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Cytochrome P450 Derived Epoxyeicosatrienoic Acid Retard Adipogenesis in Mesenchymal Stem cells by Heme Oxygenase‐ AKT Signaling
Author(s) -
Kim Dong Hyun,
Puri Nitin,
Schwartzman Michal L
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1121.3
Subject(s) - adipogenesis , endocrinology , medicine , chemistry , protein kinase b , heme oxygenase , adiponectin , downregulation and upregulation , mesenchymal stem cell , heme , signal transduction , biology , microbiology and biotechnology , biochemistry , adipose tissue , insulin , insulin resistance , enzyme , gene
Human mesenchymal stem cells (MSCs) expressed substantial levels of CYP2J2, a major CYP450 involved in epoxyeicosatrienoic acid (EET) formation and their metabolites (DiHETs). We examined the effect of 12‐(3‐hexylureido)dodec‐ 8(Z)‐enoic acid, an EET agonist, on MSC‐derived adipocytes and demonstrated an increased number of healthy small adipocytes, attenuated PPARγ, C/EBPα, FAS levels (p<0.01), and lipid accumulation (p<0.05). These effects were accompanied by increased levels of heme oxygenase (HO)‐1 and adiponectin (p<0.05). Inhibition of HO activity or AKT by tin mesoporphyrin (SnMP) and LY2940002, respectively, reversed EET‐induced inhibition of adipogenesis, demonstrated an increase in number of small healthy adipocytes, attenuation of fatty acid synthase (FAS) expression (p<0.01) and reduction in lipid accumulation (p<0.05). These effects were accompanied by increased levels of HO‐1 and adiponectin (p<0.05). These findings suggest that EETs decrease adipocyte differentiation by upregulation of HO‐1‐adiponectin‐ AKT signaling and play essential roles in the regulation of adipogenesis by inhibiting PPARγ, C/EBPαand FAS. These novel observations highlight the seminal role of arachidonic acid metabolism in MSCs and suggest that an EET agonist may have potential therapeutic use in the treatment of dyslipidemia, diabetes, and the metabolic syndrome.