Jiang Tiantuan, Shi Xiaochen, Yan Zunqiang, Wang Xin, Gun Shuangbao
College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, Gansu 730070, P.R. China.
Gansu Research Center for Swine Production Engineering and Technology, Lanzhou, Gansu 730070, P.R. China.
Exp Ther Med. 2019 Sep;18(3):2160-2166. doi: 10.3892/etm.2019.7820. Epub 2019 Jul 26.
Lipodystrophic patients have an adipose tissue triglyceride storage defect that causes ectopic lipid accumulation, leading to severe insulin resistance. The present study investigated the potential role of isoimperatorin on 3T3-L1 adipocyte differentiation. mRNA and protein levels of differentiation- and lipid accumulation-associated genes, as well as the adipogenesis-related signaling pathway were analyzed in control and isoimperatorin-treated differentiated 3T3-L1 adipocytes using reverse transcription-quantitative PCR and western blot analysis. Results determined that isoimperatorin promoted 3T3-L1 fibroblast adipogenesis in a dose-dependent manner compared with standard differentiation inducers. Isoimperatorin significantly increased mRNA and protein expression of the crucial adipogenic transcription factors peroxisome proliferator activated receptor-γ (PPARγ) and CCAAT enhancer binding protein-α (C/EBPα). mRNA expression of the downstream adipogenesis-related genes sterol regulatory element-binding transcription factor 1c, adipocyte protein 2, fatty acid synthase, adiponectin and diacylglycerol -acyltransferase 2 were also significantly increased following isoimperatorin treatment. The underlying mechanism likely involved activation of the Akt signaling pathway. Taken together, the present findings indicated that isoimperatorin may alter PPARγ and C/EBPα expression via the Akt signaling pathway, resulting in promotion of adipogenesis. The results highlighted the potential use of isoimperatorin as a therapeutic agent for preventing diabetes.
脂肪营养不良患者存在脂肪组织甘油三酯储存缺陷，导致异位脂质蓄积，进而引发严重的胰岛素抵抗。本研究调查了异欧前胡素对3T3-L1脂肪细胞分化的潜在作用。使用逆转录定量PCR和蛋白质印迹分析，在对照和经异欧前胡素处理的分化3T3-L1脂肪细胞中，分析了分化和脂质蓄积相关基因的mRNA和蛋白质水平，以及脂肪生成相关信号通路。结果表明，与标准分化诱导剂相比，异欧前胡素以剂量依赖的方式促进3T3-L1成纤维细胞脂肪生成。异欧前胡素显著增加关键脂肪生成转录因子过氧化物酶体增殖物激活受体γ（PPARγ）和CCAAT增强子结合蛋白α（C/EBPα）的mRNA和蛋白质表达。异欧前胡素处理后，下游脂肪生成相关基因固醇调节元件结合转录因子1c、脂肪细胞蛋白2、脂肪酸合酶、脂联素和二酰甘油酰基转移酶2的mRNA表达也显著增加。潜在机制可能涉及Akt信号通路的激活。综上所述，本研究结果表明，异欧前胡素可能通过Akt信号通路改变PPARγ和C/EBPα的表达，从而促进脂肪生成。这些结果突出了异欧前胡素作为预防糖尿病治疗药物的潜在用途。
