Olaparib induces browning of in vitro cultures of human primary white adipocytes

Nagy, Lilla Nikoletta and Rauch, Boglárka and Balla, Noémi and Ujlaki, Gyula and Kis, Gréta and Kristóf, Endre and Sipos, Adrienn and Antal, Miklós and Tóth, Attila and Debreceni, Tamás and Horváth, Ambrus and Maros, Tamás and Csizmadia, Péter and Szerafin, Tamás and Bai, Péter (2019) Olaparib induces browning of in vitro cultures of human primary white adipocytes. BIOCHEMICAL PHARMACOLOGY, 167. pp. 76-85. ISSN 0006-2952


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Mitochondrial biogenesis is a key feature of energy expenditure and organismal energy balance. Genetic deletion of PARP1 or PARP2 was shown to induce mitochondrial biogenesis and energy expenditure. In line with that, PARP inhibitors were shown to induce energy expenditure in skeletal muscle. We aimed to investigate whether pharmacological inhibition of PARPs induces brown or beige adipocyte differentiation. SVF fraction of human pericardial adipose tissue was isolated and human adipose-derived mesenchymal stem cells (hADMSCs) were differentiated to white and beige adipocytes. A subset of hADMSCs were differentiated to white adipocytes in the presence of Olaparib, a potent PARP inhibitor currently in clinical use, to induce browning. Olaparib induced morphological changes (smaller lipid droplets) in white adipocytes that is a feature of brown/beige adipocytes. Furthermore, Olaparib induced mitochondrial biogenesis in white adipocytes and enhanced UCP1 expression. We showed that Olaparib treatment inhibited nuclear and cytosolic PAR formation, induced NAD+/NADH ratio and consequently boosted SIRT1 and AMPK activity and the downstream transcriptional program leading to increases in OXPHOS. Olaparib treatment did not induce the expression of beige adipocyte markers in white adipocytes, suggesting the formation of brown or brown-like adipocytes. PARP1, PARP2 and tankyrases are key players in the formation of white adipose tissue. Hereby, we show that PARP inhibition induces the transdifferentiation of white adipocytes to brown-like adipocytes suggesting that PARP activity could be a determinant of the differentiation of these adipocyte lineages.

Item Type: Article
Subjects: R Medicine / orvostudomány > RZ Other systems of medicine / orvostudomány egyéb területei
Depositing User: MTMT SWORD
Date Deposited: 15 Sep 2019 12:25
Last Modified: 26 Jun 2020 23:15

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