Melatonin and Vitamin D Interfere with the Adipogenic Fate of Adipose-Derived Stem Cells.

Valentina Basoli,Carlo Ventura,Margherita Maioli,Pier Serra,Alessandro Delitala,Sara Santaniello,Giorgio Ginesu,Sara Cruciani,Maria Cossu

doi:10.3390/ijms18050981

Abstract

Adipose-derived stem cells (ADSCs) represent one of the cellular populations resident in adipose tissue. They can be recruited under certain stimuli and committed to become preadipocytes, and then mature adipocytes. Controlling stem cell differentiation towards the adipogenic phenotype could have a great impact on future drug development aimed at counteracting fat depots. Stem cell commitment can be influenced by different molecules, such as melatonin, which we have previously shown to be an osteogenic inducer. Here, we aimed at evaluating the effects elicited by melatonin, even in the presence of vitamin D, on ADSC adipogenesis assessed in a specific medium. The transcription of specific adipogenesis orchestrating genes, such as aP2, peroxisome proliferator-activated receptor γ (PPAR-γ), and that of adipocyte-specific genes, including lipoprotein lipase (LPL) and acyl-CoA thioesterase 2 (ACOT2), was significantly inhibited in cells that had been treated in the presence of melatonin and vitamin D, alone or in combination. Protein content and lipid accumulation confirmed a reduction in adipogenesis in ADSCs that had been grown in adipogenic conditions, but in the presence of melatonin and/or vitamin D. Our findings indicate the role of melatonin and vitamin D in deciding stem cell fate, and disclose novel therapeutic approaches against fat depots.

Highlights

Adipose tissue represents a widespread component in the human body
This effect was evident in adipose-derived stem cells (ADSCs) that had been concomitantly exposed to vitamin D (10−6 M) and melatonin
The same figure shows the effect of the different conditioned media on the gene expression of adipocyte fatty acid binding protein, aP2, in ADSCs cultured under different conditioned media (Figure 1B). This gene was actively expressed during adipogenic differentiation induced by culturing cells in differentiation medium (DM), while under the other experimental conditions tested aP2 gene expression was significantly inhibited, being only faintly detectable when ADSCs were committed towards the adipogenic phenotype in the presence of both vitamin D (10−6 and 10−8 M) and melatonin

Summary

Introduction

Adipose tissue represents a widespread component in the human body. It can be found as subcutaneous fat, >80% of the total fat in the body, mainly dealing with energy balance as abdominal, gluteal and femoral depots [1].Several studies have highlighted visceral fat, which protect internal organs, as a risk factor for many unhealthy conditions such as insulin-resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, and metabolic syndrome [2].Besides mature adipocytes, fat tissue contains several other cell types, such as stromal-vascular cells (SVC), fibroblasts, smooth muscle cells, pericytes, endothelial cells, and adipogenic progenitor cells or preadipocytes [3].These adipogenic progenitor cells retain the ability to develop during adulthood, their development mainly happens in early postnatal life [3,4,5,6]. Adipose tissue represents a widespread component in the human body. It can be found as subcutaneous fat, >80% of the total fat in the body, mainly dealing with energy balance as abdominal, gluteal and femoral depots [1]. Fat tissue contains several other cell types, such as stromal-vascular cells (SVC), fibroblasts, smooth muscle cells, pericytes, endothelial cells, and adipogenic progenitor cells or preadipocytes [3]. These adipogenic progenitor cells retain the ability to develop during adulthood, their development mainly happens in early postnatal life [3,4,5,6]. Adipose tissue contains adipose precursor cells, called preadipocytes, which arise from mesenchymal stem cells (MSCs) resident in a particular tissue zone called the “niche” [7,8], a specific environment defined at the nanoscale level which fashions topographies that can either promote or erase pluripotency of the embedded cells [5]

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