Effects of the peroxisome proliferator perfluoro-n-decanoic acid on hepatic gluconeogenesis and glycogenesis: a 13C NMR investigation.
Carbon-13 NMR spectroscopy was used to study the effects of the peroxisome proliferator perfluoro-n-decanoic acid (PFDA) on hepatic carbohydrate metabolism in male Fischer-344 rats. The data indicate that PFDA-treated rats display an inhibition in hepatic [1-13C]glucose and [3-13C]alanine utilization on day 5 posttreatment. PFDA rats show hepatic mean glucose and alanine intensities which are significantly greater (ca. 10-100%) than controls. With [1-13C]-glucose as substrate, PFDA rats show severe to complete inhibition in glycogenesis on days 3 and 5 posttreatment. With [3-13C]alanine as substrate, both groups show functional gluconeogenesis and glycogenesis; however, treated rats show a more transient and less intense C1-glycogen resonance relative to control. These data suggest that PFDA inhibits either the hepatocellular transport of glucose and/or its phosphorylation by glucokinase. The effect of PFDA on TCA cycle activity was determined by monitoring the flow of [3-13C]alanine into glutamate. The relative activity of pyruvate carboxylase (PC) versus pyruvate dehydrogenase (PDH) is represented by the ratio of the glutamate NMR signal intensities (C2 + C3)/C4. PFDA rats show a lower (C2 + C3)/C4 glutamate ratio, suggesting greater relative activity of PDH versus PC in PFDA rats relative to controls. Differences in PDH activity may arise from differences in lipolytic activity. Our data suggest a dysfunction in fatty acid metabolism in PFDA rats and corroborate other studies which show that PFDA inhibits fatty acid oxidation.
Goecke
C M
CM
Department of Biochemistry and Molecular Biology/Kettering-Scott Magnetic Resonance Laboratory, Wright State University, Dayton, Ohio 45429.
Jarnot
B M
BM
Reo
N V
NV
D000409:Alanine / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D003652:Decanoic Acids / Q000494:pharmacology*; D005466:Fluorocarbons / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008830:Microbodies / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D002247:Carbon Isotopes; D003652:Decanoic Acids; D005466:Fluorocarbons; C036567:perfluorodecanoic acid; D006003:Glycogen; D005947:Glucose; D000409:Alanine