Metformin and Vitamin D Modulate Inflammation and Autophagy during Adipose-Derived Stem Cell Differentiation.
Sara CrucianiGiuseppe GarroniRenzo PalaMaria Laura CossuGiorgio Carlo GinesuCarlo VenturaMargherita MaioliPublished in: International journal of molecular sciences (2021)
Adipose-derived stem cells (ADSCs) came out from the regenerative medicine landscape for their ability to differentiate into several phenotypes, contributing to tissue regeneration both in vitro and in vivo. Dysregulation in stem cell recruitment and differentiation during adipogenesis is linked to a chronic low-grade inflammation and macrophage infiltration inside the adipose tissue, insulin resistance, cardiovascular disease and obesity. In the present paper we aimed to evaluate the role of metformin and vitamin D, alone or in combination, in modulating inflammation and autophagy in ADSCs during adipogenic commitment. ADSCs were cultured for 21 days in the presence of a specific adipogenic differentiation medium, together with metformin, or vitamin D, or both. We then analyzed the expression of FoxO1 and Heat Shock Proteins (HSP) and the secretion of proinflammatory cytokines IL-6 and TNF-α by ELISA. Autophagy was also assessed by specific Western blot analysis of ATG12, LC3B I, and LC3B II expression. Our results showed the ability of the conditioned media to modulate adipogenic differentiation, finely tuning the inflammatory response and autophagy. We observed a modulation in HSP mRNA levels, and a significant downregulation in cytokine secretion. Taken together, our findings suggest the possible application of these molecules in clinical practice to counteract uncontrolled lipogenesis and prevent obesity and obesity-related metabolic disorders.
Keyphrases
- insulin resistance
- oxidative stress
- heat shock
- high fat diet induced
- adipose tissue
- stem cells
- signaling pathway
- low grade
- cell death
- metabolic syndrome
- endoplasmic reticulum stress
- type diabetes
- inflammatory response
- high fat diet
- cardiovascular disease
- heat shock protein
- weight loss
- poor prognosis
- heat stress
- skeletal muscle
- clinical practice
- high grade
- weight gain
- pi k akt
- binding protein
- simultaneous determination
- rheumatoid arthritis
- cell therapy
- endothelial cells
- toll like receptor
- south africa
- lipopolysaccharide induced
- wound healing
- cardiovascular events
- cell proliferation
- drug induced
- tandem mass spectrometry
- transcription factor
- single cell
- cell fate