LAUSR

BACKGROUND Caffeine has an anti-obesity effect, but chronic excessive caffeine consumption also causes caffeinism, which is marked by increased anxiety or depression among other symptoms. The goal of this study was to investigate whether the addition of flavonoids such as astilbin can reduce caffeine dose needed to inhibit obesity. RESULTS ICR mice (n=80) were fed with normal diet, high-fat diet (HFD), HFD supplemented with astilbin, caffeine, or astilbin + caffeine for 12 weeks. When diets supplemented with astilbin, 0.3 g kg-1 diet caffeine had the same effect as 0.6 g kg-1 diet caffeine alone, and 0.6 g kg-1 diet caffeine combined with astilbin most effectively inhibited HFD-induced obesity. Astilbin improved the anti-obesity effects of caffeine on lipid accumulation via the activation of AMP-activated protein kinase α (AMPKα) through the following process: (1) Activated AMPKα decreased lipid biosynthesis by suppressing the activity or mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase, sterol regulatory elements binding protein 1c, and its target gene fatty acid synthase. (2) Activated AMPKα also upregulated lipolysis by enhancing the expression of adipose triglyceride lipase and increasing phosphorylation of hormone-sensitive lipase. (3) Finally, activated AMPKα increased the carnitine acyltransferase and acyl-CoA oxidase activities, which further promoted fatty acid β-oxidation. CONCLUSION These results indicate that astilbin may decrease the effective dose of caffeine needed for an anti-obesity effect and that it suppresses fat accumulation via the activation of AMPK. This article is protected by copyright. All rights reserved.