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Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance

  • Peter J. Havel (a1)


Adipose tissue performs complex metabolic and endocrine functions. Among the endocrine products produced by adipose tissue are tumour necrosis factor α, interleukin 6, acylation-stimulating protein and leptin. The present review will focus primarily on mechanisms regulating leptin production and leptin action, and the implications of this regulation in the control of energy balance. Leptin acts in the central nervous system where it interacts with a number of hypothalamic neuropeptide systems to regulate feeding behaviour and energy expenditure. The presence of extreme obesity in animals and human subjects with mutations of the leptin gene or the leptin receptor demonstrates that normal leptin production and action are critical for maintaining energy balance. Insulin is the major regulator of leptin production by adipose tissue. Insulin infusions increase circulating leptin concentrations in human subjects. Plasma leptin levels are markedly decreased in insulin-deficient diabetic rodents, and the low leptin levels contribute to diabetic hyperphagia. Based on in vitro studies, the effect of insulin to stimulate leptin production appears to involve increased glucose metabolism. Blockade of glucose transport or glycolysis inhibits leptin expression and secretion in isolated adipocytes. Evidence suggests that anaerobic metabolism of glucose to lactate does not stimulate leptin production. Alterations in insulin-mediated glucose metabolism in adipose tissue are likely to mediate the effects of energy restriction to decrease, and refeeding to increase, circulating leptin levels. Changes in glucose metabolism may also explain the observation that high-fat meals lower 24 h circulating leptin levels relative to high-carbohydrate meals in human subjects, suggesting a mechanism that may contribute to the effects that high-fat diets have in promoting increased energy intake, weight gain and obesity. The decreased circulating leptin observed during energy restriction is related to increased sensations of hunger in human subjects. Thus, decreases in leptin during energy-restricted weight-loss regimens may contribute to the strong propensity for weight regain. A better understanding of the precise mechanisms regulating leptin production and leptin action may lead to new approaches for managing obesity.

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Corresponding author

Corresponding author: Dr Peter J. Havel, fax +1 530 752–1297, email


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Ahima, RS, Prabakaran, D, Mantzoros, C, Qu, D, Lowell, B, Maratos-Flier, E & Flier, JS (1996) Role of leptin in the neuroendocrine response to fasting. Nature 382, 250252.
Ahren, B (1999) Plasma leptin and insulin in C57BI/6J mice on a high-fat diet: relation to subsequent changes in body weight. Acta Physiologica Scandinavica 165, 233240.
Ahren, B & Havel, PJ (1999a) Leptin increases circulating glucose, insulin and glucagon via sympathetic neural activation in fasted mice. International Journal of Obesity and Related Metabolic Disorders 23, 660665.
Ahren, B & Havel, PJ (1999b) Leptin inhibits insulin secretion induced by cellular cAMP in INS-1 cells. American Journal of Physiology 277, R959R966.
Ahren, B, Mansson, S, Gingerich, RL & Havel, PJ (1997) Regulation of plasma leptin in mice: Influence of age, high-fat diet and fasting. American Journal of Physiology 273, R113R120.
Barash, IA, Cheung, CC, Weigle, DS, Ren, H, Kabigting, EB, Kuijper, JL, Clifton, DK & Steiner, RA (1996) Leptin is a metabolic signal to the reproductive system. Endocrinology 137, 31443147.
Barzilai, N, Wang, J, Massilon, D, Vuguin, P, Hawkins, M & Rossetti, L (1997) Leptin selectively decreases visceral adiposity and enhances insulin action. Journal of Clinical Investigation 100, 31053110.
Blevins, JE, Havel, PJ & Gietzen, DW (1999) Injections of leptin into the anterior piriform cortex inhibit food intake in rats. Nutritional Neuroscience 2, 357367.
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, 34193423.
Bornstein, SR, Uhlmann, K, Haidan, A, Ehrhart-Bornstein, M & Scherbaum, WA (1997) Evidence for a novel peripheral action of leptin as a metabolic signal to the adrenal gland: leptin inhibits cortisol release directly. Diabetes 46, 12351238.
Bouloumie, A, Drexler, HC, Lafontan, M & Busse, R (1998) Leptin, the product of Ob gene, promotes angiogenesis. Circulation Research 83, 10591066.
Bray, GA & Popkin, BM (1998) Dietary fat intake does affect obesity! American Journal of Clinical Nutrition 68, 11571173.
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, 546549.
Cao, GY, Considine, RV & Lynn, RB (1997) Leptin receptors in the adrenal medulla of the rat. American Journal of Physiology 273, E448E452.
Caro, JF, Kolaczynski, JW, Nyce, MR, Ohannesian, JP, Opentanova, I, Goldman, WH, Lynn, RB, Zhang, PL, Sinha, MK & Considine, RV (1996a) Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 348, 159161.
Caro, JR, Sinha, MK, Kolaczynski, JW, Zhang, PL & Considine, RV (1996b) Leptin: the tale of an obesity gene. Diabetes 45, 14551461.
Chehab, FF, Lim, ME & Lu, R (1996) Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nature Genetics 12, 318320.
Chehab, FF, Mounzih, K, Lu, R & Lim, ME (1997) Early onset of reproductive function in normal female mice treated with leptin. Science 275, 8890.
Chen, H, Charlat, O, Tartaglia, LA, Woolf, EA, Weng, X, Ellis, SJ, Lakey, ND, Culpepper, J, Moore, KJ, Breitbart, RE, Duyk, GM, Tepper, RI & Morgenstern, JP (1996a) Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84, 491495.
Chen, G, Koyama, K, Yuan, X, Lee, Y, Zhou, YT, O'Doherty, R, Newgard, CB & Unger, RH (1996b) Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy. Proceedings of the National Academy of Sciences 93, 1479514799.
Chessler, SD, Fujimoto, WY, Shofer, JB, Boyko, EJ & Weigle, DS (1998) Increased plasma leptin levels are associated with fat accumulation in Japanese Americans. Diabetes 47, 239243.
Cheung, CC, Thornton, JE, Kuijper, JL, Weigle, DS, Clifton, DK & Steiner, RA (1997) Leptin is a metabolic gate for the onset of puberty in the female rat. Endocrinology 138, 855858.
Cianflone, K, Maslowska, M & Sniderman, AD (1999) Acylation stimulating protein (ASP), an adipocyte autocrine: new directions. Seminars in Cell and Development Biology 10, 3141.
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 (1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392, 398401.
Coleman, DL (1973) Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 9, 294298.
Coleman, DL & Hummel, KP (1969) Effects of parabiosis of normal with genetically diabetic mice. American Journal of Physiology 217, 12981304.
Considine, RV, Considine, EL, Williams, CJ, Hyde, TM & Caro, JF (1996a) The hypothalamic leptin receptor in humans: identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations. Diabetes 45, 992994.
Considine, RV, Sinha, MK, Heiman, ML, Kríauciunas, A, Stephens, TW, Nyce, MR, Ohannesian, JP, Marco, CC, McKee, LJ, Bauer, TL & Caro, JF (1996b) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New England Journal of Medicine 334, 292295.
Cunningham, MJ, Clifton, DK & Steiner, RA (1999) Leptin's actions on the reproductive axis: perspectives and mechanisms. Biology of Reproduction 60, 216222.
Cusin, I, Sainsbury, A, Doyle, P, Rohner-Jeanrenaud, F & Jeanrenaud, B (1995) The ob gene and insulin: a relationship leading to clues to the understanding of obesity. Diabetes 44, 14671470.
Dagogo-Jack, S, Fanelli, C, Paramore, D, Brothers, J & Landt, M (1996) Plasma leptin and insulin relationships in obese and nonobese humans. Diabetes 45, 695698.
Doring, H, Schwarzer, K, Nuesslein-Hildesheim, B & Schmidt, I (1998) Leptin selectively increases energy expenditure of food-restricted lean mice. International Journal of Obesity and Related Metabolic Disorders 22, 8388.
Dubuc, GR, Phinney, SD, Stern, JS & Havel, PJ (1998) Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women. Metabolism 47, 429434.
Echwald, SM, Sorensen, TD, Sorensen, TI, Tybjaerg-Hansen, A, Andersen, T, Chung, WK, Leibel, RL & Pedersen, O (1997) Amino acid variants in the human leptin receptor: lack of association to juvenile onset obesity. Biochemical and Biophysical Research Communications 233, 248252.
Emilsson, V, Liu, YL, Cawthorne, MA, Morton, NM & Davenport, M (1997) Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes 46, 313316.
Emond, M, Schwartz, GJ, Ladenheim, EE & Moran, TH (1999) Central leptin modulates behavioral and neural responsivity to CCK. American Journal of Physiology 276, R1545-R1549.
Farooqi, IS, Jebb, SA, Langmack, G, Lawrence, E, Cheetham, CH, Prentice, AM, Hughes, IA, McCamish, MA & O'Rahilly, S (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. New England Journal of Medicine 341, 879884.
Fujioka, K, Patane, J, Lubina, J & Lau, D (1999) CSF leptin levels after exogenous administration of recombinant methionyl human leptin. Journal of the American Medical Association 282, 15171518.
Funahashi, T, Nakamura, T, Shimomura, I, Maeda, K, Kuriyama, H, Takahashi, M, Arita, Y, Kihara, S & Matsuzawa, Y (1999) Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity. Internal Medicine 38, 202206.
Gainsford, T, Willson, TA, Metcalf, D, Handman, E, McFarlane, C, Ng, A, Nicola, NA, Alexander, WS & Hilton, DJ (1996) Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proceedings of the National Academy of Sciences 93, 1456414568.
Greenberg, AS, Fujioka, K, Heymsfield, S, Lau, D, Lubina, J, Patane, J & McCamish, M (1999) Clinical effects of leptin in obesity. Proceedings of the 81st Annual Meeting of the Endocrine Society, San Diego, CA, pp 5354, S54–S63 Abstr (
Grinspoon, SK, Askari, H, Landt, ML, Nathan, DM, Schoenfeld, DA, Hayden, DL, Laposata, M, Hubbard, J & Klibanski, A (1997) Effects of fasting and glucose infusion on basal and overnight leptin concentrations in normal-weight women. American Journal of Clinical Nutrition 6, 13521356.
Haffner, SM, Mykkanen, LA, Gonzalez, CC & Stern, MP (1998) Leptin concentrations do not predict weight gain: the Mexico City Diabetes Study. International Journal of Obesity and Related Metabolic Disorders 22, 695699.
Halaas, JL, Boozer, C, Blair-West, J, Fidahusein, N, Denton, DA & Friedman, JM (1997) Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proceedings of the National Academy of Sciences 94, 88788883.
Halaas, JL, Gajiwala, KS, Maffei, M, Cohen, SL, Chait, BT, Rabinowitz, D, Lallone, RL, Burley, SK & Friedman, JM (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269, 543546.
Hardie, LJ, Guilhot, N & Trayhurn, P (1996a) Regulation of leptin production in cultured mature white adipocytes. Hormone and Metabolic Research 28, 685689.
Hardie, LJ, Rayner, DV, Holmes, S & Trayhurn, P (1996b) 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, 660665.
Harris, RB & Martin, RJ (1984) Specific depletion of body fat in parabiotic partners of tube-fed obese rats. American Journal of Physiology 247, R380-R386.
Havel, PJ (1997) Glucose infusion increases circulating leptin in proportion to adipose stores in rhesus monkeys. Journal of Experimental Endocrinology and Diabetes 105, 3738.
Havel, PJ (1998) Leptin production and action: relevance to energy balance in humans. American Journal of Clinical Nutrition 67, 355356.
Havel, PJ (1999) Mechanisms regulating leptin production: implications for the control of energy balance. American Journal of Clinical Nutrition 70, 305306.
Havel, PJ, Busch, BL, Curry, DL, Johnson, PR, Dallman, MF & Stern, JS (1996a) Predominately glucocorticoid agonist actions of RU-486 in young specific-pathogen-free Zucker rats. American Journal of Physiology 271, R710-R717.
Havel, PJ, Kasim-Karakas, S, Dubuc, GR, Mueller, WM & Phinney, SD (1996b) Gender differences in plasma leptin concentrations. Nature Medicine 2, 949950.
Havel, PJ, Kasim-Karakas, S, Mueller, W, Johnson, PR, Gingerich, RL & Stern, JS (1996c) Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: Effects of dietary fat content and sustained weight loss. Journal of Clinical Endocrinology and Metabolism 81, 44064413.
Havel, PJ, Larsen, PJ & Cameron, JL (2000) Control of food intake. In Neuroendocrinology in Physiology and Medicine, pp. 335352 [Conn, PM and Freeman, ME, editors]. Totowa, NJ: Humana Press.
Havel, PJ & Pelleymounter, M (1997) Acute adrenergically-mediated increases of circulating glucose and lactate after leptin administration in rhesus monkeys. Obesity Research 5, Suppl. 1, 17S.
Havel, PJ, Townsend, R, Chaump, L & Teff, K (1999) High fat meals reduce 24 h circulating leptin concentrations in women. Diabetes 48, 334341.
Havel, PJ, Uriu-Hare, JY, Liu, T, Stanhope, KL, Stern, JS, Keen, CL & Ahren, B (1998) Rapid and marked decreases of circulating leptin in streptozotocin diabetic rats: Reversal by insulin. American Journal of Physiology 274, R1482-R1491.
Haynes, WG, Morgan, DA, Walsh, SA, Mark, AL & Sivitz, WI (1997) Receptor-mediated regional sympathetic nerve activation by leptin. Journal of Clinical Investigation 100, 270278.
Heymsfield, SB, Greenberg, AS, Fujioka, K, Dixon, RM, Kushner, R, Hunt, T, Lubina, JA, Patane Self, B, Hunt, P & Mc, Camish (1999) Recombinant leptin for weight loss in lean and obese adults: a randomized, controlled, dose-escalation trial. Journal of the American Medical Association 282, 15681575.
Hill, JO, Lin, D, Yakubu, F & Peters, JC (1992) Development of dietary obesity in rats: influence of amount and composition of dietary fat. International Journal of Obesity 16, 321333.
Horton, TJ, Drougas, H, Brachey, A, Reed, GW, Peters, JC & Hill, JO (1995) Fat and carbohydrate overfeeding: different effects on energy storage. American Journal of Clinical Nutrition 62, 1929.
Hotamisligil, GS (1999) The role of TNFalpha and TNF receptors in obesity and insulin resistance.Journal of Internal Medicine 245, 621625.
Jacob, RJ, Dziura, J, Medwick, MB, Leone, P, Caprio, S, During, M, Shulman, GI & Sherwin, RS (1997) The effect of leptin is enhanced by microinjection into the ventromedial hypothalamus. Diabetes 46, 150152.
Keim, NL, Stern, JS & Havel, PJ (1998) Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. American Journal of Clinical Nutrition 68, 794801.
Kennedy, AG (1953) The role of the fat depot in the hypothalamic control of food intake in the rat. Proceedings of the Royal Society of London 140, 578592.
Kieffer, TJ, Heller, RS, Leech, CA, Holz, GG & Habener, JF (1997) Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. Diabetes 46, 10871093.
Kolaczynski, JW, Considine, RV, Ohannesian, J, Marco, C, Opentanova, I, Nyce, MR, Myint, M & Caro, JF (1996a) Responses of leptin to short-term fasting and refeeding in humans: a link with ketogenesis but not ketones themselves. Diabetes 45, 15111515.
Kolaczynski, JW, Nyce, MR, Considine, RV, Boden, G, Nolan, JJ, Henry, R, Mudaliar, SR, Olefsky, J & Caro, JF (1996b) Acute and chronic effects of insulin on leptin production in humans: Studies in vivo and in vitro. Diabetes 45, 699701.
Kolaczynski, JW, Ohannesian, JP, Considine, RV, Marco, CC & Caro, JF (1996c) Response of leptin to short-term and prolonged overfeeding in humans. Journal of Clinical Endocrinology and Metabolism 81, 41624165
Kopp, W, Blum, WF, Ziegler, A, Mathiak, K, Lubbert, H, Herpertz, S, Deter, HC & Hebebrand, J (1998) Serum leptin and body weight in females with anorexia and bulimia nervosa. Hormone and Metabolic Research 30, 52725275.
Landt, M, Gingerich, RL, Havel, PJ, Mueller, WM, Schoner, B, Hale, JE & Heiman, ML (1998) Radioimmunoassay of rat leptin: sexual dimorphism reversed from humans. Clinical Chemistry 44, 565570.
Laughlin, GA & Yen, SSC (1997) Hypoleptinemia in women athletes: absence of diurnal rhythm with amenorrhea. Journal of Clinical Endocrinology and Metabolism 82, 318321.
Leroy, P, Dessolin, S, Villageois, P, Moon, BC, Friedman, JM, Ailhaud, G & Dani, C (1996) Expression of ob gene in adipose cells: regulation by insulin. Journal of Biological Chemistry 271, 23652368.
Levin, N, Nelson, C, Gurney, A, Vandlen, R & de Sauvage, F (1996) Decreased food intake does not completely account for adiposity reduction after ob protein infusion. Proceedings of the National Academy of Sciences 93, 17261730.
Loffreda, S, Yang, SQ, Lin, HZ, Karp, CL, Brengman, ML, Wang, DJ, Klein, AS, Bulkley, GB, Bao, C, Noble, PW, Lane, MD & Diehl, AM (1998) Leptin regulates proinflammatory immune responses. FASEB Journal 12, 5765.
Lord, GM, Matarese, G, Howard, JK, Baker, RJ, Bloom, SR & Lechler, RI (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394, 897901.
Maffei, M, Halaas, J, Ravussin, E, Pratley, RE, Lee, GH, Zhang, Y, Fei, H, Lallone, R, Ranganathan, S, Kern, PA & Friedman, JM (1995) Leptin levels in human and rodents: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Medicine 1, 11551161.
Malmstrom, R, Taskinen, MR, Karonen, SL & Yki-Harvinen, H (1996) Insulin increases plasma leptin concentrations in normal subjects and in patients with NIDDM. Diabetologia 39, 993996.
Matkovic, V, Ilich, JZ, Badenhop, NE, Skugor, M, Clairmont, A, Klisovic, D & Landoll, JD (1997) Gain in body fat is inversely related to the nocturnal rise in serum leptin level in young females. Journal of Clinical Endocrinology and Metabolism 82, 13681372.
Matson, CA, Wiater, MF, Kuijper, JL & Weigle, DS (1997) Synergy between leptin and cholecystokinin (CCK) to control daily caloric intake. Peptides 18, 12751278.
Matsuoka, N, Ogawa, Y, Hosoda, K, Matsuda, J, Masuzaki, H, Miyawaki, T, Azuma, N, Natsui, K, Nishimura, H, Yoshimasa, Y, Nishi, S, Thompson, DB & Nakao, K (1997) Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity. Diabetologia 40, 12041210.
Medina, EA, Stanhope, KL, Mizuno, TM, Mobbs, CV, Gregoire, F, Hubbard, NE, Erickson, KL & Havel, PJ (1999) Effects of tumour necrosis factor alpha (TNFα) on leptin secretion and gene expression: relationship to changes of glucose metabolism in isolated rat adipocytes. International Journal of Obesity and Related Metabolic Disorders 23, 896903.
Mohamed-Ali, V, Pinkney, JH & Coppack, SW (1998) Adipose tissue as an endocrine and paracrine organ. International Journal of Obesity and Related Metabolic Disorders 22, 11451158.
Montague, CT, Farooqi, IS, Whitehead, JP, Soos, MA, Rau, H, Wareham, NJ, Sewter, CP, Digby, JE, Mohammed, SN, Hurst, JA, Cheetham, CH, Earley, AR, Barnett, AH, Prins, JB & O'Rahilly, S (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387, 903908.
Mueller, WM, Gregoire, FM, Stanhope, KL, Mobbs, CV, Mizuno, TM, Warden, CH, Stern, JS & Havel, PJ (1998) Evidence that glucose metabolism regulates leptin secretion from cultured adipocytes. Endocrinology 139, 551558.
O'Donnell, CP, Schaub, CD, Haines, AS, Berkowitz, DE, Tankersley, CG, Schwartz, AR & Smith, PL (1999) Leptin prevents respiratory depression in obesity. American Journal of Respiratory and Critical Care Medicine 159, 14771484.
Pelleymounter, MA, Cullen, MJ, Baker, MB, Hecht, R, Winters, D, Boone, T & Collins, F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540543.
Ravussin, E, Pratley, RE, Maffei, M, Wang, H, Friedman, JM, Bennett, PH & Bogardus, C (1996) Relatively low plasma leptin concentrations precede weight gain in Pima Indians. Nature Medicine 2, 238240.
Rebrin, K, Steil, GM, Getty, L & Bergman, RN (1995) Free fatty acid as a link in the regulation of hepatic glucose output by peripheral insulin. Diabetes 44, 10381045.
Rentsch, J & Chiesi, M (1996) Regulation of ob gene mRNA levels in cultured adipocytes. FEBS Letters 379, 5559.
Rosenbaum, M, Nicolson, M, Hirsch, J, Heymsfield, SB, Gallagher, D, Chu, F & Leibel, RL (1996) Effects of gender, body composition, and menopause on plasma concentrations of leptin. Journal of Clinical Endocrinology and Metabolism 81, 34243427.
Rossetti, L, Massillon, D, Barzilai, N, Vuguin, P, Chen, W, Hawkins, M, Wu, J & Wang, J (1997) Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action. Journal of Biological Chemistry 272, 2775827763.
Saad, MF, Khan, A, Sharma, A, Michael, R, Riad-Gabriel, MG, Boyadjian, R, Jinagouda, SD, Steil, GM & Kamdar, V (1998a) Physiological insulinemia acutely modulates plasma leptin. Diabetes 47, 544549.
Saad, MF, Riad-Gabriel, MG, Khan, A, Sharma, A, Michael, R, Jinagouda, SD, Boyadjian, R & Steil, GM (1998b) Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity. Journal of Clinical Endocrinology and Metabolism 83, 24532459.
Saladin, R, De Vos, P, Guerre-Millo, M, Leturque, A, Girard, J, Staels, B & Auwerx, J (1995) Transient increase in obese gene expression after food intake or insulin administration. Nature 377, 527529.
Satoh, N, Ogawa, Y, Katsuura, G, Hayase, M, Tsuji, T, Imagawa, K, Yoshimasa, Y, Nishi, S, Hosoda, K & Nakao, K (1997) The arcuate nucleus as a primary site of satiety effect of leptin in rats. Neuroscience Letters 224, 149152.
Scarpace, PJ & Matheny, M (1998) Leptin induction of UCP1 gene expression is dependent on sympathetic innervation. American Journal of Physiology 275, E259-E264.
Scarpace, PJ, Matheny, M, Pollock, BH & Tumer, N (1997) Leptin increases uncoupling protein expression and energy expenditure. American Journal of Physiology 273, E226-E230.
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, 18821887.
Schwartz, MW, Baskin, DG, Kaiyala, KJ & Woods, SC (1999) Model for the regulation of energy balance and adiposity by the central nervous system. American Journal of Clinical Nutrition 69, 584596.
Schwartz, MW, Figlewicz, DP, Baskin, DG, Woods, SC & Porte, D (1994) Insulin and the central regulation of energy balance. In Monographs 2; The Endocrine Pancreas, Insulin Action, and Diabetes. Endocrine Reviews, pp. 81113 [Negro Vilar, A and Underwood, LE, editors]. Bethesda, MD: The Endocrine Society.
Schwartz, MW, Peskind, E, Raskind, M, Boyko, EJ & Porte, D Jr (1996a) Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nature Medicine 2, 589593.
Schwartz, MW, Seeley, RJ, Campfield, LA, Burn, P & Baskin, DG (1996b) Identification of targets of leptin action in rat hypothalamus. Journal of Clinical Investigation 98, 11011106.
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 (1998) Biological action of leptin as an angiogenic factor. Science 281, 16831686.
Sindelar, DK, Chu, CA, Rohlie, M, Neal, DW, Swift, LL & Cherrington, AD (1997) The role of fatty acids in mediating the effects of peripheral insulin on hepatic glucose production in the conscious dog. Diabetes 46, 187196.
Sindelar, DK, Havel, PJ, Seeley, RJ, Wilkinson, CW, Woods, SC & Schwartz, MW (1999) Low plasma leptin levels contribute to diabetic hyperphagia in rats. Diabetes 48, 12751280.
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, 13441347.
Sivitz, WI, Walsh, S, Morgan, D, Donohue, P, Haynes, W & Leibel, RL (1998) Plasma leptin in diabetic and insulin-treated diabetic and normal rats. Metabolism 47, 584591.
Sonnenberg, GE, Krakower, GR, Hoffmann, RG, Maas, DL, Hennes, MMI & Kissebah, AH (1996) Plasma leptin concentrations: Effects of extended fasting and stepwise increases in glucose infusions. Obesity Research 4, 13S Abstr.
Strobel, A, Issad, T, Camoin, L, Ozata, M & Strosberg, AD (1998) A leptin missense mutation associated with hypogonadism and morbid obesity. Nature Genetics 18, 213215.
Surwit, RS, Petro, AE, Parekhand, P & Collins, S (1997) Low plasma leptin in response to dietary fat in diabetes- and obesity-prone mice. Diabetes 46, 15161520.
Tang-Christensen, M, Havel, PJ, Jacobs, RR, Larsen, PJ & Cameron, JL (1999a) Central administration of leptin inhibits food intake and activates the sympathetic nervous system in rhesus macaques. Journal of Clinical Endocrinology and Metabolism 84, 711717.
Tang-Christensen, M, Holst, JJ, Hartmann, B & Vrang, N (1999b) The arcuate nucleus is pivotal in mediating the anorectic effects of centrally administered leptin. NeuroReport 10, 11831187.
Tartaglia, LA (1997) The leptin receptor. Journal of Biological Chemistry 272, 60936096.
Tartaglia, LA, Dembski, M, Weng, X, Deng, N, Culpepper, J, Devos, R, Richards, GJ, Campfield, LA, Clark, FT & Deeds, J (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83, 12631271.
Tataranni, PA & Ravussin, E (1997) Effect of fat intake on energy balance. Annals of the New York Academy of Sciences 819, 3743.
Trayhurn, P, Duncan, JS, Hoggard, N & Rayner, DV (1998) Regulation of leptin production: a dominant role for the sympathetic nervous system? Proceedings of the Nutrition Society 57, 413419.
Tremblay, A, Plourde, G, Despres, JP & Bouchard, C (1998) Impact of dietary fat content and fat oxidation on energy intake in humans. American Journal of Clinical Nutrition 49, 799805.
Utriainen, R, Malmstrom, R, Makimattila, S & Yki-Jarvinen, H (1996) Supraphysiological hyperinsulinemia increases plasma leptin concentrations after 4 h in normal subjects. Diabetes 45, 13641366.
Van Heek, M, Compton, DS, France, CF, Tedesco, RP, Fawzi, AB, Graziano, MP, Sybertz, EJ, Strader, CD & Davis, HR Jr (1997) Diet-induced obese mice develop peripheral, but not central, resistance to leptin. Journal of Clinical Investigation 99, 385390.
Wabitsch, M, Jensen, PB, Blum, WF, Christoffersen, CT, Englaro, P, Heinze, E, Rascher, W, Teller, W, Tornqvist, H & Hauner, H (1996) Insulin and cortisol promote leptin production in cultured human fat cells. Diabetes 45, 14351438.
Wang, J, Liu, R, Hawkins, M, Barzilai, N & Rossetti, L (1998) A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature 393, 684688.
Weigle, DS, Duell, PB, Connor, WE, Steiner, RA, Soules, MR & Kuijper, JL (1997) Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. Journal of Clinical Endocrinology and Metabolism 82, 561565.
Weigle, DS, Hutson, AM, Kramer, JM, Fallon, MG, Lehner, JM, Lok, S & Kuijper, JL (1998a) Leptin does not fully account for the satiety activity of adipose tissue-conditioned medium. American Journal of Physiology 275, R976-R985.
Weigle, DS, Selfridge, LE, Schwartz, MW, Seeley, RJ, Cummings, DE, Havel, PJ, Kuijper, JL & Beltran del Rio, H (1998b) Elevated free fatty acids induce uncoupling protein 3 expression in muscle: a potential explanation for the effect of fasting. Diabetes 147, 298302.
West, DB, Fey, D & Woods, SC (1984) Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. American Journal of Physiology 246, R776-R787.
Widdowson, PS, Upton, R, Buckingham, R, Arch, J & Williams, G (1997) Inhibition of food response to intracerebroventricular injection of leptin is attenuated in rats with diet-induced obesity. Diabetes 46, 17821785.
Wilson, BE, Meyer, GE, Cleveland JC, Jr & Weigle, DS (1990) Identification of candidate genes for a factor regulating body weight in primates. American Journal of Physiology 259, R1148-R1155.
Wiman, B & Hamsten, A (1990) The fibrinolytic enzyme system and its role in the etiology of thromboembolic disease. Seminars in Thrombosis and Hemostasis 16, 207216.
Wisse, BE, Campfield, LA, Marliss, EB, Morais, JA, Tenenbaum, R & Gougeon, R (1999) Effects of prolonged moderate and severe energy restriction and refeeding on plasma leptin concentrations in obese women. American Journal of Clinical Nutrition 70, 321330.
Woods, SC, Chavez, M, Park, CR, Riedy, C, Kaiyala, K, Richardson, RD, Figlewicz, DP, Schwartz, MW, Porte, D & Seeley, RJ (1996) The evaluation of insulin as a metabolic signal influencing behavior via the brain. Neuroscience and Biobehavior Reviews 20, 139144.
Woods, SC, Seeley, RJ, Porte, D Jr & Schwartz, MW (1998) Signals that regulate food intake and energy homeostasis. Science 280, 13781383.
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, 425432.


Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance

  • Peter J. Havel (a1)


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