 gene and characterized a 1700 bp promoter region containing several transcription factor binding sites, including a critical Fxr element essential for fgf19 transcriptional activation. Deletion and mutational analysis revealed that Fxr directly activates fgf19 transcription by binding to the −354 to −345 bp site of the fgf19 gene promoter. Recombinant Fgf19 application reduced lipid deposition in hepatocytes by modulating key lipogenic and lipolytic genes, an effect that was disrupted upon inhibition of fibroblast growth factor receptor 4 (Fgfr4). Collectively, our findings indicate that Fxr activation modulates liver lipid metabolism in yellow catfish via the Fgf19-Fgfr4 signaling axis, providing novel insights and a potential therapeutic target for combating fatty liver disease in aquaculture.
研究领域:
水产养殖
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分子生物学
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内分泌学
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脂质代谢
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比较生理学
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产品关联
DOI
高影响因子
GENE
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2023
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IF 3.5
Qing-Lin Li,Hua Zheng,Zhi Luo,Li-Xiang Wu,Peng-Cheng Xu,Jia-Cheng Guo,Yu-Feng Song,Xiao-Ying Tan
SREBPs, such as SREBP1 and SREBP2, were the key transcriptional factors regulating lipid metabolism. The processing of SREBPs involved many genes, such as scap , s1p , s2p , cideb . Here, we deciphered the full-length cDNA sequences of scap, srebp1, srebp2, s1p, s2p, cideb and cidec from yellow catfish Pelteobagrus fulvidraco. Their full-length cDNA sequences ranged from 1587 to 3884 bp, and their ORF length from 1191 to 2979 bp, encoding 396–992 amino acids. Some conservative domains were predicted, including the multiple transmembrane domains in SCAP, the bHLH-ZIP domain in SREBP1 and SREBP2, the ApoB binding region, ER targeting region and LD targeting region in CIDEb, the LD targeting region in the CIDEc, the conserved catalytic site and processing site in S1P, and the transmembrane helix domain in S2P. Their mRNA expression could be observed in the heart, spleen, liver, kidney, brain, muscle, intestine and adipose, but varied with tissues. The changes of their mRNA expression in responses to high-fat (HFD) and bile acid (BA) diets were also investigated in the brain, heart, intestine, kidney and spleen tissues. In the brain, HFD significantly increased the mRNA expression of seven genes ( scap, srebp1, srebp2, s1p, s2p, cideb and cidec ), and the BA attenuated the increase of scap, srebp1, srebp2, s1p, s2p, cideb and cidec mRNA expression induced by HFD. In the heart, HFD significantly increased the mRNA abundances of six genes ( srebp1, srebp2, scap, s2p, cideb and cidec ), and BA attenuated the increase of their mRNA abundances induced by HFD. In the intestine, HFD increased the cideb , s1p and s2p mRNA abundances, and BA attenuated the HFD-induced increment of their mRNA abundances. In the kidney, HFD significantly increased the scap, cidec and s1p mRNA expression, and BA diet attenuated the increment of their mRNA expression. In the spleen, HFD treatment increased the scap , srebp2, s1p and s2p mRNA expression, and BA diet attenuated HFD-induced increment of their mRNA expression. Taken together, our study elucidated the characterization, expression profiles and transcriptional response of seven lipid metabolic genes, which would serve as the good basis for the further exploration into their function and regulatory mechanism in fish.
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产品关联
DOI
PubMed
高影响因子
AQUACULTURE
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2024
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IF 3.9
Qing-Lin Li,Biao Wang,Hua Zheng,Li-Xiang Wu,Peng-Cheng Xu,Xiao-Ying Tan
This present study was undertaken to explore the influences of phospholipids (PL) addition in the high-fat diet (HFD) on growth performance, nutritional composition, oxidative stress, lipid and protein metabolism in the muscle tissue of yellow catfish Pelteobagrus fulvidraco. The five experimental diets were formulated, which included the control (10.31 % normal dietary lipid without PL addition), high-fat dietary group (HFD, 14.99 % dietary lipid without PL addition), 0.1 % PL group (PL1,10.83 % dietary lipid with 0.1 % PL addition), high-fat diet +0.1 % PL group (HFD + PL1, 14.93 % dietary lipid with 0.1 % PL addition) and high-fat diet +0.2 % PL group (HFD + PL2, 14.76 % dietary lipid with 0.2 % PL addition). The feeding experiment continued for 10wk, and then the muscle samples were taken. Compared to the control, HFD reduced growth performance, feed utilization, muscle crude protein and total PL content, induced oxidative stress, lipogenesis and caused muscle lipid accumulation, and PL addition alleviated the HFD-induced changes above. HFD group had the smaller (100-249 μm) myofiber areas, while other groups showed a higher proportion of greater myofiber areas (>350 μm). Additionally, HFD suppressed the expression of muscle regulatory factors and protein synthesis, triggered protein degradation, whereas the PL addition in the diet mitigated the suppressive effects induced by HFD. Furthermore, the HFD inhibited the expression of muscle regulatory factors and protein synthesis, induced protein degradation; PL addition alleviated the HFD-induced inhibition of muscle regulatory factors and protein synthesis, and alleviated the HFD-induced protein degradation. Mechanistically, HFD enhanced the MYOG/FOXO3 binding with the atrogin-1/murf-1 promoters and increased their expression, and PL addition alleviated these effects induced by HFD. Taken together, our research demonstrated that dietary phospholipids could alleviate the adverse effects induced by HFD, and accordingly are beneficial additives for aquatic feeds. Our results also provided innovative insights into the regulatory mechanism of muscle development and growth in the vertebrates. Statement of relevance Our results indicated that dietary PL alleviated adverse effects of HFD on growth performance, oxidative stress, lipid and protein metabolism in the muscle of fish, and accordingly was a good additive in the aquafeeds.
研究领域:
水产养殖学
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营养学
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分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2022
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IF 3.318
Qing Shen,Huijuan Yang,Yunyan Li,Shiyan Li,Kang Chen,Honghai Wang,Haixing Wang,Jianfeng Ma
Yellow catfish ( Pelteobagrus fulvidraco ) is commonly contaminated by protease inhibitors because of the illegal use of antiviral drugs in aquaculture, so the determination of antiviral drugs is essential in food safety supervision. In this study, a novel sorbent, graphene and silica nanospheres composite (G/KCC-1), was synthesized for pipette-tip-based solid-phase extraction (PT-SPE) and purification of ritonavir, saquinavir, and indinavir in yellow catfish, followed by ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) analysis. The wrinkly structure of G/KCC-1 with center-radial nanowrinkles enlarged the surface area and increased the capacity of absorbing the target analyte. With the proposed G/KCC-1 based PT-SPE UPLC-MS/MS method, the pH of sample solution, aspirating/dispensing cycles for extraction and elution were optimized to be 4.0, 25, and 10 respectively, and the eluting solvent was methanol/ammonia (95:5, v/v) with 0.02 M sodium chloride. This new method was further validated to be linear (correlation coefficient R 2 , 0.9993–0.9996), sensitive (limit of detection, LOD ≤ 0.8 ng mL −1 ), accurate (89.3–114.2%), and precise (relative standard deviation, RSD ≤ 6.23%). These results indicated that the proposed method is qualified in bioanalytical method validation and meets the requirements for detecting illegally used antiviral drugs in yellow catfish. The demonstrated G/KCC-1 based PT-SPE UPLC-MS/MS method is a potential analytical method in food and drug administration.
研究领域:
食品安全
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分析化学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）