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Polybrominated Diphenylether (PBDE) Suppression of Phosphoenolpyruvate Carboxykinase (PEPCK) Activity Alters Liver Lipid Metabolism
Author(s) -
Cowens Kylie,
Carey Gale
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.817.2
Subject(s) - phosphoenolpyruvate carboxykinase , chemistry , ketone bodies , metabolism , medicine , polybrominated diphenyl ethers , lipid metabolism , corn oil , weanling , fatty acid , endocrinology , biochemistry , enzyme , food science , biology , organic chemistry , pollutant
PBDE, a class of flame retardant chemicals that leach into the environment and enter the human body, have been shown to suppress activity of PEPCK (Nash et al., 2013), a key enzyme in fatty acid esterification via hepatic glyceroneogenesis. The objective of this research was to evaluate the metabolic fate of fatty acids in liver of PBDE‐treated rats. Two separate studies were conducted with identical experimental design. Male, weanling Wistar rats were gavaged daily for 28 days with 14 mg/kg body weight commercial PBDE mixture (TRT) or corn oil (CON). After a 48 hour fast, rats were euthanized, blood sampled, and livers removed. In study 1 (n=8 per group), serum ketone bodies were elevated in TRT rats compared to CON (27.7 vs 21.8 mg/dL, respectively, p<0.05) In study 2 (n=6 per group), hepatic glyceroneogenesis, as measured by 14 C‐pyruvate incorporation into triglycerides, was 41% lower in explants from TRT rats compared to CON (8.21 vs 13.97 pmol/hr/mg tissue, respectively, p<0.05). Liver lipid content was 29% lower in TRT compared to CON (2.69% vs 3.80%, respectively, p<0.05). Taken together, these findings suggest that a PBDE‐induced suppression in hepatic PEPCK activity alters lipid metabolism by redirecting fatty acids away from esterification and storage, and toward ketone synthesis. Supported by NH Agricultural Experiment Station Grant NH00541