title: Systems biological responses to chronic perfluorododecanoic acid exposure by integrated metabonomic and transcriptomic studies.
abstract: Perfluorocarboxylic acids (PFCAs) have been widely used in consumer and industrial products, such as food packaging, and found in the blood of both humans and wildlife. Although studies showed a high tendency toward biological accumulation and a variety of toxic effects for PFCAs, the mechanistic aspects of their toxicity remain unknown. In present study, we investigated the dosage-dependent metabonomic and transcriptomic responses of male rats to the exposure to perfluorododecanoic acid (PFDoA) over 110 days. Our NMR-based metabonomics results for both liver tissues and serum demonstrated that PFDoA exposure led to hepatic lipidosis, which was characterized by a severe elevation in hepatic triglycerides and a decline in serum lipoprotein levels. The results from transcriptomic changes induced by PFDoA corroborated these results with changes in gene transcript levels associated with fatty acid homeostasis. These results demonstrate that PFDoA induces hepatic steatosis via perturbations to fatty acid uptake, lipogenesis, and fatty acid oxidation. Several serum metabolites exhibited dose-dependences, providing thorough descriptions of changes induced by PFDoA exposure. These observations yielded novel insights regarding the toxicological mechanism of PFCAs at the systems level.
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Lina
authors.initials: L
authors.lastname: Ding
authors.forename: Fuhua
authors.initials: F
authors.lastname: Hao
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Shi
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhang
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
authors.forename: Jiayin
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000378:metabolism; D005466:Fluorocarbons; D020869:Gene Expression Profiling; D007850:Lauric Acids / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008111:Liver Function Tests; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D019906:Nuclear Magnetic Resonance, Biomolecular; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049490:Systems Biology / Q000379:methods*; D036401:Toxicity Tests, Chronic; D043922:Toxicogenetics
chemical_list: D005466:Fluorocarbons; D007850:Lauric Acids; C522391:perfluorododecanoic acid