Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1976 Aug;58(2):421–431. doi: 10.1172/JCI108486

Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm.

G R Dagenais, R G Tancredi, K L Zierler
PMCID: PMC333197  PMID: 956375

Abstract

The objects of these experiments were to determine to what extent oleic acid, removed from plasma by forearm muscles, was oxidized immediately, and to search for evidence of an intramuscular lipid pool which may be composed to triglycerides synthesized from plasma free fatty acids and which may supply substantial portions of lipid substrates for oxidation by muscle. To these ends (1-14C]oleic acid was infused at constant rate into the brachial artery of seven healthy young men at rest in the postabsorptive state. Results were: (1) muscle respiratory quotient (0.76) implied that about 80% of the oxygen consumed was for the oxidation of lipid. (2) Muscle free fatty acid uptake, had it been oxidized directly, could account for more than 100% of observed oxygen uptake. (3) There was a lag of at least 30 min before 14CO2 appeared in forearm venous blood. (4) 14CO2 release from forearm muscle tended to reach an apparent plateau after 3 h of infusion of [14C]oleic acid. (5) During the time of plateau 14CO2 release, oleic acid extracted from plasma could account for only 20% of oxygen consumption; most of the oleic acid taken up was not oxidized directly. (6) 14CO2 release persisted at a high level during the 1-3 h follow-up period after the infusion ended. (7) Neither the delay in initial appearance of 14CO2 nor its continued release after cessation of infusion was due to delay and distribution in a forearm CO2 pool, since intra-arterial infusion of NaH14CO3 in additional subjects demonstrated much more rapid distribution of 14CO2 in the forearm. Results show that most, if not all, free fatty acids taken up by resting muscle are not oxidized directly, but probably enter an intramuscular pool which has a slow turnover during resting metabolism and is the immediate source of oxidized lipid substrate.

Full text

PDF
421

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ANDRES R., CADER G., ZIERLER K. L. The quantitatively minor role of carbohydrate in oxidative metabolism by skeletal muscle in intact man in the basal state; measurements of oxygen and glucose uptake and carbon dioxide and lactate production in the forearm. J Clin Invest. 1956 Jun;35(6):671–682. doi: 10.1172/JCI103324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. ANDRES R., ZIERLER K. L., ANDERSON H. M., STAINSBY W. N., CADER G., GHRAYYIB A. S., LILIENTHAL J. L., Jr Measurement of blood flow and volume in the forearm of man; with notes on the theory of indicator-dilution and on production of turbulence, hemolysis, and vasodilatation by intra-vascular injection. J Clin Invest. 1954 Apr;33(4):482–504. doi: 10.1172/JCI102919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BALLARD F. B., DANFORTH W. H., NAEGLE S., BING R. J. Myocardial metabolism of fatty acids. J Clin Invest. 1960 May;39:717–723. doi: 10.1172/JCI104088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BALTZAN M. A., ANDRES R., CADER G., ZIERLER K. L. Heterogeneity of forearm metabolism with special reference to free fatty acids. J Clin Invest. 1962 Jan;41:116–125. doi: 10.1172/JCI104453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BING R. J., SIEGEL A., UNGAR I., GILBERT M. Metabolism of the human heart. II. Studies on fat, ketone and amino acid metabolism. Am J Med. 1954 Apr;16(4):504–515. doi: 10.1016/0002-9343(54)90365-4. [DOI] [PubMed] [Google Scholar]
  6. BING R. J., SIEGEL A., VITALE A., BALBONI F., SPARKS E., TAESCHLER M., KLAPPER M., EDWARDS S. Metabolic studies on the human heart in vivo. I. Studies on carbohydrate metabolism of the human heart. Am J Med. 1953 Sep;15(3):284–296. doi: 10.1016/0002-9343(53)90082-5. [DOI] [PubMed] [Google Scholar]
  7. COOPER K. E., EDHOLM O. G., MOTTRAM R. F. The blood flow in skin and muscle of the human forearm. J Physiol. 1955 May 27;128(2):258–267. doi: 10.1113/jphysiol.1955.sp005304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DOLE V. P. A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J Clin Invest. 1956 Feb;35(2):150–154. doi: 10.1172/JCI103259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. EDHOLM O. G., FOX R. H., MACPHERSON R. K. The effect of body heating on the circulation in skin and muscle. J Physiol. 1956 Dec 28;134(3):612–619. doi: 10.1113/jphysiol.1956.sp005669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FRIEDBERG S. J., KLEIN R. F., TROUT D. L., BOGDONOFF M. D., ESTES E. H., Jr The characteristics of the peripheral transport of C14-labeled palmitic acid. J Clin Invest. 1960 Oct;39:1511–1515. doi: 10.1172/JCI104170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. GEORGE J. C., NAIK R. M. Relative distribution and chemical nature of the fuel store of the two types of fibres in the pectoralis major muscle of the pigeon. Nature. 1958 Mar 8;181(4610):709–711. doi: 10.1038/181709b0. [DOI] [PubMed] [Google Scholar]
  12. GOLDRICK B., HIRSCH J. A TECHNIQUE FOR QUANTITATIVE RECOVERY OF LIPIDS FROM CHROMATOPLATES. J Lipid Res. 1963 Oct;4:482–483. [PubMed] [Google Scholar]
  13. GORDON R. S., Jr Unesterified fatty acid in human blood plasma. II. The transport function of unesterified fatty acid. J Clin Invest. 1957 Jun;36(6 Pt 1):810–815. doi: 10.1172/JCI103486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. HAVEL R. J., NAIMARK A., BORCHGREVINK C. F. Turnover rate and oxidation of free fatty acids of blood plasma in man during exercise: studies during continuous infusion of palmitate-1-C14. J Clin Invest. 1963 Jul;42:1054–1063. doi: 10.1172/JCI104791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hagenfeldt L., Wahren J. Human forearm muscle metabolism during exercise. VII. FFA uptake and oxidation at different work intensities. Scand J Clin Lab Invest. 1972 Dec;30(4):429–436. doi: 10.3109/00365517209080281. [DOI] [PubMed] [Google Scholar]
  16. Hagenfeldt L., Wahren J. Simultaneous uptake and release of individual free fatty acids in human forearm muscle during exercise. Life Sci. 1966 Feb;5(4):357–364. doi: 10.1016/0024-3205(66)90021-x. [DOI] [PubMed] [Google Scholar]
  17. Havel R. J., Ekelund L. G., Holmgren A. Kinetic analysis of the oxidation of palmitate-1-14C in man during prolonged heavy muscular exercise. J Lipid Res. 1967 Jul;8(4):366–373. [PubMed] [Google Scholar]
  18. NEPTUNE E. M., Jr, SUDDUTH H. C., FOREMAN D. R., FASH F. J. Phospholipid and triglyceride metabolism of excised rat diaphragm and the role of these lipids in fatty acid uptake and oxidation. J Lipid Res. 1960 Apr;1:229–235. [PubMed] [Google Scholar]
  19. RABINOWITZ D., ZIERLER K. L. Role of free fatty acids in forearm metabolism in man, quantitated by use of insulin. J Clin Invest. 1962 Dec;41:2191–2197. doi: 10.1172/JCI104678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. SPITZER J. J., GOLD M. FREE FATTY ACID METABOLISM BY SKELETAL MUSCLE. Am J Physiol. 1964 Jan;206:159–164. doi: 10.1152/ajplegacy.1964.206.1.159. [DOI] [PubMed] [Google Scholar]
  21. Saba T. M., Di Luzio N. R. Method for collection and determination of 14CO-2 for in vitro metabolic studies. J Lipid Res. 1966 Jul;7(4):566–567. [PubMed] [Google Scholar]
  22. Spitzer J. J., Hori S. Oxidation of free fatty acids by skeletal muscle during rest and electrical stimulation in control and diabetic dogs. Proc Soc Exp Biol Med. 1969 Jun;131(2):555–559. doi: 10.3181/00379727-131-33924. [DOI] [PubMed] [Google Scholar]
  23. Tancredi R. G., Dagenais G. R., Zierler K. L. Free fatty acid metabolism in the forearm at rest: muscle uptake and adipose tissue release of free fatty acids. Johns Hopkins Med J. 1976 May;138(5):167–179. [PubMed] [Google Scholar]
  24. VOLK M. E., MILLINGTON R. H., WEINHOUSE S. Oxidation of endogenous fatty acids of rat tissues in vitro. J Biol Chem. 1952 Apr;195(2):493–501. [PubMed] [Google Scholar]
  25. Zelis R., Mason D. T., Braunwald E. Partition of blood flow to the cutaneous and muscular beds of the forearm at rest and during leg exercise in normal subjects and in patients with heart failure. Circ Res. 1969 Jun;24(6):799–806. doi: 10.1161/01.res.24.6.799. [DOI] [PubMed] [Google Scholar]
  26. Zierler K. L. Intra-arterial tracer injection methods for evaluating blood flow, volumes of distribution, and trans-capillary exchange in the extremities. Scand J Clin Lab Invest Suppl. 1967;99:65–69. [PubMed] [Google Scholar]
  27. Zierler K. L., Maseri A., Klassen G., Rabinowitz D., Burgess J. Muscle metabolism during exercise in man. Trans Assoc Am Physicians. 1968;81:266–273. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES