Che Liqun, Ren Bo, Jia Yuanyuan, Dong Yujia, Wang Yanbing, Shan Jie, Wang Yuchun
Department of Endocrinology Ward 3, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161006, China.
Department of pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, China.
ACS Omega. 2021 Mar 7;6(10):6674-6680. doi: 10.1021/acsomega.0c05470. eCollection 2021 Mar 16.
Excessive lipid accumulation in adipose tissues and deregulation of adipogenesis-induced obesity affect millions of people worldwide. Feprazone, a nonsteroidal anti-inflammatory drug, has a wide clinical use. However, it is unknown whether Feprazone possesses an antiadipogenic ability. The aim of this study is to investigate whether Feprazone possesses an antiadipogenic ability in 3 T3-L1 cells and an antiobesity capacity in mouse models.
An MTT assay was used to determine the optimized incubation concentrations of Feprazone in 3 T3-L1 cells. The lipid accumulation was evaluated using Oil Red O staining. The concentrations of triglyceride and glycerol release were detected to check the lipolysis during 3 T3-L1 adipogenesis. A quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expressions of sterol regulatory element-binding protein-1C (SREBP-1C) and fatty acid binding protein 4 (FABP4) in treated cells. The expressions of peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein α (C/EBP-α), adipose triglyceride lipase (ATGL), and aquaporin-7 (AQP-7) were detected using qRT-PCR and Western blot analysis. After the high-fat diet (HFD) mice were treated with Feprazone, the pathological state of adipocyte tissues was evaluated using HE staining. The adipocyte size, visceral adipocyte tissue weight, and bodyweights were recorded.
According to the proliferation result, 30 and 60 μM Feprazone were used as the optimized concentrations of Feprazone. In the in vitro study, lipid accumulation, elevated production of triglycerides, the release of glycerol, upregulated SREBP-1C, FABP4, PPAR-γ, and C/EBP-α and downregulated ATGL and AQP-7 in the 3 T3-L1 adipocytes induced by the adipocyte differentiation cocktail medium were significantly reversed by treatment with Feprazone. In the in vivo experiment, we found that the increased adipocyte size, visceral adipocyte tissue weight, and body weights induced by HFD feeding in mice were significantly suppressed by the administration of Feprazone.
Feprazone might display anti-adipogenic and antiobesity capacities in in vitro 3 T3-L1 cells and in vivo mice.
脂肪组织中过量的脂质积累以及脂肪生成失调导致的肥胖影响着全球数百万人。非甾体抗炎药非普拉宗具有广泛的临床应用。然而，非普拉宗是否具有抗脂肪生成能力尚不清楚。本研究的目的是探讨非普拉宗在3T3-L1细胞中是否具有抗脂肪生成能力以及在小鼠模型中是否具有抗肥胖能力。
采用MTT法确定非普拉宗在3T3-L1细胞中的最佳孵育浓度。使用油红O染色评估脂质积累。检测甘油三酯和甘油释放浓度以检查3T3-L1脂肪生成过程中的脂解作用。采用定量实时聚合酶链反应（qRT-PCR）测定处理后细胞中固醇调节元件结合蛋白-1C（SREBP-1C）和脂肪酸结合蛋白4（FABP4）的表达。使用qRT-PCR和蛋白质免疫印迹分析检测过氧化物酶体增殖物激活受体-γ（PPAR-γ）、CCAAT/增强子结合蛋白α（C/EBP-α）、脂肪甘油三酯脂肪酶（ATGL）和水通道蛋白7（AQP-7）的表达。在用非普拉宗处理高脂饮食（HFD）小鼠后，使用苏木精-伊红（HE）染色评估脂肪细胞组织的病理状态。记录脂肪细胞大小、内脏脂肪细胞组织重量和体重。
根据增殖结果，30和60μM的非普拉宗被用作非普拉宗的最佳浓度。在体外研究中，脂肪细胞分化混合培养基诱导的3T3-L1脂肪细胞中的脂质积累、甘油三酯产量升高、甘油释放、SREBP-1C、FABP4、PPAR-γ和C/EBP-α上调以及ATGL和AQP-7下调，通过非普拉宗处理得到显著逆转。在体内实验中，我们发现高脂饮食喂养诱导的小鼠脂肪细胞大小增加、内脏脂肪细胞组织重量和体重增加，通过给予非普拉宗得到显著抑制。
非普拉宗可能在体外3T3-L1细胞和体内小鼠中表现出抗脂肪生成和抗肥胖能力。
