Hydroxychloroquine Improves Obesity-Associated Insulin Resistance and Hepatic Steatosis by Regulating Lipid Metabolism

• Main Authors: Xin Qiao, Zhuo-Chao Zhou, Rui Niu, Yu-Tong Su, Yue Sun, Hong-Lei Liu, Jia-Lin Teng, Jun-Na Ye, Hui Shi, Cheng-De Yang, Xiao-Bing Cheng
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-08-01
• Series: Frontiers in Pharmacology
• Subjects: hydroxychloroquine; hepatic steatosis; dyslipidemia; insulin resistance; peroxisome proliferator-activated receptor gamma
• Online Access: https://www.frontiersin.org/article/10.3389/fphar.2019.00855/full

The burden of obesity and associated cardiometabolic diseases has been considered as an important risk factor for lupus patients. Therefore, whether obesity is involved in the over-activation of autoimmune response has attracted more and more attention. Hydroxychloroquine is a synthetic antimalarial drug and has been the clinical treatment of rheumatic diseases irreplaceable first-line drugs. Hydroxychloroquine has been suggested to have beneficial effects on lipids and insulin sensitivity, which may contribute in lowering high cardiovascular risk in SLE patients. However, its mechanism on insulin sensitivity and lipid disorders is far from being completely understood. In the present study, the therapeutic effects of hydroxychloroquine were evaluated under pathological conditions in vivo. Obesity was induced in C57BL/6 mice fed with high-fed diet, or in mice fed with high-fat diet and hydroxychloroquine. In addition, healthy mice that received normal chow diet were also monitored. The present results revealed that hydroxychloroquine reduced weight, hepatic steatosis, glucose, and insulin resistance. Furthermore, hydroxychloroquine downregulated the expression of peroxisome proliferator-activated receptor gamma in the liver. According to these present results, genes about lipid metabolism went down in high-fat mice liver. Hydroxychloroquine shows potential in ameliorating obesity-induced pathology, which acts though PPARγ to facilitate the healthy function of hepatic tissues. This evidence shows that hydroxychloroquine plays a role in improving obesity-induced lipotoxicity and insulin resistance though the peroxisome proliferator-activated receptor gamma pathway.