Reduction of NADPH oxidase 4 in adipocytes contributes to the anti-obesity effect of dihydroartemisinin. Issue 3 (March 2023)

• Record Type: Journal Article
• Authors: Hua, Hu; Wu, Mengqiu; Wu, Tong; Ji, Yong; Jin, Lv; Du, Yang; Zhang, Yue; Huang, Songming; Zhang, Aihua; Ding, Guixia; Liu, Qianqi; Jia, Zhanjun
• Is Part Of: Heliyon. Volume 9:Issue 3(2023)
• Publication Date: 2023-03
• Subjects: Dihydroartemisinin -- Obesity -- NOX4 -- Adipocyte differentiation -- Lipid accumulation; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2023.e14028
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: Artemisinin derivatives have been found to have anti-obesity effects recently, but the mechanism is still controversial. Herein, long-term DHA treatment in obese mice significantly reduced the body weight and improved glucose metabolism. However, short-term DHA treatment did not affect glucose metabolism in obese mice, suggesting that the improved glucose metabolism in mice with DHA treatment could be secondary to body weight reduction. Consistent with previous reports, we observed that DHA inhibited the differentiation of adipocytes. Mechanistically, DHA significantly reduced the expression of NADPH oxidase 4 (NOX4) in white adipose tissue (WAT) of mice and differentiated adipocytes, and using NOX4 siRNA or the NOX4 inhibitor GKT137831 significantly attenuated adipocyte differentiation. Over-expression of NOX4 partially reversed the inhibition effect of DHA on adipogenic differentiation of preadipocytes. In addition, targeted proteomics analysis showed that DHA improved the abnormality of metabolic pathways. In conclusion, DHA significantly reduced fat mass and improved glucose metabolism in obese mice, possibly by inhibiting NOX4 expression to suppress adipocyte differentiation and lipid accumulation in adipocytes. Highlights: DHA improved glucose metabolism in obese mice possibly by ameliorating obesity. DHA attenuated lipid accumulation in white adipose tissues and differentiated adipocytes. DHA inhibited adipocyte differentiation possibly by inhibiting NOX4 expression. DHA improved the abnormality of metabolic pathways.