Metabolic and Endocrine Factors in Regulation of Nutrient Balance

  • G. A. Bray
Conference paper


In mammals, fat deposits represent the major store of energy. In a normal human being, for example, the nutrient intake may average 2000 kcal/day in an individual whose energy stores are 150000 kcal or 75 times larger than the daily intake. Energy intake occurs as discreet, periodic meals which are used for metabolic needs and for repletion of nutrient stores. The energy stores, on the other hand, supply metabolic fuels between meals and during longer periods of deprivation.


Sympathetic Nervous System Brown Adipose Tissue Corticotropin Release Factor Lateral Hypothalamus Ventromedial Hypothalamus 
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  1. Addison T (1855) On the constitutional and local effects of disease of the supra-renal capsules. Samuel Highley, London, pp 1–43Google Scholar
  2. Anand B, Brobeck JR (1951) Hypothalamic control of food intake in rats and cats. Yale J Biol Med 24: 123–140PubMedGoogle Scholar
  3. Arase K, York DA, Shargill NS, Bray GA (1987a) Effect of cerebroventricular infusions of insulin and beta-hydroxy-butyrate on food intake and thermogenesis in the rat. Clin Res 35: 164AGoogle Scholar
  4. Arase K, York DA, Bray GA (1987b) Corticosterone inhibition of the intracerebroventricular effect of 2-deoxy-n-glucose on brown adipose tissue thermogenesis. Physiol Behav 40: 489–495PubMedCrossRefGoogle Scholar
  5. Atkinson RL (1982) Naloxone decreases food intake in obese humans. J Clin Endo Metab 55: 196–198CrossRefGoogle Scholar
  6. Baile CA, Della-Fera MA (1986) Peptidergic control of food intake in food-producing animals. Physiol Rev 43: 2898–2902Google Scholar
  7. Bailey CJ, Day C, Bray GA, Lipson LG, Flatt PR (1986) Role of adrenal glands in the development of abnormal glucose and insulin homeostasis in genetically obese (ob/ob) mice. Horm Metab Res 18: 357–360PubMedCrossRefGoogle Scholar
  8. Ball GG (1974) Vagotomy: effect on electrically elicited eating and self-stimulated in the lateral hypothalamus. Science 184: 484–485PubMedCrossRefGoogle Scholar
  9. Berthoud H-R, Jeanrenaud B (1979) Acute hyperinsulinemia and its reversal by vagotomy following lesions of the ventromedial hypothalamus in anesthetized rats. Endo 105: 146–151Google Scholar
  10. Bray GA (1969) Calorigenic effect of human growth hormone in obesity. J Clin Endo Metab 29: 119–122CrossRefGoogle Scholar
  11. Bray GA, Campfield LA (1975) Metabolic factors in the control of energy stores. Metab 24: 99–117CrossRefGoogle Scholar
  12. Bray GA, Gallagher TF (1975) Manifestations of hypothalamic obesity in man: a comprehensive investigation of eight patients and a review of the literature. Medicine 54: 301–330PubMedCrossRefGoogle Scholar
  13. Bray GA (1976) The obese patient. Major problems in internal medicine, vol 9. Sauners, Philadel-phia, pp 1–450Google Scholar
  14. Bray GA, Nishizawa Y (1978) Ventromedial hypothalamus modulates fat mobilization during fasting. Nature 27: 900–902CrossRefGoogle Scholar
  15. Bray GA, York DA (1979) Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol Rev 59: 719–809PubMedGoogle Scholar
  16. Bray GA, Inoue S, Nishizawa Y (1981) Hypothalamic obesity. The autonomic hypothesis and lateral hypolthalamus. Diabetologia 20: 366–377Google Scholar
  17. Bray GA (1982) Regulation of energy balance: studies on genetic, hypothalamic and dietary obesity. Proc Nutr Soc 41: 95–108PubMedCrossRefGoogle Scholar
  18. Bray GA, Scalafani A, Novin D (1982) Obesity-induced hypothalamic knife cuts: effects on lipolysis and blood insulin levels. Am J Physiol 23: R445 - R449Google Scholar
  19. Bray GA (1986) Autonomic and endocrine factors in the regulation of energy balance. Fed Proc 45: 1404–1410PubMedGoogle Scholar
  20. Bray GA (1987) Obesity–a disease of nutrient or energy balance? Nutr Rev 45 (2): 33–43PubMedGoogle Scholar
  21. Bray GA, Teague RI, Lee CK (1987) Brain uptake of ketones in rats with differing susceptibility to dietary obesity. Metabolism 36: 27–30PubMedCrossRefGoogle Scholar
  22. Brown MR, Fisher J, Spiess J, Rivier J, Vale W (1982) Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology III: 928–931CrossRefGoogle Scholar
  23. Bruce BC, King BM, Phelps GR, Veitia MC (1982) Effects of adrenalectomy and corticosterone administration on hypothalamic obesity in rats. Am J Physiol 243: E152 - E157PubMedGoogle Scholar
  24. Campfield LA, Brandon P, Smith FJ (1985) On-line continuous measurement of blood glucose and meal pattern in free-feeding rats: the role of glucose in meal initiation. Brain Res Bull 14 (6): 605–616PubMedCrossRefGoogle Scholar
  25. Cox JE, Powley TL (1981) Prior vagotomy blocks VMH obesity in pair-fed rats. Am J Physiol 240: E573 — E583PubMedGoogle Scholar
  26. Cushing HW (1932) The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). Bull Johns Hopkins Hosp 50: 137–195Google Scholar
  27. Davis JD, Wirshafter D, Asin KE, Brief D (1981) Sustained intracerebroventricular infusion of brain fuels reduces body weight and food intake in rats. Science 212: 81–83PubMedCrossRefGoogle Scholar
  28. Debons AF, Siclari E, Das KC, Fuhr B (1982) Gold thioglucose induced hypothalamic damage, hyperphagia and obesity: dependence on the adrenal gland. Endocrinology 110: 2024–2029PubMedCrossRefGoogle Scholar
  29. Donhoffer SF, Vonotzky J (1947) The effect of thyroxine on food intake and selection. Am J Physiol 150: 334–339PubMedGoogle Scholar
  30. Eng R, Gold RM, Wade GN (1979) Ovariectomy — induced obesity is not prevented by subdiaphrugimiates vagotomy in rats. Physiol Behav 22: 353–356PubMedCrossRefGoogle Scholar
  31. Epstein AN, Teitelbaum P (1967) Specific loss of the hypoglycemic controls of feeding in recovered lateral rats. Am J Physiol 213: 1159–1167PubMedGoogle Scholar
  32. Forbes GB, Reina JC (1970) Adult lean body mass declines with age: Some longitudinal observations. Metabolism 19: 653–663Google Scholar
  33. Friedman MI, Tordoff MG (1975) Fatty acid oxidation and glucose utilization interact to control food intake in rats. Am J Physiol 20: R840 — R845Google Scholar
  34. Fukushima M, Lupien J, Bray GA (1985) Interaction of light and corticosterone on food intake and interscapular brown adipose tissue of rats. Am J Physiol 249: E519 — E524Google Scholar
  35. Galpin KS, Henderson RB, James WPT, Trayhurn P (1983) GDP binding to brown-adipose tissue mitochondria of mice treated chronically with corticosterone. Biochem J 214: 265–268PubMedGoogle Scholar
  36. Geary N, Langhans W, Scharrer E (1981) Metabolic concomitants of glucagon induced suppression of feeding in the rat. Am J Physiol 241: R330 — R335PubMedGoogle Scholar
  37. Gibbs J, Young RC, Smith GP (1973) Choleystokinin decreases food intake in rats. J Comp Physiol Psychol 84: 488–495PubMedCrossRefGoogle Scholar
  38. Gold RM, Sawchenko PE, DeLuca C, Alexander J, Eng R (1980) Vagal mediated of hypothalamic obesity but not of supermarked dietary obesity. Am J Physiol 238: R447 — R453PubMedGoogle Scholar
  39. Grandison L, Guidotti A (1977) Stimulation of food intake by muscimol and beta-endorphin. Neurology 16: 533–536Google Scholar
  40. Gray JM, Wade GN (1981) Food intake, body weight, and adiposity in female rats: actions and interactions of progestins and antiestrogens. Am J Physiol 240: E474 — E481PubMedGoogle Scholar
  41. Grossman SP (1962) Direct adrenergic and cholinergic stimulation of hypothalamic mechanisms. Am J Physiol 202: 872–882PubMedGoogle Scholar
  42. Himms-Hagen J (1985) Brown adipose tissue metabolism and thermogenesis. Annu Rev Nutr 5: 69–94PubMedCrossRefGoogle Scholar
  43. Hogan S, Himms-Hagen J, Coscina DV (1985) Lack of diet-induced thermogenesis in brown adipose tissue of obese medial hypothalamic-lesioned rats. Physiol Behav 35: 287–294PubMedCrossRefGoogle Scholar
  44. Holt S, York DA (1982) The effect of adrenalectomy on GDP binding to brown adipose tissue mitochondria of obese rats. Biochem J 208: 819–822PubMedGoogle Scholar
  45. Inoue S, Bray GA (1977) The effect by subdiaphragmatic vagotomy in rats with ventromedial hypothalamic obesity. Endocrinology 100: 108–114PubMedCrossRefGoogle Scholar
  46. Keesey RE, Powley TL (1986) The regulation of body weight. Annu Rev Psychol 37: 109–133PubMedCrossRefGoogle Scholar
  47. Leibowitz SF (1975) Ingestion in the satieted rat: role of alpha and beta receptors in mediating effects of hypothalamic adrenergic stimulation. Physiol Behav 14: 743–754PubMedCrossRefGoogle Scholar
  48. Leibowitz SF (1978) Paraventricular nucleus: a primary site mediating adrenergic stimulation of feeding and drinking. Pharmacol Biochem Behav 8: 163–175PubMedCrossRefGoogle Scholar
  49. Leibowitz SF, Rossakis C (1978) Pharmacological characterization of perifornical hypothalamic I3-adrenergic receptors mediating feeding inhibition in the rat. Neuropharmacology 17: 691–702PubMedCrossRefGoogle Scholar
  50. Leibowitz SF (1980) Neurochemical systems of the hypothalamus in control of feeding and drinking behavior and water-electrolyte excretion. In: Morgane PJ, Panksepp J (eds) Handbook of the hypothalamus, vol 3a. Dekker, New York, pp 299–437Google Scholar
  51. Leibowitz SF, Roland CR, Hor L, Squillari V (1984) Noradrenergic feeding elicited via the para-ventricular nucleus is dependent upon circulating corticosterone. Physiol Behav 32: 857–864PubMedCrossRefGoogle Scholar
  52. Leibowitz SF (1986) Brain monoamines and peptides: role in the control of eating behavior. Fed Proc 45: 1396–1403PubMedGoogle Scholar
  53. LeMagnen J (1983) Body energy balance and food intake: a neuroendocrine regulatory mechanism. Physiol Rev 63: 315–386Google Scholar
  54. Levine AS, Rogers B, Kneip J, Grace M, Morley JE (1983) Effects of centrally administered corticotropin releasing factor ( CRF) on multiple feeding paradigms. Neuropharmacology 22: 337–339PubMedCrossRefGoogle Scholar
  55. Luiten PGM, ter Horst GJ, Steffens AB (1987) The hypothalamus, intrinsic connections and outflow pathways to the endocrine system in relation to the control of feeding and metabolism (review). Prog Neuro 28: 1–54CrossRefGoogle Scholar
  56. Lupien JR, Shargill NS, Bray GA (1985) Adrenelectomy in genetically ob/ob and db/db mice increases the proton conductance pathway. Fed Proc 44 (4)Google Scholar
  57. Maggio CA, Presta E, Brecco EF, Vasseli JR, Kissileff HR, Pfohl DN, Hashim SA (1985) Naltrexone and human eating behavior: a dose-ranging inpatient trial in moderately obese men. Brain Res Bull 14 (6): 657–661PubMedCrossRefGoogle Scholar
  58. Malcolm R, O’Neil O, Sexauer JB, Riddle FE, Currey HS, Counts C (1985) A controlled trial of naltrexone in obese humans. Intern J Obesity 9: 347–353Google Scholar
  59. Marchington D, Rothwell NJ, Stock MJ, York DA (1983) Energy balance, diet-induced thermogenesis and brown adipose tissue in lean and obese (fa/fa) Zucker rats after adrenalectomy. J Nutr 113: 1395–1402PubMedGoogle Scholar
  60. McHugh PR and Moran TH (1986) The stomach, cholecystokinin and satiety. Fed Proc 45 (5): 1384–1390PubMedGoogle Scholar
  61. Mook DG, Kenney NJ, Roberts S, Nussbaum AI, Rodier IIIWI (1972) Ovarian-adrenal inter-actions in regulation of body weight by female rats. J Comp Physiol Psychol 81: 198–211PubMedCrossRefGoogle Scholar
  62. Morley JE, Levine AS, Gosnell BA, Billington CJ (1984) Neuropeptides and appetite: contribution of neuropharmacological modeling. Fed Proc 43: 2903–2907PubMedGoogle Scholar
  63. Nagai K, Nishio T, Nakagawa H, Nakamura S, Fukuda Y (1978) Effect of bilateral lesions of the suprachiasmatic nuclei on the circadian rhythm of food-intake. Brain Res 142: 384–389PubMedCrossRefGoogle Scholar
  64. Niijima A, Rohner-Jeanrenaud F, Jeanrenaud B (1984) Electrophysiological studies on the role of the ventromedial hypothalamus on the sympathetic efferent nerve activity of brown adipose tissue in the rat. Am J Physiol 247: R650 — R654PubMedGoogle Scholar
  65. Niijima A (1985) Blood glucose levels modulate efferent activity in the vagal supply to the rat liver. J Physiol (Lonel) 364: 105–112Google Scholar
  66. Nishizawa Y, Bray GA (1978) Ventromedial hypothalamic lesions and the mobilization of fatty acids. J Clin Invest 61: 714–721PubMedCrossRefGoogle Scholar
  67. Nunez AA, Grundman M (1982) Testosterone affects food intake and body weight of weanling male rats. Pharm Biochem Behav 16: 933–936CrossRefGoogle Scholar
  68. Ohshima K, Shargill NS, Chan TM, Bray GA (1984) Adrenalectomy reverses insulin resistance in muscle from obese (ob/ob) mice. Am J Physiol 246: E193 — E197PubMedGoogle Scholar
  69. Oomura Y, Kita H (1981) Insulin acting as a modulator of feeding through the hypothalamus. Diabetologia 20: 290–298PubMedCrossRefGoogle Scholar
  70. Oomura Y (1983) Glucose as a regulator of neuronal activity. Adv Metabolic Disorders 10: 31–65Google Scholar
  71. Panksepp J, Bishop P, Rossi J (1979) Neurohumoral and endocrine control of feeding. Psychoneuroendocrinology 4: 89–106PubMedCrossRefGoogle Scholar
  72. Perkins MN, Rothwell NJ, Stock MJ, Stone TW (1981) Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus. Nature 289: 401–402PubMedCrossRefGoogle Scholar
  73. Powley TL (1977) The ventromedial hypothalamic syndrome, satiety and a cephalic phase hypothesis. Psychol Rev 84: 89–126PubMedCrossRefGoogle Scholar
  74. Powley TL, Opsahl CA (1974) Ventromedial hypothalamic obesity abolished by subdiaphragmatic vagotomy. Am J Physiol 226: 25–33Google Scholar
  75. Saito M, Bray GA (1983) Diurnal rhythm for corticosterone in obese (ob/ob) diabetes (db/db) and gold-thioglucose-induced obesity in mice. Endocrinology 113: 2181–2185PubMedCrossRefGoogle Scholar
  76. Saito M, Bray GA (1984) Adrenalectomy and food restriction in the genetically obese (ob/ob) mouse. Am J Physiol 246: R20–25PubMedGoogle Scholar
  77. Sakaguchi T, Bray GA (1987) The effect of intrahypothalamic injections of glucose on sympathetic efferent firing rate. Brain Res Bull 18: 591–595PubMedCrossRefGoogle Scholar
  78. Sakaguchi T, Eddlestone, Bray GA (1986) Sympathetic activity in interscapular brown adipose tissue after hypothalamic paraventricular (Pvn) and ventromedial (VMH) lesions in rats. Clin Res 34(2): 804A (Abs)Google Scholar
  79. Sakaguchi T, Bray GA (1987) Intrahypothalamic insulin decreases sympathetic firing. Natl Acad Sci 84: 2012–2014CrossRefGoogle Scholar
  80. Schemmel RA, Teague RJ, Bray GA (1982) Obesity in Osborne-Mendel and S5B/PI rats: effects of sucrose solutions, castration, and treatment with estradiol or insulin. Am J Physiol 243: R347 — R353PubMedGoogle Scholar
  81. Sclafani A, Aravich PF, Landman M (1981) Vagotomy blocks hypothalamic-hyperphagia in rats on a chow diet and sucrose solution but not on a palatable mixed diet. J Comp Physiol Psychol 195: 720–734CrossRefGoogle Scholar
  82. Sclafani A, Berner CN (1977) Hyperphagia and obesity produced by parasagittal and coronal hypothalamic knife cuts — further evidence for a longitudinal feeding inhibitory pathway. J Comp Physiol Psycho! 91: 1000–1019CrossRefGoogle Scholar
  83. Shargill NS, Ohshima K, Bray GA, Chan TM (1984) Muscle protein in turnover in skeletal muscle of lean and db/db/mice. Diabetes 33: 1160–1164PubMedCrossRefGoogle Scholar
  84. Shimazu T (1981) Central nervous system regulation of liver and adipose tissue metabolism. Diabetologia 20: 343–356PubMedCrossRefGoogle Scholar
  85. Shimomura Y, Bray GA, York DA (1981) Effects of thyroid hormone and adrenalectomy on (NA+ + K+) ATPase in the ob/ob mouse. Horm Metab Res 13: 249–253CrossRefGoogle Scholar
  86. Smith GP, Jerome C. Cushin B, Eterno R, Simansky HJ (1981) Abdominal vagotomy blocks satiety effects of cholecystokinin in rats. Science 213: 1036–1037Google Scholar
  87. Smith GP (1983) The peripheral control of appetite. Lancet 2: 88–90PubMedCrossRefGoogle Scholar
  88. Smith GP, Gibbs J (1984) Gut peptides and postprandial satiety. Fed Proc 43: 2889–2892PubMedGoogle Scholar
  89. Stanley BG, Leibowitz SF (1985) Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior. Proc Natl Acad Sci USA 83: 3940–3943CrossRefGoogle Scholar
  90. Steffens AB (1975) Influence of reversible obesity on eating behavior, blood glucose and insulin in the rat. Ani J Physiol 228: 1738–1744Google Scholar
  91. Stellar E (1954) The physiology of motivation. Psychol Rev 61: 5–22PubMedCrossRefGoogle Scholar
  92. Stern J, Brown JS, Stanhope K, Uriu J, Castonguay TW, Bray GA (1983) Adrenalectomy reduced weight gain, adipose cell size and lipoprotein lipase activity in obese male Zucker rats (fafa). Fed Proc 42: 393 (Abs)Google Scholar
  93. Swanson LW, Sawchenko PE, Rivier J, Vale WW (1983) Organization of ovine corticotropin-releasing factor immunoreactory cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinol 36: 165–186CrossRefGoogle Scholar
  94. Teitelbaum P, Cheng MF, Rozin P (1965) Stages of recovery and development of lateral hypothalamic control of food and water intake. Ann NY Acad Sci 63: 558–565Google Scholar
  95. Thompson DA, Campbell RG (1977) Hunger in humans induced by 2-deoxy-n-glucose: glucoprivic control of taste preference and food intake. Science 198: 1065–1068PubMedCrossRefGoogle Scholar
  96. Tokunaga K, Fukushima M, Kemnitz JW, Bray GA (1986) Comparison of ventromedial and para-ventricular lesions in rats that become obese. Am J Physiol 251: R1221 — R1227PubMedGoogle Scholar
  97. Ungerstedt U (1971) Sterotaxic mapping of the monoamine pathways in the rat brain. Acta Physio Scand [Suppl] 367: 1–48Google Scholar
  98. vander Tuig JG, Knehans AW, Romsos DR (1982) Reduced sympathetic nervous system activity in rats with ventromedial hypothalamic lesions. Life Sciences 30: 913–920CrossRefGoogle Scholar
  99. vander Tuig JG, Ohshima K, Yoshida T, Romsos DR, Bray GA (1982b) Adrenalectomy increases norepinephrine turnover in brown adipose tissue of obese (ob/ob) mice. Life Sciences 30: 1423–1432CrossRefGoogle Scholar
  100. Vanderweele DA, Pi-Sunyer FX, Novin D, Bush MJ (1980) Chronic insulin infusion suppresses food ingestion and body weight gain in rats. Brain Res Bull 5: 7–11CrossRefGoogle Scholar
  101. Wade GH, Zucker I (1978) Modulation of food intake and locomotor activity in female rats by diencephalic hormone implants. J Comp Physiol Psychol 72: 328–336CrossRefGoogle Scholar
  102. Wexler BC, McMurtry JP (1984) Dexamethasone suppression of cushingoid degenerative changes in obese spontaneously hypertensive rats ( SHR ). Metab 33: 281–288Google Scholar
  103. Woods SC, Lotter EC, McKay LD (1974) Metabolic hormones and regulation of body weight. Psych Rev 81: 26–43CrossRefGoogle Scholar
  104. Woods SC, Lotter EC, McKay LD, Porte D Jr. (1979) Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 285: 503–505CrossRefGoogle Scholar
  105. Yoshida T, Bray GA (1984) Catecholamine turnover in rats with ventromedial hypothalamic lesions. Am J Physiol 246: R558 — R565PubMedGoogle Scholar
  106. Yoshida T, Kemnitz JW, Bray GA (1983) Lateral hypothalamic lesions and norepinephrine turnover in rats. J Clin Invest 72: 919–927PubMedCrossRefGoogle Scholar
  107. Yoshimatsu H, Niijima A, Oomura Y, Kamabe K, Kataguchi T (1984) Effects of hypothalamic lesion on pancreatic autonomic nerve activity in the rat. Brain Res 303: 147–152PubMedCrossRefGoogle Scholar
  108. Young JB, Landsberg L (1980) Impaired suppression of sympathetic activity during fasting in the gold thioglucose-treated mouse. J Clin Invest 65: 1086–1094PubMedCrossRefGoogle Scholar
  109. Yukimura Y, Bray GA (1978a) Effect of adrenalectomy of thyroid function and insulin levels in obese (ob/ob) mice. Proc Soc Exp Bio Med 159: 364–367Google Scholar
  110. Yukimura Y, Bray GA (1978b) Effects of adrenalectomy on body weight and the size and number of fat cells in the Zucker (fatty) rat. Endo Res Commun 5: 189–198CrossRefGoogle Scholar
  111. Yukimura Y, Bray GA, Wolfsen AR (1978) Some effects of adrenalectomy in the fatty rat. Endo 103: 1924–1928Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • G. A. Bray
    • 1
  1. 1.Section of Diabetes and Clinical NutritionUniversity of Southern California, USC School of MedicineLos AngelesUSA

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