Metabolic pathways for ketone body production. Carbon-13 NMR spectroscopy of rat liver in vivo using carbon-13-multilabeled fatty acids

The hormonal regulation of ketogenesis in the liver of living rat has been studied noninvasively with 13C nuclear magnetic resonance. The protocol involved the use of a surface coil that was placed on the skin of the rat, directly over the normal location of the liver. Signals from superficial tissue were suppressed with a 180 degrees pulse at the center of the coil. A resolution of 0.6 ppm was obtained in the 13C NMR spectra at 20.1 MHz, which was equal to or better than that observed in experiments where the liver was surgically exposed and surrounded with radiofrequency coil. The spatial selection for the liver was better than 90%, with extrahepatic adipose tissue contributing only a very small amount of signal. The metabolic activities of the liver were investigated by infusion of 13C-labeled butyrate in the jugular vein of the anesthetized rat. The rate of butyrate infusion was chosen to be close to the maximum oxidative capacity of the rat liver, and the 13C signal intensities were enhanced by using doubly labeled [1,3-13C]butyrate as a substrate. Different 13C NMR spectra and hence different metabolites were observed depending on the hormonal state of the animal. In the fasted rat, the most intense 13C signal came from the end product of the Krebs cycle, namely, HCO3, with additional resonances from glutamine and glutamate. Weak resonances of the ketone bodies 3-hydroxybutyrate and acetoacetate could also be detected and allowed an evaluation of the "redox state" of the in vivo liver.(ABSTRACT TRUNCATED AT 250 WORDS)