title: Polybrominated Diphenyl Ether (PBDE)-Induced Suppression of Phosphoenolpyruvate Carboxykinase (PEPCK) Decreases Hepatic Glyceroneogenesis and Disrupts Hepatic Lipid Homeostasis.
abstract: Polybrominated diphenyl ethers (PBDE) are a class of flame-retardant chemicals that leach into the environment and enter the human body. PBDE have been shown to suppress activity of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in fatty acid esterification via hepatic glyceroneogenesis. The objective of this investigation was to assess hepatic glyceroneogenesis and lipid metabolism in PBDE-treated rats. Male, weanling Wistar rats were gavaged daily for 28 d with 14 mg/kg body weight of either DE-71, a commercial PBDE mixture (treated), or corn oil (control). After a 48-h fast, rats were euthanized, blood was obtained, and livers were excised. Suppression of hepatic PEPCK activity by 40% was noted. Serum ketone bodies were elevated by 27% in treated rats compared to controls, while hepatic glyceroneogenesis as measured by (14)C-pyruvate incorporation into triglycerides was 41% lower in explants from treated rats compared to controls. Liver lipid content was 29% lower in treated animals compared to controls. Taken together, these findings suggest that DE-71-induced inhibition of hepatic PEPCK activity alters lipid metabolism by redirecting fatty acids away from esterification and storage toward ketone synthesis.
authors.affiliation: a Department of Molecular, Cellular, and Biomedical Sciences , University of New Hampshire , Durham , New Hampshire , USA.
authors.forename: Kylie R
authors.initials: KR
authors.lastname: Cowens
authors.affiliation: a Department of Molecular, Cellular, and Biomedical Sciences , University of New Hampshire , Durham , New Hampshire , USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Simpson
authors.affiliation: a Department of Molecular, Cellular, and Biomedical Sciences , University of New Hampshire , Durham , New Hampshire , USA.
authors.forename: W Kelley
authors.initials: WK
authors.lastname: Thomas
authors.affiliation: a Department of Molecular, Cellular, and Biomedical Sciences , University of New Hampshire , Durham , New Hampshire , USA.
authors.forename: Gale B
authors.initials: GB
authors.lastname: Carey
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000633:toxicity*; D005411:Flame Retardants / Q000633:toxicity; D005994:Glycerophosphates / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D005411:Flame Retardants; D005994:Glycerophosphates; D055768:Halogenated Diphenyl Ethers; D047908:Intracellular Signaling Peptides and Proteins; D014280:Triglycerides; C029620:alpha-glycerophosphoric acid; C582554:Pck1 protein, rat; D010729:Phosphoenolpyruvate Carboxykinase (GTP)