Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, Beijing 100044, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7163-7169. doi: 10.3892/mmr.2017.7450. Epub 2017 Sep 8.
The aim of the present study was to investigate the effects of AdipoRon, an adiponectin receptor agonist, on adipogenesis in C3H10T1/2 cells and to explore the underlying mechanisms. C3H10T1/2 cells were treated with increasing doses of AdipoRon for 8 days, and Oil Red O staining was used to assess lipid accumulation. The protein and mRNA expression levels of adipogenic transcription factors and adipocyte‑specific genes were examined by western blotting and reverse transcription quantitative polymerase chain reaction, respectively. AdipoRon treatment inhibited lipid accumulation in C3H10T1/2 cells in a dose‑dependent manner and significantly suppressed the expression of adipogenic transcription factors, including peroxisome proliferator‑activated receptor γ, CAAT/enhancer binding protein (C/EBP)‑β and C/EBPα. In addition, cells treated with AdipoRon exhibited a significant decrease in the expression of adipocyte‑specific genes, including fatty acid binding protein 4, fatty acid synthase, leptin, adiponectin, and stearoyl‑CoA desaturase‑1. Notably, AdipoRon significantly increased the phosphorylation of adenosine monophosphate‑activated protein kinase (AMPK) and acetyl‑CoA carboxylase (ACC). The results indicated that AdipoRon exerted an inhibitory effect on adipogenesis in C3H10T1/2 cells by downregulating the expression of adipogenic transcription factors and adipocyte‑specific genes and by promoting the phosphorylation of AMPK and ACC, which suggested that AdipoRon may be a potential drug to prevent and treat diseases caused by abnormal adipogenesis, such as obesity.
本研究旨在探讨脂联素受体激动剂 AdipoRon 对 C3H10T1/2 细胞脂肪生成的影响,并探讨其潜在机制。用不同浓度的 AdipoRon 处理 C3H10T1/2 细胞 8 天,用油红 O 染色法评估脂质积累。通过 Western blot 和逆转录定量聚合酶链反应分别检测脂肪生成转录因子和脂肪细胞特异性基因的蛋白和 mRNA 表达水平。AdipoRon 处理以剂量依赖性方式抑制 C3H10T1/2 细胞中的脂质积累,并显著抑制脂肪生成转录因子的表达,包括过氧化物酶体增殖物激活受体 γ、CAAT/增强子结合蛋白(C/EBP)-β 和 C/EBPα。此外,用 AdipoRon 处理的细胞中脂肪细胞特异性基因的表达显著下降,包括脂肪酸结合蛋白 4、脂肪酸合成酶、瘦素、脂联素和硬脂酰辅酶 A 去饱和酶-1。值得注意的是,AdipoRon 显著增加了腺苷单磷酸激活蛋白激酶(AMPK)和乙酰辅酶 A 羧化酶(ACC)的磷酸化。结果表明,AdipoRon 通过下调脂肪生成转录因子和脂肪细胞特异性基因的表达以及促进 AMPK 和 ACC 的磷酸化,对 C3H10T1/2 细胞脂肪生成发挥抑制作用,提示 AdipoRon 可能是预防和治疗肥胖等异常脂肪生成相关疾病的潜在药物。