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Hydroxytyrosol Induces Dyslipidemia in an ApoB100 Humanized Mouse Model
María-Carmen López de Las Hazas1, Andrea Del Saz-Lara1,2,3, Lídia Cedó4,5,6
1Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, CEI UAM+CSIC, Madrid, 28049, Spain.
Molecular Nutrition & Food Research
|November 7, 2023
Summary
Excessive hydroxytyrosol (HT) intake in mice led to adverse effects on lipid and glucose metabolism, despite its known heart benefits. Further research is needed to understand these impacts in humans.
Area of Science:
- Biochemistry
- Metabolic studies
- Nutritional science
Background:
- Extra virgin olive oil, rich in hydroxytyrosol (HT), offers cardioprotective benefits.
- However, excessive HT consumption may negatively impact systemic lipoprotein metabolism.
- Rodent models may not accurately reflect human lipoprotein metabolism.
Purpose of the Study:
- To investigate the effects of HT supplementation on lipoprotein metabolism and glucose homeostasis.
- To utilize a humanized mouse model that better mimics human lipoprotein metabolism.
- To explore the molecular mechanisms underlying HT's metabolic effects.
Main Methods:
- Administration of a control diet or a diet enriched with HT to humanized mice.
- Analysis of serum lipids and lipoproteins at 4 and 8 weeks post-supplementation.
- Gene and microRNA expression profiling using microarrays and bioinformatic analysis.
Main Results:
- HT supplementation increased body weight without altering food intake.
- Accumulation of triacylglycerols, but not cholesterol, was observed in tissues.
- Systemic dyslipidemia and impaired glucose metabolism were induced by HT.
- HT modulated the expression of key lipid metabolism genes, including Pltp and Lpl.
Conclusions:
- Hydroxytyrosol (HT) supplementation in humanized mice resulted in systemic dyslipidemia and impaired glucose metabolism.
- While HT has beneficial effects, these adverse metabolic outcomes warrant further investigation.
- Carefully designed human studies are necessary to confirm these findings and assess risks versus benefits.
