Heme oxygenase (HO-1) rescue of adipocyte dysfunction in ho-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin

Angela P H Burgess; Luca Vanella; Lars Bellner; Katherine Gotlinger; John R. Falck; Nader G. Abraham; Michal L. Schwartzman; Attallah Kappas

doi:10.1159/000337591

Heme oxygenase (HO-1) rescue of adipocyte dysfunction in ho-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin

Angela P H Burgess, Luca Vanella, Lars Bellner, Katherine Gotlinger, John R. Falck, Nader G. Abraham, Michal L. Schwartzman, Attallah Kappas

Biochemistry

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

41 Scopus citations

Abstract

Background/Aims: HO-1 and EETs are functionally linked and their interactions influence body weight, insulin sensitivity, and serum levels of inflammatory cytokines in metabolic syndrome phenotype of HO-2 null mice. The HO-2 isozyme is essential for regulating physiological levels of ROS. Recent studies have suggested a potential role of EET in modifying adipocyte differentiation through up-regulation of HO-1-adiponectin-AkT signaling in human mesenchymal stem cells (MSCs). Our aim was to examine the consequences of HO deficiency on MSC-derived adipogenesis in vitro using MSC derived from HO-2 null and WT mice in vivo. Methods: Four-month-old HO-2 null (HO-2 ^-/- ) and B6/129SF2/J (WT) mice were divided into three groups (four mice/group): WT, HO-2 ^-/- , and HO-2 ^-/- +CoPP. Adipogenesis was performed on purified MSC-derived adipocytes cultured in adipogenic differentiation media and an EET-agonist was added every 3 days. Results: HO-2 depletion of MSC adipocytes resulted in increased adipogenesis (p<0.01) and increased levels of inflammatory cytokines including (TNF)-alpha (p<0.05), (MCP)-1 (p<0.05), and (IL-1)-beta (p<0.05). These results were accompanied by decreases in HO-1 (p<0.05) and subsequently EET and HO activity (p<0.05). Up-regulation of HO-1 resulted in decreased MSC-derived adipocyte differentiation, decreased production of TNF-alpha and MCP-1 and increased levels of adiponectin (p<0.05). Cyp2J5 (p<0.05), HO-1 (p<0.05), and adiponectin mRNA levels (p<0.05) were also decreased in visceral adipose tissue isolated from HO-2 null compared to WT mice. EET agonist stimulation of MSC adipocytes derived from HO-2 null mice yielded similar results. Conclusion: Increased levels of EET and HO-1 are essential for protection against the adverse effects of adipocyte hypertrophy and the ensuing metabolic syndrome. These results offer a portal into therapeutic approaches for the prevention of the metabolic syndrome.

Original language	English (US)
Pages (from-to)	99-110
Number of pages	12
Journal	Cellular Physiology and Biochemistry
Volume	29
Issue number	1-2
DOIs	https://doi.org/10.1159/000337591
State	Published - 2012

Keywords

Antioxidants
Bilirubin
Carbon monoxide
Cardiovascular
Diabetes
HO
Stress response genes

ASJC Scopus subject areas

General Medicine

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10.1159/000337591

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@article{04fc5cb6adff416b8c882d045c64e57a,

title = "Heme oxygenase (HO-1) rescue of adipocyte dysfunction in ho-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin",

abstract = " Background/Aims: HO-1 and EETs are functionally linked and their interactions influence body weight, insulin sensitivity, and serum levels of inflammatory cytokines in metabolic syndrome phenotype of HO-2 null mice. The HO-2 isozyme is essential for regulating physiological levels of ROS. Recent studies have suggested a potential role of EET in modifying adipocyte differentiation through up-regulation of HO-1-adiponectin-AkT signaling in human mesenchymal stem cells (MSCs). Our aim was to examine the consequences of HO deficiency on MSC-derived adipogenesis in vitro using MSC derived from HO-2 null and WT mice in vivo. Methods: Four-month-old HO-2 null (HO-2 -/- ) and B6/129SF2/J (WT) mice were divided into three groups (four mice/group): WT, HO-2 -/- , and HO-2 -/- +CoPP. Adipogenesis was performed on purified MSC-derived adipocytes cultured in adipogenic differentiation media and an EET-agonist was added every 3 days. Results: HO-2 depletion of MSC adipocytes resulted in increased adipogenesis (p<0.01) and increased levels of inflammatory cytokines including (TNF)-alpha (p<0.05), (MCP)-1 (p<0.05), and (IL-1)-beta (p<0.05). These results were accompanied by decreases in HO-1 (p<0.05) and subsequently EET and HO activity (p<0.05). Up-regulation of HO-1 resulted in decreased MSC-derived adipocyte differentiation, decreased production of TNF-alpha and MCP-1 and increased levels of adiponectin (p<0.05). Cyp2J5 (p<0.05), HO-1 (p<0.05), and adiponectin mRNA levels (p<0.05) were also decreased in visceral adipose tissue isolated from HO-2 null compared to WT mice. EET agonist stimulation of MSC adipocytes derived from HO-2 null mice yielded similar results. Conclusion: Increased levels of EET and HO-1 are essential for protection against the adverse effects of adipocyte hypertrophy and the ensuing metabolic syndrome. These results offer a portal into therapeutic approaches for the prevention of the metabolic syndrome.",

keywords = "Antioxidants, Bilirubin, Carbon monoxide, Cardiovascular, Diabetes, HO, Stress response genes",

author = "Burgess, {Angela P H} and Luca Vanella and Lars Bellner and Katherine Gotlinger and Falck, {John R.} and Abraham, {Nader G.} and Schwartzman, {Michal L.} and Attallah Kappas",

year = "2012",

doi = "10.1159/000337591",

language = "English (US)",

volume = "29",

pages = "99--110",

journal = "Cellular Physiology and Biochemistry",

issn = "1015-8987",

publisher = "S. Karger AG",

number = "1-2",

}

TY - JOUR

T1 - Heme oxygenase (HO-1) rescue of adipocyte dysfunction in ho-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin

AU - Burgess, Angela P H

AU - Vanella, Luca

AU - Bellner, Lars

AU - Gotlinger, Katherine

AU - Falck, John R.

AU - Abraham, Nader G.

AU - Schwartzman, Michal L.

AU - Kappas, Attallah

PY - 2012

Y1 - 2012

N2 - Background/Aims: HO-1 and EETs are functionally linked and their interactions influence body weight, insulin sensitivity, and serum levels of inflammatory cytokines in metabolic syndrome phenotype of HO-2 null mice. The HO-2 isozyme is essential for regulating physiological levels of ROS. Recent studies have suggested a potential role of EET in modifying adipocyte differentiation through up-regulation of HO-1-adiponectin-AkT signaling in human mesenchymal stem cells (MSCs). Our aim was to examine the consequences of HO deficiency on MSC-derived adipogenesis in vitro using MSC derived from HO-2 null and WT mice in vivo. Methods: Four-month-old HO-2 null (HO-2 -/- ) and B6/129SF2/J (WT) mice were divided into three groups (four mice/group): WT, HO-2 -/- , and HO-2 -/- +CoPP. Adipogenesis was performed on purified MSC-derived adipocytes cultured in adipogenic differentiation media and an EET-agonist was added every 3 days. Results: HO-2 depletion of MSC adipocytes resulted in increased adipogenesis (p<0.01) and increased levels of inflammatory cytokines including (TNF)-alpha (p<0.05), (MCP)-1 (p<0.05), and (IL-1)-beta (p<0.05). These results were accompanied by decreases in HO-1 (p<0.05) and subsequently EET and HO activity (p<0.05). Up-regulation of HO-1 resulted in decreased MSC-derived adipocyte differentiation, decreased production of TNF-alpha and MCP-1 and increased levels of adiponectin (p<0.05). Cyp2J5 (p<0.05), HO-1 (p<0.05), and adiponectin mRNA levels (p<0.05) were also decreased in visceral adipose tissue isolated from HO-2 null compared to WT mice. EET agonist stimulation of MSC adipocytes derived from HO-2 null mice yielded similar results. Conclusion: Increased levels of EET and HO-1 are essential for protection against the adverse effects of adipocyte hypertrophy and the ensuing metabolic syndrome. These results offer a portal into therapeutic approaches for the prevention of the metabolic syndrome.

AB - Background/Aims: HO-1 and EETs are functionally linked and their interactions influence body weight, insulin sensitivity, and serum levels of inflammatory cytokines in metabolic syndrome phenotype of HO-2 null mice. The HO-2 isozyme is essential for regulating physiological levels of ROS. Recent studies have suggested a potential role of EET in modifying adipocyte differentiation through up-regulation of HO-1-adiponectin-AkT signaling in human mesenchymal stem cells (MSCs). Our aim was to examine the consequences of HO deficiency on MSC-derived adipogenesis in vitro using MSC derived from HO-2 null and WT mice in vivo. Methods: Four-month-old HO-2 null (HO-2 -/- ) and B6/129SF2/J (WT) mice were divided into three groups (four mice/group): WT, HO-2 -/- , and HO-2 -/- +CoPP. Adipogenesis was performed on purified MSC-derived adipocytes cultured in adipogenic differentiation media and an EET-agonist was added every 3 days. Results: HO-2 depletion of MSC adipocytes resulted in increased adipogenesis (p<0.01) and increased levels of inflammatory cytokines including (TNF)-alpha (p<0.05), (MCP)-1 (p<0.05), and (IL-1)-beta (p<0.05). These results were accompanied by decreases in HO-1 (p<0.05) and subsequently EET and HO activity (p<0.05). Up-regulation of HO-1 resulted in decreased MSC-derived adipocyte differentiation, decreased production of TNF-alpha and MCP-1 and increased levels of adiponectin (p<0.05). Cyp2J5 (p<0.05), HO-1 (p<0.05), and adiponectin mRNA levels (p<0.05) were also decreased in visceral adipose tissue isolated from HO-2 null compared to WT mice. EET agonist stimulation of MSC adipocytes derived from HO-2 null mice yielded similar results. Conclusion: Increased levels of EET and HO-1 are essential for protection against the adverse effects of adipocyte hypertrophy and the ensuing metabolic syndrome. These results offer a portal into therapeutic approaches for the prevention of the metabolic syndrome.

KW - Antioxidants

KW - Bilirubin

KW - Carbon monoxide

KW - Cardiovascular

KW - Diabetes

KW - HO

KW - Stress response genes

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DO - 10.1159/000337591

M3 - Article

C2 - 22415079

AN - SCOPUS:84859838894

SN - 1015-8987

VL - 29

SP - 99

EP - 110

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

IS - 1-2

ER -

Heme oxygenase (HO-1) rescue of adipocyte dysfunction in ho-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin

Abstract

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