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

Bioorg Med Chem Lett. 2013 Jun 1;23(11):3273-6. doi: 10.1016/j.bmcl.2013.03.117. Epub 2013 Apr 4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis / drug effects
  • Animals
  • Antidiuretic Agents / chemical synthesis
  • Antidiuretic Agents / chemistry*
  • Antidiuretic Agents / pharmacology
  • Bone Marrow Cells / cytology*
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Monoamine Oxidase / chemistry*
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Phenelzine / chemistry
  • Phenelzine / pharmacology
  • Tranylcypromine / chemistry
  • Tranylcypromine / pharmacology

Substances

  • Antidiuretic Agents
  • Monoamine Oxidase Inhibitors
  • Tranylcypromine
  • Monoamine Oxidase
  • Phenelzine