Effect of fatty acids on renal ammoniagenesis in in vivo and in vitro studies.
Intravenous or renal intra-arterial infusion of sodium octanoate results in a 60% decrease in renal ammoniagenesis in the acidotic dog. Mobilization of endogenous fatty acids by levarterenol infusion is accompanied by a 30% fall in renal ammoniagenesis which coincides with considerable increase in renal extraction of fatty acids. In both types of experiments, the renal extraction of glutamine falls in proportion with decreased ammoniagenesis. The effect of octanoate and levarterenol infusion cannot be explained by changes in acid-base equilibrium, renal hemodynamics, or the release of insulin. In vitro experiments using kidney cortical slices from acidotic dogs show that addition of sodium octanoate (0.05-10 mM) or sodium palmitate (0.1-2.5 mM) to the incubation medium induces a 35% decrease in both ammonia and glucose production when L-glutamine (1 mM) is used as the basic ammoniagenic and gluconeogenic substrate. Glutamine uptake decreases concomitantly, whereas tissue glutamate either rises or remains unchanged. The same results were observed when L-glutamate (5 mM) was used as substrate. Glycerol (5 mM) in the medium has no effect on ammoniagenesis, whereas gluconeogenesis increases by 81%. The present studies demonstrate that fatty acids may interfere with renal ammoniagenesis from glutamine during acidosis. The effect is probably related to substrate availability and competition. Fatty acids appear to inhibit ammoniagenesis in the mitochondria through a direct metabolic effect linked with their oxidation and not through modification of glutamine transport across the mitochondrial membrane.
D000138:Acidosis / Q000378:metabolism*; D000641:Ammonia / Q000096:biosynthesis*; D000818:Animals; D002210:Caprylates / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D005990:Glycerol / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D008053:Lipid Mobilization; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010169:Palmitic Acids / Q000494:pharmacology
D002210:Caprylates; D005227:Fatty Acids; D007328:Insulin; D010169:Palmitic Acids; D005973:Glutamine; D000641:Ammonia; D005947:Glucose; D005990:Glycerol; D009638:Norepinephrine