Metformin and vitamin D modulate adipose-derived stem cell differentiation towards the beige phenotype
Sara Cruciani,
Giuseppe Garroni,
Renzo Pala,
Donatella Coradduzza,
Maria Laura Cossu,
Giorgio Carlo Ginesu,
Giampiero Capobianco,
Salvatore Dessole,
Carlo Ventura,
Margherita Maioli
Affiliations
Sara Cruciani
Department of Biomedical Sciences, University of Sassari, Sassari, Italy
Giuseppe Garroni
Department of Biomedical Sciences, University of Sassari, Sassari, Italy
Renzo Pala
Department of Biomedical Sciences, University of Sassari, Sassari, Italy
Donatella Coradduzza
Department of Biomedical Sciences, University of Sassari, Sassari, Italy
Maria Laura Cossu
General Surgery Unit 2 “Clinica Chirurgica” Medical, Surgical and Experimental Sciences Department, University of Sassari, Sassari, Italy
Giorgio Carlo Ginesu
General Surgery Unit 2 “Clinica Chirurgica” Medical, Surgical and Experimental Sciences Department, University of Sassari, Sassari, Italy
Giampiero Capobianco
Department of Medical, Surgical and Experimental Sciences, Gynecologic and Obstetric Clinic, University of Sassari, Sassari, Italy
Salvatore Dessole
Department of Medical, Surgical and Experimental Sciences, Gynecologic and Obstetric Clinic, University of Sassari, Sassari, Italy
Carlo Ventura
Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems - Eldor Lab, Innovation Accelerator, Consiglio Nazionale delle Ricerche, Bologna, Italy
Margherita Maioli
Department of Biomedical Sciences, University of Sassari, Sassari, Italy
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.
