HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oakes, N. D. Articles by Ljung, B. Search for Related Content PubMed PubMed Citation Articles by Oakes, N. D. Articles by Ljung, B. Social Bookmarking                      What's this?

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Koutsari, D. A. Dumesic, B. W. Patterson, S. B. Votruba, and M. D. Jensen Plasma Free Fatty Acid Storage in Subcutaneous and Visceral Adipose Tissue in Postabsorptive Women Diabetes, May 1, 2008; 57(5): 1186 - 1194. [Abstract] [Full Text] [PDF]

				E. Diakogiannaki, S. Dhayal, C. E Childs, P. C Calder, H. J Welters, and N. G Morgan Mechanisms involved in the cytotoxic and cytoprotective actions of saturated versus monounsaturated long-chain fatty acids in pancreatic {beta}-cells J. Endocrinol., August 1, 2007; 194(2): 283 - 291. [Abstract] [Full Text] [PDF]

				N. M. Borradaile, X. Han, J. D. Harp, S. E. Gale, D. S. Ory, and J. E. Schaffer Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death J. Lipid Res., December 1, 2006; 47(12): 2726 - 2737. [Abstract] [Full Text] [PDF]

				H. A. Parkes, E. Preston, D. Wilks, M. Ballesteros, L. Carpenter, L. Wood, E. W. Kraegen, S. M. Furler, and G. J. Cooney Overexpression of acyl-CoA synthetase-1 increases lipid deposition in hepatic (HepG2) cells and rodent liver in vivo Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E737 - E744. [Abstract] [Full Text] [PDF]

				K. Fosgerau, C. Fledelius, K. E Pedersen, J. B Kristensen, J. R Daugaard, M. A Iglesias, E. W Kraegen, and S. M Furler Oral administration of glucose promotes intracellular partitioning of fatty acid toward storage in white but not in red muscle. J. Endocrinol., September 1, 2006; 190(3): 651 - 658. [Abstract] [Full Text] [PDF]

				N. D. Oakes, P. Thalen, E. Aasum, A. Edgley, T. Larsen, S. M. Furler, B. Ljung, and D. Severson Cardiac metabolism in mice: tracer method developments and in vivo application revealing profound metabolic inflexibility in diabetes Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E870 - E881. [Abstract] [Full Text] [PDF]

				A. D. Hafstad, G. H. Solevag, D. L. Severson, T. S. Larsen, and E. Aasum Perfused hearts from Type 2 diabetic (db/db) mice show metabolic responsiveness to insulin Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1763 - H1769. [Abstract] [Full Text] [PDF]

				M. A. Iglesias, S. M. Furler, G. J. Cooney, E. W. Kraegen, and J.-M. Ye AMP-Activated Protein Kinase Activation by AICAR Increases Both Muscle Fatty Acid and Glucose Uptake in White Muscle of Insulin-Resistant Rats In Vivo Diabetes, July 1, 2004; 53(7): 1649 - 1654. [Abstract] [Full Text] [PDF]

				B. D. Hegarty, S. M. Furler, N. D. Oakes, E. W. Kraegen, and G. J. Cooney Peroxisome Proliferator-Activated Receptor (PPAR) Activation Induces Tissue-Specific Effects on Fatty Acid Uptake and Metabolism in Vivo--A Study Using the Novel PPAR{alpha}/{gamma} Agonist Tesaglitazar Endocrinology, July 1, 2004; 145(7): 3158 - 3164. [Abstract] [Full Text] [PDF]

				B. P. Atshaves, S. M. Storey, and F. Schroeder Sterol carrier protein-2/sterol carrier protein-x expression differentially alters fatty acid metabolism in L cell fibroblasts J. Lipid Res., September 1, 2003; 44(9): 1751 - 1762. [Abstract] [Full Text] [PDF]

				B. Teusink, P. J. Voshol, V. E.H. Dahlmans, P. C.N. Rensen, H. Pijl, J. A. Romijn, and L. M. Havekes Contribution of Fatty Acids Released From Lipolysis of Plasma Triglycerides to Total Plasma Fatty Acid Flux and Tissue-Specific Fatty Acid Uptake Diabetes, March 1, 2003; 52(3): 614 - 620. [Abstract] [Full Text] [PDF]

				B. D. Hegarty, G. J. Cooney, E. W. Kraegen, and S. M. Furler Increased Efficiency of Fatty Acid Uptake Contributes to Lipid Accumulation in Skeletal Muscle of High Fat-Fed Insulin-Resistant Rats Diabetes, May 1, 2002; 51(5): 1477 - 1484. [Abstract] [Full Text] [PDF]

				M. Cnop, J. C. Hannaert, A. Hoorens, D. L. Eizirik, and D. G. Pipeleers Inverse Relationship Between Cytotoxicity of Free Fatty Acids in Pancreatic Islet Cells and Cellular Triglyceride Accumulation Diabetes, August 1, 2001; 50(8): 1771 - 1777. [Abstract] [Full Text] [PDF]