Abstract
Free fatty acid (FFA) metabolism was studied in 18 traumatized and/or septic patients. Each patient was studied while receiving 5% dextrose (D5W) and after 4 to 7 days of total parenteral nutrition (TPN). Nonprotein energy during TPN was given either entirely as glucose (Glucose System) or as equal portions of intravenous fat and glucose (Lipid System). Plasma FFA concentrations were in the normal range on D5W and decreased markedly with TPN. FFA turnover was higher than normal on D5W and did not decrease significantly with TPN. The poor correlation between these two variables emphasizes the need to perform kinetic studies to characterize FFA metabolism in trauma and sepsis. Plasma FFA oxidation and net whole body fat oxidation measured by indirect calorimetry were in the normal range on D5W, 35 and 82%, respectively, of resting energy expenditure (REE). With a glucose intake averaging 108% of REE, plasma FFA oxidation and net fat oxidation decreased to 17 and 13%, respectively, of REE. Nonprotein RQ increased only to 0.94 despite administration of glucose in excess of REE, indicating an abnormal persistence of fat oxidation. During D5W administration, plasma FFA accounted for less than one half of total fat oxidation, indicating that unlabeled fat, such as tissue or plasma triglycerides not in rapid equilibrium with plasma FFA, accounted for the bulk of fat oxidation. Glucagon concentrations which were high on D5W did not decrease significantly with TPN. Insulin concentrations were normal on D5W and increased in response to TPN. The abnormal hormonal milieu may account for much of the abnormal fat metabolism. Administration of large amounts of glucose decreased FFA oxidation much more than FFA mobilization. Thus, the infused glucose acts to increase the rate of "futile cycling" of FFA in these acutely ill patients.
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Selected References
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- Askanazi J., Carpentier Y. A., Elwyn D. H., Nordenström J., Jeevanandam M., Rosenbaum S. H., Gump F. E., Kinney J. M. Influence of total parenteral nutrition on fuel utilization in injury and sepsis. Ann Surg. 1980 Jan;191(1):40–46. doi: 10.1097/00000658-198001000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Black P. R., Brooks D. C., Bessey P. Q., Wolfe R. R., Wilmore D. W. Mechanisms of insulin resistance following injury. Ann Surg. 1982 Oct;196(4):420–435. doi: 10.1097/00000658-198210000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blackburn G. L., Flatt J. P., Clowes G. H., Jr, O'Donnell T. F., Hensle T. E. Protein sparing therapy during periods of starvation with sepsis of trauma. Ann Surg. 1973 May;177(5):588–594. doi: 10.1097/00000658-197305000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bucolo G., David H. Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem. 1973 May;19(5):476–482. [PubMed] [Google Scholar]
- Burke J. F., Wolfe R. R., Mullany C. J., Mathews D. E., Bier D. M. Glucose requirements following burn injury. Parameters of optimal glucose infusion and possible hepatic and respiratory abnormalities following excessive glucose intake. Ann Surg. 1979 Sep;190(3):274–285. doi: 10.1097/00000658-197909000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cahill G. F., Jr, Herrera M. G., Morgan A. P., Soeldner J. S., Steinke J., Levy P. L., Reichard G. A., Jr, Kipnis D. M. Hormone-fuel interrelationships during fasting. J Clin Invest. 1966 Nov;45(11):1751–1769. doi: 10.1172/JCI105481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carlson L. A., Lijedahl S. O. Lipid metabolism and trauma. IV. Effect of treatment with intravenous fat emulsion on plasma lipids, proteins and clinical condition of burned patients. Acta Chir Scand. 1971;137(2):123–129. [PubMed] [Google Scholar]
- DOLE V. P., MEINERTZ H. Microdetermination of long-chain fatty acids in plasma and tissues. J Biol Chem. 1960 Sep;235:2595–2599. [PubMed] [Google Scholar]
- Dagenais G. R., Tancredi R. G., Zierler K. L. Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm. J Clin Invest. 1976 Aug;58(2):421–431. doi: 10.1172/JCI108486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elwyn D. H., Gump F. E., Munro H. N., Iles M., Kinney J. M. Changes in nitrogen balance of depleted patients with increasing infusions of glucose. Am J Clin Nutr. 1979 Aug;32(8):1597–1611. doi: 10.1093/ajcn/32.8.1597. [DOI] [PubMed] [Google Scholar]
- Elwyn D. H., Kinney J. M., Jeevanandam M., Gump F. E., Broell J. R. Influence of increasing carbohydrate intake on glucose kinetics in injured patients. Ann Surg. 1979 Jul;190(1):117–127. doi: 10.1097/00000658-197907000-00023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FLEISCH A. Le métabolisme basal standard et sa détermination au moyen du "metabocalculator". Helv Med Acta. 1951 Feb;18(1):23–44. [PubMed] [Google Scholar]
- FREDRICKSON D. S., GORDON R. S., Jr The metabolism of albumin-bound C14-labeled unesterified fatty acids in normal human subjects. J Clin Invest. 1958 Nov;37(11):1504–1515. doi: 10.1172/JCI103742. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FREDRICKSON D. S., GORDON R. S., Jr Transport of fatty acids. Physiol Rev. 1958 Oct;38(4):585–630. doi: 10.1152/physrev.1958.38.4.585. [DOI] [PubMed] [Google Scholar]
- FRITZ I. B. Factors influencing the rates of long-chain fatty acid oxidation and synthesis in mammalian systems. Physiol Rev. 1961 Jan;41:52–129. doi: 10.1152/physrev.1961.41.1.52. [DOI] [PubMed] [Google Scholar]
- GOLD M., SPITZER J. J. METABOLISM OF FREE FATTY ACIDS BY MYOCARDIUM AND KIDNEY. Am J Physiol. 1964 Jan;206:153–158. doi: 10.1152/ajplegacy.1964.206.1.153. [DOI] [PubMed] [Google Scholar]
- Gilbert C. H., Kaye J., Galton D. J. The effect of a glucose load on plasma fatty acids and lipolysis in adipose tissue of obese diabetic and non-diabetic patients. Diabetologia. 1974 Apr;10(2):135–138. doi: 10.1007/BF01219669. [DOI] [PubMed] [Google Scholar]
- Grant J. P., Cox C. E., Kleinman L. M., Maher M. M., Pittman M. A., Tangrea J. A., Brown J. H., Gross E., Beazley R. M., Jones R. S. Serum hepatic enzyme and bilirubin elevations during parenteral nutrition. Surg Gynecol Obstet. 1977 Oct;145(4):573–580. [PubMed] [Google Scholar]
- Gump F. E., Long C., Killian P., Kinney J. M. Studies of glucose intolerance in septic injured patients. J Trauma. 1974 May;14(5):378–388. doi: 10.1097/00005373-197405000-00004. [DOI] [PubMed] [Google Scholar]
- 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]
- HOWARD J. M. Studies of the absorption and metabolism of glucose following injury; the systemic response to injury. Ann Surg. 1955 Mar;141(3):321–326. doi: 10.1097/00000658-195503000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall S. E., Saunders J., Sönksen P. H. Glucose and free fatty acid turnover in normal subjects and in diabetic patients before and after insulin treatment. Diabetologia. 1979 May;16(5):297–306. doi: 10.1007/BF01223618. [DOI] [PubMed] [Google Scholar]
- Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
- Issekutz B., Jr, Bortz W. M., Miller H. I., Paul P. Turnover rate of plasma FFA in humans and in dogs. Metabolism. 1967 Nov;16(11):1001–1009. doi: 10.1016/0026-0495(67)90093-5. [DOI] [PubMed] [Google Scholar]
- Jeejee hoy K. N., Anderson G. H., Nakhooda A. F., Greenberg G. R., Sanderson I., Marliss E. B. Metabolic studies in total parenteral nutrition with lipid in man. Comparison with glucose. J Clin Invest. 1976 Jan;57(1):125–136. doi: 10.1172/JCI108252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KINNEY J. M., MORGAN A. P., DOMINGUES F. J., GILDNER K. J. A METHOD FOR CONTINUOUS MEASUREMENT OF GAS EXCHANGE AND EXPIRED RADIOACTIVITY IN ACUTELY ILL PATIENTS. Metabolism. 1964 Mar;13:205–211. doi: 10.1016/0026-0495(64)90099-x. [DOI] [PubMed] [Google Scholar]
- Kinney J. M., Duke J. H., Jr, Long C. L., Gump F. E. Tissue fuel and weight loss after injury. J Clin Pathol Suppl (R Coll Pathol) 1970;4:65–72. doi: 10.1136/jcp.s3-4.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Long C. L., Kinney J. M., Geiger J. W. Nonsuppressability of gluconeogenesis by glucose in septic patients. Metabolism. 1976 Feb;25(2):193–201. doi: 10.1016/0026-0495(76)90049-4. [DOI] [PubMed] [Google Scholar]
- Nordenström J., Carpentier Y. A., Askanazi J., Robin A. P., Elwyn D. H., Hensle T. W., Kinney J. M. Metabolic utilization of intravenous fat emulsion during total parenteral nutrition. Ann Surg. 1982 Aug;196(2):221–231. doi: 10.1097/00000658-198208000-00016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nordenström J., Jeevanandam M., Elwyn D. H., Carpentier Y. A., Askanazi J., Robin A., Kinney J. M. Increasing glucose intake during total parenteral nutrition increases norepinephrine excretion in trauma and sepsis. Clin Physiol. 1981 Oct;1(5):525–534. doi: 10.1111/j.1475-097x.1981.tb00919.x. [DOI] [PubMed] [Google Scholar]
- Randle P. J., Garland P. B., Newsholme E. A., Hales C. N. The glucose fatty acid cycle in obesity and maturity onset diabetes mellitus. Ann N Y Acad Sci. 1965 Oct 8;131(1):324–333. doi: 10.1111/j.1749-6632.1965.tb34800.x. [DOI] [PubMed] [Google Scholar]
- Robin A. P., Greenwood M. R., Askanazi J., Elwyn D. H., Kinney J. M. Influence of total parenteral nutrition on tissue lipoprotein lipase activity during chronic and acute illness. Ann Surg. 1981 Dec;194(6):681–686. doi: 10.1097/00000658-198112000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rössner S., Boberg J., Carlson L. A., Freyschuss U., Lassers B. W. Comparison between fractional turnover rate of endogenous plasma triglycerides and of intralipid (intravenous fat tolerance test) in man. Eur J Clin Invest. 1974 Apr;4(2):109–114. doi: 10.1111/j.1365-2362.1974.tb00380.x. [DOI] [PubMed] [Google Scholar]
- Sandhofer F., Sailer S., Braunsteiner H. Fettsäure- und Triglyceridumsatz bei Schilddrüsenüberfunktion. Klin Wochenschr. 1966 Dec 15;44(24):1389–1393. doi: 10.1007/BF01752479. [DOI] [PubMed] [Google Scholar]
- Sheldon G. F., Peterson S. R., Sanders R. Hepatic dysfunction during hyperalimentation. Arch Surg. 1978 Apr;113(4):504–508. doi: 10.1001/archsurg.1978.01370160162028. [DOI] [PubMed] [Google Scholar]
- Spencer J. L., Zikria B. A., Kinney J. M., Broell J. R., Michailoff T. M., Lee A. B. A system for continuous measurement of gas exchange and respiratory functions. J Appl Physiol. 1972 Oct;33(4):523–528. doi: 10.1152/jappl.1972.33.4.523. [DOI] [PubMed] [Google Scholar]
- Stoner H. B., Frayn K. N., Barton R. N., Threlfall C. J., Little R. A. The relationships between plasma substrates and hormones and the severity of injury in 277 recently injured patients. Clin Sci (Lond) 1979 Jan;56(6):563–573. doi: 10.1042/cs0560563. [DOI] [PubMed] [Google Scholar]
- TZUR R., TAL E., SHAPIRO B. ALPHA-GLYCEROPHOSPHATE AS REGULATORY FACTOR IN FATTY ACID ESTERIFICATION. Biochim Biophys Acta. 1964 Feb 24;84:18–23. doi: 10.1016/0926-6542(64)90096-4. [DOI] [PubMed] [Google Scholar]
- Unger R. H., Aguilar-Parada E., Müller W. A., Eisentraut A. M. Studies of pancreatic alpha cell function in normal and diabetic subjects. J Clin Invest. 1970 Apr;49(4):837–848. doi: 10.1172/JCI106297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waterhouse C., Baker N., Rostami H. Effect of glucose ingestion on the metabolism of free fatty acids in human subjects. J Lipid Res. 1969 Sep;10(5):487–494. [PubMed] [Google Scholar]
- Wolfe B. M., Ahuja S. P. Effects of intravenously administered fructose and glucose on splanchnic secretion of plasma triglycerides in hypertriglyceridemic men. Metabolism. 1977 Sep;26(9):963–978. doi: 10.1016/0026-0495(77)90014-2. [DOI] [PubMed] [Google Scholar]
- Wolfe B. M., Culebras J. M., Sim A. J., Ball M. R., Moore F. D. Substrate interaction in intravenous feeding: comparative effects of carbohydrate and fat on amino acid utilization in fasting man. Ann Surg. 1977 Oct;186(4):518–540. doi: 10.1097/00000658-197710000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ZILVERSMIT D. B. The design and analysis of isotope experiments. Am J Med. 1960 Nov;29:832–848. doi: 10.1016/0002-9343(60)90117-0. [DOI] [PubMed] [Google Scholar]