Asakawa Akihiro, Toyoshima Megumi, Harada Kouji H, Fujimiya Mineko, Inoue Kayoko, Koizumi Akio
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Int J Mol Med. 2008 Apr;21(4):439-45.
Perfluorinated compounds (PFCs) have been employed as surface treatment agents in a variety of products. Perfluorooctanoic acid (PFOA), a PFC that is found globally in the environment and in human tissues, has been increasing significantly in serum levels over the past 50 years. Here, we demonstrated that PFOA inhibits feeding behavior as potently as the endogenous peroxisome proliferator-activated receptor (PPAR)-alpha ligand, oleoylethanolamide (OEA), via the activation of PPAR-alpha, the vagal nerve and hypothalamic neuropeptides. Peripherally administered PFOA decreased food intake as potently as OEA. PFOA decreased gastric emptying and increased the expression level of the gene encoding urocortin 1 in the hypothalamus and the immunoreaction for urocortin 1 in the paraventricular nucleus. Vagotomy attenuated the inhibitory effects of PFOA on feeding. The inhibition of food intake and body-weight gain by PFOA was completely mitigated in PPAR-alpha-/-mice. Our studies demonstrated that the ubiquitous environmental pollutant PFOA works as an imitator of OEA mimicking its action in the feeding regulatory system, providing a new mode of action as represented by environmental 'anorexigens'.
全氟化合物（PFCs）已被用作多种产品的表面处理剂。全氟辛酸（PFOA）是一种在全球环境和人体组织中均有发现的全氟化合物，在过去50年中其血清水平显著上升。在此，我们证明，PFOA通过激活过氧化物酶体增殖物激活受体（PPAR）-α、迷走神经和下丘脑神经肽，对摄食行为的抑制作用与内源性PPAR-α配体油酰乙醇胺（OEA）一样有效。外周给予PFOA对食物摄入的减少作用与OEA一样显著。PFOA减缓了胃排空，并增加了下丘脑编码尿皮质素1的基因表达水平以及室旁核中尿皮质素1的免疫反应。迷走神经切断术减弱了PFOA对摄食的抑制作用。在PPAR-α基因敲除小鼠中，PFOA对食物摄入和体重增加的抑制作用完全消除。我们的研究表明，这种普遍存在的环境污染物PFOA作为OEA的模仿物，在摄食调节系统中模拟其作用，提供了一种以环境“厌食剂”为代表的新作用模式。
