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The Journal of Lipid Research, Vol. 40, 1155-1169, June 1999
Copyright © 1999 by Lipid Research, Inc.

Methods

Development and initial evaluation of a novel method for assessing tissue-specific plasma free fatty acid utilization in vivo using (R)-2-bromopalmitate tracer

Correspondence to: Nicholas D. Oakes

We describe a method for assessing tissue-specific plasma free fatty acid (FFA) utilization in vivo using a non-ß-oxidizable FFA analog, [9,10-³H]-(R)-2-bromopalmitate (³H-R-BrP). Ideally ³H-R-BrP would be transported in plasma, taken up by tissues and activated by the enzyme acyl-CoA synthetase (ACS) like native FFA, but then ³H-labeled metabolites would be trapped. In vitro we found that 2-bromopalmitate and palmitate compete equivalently for the same ligand binding sites on albumin and intestinal fatty acid binding protein, and activation by ACS was stereoselective for the R-isomer. In vivo, oxidative and non-oxidative FFA metabolism was assessed in anesthetized Wistar rats by infusing, over 4 min, a mixture of ³H-R-BrP and [U-¹⁴C] palmitate (¹⁴C-palmitate). Indices of total FFA utilization (R*_f) and incorporation into storage products (R_fs') were defined, based on tissue concentrations of ³H and ¹⁴C, respectively, 16 min after the start of tracer infusion. R*_f, but not R_fs', was substantially increased in contracting (sciatic nerve stimulated) hindlimb muscles compared with contralateral non-contracting muscles. The contraction-induced increases in R*_f were completely prevented by blockade of ß-oxidation with etomoxir. These results verify that ³H-R-BrP traces local total FFA utilization, including oxidative and non-oxidative metabolism. Separate estimates of the rates of loss of ³H activity indicated effective ³H metabolite retention in most tissues over a 16-min period, but appeared less effective in liver and heart.

In conclusion, simultaneous use of ³H-R-BrP and [¹⁴C]palmitate tracers provides a new useful tool for in vivo studies of tissue-specific FFA transport, utilization and metabolic fate, especially in skeletal muscle and adipose tissue.—Oakes, N. D., A. Kjellstedt, G-B. Forsberg, T. Clementz, G. Camejo, S. M. Furler, E. W. Kraegen, M. Ölwegård-Halvarsson, A. B. Jenkins, and B. Ljung. Development and initial evaluation of a novel method for assessing tissue-specific plasma free fatty acid utilization in vivo using (R)-2-bromopalmitate tracer. J. Lipid Res. 1999. 40: 1155–1169.

Supplementary key words: metabolism, turnover, analog, muscle, liver, heart, adipose tissue, kinetics

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