title: beta-Hydroxybutyrate inhibits myocardial fatty acid oxidation in vivo independent of changes in malonyl-CoA content.
abstract: This study tested the hypothesis that an acute infusion of beta-hydroxybutyrate inhibits myocardial fatty acid uptake and oxidation in vivo. Anesthetized pigs were untreated (n = 6) or treated with an intravenous infusion of fat emulsion (n = 7) to elevate plasma free fatty acid levels. A third group received fat emulsion plus an intravenous infusion of beta-hydroxybutyrate (25 micromol.kg-1.min-1; n = 7) for 60 min. All animals received a continuous infusion of [3H]palmitate, and myocardial fatty acid oxidation was measured from the cardiac production of 3H2O. Plasma free fatty acid concentrations were elevated in the fat emulsion group (0.77 +/- 0.11 mM) compared with the untreated group (0.15 +/- 0.03 mM), which resulted in greater myocardial free fatty acid oxidation. In contrast, the group receiving beta-hydroxybutyrate in addition to fat emulsion had elevated beta-hydroxybutyrate concentration (0.87 +/- 0.11 vs. 0.04 +/- 0.01 mM), but suppressed fatty acid oxidation (0.053 +/- 0.013 micromol.g-1.min-1) (P < 0.05) compared with the fat emulsion group (0.116 +/- 0.029 micromol.g-1.min-1). There were no differences among the three groups in the tissue content for malonyl-CoA, acetyl-CoA, or free CoA or the activity of acetyl-CoA carboxylase; thus the inhibition of fatty acid oxidation by elevated beta-hydroxybutyrate did not appear to be due to malonyl-CoA inhibition of carnitine palmitoyl transferase-I or to an increase in the acetyl-CoA-to-free CoA ratio. In conclusion, fatty acid uptake and oxidation is blocked by an infusion of beta-hydroxybutyrate; this effect was not due to elevated myocardial malonyl-CoA content.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-4970, USA. WCS4@po.cwru.edu
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meadows
authors.forename: Krista M
authors.initials: KM
authors.lastname: Kivilo
authors.forename: Bridgette A
authors.initials: BA
authors.lastname: Roth
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D010084:Oxidation-Reduction / Q000187:drug effects; D013552:Swine
chemical_list: D005217:Fat Emulsions, Intravenous; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D008316:Malonyl Coenzyme A; D020155:3-Hydroxybutyric Acid