Metformin and vitamin D modulate adipose-derived stem cell differentiation towards the beige phenotype.
Sara CrucianiGiuseppe GarroniRenzo PalaDonatella CoradduzzaMaria Laura CossuGiorgio Carlo GinesuGiampiero CapobiancoSalvatore DessoleCarlo VenturaMargherita MaioliPublished in: Adipocyte (2022)
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.
Keyphrases
- high fat diet induced
- stem cells
- poor prognosis
- insulin resistance
- transcription factor
- gene expression
- genome wide
- metabolic syndrome
- binding protein
- dna methylation
- genome wide identification
- dna repair
- quality improvement
- long non coding rna
- drug delivery
- cancer therapy
- weight gain
- small molecule
- heat shock
- bone marrow
- heat stress