Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A1 Receptor Ligands.

Mariachiara Zuccarini,Rosaria Volpini,Marzia Carluccio,Catia Lambertucci,Maurizio Ronci,Renata Ciccarelli,Andrea Spinaci,Patricia Giuliani,Patrizia Di Iorio

doi:10.3390/cells10123560

Mariachiara Zuccarini, Rosaria Volpini + Show 7 more

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https://doi.org/10.3390/cells10123560

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Journal: Cells	Publication Date: Dec 17, 2021
Citations: 1	License type: CC BY 4.0

Affiliation: University of Chieti-Pescara, Università di Camerino

Abstract

Adenosine A1 receptor (A1R) activation, stimulating lipogenesis and decreasing insulin resistance, could be useful for metabolic syndrome management in obese subjects. Since full A1R agonists induce harmful side-effects, while partial agonists show a better pharmacological profile, we investigated the influence of two derivatives of the full A1R agonist 2-chloro-N6-cyclopentyladenosine (CCPA), C1 and C2 behaving as A1R partial agonists in animal models, on the adipogenic differentiation of stromal/stem cells (ASCs) from human subcutaneous adipose tissue, which mainly contribute to increase fat mass in obesity. The ASCs from normal-weight subjects showed increased proliferation and A1R expression but reduced adipogenic differentiation compared to obese individual-derived ASCs. Cell exposure to CCPA, C1, C2 or DPCPX, an A1R antagonist, did not affect ASC proliferation, while mainly C2 and DPCPX significantly decreased adipogenic differentiation of both ASC types, reducing the activity of glycerol-3-phosphate dehydrogenase and the expression of PPARγ and FABP-4, all adipogenic markers, and phosphorylation of Akt in the phosphatidylinositol-3-kinase pathway, which plays a key-role in adipogenesis. While requiring confirmation in in vivo models, our results suggest that A1R partial agonists or antagonists, by limiting ASC differentiation into adipocytes and, thereby, fat mass expansion, could favor development/worsening of metabolic syndrome in obese subjects without a dietary control.

Highlights

IntroductionSevere pathologies such as diabetes and/or cardiovascular diseases are caused by or associated with obesity [1], whose prevalence has tripled worldwide in the last four decades
We first characterized some properties of the adipogenic differentiation of stromal/stem cells (ASCs) derived from the subcutaneous adipose tissue of normal weight and obese subjects
We observed that the number of viable cells counted by the trypan blue exclusion method was lower for both cell types when they were induced towards adipogenic differentiation (Figure 2A); the number of live ASCs from normal-weight subjects was mostly greater than those of obese subjects both when undifferentiated and grown in adipogenic medium for 10 days in vitro (DIV)

Summary

Introduction

Severe pathologies such as diabetes and/or cardiovascular diseases are caused by or associated with obesity [1], whose prevalence has tripled worldwide in the last four decades. WAT is constituted by two fat depots named subcutaneous (SAT) and visceral (VAT) adipose tissues, due to their different locations below the skin and in the trunk cavity, respectively [4]. These tissues are morphologically similar, it has been recently demonstrated that they exhibit different metabolic characteristics. In obesity, while the increase in SAT is regarded as protective, by improving insulin sensitivity and decreasing the risk of developing type 2 diabetes, the accumulation of visceral fat is associated with metabolic disease and its harmful sequelae

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