Abstract
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.
Highlights
For several decades, industrialized countries have been faced with the increasing prevalence of autoimmune-mediated diseases (Pedersen et al, 2007; Patterson et al, 2009)
It has been demonstrated by several studies that synthesis of lipid is correlated to high serum glucose levels, insulin resistance, and pathogenesis of diabetes (Winzell and Ahren, 2004; Kusminski et al, 2016)
These results indicate that high-fat diet (HFD) effectively induced obesity and HCQ reduced body weight and fat mass in HFDinduced obese mice
Summary
For several decades, industrialized countries have been faced with the increasing prevalence of autoimmune-mediated diseases (Pedersen et al, 2007; Patterson et al, 2009). These diseases are the result of complex genetic backgrounds interacting with multiple environmental factors. Νonalcoholic fatty liver disease (NAFLD), which has been characterized as an increase in hepatic triglycerides (TGs) content, is usually found in obese subjects (Matteoni et al, 1999), and a risk factor for many metabolic diseases, including type-2 diabetes mellitus (Lallukka and Yki-Järvinen, 2016) and cardiovascular disease (Targher et al, 2010)
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