Novel discovery of Averrhoa bilimbi ethanolic leaf extract in the stimulation of brown fat differentiation program in combating diet-induced obesity

BMC Complement Altern Med. 2019 Sep 5;19(1):243. doi: 10.1186/s12906-019-2640-3.

Abstract

Background: Brown adipocytes are known to promote energy expenditure and limit weight gain to combat obesity. Averrhoa bilimbi, locally called belimbing buluh (DBB), is mainly used as an ethnomedicine in the treatment of metabolic disorders including diabetes mellitus, hypertension and obesity. The present study aims to investigate the browning activity on white adipocytes by A. bilimbi leaf extract and to evaluate the potential mechanisms.

Methods: Ethanolic leaf extract of A. bilimbi was exposed to Myf5 lineage precursor cells to stimulate adipocyte differentiation. Protein expressions of brown adipocyte markers were determined through high content screening analysis and validated through western blotting. Mito Stress Test assay was conducted to evaluate the cellular oxygen consumption rate upon A. bilimbi treatment.

Results: A. bilimbi ethanolic leaf extract exhibited an adipogenesis effect similar to a PPARgamma agonist. It also demonstrated brown adipocyte differentiation in myoblastic Myf5-positive precursor cells. Expression of UCP1 and PRDM16 were induced. The basal metabolic rate and respiratory capacity of mitochondria were increased upon A. bilimbi treatment.

Conclusions: The findings suggest that Averrhoa bilimbi ethanolic leaf extract induces adipocyte browning through PRDM16 activation and enhances mitochondria activity due to UCP1 up-regulation.

Keywords: Averrhoa bilimbi; Brown adipocytes; Extract; Obesity; White adipocytes.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / drug effects*
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Averrhoa / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Diet, High-Fat / adverse effects
  • Humans
  • Mice
  • Obesity / drug therapy
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / physiopathology*
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism

Substances

  • DNA-Binding Proteins
  • Plant Extracts
  • Prdm16 protein, mouse
  • Transcription Factors
  • Ucp1 protein, mouse
  • Uncoupling Protein 1