Comparative evaluation of the metabolic effects of hydroxytyrosol and its lipophilic derivatives (hydroxytyrosyl acetate and ethyl hydroxytyrosyl ether) in hypercholesterolemic rats

Abstract

Hydroxytyrosol (HT), a virgin olive oil phenolic phytochemical with proven health benefits, has been used to generate new lipophilic antioxidants to preserve fats and oils against autoxidation. The aim of this work is to comparatively evaluate the physiological effects of HT and its lipophilic derivatives, hydroxytyrosyl acetate (HT-Ac) and ethyl hydroxytyrosyl ether (HT-Et), in high-cholesterol fed animals. Male Wistar rats (n ¼ 8)were fed a standard diet (C group), a cholesterol-rich diet (Chol group) or a cholesterol-rich diet supplemented with phenolic compounds (HT group, HT-Ac group and HT-Et group) for 8 weeks. Body and tissue weights, the lipid profile, redox status, and biochemical, hormonal, and inflammatory biomarkers were evaluated. Plasma levels of total cholesterol, LDL cholesterol, glucose, insulin and leptin, as well as malondialdehyde in serum increased in Chol compared to C (p < 0.05). Rats fed the test diets had improved glucose, insulin, leptin and MDA levels and antioxidant capacity status, with HT-Ac being the most effective compound. The studied phenolic compounds also modulated TNF-a and IL-1b plasma levels compared to Chol. HT-Ac and HT-Et improved adipose tissue distribution and adipokine production, decreasing MCP-1 and IL-1b levels. Our results confirm the metabolic effects of HT, which are maintained and even improved by hydrophobic derivatives, particularly HT-Ac.

Hydroxytyrosol supplementation modulates the expression of miRNAs in rodents and in humans

“…Our transcriptomic analysis confirms previous results from our group [13] and those of other groups [23][24][25] pointing towards physiological effects of HT on oxidation-reduction processes. We now provide evidence that, in the small intestine, long-term HT supplementation also influences these pathways.…”

“…We now found that cholesterol concentrations were not modified by HT supplementation, which is also reflected by the plasma lipoprotein profile. Other studies also found no changes in plasma cholesterol after HT supplementation [24]. We also evaluated tissue cholesterol levels in both the intestine and liver and found no significant changes.…”

Serum lipid profile and inflammatory markers in the aorta of cholesterol-fed rats supplemented with extra virgin olive oil, sunflower oils and oil-products

“…Similarly, phenols stripped-EVOO resulted in the same serum lipid profile as EVOO. Our results are not in agreement with other studies, where a HCD was co-administered with phenolic compounds in rats (Jemai et al, 2008;Tabernero et al, 2014). However, in these studies, phenolic compounds were evaluated individually and not as native food components.…”

Amelioration of oxidative and inflammatory status in hearts of cholesterol-fed rats supplemented with oils or oil-products with extra virgin olive oil components

“…Other studies on cholesterol-fed rats supplemented with phenolics are not in agreement with this finding [36,37]; yet, in these studies isolated phenolic compounds were supplied in the absence of other oil components. Heart tissue has been affected by hyperlipidemia; oxidation was indicated by increase in MDA in cholesterol-fed rats and inflammation by increase in TNF-α, in compliance with other studies [38].…”