4.2 Article

POLYBROMINATED DIPHENYL ETHER (PBDE)-INDUCED SUPPRESSION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK) DECREASES HEPATIC GLYCERONEOGENESIS AND DISRUPTS HEPATIC LIPID HOMEOSTASIS

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Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/15287394.2015.1098580

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Funding

  1. New Hampshire Agricultural Experiment Station
  2. USDA National Institute of Food and Agriculture Hatch Project [0223362]
  3. NIFA [0223362, 595797] Funding Source: Federal RePORTER

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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 C-14-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.

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