Abstract
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.
Highlights
Adipose-derived stem cells (ADSCs) are largely involved in therapeutic applications and regenerative medicine, being linked to the maintenance of adipose tissue homeostasis and regeneration [1]
The same Figure shows that ADSCs cultured in MD alone exhibited a typical mature adipocyte morphology (Figure 1)
We recently described the effect of metformin, alone or in combination with vitamin D, in controlling ADSC adipogenic differentiation, acting on vitamin D metabolism through epigenetic modification and miRNAs [33]
Summary
Adipose-derived stem cells (ADSCs) are largely involved in therapeutic applications and regenerative medicine, being linked to the maintenance of adipose tissue homeostasis and regeneration [1]. Dysregulation in stem cell recruitment and differentiation leads to the secretion of pro-inflammatory cytokines, metabolic stress, insulin resistance, cardiovascular diseases, and obesity [6,7]. As it occurs in obesity, is accompanied by the secretion of proinflammatory cytokines, as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) [5,8,9]. Forkhead box-O1 (FoxO1) is a transcription factor exerting an essential role in controlling lipid metabolism and energy homeostasis, modulating adipocyte terminal differentiation [12,13]
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