The opposite effect of isotype-selective monoamine oxidase inhibitors on adipogenesis in human bone marrow mesenchymal stem cells

• Published in: Bioorganic & medicinal chemistry letters 2013-06, Vol.23 (11), p.3273-3276
• Main Authors: Byun, Youngjoo, Park, Jongho, Hong, Soo Hyun, Han, Mi Hwa, Park, Suzie, Jung, Hyo-Il, Noh, Minsoo
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; adipocytes; Adipogenesis; Adipogenesis - drug effects; adiponectin; amine oxidase (flavin-containing); Animals; Anti-diabetes; Antidiuretic Agents - chemical synthesis; Antidiuretic Agents - chemistry; Antidiuretic Agents - pharmacology; bone marrow; Bone Marrow Cells - cytology; chemistry; Drug repositioning; Human mesenchymal stem cells; Humans; hypoglycemic agents; insulin resistance; Mesenchymal Stromal Cells - cytology; Mice; Monoamine Oxidase - chemistry; Monoamine Oxidase - metabolism; Monoamine oxidase inhibitor; Monoamine Oxidase Inhibitors - chemical synthesis; Monoamine Oxidase Inhibitors - chemistry; Monoamine Oxidase Inhibitors - pharmacology; pharmacology; Phenelzine - chemistry; Phenelzine - pharmacology; stem cells; Tranylcypromine - chemistry; Tranylcypromine - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.03.117

Adiponectin production during adipocyte differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) can be used to evaluate the pharmacological activity of anti-diabetic drugs to improve insulin sensitivity. Monoamine oxidase (MAO) inhibitors such as phenelzine and pargyline inhibit adipogenesis in murine pre-adipocytes. In this study, however, we found that selective MAO-A inhibitors, moclobemide and Ro41-1049, and a selective MAO-B inhibitor, selegiline, promoted adiponectin production during adipocyte differentiation in hBM-MSCs, which suggested the anti-diabetic potential of these drugs. In contrast, non-selective MAO inhibitors, phenelzine and tranylcypromine, inhibited adipocyte differentiation of hBM-MSCs. Concomitant treatments of MAO-A and MAO-B selective inhibitors did not change the stimulatory effect on adiponectin production in hBM-MSCs. Taken together, the opposite effects of isotype-selective MAO inhibitors on adiponectin production during adipogenesis in hBM-MSCs may not be directly associated with the inhibitory effects of MAO, suggested that the structure of MAO inhibitors may contain a novel anti-diabetic pharmacophore.