Cathepsin S inhibitor reduces high-fat-induced adipogenesis, inflammatory infiltration, and hepatic lipid accumulation in obese mice

作者：Jing Zheng, Hui-jun Zhuang, Tian Zhang, Yanni Wang, Ting Ran, Juan He, Na Han, Juan Duan · 发表于：Annals of Translational Medicine · 年份：2022 · DOI：10.21037/atm-22-5145 · 被引用次数：13 · 研究领域：Protease and Inhibitor Mechanisms、Adipokines, Inflammation, and Metabolic Diseases、Calpain Protease Function and Regulation

Background: Obesity, which results from a caloric intake and energy expenditure imbalance, is highly prevalent worldwide. Cathepsin S (CTSS), which is a cysteine protease, is elevated in obesity and may regulate a variety of physiological processes. This study sought to investigate the functional role of CTSS in obesity. Methods: and fed a high-fat diet (HFD) to induce obesity. The weights of the mice fed a normal-chow diet and a HFD were measured. The expression levels of total triglycerides (TG), total cholesterol (TC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and monocyte chemoattractant protein-1 (MCP-1) were assessed using appropriate corresponding assay kits. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to estimate the messenger ribonucleic acid (mRNA) expression of CTSS in the serum and the release of M1- and M2-type cytokines, and western blot was used to measure the phosphorylated-nuclear factor kappaB (NF-kappaB) p65 and NF-κB p65 proteins. The mRNA and protein expressions of sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FASN), leptin, and adiponectin were also evaluated by RT-qPCR and western blot. Further, hematoxylin and eosin (H&E), immunohistochemical, and red oil O staining were employed to detect the pathological changes of the epididymal white adipose tissue (eWAT), the macrophage infiltration in the eWAT, and lipid accumulation, respectively. Results: We found that CTSS...