{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lourenco T"],"funding":["ICBAS - School of Medicine and Biomedical Sciences","Fundação para a Ciência e Tecnologia"],"pagination":["219"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10974606"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(3)"],"pubmed_abstract":["The impacts of hypolipidemic pharmaceuticals on fish lipid metabolism remain unexplored. However, data points to similar effects and mechanisms of action between fish and humans. Therefore, fish may be a strong model for screening hypolipidemic drug candidates and water pollution by lipid-modulating agents. This study aimed to test a new hypolipidemic model assay with juvenile brown trout using atorvastatin (ATV)-a hypolipidemic chemical. We selected 17α-ethinylestradiol (EE2), known to cause hyperlipidemia in fish, to ensure model functionality. Fish received intramuscular injections of 4 μL/g for two weeks under the following experimental conditions: control-C (0.7% NaCl), solvent control-SC (0.7% NaCl, 0.9% ethanol, 0.1% dimethyl sulfoxide), ATV (0.3 μg/g), EE2 (2 μg/g), and a mixture of both compounds-MIX (0.3 μg/g ATV and 2 μg/g EE2). Endpoints included blood lipid biochemistry, hepatic lipid droplet quantification, and liver mRNA expression of lipid-related target genes (related to lipogenesis, lipid transport, and β-oxidation pathways). ATV lowered blood total cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) levels, whilst triglycerides and very-low-density lipoproteins (VLDL) were highest under EE2. Hepatic lipid droplet deposition significantly increased in the ATV, EE2, and MIX groups. ATV and MIX caused a significant downregulation of the peroxisome proliferator-activated receptor γ (<i>pparγ</i>) and acetyl Co-A oxidase 3 (<i>acox3</i>). EE2 upregulated acyl-CoA long-chain synthetase 1 (<i>acsl1</i>) and downregulated both fatty acid binding protein 1 (<i>fabp1</i>) and acetyl Co-A oxidase 1-3I (<i>acox1-3I</i>). ATV caused hypolipidemic effects in juvenile brown trout and could even counteract EE2-stimulated hyperlipidemia, reinforcing the potential of fish hypo- and hyperlipidemic models."],"journal":["Toxics"],"pubmed_title":["A Proof-of-Concept for a Hypolipidemic Brown Trout Model."],"pmcid":["PMC10974606"],"funding_grant_id":["UIDB/04423/2020 and UIDP/04423/2020","Marine Sciences-Marine Resources Master"],"pubmed_authors":["Lourenco T","Goncalves JF","Rocha MJ","Rocha E","Madureira TV"],"additional_accession":[]},"is_claimable":false,"name":"A Proof-of-Concept for a Hypolipidemic Brown Trout Model.","description":"The impacts of hypolipidemic pharmaceuticals on fish lipid metabolism remain unexplored. However, data points to similar effects and mechanisms of action between fish and humans. Therefore, fish may be a strong model for screening hypolipidemic drug candidates and water pollution by lipid-modulating agents. This study aimed to test a new hypolipidemic model assay with juvenile brown trout using atorvastatin (ATV)-a hypolipidemic chemical. We selected 17α-ethinylestradiol (EE2), known to cause hyperlipidemia in fish, to ensure model functionality. Fish received intramuscular injections of 4 μL/g for two weeks under the following experimental conditions: control-C (0.7% NaCl), solvent control-SC (0.7% NaCl, 0.9% ethanol, 0.1% dimethyl sulfoxide), ATV (0.3 μg/g), EE2 (2 μg/g), and a mixture of both compounds-MIX (0.3 μg/g ATV and 2 μg/g EE2). Endpoints included blood lipid biochemistry, hepatic lipid droplet quantification, and liver mRNA expression of lipid-related target genes (related to lipogenesis, lipid transport, and β-oxidation pathways). ATV lowered blood total cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) levels, whilst triglycerides and very-low-density lipoproteins (VLDL) were highest under EE2. Hepatic lipid droplet deposition significantly increased in the ATV, EE2, and MIX groups. ATV and MIX caused a significant downregulation of the peroxisome proliferator-activated receptor γ (<i>pparγ</i>) and acetyl Co-A oxidase 3 (<i>acox3</i>). EE2 upregulated acyl-CoA long-chain synthetase 1 (<i>acsl1</i>) and downregulated both fatty acid binding protein 1 (<i>fabp1</i>) and acetyl Co-A oxidase 1-3I (<i>acox1-3I</i>). ATV caused hypolipidemic effects in juvenile brown trout and could even counteract EE2-stimulated hyperlipidemia, reinforcing the potential of fish hypo- and hyperlipidemic models.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-22T21:32:04.805Z","creation":"2025-04-22T21:32:04.805Z"},"accession":"S-EPMC10974606","cross_references":{"pubmed":["38535952"],"doi":["10.3390/toxics12030219"]}}