title: Transcriptional profiling of rat white adipose tissue response to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin.
abstract: Polychlorinated dibenzodioxins are environmental contaminants commonly produced as a by-product of industrial processes. The most potent of these, 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), is highly lipophilic, leading to bioaccumulation. White adipose tissue (WAT) is a major site for energy storage, and is one of the organs in which TCDD accumulates. In laboratory animals, exposure to TCDD causes numerous metabolic abnormalities, including a wasting syndrome. We therefore investigated the molecular effects of TCDD exposure on WAT by profiling the transcriptomic response of WAT to 100μg/kg of TCDD at 1 or 4days in TCDD-sensitive Long-Evans (Turku/AB; L-E) rats. A comparative analysis was conducted simultaneously in identically treated TCDD-resistant Han/Wistar (Kuopio; H/W) rats one day after exposure to the same dose. We sought to identify transcriptomic changes coinciding with the onset of toxicity, while gaining additional insight into later responses. More transcriptional responses to TCDD were observed at 4days than at 1day post-exposure, suggesting WAT shows mostly secondary responses. Two classic AHR-regulated genes, Cyp1a1 and Nqo1, were significantly induced by TCDD in both strains, while several genes involved in the immune response, including Ms4a7 and F13a1 were altered in L-E rats alone. We compared genes affected by TCDD in rat WAT and human adipose cells, and observed little overlap. Interestingly, very few genes involved in lipid metabolism exhibited altered expression levels despite the pronounced lipid mobilization from peripheral fat pads by TCDD in L-E rats. Of these genes, the lipolysis-associated Lpin1 was induced slightly over 2-fold in L-E rat WAT on day 4.
authors.affiliation: Informatics and Bio-Computing Program, Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Houlahan
authors.affiliation: Informatics and Bio-Computing Program, Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Stephenie D
authors.initials: SD
authors.lastname: Prokopec
authors.affiliation: Informatics and Bio-Computing Program, Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Ren X
authors.initials: RX
authors.lastname: Sun
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.
authors.forename: Ivy D
authors.initials: ID
authors.lastname: Moffat
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Jere
authors.initials: J
authors.lastname: Lindén
authors.affiliation: Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä, Finland; Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Lensu
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Okey
authors.affiliation: Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki, Finland. Electronic address: raimo.pohjanvirta@helsinki.fi.
authors.forename: Raimo
authors.initials: R
authors.lastname: Pohjanvirta
authors.affiliation: Informatics and Bio-Computing Program, Ontario Institute for Cancer Research, Toronto, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada. Electronic address: Paul.Boutros@oicr.on.ca.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Boutros
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D004785:Environmental Pollutants / Q000633:toxicity*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D013045:Species Specificity; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins
keywords: AHR; Feed restriction; TCDD; Transcriptomic profiling; White adipose tissue