Cathepsin S inhibitor reduces high-fat-induced adipogenesis, inflammatory infiltration, and hepatic lipid accumulation in obese mice.
Cathepsin S inhibitor reduces high-fat-induced adipogenesis, inflammatory infiltration, and hepatic lipid accumulation in obese mice.
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组织蛋白酶 S 抑制剂可减少肥胖小鼠高脂肪诱导的脂肪生成、炎症浸润和肝脂质积累
DOI：
10.21037/atm-22-5145
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发表时间：
2022-11
影响因子：
--
通讯作者：
Duan, Juan
中科院分区：
文献类型：
--
作者：
Zheng, Jing;Zhuang, Huijun;Zhang, Tian;Wang, Yanni;Ran, Ting;He, Juan;Han, Na;Duan, Juan
关键词：
背景 肥胖是由热量摄入和能量消耗不平衡引起的，在世界范围内非常普遍。组织蛋白酶 S (CTSS) 是一种半胱氨酸蛋白酶，在肥胖时会升高，并可调节多种生理过程。本研究旨在探讨 CTSS 在肥胖中的功能作用。方法给小鼠体内给予60 mg/kg RO5444101并喂食高脂饮食（HFD）以诱导肥胖。测量了喂食正常饮食和高脂饮食的小鼠的体重。使用适当的相应测定试剂盒评估总甘油三酯（TG）、总胆固醇（TC）、天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和单核细胞趋化蛋白-1（MCP-1）的表达水平。采用逆转录定量聚合酶链反应（RT-qPCR）测定血清中 CTSS 信使核糖核酸（mRNA）的表达以及 M1 和 M2 型细胞因子的释放，采用蛋白质印迹法测定磷酸化核因子 kappaB（NF-kappaB）p65 和 NF-κB p65 蛋白。还通过 RT-qPCR 和蛋白质印迹评估了甾醇调节元件结合蛋白 1 (SREBP1)、脂肪酸合成酶 (FASN)、瘦素和脂联素的 mRNA 和蛋白表达。进一步采用苏木精和伊红（H&E）、免疫组化和红油O染色分别检测附睾白色脂肪组织（eWAT）的病理变化、eWAT中巨噬细胞的浸润和脂质积累。结果我们发现肥胖小鼠的血浆、内脏脂肪和肝组织中 CTSS 升高。给予60 mg/kg RO5444101后，肥胖小鼠体重下降，胰岛素抵抗受到抑制，脂肪细胞形成受到抑制。 CTSS 抑制剂还降低了 HFD 诱导的小鼠 eWAT 中的巨噬细胞浸润水平、MCP-1 表达以及 M1 和 M2 型细胞因子的释放。 CTSS 抑制剂似乎可以改善 HFD 诱导的小鼠的肝功能参数和脂质积累。 CTSS 抑制剂似乎还可以改善 HFD 诱导的小鼠的炎症损伤。结论 CTSS 抑制剂有助于防止肥胖小鼠 HFD 诱导的脂肪形成、炎症浸润和肝脏脂质积累。
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 Mice were administrated 60 mg/kg of RO5444101 in vivo 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 was elevated in the plasma, visceral adipose, and liver tissues of the obese mice. After the administration of 60 mg/kg of RO5444101, the weight of the obese mice decreased, insulin resistance was inhibited, and adipocyte formation was suppressed. The CTSS inhibitor also decreased the level of macrophage infiltration in the eWAT, MCP-1 expression, and the release of M1- and M2-type cytokines in the HFD-induced mice. The CTSS inhibitor appeared to improve the hepatic function parameters and lipid accumulation of the HFD-induced mice. The CTSS inhibitor also appeared to improve the inflammatory damage in the HFD-induced mice. Conclusions CTSS inhibitor helped to protect against HFD-induced adipogenesis, inflammatory infiltration, and hepatic lipid accumulation in obese mice.
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影响因子：
7.3
作者：
Hirahara L;Takase-Minegishi K;Kirino Y;Iizuka-Iribe Y;Soejima Y;Yoshimi R;Nakajima H
通讯作者：
Nakajima H
影响因子：
7.7
作者：
Kitade H;Sawamoto K;Nagashimada M;Inoue H;Yamamoto Y;Sai Y;Takamura T;Yamamoto H;Miyamoto K;Ginsberg HN;Mukaida N;Kaneko S;Ota T
通讯作者：
Ota T
影响因子：
4.1
作者：
Rauner, M.;Foeger-Samwald, U.;Pietschmann, P.
通讯作者：
Pietschmann, P.
结直肠癌患者血清组织蛋白酶S水平的评价。
影响因子：
1.7
作者：
Ghanadi, Koroush;Ashorzadeh, Saber;Aliyepoor, Asghar;Anbari, Khatereh
通讯作者：
Anbari, Khatereh
影响因子：
2.7
作者：
Li J;Gong L;Xu Q
通讯作者：
Xu Q