Quercetin Induces Hepatic Lipid Omega-Oxidation and Lowers Serum Lipid Levels in Mice

Abstract

Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to quantitatively measure serum lipid profiles. Whole genome microarray analysis of liver tissue was used to identify possible mechanisms underlying altered circulating lipid levels. Body weight, energy intake and hepatic lipid accumulation did not differ significantly between the quercetin and the control group. In serum of quercetin-fed mice, triglycerides (TG) were decreased with 14% (p<0.001) and total poly unsaturated fatty acids (PUFA) were increased with 13% (p<0.01). Palmitic acid, oleic acid, and linoleic acid were all decreased by 9–15% (p<0.05) in quercetin-fed mice. Both palmitic acid and oleic acid can be oxidized by omega (ω)-oxidation. Gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially ω-oxidation. At the gene level, this was reflected by the up-regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3) were also up-regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid ω-oxidation and lowered corresponding circulating lipid levels, which may contribute to potential beneficial effects on CVD.

Breast milk nutrient content and infancy growth

“…Triglyceride concentration was used as a surrogate for total fat content, as this contributes 95–98% of total HM lipid content 12. A further ten lipid species were also quantified: linoleic acid, diglycerides, monoglycerides, docosahexaenoic acid, 18:1/16:1, esterified cholesterol, free cholesterol, total cholesterol, omega 3, monounsaturated fatty acid and polyunsaturated fatty acids, as described previously 13. Lactose, the major HM carbohydrate, was measured from the polar fraction of the milk sample, using 1 H 1D NOESY spectroscopy.…”

Quercetin decreases high-fat diet induced body weight gain and accumulation of hepatic and circulating lipids in mice

“…It is not clear which combination of factors, like dose of quercetin, dietary en% of fat or duration causes these effects on lipids. Previously, we have observed an effect of quercetin on serum lipid lowering and hepatic lipid x-oxidation using a mild high-fat diet (30 en%) for 12 weeks (Hoek-van den Hil et al 2013). Here, we examined whether the same effects would be observed using the same amount of quercetin and the same duration, but using a high-fat diet (40 en%), which is expected to induce body weight gain as well as hepatic lipid accumulation.…”

“…During the intervention, the mice (n = 12) received high-fat diet (40 en% fat) without or with supplementation of 0.33 % (w/w) quercetin (Sigma, Zwijndrecht, the Netherlands). The percentage of quercetin in the diet was identical to that used in our previous study (Hoek-van den Hil et al 2013). Body weight and food intake of individual mice were weekly monitored.…”

“…Other rodent studies with quercetin supplementation that investigated lipid lowering effects showed reduction in body weight, serum lipid levels, hepatic lipid accumulation, and/or white adipose tissue mass. However, these effects were not seen in all studies and were sometimes conflicting (de Boer et al 2006;Hoek-van den Hil et al 2013;Jung et al 2013;Kobori et al 2011;Odbayar et al 2006;Stewart et al 2009;Wein et al 2010). It is not clear which combination of factors, like dose of quercetin, dietary en% of fat or duration causes these effects on lipids.…”

“…In the Western diet, quercetin is the major dietary flavonol, a subclass of the flavonoids, and is present in, for example, apples, tea, red wine, and onions. Our previous results in mice showed that a quercetin supplemented mild high-fat diet increased hepatic lipid metabolism, especially omega (x)-oxidation, and reduced corresponding circulating lipid levels (Hoekvan den Hil et al 2013). The cardiovascular protective properties of quercetin might therefore be explained by the lipid lowering effect of quercetin, since increased circulating levels of free fatty acids and triglycerides are known risk factors for CVD (Boden 2008;Harchaoui et al 2009;Jouven et al 2001).…”