Artepillin C, a Typical Brazilian Propolis-Derived Component, Induces Brown-Like Adipocyte Formation in C3H10T1/2 Cells, Primary Inguinal White Adipose Tissue-Derived Adipocytes, and Mice

PLoS One. 2016 Sep 6;11(9):e0162512. doi: 10.1371/journal.pone.0162512. eCollection 2016.

Abstract

Induction of brown-like adipocytes (beige/brite cells) in white adipose tissue (WAT) suggests a new approach for preventing and treating obesity via induction of thermogenesis associated with uncoupling protein 1 (UCP1). However, whether diet-derived factors can directly induce browning of white adipocytes has not been well established. In addition, the underlying mechanism of induction of brown-like adipocytes by diet-derived factors has been unclear. Here, we demonstrate that artepillin C (ArtC), which is a typical Brazilian propolis-derived component, significantly induces brown-like adipocytes in murine C3H10T1/2 cells and primary inguinal WAT (iWAT)-derived adipocytes. This significant induction is due to activation of peroxisome proliferator-activated receptor γ and stabilization of PRD1-BF-1-RIZ1 homologous domain-containing protein-16 (PRDM16). Furthermore, the oral administration of ArtC (10 mg/kg) for 4 weeks significantly induced brown-like adipocytes accompanied by significant expression of UCP1 and PRDM16 proteins in iWAT of mice, and was independent of the β3-adrenergic signaling pathway via the sympathetic nervous system. These findings may provide insight into browning of white adipocytes including the molecular mechanism mediated by dietary factors and demonstrate that ArtC has a novel biological function with regard to increasing energy expenditure by browning of white adipocytes.

MeSH terms

  • Adipocytes, Brown / cytology
  • Adipocytes, Brown / drug effects*
  • Adipocytes, Brown / metabolism
  • Adipocytes, White / cytology
  • Adipocytes, White / drug effects*
  • Adipocytes, White / metabolism
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Administration, Oral
  • Animals
  • Anti-Obesity Agents / isolation & purification
  • Anti-Obesity Agents / pharmacology*
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Energy Metabolism / drug effects*
  • Energy Metabolism / genetics
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / pathology
  • Obesity / prevention & control*
  • PPAR gamma / agonists
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Phenylpropionates / isolation & purification
  • Phenylpropionates / pharmacology*
  • Primary Cell Culture
  • Propolis / chemistry
  • Signal Transduction
  • Thermogenesis / drug effects
  • Thermogenesis / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Uncoupling Protein 1 / agonists
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism

Substances

  • Anti-Obesity Agents
  • DNA-Binding Proteins
  • PPAR gamma
  • Phenylpropionates
  • Prdm16 protein, mouse
  • Transcription Factors
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • artepillin C
  • Propolis

Grant support

This work was supported by Grants-in-Aid for Scientific Research (No. 26450168) from the Japan Society for Promotion of Science and Yamada Research Grant. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.