Resveratrol mimics insulin activity in the adipogenic commitment of human bone marrow mesenchymal stromal cells

Int J Biochem Cell Biol. 2015 Mar;60:60-72. doi: 10.1016/j.biocel.2014.12.011. Epub 2015 Jan 3.

Abstract

Bone marrow mesenchymal stromal cells (BM-MSCs) are multipotent cells capable of differentiating toward osteoblatic and adipocytic phenotypes. BM-MSCs play several key roles including bone remodeling, establishment of hematopoietic niche and immune tolerance induction. Here, we investigated the effect of resveratrol (RSV), a therapeutically promising natural polyphenol, on the commitment of human BM-MSCs primary cultures. Cell differentiation was evaluated by means of morphological analysis, specific staining and expression of osteogenic and adipocytic master genes (Runx-2, PPARγ). To maintain BM-MSC multipotency, all experiments were performed on cells at very early passages. At any concentration RSV, added to standard medium, did not affect the phenotype of confluent BM-MSCs, while, when added to osteogenic or adipogenic medium, 1 μM RSV enhances the differentiation toward osteoblasts or adipocytes, respectively. Conversely, the addition of higher RSV concentration (25 μM) to both differentiation media resulted exclusively in BM-MSCs adipogenesis. Surprisingly, the analysis of RSV molecular effects demonstrated that the compound completely substitutes insulin, a key component of adipogenic medium. We also observed that RSV treatment is associated to enhanced phosphorylation of CREB, a critical effector of insulin adipogenic activity. Finally, our observations contribute to the mechanistic elucidation of the well-known RSV positive effect on insulin sensitivity and type 2 diabetes mellitus.

Keywords: Adipogenesis; Insulin; Mesenchymal stromal cells; Resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects
  • Bone Marrow Cells / cytology*
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Humans
  • Insulins / pharmacology*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects*
  • Phosphorylation / drug effects
  • Resveratrol
  • Stilbenes / pharmacology*

Substances

  • Insulins
  • Stilbenes
  • Resveratrol