The ubiquitous environmental pollutant perfluorooctanoicacid inhibits feeding behavior via peroxisome proliferator-activated receptor-alpha.
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'.
Asakawa
Akihiro
A
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Toyoshima
Megumi
M
Harada
Kouji H
KH
Fujimiya
Mineko
M
Inoue
Kayoko
K
Koizumi
Akio
A
D000818:Animals; D001483:Base Sequence; D002210:Caprylates / Q000008:administration & dosage / Q000633:toxicity*; D017931:DNA Primers / Q000235:genetics; D004435:Eating / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000633:toxicity*; D005508:Food Deprivation; D005746:Gastric Emptying / Q000187:drug effects; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054832:Urocortins / Q000235:genetics; D014628:Vagotomy
D002210:Caprylates; D017931:DNA Primers; D004785:Environmental Pollutants; D005466:Fluorocarbons; D047493:PPAR alpha; D012333:RNA, Messenger; D054832:Urocortins; C023036:perfluorooctanoic acid