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BGM,一种新合成的硼化合物,通过抑制 3T3-L1 脂肪细胞中的 PPARγ 和 CTRP3 来诱导细胞凋亡和减少氧化应激,从而抑制脂肪生成。

BGM, a Newly Synthesised Boron Compound, Induces Apoptosis and Reduces Oxidative Stress by Inhibiting Lipogenesis in 3T3-L1 Adipocytes via PPARγ and CTRP3.

机构信息

Department of Basic Sciences of Engineering, Faculty of Engineering and Natural Sciences, Kutahya Health Sciences University, Kutahya, Turkey.

出版信息

Biol Trace Elem Res. 2022 Nov;200(11):4807-4816. doi: 10.1007/s12011-022-03261-z. Epub 2022 May 4.

Abstract

Obesity is a chronic disease associated with increased morbidity and mortality. The rapidly increasing prevalence of obesity makes it a global health problem, while treatment options remain limited. Given the potential of boron in the treatment of obesity, the aim of this study is to investigate the anti-adipogenic activity of the newly synthesised boron glycine monoester compound (BGM) using 3T3-L1 adipocytes by analysing lipid accumulation, CTRP3 and PPARy gene expression, oxidative stress and apoptotic effects. 3T3-L1 fibroblast cells (ATCC® CL-173) were transformed into adipocyte cells in vitro. Fat accumulation in the 3T3-L1 adipocyte cells was detected by Oil Red O staining. Gene expression levels were determined with qPCR. Biochemical analyzes were performed using spectrophotometric method (CAT, ALP and ACP) and ELISA kit (TAS, TOS, NADP-IDH). Apoptosis studies were performed on the muse cell nalyser using the Muse Annexin V & Dead Cell Assay Kit. When BGM-treated cells were compared to control adipocyte cells, lipid accumulation decreased in a dose-dependent manner. BGM-treated adipocyte cells had higher CTRP3 expression levels and lower PPAR-γ gene expression levels compared to control adipocyte cells (p < 0.001). While BGM application increased the TAS level, it showed an antioxidant effect by regulating the activity of oxidative metabolism enzymes (p < 0.001). BGM application increased total apoptosis by 1.5-fold. These results show that BGM is a potential therapeutic agent for obesity by regulating the expression of genes related to adipogenesis and lipogenesis in adipocyte cells and by affecting the activity of enzymes of oxidative metabolism and apoptosis.

摘要

肥胖是一种与发病率和死亡率增加相关的慢性疾病。肥胖的患病率迅速增加,使其成为一个全球性的健康问题,而治疗选择仍然有限。鉴于硼在治疗肥胖方面的潜力,本研究旨在通过分析脂肪积累、CTRP3 和 PPARγ 基因表达、氧化应激和细胞凋亡作用,用新合成的硼甘氨酸单酯化合物(BGM)研究其对 3T3-L1 脂肪细胞的抗脂肪生成活性。3T3-L1 成纤维细胞(ATCC® CL-173)在体外转化为脂肪细胞。用油红 O 染色法检测 3T3-L1 脂肪细胞中的脂肪积累。用 qPCR 测定基因表达水平。用分光光度法(CAT、ALP 和 ACP)和 ELISA 试剂盒(TAS、TOS、NADP-IDH)进行生化分析。用 muse 细胞分析仪通过 Muse Annexin V & 死细胞检测试剂盒进行细胞凋亡研究。与对照脂肪细胞相比,当用 BGM 处理细胞时,细胞中的脂质积累呈剂量依赖性减少。与对照脂肪细胞相比,BGM 处理的脂肪细胞中的 CTRP3 表达水平更高,PPAR-γ 基因表达水平更低(p<0.001)。BGM 应用增加了 TAS 水平,通过调节氧化代谢酶的活性表现出抗氧化作用(p<0.001)。BGM 应用使总凋亡增加了 1.5 倍。这些结果表明,BGM 通过调节脂肪细胞中与脂肪生成和脂肪生成相关的基因表达,并通过影响氧化代谢和细胞凋亡相关酶的活性,是一种治疗肥胖的潜在治疗剂。

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