Lili Nimri, Michal Slutzki, Hadar Amartely, Antonella Di Pizio, Tom Oren, Assaf Friedler, Betty Schwartz, Irena Peri, Masha Y. Niv, Lutz Graeve, Katy Staikin, Einav Yehuda-Shnaidman, Yitzhak Hadar
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.
The fungal protein ostreolysin (Oly), which has been previously shown to bind to cholesterol-enriched raft-like membrane domains (lipid rafts) of mammalian cells, is a suitable candidate for interaction with brown preadipocytes. We used a recombinant version of ostreolysin (rOly), and we demonstrate that rOly affects morphology, lipid accumulation, respiration rate due to enhanced expression of uncoupling protein 1, and concomitantly differentiation associated gene and protein expression, in summary induces brown adipocyte differentiation.
