Adipose tissue is now recognised as a highly active metabolic and endocrine organ. Great strides have been made in uncovering the multiple functions of the adipocyte in cellular and molecular detail, but it is essential to remember that adipose tissue normally operates as a structured whole. Its functions are regulated by multiple external influences such as autonomic nervous system activity, the rate of blood flow and the delivery of a complex mix of substrates and hormones in the plasma. Attempting to understand how all these factors converge and regulate adipose tissue function is a prime example of integrative physiology. Adipose tissue metabolism is extremely dynamic, and the supply of and removal of substrates in the blood is acutely regulated according to the nutritional state. Adipose tissue possesses the ability to a very large extent to modulate its own metabolic activities, including differentiation of new adipocytes and production of blood vessels as necessary to accommodate increasing fat stores. At the same time, adipocytes signal to other tissues to regulate their energy metabolism in accordance with the body's nutritional state. Ultimately adipocyte fat stores have to match the body's overall surplus or deficit of energy. This implies the existence of one (or more) signal(s) to the adipose tissue that reflects the body's energy status, and points once again to the need for an integrative view of adipose tissue function.
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Coleman RA, Lewin TM, Muoio D . Physiological and nutritional regulation of enzymes of triacylglycerol synthesis. Ann Rev Nutr 2000; 20: 77–103.
Langin D, Holm C, Lafontan M . Adipocyte hormone-sensitive lipase: a major regulator of lipid metabolism. Proc Nutr Soc 1996; 55: 93–109.
Holm C, Osterlund T, Laurell H, Contreras JA . Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Ann Rev Nutr 2000; 20: 365–393.
Shrago E, Spennetta T, Gordon E . Fatty acid synthesis in human adipose tissue. J Biol Chem 1969; 244: 2761–2766.
Hellerstein MK, Schwarz J-M, Neese RA . Regulation of hepatic de novo lipogenesis in humans. Annu Rev Nutr 1996; 16: 523–557.
Aarsland A, Chinkes D, Wolfe RR . Hepatic and whole-body fat synthesis in humans during carbohydrate overfeeding. Am J Clin Nutr 1997; 65: 1774–1782.
Leboeuf B . Regulation of fatty acid esterification in adipose tissue incubated in vitro. In: Renold AE, Cahill GF (eds). Handbook of physiology Section 5: adipose tissue. American Physiological Society: Washington DC, 1965. pp 385–391.
Harper RD, Saggerson ED . Factors affecting fatty acid oxidation in fat cells isolated from rat white adipose tissue. J Lipid Res 1976; 17: 516–526.
Sadur CN, Eckel RH . Insulin stimulation of adipose tissue lipoprotein lipase. Use of the euglycemic clamp technique. J Clin Invest 1982; 69: 1119–1125.
Frayn KN, Shadid S, Hamlani R, Humphreys SM, Clark ML, Fielding BA, Boland O, Coppack SW . Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition. Am J Physiol 1994; 266: E308–E317.
Baldo A, Sniderman AD, St-Luce S, Avramoglu RK, Maslowska M, Hoang B, Monge JC, Bell A, Mulay S, Cianflone K . The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis. J Clin Invest 1993; 92: 1543–1547.
Cianflone K, Vu H, Walsh M, Baldo A, Sniderman A . Metabolic response of acylation stimulating protein to an oral fat load. J Lipid Res 1989; 30: 1727–1733.
Choy LN, Rosen BS, Spiegelman BM . Adipsin and an endogenous pathway of complement from adipose cells. J Biol Chem 1992; 267: 12736–12741.
Maslowska M, Scantlebury T, Germinario R, Cianflone K . Acute in vitro production of acylation stimulating protein in differentiated human adipocytes. J Lipid Res 1997; 38: 1–11.
Saleh J, Summers L, Cianflone K, Fielding B, Sniderman A, Frayn K . Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period. J Lipid Res 1998; 39: 884–891.
Campbell PJ, Carlson MG, Hill JO, Nurjhan N . Regulation of free fatty acid metabolism by insulin in humans: role of lipolysis and reesterification. Am J Physiol 1992; 263: E1063–E1069.
Rizza RA, Mandarino LJ, Gerich JE . Dose–response characteristics for effects of insulin on production and utilization of glucose in man. Am J Physiol 1981; 240: E630–E639.
Coppack SW, Frayn KN, Humphreys SM, Dhar H, Hockaday TDR . Effects of insulin on human adipose tissue metabolism in vivo. Clin Sci 1989; 77: 663–670.
Sztalryd C, Kraemer FB . Regulation of hormone-sensitive lipase during fasting. Am J Physiol 1994; 266: E179–E185.
Clifford GM, Londos C, Kraemer FB, Vernon RG, Yeaman SJ . Translocation of hormone-sensitive lipase and perilipin upon lipolytic stimulation of rat adipocytes. J Biol Chem 2000; 275: 5011–5015.
Arner P, Kriegholm E, Engfeldt P, Bolinder J . Adrenergic regulation of lipolysis in situ at rest and during exercise. J Clin Invest 1990; 85: 893–898.
Samra JS, Clark ML, Humphreys SM, Macdonald IA, Bannister PA, Matthews DR, Frayn KN . Suppression of the nocturnal rise in growth hormone reduces subsequent lipolysis in subcutaneous adipose tissue. Eur J Clin Invest 1999; 29: 1045–1052.
Samra JS, Clark ML, Humphreys SM, Macdonald IA, Matthews DR, Frayn KN . Effects of morning rise in cortisol concentration on regulation of lipolysis in subcutaneous adipose tissue. Am J Physiol 1996; 271: E996–E1002.
Sengenes C, Berlan M, De Glisezinski I, Lafontan M, Galitzky J . Natriuretic peptides: a new lipolytic pathway in human adipocytes. FASEB J 2000; 14: 1345–1351.
Julien P, Despres J-P, Angel A . Scanning electron microscopy of very small fat cells and mature fat cells in human obesity. J Lipid Res 1989; 30: 293–299.
Peeva E, Brun DL, Ven Murthy MR, Després J-P, Normand T, Gagné C, Lupien P-J, Julien P . Adipose cell size and distribution in familial lipoprotein lipase deficiency. Int J Obes Relat Metab Disord 1992; 16: 737–744.
Weinstock PH, Levak Frank S, Hudgins LC, Radner H, Friedman JM, Zechner R, Breslow JL . Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase. Proc Natl Acad Sci USA 1997; 94: 10261–10266.
Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese Jr RV . Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet 2000; 25: 87–90.
Chen HC, Ladha Z, Smith SJ, Farese Jr RV . Analysis of energy expenditure at different ambient temperatures in mice lacking DGAT1. Am J Physiol Endocrinol Metab 2003; 284: E213–E218.
Osuga J, Ishibashi S, Oka T, Yagyu H, Tozawa R, Fujimoto A, Shionoiri F, Yahagi N, Kraemer FB, Tsutsumi O, Yamada N . Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc Natl Acad Sci USA 2000; 97: 787–792.
Wang SP, Laurin N, Himms-Hagen J, Rudnicki MA, Levy E, Robert M-F, Pan L, Oligny L, Mitchell GA . The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice. Obes Res 2001; 9: 119–128.
Tansey JT, Sztalryd C, Gruia-Gray J, Roush DL, Zee JV, Gavrilova O, Reitman ML, Deng CX, Li C, Kimmel AR, Londos C . Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity. Proc Natl Acad Sci USA 2001; 98: 6494–6499.
Frayn KN, Coppack SW, Fielding BA, Humphreys SM . 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. Adv Enzyme Regul 1995; 35: 163–178.
Hauner H, Entenmann G, Wabitsch M, Gaillard D, Ailhaud G, Negrel R, Pfeiffer EF . Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest 1989; 84: 1663–1670.
Ailhaud G . Molecular mechanisms of adipocyte differentiation. J Endocrinol 1997; 155: 201–202.
Darlington GJ, Ross SE, MacDougald OA . The role of C/EBP genes in adipocyte differentiation. J Biol Chem 1998; 273: 30057–30060.
Rosen ED, Spiegelman BM . Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol 2000; 16: 145–171.
Amri EZ, Bonino F, Ailhaud G, Abumrad NA, Grimaldi PA . Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors. J Biol Chem 1995; 270: 2367–2371.
Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM . 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 1995; 83: 803–812.
Kim JB, Sarraf P, Wright M, Yao KM, Mueller E, Solanes G, Lowell BB, Spiegelman BM . Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest 1998; 101: 1–9.
Gondret F, Ferré P, Dugail I . ADD-1/SREBP-1 is a major determinant of tissue differential lipogenic capacity in mammalian and avian species. J Lipid Res 2001; 42: 106–113.
Bouloumié A, Drexler HC, Lafontan M, Busse R . Leptin, the product of Ob gene, promotes angiogenesis. Circ Res 1998; 83: 1059–1066.
Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ, Flores-Riveros JR . Biological action of leptin as an angiogenic factor. Science 1998; 281: 1683–1686.
Bouloumié A, Sengenès C, Portolan G, Galitzky J, Lafontan M . Adipocyte produces matrix metalloproteinases 2 and 9: involvement in adipose differentiation. Diabetes 2001; 50: 2080–2086.
Morimura M, Ishiko O, Sumi T, Yoshida H, Ogita S . Angiogenesis in adipose tissues and skeletal muscles with rebound weightgain after diet-restriction in rabbits. Int J Mol Med 2001; 8: 499–503.
Li J, Yu X, Pan W, Unger RH . Gene expression profile of rat adipose tissue at the onset of high-fat-diet obesity. Am J Physiol Endocrinol Metab 2002; 282: E1334–E1341.
Rupnick MA, Panigrahy D, Zhang C-Y, Dallabrida SM, Lowell BB, Langer R, Folkman MJ . Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci USA 2002; 99: 10730–10735.
Prins JB, Niesler CU, Winterford CM, Bright NA, Siddle K, O'Rahilly S, Walker NI, Cameron DP . Tumor necrosis factor-α induces apoptosis of human adipose cells. Diabetes 1997; 46: 1939–1944.
Wabitsch M . The acquisition of obesity: insights from cellular and genetic research. Proc Nutr Soc 2000; 59: 325–330.
Sorisky A, Magun R, Gagnon AM . Adipose cell apoptosis: death in the energy depot. Int J Obes Relat Metab Disord 2000; 24(Suppl 4): S3–S7.
Elia M, Kurpad A . What is the blood flow to resting human muscle? Clin Sci 1993; 84: 559–563.
Bülow J, Astrup A, Christensen NJ, Kastrup J . Blood flow in skin, subcutaneous adipose tissue and skeletal muscle in the forearm of normal man during an oral glucose load. Acta Physiol Scand 1987; 130: 657–661.
Samra JS, Frayn KN, Giddings JA, Clark ML, Macdonald IA . Modification and validation of a commercially available portable detector for measurement of adipose tissue blood flow. Clin Physiol 1995; 15: 241–248.
Summers LKM, Samra JS, Humphreys SM, Morris RJ, Frayn KN . Subcutaneous abdominal adipose tissue blood flow: variation within and between subjects and relationship to obesity. Clin Sci 1996; 91: 679–683.
Summers LKM, Callow J, Samra JS, Macdonald IA, Matthews DR, Frayn KN . The effect on adipose tissue blood flow of isoenergetic meals containing different amounts and types of fat. Int J Obes Relat Metab Disord 2001; 25: 1294–1299.
Karpe F, Fielding BA, Ardilouze J-L, Ilic V, Macdonald IA, Frayn KN . Effects of insulin on adipose tissue blood flow in man. J Physiol 2002; 540: 1087–1093.
Karpe F, Fielding BA, Ilic V, Macdonald IA, Summers LKM, Frayn KN . Impaired postprandial adipose tissue blood flow response is related to aspects of insulin sensitivity. Diabetes 2002; 51: 2467–2473.
Simonsen L, Bülow J, Astrup A, Madsen J, Christensen NJ . Diet-induced changes in subcutaneous adipose tissue blood flow in man: effect of β-adrenoceptor inhibition. Acta Physiol Scand 1990; 139: 341–346.
Romanski SA, Nelson RM, Jensen MD . Meal fatty acid uptake in adipose tissue: gender effects in nonobese humans. Am J Physiol Endocrinol Metab 2000; 279: E455–E462.
Bülow J, Madsen J . Adipose tissue blood flow during prolonged, heavy exercise. Pflügers Arch 1976; 363: 231–234.
Al Mulla N, Simonsen L, Bülow J . Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans: the effects of exercise intensity. J Physiol 2000; 524: 919–928.
Hagström-Toft E, Bolinder J, Ungerstedt U, Arner P . A circadian rhythm in lipid mobilization which is altered in IDDM. Diabetologia 1997; 40: 1070–1078.
Klein S, Horowitz JF, Landt M, Goodrick SJ, Mohamed Ali V, Coppack SW . Leptin production during early starvation in lean and obese women. Am J Physiol Endocrinol Metab 2000; 278: E280–E284.
Patel JN, Coppack SW, Goldstein DS, Miles JM, Eisenhofer G . Norepinephrine spillover from human adipose tissue before and after a 72-hour fast. J Clin Endocrinol Metab 2002; 87: 3373–3377.
Samra JS, Simpson EJ, Clark ML, Forster CD, Humphreys SM, Macdonald IA, Frayn KN . Effects of epinephrine infusion on adipose tissue: interactions between blood flow and lipid metabolism. Am J Physiol 1996; 271: E834–E839.
Frayn KN, Macdonald IA . Adipose tissue circulation. In: Bennett T, Gardiner SM (eds). Nervous control of blood vessels. Harwood Academic: Amsterdam, 1996. pp 505–539.
Hjemdahl P, Linde B, Daleskog M, Belfrage E . Sympatho-adrenal regulation of adipose tissue blood flow in dog and man. Gen Pharmacol 1983; 14: 175–177.
Galitzky J, Lafontan M, Nordenström J, Arner P . Role of vascular alpha-2 adrenoceptors in regulating lipid mobilization from human adipose tissue. J Clin Invest 1993; 91: 1997–2003.
Stallknecht B, Lorentsen J, Enevoldsen LH, Bülow J, Biering-Sørensen F, Galbo H, Kjaer M . Role of the sympathoadrenergic system in adipose tissue metabolism during exercise in humans. J Physiol 2001; 536: 283–294.
Bülow J, Madsen J, Astrup A, Christensen NJ . Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo. Acta Physiol Scand 1985; 125: 661–667.
Boschmann M, Ringel J, Klaus S, Sharma AM . Metabolic and hemodynamic response of adipose tissue to angiotensin II. Obes Res 2001; 9: 486–491.
Andersson K, Arner P . Cholinoceptor-mediated effects on glycerol output from human adipose tissue using in situ microdialysis. Br J Pharmacol 1995; 115: 1155–1162.
Wirsén C . Adrenergic innervation of adipose tissue examined by fluorescence microscopy. Nature 1964; 202: 913.
Ballard K, Malmfors T, Rosell S . Adrenergic innervation and vascular patterns in canine adipose tissue. Microvasc Research 1974; 8: 164–171.
Slavin BG, Ballard KW . Morphological studies on the adrenergic innervation of white adipose tissue. Anat Rec 1978; 191: 377–389.
Rebuffé-Scrive M . Neuroregulation of adipose tissue: molecular and hormonal mechanisms. Int J Obes Relat Metab Disord 1991; 15(Suppl 2): 83–86.
Youngstrom TG, Bartness TJ . Catecholaminergic innervation of white adipose tissue in Siberian hamsters. Am J Physiol 1995; 268: R744–R751.
Barbe P, Millet L, Galitzky J, Lafontan M, Berlan M . In situ assessment of the role of the β1-, β2- and β3-adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue. Br J Pharmacol 1996; 117: 907–913.
Langin D, Lucas S, Lafontan M . Millennium fat-cell lipolysis reveals unsuspected novel tracks. Horm Metab Res 2000; 32: 443–452.
Lafontan M, Bousquet-Melou A, Galitzky J, Barbe P, Carpene C, Langin D, Berlan M, Valet P, Castan I, Bouloumie A . Adrenergic receptors and fat cells: differential recruitment by physiological amines and homologous regulation. Obes Res 1995; 3(Suppl 4): 507S–514S.
Horowitz JF, Coppack SW, Paramore D, Cryer PE, Zhao G, Klein S . Effect of short-term fasting on lipid kinetics in lean and obese women. Am J Physiol 1999; 276: E278–E284.
Patel JN, Eisenhofer G, Coppack SW, Miles JM . Norepinephrine spillover in forearm and subcutaneous adipose tissue before and after eating. J Clin Endocrinol Metab 1999; 84: 2815–2819.
Cousin B, Casteilla L, Lafontan M, Ambid L, Langin D, Berthault MF, Penicaud L . Local sympathetic denervation of white adipose tissue in rats induces preadipocyte proliferation without noticeable changes in metabolism. Endocrinology 1993; 133: 2255–2262.
Youngstrom TG, Bartness TJ . White adipose tissue sympathetic nervous system denervation increases fat pad mass and fat cell number. Am J Physiol Reg Integr Comp Physiol 1998; 275: R1488–R1493.
Tanida M, Iwashita S, Ootsuka Y, Terui N, Suzuki M . Leptin injection into white adipose tissue elevates renal sympathetic nerve activity dose-dependently through the afferent nerves pathway in rats. Neurosci Lett 2000; 293: 107–110.
Bamshad M, Aoki VT, Adkison MG, Warren WS, Bartness TJ . Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue. Am J Physiol 1998; 275: R291–R299.
Strack AM, Sawyer WB, Hughes JH, Platt KB, Loewy AD . A general pattern of CNS innervation of the sympathetic outflow demonstrated by transneuronal pseudorabies viral infections. Brain Res 1989; 491: 156–162.
Kreier F, Fliers E, Voshol PJ, Van Eden CG, Havekas LM, Kalsbeek A, Van Heijningen CL, Sluiter AA, Mettenleiter TC, Romijn JA, Sauerwein HP, Buijs RM . Selective parasympathetic innervation of subcutaneous and intra-abdominal fat—functional implications. J Clin Invest 2002; 110: 1243–1250.
Bartness TJ . Dual intervention of white adipose tissue: some evidence for parasympathetic nervous system involvement. J Clin Invest 2002; 110: 1235–1237.
Pond CM . The natural history of adipocytes. Sci Prog Oxford 1986; 70: 45–71.
Pond CM . An evolutionary and functional view of mammalian adipose tissue. Proc Nutr Soc 1992; 51: 367–377.
Frayn KN, Coppack SW, Humphreys SM, Clark ML, Evans RD . Periprandial regulation of lipid metabolism in insulin-treated diabetes mellitus. Metabolism 1993; 42: 504–510.
Vague J . La différenciation sexuelle, facteur déterminant des formes de l'obésité. Presse Méd 1947; 30: 339–340.
Vague J . The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout and uric calculous disease. Am J Clin Nutr 1956; 4: 20–34.
Östman J, Arner P, Engfeldt P, Kager L . Regional differences in the control of lipolysis in human adipose tissue. Metabolism 1979; 28: 1198–1205.
Mauriège P, Galitzky J, Berlan M, Lafontan M . Heterogeneous distribution of beta and alpha-2 adrenoceptor binding sites in human fat cells from various fat deposits: functional consequences. Eur J Clin Invest 1987; 17: 156–165.
Engfeldt P, Arner P . Lipolysis in human adipocytes, effects of cell size, age and of regional differences. Horm Metab Res Suppl 1988; 19: 26–29.
Van Harmelen V, Lönnqvist F, Thörne A, Wennlund A, Large V, Reynisdottir S, Arner P . Noradrenaline-induced lipolysis in isolated mesenteric, omental and subcutaneous adipocytes from obese subjects. Int J Obes Relat Metab Disord 1997; 21: 972–979.
Arner P . Catecholamine-induced lipolysis in obesity. Int J Obes Relat Metab Disord 1999; 23(Suppl 1): 10–13.
Jones PR, Edwards DA . Areas of fat loss in overweight young females following an 8-week period of energy intake reduction. Ann Hum Biol 1999; 26: 151–162.
Frayn KN . Visceral fat and insulin resistance—causative or correlative? Br J Nutr 2000; 83(Suppl 1): S71–S77.
Mårin P, Andersson B, Ottosson M, Olbe L, Chowdhury B, Kvist H, Holm G, Sjöström L, Björntorp P . The morphology and metabolism of intraabdominal adipose tissue in men. Metabolism 1992; 41: 1242–1248.
Pedersen SB, Jønler M, Richelsen B . Characterization of regional and gender differences in glucocorticoid receptors and lipoprotein lipase activity in human adipose tissue. J Clin Endocrinol Metab 1994; 78: 1354–1359.
Mauriège P, Marette A, Atgie C, Bouchard C, Theriault G, Bukowiecki LK, Marceau P, Biron S, Nadeau A, Després JP . Regional variation in adipose tissue metabolism of severely obese premenopausal women. J Lipid Res 1995; 36: 672–684.
Lefebvre A-M, Laville M, Vega N, Riou JP, van Gaal L, Auwerx J, Vidal H . Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes 1998; 47: 98–103.
Maslowska MH, Sniderman AD, MacLean LD, Cianflone K . Regional differences in triacylglycerol synthesis in adipose tissue and in cultured preadipocytes. J Lipid Res 1993; 34: 219–228.
Martin ML, Jensen MD . Effects of body fat distribution on regional lipolysis in obesity. J Clin Invest 1991; 88: 609–613.
Guo Z, Hensrud DD, Johnson CM, Jensen MD . Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes 1999; 48: 1586–1592.
Montague CT, Prins JB, Sanders L, Zhang J, Sewter CP, Digby J, Byrne CD, O'Rahilly S . Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 1998; 47: 1384–1391.
Van Harmelen V, Reynisdottir S, Eriksson P, Thörne A, Hoffstedt J, Lönnqvist F, Arner P . Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 1998; 47: 913–917.
Siiteri PK . Adipose tissue as a source of hormones. Am J Clin Nutr 1987; 45: 277–282.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–432.
Coleman RA, Herrmann TS . Nutritional regulation of leptin in humans. Diabetologia 1999; 42: 639–646.
Hilton LK, Loucks AB . Low energy availability, not exercise stress, suppresses the diurnal rhythm of leptin in healthy young women. Am J Physiol Endocrinol Metab 2000; 278: E43–E49.
Coppack SW, Stanner S, Rawesh A, Goodrick S, Mohamed-Ali V . In vivo adipose tissue leptin production before and after a high carbohydrate meal. Int J Obesity Relat Metab Disord 1997; 21: S33.
Friedman JM, Halaas JL . Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763–770.
Auwerx J, Staels B . Leptin. Lancet 1998; 351: 737–742.
Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM . Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 543–546.
Minokoshi Y, Kim Y-B, Peroni OD, Fryer LGD, Müller C, Carling D, Kahn BB . Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 2002; 415: 339–343.
Bray GA . Obesity and reproduction. Hum Reprod 1997; 12(Suppl 1): 26–32.
Balligand JL, Brichard SM, Brichard V, Desager JP, Lambert M . Hypoleptinemia in patients with anorexia nervosa: loss of circadian rhythm and unresponsiveness to short-term refeeding. Eur J Endocrinol 1998; 138: 415–420.
Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B . A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998; 392: 398–401.
Ozata M, Ozdemir IC, Licinio J . Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab 1999; 84: 3686–3695.
Hileman SM, Pierroz DD, Flier JS . Leptin, nutrition, and reproduction: timing is everything. J Clin Endocrinol Metab 2000; 85: 804–807.
Mohamed-Ali V, Pinkney JH, Coppack SW . Adipose tissue as an endocrine and paracrine organ. Int J Obes Relat Metab Disord 1998; 22: 1145–1158.
Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW . Subcutaneous adipose tissue secretes interleukin-6 but not tumor necrosis-factor-α in vivo. J Clin Endocr Metab 1997; 82: 4196–4200.
Mohamed-Ali V, Goodrick S, Bulmer K, Holly JM, Yudkin JS, Coppack SW . Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo. Am J Physiol 1999; 277: E971–E975.
Yudkin JS, Kumari M, Humphries SE, Mohamed Ali V . Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 2000; 148: 209–214.
Yudkin JS, Coppack SW, Bulmer K, Rawesh A, Mohamed Ali V . Lack of evidence for secretion of plasminogen activator inhibitor-1 by human subcutaneous adipose tissue in vivo. Thromb Res 1999; 96: 1–9.
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM . Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. J Clin Invest 1995; 95: 2409–2415.
Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M, Kuriyama H, Kishida K, Nishizawa H, Hotta K, Muraguchi M, Ohmoto Y, Yamashita S, Funahashi T, Matsuzawa Y . Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001; 103: 1057–1063.
Kappes A, Loffler G . Influences of ionomycin, dibutyryl-cycloAMP and tumour necrosis factor-α on intracellular amount and secretion of apM1 in differentiating primary human preadipocytes. Horm Metab Res 2000; 32: 548–554.
Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA . Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930–1935.
Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y . Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20: 1595–1599.
Berg AH, Combs TP, Du X, Brownlee M, Scherer PE . The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001; 7: 947–953.
Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T . The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7: 941–946.
Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y . Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999; 100: 2473–2476.
Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, Matsuzawa Y . Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 2001; 50: 1126–1133.
Okamoto Y, Arita Y, Nishida M, Muraguchi M, Ouchi N, Takahashi M, Igura T, Inui Y, Kihara S, Nakamura T, Yamashita S, Miyagawa J, Funahashi T, Matsuzawa Y . An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res 2000; 32: 47–50.
Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y . Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000; 96: 1723–1732.
Kersten S, Mandard S, Tan NS, Escher P, Metzger D, Chambon P, Gonzalez FJ, Desvergne B, Wahli W . Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. J Biol Chem 2000; 275: 28488–28493.
Yoon JC, Chickering TW, Rosen ED, Dussault B, Qin Y, Soukas A, Friedman JM, Holmes WE, Spiegelman BM . Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol Cell Biol 2000; 20: 5343–5349.
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Rexford SA, Lazar MA . The hormone resistin links obesity to diabetes. Nature 2001; 409: 307–312.
Way JM, Görgün CZ, Tong Q, Uysal KT, Brown KK, Harrington WW, Oliver Jr WR, Willson TM, Kliewer SA, Hotamisligil GS . Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor γ agonists. J Biol Chem 2001; 276: 25651–25653.
Nagaev I, Smith U . Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun 2001; 285: 561–564.
Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O'Rahilly S . Resistin Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 2001; 50: 2199–2202.
Janke J, Engeli S, Gorzelniak K, Luft FC, Sharma AM . Resistin gene expression in human adipocytes is not related to insulin resistance. Obes Res 2002; 10: 1–5.
McTernan CL, McTernan PG, Harte AL, Levick PL, Barnett AH, Kumar S . Resistin, central obesity, and type 2 diabetes. Lancet 2002; 359: 46–47.
Coppack SW, Yost TJ, Fisher RM, Eckel RH, Miles JM . Periprandial systemic and regional lipase activity in normal humans. Am J Physiol 1996; 270: E718–E722.
Karpe F, Olivecrona T, Olivecrona G, Samra JS, Summers LK, Humphreys SM, Frayn KN . Lipoprotein lipase transport in plasma: role of muscle and adipose tissues in regulation of plasma lipoprotein lipase concentrations. J Lipid Res 1998; 39: 2387–2393.
Pond CM, Mattacks CA . Interactions between adipose tissue around lymph nodes and lymphoid cells in vitro. J Lipid Res 1995; 36: 2219–2231.
Pond CM . Physiological specialisation of adipose tissue. Prog Lipid Res 1999; 38: 225–248.
Pond CM, Mattacks CA . In vivo evidence for the involvement of the adipose tissue surrounding lymph nodes in immune responses. Immunol Lett 1998; 63: 159–167.
Mattacks CA, Pond CM . Interactions of noradrenalin and tumour necrosis factor alpha, interleukin 4 and interleukin 6 in the control of lipolysis from adipocytes around lymph nodes. Cytokine 1999; 11: 334–346.
Boulton KL, Hudson DU, Coppack SW, Frayn KN . Steroid hormone interconversions in human adipose tissue in vivo. Metabolism 1992; 41: 556–559.
Katz JR, Mohamed-Ali V, Wood PJ, Yudkin JS, Coppack SW . An in vivo study of the cortisol–cortisone shuttle in subcutaneous abdominal adipose tissue. Clin Endocrinol 1999; 50: 63–68.
Katz JR . Production and interconversion of steroid hormones in obesity and polycystic ovary syndrome [MD]. University of London, London; 1999.
Frühbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA . The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab 2001; 280: E827–E847.
Trayhurn P, Beattie JH . Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc 2001; 60: 329–339.
Sinha MK, Sturis J, Ohannesian J, Magosin S, Stephens T, Heiman ML, Polonsky KS, Caro JF . Ultradian oscillations of leptin secretion in humans. Biochem Biophys Res Commun 1996; 228: 733–738.
Licinio J, Negrao AB, Mantzoros C, Kaklamani V, Wong ML, Bongiorno PB, Mulla A, Cearnal L, Veldhuis JD, Flier JS, McCann SM, Gold PW . Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women. Proc Natl Acad Sci USA 1998; 95: 2541–2546.
Licinio J, Mantzoros C, Negrao AB, Cizza G, Wong ML, Bongiorno PB, Chrousos GP, Karp B, Allen C, Flier JS, Gold PW . Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nat Med 1997; 3: 575–579.
Ahmad AM, Guzder R, Wallace AM, Thomas J, Fraser WD, Vora JP . Circadian and ultradian rhythm and leptin pulsatility in adult GH deficiency: effects of GH replacement. J Clin Endocrinol Metab 2001; 86: 3499–3506.
Hücking K, Hamilton-Wessler M, Ellmerer M, Bergman RN . Burst-like control of lipolysis by the sympathetic nervous system in vivo. J Clin Invest 2003; 111: 257–264.
Getty L, Panteleon AE, Mittelman SD, Dea MK, Bergman RN . Rapid oscillations in omental lipolysis are independent of changing insulin levels in vivo. J Clin Invest 2000; 106: 421–430.
Muntzel MS, Morgan DA, Mark AL, Johnson AK . Intracerebroventricular insulin produces nonuniform regional increases in sympathetic nerve activity. Am J Physiol 1994; 267: R1350–R1355.
Cox HS, Kaye DM, Thompson JM, Turner AG, Jennings GL, Itsiopoulos C, Esler MD . Regional sympathetic nervous activition after a large meal in humans. Clin Sci 1995; 89: 145–154.
Samra J, Giles S, Summers L, Evans R, Arner P, Humphreys S, Clark M, Frayn K . Peripheral fat metabolism during infusion of an exogenous triacylglycerol emulsion. Int J Obes Relat Metab Disord 1998; 22: 806–812.
Evans K, Clark ML, Frayn KN . Effects of an oral and intravenous fat load on adipose tissue and forearm lipid metabolism. Am J Physiol 1999; 276: E241–E248.
We thank the Wellcome Trust for support of our studies on the integrative physiology of human adipose tissue.
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Frayn, K., Karpe, F., Fielding, B. et al. Integrative physiology of human adipose tissue. Int J Obes 27, 875–888 (2003). https://doi.org/10.1038/sj.ijo.0802326
- adipose tissue
- integrative physiology
- fat balance
- blood flow
- autonomic innervation
- secretory activity
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