Effects of the peroxisome proliferator perfluoro-n-decanoic acid on hepatic gluconeogenesis and glycogenesis: a 13C NMR investigation
| Autor: | Carol M. Goecke, Nicholas V. Reo, Bruce M. Jarnot |
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| Rok vydání: | 1994 |
| Předmět: |
Male
medicine.medical_specialty Magnetic Resonance Spectroscopy Biology Toxicology Microbodies chemistry.chemical_compound Internal medicine medicine Animals Beta oxidation Alanine Carbon Isotopes Fluorocarbons Fatty acid metabolism Gluconeogenesis General Medicine Pyruvate dehydrogenase complex Rats Inbred F344 Pyruvate carboxylase Rats Citric acid cycle Endocrinology Glucose Biochemistry chemistry Liver Glycogenesis Decanoic Acids Glycogen |
| Zdroj: | Chemical research in toxicology. 7(1) |
| ISSN: | 0893-228X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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