Aronia melanocarpa Extract Ameliorates Hepatic Lipid Metabolism through PPARγ2 Downregulation

PLoS One. 2017 Jan 12;12(1):e0169685. doi: 10.1371/journal.pone.0169685. eCollection 2017.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Studies have demonstrated that anthocyanin-rich foods may improve hyperlipidemia and ameliorate hepatic steatosis. Here, effects of Aronia melanocarpa (AM), known to be rich of anthocyanins, on hepatic lipid metabolism and adipogenic genes were determined. AM was treated to C57BL/6N mice fed with high fat diet (HFD) or to FL83B cells treated with free fatty acid (FFA). Changes in levels of lipids, enzymes and hormones were observed, and expressions of adipogenic genes involved in hepatic lipid metabolism were detected by PCR, Western blotting and luciferase assay. In mice, AM significantly reduced the body and liver weight, lipid accumulation in the liver, and levels of biochemical markers such as fatty acid synthase, hepatic triglyceride and leptin. Serum transaminases, indicators for hepatocyte injury, were also suppressed, while superoxide dismutase activity and liver antioxidant capacity were significantly increased. In FL83B cells, AM significantly reduced FFA-induced lipid droplet accumulation. Protein synthesis of an adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 (PPARγ2) was inhibited in vivo. Furthermore, transcriptional activity of PPARγ2 was down-regulated in vitro, and mRNA expression of PPARγ2 and its downstream target genes, adipocyte protein 2 and lipoprotein lipase were down-regulated by AM both in vitro and in vivo. These results show beneficial effects of AM against hepatic lipid accumulation through the inhibition of PPARγ2 expression along with improvements in body weight, liver functions, lipid profiles and antioxidant capacity suggesting the potential therapeutic efficacy of AM on NAFLD.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cell Line
  • Diet, High-Fat
  • Down-Regulation / drug effects*
  • Fatty Acids, Nonesterified / pharmacology
  • Leptin / analysis
  • Leptin / blood
  • Lipid Metabolism / drug effects*
  • Lipoprotein Lipase / genetics
  • Lipoprotein Lipase / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics*
  • Photinia / chemistry*
  • Photinia / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • RNA Interference
  • Superoxide Dismutase / metabolism
  • Transaminases / blood
  • Triglycerides / analysis

Substances

  • Fatty Acids, Nonesterified
  • Leptin
  • PPAR gamma
  • Plant Extracts
  • Triglycerides
  • Superoxide Dismutase
  • Transaminases
  • Lipoprotein Lipase

Grants and funding

This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2015R1A2A1A15052783). There was no additional external funding received for this study. MushMed Co., LTD. provided support in the form of salaries for HJP, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section, and this does not alter our adherence to PLOS ONE policies on sharing data and materials.