Hydroxytyrosol Induces Dyslipidemia in an ApoB100 Humanized Mouse Model

ScopeExtra virgin olive oil has numerous cardiopreventive effects, largely due to its high content of (poly)phenols such as hydroxytyrosol (HT). However, some animal studies suggest that its excessive consumption may alter systemic lipoprotein metabolism. Because human lipoprotein metabolism differs from that of rodents, this study examines the effects of HT in a humanized mouse model that approximates human lipoprotein metabolism.Methods and resultsMice are treated as follows: control diet or diet enriched with HT. Serum lipids and lipoproteins are determined after 4 and 8 weeks. We also analyzed the regulation of various genes and miRNA by HT, using microarrays and bioinformatic analysis.An increase in body weight is found after supplementation with HT, although food intake was similar in both groups. In addition, HT induced the accumulation of triacylglycerols but not cholesterol in different tissues. Systemic dyslipidemia after HT supplementation and impaired glucose metabolism are observed. Finally, HT modulates the expression of genes related to lipid metabolism, such as Pltp or Lpl.Methods and resultsMice are treated as follows: control diet or diet enriched with HT. Serum lipids and lipoproteins are determined after 4 and 8 weeks. We also analyzed the regulation of various genes and miRNA by HT, using microarrays and bioinformatic analysis.An increase in body weight is found after supplementation with HT, although food intake was similar in both groups. In addition, HT induced the accumulation of triacylglycerols but not cholesterol in different tissues. Systemic dyslipidemia after HT supplementation and impaired glucose metabolism are observed. Finally, HT modulates the expression of genes related to lipid metabolism, such as Pltp or Lpl.ConclusionHT supplementation induces systemic dyslipidemia and impaired glucose metabolism in humanized mice. Although the numerous health-promoting effects of HT far outweigh these potential adverse effects, further carefully conducted studies are needed. In animal models, hydroxytyrosol (HT) consumption may alter systemic lipoprotein metabolism. ApoB100 humanized mouse model better reflects the human lipoprotein metabolism. HT supplementation increases body weight, induces systemic dyslipidemia, causes impaired glucose metabolism, and induces the accumulation of TG in different tissues. HT modulates the expression of genes related to lipid metabolism and several miRNAs, including miR-21.image