title: Impaired liver function in Xenopus tropicalis exposed to benzo[a]pyrene: transcriptomic and metabolic evidence.
abstract: BACKGROUND
  Despite numerous studies suggesting that amphibians are highly sensitive to cumulative anthropogenic stresses, the role pollutants play in the decline of amphibian populations remains unclear. Amongst the most common aquatic contaminants, polycyclic aromatic hydrocarbons (PAHs) have been shown to induce several adverse effects on amphibian species in the larval stages. Conversely, adults exposed to high concentrations of the ubiquitous PAH, benzo[a]pyrene (BaP), tolerate the compound thanks to their highly efficient hepatic detoxification mechanisms. Due to this apparent lack of toxic effect on adults, no studies have examined in depth the potential toxicological impact of PAH on the physiology of adult amphibian livers. This study sheds light on the hepatic responses of Xenopus tropicalis when exposed to high environmentally relevant concentrations of BaP, by combining a high throughput transcriptomic approach (mRNA deep sequencing) and a characterization of cellular and physiological modifications to the amphibian liver.
  
  
  RESULTS
  Transcriptomic changes observed in BaP-exposed Xenopus were further characterized using a time-dependent enrichment analysis, which revealed the pollutant-dependent gene regulation of important biochemical pathways, such as cholesterol biosynthesis, insulin signaling, adipocytokines signaling, glycolysis/gluconeogenesis and MAPK signaling. These results were substantiated at the physiological level with the detection of a pronounced metabolic disorder resulting in a possible insulin resistance-like syndrome phenotype. Hepatotoxicity induced by lipid and cholesterol metabolism impairments was clearly identified in BaP-exposed individuals.
  
  
  CONCLUSIONS
  Our data suggested that BaP may disrupt overall liver physiology, and carbohydrate and cholesterol metabolism in particular, even after short-term exposure. These results are further discussed in terms of how this deregulation of liver physiology can lead to general metabolic impairment in amphibians chronically exposed to contaminants, thereby illustrating the role xenobiotics might play in the global decline in amphibian populations.
authors.forename: Christophe
authors.initials: C
authors.lastname: Regnault
authors.forename: Isabelle A M
authors.initials: IA
authors.lastname: Worms
authors.forename: Christine
authors.initials: C
authors.lastname: Oger-Desfeux
authors.forename: Christelle
authors.initials: C
authors.lastname: MelodeLima
authors.forename: Sylvie
authors.initials: S
authors.lastname: Veyrenc
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Bayle
authors.forename: Bruno
authors.initials: B
authors.lastname: Combourieu
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bonin
authors.forename: Julien
authors.initials: J
authors.lastname: Renaud
authors.forename: Muriel
authors.initials: M
authors.lastname: Raveton
authors.affiliation: University Grenoble Alpes, LECA, F-38000 Grenoble, France. stephane.reynaud@ujf-grenoble.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Reynaud
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D001692:Biological Transport; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004777:Environment; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D007700:Kinetics; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D013256:Steroids / Q000096:biosynthesis; D014981:Xenopus
chemical_list: D004785:Environmental Pollutants; D012333:RNA, Messenger; D013256:Steroids; D001564:Benzo(a)pyrene; D005947:Glucose
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