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

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.

Humanin and Its Pathophysiological Roles in Aging: A Systematic Review

“…Additionally, Muzumdar et al conducted an in vivo study on 101 rats to investigate the role of central and peripheral HN on insulin action. It was demonstrated that continuous intra-cerebro-ventricular infusion of HN significantly improved overall insulin sensitivity [ 29 , 97 ]. Activation of hypothalamic STAT-3 signaling was associated with central effects of HN on insulin action; such effects were canceled by co-inhibition of hypothalamic STAT-3.…”

“…Some authors speculate that mitochondrial dysfunction may be beneficial to the cell because it may elicit an effective stress response [ 72 ]. Through these, mitochondria regulate not only energy production but a cellular homeostasis that includes a range of processes such as immune/inflammatory responses, proteostasis, adaptive responses to stress, and apoptosis [ 96 , 97 , 98 ]. Muscle humanin expression is upregulated in humans, in response to exercise stress, mtDNA mutation-associated diseases, and healthy aging, suggesting a tissue-specific response aimed at restoring mitochondrial homeostasis [ 102 ] in response to stress from, for example, acute exercise [ 102 ].…”

Management of Obesity and Obesity-Related Disorders: From Stem Cells and Epigenetics to Its Treatment

“…When upregulated, miR-148a promotes adipogenic differentiation, 116 while it inhibits preadipocyte differentiation when miR-145 is upregulated and miR-148 117 is downregulated [51] (Figure 1). These molecules are also able to modulate inflammation 118 and the expression of other key genes involved in adipogenic differentiation, 119 counteracting WAT formation, and inducing a "brown-like" phenotype [52,53]. The use 120 of bioactive molecules and chemical stimuli can then control the de-novo lipogenesis, 121 differentiation, and physiology of adipose tissue, for the in vivo treatment of chronic 122 pathological conditions of difficult resolution.…”