Targeting adenosine receptor by polydeoxyribonucleotide: An effective therapeutic strategy to induce white-to-brown adipose differentiation and to curb obesity
| Autor: | Violetta Squadrito, Domenica Altavilla, Giovanni Pallio, Federica Mannino, Francesco Squadrito, Domenico Antonio Giorgi, Natasha Irrera, Alessandra Bitto, Letteria Minutoli, Vincenzo Arcoraci, Igor Pirrotta |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Ucp1 adipocytes Pharmaceutical Science Adipose tissue White adipose tissue Article A2A receptor 2A receptor Adipocytes Browning process Polydeoxyribonucleotide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacy and materia medica Adipocyte Internal medicine Lipid droplet Drug Discovery Brown adipose tissue medicine Oil Red O PRDM16 Adiponectin browning process RS1-441 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Molecular Medicine Medicine polydeoxyribonucleotide 030217 neurology & neurosurgery |
| Zdroj: | Pharmaceuticals, Vol 14, Iss 728, p 728 (2021) Pharmaceuticals Volume 14 Issue 8 |
| Popis: | Obesity is a worldwide chronic metabolic disease characterized by an abnormal fat accumulation and represents one of the main risk factors for several diseases. White adipose tissue is the primary site for energy storage in the form of triglycerides, whereas brown adipose tissue does not store energy-providing lipids but rather dissipates it by producing heat. White-to-brown adipocyte trans-differentiation could represent a new target of anti-obesity strategies and result in fat reduction. Previous studies indicated that adenosine receptor activation induces trans-differentiation of white adipocytes to brown adipocytes. The aim of this study was to evaluate the effects of polydeoxyribonucleotide (PDRN), an A2Ar receptor agonist, in an in vitro model of browning. Mouse 3T3-L1 pre-adipocytes were differentiated in mature adipocytes with specific culture media and then treated with PDRN (10 µg/mL), PDRN + ZM241385 (1 µM), CGS21680 (1 µM) and CGS + ZM241385 for 24 h. Cell viability was studied by MTT assay, and browning induction was evaluated by Oil Red O staining and by RT-qPCR to study gene expression of browning markers. PDRN, as well as CGS21680, reduced the accumulation of lipids, cell volume and lipid droplet size increased the expression of UCP1, PRDM16 and DIO2, considered as browning markers and reduced the expression of FASn and FABP4, considered as whitening markers. In addition, PDRN decreased leptin expression and enhanced adiponectin mRNA levels. All these effects were abrogated when PDRN was co-incubated with the A2Ar antagonist ZM241385. In conclusion, these results suggest that PDRN is able to induce the white-to-brown adipose differentiation through A2Ar stimulation. Since PDRN is a safe drug already available in the market for other therapeutic indications, its “anti-obesity” potential warrants investigation in a clinical scenario. |
| Databáze: | OpenAIRE |
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