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Long Chain Fatty Acid Uptake In Vivo: Comparison of [125I]-BMIPP and [3H]-Bromopalmitate

  • Original Article
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Lipids

Abstract

Insulin resistance is characterized by increased metabolic uptake of fatty acids. Accordingly, techniques to examine in vivo shifts in fatty acid metabolism are of value in both clinical and experimental settings. Partially metabolizable long chain fatty acid (LCFA) tracers have been recently developed and employed for this purpose: [9,10-3H]-(R)-2-bromopalmitate ([3H]-BROMO) and [125I]-15-(ρ-iodophenyl)-3-R,S-methylpentadecanoic acid ([125I]-BMIPP). These analogues are taken up like native fatty acids, but once inside the cell do not directly enter β-oxidation. Rather, they become trapped in the slower processes of ω and α-oxidation. Study aims were to (1) simultaneously assess and compare [3H]-BROMO and [125I]-BMIPP and (2) determine if tracer breakdown is affected by elevated metabolic demands. Catheters were implanted in a carotid artery and jugular vein of Sprague–Dawley rats. Following 5 days recovery, fasted animals (5 h) underwent a rest (n = 8) or exercise (n = 8) (0.6 mi/h) protocol. An instantaneous bolus containing both [3H]-BROMO and [125I]-BMIPP was administered to determine LCFA uptake. No significant difference between [125I]-BMIPP and [3H]-BROMO uptake was found in cardiac or skeletal muscle during rest or exercise. In liver, rates of uptake were more than doubled with [3H]-BROMO compared to [125I]-BMIPP. Analysis of tracer conversion by TLC demonstrated no difference at rest. Exercise resulted in greater metabolism and excretion of tracers with ∼37% and ∼53% of [125I]-BMIPP and [3H]-BROMO present in conversion products at 40 min. In conclusion, [3H]-BROMO and [125I]-BMIPP are indistinguishable for the determination of tissue kinetics at rest in skeletal and cardiac muscle. Exercise preferentially exacerbates the breakdown of [3H]-BROMO, making [125I]-BMIPP the analogue of choice for prolonged (>30 min) experimental protocols with elevated metabolic demands.

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Abbreviations

[125I]-BMIPP:

[125I]-15-(ρ-Iodophenyl)-3-R,S-methylpentadecanoic acid

([3H]-BROMO):

[9,10-3H]-(R)-2-Bromopalmitate

K t :

Tissue long chain fatty acid clearance

LCFA:

Long chain fatty acid

NEFA:

Nonesterified fatty acid

R t :

Index of tissue long chain fatty acid uptake

TLC:

Thin layer chromatography

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Acknowledgments

This work would not have been possible with the contribution of BMIPP from Dr. Russ Knapp, Nuclear Medicine Program, Oak Ridge National Laboratory, TN. The authors gratefully acknowledge his generosity and technical advice. JS holds salary support awards from the Alberta Heritage Foundation for Medical Research, the Heart and Stroke Foundation and the Canadian Diabetes Association. This work is supported by the CIHR (JS), Genome Canada (JS), NIDDK (DK-54902, U24-DK-59637). The authors wish to acknowledge the technical contributions of Wanda Sneed, Angela Slater, Carla Harris and Freyja James.

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Authors and Affiliations

  1. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA

    Jane Shearer, Kimberly R. Coenen, R. Richard Pencek & David H. Wasserman

  2. Department of Pathology, Vanderbilt University, Nashville, TN, USA

    Larry L. Swift

  3. Department of Cardiology, Vanderbilt University, Nashville, TN, USA

    Jeffrey N. Rottman

  4. The Mouse Metabolic Phenotyping Center, Vanderbilt University, Nashville, TN, USA

    David H. Wasserman & Jeffrey N. Rottman

  5. Departments of Kinesiology, Biochemistry and Molecular Biology, University of Calgary, 2500 University Drive NW, T2N 1N4, Calgary, AB, Canada

    Jane Shearer

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  1. Jane Shearer
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  2. Kimberly R. Coenen
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  6. Jeffrey N. Rottman
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Correspondence to Jane Shearer.

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Shearer, J., Coenen, K.R., Pencek, R.R. et al. Long Chain Fatty Acid Uptake In Vivo: Comparison of [125I]-BMIPP and [3H]-Bromopalmitate. Lipids 43, 703–711 (2008). https://doi.org/10.1007/s11745-008-3183-4

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  • DOI: https://doi.org/10.1007/s11745-008-3183-4

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