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

Tom Oren; Lili Nimri; Einav Yehuda-Shnaidman; Katy Staikin; Yitzhak Hadar; Assaf Friedler; Hadar Amartely; Michal Slutzki; Antonella Di Pizio; Masha Y. Niv; Irena Peri; Lutz Graeve; Betty Schwartz

doi:10.1002/mnfr.201700057

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

Tom Oren, Lili Nimri, Einav Yehuda-Shnaidman, Katy Staikin, Yitzhak Hadar, Assaf Friedler, Hadar Amartely, Michal Slutzki, Antonella Di Pizio, Masha Y. Niv, Irena Peri, Lutz Graeve, Betty Schwartz^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	American English
Article number	1700057
Journal	Molecular Nutrition and Food Research
Volume	61
Issue number	9
DOIs	https://doi.org/10.1002/mnfr.201700057
State	Published - Sep 2017

Bibliographical note

Funding Information:
B.S. and T.O. conceived and designed the experiments. T.O. performed most of the experiments and data analysis. M.S., A.D.P., and M.Y.N. modeled, analyzed, and visualized the 3D structure of the protein. A.F. and H.A. performed the chemical analyses of the protein. L.G. performed the proteomic analyses. I.P. provided technical assistance. K.S. performed some preliminary experiments. Y.H. conceived some of the experiments. B.S. contributed reagents, materials, and analytical tools. T.O. and B.S. wrote the manuscript and all of the authors made critical revisions. This research was partially funded by a grant number 390093, from Nofar, Chief Scientist, Israel. ERA-NET TargetECM network funding via Chief Science Ministry of Health, is gratefully acknowledged. A.D.P. is a recipient of the Lady Davis postdoctoral fellowship.

Funding Information:
This research was partially funded by a grant number 390093, from Nofar, Chief Scientist, Israel. ERA-NET TargetECM network funding via Chief Science Ministry of Health, is gratefully acknowledged. A.D.P. is a recipient of the Lady Davis postdoctoral fellowship.

Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

Brown adipocyte differentiation
Brown adipose tissue
Lipid droplet
Obesity
Ostreolysin

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/mnfr.201700057

Cite this

@article{1078283519e7478888c82df9fe94007c,

title = "Recombinant ostreolysin induces brown fat-like phenotype in HIB-1B cells",

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",

author = "Tom Oren and Lili Nimri and Einav Yehuda-Shnaidman and Katy Staikin and Yitzhak Hadar and Assaf Friedler and Hadar Amartely and Michal Slutzki and Pizio, {Antonella Di} and Niv, {Masha Y.} and Irena Peri and Lutz Graeve and Betty Schwartz",

note = "Funding Information: B.S. and T.O. conceived and designed the experiments. T.O. performed most of the experiments and data analysis. M.S., A.D.P., and M.Y.N. modeled, analyzed, and visualized the 3D structure of the protein. A.F. and H.A. performed the chemical analyses of the protein. L.G. performed the proteomic analyses. I.P. provided technical assistance. K.S. performed some preliminary experiments. Y.H. conceived some of the experiments. B.S. contributed reagents, materials, and analytical tools. T.O. and B.S. wrote the manuscript and all of the authors made critical revisions. This research was partially funded by a grant number 390093, from Nofar, Chief Scientist, Israel. ERA-NET TargetECM network funding via Chief Science Ministry of Health, is gratefully acknowledged. A.D.P. is a recipient of the Lady Davis postdoctoral fellowship. Funding Information: This research was partially funded by a grant number 390093, from Nofar, Chief Scientist, Israel. ERA-NET TargetECM network funding via Chief Science Ministry of Health, is gratefully acknowledged. A.D.P. is a recipient of the Lady Davis postdoctoral fellowship. Publisher Copyright: {\textcopyright} 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2017",

month = sep,

doi = "10.1002/mnfr.201700057",

language = "American English",

volume = "61",

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T1 - Recombinant ostreolysin induces brown fat-like phenotype in HIB-1B cells

AU - Oren, Tom

AU - Nimri, Lili

AU - Yehuda-Shnaidman, Einav

AU - Staikin, Katy

AU - Hadar, Yitzhak

AU - Friedler, Assaf

AU - Amartely, Hadar

AU - Slutzki, Michal

AU - Pizio, Antonella Di

AU - Niv, Masha Y.

AU - Peri, Irena

AU - Graeve, Lutz

AU - Schwartz, Betty

N1 - Funding Information: B.S. and T.O. conceived and designed the experiments. T.O. performed most of the experiments and data analysis. M.S., A.D.P., and M.Y.N. modeled, analyzed, and visualized the 3D structure of the protein. A.F. and H.A. performed the chemical analyses of the protein. L.G. performed the proteomic analyses. I.P. provided technical assistance. K.S. performed some preliminary experiments. Y.H. conceived some of the experiments. B.S. contributed reagents, materials, and analytical tools. T.O. and B.S. wrote the manuscript and all of the authors made critical revisions. This research was partially funded by a grant number 390093, from Nofar, Chief Scientist, Israel. ERA-NET TargetECM network funding via Chief Science Ministry of Health, is gratefully acknowledged. A.D.P. is a recipient of the Lady Davis postdoctoral fellowship. Funding Information: This research was partially funded by a grant number 390093, from Nofar, Chief Scientist, Israel. ERA-NET TargetECM network funding via Chief Science Ministry of Health, is gratefully acknowledged. A.D.P. is a recipient of the Lady Davis postdoctoral fellowship. Publisher Copyright: © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2017/9

Y1 - 2017/9

N2 - 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.

AB - 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.

KW - Brown adipocyte differentiation

KW - Brown adipose tissue

KW - Lipid droplet

KW - Obesity

KW - Ostreolysin

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SN - 1613-4125

VL - 61

JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

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ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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