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The sympathetic nervous system in white adipose tissue regulation

Published online by Cambridge University Press:  05 March 2007

D. Vernon Rayner
D. Vernon Rayner*
Affiliation:
Molecular Physiology Group, Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, UK
*
Corresponding Author: Dr Vernon Rayner, fax +44 1224 716686, email [email protected]
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Abstract

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Sympathetic stimulation has long been recognized to mobilise fatty acids from white adipose tissue. However, it is now apparent that adipose tissue is not only concerned with energy storage as fat, but is a major endocrine and secretory organ. This change has resulted from the identification of leptin as a hormone of energy balance secreted by white adipose tissue. The sympathetic system is a key regulator of leptin production in white fat. Sympathomimetic amines, cold exposure or fasting (which lead to sympathetic stimulation of white fat), decrease ob gene expression in the tissue and leptin production. On the other hand, sympathetic blockade often increases circulating leptin and ob gene expression, and it is postulated that the sympathetic system has a tonic inhibitory action on leptin synthesis. In rodents this action is through stimulation of b3-adrenoceptors. The adrenal medulla (as opposed to the direct sympathetic innervation) has been thought to play only a minor role in the catecholaminergic regulation of white adipose tissue. However, in rodents responses of the leptin system to adrenergic blockade vary with the method used. Changes in leptin and ob gene expression are considerably less using methods of blockade that only effect the terminal adrenergic innervation, rather than medullary secretions as well. Stimulation of the leptin system increases sympathetic activity and hence metabolic activity in many tissues. As well as leptin, other (but not all) secretions from white adipose tissue are subject to sympathetic regulation. In obesity the sympathetic sensitivity of adipose tissue is reduced and this factor may underlie the dysregulation of leptin production and other adipose tissue secretions.

Keywords

Sympathetic nervous systemWhite adipose tissueLeptin productionβ-AdrenoceptorsObesity
Type
Symposium on ‘New perspectives on adipose tissue function’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 3 , August 2001 , pp. 357 - 364
Copyright
Copyright © The Nutrition Society 2001

References

Ahima, RS, Prabakaran, D, Mantzoros, C, Qu, DO, Lowell, B, Maratosflier, E & Flier, JS (1996) Role of leptin in the neuroendocrine response to fasting. Nature 382, 250–252.CrossRefGoogle ScholarPubMed
Arch, JRS & Wilson, S (1996) β3-Adrenoceptors and the regulation of metabolism in adipose tissues. Biochemical Society Transactions 24, 412–418.CrossRefGoogle Scholar
Arita, Y, Kihara, S, Ouchi, N, Takahashi, M, Maeda, K, Miyagawa, J, Hotta, K, Shimomura, I, Nakamura, T, Miyaoka, K, Kuriyama, H, Nishida, M, Yamashita, S, Okubo, K, Matsubara, K, Muraguchi, M, Ohmoto, Y, Funahashi, T & Matsuzawa, Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochemical and Biophysical Research Communications 257, 79–83.CrossRefGoogle ScholarPubMed
Bartness, TJ & Bamshad, M (1998) Innervation of mammalian white adipose tissue: implications for the regulation of total body fat. American Journal of Physiology 275, R1399–R1411.Google ScholarPubMed
Berkowitz, DE, Brown, D, Lee, KM, Emala, C, Palmer, D, An, Y & Breslow, M (1998) Endotoxin-induced alteration in the expression of leptin and beta(3)-adrenergic receptor in adipose tissue. American Journal of Physiology 274, E992–E997.Google Scholar
Bertin, R, Triconnet, M & Portet, R (1985) Effects of cold acclimation on the activity of lipoprotein lipase in adipose tissues of genetically obese Zucker rats. Comparative Biochemistry and Physiology 81B, 797–801.Google Scholar
Bing, C, Pickavance, L, Wang, Q, Frankish, H, Trayhurn, P & Williams, G (1997) Role of hypothalamic neuropeptide Y neurons in the defective thermogenic response to acute cold exposure in fatty Zucker rats. Neuroscience 80, 277–284.Google Scholar
Boden, G, Chen, X, Mozzoli, M & Ryan, I (1996) Effect of fasting on serum leptin in normal human subjects. Journal of Clinical Endocrinology and Metabolism 81, 3419–3423.Google ScholarPubMed
Boss, O, Samec, S, Dulloo, A, Seydoux, J, Muzzin, P & Giacobino, JP (1997) Tissue-dependent upregulation of rat uncoupling protein-2 expression in response to fasting or cold. FEBS Letters 412, 111–114.CrossRefGoogle ScholarPubMed
Boss, O, Samec, S, Kuhne, F, Bijlenga, P, Assimacopoulos-Jeannet, F, Seydoux, J, Giacobino, JP & Muzzin, P (1998) Uncoupling protein-3 expression in rodent skeletal muscle is modulated by food intake but not by changes in environmental temperature. Journal of Biological Chemistry 273, 5–8.CrossRefGoogle Scholar
Breslow, MJ, An, Y & Berkowitz, DE (1997) Beta-3 adrenoceptor (beta-3AR) expression in leptin treated Ob/Ob mice. Life Sciences 61, 59–64.Google Scholar
Campfield, LA, Smith, FJ, Guisez, Y, Devos, R & Burn, P (1995) Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 269, 546–549.Google Scholar
Cannon, WB (1929) Bodily Changes in Pain, Hunger, Fear and Rage. New York and London: D. Appleton and Co.CrossRefGoogle Scholar
Carlson, SH, Shelton, J, White, CR & Wyss, JM (2000) Elevated sympathetic activity contributes to hypertension and salt sensitivity in diabetic obese Zucker rats. Hypertension 35, 403–408.Google Scholar
Cinti, S (1999) The Adipose Organ. Milan: Editrice Kurtis s.r.l.Google Scholar
Cinti, S (2001) The adipose organ: morphological perspectives of adipose tissues. Proceedings of the Nutrition Society 60, 319–328.CrossRefGoogle ScholarPubMed
Collins, S, Daniel, KW, Petro, AE & Surwit, RS (1997) Strain-specific response to beta(3)-adrenergic receptor agonist treatment of diet-induced obesity in mice. Endocrinology 138, 405–413.CrossRefGoogle ScholarPubMed
Collins, S, Daniel, KW & Rohlfs, EM (1999) Depressed expression of adipocyte beta-adrenergic receptors is a common feature of congenital and diet-induced obesity in rodents. International Journal of Obesity 23, 669–677.CrossRefGoogle ScholarPubMed
Collins, S, Daniel, KW, Rholfs, EM, Ramkumar, V, Taylor, IL & Gettys, TW (1994) Impaired expression and functional activity of the β3- and β1-adrenergic receptors in adipose tissue of congenitally obese (C57B1/6J ob/ob) mice. Molecular Endocrinology 8, 518–527.Google Scholar
Collins, S, Kuhn, CM, Petro, AE, Swick, AG, Chrunyk, BA & Surwit, RS (1996) Role of leptin in fat regulation. Nature 380, 677.Google Scholar
Deshaies, Y, Géloën, A, Paulin, A, Marette, A & Bukowiecki, LJ (1993) Tissue-specific alterations in lipoprotein lipase activity in the rat after chronic infusion of isoproterenol. Hormone and Metabolic Research 25, 13–16.CrossRefGoogle ScholarPubMed
Dunbar, JC, Hu, YG & Lu, HQ (1997) Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes 46, 2040–2043.CrossRefGoogle ScholarPubMed
Emilsson, V, Summers, RJ, Hamilton, S, Liu, YL & Cawthorne, MA (1998) The effects of the beta(3)-adrenoceptor agonist BRL 35135 on UCP isoform mRNA expression. Biochemical and Biophysical Research Communications 252, 450–454.CrossRefGoogle Scholar
Enocksson, S, Shimizu, M & Lönnqvist, F (1995) Demonstration of an in vivo functional β3a-adrenoceptor in man. Journal of Clinical Investigation 95, 2239–2245.Google Scholar
Faintrenie, G & Geloen, A (1996) Alpha-1 adrenergic regulation of lactate production by white adipocytes. Journal of Pharmacology and Experimental Therapeutics 277, 235–238.Google ScholarPubMed
Faloia, E, Giacchetti, G & Mantero, F (2000) Obesity and hypertension. Journal of Endocrinological Investigation 23, 54–62.CrossRefGoogle ScholarPubMed
Fleury, C, Neverova, M, Collins, S, Raimbault, S, Champigny, O, Levimeyrueis, C, Bouillaud, F, Seldin, MF, Surwit, RS, Ricquier, D & Warden, CH (1997) Uncoupling protein-2: A novel gene linked to obesity and hyperinsulinemia. Nature Genetics 15, 269–272.CrossRefGoogle ScholarPubMed
Frederich, RC, Kahn, BB, Peach, MJ & Flier, JS (1992) Tissue-specific nutritional regulation of angiotensinogen in adipose tissue. Hypertension 19, 339–344.CrossRefGoogle ScholarPubMed
Garofalo, MAR, Kettelhut, IC, Roselino, JES & Migliorini, RH (1996) Effect of acute cold exposure on norepinephrine turnover rates in rat adipose tissue. Journal of the Autonomic Nervous System 60, 206–208.Google Scholar
Giacobino, JP (1996) Role of the b(3)-adrenoceptor in the control of leptin expression. Hormone and Metabolic Research 28, 633–637.CrossRefGoogle Scholar
Gilgen, A, Maickel, RP, Nikoulina, SE & Brodie, BB (1962) Essential role of catecholamines in the mobilisation of free fatty acids and glucose after exposure to cold. Life Sciences 1, 709–715.CrossRefGoogle ScholarPubMed
Gomez-Ambrosi, J, Fruhbeck, G & Martinez, JA (1999) Leptin, but not a beta(3)-adrenergic agonist, upregulates muscle uncoupling protein-3 messenger RNA expression: short-term thermogenic interactions. Cellular and Molecular Life Sciences 55, 992–997.Google Scholar
Gottschling-Zeller, H, Birel, M & Hauner, H (1999) Effect of β-adrenoceptor agonists on plasminogen activator inhibitor-1 secretion from human adipocytes in suspension culture. International Journal of Obesity 23, Suppl. 5, S25.Google Scholar
Halleux, CM, Declerck, PJ, Tran, SL, Detry, R & Brichard, SM (1999) Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines. Journal of Clinical Endocrinology and Metabolism 84, 4097–4105.Google ScholarPubMed
Haque, MS, Minokoshi, Y, Hamai, M, Iwai, M, Horiuchi, M & Shimazu, T (1999) Role of the sympathetic nervous system and insulin in enhancing glucose uptake in peripheral tissues after intrahypothalamic injection of leptin in rats. Diabetes 48, 1706–1712.CrossRefGoogle ScholarPubMed
Hardie, LJ, Rayner, DV, Holmes, S & Trayhurn, P (1996) Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. Biochemical and Biophysical Research Communications 223, 660–665.Google Scholar
Haynes, WG, Morgan, DA, Walsh, SA, Mark, AL & Sivitz, WI (1997) Receptor-mediated regional sympathetic nerve activation by leptin. Journal of Clinical Investigation 100, 270–278.CrossRefGoogle ScholarPubMed
Himms-Hagen, J (1999) Physiological roles of the leptin endocrine system: Differences between mice and humans. Critical Reviews in Clinical and Laboratory Science 36, 575–655.CrossRefGoogle ScholarPubMed
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
Hoffstedt, J, Arner, P, Hellers, G & Lönnqvist, 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.Google Scholar
Jones, BH, Standridge, MK, Taylor, JW & Moustaid, N (1997) Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control. American Journal of Physiology 273, R236–R242.Google ScholarPubMed
Kamora, S, Burcelin, R, Halaas, JL, Friedman, JM & Charron, MJ (1997) Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389, 374–377.CrossRefGoogle Scholar
Kersten, S, Mandarino, LJ, Tan, NS, Escher, P, Metzger, D, Chambon, P, Gonzalez, FJ, Desvergne, B & Wahli, W (2000) Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. Journal of Biological Chemistry 275, 28488–28493.Google Scholar
Kolaczynski, JW, Ohannesian, JP, Considine, RV, Marco, CC & Caro, JF (1996) Response of leptin to short-term and prolonged overfeeding in humans. Journal of Clinical Endocrinology and Metabolism 81, 4162–4165.Google ScholarPubMed
Kopin, IJ (1989) Plasma levels of catecholamines and dopamine-b-hydroxylase. In Handbook of Experimental Pharmacology, Catecholamines II, pp. 211–275 [Trendelenberg, U and Weiner, N, editors]. Berlin: Springer Verlag.Google Scholar
Lafontan, M & Berlan, M (1993) Fat cell adrenergic receptors and the control of white and brown fat cell function. Journal of Lipid Research 34, 1057–1091.Google Scholar
Lansberg, L & Young, JB (1978) Fasting, feeding and regulation of the sympathetic nervous system. New England Journal of Medicine 298, 1295–1301.CrossRefGoogle Scholar
Licinio, J, Mantzoros, C, Negrao, AB, Cizza, G, Wong, ML, Bongiorno, PB, Chrousos, GP, Karp, B, Allen, C, Flier, JS & Gold, PW (1997) Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nature Medicine 3, 575–579.Google Scholar
Liu, Q, Bai, C, Chen, F, Wang, RP, Macdonald, T, Gu, MC, Zhang, Q, Morsy, MA & Caskey, CT (1998) Uncoupling protein-3: a muscle-specific gene upregulated by leptin in ob/ob mice. Gene 207, 1–7.CrossRefGoogle ScholarPubMed
Mercer, JG, Moar, KM & Hoggard, N (1998) Localization of leptin receptor (Ob-R) messenger ribonucleic acid in the rodent hindbrain. Endocrinology 139, 29–34.Google Scholar
Migliorini, RH, Garofalo, MAR & Kettelhut, IC (1997) Increased sympathetic activity in rat white adipose tissue during prolonged fasting. American Journal of Physiology 272, R656–R661.Google Scholar
Minokoshi, Y, Haque, MS & Shimazu, T (1999) Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats. Diabetes 48, 287–291.Google Scholar
Mohamed-Ali, V, Bulmer, K, Clarke, D, Goodrick, S, Coppack, SW & Pinkney, JH (2000) beta-Adrenergic regulation of proinflammatory cytokines in humans. International Journal of Obesity 24, S154–S155.CrossRefGoogle ScholarPubMed
Mohamed-Ali, V, Pinkney, JH & Coppack, SW (1998) Adipose tissue as an endocrine and paracrine organ. International Journal of Obesity 22, 1145–1158.Google Scholar
Moinat, M, Deng, CJ, Muzzin, P, Assimacopoulos-Jeannet, F, Seydoux, J, Dulloo, AG & Giacobino, JP (1995) Modulation of obese gene expression in rat brown and white adipose tissues. FEBS Letters 373, 131–134.CrossRefGoogle Scholar
Montague, CT, Prins, JB & Sanders, I (1998) Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 47, 1384–1391.Google Scholar
Muzzin, P, Revelli, J-P, Kuhne, F, Gocayne, JD, McCombie, WR, Venter, JC, Giacobino, J-P, & Fraser, CM (1991) An adipose tissue-specific β-adrenergic receptor. Molecular cloning and down-regulation in obesity. Journal of Biological Chemistry 266, 24053–24058.Google Scholar
Niijima, A (1998) Afferent signals from leptin sensors in the white adipose tissue of the epididymis, and their reflex effect in the rat. Journal of the Autonomic Nervous System 73, 19–25.CrossRefGoogle ScholarPubMed
Orban, Z, Remaley, AT, Sampson, M, Trajanoski, Z & Chrousos, GP (1999) The differential effect of food intake and beta-adrenergic stimulation on adipose-derived hormones and cytokines in man. Journal of Clinical Endocrinology and Metabolism 84, 2126–2133.Google Scholar
Pellymounter, MA, Cullen, MJ, Baker, MB, Hecht, R, Winter, D, Boone, T & Collins, F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540–543.Google Scholar
Picard, F, Richard, D, Timofeeva, E & Deshaies, Y (2000) Abnormal insulin and beta-adrenergic modulation of lipoprotein lipase during refeeding after prolonged fasting in the Zucker rat. Diabetologia 43, 866–874.Google Scholar
Rayner, DV, Simon, E, Duncan, JS & Trayhurn, P (1998) Hyperleptinaemia in mice induced by administration of the tyrosine hydroxylase inhibitor a-methyl-p-tyrosine. FEBS Letters 429, 395–398.Google Scholar
Rebuffé-Scrive, M (1991) Neuroregulation of adipose tissue: Molecular and hormonal mechanisms. International Journal of Obesity 15, 83–86.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 prostoglandin E2. Metabolism 40, 990–996.Google Scholar
Ricquier, D & Bouillaud, F (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochemical Journal 345, 161–179.CrossRefGoogle ScholarPubMed
Rumantir, MS, Vaz, M, Jennings, GL, Collier, G, Kaye, DM, Seals, DR, Wiesner, GH, BrunnerLaRocca, HP & Esler, MD (1999) Neural mechanisms in human obesity-related hypertension. Journal of Hypertension 17, 1125–1133.CrossRefGoogle ScholarPubMed
Samad, F, Uysal, KT, Wiesbrock, SM, Pandey, M, Hotamisligil, GS & Loskutoff, DJ (1999) Tumor necrosis factor alpha is a key component in the obesity-linked elevation of plasminogen activator inhibitor 1. Proceedings of the National Academy of Sciences USA 96, 6902–6907.Google Scholar
Satoh, N, Ogawa, Y, Katsuura, G, Numata, Y, Tsuji, T, Hayase, M, Ebihara, K, Masuzaki, H, Hosoda, K, Yoshimasa, Y & Nakao, K (1999) Sympathetic activation of leptin via the ventromedial hypothalamus – Leptin-induced increase in catecholamine secretion. Diabetes 48, 1787–1793.Google Scholar
Savontaus, E, Rouru, J, Boss, O, Huupponen, R & Koulu, M (1998) Differential regulation of uncoupling proteins by chronic treatments with beta(3)-adrenergic agonist BRL 35135 and metformin in obese fa/fa Zucker rats. Biochemical and Biophysical Research Communications 246, 899–904.Google Scholar
Scarpace, PJ & Matheny, M (1998) Leptin induction of UCP1 gene expression is dependent on sympathetic innervation. American Journal of Physiology 275, E259–E264.Google ScholarPubMed
Scarpace, PJ, Matheny, M, Pollock, BH & Tumer, N (1997) Leptin increases uncoupling protein expression and energy expenditure. American Journal of Physiology 273, E226–E230.Google Scholar
Scarpace, PJ, Nicolson, M & Matheny, M (1998) UCP2, UCP3 and leptin gene expression: modulation by food restriction and leptin. Journal of Endocrinology 159, 349–357.CrossRefGoogle ScholarPubMed
Schoeller, DA, Cella, LK, Sinha, MK & Caro, JF (1997) Entrainment of the diurnal rhythm of plasma leptin to meal timing. Journal of Clinical Investigation 100, 1882–1887.Google Scholar
Sennitt, MV, Kaumann, AJ, Molenaar, P, Beeley, LJ, Young, PW, Kelly, J, Chapman, H, Henson, SM, Berge, JM, Dean, DK, Kotecha, NR, Morgan, HK, Rami, HK, Ward, RW, Thompson, M, Wilson, S, Smith, SA, Cawthorne, MA, Stock, MJ & Arch, JR (1998) The contribution of classical (beta 1/2-) and atypical beta-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel beta3-adrenoceptor agonists of differing selectivities. Journal of Pharmacology and Experimental Therapeutics 285, 1084–1095.Google Scholar
Sinha, MK, Ohannesian, JP, Heiman, ML, Kriauciunas, A, Stephens, TW, Magosin, S, Marco, C & Caro, JF (1996) Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. Journal of Clinical Investigation 97, 1344–1347.Google Scholar
Sivitz, WI, Fink, BD, Morgan, DA, Fox, JM, Donohoue, PA & Haynes, WG (1999) Sympathetic inhibition, leptin, and uncoupling protein subtype expression in normal fasting rats. American Journal of Physiology 277, E668–E677.Google Scholar
Steppan, CM, Bailey, ST, Bhat, S, Brown, EJ, Banerjee, RR, Wright, CM, Patel, HR, Ahima, RS & Lazar, MA (2001) The hormone resistin links obesity to diabetes. Nature 409, 307–312.Google Scholar
Tate, KM, Briend-Sutren, M-M, Emorine, LJ, Delavier-Klutchko, C, Marullo, S & Strosberg, AD (1991) Expression of three human β-adrenergic-receptor subtypes in transfected chinese hamster ovary cells. European Journal of Biochemistry 196, 357–361.Google Scholar
Tavernier, G, Barbe, P, Galitzky, J, Berlan, M, Caput, D, Lafontan, M & Langin, D (1996) Expression of β3-adrenoceptors with low lipolytic action in human subcutaneous white adipose tissue. Journal of Lipid Research 37, 87–97.Google Scholar
Thomas, SA & Palmiter, RD (1997) Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature 387, 94–97.Google Scholar
Trayhurn, P & Beattie, JH (2001) Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proceedings of the Nutrition Society 60, 329–339.Google Scholar
Trayhurn, P, Duncan, JS & Rayner, DV (1995a) Acute cold-induced suppression of ob (obese) gene expression in white adipose tissue of mice: Mediation by the sympathetic system. Biochemical Journal 311, 729–733.Google Scholar
Trayhurn, P, Duncan, JS, Rayner, DV & Hardie, LJ (1996) Rapid inhibition of ob gene expression and circulating leptin levels in lean mice by the beta 3-adrenoceptor agonists BRL 35135A and ZD2079. Biochemical and Biophysical Research Communications 228, 605–610.Google Scholar
Trayhurn, P, Duncan, JS, Wood, AM & Beattie, JH (2000) Metallothionein gene expression and secretion by white adipose tissue. American Journal of Physiology 279, R2329–R2335.Google Scholar
Trayhurn, P, Thomas, MEA, Duncan, JS & Rayner, DV (1995b) Effects of fasting and refeeding on ob gene expression in white adipose tissue of lean and obese (ob/ob) mice. FEBS Letters 368, 488–490.Google Scholar
Young, JB & Lansberg, L (1977) Suppression of sympathetic nervous system during fasting. Science 196, 1473–1475.Google Scholar
Young, JB, Rosa, RM & Landsberg, L (1984) Dissociation of sympathetic nervous system and adrenal medullary responses. American Journal of Physiology 247, E35–E40.Google Scholar
Zhang, Y, Proenca, R, Maffei, M, Barone, M, Leopold, L & Friedman, JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432.Google Scholar
Zhou, YT, Shimabukuro, M, Koyama, K, Lee, Y, Wang, MY, Trieu, F, Newgard, CB & Unger, RH (1997) Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation. Proceedings of the National Academy of Sciences USA 94, 6386–6390.Google Scholar