Regulation of Food Intake and Body Weight

  • Michael W. Schwartz
  • Denis G. Baskin
  • Karl J. Kaiyala
  • Steven C. Woods
  • Daniel PorteJr.
Part of the Contemporary Biomedicine book series (CB, volume 15)


The concept that body adiposity is homeostatically regulated is rooted in the observation that most mammals maintain a stable level of adiposity over long time periods. Since the amount of the body’s energy that is stored as adipose tissue is determined by the net difference between caloric intake and expenditure, this observation suggested to early investigators that energy intake and expenditure must be balanced with some precision (1,2). Rejecting the notion that maintenance of energy balance could be achieved by random processes, investigators proposed many decades ago that food intake and adipose mass are coupled elements of a homeostatic regulatory loop. This view was supported by the discovery that changes in energy expenditure and adiposity elicit compensatory changes in caloric intake. In 1953, these observations led Kennedy (3) to propose that changes in body adiposity are signaled to the brain, thereby modifying the drive to eat. Subsequently, other investigators postulated that a change in adiposity also elicits adaptive changes in energy expenditure, a view now supported by a large body of literature (1,4) that includes studies in humans (5). Through these mechanisms, adiposity-proportional afferent signals were proposed to enable the brain to restore adipose mass to its regulated level. Obesity was viewed, therefore, as a disorder arising from impaired body weight regulation, rather than a lack of dietary restraint.


Food Intake Brown Adipose Tissue Arcuate Nucleus Body Adiposity Circulate Insulin Level 
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  1. 1.
    Keesey RE. A set-point theory of obesity. In: Handbook of Eating Disorders: Psychology, and Treatment of Obesity, Anorexia and Bulimia. Brownell KD, Foreyt JP, eds. New York: Basic Books, pp. 63–87, 1986.Google Scholar
  2. 2.
    Stallone DD, Stunkard AJ. The regulation of body weight: evidence and clinical implications. Ann Behav Med 1991; 13: 220–230.Google Scholar
  3. 3.
    Kennedy GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond (Biol) 1953; 140: 579–592.Google Scholar
  4. 4.
    Keesey RE. Physiological regulation of body weight and the issue of obesity. Med Clin North Am 1989; 73: 15–27.PubMedGoogle Scholar
  5. 5.
    Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. New Engl J Med 1995; 332: 621–628.PubMedGoogle Scholar
  6. 6.
    Bolles RC Some functionalist thoughts about regulation. In: Analysis of Motivational Processes. Toates FM, Halliday PR, eds. London: Academic, pp. 63–75, 1980.Google Scholar
  7. 7.
    Zhang Y, Proenca R, Maffie M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 435–432.Google Scholar
  8. 8.
    Campfield LA, Smith FJ, Gulsez Y, Devos R, Bum R Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995; 269: 546–549.PubMedGoogle Scholar
  9. 9.
    Halaas JL, Gajiwala KS, Maffel 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.PubMedGoogle Scholar
  10. 10.
    Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269: 540–543.PubMedGoogle Scholar
  11. 11.
    Kaiyala KJ, Woods SC, Schwartz MW. New model for the regulation of energy balance by the central nervous system. Am J Clin Nutr 1995; 62: 11235–1134S.Google Scholar
  12. 12.
    Bernstein IL, Lotter EC, Kulkosky PJ. Effect of force-feeding upon basal insulin levels in rats. Proc Soc Exp Biol Med 1975; 150: 546–548.PubMedGoogle Scholar
  13. 13.
    Harris RBS, Kasser TR, Martin RJ. Dynamics of recovery of body composition after overfeeding, food restriction or starvation of mature female rates. J Nutr 1986; 116: 2536–2546.PubMedGoogle Scholar
  14. 14.
    Keys BA, Henschel A, Mickelson O, Taylor HL. The Biology of Human Starvation. The University of Minnesota Press, 1950.Google Scholar
  15. 15.
    Gamer DM, Wooley SC. Confronting the failure of behavioral and dietary treatments for obesity. Clin Psych Rev 1991; 11 (6): 729–780.Google Scholar
  16. 16.
    Keesey RE, Corbett SW. Adjustments in daily energy expenditure to caloric restriction and weight loss by adult obese and lean zucker rats. Int J Obes 1990; 14: 1079–1084.PubMedGoogle Scholar
  17. 17.
    Weigle DS, Sande KJ, Iverus PH, Monsen ER, Brunzell JD. Weight loss leads to marked decrease in non-resting energy expenditure in ambulatory human subjects. Metabolism 1988; 37: 930–936.PubMedGoogle Scholar
  18. 18.
    Cohn C, Joseph D. Influence of body weight and body fat on appetite of “normal” lean and obese rats. Yale J Biol 1962; 34: 598–607.PubMedGoogle Scholar
  19. 19.
    Harris RBS, Martin RJ. Changes in lipogenesis and lipolysis associated with recovery from reversible obesity in mature female rats. Proc Soc Exp Biol Med 1989; 191: 82–89.PubMedGoogle Scholar
  20. 20.
    Wilson BE, Meyer GE, Cleveland JC, Weigle DC. Identification of candidate genes for a factor regulating body weight in primates. Am J Physiol 1990; 259: R1148 - R1155.PubMedGoogle Scholar
  21. 21.
    Levitsky DA, Faust I, Glassman M. The ingestion of food and the recovery of body weight following fasting in the naive rat. Physiol Behav 1976; 17: 575–580.PubMedGoogle Scholar
  22. 22.
    Obersanik F, Levitsky DA. Weight gain through overeating and return to normal without undereating. Fed Proc 1984; 43: 1057.Google Scholar
  23. 23.
    Gasnier A, Mayer A. Recherche sur la regulation de la nurtrition. II. Mecanismes regulateurs de la nutrition chez le lapin domestique. Ann Physiol Physiochim Biol 1939; 15: 157–185.Google Scholar
  24. 24.
    Woo, R, Garrow JS, Pi-Sunyer FX. Effects of increased physical activity on voluntary food intake in lean women. Metab Clin Exp 1985; 34: 836–841.PubMedGoogle Scholar
  25. 25.
    Mayer J, Roy P, Mitra KP. Relationship between caloric intake, body weight, and physical work: studies in an industrial male population in West Bengal. Am J Clin Nutr 1956; 4: 169–175.Google Scholar
  26. 26.
    Mayer J, Thomas DW. Regulation of food intake and obesity. Science 1967; 156: 328–337.PubMedGoogle Scholar
  27. 27.
    Woo R, Garrow JS, Pi-Sunyer FX. Voluntary food intake during prolonged exercise in obese women. Am J Clin Nutr 1982; 36: 478–484.PubMedGoogle Scholar
  28. 28.
    Schwartz RS, Shuman WP, Larson V, Cain KC, Fellingham GW, Beard JC, Kahn SE, Stratton JR, Cerqueira MD, Itamar BA. The effect of intensive endurance exercise training on body fat distribution in young and older men. Metabolism 1991; 40: 545–551.PubMedGoogle Scholar
  29. 29.
    Wilmore JH. Body composition in sport and exercise. Med Sci Sports Exerc 1983; 15: 21–31.PubMedGoogle Scholar
  30. 30.
    Ballor DL, Keesey RE. A meta-analysis of the factors affecting exercise-induced changes in body mass, fat mass and fat-free mass in males and females. Int J Obes 1991; 15: 717–726.PubMedGoogle Scholar
  31. 31.
    Smith MS. Lactation alters neuropeptide-Y and proopiomelanocortin gene expression in the arcuate nucleus of the rat. Endocrinology 1993; 133: 1258–1265.PubMedGoogle Scholar
  32. 32.
    Liebelt RA, Ichinoe S, Nicholson N. Regulatory influences of adipose tissue on food intake and body weight. Ann NY Acad Sci 1965; 131: 559–582.PubMedGoogle Scholar
  33. 33.
    Faust IM, Johnson PR, Hirsch J. Adipose tissue regeneration following lipectomy. Science 1977; 197: 391–393.PubMedGoogle Scholar
  34. 34.
    Hervey GR. The effects of lesions in the hypothalamus in parabiotic rats. J Physiol (Lond) 1959; 145: 336–352.Google Scholar
  35. 35.
    Coleman DL, Hummel KP. Effects of parabiosis of normal with genetically diabetic mice. Am J Physiol 1969; 217: 1298–1304.Google Scholar
  36. 36.
    Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Dibetologia 1973; 9: 294–298.Google Scholar
  37. 37.
    Masuzaki H, Ogawa Y, Isse N, Satoh N, Okazaki T, Shigemoto M, Mori K, Tamura N, Hosoda K, Yoshimas Y, et al. Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes 1195; 44: 855–888.Google Scholar
  38. 38.
    Maffei M, Fei H, Lee GH, Dani C, Leory P, Zhang Y, Proenca R, Negrel R, Ailhaud G, Friedman JM. Increased expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus. Proc. Natl. Acad. Sci. USA 1995; 92: 6957–6960.PubMedGoogle Scholar
  39. 39.
    Murakami T, Shima K. Cloning of rat obese cDNA and its expression in obese rats. Biochem Biophys Res Commun 1995; 209: 944–952.PubMedGoogle Scholar
  40. 40.
    Ogawa Y, Masuzaki H, Isse N, Mori K, Shigemoto M, Satoh N, Tamura N, Hosoda K, Yoshimasa Y, Jingami H, Kawada T, Nakao K. Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese zucker fatty (fa/fa) rats. J Clin Invest 1995; 96: 1647–1652.PubMedGoogle Scholar
  41. 41.
    Funahashi T, Shimomura I, Hiraoka H, Arai T, Takahashi M, Nakamura T, Nozaki S, Yamashita S, Takemura K, Tokunaga K, Matsuzawa Y. Enhanced expression of rat obese (ob) gene in adipose tissues of ventromedial hypothalamus (VMH)-lesioned rats. Biochem Biophys Res Commun 1995; 211: 469–475.PubMedGoogle Scholar
  42. 42.
    Lonnqvist F, Amer P, Nordfors L, Schalling M. Overexpression of the obest (ob) gene in adipose tissue of human obese subjects. Nature Med 1995; 1: 950–953.PubMedGoogle Scholar
  43. 43.
    Hamilton BS, Paglia D, Kwan AYM, Deitel M. Increased obese mRNA expression in omental fat cells from massively obese humans. Nature Med 1995; 1: 953–955.PubMedGoogle Scholar
  44. 44.
    Considine RV, Considine EL, Williams CJ, Nyce MR, Magosin SA, Bauer TL, Rosato EL, Col-berg J, Caro JF. Evident against either a premature stop condon or the absence of obese gene mRNA in human obesity. J Clin Invest 1995; 96: 2720–2728.Google Scholar
  45. 45.
    Frederich RC, Lollmann B, Hamann A, Napolitano-Rosen A, Kahn BB, Lowell BB, Flier JS. Expression of ob mRNA and its encoded protein in rodents. L Clin Invest 1995; 96: 1658–1663.Google Scholar
  46. 46.
    MacDougald OA, Hwang C-S, Fan H, Lane MD. Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3–L1 adipocytes. Proc Natl Acad Sci 1995; 92: 9034–9037.PubMedGoogle Scholar
  47. 47.
    Flier JS. The adipocyte: storage depot or node on the energy information superhighway? Cell 1995; 80: 15–18.PubMedGoogle Scholar
  48. 48.
    Saladin R, DeVos P, Guerre-Millo M, Leturque A, Girad J, Staels B, Auwerx J. Transient increase in obese gene expression after food intake or insulin administration. Nature 1995; 377: 527–529.PubMedGoogle Scholar
  49. 49.
    Smith SR, Ramsay TG, Harris RB. Ob mRNA level is responsive to insulin status in diabetic rats. Obes Res 1995; 3: 399s.Google Scholar
  50. 50.
    Weigle DS, Bukowski TR, Foster DC, Holderman S, Kramer JM, Lasser G, Lofton-Day CE, Prunkard DE, Raymond C, Kuijper JL. Recombinant ob protein reduces feeding and body weight in the ob/ob mouse. J Clin Invest, 1995; 96 (4): 2065–2070.PubMedGoogle Scholar
  51. 51.
    Stephens TW, Baslnski M, Bristow PK, Bue-Valleskey JM, Burgett SG, Craft L, Hale J, Hoffmann J, Halung HM, Kriauclunas A, MacKellar W, Rostack J, Schoner PRB, Smith D, Tinsley FC, Zhang X, Helman M. The role of neuropeptide Y In the antiobesity action of the obese gene product. Nature 1995; 377: 530–532.PubMedGoogle Scholar
  52. 52.
    Schwartz MW, Baskin DG, Bukowski TR, Kuijper JL, Foster D, Lasser G, Prunkard DE, Porte D, Woods SC, Seeley RJ, Weigle DS. Specificity of OB protein action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes, 1995; 45 (4): 531–535.Google Scholar
  53. 53.
    Stanley BG, Kyrkouli SE, Lampert S, Leibowitz SF. Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 1986; 7: 1189–1192.PubMedGoogle Scholar
  54. 54.
    Zarjevski N, Cusin I, Vetter R, Rohner-Jeanrenaud F, Jeanrenaud B. chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endocrinology 1993; 133: 1753–1758.PubMedGoogle Scholar
  55. 55.
    Wilding JPH, Gilbey SG, Bailey CJ, Batt RAL, Williams G, Ghatei MA, Bloom SR. Increased neuropeptide-Y messenger ribonucleic acid (mRNA) and decreased neurotensin mRNA in the hypothalamus of the obese (ob/ob) mouse. Endocrinology 1993; 132: 1939–1944.PubMedGoogle Scholar
  56. 56.
    Bagdade JD, Bierman EL, Porte D Jr. The significance of basal insulin levels in the evaluation of the insulin response to glucose in diabetic and nondiabetic subjects. J Clin Invest 1967; 46: 1549–1557.PubMedGoogle Scholar
  57. 57.
    Woods SC, Porte D Jr. Insulin and the set-point regulation of body weight. In: Hunger: Basic Mechanisms and Clinical Implications. Novin D, Bray GA, Wyrwichka W, eds. New York: Raven, pp. 273–280, 1976.Google Scholar
  58. 58.
    Polonsky KS, Given BD, Hirsch L, Shapiro ET, Tillil H, Beebe C, Galloway JA, Frank BH, Karrison T, Van-Cauter E. Quantitative study of insulin secretion and clearance in normal and obese subjects. J Clin Invest 1988; 81: 435–441.PubMedGoogle Scholar
  59. 59.
    Baura G, Foster D, Porte D, Jr, Kahn SE, Bergman RN, Cobelli C, Schwartz MW. Saturable transport of insulin from plasma into the central nervous system of dogs in vivo: a mechanism for regulated insulin delivery to the brain. J Clin Invest 1993; 92: 1824–1830.PubMedGoogle Scholar
  60. 60.
    Unger JW, Livingston JN, Moss AM. Insulin receptors in the central nervous system: localization, signalling mechanisms and functional aspects. Prog Neurobiol 1991; 36: 343–362.PubMedGoogle Scholar
  61. 61.
    Baskin DG, Marks JL, Schwartz MW, Figewicz DP, Woods SC, Porte D Jr. Insulin and insulin receptors in the brain in relation to food intake and body weight. In: Endocrine and Nutritional Control of Basic Biological Functions. Lehner H, Murison R, Weiner H, Hellhammer D, Beyer J, eds. Stuttgart: Hogrefe & Huber, pp. 202–222, 1990.Google Scholar
  62. 62.
    Baskin DG, Wilcox BJ, Figlewicz DP, Dorsa DM. Insulin and insulin-like growth factors in the CNS. Trends Neurosci 1988; 11: 107–111.PubMedGoogle Scholar
  63. 63.
    Schwartz MW, Figlewicz DP, Baskin DG, Woods SC, Porte D Jr. Insulin in the brain: a hormonal regulator of energy balance. Endocr Rev 1992; 13: 387–414.PubMedGoogle Scholar
  64. 64.
    Schwartz MW, Sipols AJ, Marks JL, Sanacora G, White JD, Scheurinck A, Kahn SE, Baskin DG, Woods SC, Figlewicz DP, Porte D Jr. Inhibition of hypothalamic neuropeptide Y gene expression by insulin. Endocrinology 1992; 130: 3608–3616.PubMedGoogle Scholar
  65. 65.
    Sipols AJ, Baskin DG, Schwartz MW. Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. Diabetes 1995; 44: 147–151.PubMedGoogle Scholar
  66. 66.
    Schwartz MW, Figlewicz DP, Woods SC, Porte D, Baskin DG. Insulin, neuropeptide Y and food intake. Ann NYAcad Sci 1993; 692: 60–71.Google Scholar
  67. 67.
    Schwartz MW, Marks J, Sipols AJ, Baskin DG, Woods SC, Kahn SE, Porte D Jr. Central insulin administration reduces neuropeptide Y mRNA expression in the arcuate nucleus of food-deprived lean (Fa/Fa) but not obese (fa/fa) Zucker rats. Endocrinology 1991; 128: 2645–2647.PubMedGoogle Scholar
  68. 68.
    Woods SC, Stein LJ, McKay LD, Porte D Jr. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 1979; 282: 503–505.PubMedGoogle Scholar
  69. 69.
    Brief DJ, Davis JD. Reduction of food intake and body weight by chronic intraventricular insulin infusion. Brain Res Bull 1984; 12: 571–575.PubMedGoogle Scholar
  70. 70.
    Arase K, Eisler JS, Shargill NS, York DA, Bray GA. Intracerebroventricular infusions of 3-OHB and insulin in a rat model of dietary obesity. Am J Physiol 1988; 255: R974 - R981.PubMedGoogle Scholar
  71. 71.
    Ikeda H, West DB, Pustek JJ, Figlewicz DP, Greenwood MRC, Porte D Jr, Woods SC. Intraventricular insulin reduces food intake and body weight of lean but not obese Zucker rats. Appetite 1986; 7: 381–386.PubMedGoogle Scholar
  72. 72.
    Foster LA, Ames NK, Emery RS. Food intake and serum insulin responses to intraventricular infusions of insulin and IGF-I. Physiol Behav 1991; 50 (4): 745–749.PubMedGoogle Scholar
  73. 73.
    Polonsky KS, Given BD, VanCauter E. Twenty-four hour profiles and pulatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 1988; 81: 442–448.PubMedGoogle Scholar
  74. 74.
    King GL, Johnson SM. Receptor-mediated transport of insulin across endothelial cells. Science 1985; 227: 1583–1586.PubMedGoogle Scholar
  75. 75.
    Pardrige WM. Receptor-mediated peptide transport through the blood-brain barrier. Endocr Rev 1986; 7: 314–330.Google Scholar
  76. 76.
    Strubbe JH, Mein CG. Increased feeding in response to bilateral injection of insulin antibodies in the VMH. Physiol Behav 1977; 19: 309–313.PubMedGoogle Scholar
  77. 77.
    McGowan MK, Andrews KM, Kelly J, Grossman SP. Effects of chronic intrahypothalamic infusion of insulin on food intake and diurnal meal patterning in the rat. Behav Neurosci 1990; 104: 373–385.PubMedGoogle Scholar
  78. 78.
    Chavez M, Seeley RJ, Woods SC. A comparison between effects of intraventricular insulin and intraperitoneal lithium chloride on three measures sensitive to emetic agents. Behav Neurosci 1995; 109: 547–550.PubMedGoogle Scholar
  79. 79.
    Chavez M, Kaiyala KJ, Madden L, Schwartz MW, Woods SC. Intraventricular insulin and the level of maintained body weight in rats. Behav Neurosci 1995; 109 (3): 528–531.PubMedGoogle Scholar
  80. 80.
    Grossman SP. The role of glucose, insulin and glucagon in the regulation of food intake and body weight. Neurosci Biobehav Rev 1986; 10: 295–315.PubMedGoogle Scholar
  81. 81.
    Vanderweele DA, Haraczkiewicz E, Van Itallie TB. Elevated insulin and satiety in obese and normal weight rats. Appetite 1982; 3: 99–109.PubMedGoogle Scholar
  82. 82.
    The DCCT Study Group. Weight gain associated with intensive therapy in the diabetes control and complications trial. Diabetes Care 1988; 11: 567–573.Google Scholar
  83. 83.
    Schwartz MW, Figlewicz DP, Baskin DG, Woods SC, Porte D Jr. Insulin and the central regulation of energy balance: update 1994. Endocr Rev Monog 1994; 2: 109–113.Google Scholar
  84. 84.
    Seeley RJ, Matson CA, Chavez M, Woods SC, Schwartz MW. Behavioral and hypothalamic responses to involuntary positive energy balance. Obes Res 1995; 3: 373s.Google Scholar
  85. 85.
    Dallman MF, Strack AM, Akana SF, Bradbury MJ, Hanson EF, Scribner KA, Smith M. Feast and famine: critical role of glucocorticoids with insulin in daily energy flow. Front Neuroendocrinol 1993; 14: 303–347.PubMedGoogle Scholar
  86. 86.
    Green PK, Wilkinson CW, Woods SC. Intraventricular corticosterone increases the rate of body weight gain in underweight adrenalectomized rats. Endocrinology 1992; 130: 269–275.PubMedGoogle Scholar
  87. 87.
    Strack AM, Sebastian RJ, Schwartz MW, Dallman MF. Glucocorticoids and insulin: reciprocal signals for energy balance. Am J Physiol 1995; 268: 142–149.Google Scholar
  88. 88.
    Bray GA, Fisler J, York DA. Neuroendocrine control of the development of obesity: understanding gained from studies of experimental animal models. Front Neuroendocrinol 1990; 11: 128–181.Google Scholar
  89. 89.
    Gosink PD, Chavez M, Green PK, Woods SC, Figlewicz DP, Wilkinson CW, Baskin DG, Schwartz MW. Central insulin administration lowers body weight via a glucocorticoid-sensitive mechanism. Clin Res 1992; 40: 55A.Google Scholar
  90. 90.
    Bai FL, Yamno M, Shiotani Y, Emson PC, Smith AD, Powell JP, Tohyama M. An arucato-paraventricular and dorsomedial hypothalamic neuropeptide Y-containing system which lacks noradrenalin in the rat. Brain Res 1985; 331: 172–175.PubMedGoogle Scholar
  91. 91.
    Sahu A, Kalra PS, Kalra SP. Food deprivation and ingestion induce reciprocal changes in neuropeptide Y concentrations in the paraventricular nucleus. Peptides 1988; 9: 83–86.PubMedGoogle Scholar
  92. 92.
    Beck B, Stricker-Krongrad A, Nicolas JP, Burlet C. Chronic and continous intracerebronventricular infusion of neuropeptide Y in Lon-Evans rats mimics the feeding behaviour of obese Zucker rats. Int J Obes 1991; 16: 295–302.Google Scholar
  93. 93.
    Clark JT, Kalra PS, Crowely WR, Kalra SP. Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endo 1984; 115: 427–429.Google Scholar
  94. 94.
    Kalra SP, Dube MG, Kalra PS. Continuous intraventricular infusion of neuropeptide Y evokes episodic food intake in satiated female rats: effects of adrenalectomy and cholecystokinin. Peptides 1988; 9: 723–728.PubMedGoogle Scholar
  95. 95.
    Paez X, Myers RD. Insatiable feeding evoked in rats by recurrent perfusion of neuropeptide Y in the hypothalamus. Peptides 1991; 12: 609–616.PubMedGoogle Scholar
  96. 96.
    Egawa M, Yoshimatsu H, Bray GA. Neuropeptide Y suppress sympathetic activity to inter-scapular brown adipose tissue in rats. Am J Physiol 1991; 260: R328 - R334.PubMedGoogle Scholar
  97. 97.
    Billington CJ, Briggs JE, Grace M, Levine AS. Effects of intarcerebroventricular injection of neuropeptide Y on energy metabolism. Am J Physiol 1991; 260: R321 - R327.PubMedGoogle Scholar
  98. 98.
    Bray G. Peptides affect the intake of specific nutrients and the sympathetic nervous system. Am J Clin Nutr 1992; 55: 265–271.Google Scholar
  99. 99.
    Morley JE, Levine AS, Gosnell BA, Kneip J, Grace M. Effect of neuropeptide Y on ingestive behaviors in the rat. Am J Physiol 1987; 252: R599 - R609.PubMedGoogle Scholar
  100. 100.
    Stanley BG. Neuropeptide Y in multiple hypothalamic sites controls eating behavior, endocrine, and autonomic systems for energy balance. In The Biology of Neuropeptide Y and Related Peptides. Colmers WF, Wahlestedt C eds. Totowa, NJ: Humana, pp. 457–509, 1993.Google Scholar
  101. 101.
    White JD, Kershaw M. Increased hypothalamic neuropeptide Y expression following food deprivation. Mol Cell Neurosci 1989; 1: 41–48.Google Scholar
  102. 102.
    Schwartz MW, Sipols AJ, Grubin CE, Baskin DG. Differential effect of fasting on hypothalamic expression of genes encoding neuropeptide Y, galanin and glutamic acid decarboxylase. Brain Res Bull 1993; 31: 361–367.Google Scholar
  103. 103.
    Davies L, Marks JL. Role of hypothalamic neuropeptide Y gene expression in body weight regulation. Am J Physiol 1994; 266: R1687 - R1691.PubMedGoogle Scholar
  104. 104.
    Ka1ra SP, Dube MG, Sahu A, Phelps CP, Kalra R. Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food. Proc Natl Acad Sci USA 1991; 88: 10, 931–10, 935.Google Scholar
  105. 105.
    Lewis DE, Shellard L, Koeslag DG, Boer DE, McCarthy HD, McKibbin PE, Russell JC, Williams G. Intense exercise and food restriction cause similar hypothalamic neuropeptide Y increases in rats. Am J Physiol 1993; 264: E279 - E284.PubMedGoogle Scholar
  106. 106.
    Williams G, Gill JS, Lee YC, Cardoso HM, Okpere BE, Bloom SR. Increased neuropeptide Y concentrations in specific hypothalamic regions of streptozocin-induced diabetic rats. Diabetes 1989; 38: 321–327.PubMedGoogle Scholar
  107. 107.
    McKibbin PE, McCarthy HD, Shaw P, Williams G. Insulin deficiency is a specific stimulus to hypothalamic neuropeptide Y: a comparison of the effects of insulin replacement and food restriction in streptozotocin-diabetic rats. Peptides 1992; 13: 721–727.PubMedGoogle Scholar
  108. 108.
    Akabayashi A, Wahlestedt C, Alexander JT, Leibowitz SF. Specific inhibition of endogenous neuropeptide Y synthesis in arcuate nucleus by antisense oligonucleotides suppresses feeding behavior and insulin secretion. Brain Res 1994; 21: 55–61.Google Scholar
  109. 109.
    Morley JE. Neuropeptide regulation of appetite and weight. Endocr Rev 1987; 8: 256–287.PubMedGoogle Scholar
  110. 110.
    Stanley BG, Magdalin W, Seirafi A, Nguyen MM, Leibowitz SF. Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide’s effect. Peptides 1992; 13: 581–587.PubMedGoogle Scholar
  111. 111.
    Shibasaki T, Oda T, Imaki T, Ling N, Demura H. Injection of anti-neuropeptid Y g-globulin into the hypothalamic paraventricular nucleus decreases food intake in rats. Brain Res 1993; 601: 313–316.PubMedGoogle Scholar
  112. 112.
    White BD, Dean RG, Martin RJ. Adrenalectomy decreases neuropeptide Y mRNA levels in the arcuate nucleus. Brain Res Bull 1990; 25: 711–715.PubMedGoogle Scholar
  113. 113.
    Wilding JP, Gilbey SG, Lambert PD, Ghatei MA, Bloom SR. Increases in neuropeptide Y content and gene expression in the hypothalamus of rats treated with dexamethasone are prevented by insulin. Neuroendocrinology 1993; 57: 581–587.PubMedGoogle Scholar
  114. 114.
    Ponsalle P, Srivastava LS, Uht RM, White JD. Glucocorticoids are required for food deprivation-induced increases in hypothalamic neuropeptide Y expression. J Neuroendocrinol 1993; 4: 585–591.Google Scholar
  115. 115.
    Rothwell N. Central effects of CRF on metabolism and energy balance. Neurosci Biobehav Rev 1989; 14: 263–271.Google Scholar
  116. 116.
    Heinrichs SC, Menzaghi F, Pich EM, Hauger RL, Koob GF. Cortioctropin-releasing factor in the paraventricular nucleus modulates feeding induced by neuropeptide Y. Brain Res 1993; 611: 18–24.PubMedGoogle Scholar
  117. 117.
    Krahn DD, Gosnell Ba. Behavioral effects of corticotropin-releasing factor: localization and characterization of central effects. Brain Res 1988; 443: 63–69.PubMedGoogle Scholar
  118. 118.
    Beyer HS, Matta SG, Sharp BM. Regulation of the messenger ribonucleic acid for corticotropinreleasing factor in the paraventricular nucleus and other brain sites of the rat. Endocrinology 1988; 123: 2117–2123.PubMedGoogle Scholar
  119. 119.
    Arase K, York DA, Shimizu H, Shargil NS, Bray GA. Effects of corticotropin releasing factor on food intake and brown adipose tissue thermogenesis in rats. Am J Physiol 1988; 255: E255–259.PubMedGoogle Scholar
  120. 120.
    Arase K, Shargill NS, Bray GA. Effects of intraventricular infusion of corticotropin-releasing factor on VMH-lesioned obese rats. Am J Physiol 1989; 256: R751–756.PubMedGoogle Scholar
  121. 121.
    Glowa J, Gold R Corticotropin releasing hormone produces profound anorexigenic effects in the rhesus monkey. Neuropeptides 1991; 55–61.Google Scholar
  122. 122.
    Krahn DD, Gosness BA, Crane M, Levine AS. CRF antagonist partially reverses CRF and stress induced effects on feeding. Brain Res Bull 1986; 17: 285–289.PubMedGoogle Scholar
  123. 123.
    Hotta M, Shibasaki T, Yamauchi N, Ohno H, Benoit R, Lin N, Demura H. The effects of chronic central administration of corticotropin-releasing factor on food intake, body weight, and hypothalamic-pituitary-adrenocortical hormones in rats. Life Sci 1991; 48: 1483–1491.PubMedGoogle Scholar
  124. 124.
    Brown M, Fisher L, Spiess J, Rivier C, Riveri J, Vale W. Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology 1982; 111: 928–931.PubMedGoogle Scholar
  125. 125.
    Egawa H, Yoshimatsu H, Bray GA. Effect of corticotropin releasing hormone and neuropeptide Y on electrophysiological activity of sympathetic nerves to interscapular brown adipose tissue. Neuroscience 1990; 771–775.Google Scholar
  126. 126.
    LeFeuvre RA, Rothwell NJ, Stock MJ. Activation of brown fat thermogenesis in response to central injection of CRF in the rat. Neuropharmacology 198; 26: 1217–1221.Google Scholar
  127. 127.
    LeFeuvre RA, Rothwell JJ, White A. comparison of the thermogenic effects of CRF, sauvagine, and urotensin 1 in the rat. Horm Metab Res 1989; 21: 525–526.Google Scholar
  128. 128.
    Brady LS, Smith MA, Gold PW, Herkenham M. Altered expression of hypothalamic neuropeptide mRNAs in food restricted and food-deprived rats. Neuroendocrinology 1990; 52: 441–447.PubMedGoogle Scholar
  129. 129.
    Brobeck JR. Food intake as a mechanism of temperature regulation. Yale J Biol Med 1948; 20: 545–552.PubMedGoogle Scholar
  130. 130.
    Himms-Hagen J. Role of brown adipose tissue thermogenesis in control of thermoregulatory feeding in rats: a new hypothesis that links thermostatic and glucostatic hypotheses for control of food intake. Proc Soc Exp Biol Med 1995; 208: 159–169.PubMedGoogle Scholar
  131. 131.
    Nicoliaidis S, Even P. Mesure du metabolisme de fond en relation avec la prise alimentaire: Hypothese iscymetrique. Comptes Rendus Academie de Sciences, Paris 1984; 298: 295–300.Google Scholar
  132. 132.
    Friedman MI, Tordoff MG, Ramirez I. Integrated metabolic control of food intake. Brain Res Bul 1991; 17: 855–859.Google Scholar
  133. 133.
    MacKay EM, Calloway JW, Barnes RH. Hyperalimentation in normal animals produced by protamine insulin. J Nutr 1940; 20: 59–66.Google Scholar
  134. 134.
    Steffens AB. The influence of insulin injections and infusions on eating and blood glucose levels in the rat. Physiol Behav 1969; 4: 823–828.Google Scholar
  135. 135.
    Booth DA. Modulation of the feeding response to peripheral insulin, 2-deoxy-D-glucose or 3O-methyl-glucose injection. Physiol Behav 1972; 8: 1069–1076.PubMedGoogle Scholar
  136. 136.
    Lotter EC, Woods SC. Injections of insulin and changes of body weight. Physiol Behav 1977; 18: 293–297.PubMedGoogle Scholar
  137. 137.
    Smith GP, Epstein AN. Increased feeding in response to decreased glucose utilization in rat and monkey. Am J Physiol 1969; 217: 1083–1087.PubMedGoogle Scholar
  138. 138.
    Parrot RF, Baldwin BA. Effects of intracerebroventricular injections of 2-deoxy-D-glucose and xylose on operant feeding in pigs. Physiol Behav 1978; 21: 329–331.Google Scholar
  139. 139.
    Thompson DA. Hunger in humans induced by 2-deoxy-D-glucose: glucoprivic control of taste preference and food intake. Science 1977; 198: 1065–1068.PubMedGoogle Scholar
  140. 140.
    Welle SL, Thompson DA, Campbell RG, et al. Increased hunger and thirst during glucoprivation in humans. Physiol Behav 1980; 25: 397–403.PubMedGoogle Scholar
  141. 141.
    Frohman LA, Muller EE, Cocchi D. Central nervous system mediated inhibition of insulin secretion due to 2-deoxyglucose. Horm Metab Res 1973; 5: 21–26.PubMedGoogle Scholar
  142. 142.
    Brown J. Effects of 2-deoxy-D-glucose on carbohydrate metabolism: review of the literature and studies in the rat. Metabolism 1962; 11: 1098–1112.PubMedGoogle Scholar
  143. 143.
    Woods SC. The eating paradox: how we tolerate food. Psych Rev 1991; 98: 488–505.Google Scholar
  144. 144.
    Woods SC, Strubbe JH. The psychobiology of meals. Psych Bull Rev 1994; 1: 141–155.Google Scholar
  145. 145.
    Campfield LA, Smith FJ. Transient declines in blood glucose signal meal initiation. Int J Obes 1990; 14: 15–33.PubMedGoogle Scholar
  146. 146.
    Campfield LA, Smith FJ. The glucostatic hypothesis-1995 update-transient declines in blood glucose as signals for meal initiation. Obes Res 1995; 3: 311s.Google Scholar
  147. 147.
    Campfield LA, Smith FJ. Blood glucose and meal initiation: a role for insulin? Soc Neurosci Abstracts 1986; 12: 109.Google Scholar
  148. 148.
    Woods SC, Stein LJ, McKay LD, Porte D Jr. Suppression of food intake by intravenous nutrients and insulin in the baboon. Am J Physiol 1984; 247: R393 - R401.PubMedGoogle Scholar
  149. 149.
    Langhans W, Scharrer E. Metabolic control of eating, energy expenditure and bioenergetics of obesity. In World Review of Nutrition and Dietetics. Simopoulos AP, ed. Basel Switzerland: Karger, pp. 1–67, 1992.Google Scholar
  150. 150.
    Ritter S, Taylor JS. Vagal sensory neurons are required for kiporivic but not glucoprivic feeding in rats. Am J Physiol 1990; 258: R1395 - R1401.PubMedGoogle Scholar
  151. 151.
    Kamoda N, Calne RY. Orthotopic liver transplantation in the rat. Transplantation 1979; 28: 47–50.Google Scholar
  152. 152.
    Scheurink AJ, Steffens AB. Central and peripheral control of sympathoadrenal activity and energy metabolism in rats. Physiol Behav 1990; 48: 909–920.PubMedGoogle Scholar
  153. 153.
    Gibbs J, Young RC, Smith GP. Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol 1973; 84: 488–495.PubMedGoogle Scholar
  154. 154.
    Smith GP, Gibbs J. The development and proof of the CCK hypothesis of satiety. In: Multiple Cholecystokinin Receptors in the CNS. Dourish CT, Cooper SJ, Iversen SD, Iverson LL, eds. Oxford: Oxford University Press, pp. 166–182, 1992.Google Scholar
  155. 155.
    Greenberg D, Smith GP. Hepatic-portal infusion reduces the satiating potency of CCK-8. Physiol Behav 1988; 44: 535–538.PubMedGoogle Scholar
  156. 156.
    Smith GP, Jerome C, Cushin BJ, Eterno R, Simansky KJ. Abdominal vagotomy blocks the satiety effect of cholecystokinin in the rat. Science 1981; 213: 1036–1037.PubMedGoogle Scholar
  157. 157.
    Sankaran H, Deveney CW, Goldfine ID, Williams JA. Preparation of biologically active radioiodinated cholecystokinin for radioreceptor assay and radioimmunoassay. J Biol Chem 1979; 254: 9349–9351.PubMedGoogle Scholar
  158. 158.
    Della-Fera MA, Balle CA. CCK-octapeptide injected in CSF decreases meal size and daily food intake in sheep. Peptides 1980; 1: 51–54.PubMedGoogle Scholar
  159. 159.
    Figlewicz DP, Sipols AJ, Porte DJ, Woods SC. Intraventricular CCK inhibits food intake and gastric emptying in baboons. Am J Physio11988; 256: R1313 - R1317.Google Scholar
  160. 160.
    Schick RR, Yaksh TL, Roddy DR, Go VW. Release of hypothalamic cholecystokinin in cats: effects of nutrient and volume loading. Am J Physiol 1989; 25: R248 - R254.Google Scholar
  161. 161.
    West DB, Fey D, Woods SC. Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am J Physiol 1984; 246; R776–787.PubMedGoogle Scholar
  162. 162.
    Edholm OG. Energy balance in man. J Hum Nutr 1977; 31: 413–431.PubMedGoogle Scholar
  163. 163.
    Figlewicz DP, Stein LJ, West D. Porte D Jr, Woods SC. Intracisternal insulin alters sensitivity to CCK-induced meal suppression in baboons. Am J Physiol 1986; 250: R856 - R860.PubMedGoogle Scholar
  164. 164.
    Riedy CA, Chavez M, Figlewicz DP, Woods SC. Intraventricular insulin increases sensitivity to CCK in rats. Soc Neurosci Abstracts 1991; 17: 543 (abstract).Google Scholar
  165. 165.
    Arch JRS, Kaumann AJ. B3 and atypical B-adrenoceptors. Med Res Rev 1993; 13: 663–729.PubMedGoogle Scholar
  166. 166.
    Clement K, Vaisse C, Manning BJ, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosber AD. Genetic variation in the B3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. New Engl J Med 1995; 333: 352–354.PubMedGoogle Scholar
  167. 167.
    Ravussin E, Lillioja MB, Knowler WC, Christin L, Freymond D, Abbott WG, Boyce V, Howard BV, Bogardus C. Reduced rate of energy expenditure as a risk factor for body-weight-gain. New Engl J Med 1988; 318: 467–472.PubMedGoogle Scholar
  168. 168.
    Ravussin E, Bogardus C. A brief overview of human energy metabolism and its relationship to essential obesity. Am J Clin Nutr 1992; 55: 242S - 245S.PubMedGoogle Scholar
  169. 169.
    Bouchard C, Savard R, Despres JP, Tremblay A, Leblanc C. Body composition in adopted and biological siblings. Hum Biol 1985; 57: 61–75.PubMedGoogle Scholar
  170. 170.
    Stunkard AJ, Sorensen T, Hanis C. An adoption study of human obesity. New Engl J Med 1986; 314: 193–198.PubMedGoogle Scholar
  171. 171.
    Kuczmarski R, Flegal K, Campbell S, Johnson C. Increasing prevalence of overweight among US adults. The national health and nutrition examination surveys, 1960 to 1991. JAMA 1994; 272: 205–211.Google Scholar
  172. 172.
    Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Am J Human Genet 1962; 14: 353–362.Google Scholar
  173. 173.
    Neel JV. The genetics of diabetes mellitus. Proceedings of the Serono Symposium. In: The Thrifty Genotype Revisited. Kobberling J, Tattersall R, eds. London: Academic, pp. 282–293, 1982.Google Scholar
  174. 174.
    Schwartz MW, Boyko EJ, Kahn SE, Ravussin E, Bogardus C. Reduced insulin secretion: an independent predictor of body weight gain. J Clin endocrinol Metab 1993; 80 (5): 1571–1576.Google Scholar
  175. 175.
    Boyko E, Leonetti D, Bergstrom RW, Newell-Morris L, Fujimoto WY. Low insulin secretion and high fasting insulin and C-peptide levels predict increased visceral adiposity: 5 year follow-up among initially non-diabetic Japanese American men. Diabetes, 1996; 45 (8): 1010–1015.PubMedGoogle Scholar
  176. 176.
    Safer DJ. Diet, behavior modification, and exercise: a review of obesity treatments from a longterm perspective. Southern Med J 1991; 84: 1470–1474.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Michael W. Schwartz
  • Denis G. Baskin
  • Karl J. Kaiyala
  • Steven C. Woods
  • Daniel PorteJr.

There are no affiliations available

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