biostudies-literatureLourenco TICBAS - School of Medicine and Biomedical SciencesFundação para a Ciência e Tecnologia219https://www.ebi.ac.uk/biostudies/studies/S-EPMC10974606biostudies-literatureUnknown12(3)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.ToxicsA Proof-of-Concept for a Hypolipidemic Brown Trout Model.PMC10974606UIDB/04423/2020 and UIDP/04423/2020Marine Sciences-Marine Resources MasterLourenco TGoncalves JFRocha MJRocha EMadureira TVfalseA Proof-of-Concept for a Hypolipidemic Brown Trout Model.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.2024-01-01T00:00:00Z2024 Mar2025-04-22T21:32:04.805Z2025-04-22T21:32:04.805ZS-EPMC109746063853595210.3390/toxics12030219