Metformin and vitamin D modulate adipose-derived stem cell differentiation towards the beige phenotype

Adipocyte. 2022 Dec;11(1):356-365. doi: 10.1080/21623945.2022.2085417.

Abstract

Adipose-derived stem cells (ADSCs) represent an ideal stem cell population for regenerative medicine. ADSC adipogenic differentiation is controlled by the activation of a specific transcriptional program, including epigenetic factors and key adipogenic genes. Under certain conditioned media, ADSCs can differentiate into several phenotypes. We previously demonstrated that bioactive molecules could counteract lipid accumulation and regulate adipogenesis, acting on inflammation and vitamin D metabolism. In the present paper, we aimed at evaluating the effect of metformin and vitamin D in targeting ADSC differentiation towards an intermediate phenotype, as beige adipocytes. We exposed ADSCs to different conditioned media and then we evaluated the levels of expression of main markers of adipogenesis, aP2, LPL and ACOT2. We also analysed the gene and protein expression of thermogenic UCP1 protein, and the expression of PARP1 and the beige specific marker TMEM26. Our results showed a novel effect of metformin and vitamin D not only in inhibiting adipogenesis, but also in inducing a specific 'brown-like' phenotype. These findings pave the way for their possible application in the control of de novo lipogenesis useful for the prevention of obesity and its related metabolic disorders.

Keywords: Adipose-derived stem cells; adipogenesis; cellular mechanisms; conditioned media; differentiation; gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis
  • Cell Differentiation
  • Culture Media, Conditioned / pharmacology
  • Metformin* / pharmacology
  • Phenotype
  • Vitamin D* / pharmacology

Substances

  • Culture Media, Conditioned
  • Vitamin D
  • Metformin

Grants and funding

This research was funded by ‘Fondo di Ateneo per la ricerca 2020’ (Margherita Maioli), and PRIN 2017-Giampiero Capobianco.