Lycopene inhibits hepatic steatosis via microRNA-21-induced downregulation of fatty acid-binding protein 7 in mice fed a high-fat diet
Article first published online: 12 SEP 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 56, Issue 11, pages 1665–1674, November 2012
How to Cite
Ahn, J., Lee, H., Jung, C. H. and Ha, T. (2012), Lycopene inhibits hepatic steatosis via microRNA-21-induced downregulation of fatty acid-binding protein 7 in mice fed a high-fat diet. Mol. Nutr. Food Res., 56: 1665–1674. doi: 10.1002/mnfr.201200182
- Issue published online: 24 OCT 2012
- Article first published online: 12 SEP 2012
- Manuscript Accepted: 30 JUL 2012
- Manuscript Revised: 30 JUN 2012
- Manuscript Received: 2 APR 2012
- Korea Food Research Institute and R&D. Grant Number: MKE/KEIT-10033818
- Fatty acid-binding protein 7;
- Fatty acid uptake;
- Nonalcoholic steatohepatitis
Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Here, we investigated the protective effect of lycopene on high-fat diet-induced hepatic steatosis and fatty acid-induced intracellular lipid accumulation by miRNA regulation.
Methods and results
C57BL/6J mice were fed high-fat diet with or without 0.05% lycopene for 8 weeks. Hepa 1–6 cells were treated with stearic acid (SA) after 24 h pretreatment with lycopene. Treatment of lycopene improved hepatic steatosis in high-fat-fed mice and reduced intracellular lipid accumulation induced by SA in Hepa 1–6 cells. We demonstrated that miR-21 expression was decreased in livers from high-fat diet-fed mice and Hepa 1–6 cells treated with SA. Lycopene normalized the downregulation of miR-21, which led to the downregulation of fatty acid-binding protein 7 (FABP7), a direct target of miR-21, at both the transcriptional and translational levels. This specific negative regulation of miR-21 was achieved by targeting the FABP7 3′UTR. Upregulation of miR-21 markedly blocked SA-induced intracellular lipid accumulation by blocking FABP7 expression. Moreover, silencing of FABP7 reduced SA-evoked lipid accumulation in Hepa 1–6 cells.
The results suggest that lycopene may be a useful functional compound for treating NAFLD by regulating hepatic lipid metabolism.