Title
Heme Oxygenase (HO-1) Rescue of Adipocyte Dysfunction in HO-2 Deficient Mice via Recruitment of Epoxyeicosatrienoic Acids (EETs) and Adiponectin
Document Type
Article
Publication Date
Winter 2-2012
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.
Recommended Citation
Burgess APH, Vanella L, Bellner L, Gotlinger K, Falck JR, Abraham NG, Schwartzman ML, Kappas A. Heme Oxygenase (HO-1) Rescue of Adipocyte Dysfunction in HO-2 Deficient Mice via Recruitment of Epoxyeicosatrienoic Acids (EETs) and Adiponectin. Cell Physiol Biochem 2012;29:99-110.
Comments
Copyright © 2012, Karger Publishers. All rights reserved.
doi:10.1159/000337591