Melatonin and Vitamin D Orchestrate Adipose Derived Stem Cell Fate by Modulating Epigenetic Regulatory Genes

Abstract

Melatonin, that regulates many physiological processes including circadian rhythms, is a molecule able to promote osteoblasts maturation in vitro and to prevent bone loss in vivo, while regulating also adipocytes metabolism. In this regard, we have previously shown that melatonin in combination with vitamin D, is able to counteract the appearance of an adipogenic phenotype in adipose derived stem cells (ADSCs), cultured in an adipogenic favoring condition. In the present study, we aimed at evaluating the specific phenotype elicited by melatonin and vitamin D based medium, considering also the involvement of epigenetic regulating genes. ADSCs were cultured in a specific adipogenic conditioned media, in the presence of melatonin alone or with vitamin D. The expression of specific osteogenic related genes was evaluated at different time points, together with the histone deacetylases epigenetic regulators, HDAC1 and Sirtuins (SIRT) 1 and 2.Our results show that melatonin and vitamin D are able to modulate ADSCs commitment towards osteogenic phenotype through the upregulation of HDAC1, SIRT 1 and 2, unfolding an epigenetic regulation in stem cell differentiation and opening novel strategies for future therapeutic balancing of stem cell fate toward adipogenic or osteogenic phenotype.

Tuning Adipogenic Differentiation in ADSCs by Metformin and Vitamin D: Involvement of miRNAs

“…Understanding the molecular mechanisms involved in these alterations could contribute in controlling adipogenesis and its related metabolic complications, as cardiovascular risk. Within this context, we previously demonstrated that the combination of melatonin and vitamin D is able to counteract adipogenic differentiation in ADSCs, reducing cytoplasmatic fatty acid accumulation and maintaining the pluripotency of stem cells [ 33 , 34 ]. In the present paper, we evaluated the effect of metformin and vitamin D, alone or in combination, on ADSC adipogenic differentiation.…”

Effect of rhTSH on Lipids

“…The effect of thyroid hormone on lipid metabolism is complex and poorly understood. Lipid metabolism is regulated by different enzymes, which are regulated by different specific gene and hormones [20,21] and lack of thyroid hormone causes elevation in total cholesterol and LDLc by changes in the synthesis, metabolism, and mobilisation of lipids [22].…”

Direct-to-Consumer Nutrigenetics Testing: An Overview

“…Vitamin D is important in a wide range of physiological processes, and its deficit has been related to different chronic diseases and metabolic conditions, including obesity. Nonetheless, encompassing literature studies indicated only a faint association between gene variants acting in vitamin D metabolism and the obese phenotype [33], while the environment seems to play a major role [34][35][36]. The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to the six susceptibility loci harboring genome-wide significant SNPs (recently identified in a large GWAS) is 7.5%, with statistically significant loci explaining 38% of this total [37].…”