Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains , Huanggang Normal University , Huanggang , Hubei 438000 , China.
Department of Medical Research, China Medical University Hospital , China Medical University , Taichung 40402 , Taiwan.
J Agric Food Chem. 2018 Dec 5;66(48):12685-12695. doi: 10.1021/acs.jafc.8b04624. Epub 2018 Nov 16.
Diet-induced obesity is strongly associated with nonalcoholic fatty-liver disease (NAFLD) and insulin resistance. We aimed to investigate the in vivo therapeutic value of tetrahydrocurcumin (THC) intervention in high-fat-diet (HFD)-induced obesity and hepatic steatosis. C57BL/6 mice were fed an HFD for 10 weeks, and then they received 20 or 100 mg/kg THC along with the HFD for another 10 weeks. Mice fed an HFD for 20 weeks experienced obesity, hepatic steatosis, hyperlipidemia, and insulin resistance. Tetrahydrocurcumin (THC) intervention for 10 weeks significantly reduced adiposity (epididymal-fat weights of 6.6 ± 0.4 g for the HFD-only group and 5.3 ± 0.8 and 5.6 ± 0.7 g for the HFD with 20 mg/kg THC and HFD with 100 mg/kg THC groups, respectively; p < 0.05) via downregulation of adipogenic factors. Inflammatory macrophage infiltration and polarization were decreased by THC in mouse epididymal adipose tissues. In the liver, THC markedly alleviated steatosis by approximately 28-37% ( p < 0.05) via the downregulation of lipogenesis, the activation of AMP-activated protein kinase (AMPK), and the increase of fatty acid oxidation. Elevated blood glucose and insulin resistance were also improved by THC, which might be caused by regulation of the hepatic insulin signaling cascade, gene transcription involved in glucose metabolism, and reduced macrophage infiltration in the liver and adipose tissue. Our results demonstrated the beneficial effects of THC-mediated intervention against obesity and NAFLD as well as other metabolic syndromes, revealing a novel therapeutic use of THC in obese populations.
饮食诱导的肥胖与非酒精性脂肪性肝病（NAFLD）和胰岛素抵抗密切相关。我们旨在研究四氢姜黄素（THC）干预高脂肪饮食（HFD）诱导的肥胖和肝脂肪变性的体内治疗价值。C57BL/6 小鼠喂食 HFD 10 周，然后再喂食 HFD 并同时接受 20 或 100mg/kg THC 10 周。喂食 HFD 20 周的小鼠出现肥胖、肝脂肪变性、高血脂和胰岛素抵抗。THC 干预 10 周可显著减轻肥胖（HFD 组的附睾脂肪重量为 6.6±0.4g，而 HFD 加 20mg/kg THC 组和 HFD 加 100mg/kg THC 组分别为 5.3±0.8 和 5.6±0.7g；p<0.05），下调脂肪生成因子。THC 可减少炎性巨噬细胞在小鼠附睾脂肪组织中的浸润和极化。在肝脏中，THC 通过下调脂肪生成、激活 AMP 激活的蛋白激酶（AMPK）和增加脂肪酸氧化，使脂肪变性显著缓解约 28-37%（p<0.05）。升高的血糖和胰岛素抵抗也得到了 THC 的改善，这可能是通过调节肝脏胰岛素信号级联、参与糖代谢的基因转录以及减少肝脏和脂肪组织中巨噬细胞浸润来实现的。我们的研究结果表明，THC 介导的干预对肥胖和 NAFLD 以及其他代谢综合征具有有益作用，揭示了 THC 在肥胖人群中的一种新的治疗用途。
