Hydroxytyrosol Induces Dyslipidemia in an ApoB100 Humanized Mouse Model

Abstract

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.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.

Long-Term Effect of Maternal Antioxidant Supplementation on the Lipid Profile of the Progeny According to the Sow’s Parity Number

“…This effect was attributed to faster uptake of circulating glucose and lipolysis initiation in this group of pigs [ 24 ]. In vitro studies show an inhibitory effect of oleuropein and hydroxytyrosol on lipid synthesis, and an increase in lipid oxidation [ 42 ], and recent investigations confirm that HXT induces systemic dyslipidemia in humanized mice [ 43 ]. It is of interest to remark that all these studies were developed with direct supplementation of HXT in the growing–fattening phase, without information being available on the long-term effects of maternal supplementation on the tissue composition of the piglet.…”