Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-17T18:08:38.517Z Has data issue: false hasContentIssue false
  • English
  • Français

Macronutrient metabolism of adipose tissue at rest and during exercise: a methodological viewpoint

Published online by Cambridge University Press:  12 June 2007

Keith N. Frayn
Keith N. Frayn*
Affiliation:
Oxford Lipid Metabolism Group, Radcliffe Infirmary, Oxford OX2 6HE, UK
*
Corresponding Author: Dr K.N. Frayn, fax +44 (0)1865 224652, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The metabolism of white adipose tissue is regulated by many factors, including hormones and substrates delivered in the blood, the activity of the autonomic nervous system and the rate of flow of blood through the tissue. An integrated view of adipose tissue metabolism can only be gained, therefore, from studies in vivo. Of the various techniques available for studying adipose tissue metabolism in vivo, the measurement of arterio-venous differences offers some unique possibilities. In human subjects this technique has been performed mostly by catheterization of the venous drainage of the subcutaneous abdominal depot. Studies using this technique indicate that adipose tissue has an active pattern of metabolism, responding rapidly to meal ingestion by suppressing the release of non-esterified fatty acids, or to exercise with an increase in fat mobilization. Adipose tissue blood flow may also change rapidly in these situations; for instance, it increases markedly after a meal, potentially increasing the delivery of triacylglycerol to the enzyme lipoprotein lipase (EC 3.1.1.34) for hydrolysis. During exercise, there is evidence that adipose tissue blood flow does not increase sufficiently to allow delivery of all the fatty acids released into the systemic circulation. The various adipose tissue depots have their own characteristic metabolic properties, although in human subjects these are difficult to study with the arterio-venous difference technique. A combination of tracer infusion with selective catheterization allows measurements of leg, splanchnic and non-splanchnic upper-body fat mobilization and triacylglycerol clearance. Development of such techniques may open up new possibilities in the future for obtaining an integrated picture of adipose tissue function and its depot-specific variations.

Keywords

Adipose tissueArterio-venous differencesExercise
Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 58 , Issue 4 , November 1999 , pp. 877 - 886
Copyright
The Nutrition Society

References

Ailhaud, G (1997) Molecular mechanisms of adipocyte differentiation. Journal of Endocrinology 155, 201–202.CrossRefGoogle ScholarPubMed
Andrews, JF (1998) Leptin: energy regulation and beyond to a hormone with pan-physiological function. Proceedings of the Nutrition Society 57, 409–411.CrossRefGoogle ScholarPubMed
Arner, P (1995) Differences in lipolysis between human subcutaneous and omental adipose tissues. Annals of Medicine 27, 435–438.CrossRefGoogle ScholarPubMed
Arner, P (1997) Impact of visceral fat. International Journal of Obesity 21, Suppl. 2, S20.Google Scholar
Arner, P (1999) Microdialysis: use in human exercise studies. Proceedings of the Nutrition Society 58, 913–917.Google Scholar
Arner, P & Bülow, J (1993) Assessment of adipose tissue metabolism in man: comparison of Fick and microdialysis techniques. Clinical Science 85, 247–256.CrossRefGoogle ScholarPubMed
Arner, P, Kriegholm, E, Engfeldt, P & Bolinder, J (1990) Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85, 893–898.Google Scholar
Bangsbo, J (1999) Vasoactive substances in the interstitium of contracting muscle examined by microdialysis. Proceedings of the Nutrition Society 58, 925–933.Google Scholar
Björntorp, P (1991) Metabolic implications of body fat distribution. Diabetes Care 14, 1132–1143.CrossRefGoogle ScholarPubMed
Björntorp, P (1994) Fatty acids, hyperinsulinemia, and insulin resistance: which comes first? Current Opinion in Lipidology 5, 166–174.Google Scholar
Bülow, J, Astrup, A, Christensen, NJ & Kastrup, J (1987) Blood flow in skin, subcutaneous adipose tissue and skeletal muscle in the forearm of normal man during an oral glucose load. Acta Physiologica Scandinavica 130, 657–661.CrossRefGoogle ScholarPubMed
Bülow, J & Madsen, J (1976) Adipose tissue blood flow during prolonged, heavy exercise. Pflügers Archiv 363, 231–234.CrossRefGoogle ScholarPubMed
Bülow, J & Madsen, J (1978) Human adipose tissue blood flow during prolonged exercise II. Pflügers Archiv 376, 41–45.CrossRefGoogle ScholarPubMed
Bülow, J & Madsen, J (1981) Influence of blood flow on fatty acid mobilization from lipolytically active adipose tissue. Pflügers Archiv 390, 169–174.Google Scholar
Bülow, J, Madsen, J, Astrup, A & Christensen, NJ (1985) Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo. Acta Physiologica Scandinavica 125, 661–667.CrossRefGoogle ScholarPubMed
Campbell, PJ, Carlson, MG, Hill, JO & Nurjhan, N (1992) Regulation of free fatty acid metabolism by insulin in humans: role of lipolysis and reesterification. American Journal of Physiology 263, E1063–E1069.Google ScholarPubMed
Coppack, SW, Evans, RD, Fisher, RM, Frayn, KN, Gibbons, GF, Humphreys, SM, Kirk, MJ, Potts, JL & Hockaday, TDR (1992) Adipose tissue metabolism in obesity: lipase action in vivo before and after a mixed meal. Metabolism 41, 264–272.CrossRefGoogle ScholarPubMed
Coppack, SW, Fisher, RM, Gibbons, GF, Humphreys, SM, McDonough, MJ, Potts, JL & Frayn, KN (1990) Postprandial substrate deposition in human forearm and adipose tissues in vivo. Clinical Science 79, 339–348.Google Scholar
Coppack, SW, Fisher, RM, Humphreys, SM, Clark, ML, Pointon, JJ & Frayn, KN (1996) Carbohydrate metabolism in insulin resistance: glucose uptake and lactate production by adipose and forearm tissues in vivo before and after a mixed meal. Clinical Science 90, 409–415.CrossRefGoogle ScholarPubMed
Coppack, SW, Frayn, KN, Humphreys, SM, Whyte, PL & Hockaday, TDR (1990) Arteriovenous differences across human adipose and forearm tissues after overnight fast. Metabolism 39, 384–390.Google Scholar
Coyle, EF (1995) Substrate utilization during exercise in active people. American Journal of Clinical Nutrition 61, Suppl, 968S–979S.CrossRefGoogle ScholarPubMed
Crandall, DL & DiGirolamo, M (1990) Hemodynamic and metabolic correlates in adipose tissue: pathophysiologic considerations. FASEB Journal 4, 141–147.Google Scholar
Elia, M, Folmer, P, Schlatmann, A, Goren, A & Austin, S (1988) Carbohydrate, fat, and protein metabolism in muscle and in the whole body after mixed meal ingestion. Metabolism 37, 542–551.Google Scholar
Ferrannini, E, Barrett, EJ, Bevilacqua, S & DeFronzo, RA (1983) Effect of fatty acids on glucose production and utilization in man. Journal of Clinical Investigation 72, 1737–1747.CrossRefGoogle ScholarPubMed
Flier, JS (1995) The adipocyte: Storage depot or node on the energy information superhighway? Cell 80, 15–18. .Google Scholar
Fojt, E, Ekelund, LG & Hultman, E (1976) Enzyme activities in hepatic venous blood under strenuous physical exercise. Pfügers Archiv 361, 287–296.Google Scholar
Frayn, KN (1992) Studies of human adipose tissue in vivo. In Energy Metabolism: Tissue Determinants and Cellular Corollaries, pp. 267–295 [Kinney, JM and Tucker, HN, editors.] New York: Raven Press.Google Scholar
Frayn, KN, Coppack, SW, Fielding, BA & Humphreys, SM (1995a) Coordinated regulation of hormone-sensitive lipase and lipoprotein lipase in human adipose tissue in vivo: implications for the control of fat storage and fat mobilization. Advances in Enzyme Regulation 35, 163–178.Google Scholar
Frayn, KN, Coppack, SW & Humphreys, SM (1993) Subcutaneous adipose tissue metabolism studied by local catheterization. International Journal of Obesity 17, Suppl. 3, S18–S21.Google ScholarPubMed
Frayn, KN, Coppack, SW, Humphreys, SM & Whyte, PL (1989) Metabolic characteristics of human adipose tissue in vivo. Clinical Science 76, 509–516.Google Scholar
Frayn, KN, Fielding, BA, Samra, JS & Summers, LKM (1997a) Extracellular metabolic regulation in adipose tissue. In Physiology, Stress, and Malnutrition, pp. 303–323 [Kinney, JM and Tucker, HN, editors.] Philadelphia, PA: Lippincott-Raven.Google Scholar
Frayn, KN, Fielding, BA & Summers, LKM (1997b) Investigation of human adipose tissue metabolism in vivo. Journal of Endocrinology 155, 187–189.Google Scholar
Frayn, KN, Hodgetts, V & Griffiths, AJ (1996a) Mobilization and clearance of fat in exercising humans studied by regional venous catheterization. In Biochemistry of Exercise, Vol. 9, pp. 73–88 [Maughan, RJ and Shirreffs, SM, editors.] Champaign, IL: Human Kinetics.Google Scholar
Frayn, KN, Humphreys, SM & Coppack, SW (1995b) Fuel selection in white adipose tissue. Proceedings of the Nutrition Society 54, 177–189. Frayn KN, Humphreys SM & Coppack SW (1996b) Net carbon flux across subcutaneous adipose tissue after a standard meal in normal-weight and insulin-resistant obese subjects. International Journal of Obesity 20, 795–800.Google Scholar
Frayn, KN, Khan, K, Coppack, SW & Elia, M (1991) Amino acid metabolism in human subcutaneous adipose tissue in vivo. Clinical Science 80, 471–474.CrossRefGoogle ScholarPubMed
Frayn, KN & Macdonald, IA (1996) Adipose tissue circulation. In Nervous Control of Blood Vessels, pp. 505–539 [Bennett, T and Gardiner, SM, editors.] Amsterdam: Harwood Academic.Google Scholar
Frayn, KN, Samra, JS & Summers, LKM (1997c) Visceral fat in relation to health: is it a major culprit or simply an innocent bystander? International Journal of Obesity 21, 1191–1192.CrossRefGoogle ScholarPubMed
Frayn, KN, Shadid, S, Hamlani, R, Humphreys, SM, Clark, ML, Fielding, BA, Boland, O & Coppack, SW (1994) Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition. American Journal of Physiology 266, E308–E317.Google ScholarPubMed
Frayn, KN & Summers, LKM (1998) Substrate fluxes in skeletal muscle and white adipose tissue and their importance in the development of obesity. In Clinical Obesity, pp. 129–157 [Kopelman, PG and Stock, MJ, editors.] Oxford: Blackwell Science.Google Scholar
Frid, A, Östman, J & Linde, B (1990) Hypoglycemia risk during exercise after intramuscular injection of insulin in thigh in IDDM. Diabetes Care 13, 473–477.CrossRefGoogle ScholarPubMed
Gooden, JM, Campbell, SL & van der Walt, JG (1986) Measurement of blood flow and lipolysis in the hindquarter tissues of the fat-tailed sheep in vivo. Quarterly Journal of Experimental Physiology 71, 537–547.CrossRefGoogle ScholarPubMed
Gregoire, FM, Smas, CM & Sul, HS (1998) Understanding adipocyte differentiation. Physiological Reviews 78, 783–809.CrossRefGoogle ScholarPubMed
Guerre-Millo, M, Staels, B & Auwerx, J (1996) New insights into obesity genes. Diabetologia 39, 1528–1531.CrossRefGoogle ScholarPubMed
Hellström, L, Blaak, E & Hagström-Toft, E (1996) Gender differences in adrenergic regulation of lipid mobilization during exercise. International Journal of Sports Medicine 17, 439–447.Google Scholar
Henriksson, J (1999) Microdialysis of skeletal muscle at rest. Proceedings of the Nutrition Society 58, 919–923.Google Scholar
Hjemdahl, P & Linde, B (1983) Influence of circulating NE and Epi on adipose tissue vascular resistance and lipolysis in humans. American Journal of Physiology 245, H447–H452.Google ScholarPubMed
Hodgetts, V, Coppack, SW, Frayn, KN & Hockaday, TDR (1991) Factors controlling fat mobilization from human subcutaneous adipose tissue during exercise. Journal of Applied Physiology 71, 445–451.Google Scholar
Hoffstedt, J, Arner, P, Hellers, G & Lonnqvist, F (1997) Variation in adrenergic regulation of lipolysis between omental and subcutaneous adipocytes from obese and non-obese men. Journal of Lipid Research 38, 795–804.CrossRefGoogle ScholarPubMed
Holloway, BR, Stribling, D, Freeman, S & Jamieson, L (1985) The thermogenic role of adipose tissue in the dog. International Journal of Obesity 9, 423–432.Google ScholarPubMed
Jansson, P-A, Larsson, A, Smith, U & Lönnroth, P (1994) Lactate release from the subcutaneous tissue in lean and obese men. Journal of Clinical Investigation 93, 240–246.Google Scholar
Jensen, MD, Caruso, M, Heiling, V & Miles, JM (1989) Insulin regulation of lipolysis in nondiabetic and IDDM subjects. Diabetes 38, 1595–1601.CrossRefGoogle ScholarPubMed
Jensen, MD, Heiling, V & Miles, JM (1990) Measurement of non-steady-state free fatty acid turnover. American Journal of Physiology 258, E103–E108.Google Scholar
Jensen, MD & Johnson, CM (1996) Contribution of leg and splanchnic free fatty acid (FFA) kinetics to postabsorptive FFA flux in men and women. Metabolism 45, 662–666.CrossRefGoogle ScholarPubMed
Jones, NL, Heigenhauser, GJF, Kuksis, A, Matos, CG, Sutton, JR & Toews, CJ (1980) Fat metabolism in heavy exercise. Clinical Science 59, 469–478.Google Scholar
Kowalchuk, JM, Curi, R & Newsholme, EA (1988) Glutamine metabolism in isolated incubated adipocytes of the rat. Biochemical Journal 249, 705–708.Google Scholar
Kowalski, TJ & Watford, M (1994) Production of glutamine and utilization of glutamate by rat subcutaneous adipose tissue in vivo. American Journal of Physiology 266, E151–E154.Google ScholarPubMed
Kowalski, TJ, Wu, G & Watford, M (1997) Rat adipose tissue amino acid metabolism in vivo as assessed by microdialysis and arteriovenous techniques. American Journal of Physiology 273, E613–E622. .Google ScholarPubMed
Kurpad, A, Khan, K, Calder, AG, Coppack, S, Frayn, K, Macdonald, I & Elia, M (1994) Effect of noradrenaline on glycerol turnover and lipolysis in the whole body and subcutaneous adipose tissue in humans in vivo. Clinical Science 86, 177–184.Google Scholar
Leboeuf, B (1965) Regulation of fatty acid esterification in adipose tissue incubated in vitro. In Handbook of Physiology. Section 5, Adipose Tissue, pp. 385–391 [Renold, AE and Cahill, GF, editors.] Washington, DC: American Physiological Society.Google Scholar
Mårin, P, Rebuffé-Scrive, M, Smith, U & Björntorp, P (1987) Glucose uptake in human adipose tissue. Metabolism 36, 1154–1160.CrossRefGoogle ScholarPubMed
Maslowska, M, Scantlebury, T, Germinario, R & Cianflone, K (1997) Acute in vitro production of acylation stimulating protein in differentiated human adipocytes. Journal of Lipid Research 38, 1–11.CrossRefGoogle ScholarPubMed
Newby, FD, Sykes, MN & DiGirolama, M (1988) Regional differences in adipocyte lactate production from glucose. American Journal of Physiology 255, E716–E722.Google ScholarPubMed
Nguyen, TT, Mijares, AH, Johnson, CM & Jensen, MD (1996) Postprandial leg and splanchnic fatty acid metabolism in nonobese men and women. American Journal of Physiology 271, E965–E972.Google Scholar
Oben, J, Elliott, R, Morgan, L, Fletcher, J & Marks, V (1992) The role of gut hormones in the adipose tissue metabolism of lean and genetically obese (ob/ob) mice. In Obesity in Europe 91. Proceedings of the 3rd European Congress on Obesity, pp. 269–272 [Ailhaud, G, Guy-Grand, B, Lafontan, M and Ricquier, D, editors.] London: Libby.Google Scholar
Ong, JM & Kern, PA (1989) Effect of feeding and obesity on lipoprotein lipase activity, immunoreactive protein, and messenger RNA levels in human adipose tissue. Journal of Clinical Investigation 84, 305–311.CrossRefGoogle ScholarPubMed
Randle, PJ, Garland, PB, Hales, CN & Newsholme, EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet i, 785–789.Google Scholar
Rebuffé-Scrive, M, Anderson, B, Olbe, L & Björntorp, P (1990) Metabolism of adipose tissue in intraabdominal depots in severely obese men and women. Metabolism 39, 1021–1025.CrossRefGoogle ScholarPubMed
Rebuffé-Scrive, M, Andersson, B, Olbe, L & Björntorp, P (1989) Metabolism of adipose tisue in intraabdominal depots of nonobese men and women. Metabolism 38, 453–458.Google Scholar
Rebuffé-Scrive, M, Lönnroth, P, Mårin, P, Wesslau, C, Björntorp, P & Smith, U (1987) Regional adipose tissue metabolism in men and postmenopausal women. International Journal of Obesity 11, 347–355.Google Scholar
Renold, AE & Cahill, GF (1965) Metabolism of isolated adipose tissue: a summary. In Handbook of Physiology. Section 5, Adipose Tissue, pp. 483–490 [Renold, AE and Cahill, GF, editors.] Washington, DC: American Physiological Society.Google Scholar
Richelsen, B, Pedersen, SB, Møller-Pedersen, T & Bak, JF (1991) Regional differences in triglyceride breakdown in human adipose tissue: effects of catecholamines, insulin, and prostaglandin E2. Metabolism 40, 990–996.CrossRefGoogle ScholarPubMed
Rodbell, M (1964) Metabolism of isolated fat cells. 1. Effects of hormones on glucose metabolism and lipolysis. Journal of Biological Chemistry 239, 375–380.Google Scholar
Romijn, JA, Coyle, EF, Sidossis, LS, Gastaldelli, A, Horowitz, JF, Endert, E & Wolfe, RR (1993) Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. American Journal of Physiology 265, E380–E391.Google Scholar
Sadur, CN & Eckel, RH (1982) Insulin stimulation of adipose tissue lipoprotein lipase. Use of the euglycemic clamp technique. Journal of Clinical Investigation 69, 1119–1125.Google Scholar
Saleh, J, Summers, L, Cianflone, K, Fielding, B, Sniderman, A & Frayn, K (1998) Coordinated release of acylation stimulating protein and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period. Journal of Lipid Research 39, 884–891.CrossRefGoogle ScholarPubMed
Samra, JS, Frayn, KN, Giddings, JA, Clark, ML & Macdonald, IA (1995) Modification and validation of a commercially available portable detector for measurement of adipose tissue blood flow. Clinical Physiology 15, 241–248. .CrossRefGoogle ScholarPubMed
Samra, JS, Simpson, EJ, Clark, ML, Forster, CD, Humphreys, SM, Macdonald, IA & Frayn, KN (1996) Effects of epinephrine infusion on adipose tissue: interactions between blood flow and lipid metabolism. American Journal of Physiology 271, E834-E839.Google Scholar
Simonsen, L, Bülow, J, Astrup, A, Madsen, J & Christensen, NJ (1990) Diet-induced changes in subcutaneous adipose tissue blood flow in man: effect of b-adrenoceptor inhibition. Acta Physiologica Scandinavica 139, 341–346.CrossRefGoogle Scholar
Simonsen, L, Bülow, J & Madsen, J (1994) Adipose tissue metabolism in humans determined by vein catheterization and microdialysis techniques. American Journal of Physiology 266, E357-E365.Google ScholarPubMed
Sniderman, AD & Cianflone, K (1997) The adipsin-acylation-stimulating protein pathway and microenvironmental metabolic regulation. World Review of Nutrition and Dietetics 80, 44–81.Google Scholar
Sniderman, AD, Cianflone, K, Summers, LKM, Fielding, BA & Frayn, KN (1997) The acylation-stimulating protein pathway and regulation of postprandial metabolism. Proceedings of the Nutrition Society 56, 703–712.Google Scholar
Summers, LKM, Arner, P, Ilic, V, Clark, ML, Humphreys, SM & Frayn, KN (1998) Adipose tissue metabolism in the postprandial period: microdialysis and arteriovenous techniques compared. American Journal of Physiology 274, E651-E655.Google Scholar
Summers, LKM, Samra, JS, Humphreys, SM, Morris, RJ & Frayn, KN (1996) Subcutaneous abdominal adipose tissue blood flow: variation within and between subjects and relationship to obesity. Clinical Science 91, 679–683.CrossRefGoogle ScholarPubMed
Taylor, R, Husband, DJ, Marshall, SM, Tunbridge, WMG & Alberti, KGMM (1984) Adipocyte insulin binding and insulin sensitivity in ‘brittle’ diabetes. Diabetologia 27, 441–446.Google Scholar
Taylor, R, Price, TB, Katz, LD, Shulman, RG & Shulman, GI (1993) Direct measurement of change in muscle glycogen concentration after a mixed meal in normal subjects. American Journal of Physiology 265, E224-E229.Google Scholar
Vikman, HL, Ranta, S, Kiviluoto, T & Ohisalo, JJ (1991) Different metabolic regulation by adenosine in omental and subcutaneous adipose tissue. Acta Physiologica Scandinavica 142, 405–410.CrossRefGoogle ScholarPubMed
Wijnen, JAG, van Baak, MA, de Haan, C, Struijker Boudier, HAJ, Tan, FS & Van Bortel, LMAB (1993) Beta-blockade and lipolysis during endurance exercise. European Journal of Clinical Pharmacology 45, 101–105.Google Scholar
Wolfe, RR, Klein, S, Carraro, F & Weber, J-M (1990) Role of triglyceride-fatty acid cycle in controlling fat metabolism in humans during and after exercise. American Journal of Physiology 258, E382-E389.Google ScholarPubMed
Zierler, KL (1961) Theory of the use of arteriovenous concentration differences for measuring metabolism in steady and non-steady states. Journal of Clinical Investigation 40, 2111–2125.CrossRefGoogle ScholarPubMed