Sodium salicylate induces browning of white adipocytes via M2 macrophage polarization by HO-1 upregulation
- Authors
- Choi, Hye-Eun; Jeon, Eun Jeong; Kim, Dong Young; Choi, Mi Jin; Yu, Hana; Kim, Jea Il; Cheon, Hyae Gyeong
- Issue Date
- Aug-2022
- Publisher
- Elsevier
- Keywords
- Browning; Heme oxygenase-1; M2 polarization; Salicylate
- Citation
- European Journal of Pharmacology, v.928
- Journal Title
- European Journal of Pharmacology
- Volume
- 928
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/86130
- DOI
- 10.1016/j.ejphar.2022.175085
- ISSN
- 0014-2999
- Abstract
- Browning, a white to brown-like (beige) adipocyte conversion, offers a promising therapeutic strategy for the treatment of human obesity. In the present study, the effects of sodium salicylate, a nonsteroidal anti-inflammatory drug, on adipocyte browning were investigated. We found sodium salicylate altered the macrophage phenotype to M2 in RAW264.7 cells, mediated by up-regulation of heme oxygenase-1 (HO-1), and sodium salicylate-treated conditioned medium from macrophages (Sal-M2 CM) induced browning of fully differentiated 3T3-L1 adipocytes. Conversely, the conditioned medium obtained from macrophages when treated with sodium salicylate in the presence of either ZnPP (a HO-1 inhibitor) or HO-1 siRNA did not induce browning. In association with macrophage HO-1 induction by sodium salicylate, iron production also increased, and deferoxamine (an iron chelator) blunted the browning effects of Sal-M2 CM, suggesting that iron may play a role in the Sal-M2 CM-induced browning. The in vivo browning effects of sodium salicylate were confirmed in ob/ob mice, whereas in vivo macrophage depletion by clodronate as well as HO-1 blockade by either ZnPP or adeno-associated virus carrying HO-1 shRNA (AAV–HO–1 shRNA) attenuated the browning effects of sodium salicylate. These results reveal sodium salicylate induces browning in vitro and in vivo by up-regulating HO-1 thus promoting M2 polarization. © 2022 Elsevier B.V.
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