Cholesterol dynamics in rabbit liver: High-fat diet, olive oil, and synergistic dietary effects.

Autor: Funes AK; Laboratorio de Biología Molecular del Metabolismo & Nutrición (MeNu). IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina; Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina; Laboratorio de Enfermedades Metabólicas (LEM), Universidad Juan Agustín Maza, Mendoza, Argentina., Avena V; Laboratorio de Biología Molecular del Metabolismo & Nutrición (MeNu). IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina; Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina; Laboratorio de Enfermedades Metabólicas (LEM), Universidad Juan Agustín Maza, Mendoza, Argentina., Boarelli PV; Laboratorio de Enfermedades Metabólicas (LEM), Universidad Juan Agustín Maza, Mendoza, Argentina., Monclus MA; Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina; Instituto de Investigaciones, Facultad de Ciencias Médicas, Universidad del Aconcagua, Mendoza, Argentina., Zoppino DF; Laboratorio de Fisiología Celular y Molecular. Facultad de Ciencias de la Salud. Universidad de Burgos, Burgos, Spain., Saez-Lancellotti TE; Laboratorio de Biología Molecular del Metabolismo & Nutrición (MeNu). IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina; Instituto de Investigaciones, Facultad de Ciencias Médicas, Universidad del Aconcagua, Mendoza, Argentina; Servicio de Medicina Interna, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA). Universidad de Málaga, Málaga, Spain. Electronic address: efsaez@fcm.uncu.edu.ar., Fornes MW; Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM). IHEM, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 12; Vol. 733, pp. 150675. Date of Electronic Publication: 2024 Sep 12.
DOI: 10.1016/j.bbrc.2024.150675
Abstrakt: Background & Aims: Lipid metabolism disorders contribute to a range of human diseases, including liver-related pathologies. Rabbits, highly sensitive to dietary cholesterol, provide a model for understanding the development of liver disorders. Sterol regulatory element-binding protein isoform 2 (SREBP2) crucially regulates intracellular cholesterol pathways. Extra-virgin olive oil (EVOO) has shown reducing cholesterol levels and restoring liver parameters affected by HFD. The aim was to investigate the molecular impact of an HFD and supplemented with EVOO on rabbit liver cholesterol metabolism.
Approach & Results: Male rabbits were assigned to dietary cohorts, including control, acute/chronic HFD, sequential HFD with EVOO, and EVOO. Parameters such as serum lipid profiles, hepatic enzymes, body weight, and molecular analyses. After 6 months of HFD, plasma and hepatic cholesterol increased with decreased SREBP2 and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) expression. Prolonged HFD increased cholesterol levels, upregulating SREBP2 mRNA and HMGCR protein. Combining this with EVOO lowered cholesterol, increased SREBP2 mRNA, and upregulated low-density lipoprotein receptor (LDLR) expression. HFD-induced metabolic dysfunction-associated fatty liver disease was mitigated by EVOO. In conclusion, the SREBP2 system responds to dietary changes.
Conclusions: In rabbits, the SREBP2 system responds to dietary changes. Acute HFD hinders cholesterol synthesis, while prolonged HFD disrupts regulation, causing SREBP2 upregulation. EVOO intake prompts LDLR upregulation, potentially enhancing cholesterol clearance and restoring hepatic alterations.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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