Reduction of NADPH oxidase 4 in adipocytes contributes to the anti-obesity effect of dihydroartemisinin

Hu Hua; Mengqiu Wu; Tong Wu; Yong Ji; Lv Jin; Yang Du; Yue Zhang; Songming Huang; Aihua Zhang; Guixia Ding; Qianqi Liu; Zhanjun Jia

doi:10.1016/j.heliyon.2023.e14028

Reduction of NADPH oxidase 4 in adipocytes contributes to the anti-obesity effect of dihydroartemisinin

Heliyon. 2023 Feb 25;9(3):e14028. doi: 10.1016/j.heliyon.2023.e14028. eCollection 2023 Mar.

Authors

Hu Hua^{1

2

3}, Mengqiu Wu^{1

2

3}, Tong Wu^{4

5}, Yong Ji¹, Lv Jin¹, Yang Du^{1

2

3}, Yue Zhang^{1

2

3}, Songming Huang^{1

2

3}, Aihua Zhang^{1

2

3}, Guixia Ding¹, Qianqi Liu^{4

5}, Zhanjun Jia^{1

2

3}

Affiliations

¹ Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
² Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
³ Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
⁴ Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, China.
⁵ Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China.

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.

Keywords: Adipocyte differentiation; Dihydroartemisinin; Lipid accumulation; NOX4; Obesity.