Recombinant ostreolysin induces brown fat-like phenotype in HIB-1B cells

Mol Nutr Food Res. 2017 Sep;61(9). doi: 10.1002/mnfr.201700057. Epub 2017 Jun 9.

Abstract

Scope: Brown adipose tissue (BAT) is the main regulator of thermogenesis by increasing energy expenditure through the uncoupling of oxidative metabolism from ATP synthesis. There is a growing body of evidence for BAT being the key responsible organ in combating obesity and its related disorders. Herein we propose the fungal protein ostreolysin (Oly), which has been previously shown to bind to cholesterol-enriched raft-like membrane domains (lipid rafts) of mammalian cells, as a suitable candidate for interaction with brown preadipocytes. The aim of the present study was therefore to characterize the mechanism by which a recombinant version of ostreolysin (rOly) induces brown adipocyte differentiation.

Methods and results: Primary isolated brown preadipocytes or HIB-1B brown preadipocyte cells were treated with rOly and the effects on morphology, lipid accumulation, respiration rate, and associated gene and protein expression were measured. rOly upregulated mRNA and protein levels of factors related to brown adipocyte differentiation, induced lipid droplet formation, and increased cellular respiration rate due to expression of uncoupling protein 1. rOly also upregulated β-tubulin expression, and therefore microtubules might be involved in its mechanism of action.

Conclusion: rOly promotes brown adipocyte differentiation, suggesting a new mechanism for rOly's contribution to the battle against obesity.

Keywords: Brown adipocyte differentiation; Brown adipose tissue; Lipid droplet; Obesity; Ostreolysin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / cytology
  • Adipocytes, Brown / drug effects*
  • Adipocytes, Brown / metabolism
  • Animals
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Cell Differentiation / drug effects
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism
  • Fungal Proteins / pharmacology
  • Gene Expression Regulation / drug effects
  • Hemolysin Proteins / chemistry
  • Hemolysin Proteins / metabolism
  • Hemolysin Proteins / pharmacology*
  • Lipid Metabolism / drug effects
  • Mice
  • PPAR gamma / genetics
  • Phenotype
  • Protein Structure, Secondary
  • Recombinant Proteins / pharmacology
  • Tubulin / chemistry
  • Uncoupling Protein 1 / genetics

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, mouse
  • Fungal Proteins
  • Hemolysin Proteins
  • PPAR gamma
  • Recombinant Proteins
  • Tubulin
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • ostreolysin