Umegaki Keizo, Yamazaki Yuko, Yokotani Kaori, Chiba Tsuyoshi, Sato Yoko, Shimura Fumio
National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.
Department of Food & Nutrition, Jumonji University, 2-1-28 Sugasawa, Niiza-shi, Saitama 352-8510, Japan.
Toxicol Rep. 2014 Oct 10;1:787-794. doi: 10.1016/j.toxrep.2014.09.013. eCollection 2014.
extract (CFE), an herbal ingredient, is used for weight-loss products. CFE's alleged efficacy is attributed to forskolin. However, CFE has been shown to induce fatty liver in mice, with components other than forskolin playing a part in this effect. The present study addressed the underlying mechanism of CFE-induced fatty liver by analyzing changes in CFE-treated mice of lipid concentrations and of the levels of mRNAs encoding enzymes and transcription factors known to be related to fatty liver. Mice were fed a diet containing 0, 0.3 and 1% CFE for 2 weeks. CFE at 1% clearly induced fatty liver, as demonstrated by histological examination and confirmed by increases in triglyceride concentrations in liver. However, treated mice did not exhibit elevation in plasma levels of non-esterified fatty acids. Comprehensive analysis of liver mRNA levels revealed accumulation of multiple transcripts, including mRNAs encoding enzymes acetyl-CoA carboxylase and long-chain elongase; transcription factor peroxisome proliferator-activated receptor gamma (PPARγ); and lipid-droplet-associated fat-specific protein 27 (Fsp27). These findings suggest that the de novo synthesis and accumulation of triglyceride in the liver, through the enhanced expression of specific lipogenic mRNAs, is a major underlying mechanism of fatty liver induction by CFE.
CFE是一种草药成分,用于减肥产品。CFE所谓的功效归因于福斯高林。然而,已证明CFE会在小鼠中诱发脂肪肝,除福斯高林外的其他成分也参与了这一作用。本研究通过分析经CFE处理的小鼠的脂质浓度变化以及已知与脂肪肝相关的酶和转录因子的mRNA水平变化,探讨了CFE诱发脂肪肝的潜在机制。给小鼠喂食含0%、0.3%和1% CFE的饲料,持续2周。组织学检查表明,1%的CFE明显诱发了脂肪肝,肝脏中甘油三酯浓度升高也证实了这一点。然而,经处理的小鼠血浆中非酯化脂肪酸水平并未升高。对肝脏mRNA水平的综合分析显示,多种转录本积累,包括编码乙酰辅酶A羧化酶和长链延伸酶的mRNA;转录因子过氧化物酶体增殖物激活受体γ(PPARγ);以及脂滴相关脂肪特异性蛋白27(Fsp27)。这些发现表明,通过特定脂肪生成mRNA表达的增强,肝脏中甘油三酯的从头合成和积累是CFE诱发脂肪肝的主要潜在机制。