Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A<sub>1</sub> Receptor Ligands
Adenosine A<sub>1</sub> receptor (A<sub>1</sub>R) activation, stimulating lipogenesis and decreasing insulin resistance, could be useful for metabolic syndrome management in obese subjects. Since full A<sub>1</sub>R agonists induce harmful side-effects, while part...
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MDPI AG
2021-12-01
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| author | Mariachiara Zuccarini Catia Lambertucci Marzia Carluccio Patricia Giuliani Maurizio Ronci Andrea Spinaci Rosaria Volpini Renata Ciccarelli Patrizia Di Iorio |
| author_facet | Mariachiara Zuccarini Catia Lambertucci Marzia Carluccio Patricia Giuliani Maurizio Ronci Andrea Spinaci Rosaria Volpini Renata Ciccarelli Patrizia Di Iorio |
| author_sort | Mariachiara Zuccarini |
| collection | DOAJ |
| description | Adenosine A<sub>1</sub> receptor (A<sub>1</sub>R) activation, stimulating lipogenesis and decreasing insulin resistance, could be useful for metabolic syndrome management in obese subjects. Since full A<sub>1</sub>R agonists induce harmful side-effects, while partial agonists show a better pharmacological profile, we investigated the influence of two derivatives of the full A<sub>1</sub>R agonist 2-chloro-<i>N</i><sup>6</sup>-cyclopentyladenosine (CCPA), C1 and C2 behaving as A<sub>1</sub>R 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 A<sub>1</sub>R expression but reduced adipogenic differentiation compared to obese individual-derived ASCs. Cell exposure to CCPA, C1, C2 or DPCPX, an A<sub>1</sub>R 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 A<sub>1</sub>R 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. |
| first_indexed | 2024-03-10T04:25:19Z |
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| last_indexed | 2024-03-10T04:25:19Z |
| publishDate | 2021-12-01 |
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| series | Cells |
| spelling | doaj.art-eadce9d5aa25496ea2a74c68af0bc7652023-11-23T07:39:30ZengMDPI AGCells2073-44092021-12-011012356010.3390/cells10123560Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A<sub>1</sub> Receptor LigandsMariachiara Zuccarini0Catia Lambertucci1Marzia Carluccio2Patricia Giuliani3Maurizio Ronci4Andrea Spinaci5Rosaria Volpini6Renata Ciccarelli7Patrizia Di Iorio8Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, ItalyUnit of Medicinal Chemistry, School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032 Camerino, ItalyDepartment of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, ItalyDepartment of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, ItalyDepartment of Pharmacy, University of Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, ItalyUnit of Medicinal Chemistry, School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032 Camerino, ItalyUnit of Medicinal Chemistry, School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032 Camerino, ItalyDepartment of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, ItalyDepartment of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, ItalyAdenosine A<sub>1</sub> receptor (A<sub>1</sub>R) activation, stimulating lipogenesis and decreasing insulin resistance, could be useful for metabolic syndrome management in obese subjects. Since full A<sub>1</sub>R agonists induce harmful side-effects, while partial agonists show a better pharmacological profile, we investigated the influence of two derivatives of the full A<sub>1</sub>R agonist 2-chloro-<i>N</i><sup>6</sup>-cyclopentyladenosine (CCPA), C1 and C2 behaving as A<sub>1</sub>R 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 A<sub>1</sub>R expression but reduced adipogenic differentiation compared to obese individual-derived ASCs. Cell exposure to CCPA, C1, C2 or DPCPX, an A<sub>1</sub>R 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 A<sub>1</sub>R 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.https://www.mdpi.com/2073-4409/10/12/3560adipose stromal cells (ASCs)subcutaneous adipose tissueadenosine A<sub>1</sub> receptorsadipogenic differentiationadipogenic markers |
| spellingShingle | Mariachiara Zuccarini Catia Lambertucci Marzia Carluccio Patricia Giuliani Maurizio Ronci Andrea Spinaci Rosaria Volpini Renata Ciccarelli Patrizia Di Iorio Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A<sub>1</sub> Receptor Ligands Cells adipose stromal cells (ASCs) subcutaneous adipose tissue adenosine A<sub>1</sub> receptors adipogenic differentiation adipogenic markers |
| title | Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A<sub>1</sub> Receptor Ligands |
| title_full | Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A<sub>1</sub> Receptor Ligands |
| title_fullStr | Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A<sub>1</sub> Receptor Ligands |
| title_full_unstemmed | Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A<sub>1</sub> Receptor Ligands |
| title_short | Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A<sub>1</sub> Receptor Ligands |
| title_sort | multipotent stromal cells from subcutaneous adipose tissue of normal weight and obese subjects modulation of their adipogenic differentiation by adenosine a sub 1 sub receptor ligands |
| topic | adipose stromal cells (ASCs) subcutaneous adipose tissue adenosine A<sub>1</sub> receptors adipogenic differentiation adipogenic markers |
| url | https://www.mdpi.com/2073-4409/10/12/3560 |
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