Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in mice.
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 (1)H 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.
Human and Animal Physiology, Wageningen University, Wageningen, The Netherlands.
Elise F
EF
Hoek-van den Hil
Jaap
J
Keijer
Annelies
A
Bunschoten
Jacques J M
JJ
Vervoort
Barbora
B
Stankova
Melissa
M
Bekkenkamp
Laure
L
Herreman
Dini
D
Venema
Peter C H
PC
Hollman
Eva
E
Tvrzicka
Ivonne M C M
IM
Rietjens
Evert M
EM
van Schothorst
D000818:Animals; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D000090702:Constitutive Androstane Receptor; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D011794:Quercetin / Q000494:pharmacology*
D000090702:Constitutive Androstane Receptor; D005231:Fatty Acids, Unsaturated; D008055:Lipids; C000716327:NR1I3 protein, human; C000716328:Nr1i3 protein, mouse; D011794:Quercetin