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Xanthohumol ameliorates atherosclerotic plaque formation, hypercholesterolemia, and hepatic steatosis in ApoE ‐deficient mice
Author(s) -
Doddapattar Prakash,
Radović Branislav,
Patankar Jay V.,
Obrowsky Sascha,
Jandl Katharina,
Nusshold Christoph,
Kolb Dagmar,
Vujić Nemanja,
Doshi Lalit,
Chandak Prakash G.,
Goeritzer Madeleine,
Ahammer Helmut,
Hoefler Gerald,
Sattler Wolfgang,
Kratky Dagmar
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200794
Subject(s) - endocrinology , medicine , lipogenesis , chemistry , steatosis , apolipoprotein e , sterol regulatory element binding protein , cholesterol , lipid metabolism , monocyte , triglyceride , proinflammatory cytokine , biology , sterol , inflammation , disease
Scope Xanthohumol (XN), a prenylated antioxidative and anti‐inflammatory chalcone from hops, exhibits positive effects on lipid and glucose metabolism. Based on its favorable biological properties, we investigated whether XN attenuates atherosclerosis in western‐type diet‐fed apolipoprotein‐E‐deficient ( ApoE −/− ) mice. Methods and results XN supplementation markedly reduced plasma cholesterol concentrations, decreased atherosclerotic lesion area, and attenuated plasma concentrations of the proinflammatory cytokine monocyte chemoattractant protein 1. Decreased hepatic triglyceride and cholesterol content, activation of AMP‐activated protein kinase, phosphorylation and inactivation of acetyl‐CoA carboxylase, and reduced expression levels of mature sterol regulatory element‐binding protein (SREBP)‐2 and SREBP‐1c mRNA indicate reduced lipogenesis in the liver of XN‐fed ApoE −/− mice. Concomitant induction of hepatic mRNA expression of carnitine palmitoyltransferase‐1a in ApoE −/− mice‐administered XN suggests increased fatty acid beta‐oxidation. Fecal cholesterol concentrations were also markedly increased in XN‐fed ApoE −/− mice compared with mice fed western‐type diet alone. Conclusion The atheroprotective effects of XN might be attributed to combined beneficial effects on plasma cholesterol and monocyte chemoattractant protein 1 concentrations and hepatic lipid metabolism via activation of AMP‐activated protein kinase.