Comprehensive Physiology Wiley Online Library

Physiological Responses of Mammals to Overnutrition

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Consequences of Overnutrition
1.1 Thrifty Gene: Altered Lipid Metabolism
1.2 Animal Models
1.3 Physiological Consequences
2 Factors Influencing the Response to Overnutrition
2.1 Gender
2.2 Age
2.3 Genetics
2.4 Exercise
2.5 Stress
2.6 Diet Composition
2.7 Season/Food Availability
3 Physiological Mechanisms Underlying Responses to Overnutrition
3.1 Cellular
3.2 Endocrine Mechanisms
3.3 Neural Mechanisms Mediating the Response to Overnutrition
4 Summary
Figure 1. Figure 1.

Organ weights in obese (O) and nonobese (L) victims of sudden traumatic death (controlled for sex and body length). Organ weights for heart, liver, and kidney were significantly greater in the obese accident victims (n = 26) than in the nonobese (n = 41) (*P < 0.05). No significant differences in spleen or brain. Obesity in these subjects was defined as body weights 20% greater than upper limits of desirable body weight for individuals with large frames 186.

Figure 2. Figure 2.

Weight gain vs. cumulative excess caloric intake in male volunteers. Four were overfed a mixed diet for 7 months while in prison with access to caffeine‐containing beverages and cigarette smoking; four were overfed fat for 3 months in a clinical research center with restricted activity, smoking, and caffeine‐containing beverages.

Reprinted with permission from Danforth 60
Figure 3. Figure 3.

Basic steps in lipogenesis and lipolysis in human adipocytes. Triglyceride (TG) circulates in blood in the form of lipoproteins, where it is broken down into free fatty acids (FFA) by lipoprotein lipase (LPL), which is synthesized in the white adipocyte and located on the plasma membrane of the capillary endothelial cell. The FFA diffuse into the white adipocyte where they are re‐esterified with glycerol to form TG. Insulin enhances the storage of fat as TG by increasing synthesis of LPL and facilitating the transport of glucose into the white adipocyte by stimulating the Glut 4 glucose transporter protein. Lipolysis occurs via a cAMP‐mediated cascade, which results in the phosphorylation of hormone‐sensitive lipase (HSL), an enzyme which hydrolyzes TG into FFA and glycerol. These FFA are then free to diffuse into the blood. Lipolysis is stimulated by the β1‐noradrenergic receptor [via a G‐stimulatory (Gs) protein] and inhibited by the α2‐noradrenergic and A1‐adenosine receptors [via a G‐inhibitory (Gi) protein]. Insulin inhibits lipolysis by inhibiting HSL. PDE is phosphodiesterase.

Expanded from Hirsch et al. 118


Figure 1.

Organ weights in obese (O) and nonobese (L) victims of sudden traumatic death (controlled for sex and body length). Organ weights for heart, liver, and kidney were significantly greater in the obese accident victims (n = 26) than in the nonobese (n = 41) (*P < 0.05). No significant differences in spleen or brain. Obesity in these subjects was defined as body weights 20% greater than upper limits of desirable body weight for individuals with large frames 186.



Figure 2.

Weight gain vs. cumulative excess caloric intake in male volunteers. Four were overfed a mixed diet for 7 months while in prison with access to caffeine‐containing beverages and cigarette smoking; four were overfed fat for 3 months in a clinical research center with restricted activity, smoking, and caffeine‐containing beverages.

Reprinted with permission from Danforth 60


Figure 3.

Basic steps in lipogenesis and lipolysis in human adipocytes. Triglyceride (TG) circulates in blood in the form of lipoproteins, where it is broken down into free fatty acids (FFA) by lipoprotein lipase (LPL), which is synthesized in the white adipocyte and located on the plasma membrane of the capillary endothelial cell. The FFA diffuse into the white adipocyte where they are re‐esterified with glycerol to form TG. Insulin enhances the storage of fat as TG by increasing synthesis of LPL and facilitating the transport of glucose into the white adipocyte by stimulating the Glut 4 glucose transporter protein. Lipolysis occurs via a cAMP‐mediated cascade, which results in the phosphorylation of hormone‐sensitive lipase (HSL), an enzyme which hydrolyzes TG into FFA and glycerol. These FFA are then free to diffuse into the blood. Lipolysis is stimulated by the β1‐noradrenergic receptor [via a G‐stimulatory (Gs) protein] and inhibited by the α2‐noradrenergic and A1‐adenosine receptors [via a G‐inhibitory (Gi) protein]. Insulin inhibits lipolysis by inhibiting HSL. PDE is phosphodiesterase.

Expanded from Hirsch et al. 118
References
 1. Acheson, K. J., V. Schultz, T. Bessard, E. Ravussin, E. Jequier, and J. P. Flatt. Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal. Am. J. Physiol. 246 (Endocrinol. Metab. 9): E62–E70, 1984.
 2. Ackroff, K., and A. Sclafani. Sucrose‐induced hyperphagia and obesity in rats fed a macronutrient self‐selection diet. Physiol. Behav. 44: 181–187, 1988.
 3. Ahmad, I., A. W. Steggles, A. J. Carrillo, and J. A. Finklestein. Obesity and sex‐related alterations in growth hormone mRNA levels. Mol. Cell. Endocrinol. 65: 103–109, 1989.
 4. Amir, S., M. Lagiorgia, and R. Pollock. Intra‐ventromedial hypothalamic injection of insulin suppresses brown fat ther‐mogenesis in the anaesthetized rat. Brain Res. 480: 340–343, 1989.
 5. Anand, B. K., and J. R. Brobeck. Hypothalamic control of food intake in rats and cats. Yale J. Biol. Med. 24: 123–140, 1951–1952.
 6. Anand, B. K., G. S. China, K. N. Sharma, S. Dua, and B. Singh. Activity of single neurons in the hypothalamic feeding centers: effect of glucose. Am. J. Physiol. 207: 1146–1154, 1964.
 7. Anonymous. Lipogenesis in diabetes and obesity. Nutr. Rev. 49: 255–256, 1991.
 8. Applegate, E. A., D. E. Upton, and J. S. Stern. Exercise and detraining: effect on food intake, adiposity and lipogenesis in Osborne‐Mendel rats made obese by a high fat diet. J. Nutr. 114: 447–459, 1984.
 9. Asayama, K., Y. Okada, and K. Kato. Peroxisomal beta‐oxidation in liver and muscles of gold‐thioglucose‐induced obese mice: correlation with bodyweight. Int. J. Obes. 15: 45–49, 1991.
 10. Ashlog, J., P. Randall, and B. Hoebel. Hypothalamic hyperphagia: dissociation from hyperphagia following destruction of noradrenergic neurons. Science 190: 399–401, 1975.
 11. Astrup, A., T. Andersen, O. Henriksen, N. J. Christensen, J. Bulow, J. Madsen, and F. Quaade. Impaired glucose‐induced thermogenesis in skeletal muscle in obesity. The role of the sympathoadrenal system. Int. J. Obes. 11: 51–56, 1987.
 12. Astrup, A., N. J. Christensen, L. Simonsen, and J. Bulow. Effects of nutrient intake on sympathoadrenal activity and thermogenic mechanisms. J. Neurosci. Methods 34: 187–192, 1990.
 13. Atwater, W. O., and A. P. Bryand. Results of experiments on the metabolism of matter and energy in the human body. In: Connecticut (Storrs) Agricultural Experiment Station 12th Annual Report Storrs, CT: Office of Experimental Stations, 1900, p. 73–123.
 14. Ballor, D. Exercise training elevates RMR during moderate but not severe dietary restriction in obese male rats. J. Appl. Physiol.: Respir. Environ. Exerc. Physiol. 70: 2303–2310, 1991.
 15. Ballor, D. L., V. L. Katch, M. D. Becque, and C. R. Marks. Resistance weight training during caloric restriction enhances lean body weight maintenance. Am. J. Clin. Nutr. 47: 19–25, 1988.
 16. Barakat, H. A., V. D. McLendon, J. W. Carpenter, R. H. L. Marks, N. Legett, K. O'Brien, and J. F. Caro. Lipogenic potential of liver from morbidly obese patients with and without non‐insulin‐dependent diabetes. Metabolism 40: 280–285, 1991.
 17. Bartness, T. J. Species‐specific changes in the metabolic control of food intake: integrating the animal with its environment. Int. J. Obes. 14(suppl. 3): 115–124, 1990.
 18. Bartness, T. J., and G. N. Wade. Photoperiodic control of body weight and energy metabolism in Syrian hamsters (Mesocricetus auratus): role of pineal gland, melatonin, gonads, and diet. Endocrinology 114: 492–498, 1984.
 19. Beck, B., A. Burlet, J.‐P. Nicolas, and C. Burlet. Neurotensin in microdissected brain nuclei and in the pituitary of the lean and obese Zucker rats. Neuropeptides 13: 1–7, 1989.
 20. Beck, B., A. Burlet, J. P. Nicolas, and C. Burlet. Hyperphagia in obesity is associated with a central peptidergic dysregulation in rats. J. Nutr. 120: 806–811, 1990.
 21. Beck, B., A. Stricker‐Krongrad, A. Burlet, J.‐P. Nicolas, and C. Burlet. Influence of diet composition on food intake and hypothalamic neuropeptide Y (NPY) in the rat. Neuropeptides 17: 197–203, 1990.
 22. Bell, G. E., and J. S. Stern. Evaluation of body composition of young obese and lean Zucker rats. Growth 41: 63–80, 1977.
 23. Bjorntrop, P., M. Karlsson, H. Pertoft, P. Pettersson, L. Sjostrom, and U. Smith. Isolation and characterization of cells from rat adipose tissue developing into adipocytes. J. Lipid Res. 19: 316–324, 1978.
 24. Bjorntrop, P., M. Karlsson, P. Pettersson, and G. Sypniewska. Differentiation and function of rat adipocyte precursor cells in primary culture. J. Lipid Res. 21: 714–723, 1980.
 25. Bodurtha, J. N., M. Mosteller, J. K. Hewitt, W. E. Nance, L. J. Eaves, W. B. Moskowitz, S. Katz, and R. M. Schieken. Genetic analysis of anthropometric measures in 11‐year‐old twins: the Medical College of Virginia twin study. Pediatr. Res. 28: 1–4, 1990.
 26. Bogardus, C., S. Lillioja, and E. Ravussin. The pathogenesis of obesity in man: result of studies on Pima Indians. Int. J. Obes. 14 (suppl. 1): 5–15, 1990.
 27. Bouchard, C. Genetic factors in obesity. Med. Clin. North Am. 73: 67–81, 1989.
 28. Bouchard, C. Current understanding of the etiology of obesity: genetic and nongenetic factors. Am. J. Clin. Nutr. 53: 1562S–1565S, 1991.
 29. Bouchard, C. Heredity and the path to overweight and obesity. Med. Sci. Sports. Exerc. 23: 285–291, 1991.
 30. Bouchard, C., R. J. Shephard, T. Stephens, J. R. Sutton, and B. D. McPherson (Eds). Exercise, Fitness and Health: A Concensus of Current Knowledge. Champaign, IL: Human Kinetics, 1990, p. 217–259, 293–306, 315–320, 497‐511.
 31. Bray, G. Nutrient balance and obesity: an approach to control of food intake in humans. Med. Clin. North Am. 73: 29–44, 1989.
 32. Bray, G. Obesity—a state of reduced sympathetic activity and normal or high adrenal activity (the autonomic and adrenal hypothesis revisited). Int. J. Obes. 14 (suppl. 3): 77–92, 1990.
 33. Bray, G. A. Classification and evaluation of the obesities. Med. Clin. North Am. 73: 161–184, 1989.
 34. Bray, G. A., and L. A. Campfield. Metabolic factors in the control of energy stores. Metab. Clin. Exp. 24: 99–117, 1975.
 35. Bray, G. A., D. A. York, and J. S. Fisler. Experimental obesity: a homoestatic failure due to defective nutrient stimulation of the sympathetic nervous system. Vitam. Horm. 45: 1–125, 1989.
 36. Brehm, B. A., and B. Gutin. Recovery energy expenditure for steady state exercise in runners and nonexercisers. Med. Sci. Sports Exerc. 18: 205–210, 1986.
 37. Brown, P. J., and M. Konner. An anthropological perspective on obesity. Ann. N. Y. Acad. Sci. 499: 29–46, 1987.
 38. Brownell, K. D., M. R. C. Greenwood, E. Stellar, and E. E. Shrager. The effects of repeated cycles of weight loss and regain in rats. Physiol. Behav. 38: 459–464, 1986.
 39. Bruning, P. F., J. M. G. Bonfrer, A. Ansink, N. S. Russell, and M. de Jong‐Bakker. Why is breast cancer so frequent in The Netherlands? Eur. J. Surg. Oncol. 14: 115–122, 1988.
 40. Burger, A. G., M. O'Connell, K. Scheidegger, R. Woo, and E. Danforth, Jr. Monodeiodination of triiodothyronine and reverse triiodothyronine during low and high calorie diets. J. Clin. Endocrinol. Metab. 65: 829–835, 1987.
 41. Callaway, C. W. Obesity. In: Public Health Reports, July‐Aug (suppl.), Washington, D.C.: Public Health Service, 1987, p. 26–29.
 42. Calogero, A. E., R. Bernardini, A. M. Margioris, G. Bagdy, W. T. Galluccini, P. J. Munson, L. Tamarkin, T. P. Tomai, L. Brady, P. W. Gold, and G. P. Chrousos. Effect of serotonergic agonists and antagonists on corticotropin‐releasing hormone secretion by explanted rat hypothalami. Peptides 10: 189–200, 1989.
 43. Calogero, A. E., W. T. Gallucci, G. P. Chrousos, and P. W. Gold. Catecholamine effects upon rat hypothalamic corticotropin‐releasing hormone secretion in vitro. J. Clin. Invest. 82: 839–846, 1988.
 44. Campaigne, B. N. Body fat distribution in females: metabolic consequences and implications for weight loss. Med. Sci. Sports Exerc. 22: 291–297, 1990.
 45. Campfield, L. A., and F. J. Smith. Transient declines in blood glucose signal meal initiation. Int. J. Obes. 14 (suppl.3): 15–33, 1990.
 46. Canguilhem, B., J. P. Vaultier, B. Pevet, G. Coumaros, M. Masson‐Pevet, and I. Bantz. Photoperiodic regulation of body mass, food intake, hibernation, and reproduction in intact and castrated male European hamsters, Cricetus cricetus. J. Comp. Physiol. [A] 163: 549–557, 1988.
 47. Cavallo, E., F. Armellini, M. Zamboni, R. Vicnetini, M. P. Milani, and O. Bosello. Resting metabolic rate, body composition and thyroid hormones. Short term effects of very low calorie diet. Horm. Metab. Res. 22: 632–635, 1990.
 48. Chang, S., B. Graham, F. Yakubu, D. Lin, J. C. Peters, and J. O. Hill. Metabolic differences between obesity‐prone and obesity‐resistant rats. Am. J. Physiol. 259(Regulatory Integrative Comp. Physiol. 28): R1103–R1110, 1990.
 49. Choban, P. S., L. J. Weireter, Jr., and C. Maynes. Obesity and increased mortality in blunt trauma. J. Trauma 31: 1253–1257, 1991.
 50. Clemmons, D. R., D. K. Snyder, R. Williams, and L. E. Underwood. Growth hormone administration conserves lean body mass during dietary restriction in obese subjects. J. Clin. Endocrinol. Metab. 64: 878–883, 1987.
 51. Cohen, R., R. C. Klesges, M. Summerville, and A. W. Meyers. A developmental analysis of the influence of body weight on the sociometry of children. Addict. Behav. 14: 473–476, 1989.
 52. Collins, K. J. Low indoor temperatures and morbidity in the elderly. Age Ageing 15: 212–220, 1987.
 53. Contreras, R. J., S. King, L. Rives, A. Williams, and T. Wattleton. Dietary obesity and weight cycling in rats: a model of stress‐induced hypertension? Am. J. Physiol. 261 (Regulatory Integrative Comp. Physiol. 30): R848–R857, 1991.
 54. Cooney, G. J., M. A. Vanner, J. L. Nicks, P. F. Williams, and I. D. Caterson. Changes in the lipogenic response to feeding of liver, white adipose tissue and brown adipose tissue during the development of obesity in the gold‐thioglucose‐injected mouse. Biochem. J. 259: 652–657, 1989.
 55. Cooper, J. R., F. E. Bloom, and R. H. Roth. The Biochemical Basis of Neuropharmocology (6th ed.). New York: Oxford University Press, 1991, p. 320.
 56. Copeland, K. C., R. B. Colletti, J. T. Devlin, and T. L. McAuliffe. The relationship between insulin‐like growth factor‐I, adiposity, and aging. Metabolism 39: 584–587, 1990.
 57. Coscina, D. V., and J. N. Nobrega. 6‐Hydroxydopamine‐induced blockade of hypothalamic obesity: critical role of brain dopamine‐norepinephrine interaction. Prog. Neuropsychopharmacol. Biol. Psychiatry 6: 369–372, 1982.
 58. Cox, B., T. Lee, and J. Parkes. Decreased ability to cope with heat and cold linked to a dysfunction in a central dopaminergic pathway in elderly rats. Life Sci. 28: 2039–2044, 1981.
 59. Cummings, S., and V. Seybold. Relationship of alpha‐1‐ and alpha‐2‐adrenergic binding sites to regions of the paraventricular nucleus of the hypothalamus containing corticotropin‐releasing factor and vasopressin neurons. Neuroendocrinology 47: 523–532, 1988.
 60. Danforth, E., Jr. Diet and obesity. Am. J. Clin. Nutr. 41: 1132–1145, 1985.
 61. Dark, J., I. Zucker, and G. N. Wade. Photoperiodic regulation of body mass, food intake, and reproduction in meadow voles. Am. J. Physiol. 245 (Regulatory Integrative Comp. Physiol. 16): R334–R338, 1983.
 62. Davis, D. E. Hibernation and circannual rhythms of food consumption in marmots and ground squirrels. Q. Rev. Biol. 51: 477–514, 1976.
 63. De Boer, J. O., A. J. H. Van Es, J. M. A. Van Raaij, and J. G. A. J. Hautvast. Energy requirements and energy expenditure of lean and overweight women, measured by indirect calorimetry. Am. J. Clin. Nutr. 46: 13–21, 1987.
 64. De Groot, L. C. P. G. M., A. J. H. Van Es, J. M. A. Van Raaij, J. E. Vogt, and J. G. A. J. Hautvast. Adaptation of energy metabolism of overweight women to alternating and continuous low energy intake. Am. J. Clin. Nutr. 50: 1314–1323, 1989.
 65. De Luise, M., and M. Harker. Skeletal muscle metabolism: effect of age, obesity, thyroid and nutritional status. Horm. Metabol. Res. 21: 410–415, 1989.
 66. Den Besten, C., G. Vansant, J. A. Weststrate, and P. Deurenberg. Resting metabolic rate and diet‐induced thermogenesis in abdominal and gluteal‐femoral obese women before and after weight reduction. Am. J. Clin. Nutr. 47: 840–847, 1988.
 67. Desautels, M., and R. A. Dulos. Weight gain and brown fat composition of mice selected for high body weight fed a high‐fat diet. Am. J. Physiol. 258 (Regulatory Integrative Comp. Physiol. 29): R608–R615, 1990.
 68. DeVries, H. A., and D. E. Gray. After effects of exercise upon resting metabolic rate. Res. Q. 34: 315–321, 1962.
 69. Donato, K., and D. M. Hegsted. Efficiency of utilization of various sources of energy for growth. Proc. Natl. Acad. Sci. U.S.A. 82: 4866–4870, 1985.
 70. Donnelly, J. E., N. P. Pronk, D. J. Jacobsen, S. J. Pronk, and J. M. Jakicic. Effects of a very‐low‐calorie diet and physical‐training regimens on body composition and resting metabolic rate in obese females. Am. J. Clin. Nutr. 54: 56–61, 1991.
 71. Dreon, D. M., B. Frey‐Hewitt, N. Elsworth, P. T. Williams, R. B. Terry, and P. D. Wood. Dietary fat: carbohydrate ratio and obesity in middle‐aged men. Am. J. Clin. Nutr. 47: 995–1000, 1988.
 72. Dubuc, P. U. Effects of phenotype, feeding condition and cold exposure on thyrotropin and thyroid hormones of obese and lean mice. Endocr. Regul. 25: 171–175, 1991.
 73. Dunn, A., and C. Berridge. Corticotropin‐releasing factor administration elicits a stress‐like activation of cerebral cate‐cholaminergic systems. Pharmacol. Biochem. Behav. 27: 685–691, 1987.
 74. Ernsberger, P., and D. O. Nelson. Refeeding hypertension in dietary obesity. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 25): R47–R55, 1988.
 75. Evans, D. J., R. G. Hoffmann, R. K. Kalkhjof, and A. H. Kissebah. Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women. J. Clin. Endocrinol. Metab. 57: 304–310, 1983.
 76. Ezaki, O., N. Fukuda, and H. Itakura. Role of two types of glucose transporters in enlarged adipocytes from aged obese rats. Diabetes 39: 1543–1549, 1990.
 77. Favarger, P., and J. Gerlach. Studies on the synthesis of fats from acetate or glucose. II. The relative roles of adipose tissue and other tissues in lipogenesis in mice. Helv. Physiol. Pharmacol. Acta 13: 96–105, 1955.
 78. Finklestein, J. A., P. Jervois, M. Menadue, and J. O. Willough. Growth hormone and prolactin secretion in genetically obese Zucker rats. Endocrinology 118: 1233–1236, 1986.
 79. Fisler, J. S., J. R. Lupien, R. D. Wood, G. A. Bray, and R. A. Schemmel. Brown fat thermogenesis in a rat model of dietary obesity. Am. J. Physiol. 253 (Regulatory Integrative Comp. Physiol. 24): R756–R762, 1987.
 80. Flatt, J. P. The difference in the storage capacities for carbohydrate and for fat, and its implications in the regulation of body weight. Ann. N. Y. Acad. Sci. 499: 104–123, 1987.
 81. Flatt, J. P., E. Ravussin, K. J. Acheson, and E. Jequier. Effects of dietary fat on postprandial substrate oxidation and on carbohydrate and fat balances. J. Clin. Invest. 76: 1019–1024, 1985.
 82. Forbes, G. B., and J. C. Reina. Adult lean body mass declines with age: some longitudinal observations. Metabolism 19: 653–663, 1970.
 83. Freedman‐Akabas, S., E. Colt, H. R. Kissileff, and F. X. Pi‐Sunyer. Lack of sustained increase in VO2 following exercise in fit and unfit subjects. Am. J. Clin. Nutr. 41: 545–549, 1985.
 84. Freeman, P. H., and P. J. Wellman. Brown adipose tissue thermogenesis induced by low level electrical stimulation of hypothalamus in rats. Brain Res. Bull. 18: 7–11, 1987.
 85. Friedlander, Y., J. D. Kark, N. A. Kaufmann, E. M. Berry, and Y. Stein. Familial aggregation of body mass index in ethnically diverse families in Jerusalem. The Jerusalem Lipid Research Clinic. Int. J. Obes. 12: 237–247, 1988.
 86. Friedman, M. I. Body fat and the metabolic control of food intake. Int. J. Obes. 14 (suppl. 3): 53–67, 1990.
 87. Fukushima, M., K. Tokunaga, J. Lupien, J. W. Kemnitz, and G. A. Bray. Dynamic and static phases of obesity following lesions in PVN and VMH. Am. J. Physiol. 253 (Regulatory Integrative Comp. Physiol. 24): R523–R529, 1987.
 88. Fuller, N. J., D. M. Stirling, S. Dunnett, G. P. Reynolds, and M. Ashwell. Decreased brown adipose tissue thermogenic activity following a reduction in brain serotonin by intraventricular p‐chlorophenylalanine. Biosci. Rep. 7: 121–127, 1987.
 89. Furnsinn, C., M. Komjati, O. D. Madsen, B. Schneider, and W. Waldhausl. Lifelong sequential changes in glucose tolerance and insulin secretion in genetically obese Zucker rats (fa/fa) fed a diabetogenic diet. Endocrinology 128: 1093–1099, 1991.
 90. Gerardo‐Gettens, T., B. J. Moore, J. S. Stern, and B. A. Horwitz. Prolactin stimulates food intake in the absence of ovarian progesterone. Am. J. Physiol. 256 (Regulatory Integrative Comp. Physiol. 27): R701–R706, 1989.
 91. Glass, A. R. Endocrine aspects of obesity. Med. Clin. North Am. 73: 139–160, 1989.
 92. Glick, Z., S. J. Wickler, J. S. Stern, and B. A. Horwitz. Blood flow into brown fat of rats is greater after high carbohydrate than after a high fat test meal. J. Nutr. 114: 1934–1939, 1984.
 93. Glickman, L. T., F. S. Schofer, and L. J. McKee. Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs. J. Toxicol. Environ. Health 28: 407–414, 1989.
 94. Goldman, C. K., L. Marino, and S. F. Leibowitz. Postsynaptic α2‐noradrenergic receptors mediate feeding induced by paraventricular nucleus injection of norepinephrine and clondine. Eur. J. Pharmacol. 115: 11–19, 1985.
 95. Gong, L. T. W., J. S. Stern, and B. A. Horwitz. High fat feeding increases brown fat GDP binding in lean but not obese Zucker rats. J. Nutr. 120: 786–792, 1990.
 96. Graham, B., S. Chang, D. Lin, F. Yakubu, and J. O. Hill. Effect of weight cycling on susceptibility to dietary obesity. Am. J. Physiol. 259 (Regulatory Integrative Comp. Physiol. 30): R1096–R1102, 1990.
 97. Gray, D. S. Diagnosis and prevalence of obesity. Med. Clin. North Am. 73: 1–13, 1989.
 98. Gray, D. S., J. S. Fisler, and G. A. Bray. Effects of repeated weight loss and regain on body composition in obese rats. Am. J. Nutr. 47: 393–399, 1988.
 99. Greenberg, D., and S. C. Weatherford. Obese and lean Zucker rats differ in preferences for sham‐fed corn oil or sucrose. Am. J. Physiol. 259 (Regulatory Integrative Comp. Physiol. 30): R1093–R1095, 1990.
 100. Grundy, S. M., and J. P. Barnett. Metabolic and health complications of obesity. Dis. Mon. 36: 643–696, 1990.
 101. Guesnet, Ph., J.‐M. Bourre, M. Guerre‐Millo, G. Pascal, and G. Durand. Tissue phospholipid fatty acid composition in genetically lean (Fa/‐) or obese (fa/fa) Zucker female rats on the same diet. Lipids 25: 517–522, 1990.
 102. Guichard, C., I. Dugail, X. Le Liepvre, and M. Lavau. Genetic regulation of fatty acid synthetase expression in adipose tissue: overtranscription of the gene in genetically obese rats. J. Lipid Res. 33: 679–687, 1992.
 103. Haggarty, P., K. W. J. Wahle, Peter J. Reeds, and J. M. Fletcher. Whole body fatty acid synthesis and fatty acid intake in young rats of the Zucker strain (Fa/‐ and fa/fa). Int. J. Obes. 11: 41–50, 1986.
 104. Han, P., and L. Frohman. Hyperinsulinemia in tube‐fed hypo‐physectomized rats bearing hypothalamic lesions. Am. J. Physiol. 219: 1632–2636, 1970.
 105. Han, P., and A. Lui. Obesity and impaired growth of rats force fed 40 days after hypothalamic lesions. Am. J. Physiol. 211: 229–231, 1966.
 106. Han, P. W. Hypothalamic obesity in rats without hyperphagia. Trans. N. Y. Acad. Sci. 30: 229–242, 1967.
 107. Han, P. W., C.‐H. Lin, K.‐C. Chu, J.‐Y. Mu, and A.‐C. Liu. Hypothalamic obesity in weanling rats. Am. J. Physiol. 209: 627–631, 1965.
 108. Havrankova, J., M. Brownstein, and J. Roth. Insulin and insulin receptors in rodent brain. Diabetologia 20: 268–273, 1981.
 109. Havrankova, J., and J. Roth. Insulin receptors are widely distributed in the central nervous system of the rat. Nature 272: 827–829, 1978.
 110. Heldmaier, G., S. Steinlechner, J. Rafael, and P. Vsiansky. Photoperiodic control and effects of melatonin on nonshivering thermogenesis and brown adipose tissue. Science 212: 917–919, 1981.
 111. Hering, J. L., P. A. Mole, C. N. Meredith, and J. S. Stern. Effect of suspending exercise training on resting metabolic rate in women. Med. Sci. Sports Exerc. 24: 59–65, 1992.
 112. Herman, C. P., and J. Polivy. Anxiety, restraint, and eating behavior. J. Abnorm. Psychol. 84: 666–672, 1975.
 113. Hetherington, A. W. Non‐production of hypothalamic obesity in the rat by lesions rostral or dorsal to the ventro‐medial hypothalamic nuclei. J. Comp. Neurol. 80: 33–45, 1945.
 114. Hetherington, A. W., and S. W. Ranson. Hypothalamic lesions and adiposity in the rat. Anat. Rec. 78: 149–172, 1940.
 115. Higuchi, H., H.‐Y. T. Yang, and S. L. Sabol. Rat neuropeptide Y precursor gene expression. J. Biol. Chem. 263: 6288–6293, 1987.
 116. Hill, J. O., J. C. Peters, G. W. Reed, D. G. Schlundt, T. Sharp, and H. L. Greene. Nutrient balance in humans: effects of diet composition. Am. J. Clin. Nutr. 54: 10–17, 1991.
 117. Himms‐Hagen, J. Defective brown adipose tissue thermogenesis in obese mice. Int. J. Obes. 9 (suppl. 2): 17–24, 1985.
 118. Hirsch, J., S. K. Fried, N. K. Edens, and R. L. Leibel. The fat cell. Med. Clin. North Am. 73: 83–96, 1989.
 119. Hoffman, R. A., K. Davidson, and K. Steinberg. Influence of photoperiod and temperature on weight gain, food consumption, fat pads and thyroxine in male golden hamsters. Growth 46: 150–162, 1982.
 120. Hollenberg, C. H. Perspectives in adipose tissue physiology. Int. J. Obes. 14 (suppl. 3): 135–152, 1990.
 121. Holt, S. J., H. V. Wheal, and D. A. York. Hypothalamic control of brown adipose tissue in Zucker lean and obese rats. Effect of electrical stimulation of the ventromedial nucleus and other hypothalamic centres. Brain Res. 405: 227–233, 1987.
 122. Holt, S. J., H. V. Wheal, and D. A. York. Response of brown adipose tissue to electrical stimulation of hypothalamic centres in intact and adrenalectomized Zucker rats. Neurosci. Lett. 84: 63–67, 1988.
 123. Holt, S. J., and D. A. York. Effect of lateral hypothalamic lesion on brown adipose tissue of Zucker lean and obese rats. Physiol. Behav. 43: 293–299, 1988.
 124. Holt, S. J., D. A. York, and J. T. R. Fitzsimons. The effects of corticosterone, cold exposure and overfeeding with sucrose on brown adipose tissue of obese Zucker rats (fa/fa). Biochem. J. 214: 215–223, 1983.
 125. Horswill, C. A., and W. B. Zipf. Elevated blood pressure in obese children: influence of gender, age, weight and serum insulin levels. Int. J. Obes. 15: 453–459, 1991.
 126. Horton, R., and J. F. Tait. Androstenedione production and interconversion rates measured in peripheral blood and studies on the possible site of its conversion to testosterone. J. Clin. Invest. 45: 301–313, 1966.
 127. Huang, H. H., R. W. Steger, and J. Meites. Capacity of old versus young male rats to release thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) in response to different stimuli. Exp. Aging Res. 6: 3–12, 1980.
 128. Inui, Y., S. Kawata, Y. Matsuzawa, K. Tokunaga, S. Fujioka, S. Tamura, T. Kobatake, Y. Keno, and S. Tarui. Increased level of apolipoprotein B mRNA in the liver of ventromedial hypothalamus lesioned obese rats. Biochem. Biophys. Res. Commun. 163: 1107–1112, 1989.
 129. Istfan, N. W., C. S. Plaisted, B. R. Bistrian, and G. L. Blackburn. Insulin resistance versus insulin secretion in the hypertension of obesity. Hypertension 19: 385–392, 1992.
 130. Jebb, S. A., G. R. Goldberg, W. A. Coward, P. R. Murgatroyd, and A. M. Prentice. Effects of weight cycling caused by intermittent dieting on metabolic rate and body composition in obese women. Int. J. Obes. 15: 367–374, 1991.
 131. Jeevanandam, M., D. H. Young, and W. R. Schiller. Obesity and the metabolic response to severe multiple trauma in man. J. Clin. Invest. 87: 262–269, 1991.
 132. Jeffery, R. W. Population perspectives on the prevention and treatment of obesity in minority populations. Am. J. Clin. Nutr. 53: 1621S–1624S, 1991.
 133. Jeffery, R. W., J. L. Forster, A. R. Folsom, R. V. Luepker, D. R. Jacobs, Jr., and H. Blackburn. The relationship between social status and body mass index in the Minnesota Heart Health Program. Int. J. Obes. 13: 59–67, 1989.
 134. Jhanwar‐Uniyal, M., M. H. Papamichael, and S. F. Leibowitz. Glucose‐dependent changes in α2‐noradrenergic receptors in hypothalamic nuclei. Physiol. Behav. 44: 611–617, 1988.
 135. Joanny, O., J. Steinberg, A. Zamora, C. Conte‐Devolx, Y. Millet, and C. Oliver. Corticotropin‐releasing factor release from in vitro superfused and incubated rat hypothalamus. Effect of potassium, norepinephrine and dopamine. Peptides 10: 903–911, 1989.
 136. Johnson, P., J. Stern, M. Greenwood, L. Zucker, and J. Hirsch. Effect of early nutrition on adipose cellularity and pancreatic insulin release in the Zucker rat. J. Nutr. 103: 738–743, 1973.
 137. Johnson, P. R., M. R. C. Greenwood, B. A. Horwitz, and J. S. Stern. Animal models of obesity: genetic aspects. Annu. Rev. Nutr. 11: 325–353, 1991.
 138. Jones, A., D. H. Davies, J. R. Dove, M. A. Collinson, and P. M. R. Brown. Identification and treatment of risk factors for coronary heart disease in general practice: a possible screening model. BMJ 296: 1711–1714, 1988.
 139. Kanarek, R. B., J. R. Aprille, E. Hirsch, L. Gualtiere, and C. A. Brown. Sucrose‐induced obesity: effect of diet on obesity and brown adipose tissue. Am. J. Physiol. 253 (Regulatory Integrative Comp. Physiol. 24): R158–R166, 1987.
 140. Kaplan, R. M., T. L. Patterson, J. F. Sallis, Jr., and P. R. Nader. Exercise suppresses heritability estimates for obesity in Mexican‐American families. Addict. Behav. 14: 581–588, 1989.
 141. Kayman, S., W. Bruvold, and J. S. Stern. Maintenance and relapse after weight loss in women: behavioral aspects. Am. J. Clin. Nutr. 52: 800–807, 1990.
 142. Keesey, R. E. Physiological regulation of body weight and the issue of obesity. Med. Clin. North Am. 73: 15–26, 1989.
 143. Kemnitz, J. W., R. W. Goy, T. J. Flitsch, J. J. Lohmiller, and J. A. Robinson. Obesity in male and female Rhesus monkeys: fat distribution, glucoregulation, and serum androgen. J. Clin. Endocrinol. Metab. 69: 287–293, 1989.
 144. King, A. C., and D. L. Tribble. The role of exercise in weight regulation in nonathletes. Sports Med. 11: 331–349, 1991.
 145. King, H., D. C. Rao, K. Bhatia, G. Koki, A. Collins, and P. Zimmet. Family resemblance for glucose tolerance in a Melanesian population, the Tolai. Hum. Hered. 39: 212–217, 1989.
 146. Kirchgessner, A. L., and A. Sclafani. Histochemical identification of a PVN‐hindbrain feeding pathway. Physiol. Behav. 42: 529–543, 1988.
 147. Kissebah, A. H., D. S. Freedman, and A. N. Peiris. Health risks of obesity. Med. Clin. North Am. 73: 111–138, 1989.
 148. Kjaer, M., N. J. Christensen, B. Sonne, E. A. Richter, and H. Galbo. Effect of exercise on epinephrine turnover in trained and untrained male subjects. J. Appl. Physiol.: Respir. Environ. Exerc. Physiol. 59: 1061–1067, 1985.
 149. Klem, M. L., R. C. Klesges, C. R. Bene, and M. W. Mellon. A psychometric study of restaint: the impact of race, gender, weight and marital status. Addict. Behav. 15: 147–153, 1990.
 150. Klesges, R. C., and L. H. Eck. Effects of obesity, social interactions, and physical environment on physical activity in preschoolers. Health Psychol. 9: 435–449, 1990.
 151. Knittle, J., and J. Hirsch. Effect of early nutrition on the development of rat epididymal fat pads: cellularity and metabolism. J. Clin. Invest. 47: 2091–2098, 1968.
 152. Koopmans, H. S. Endogenous gut signals and metabolites control daily food intake. Int. J. Obes. 14 (suppl. 3): 93–104, 1990.
 153. Kopelman, P. G. Neuroendocrine function in obesity. Clin. Endocrinol. 28: 675–689, 1988.
 154. Kristeller, J. L., and J. Rodin. Identifying eating patterns in male and female undergraduates using cluster analysis. Addict. Behav. 14: 631–642, 1989.
 155. Landerholm, T. E., and J. S. Stern. Adipose tissue lipolysis in vitro: a predictor of diet‐induced obesity in female rats. Am. J. Physiol. 263 (Regulatory, Integrative Comp. Physiol. 32): R1248–R1253, 1992.
 156. Landsberg, L. The sympathoadrenal system, obesity and hypertension. J. Neurosci. Methods 34: 179–186, 1990.
 157. Larkin, L. M., B. J. Moore, J. S. Stern, and B. A. Horwitz. Effect of photoperiod on body weight and food intake of obese and lean Zucker rats. Life Sci. 49: 735–745, 1991.
 158. Lean, M. E. J., P. R. Murgatroyd, I. Rothnie, I. W. Reid, and R. Harvey. Metabolic and thyroidal responses to mild cold are abnormal in obese diabetic women. Clin. Endocrinol. 28: 665–673, 1988.
 159. Leibowitz, S. F. Brain monoamines and peptides: role in the control of eating behavior. Federation Proc. 45: 1396–1403, 1986.
 160. Leiter, E. H. Control of spontaneous glucose intolerance, hyper‐insulinemia, and islet hyperplasia in nonobese C3H.SW male mice by Y‐linked locus and adrenal gland. Metabolism 37: 689–696, 1988.
 161. Lemons, A. D., S. N. Kreitzman, A. Coxon, and A. Howard. Selection of appropriate exercise regimes for weight reduction during VLCD and maintenance. Int. J. Obes. 13 (suppl. 2): 119–123, 1989.
 162. Levin, B. E., and A. C. Sullivan. Glucose‐induced norepinephrine and obesity resistance. Am. J. Physiol. 253 (Regulatory Integrative Comp. Physiol. 23): R475–R481, 1987.
 163. Levin, B. E., J. Triscari, S. Hogan, and A. C. Sullivan. Resistance to diet‐induced obesity: food intake, pancreatic sympathetic tone, and insulin. Am. J. Physiol. 252 (Regulatory Integrative Comp. Physiol. 23): R471–R478, 1987.
 164. Levin, B. E., J. Triscari, and A. C. Sullivan. The effect of diet and chronic obesity on brain catecholamine turnover in the rat. Pharmacol. Biochem. Behav. 24: 299–304, 1986.
 165. Lewis, D. S., H. A. Bertrand, C. A. McMahan, H. C. McGill, Jr., K. D. Carey, and E. J. Masoro. Influence of preweaning food intake on body composition of young adult baboons. Am. J. Physiol. 257 (Regulatory Integrative Comp. Physiol. 28): R1128–R1135, 1989.
 166. Llado, I., A. M. Proenza, F. Serra, A. Palou, and A. Pons. Dietary‐induced permanent changes in brown and white adipose tissue composition in rats. Int. J. Obes. 15: 415–419, 1990.
 167. Lopez‐Casillas, F., M. V. Ponce‐Castaneda, and K.‐H. Kim. In vivo regulation of the activity of the two promoters of the rat acetyl coenzyme‐A carboxylase gene. Endocrinology 129: 1049–1058, 1991.
 168. Lukaski, H. C. Methods for the assessment of human body composition: traditional and new. Am. J. Clin. Nutr. 46: 537–556, 1987.
 169. Ma, S. W. Y., and D. O. Foster. Brown adipose tissue, liver, and diet‐induced thermogenesis in cafeteria diet‐fed rats. Can. J. Physiol. Pharmacol. 67: 376–381, 1988.
 170. Marshall, J. D., D. W. Hazlett, D. W. Spady, and H. A. Quinney. Validity of convenient indicators of obesity. Hum. Biol. 63: 137–153, 1991.
 171. Martire, M., G. Pistritto, and P. Preziosi. Different regulation of serotonin receptors following adrenal hormone imbalance in the rat hippocampus and hypothalamus. J. Neural Transm. 78: 109–120, 1989.
 172. McDonald, R. B., B. A. Horwitz, J. S. Hamilton, and J. S. Stern. Cold‐ and norepinephrine‐induced thermogenesis in younger and older Fischer 344 rats. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 25): R457–R462, 1988.
 173. McDonald, R. B., J. S. Stern, and B. A. Horwitz. Thermogenic responses of younger and older rats to cold exposure: comparison of two strains. J. Gerontol. 44: B37–B42, 1989.
 174. McPhillips, J. B., K. M. Pellettera, E. Barrett‐Connor, D. L. Wingard, and M. H. Criqui. Exercise patterns in a population of older adults. Am. J. Prev. Med. 2: 65–72, 1989.
 175. Meisel, R. L., T. C. Hays, S. N. Del Paine, and V. R. Luttrell. Induction of obesity by group housing in female Syrian hamsters. Physiol. Behav. 47: 815–817, 1990.
 176. Mela, D. J., R. S. Cohen, and P. M. Kris‐Etherton. Lipoprotein metabolism in a rat model of diet‐induced adiposity. J. Nutr. 117: 1655–1662, 1987.
 177. Mercer, S. W., and P. Trayhurn. Effect of high fat diets on energy balance and thermogenesis in brown adipose tissue of lean and genetically obese (ob/ob) mice. J. Nutr. 117: 2147–2153, 1987.
 178. Miller, W. C. Diet composition, energy intake, and nutritional status in relation to obesity in men and women. Med. Sci. Sports Exerc. 23: 280–284, 1991.
 179. Miller, W. C. Introduction: obesity: diet composition, energy expenditure, and treatment of the obese patient. Med. Sci. Sports Exerc. 23: 273–274, 1991.
 180. Miller, W. C., A. K. Lindeman, J. Wallace, and M. Niederpruem. Diet composition, energy intake, and exercise in relation to body fat in men and women. Am. J. Clin. Nutr. 52: 426–430, 1990.
 181. Modan, M., S. Almog, Z. Fuchs, A. Chetrit, A. Lusky, and H. Halkin. Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs. Hypertension 17: 565–573, 1991.
 182. Mohs, M. E., T. K. Leonard, and R. R. Watson. Interrelationships among alcohol abuse, obesity, and type II diabetes mellitus: focus on Native Americans. World Rev. Nutr. Diet. 56: 93–172, 1988.
 183. Moore, B. J., J. S. Stern, and B. A. Horwitz. Brown fat mediates increased energy expenditure of cold‐exposed overfed neonatal rats. Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 22): R518–R524, 1986.
 184. Morton, J. L., M. Davenport, A. Beloff‐Chain, N. L. Bodkin, and B. C. Hansen. Correlation between β‐cell tropin concentrations and body weight in obese rhesus monkeys. Am. J. Physiol. 262 (Endocrinol. Metab. 25): E963–E967, 1992.
 185. Moss, N. D., and M. R. Dadds. Body weight attributions and eating self‐efficacy in adolescence. Addict. Behav. 16: 71–78, 1991.
 186. Naeye, R. L., and P. Roode. The sizes and numbers of cells in visceral organs in human obesity. Am. J. Clin. Pathol. 251–253, 1970.
 187. National Center for Health Statistics. Plan and Operation of the National Health and Nutrition Examination Survey. 1976–1980. Hyattsville, MD: U.S. Dept. of Health and Human Services, 1981.
 188. Neel, J. V. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress.” Am. J. Hum. Genet. 14: 353–362, 1962.
 189. Newby, F. D., M. DiGirolamo, G. A. Cotsonis, and M. H. Kunter. Model of spontaneous obesity in aging male Wistar rats. Am. J. Physiol. 259 (Regulatory Integrative Comp. Physiol. 30): R1117–R1125, 1990.
 190. Newsholme, E. A., and B. Crabtree. Substrate cycles in metabolic regulation and heat generation. Biochem. Soc. Symp. 41: 61–110, 1976.
 191. Nicolaidis, S., and P. C. Even. The ischymetric control of feeding. Int. J. Obes. 14 (suppl. 3): 35–52, 1990.
 192. Niijima, A., F. Rohner‐Jeanrenaud, and B. Jeanrenaud. Role of ventromedial hypothalamus on sympathetic efferents of brown adipose tissue. Am. J. Physiol. 247 (Regulatory Integrative Comp. Physiol. 18): R650–R654, 1984.
 193. Obst, B. E., R. A. Schemmel, D. Czajka‐Narins, and R. Merkel. Adipocyte size and number in dietary obesity resistant and susceptible rats. Am. J. Physiol. 240 (Endocrinol. Metab. 3): E47–E53, 1981.
 194. Olefsky, J. M., J. W. Farquhar, and G. M. Reaven. Reappraisal of the role of insulin in hypertriglyceridemia. Am. J. Med. 57: 551–560, 1974.
 195. Oscai, L. B., M. M. Brown, and W. C. Miller. Effect of dietary fat on food intake, growth and body composition in rats. Growth 48: 415–424, 1984.
 196. Oscai, L. B., W. C. Miller, and D. A. Arnall. Effects on dietary sugar and of dietary fat on food intake and body fat content in rats. Growth 51: 64–73, 1987.
 197. Pasquali, R., D. Antenucci, N. Melchionda, R. Fabbri, S. Venturoli, D. Patrono, and M. Capelli. Sex hormones in obese premenopausal women and their relationships to body fat mass and distribution, β cell function and diet composition. J. Endocrinol. Invest. 10: 345–350, 1987.
 198. Passmore, R., and R. E. Johnson. Some metabolic changes following prolonged moderate exercise. Metabol. 9: 452–455, 1960.
 199. Pedersen, O., C. R. Kahn, J. S. Flier, and B. B. Kahn. High fat feeding causes insulin resistance and a marked decrease in the expression of glucose transporters (Glut 4) in fat cells of rats. Endocrinology 129: 771–777, 1991.
 200. Phinney, S. D., A. B. Tang, D. C. Thurmond, M. T. Makamura, and J. S. Stern. Abnormal polyunsaturated lipid metabolism in the obese Zucker rat, with partial metabolic correction by γ‐linolenic acid administration. Metabolism 42: 1127–1140, 1993.
 201. Pijl, H., H. P. F. Koppeshcaar, F. L. A. Willekens, I. O. de Kamp, H. D. Veldhuis, and A. E. Meinders. Effect of serotonin reuptake inhibition by fluoxetine on body weight and spontaneous food choice in obesity. Int. J. Obes. 15: 237–242, 1991.
 202. Plaisted, C. S., L. Landsburg, J. Young, G. L. Blackburn, B. R. Bistrian, and N. W. Istfan. Insulin resistance and urinary catecholamine excretion in obese hypertensive patients undergoing weight loss [Abstract]. Int. J. Obes. 14 (suppl. 2): 74, 1990.
 203. Plotsky, P. M., K. V. Thrivikraman, A. G. Watts, and R. L. Hauger. Hypothalamic‐pituitary‐adrenal axis function in the Zucker obese rat. Endocrinology 130: 1931–1941, 1992.
 204. Powley, T. L., and W. Laughton. Neural pathways involved in the hypothalamic integration of autonomic responses. Diabetologia 20: 378–387, 1981.
 205. Price, R. A., T. I. A. Sorensen, and A. J. Stunkard. Component distributions of body mass index defining moderate and extreme overweight in Danish women and men. Am. J. Epidemiol. 130: 193–201, 1989.
 206. Price, R. A., and A. J. Stunkard. Comingling analysis of obesity in twins. Hum. Hered. 39: 121–135, 1989.
 207. Ramirez, I., and M. I. Friedman. Dietary hyperphagia in rats: role of fat, carbohydrate, and energy content. Physiol. Behav. 47: 1157–1163, 1990.
 208. Ravussin, E., and C. Bogardus. Energy expenditure in the obese: is there a thrifty gene? Infusionstherapie 17: 108–112, 1990.
 209. Rebuffe‐Scrive, M., L. Enk, N. Crona, P. Lonnroth, L. Abrahamsson, U. Smith, and P. Bjorntorp. Fat cell metabolism in different regions in women. Effect of menstrual cycle, pregnancy, and lactation. J. Clin. Invest. 75: 1973–1976, 1985.
 210. Reed, D. R., R. J. Contreras, C. Maggio, M. R. C. Greenwood, and J. Rodin. Weight cycling in female rats increases dietary fat selection and adiposity. Physiol. Behav. 42: 389–395, 1988.
 211. Ritenbaugh, C., and C. S. Goodby. Beyond the thrifty gene: metabolic implications of prehistoric migration into the New World. Med. Anthropol. 11: 227–236, 1989.
 212. Ritter, M. M., A. C. Sonnichsen, W. Mohrle, W. O. Richter, and P. Schwandt. β‐Endorphin plasma levels and their dependence on gender during an enteral glucose load in lean subjects as well as in obese patients before and after weight reduction. Int. J. Obes. 15: 421–427, 1991.
 213. Rocchini, A. P., V. Katch, J. Anderson, J. Hinderliter, D. Becque, M. Martin, and C. Marks. Blood pressure in obese adolescents: effect of weight loss. Pediatrics 82: 16–23, 1988.
 214. Rodin, J. Insulin levels, hunger, and food intake: an example of feedback loops in body weight regulation. Health Psychol. 4: 1–24, 1985.
 215. Rodin, J., D. Schank, and R. Striegel‐Moore. Psychological features of obesity. Med. Clin. North Am. 73: 47–66, 1989.
 216. Rolls, B. J., M. Hetherington, and V. J. Burley. The specificity of satiety: the influence of foods of different macronutrient content on the development of satiety. Physiol. Behav. 43: 145–153, 1988.
 217. Romanella, N. E., D. K. Wakat, B. H. Loyd, and L. E. Kelly. Physical activity and attitudes in lean and obese children and their mothers. Int. J. Obes. 15: 407–414, 1991.
 218. Romieu, I., W. C. Willett, M. J. Stampfer, G. A. Colditz, L. Sampson, B. Rosner, C. H. Hennekens, and G. E. Speizer. Energy intake and other determinants of relative weight. Am. J. Clin. Nutr. 47: 406–412, 1988.
 219. Roncari, D. A. K. Abnormalities of adipose cells in massive obesity. Int. J. Obes. 14 (suppl. 3): 187–192, 1990.
 220. Rose‐Ellis, J. R., R. B. McDonald, and J. S. Stern. A diet high in fat stimulates adipocyte proliferation in older (22 month) rats. Exp. Gerontol. 25: 141–148, 1990.
 221. Rossner, S., G. Walldus, and H. Bjorvell. Fatty acid composition in serum lipids and adipose tissue in severe obesity before and after 6 weeks of weight loss. Int. J. Obes. 13: 603–612, 1989.
 222. Rothblum, E. D. Women and weight: fad and fiction. J. Psychol. 124: 5–24, 1990.
 223. Rothwell, N. J. Central effects of CRF on metabolism and energy balance. Neurosci. Biobehav. Rev. 14: 263–271, 1990.
 224. Rothwell, N. J., M. J. Stock, and B. P. Warwick. Energy balance and brown fat activity in rats fed cafeteria diets or high fat semi‐synthetic diets at several levels of intake. Metab. Clin. Exp. 34: 474–480, 1985.
 225. Routh, V. H., J. S. Hamilton, J. S. Stern, and B. A. Horwitz. Litter size, adrenalectomy and high fat diet alter hypothalamic monoamines in genetically lean (Fa/Fa) Zucker rats. J. Nutr. 123: 74–84, 1993.
 226. Routh, V. H., D. M. Murakami, J. S. Stern, C. A. Fuller, and B. A. Horwitz. Neuronal activity in hypothalamic nuclei of obese and lean Zucker rats. Int. J. Obes. 14: 879–891, 1990.
 227. Rowland, N. E., and S. M. Antelman. Stress‐induced hyperphagia and obesity in rats: a possible model for understanding human obesity. Science 191: 310–311, 1975.
 228. Sachdev, P. S. Behavioural factors affecting physical health of the New Zealand Maori. Soc. Sci. Med. 30: 431–440, 1990.
 229. Saito, M., Y. Minokoshi, and T. Shimazu. Ventromedial hypothalamic stimulation accelerates norepinephrine turnover in brown adipose tissue of rats. Life Sci. 41: 193–197, 1987.
 230. Salmon, D. M. W., and J. P. Flatt. Effect of dietary fat content among ad libitum fed mice. Int. J. Obes. 9: 443–449, 1985.
 231. Sampliner, R. E., P. H. Bennett, L. J. Comess, et al. Gallbladder disease in Pima Indians: demonstration of high prevalence and early onset by cholecytography. N. Engl. J. Med. 283: 1358–1364, 1977.
 232. Sawchenko, P., and L. Swanson. The organization of forebrain afferents to the paraventricular and supraoptic nuclei of the rat. J. Comp. Neurol. 218: 121–144, 1983.
 233. Scallet, A. C., and J. W. Olney. Components of hypothalamic obesity: bipiperidyl‐mustard lesions add hyperphagia to mono‐sodium glutamate‐induced hyperinsulinemia. Brain Res. 374: 380–384, 1986.
 234. Scarpace, P. J., M. Matheny, and S. E. Borst. Thermogenesis and mitochondrial GDP binding with age in response to the novel agonist CGP‐12177A. Am. J. Physiol. 262 (Endocrinol. Metab. 33): E185–E190, 1992.
 235. Scarpace, P. J., A. D. Mooradian, and J. E. Morley. Age‐associated decrease in β‐adrenergic receptors and adenylate cyclase activity in rat brown adipose tissue. J. Gerontol. 43: B65–B70, 1988.
 236. Schlundt, D. G., J. O. Hill, T. Sbrocco, J. Pope‐Cordle, and T. Kasser. Obesity: a biogenetic or biobehavioral problem. Int. J. Obes. 14: 815–828, 1990.
 237. Schlundt, D. G., D. Taylor, J. O. Hill, T. Sbrocco, J. Pope‐Cordle, T. Kasser, and D. Arnold. A behavioral taxonomy of obese female participants in a weight‐loss program. Am. J. Clin. Nutr. 53: 1151–1158, 1991.
 238. Schwartz, D. H., S. McClane, L. Hernandez, and B. G. Hoebel. Feeding increases extracellular serotonin in the lateral hypothalamus of the rat as measured by microdialysis. Brain Res. 479: 349–354, 1989.
 239. Sclafani, A. Carbohydrate taste, appetite, and obesity: an overview. Neurosci. Behav. Rev. 11: 131–153, 1987.
 240. Scotellaro, P. A., L. L. Ji, J. Gorski, and L. B. Oscai. Body fat accretion: a rat model. Med. Sci. Sports Exerc. 23: 275–279, 1991.
 241. Segal, K. R., A. Dunaif, B. Gutin, J. Albu, A. Nyuman, and F. X. Pi‐Sunyer. Body composition, not body weight, is related to cardiovascular disease risk factors and sex hormone levels in man. J. Clin. Invest. 80: 1050–1055, 1987.
 242. Segal, K. R., and F. X. Pi‐Sunyer. Exercise and obesity. Med. Clin. North Am. 73: 217–236, 1989.
 243. Seim, H. C., and J. A. Fiola. A comparison of attitudes and behaviors of men and women toward food and dieting. Fam. Pract. Res. J. 10: 57–63, 1990.
 244. Shimazu, T., M. Noma, and M. Saito. Chronic infusion of norepinephrine into the ventromedial hypothalamus induces obesity in rats. Brain Res. 369: 215–223, 1986.
 245. Shimokata, Y., D. C. Muller, J. L. Fleg, J. Sorkin, A. W. Ziemba, and R. Andres. Age as an independent determinant of glucose tolerance. Diabetes 40: 44–51, 1991.
 246. Silverman, A. G. Overnutrition in the diabetic patient. Mount Sinai J. Med. 54: 211–216, 1987.
 247. Silvestrini, B. The paradoxical stress response: a possible common basis for depression and other conditions. J. Clin. Psychiatry 51 (suppl. 9): 6–8, 1990.
 248. Simopoulos, A. P. Characteristics of obesity: an overview. Ann. N. Y. Acad. Sci. 499: 4–13, 1987.
 249. Sims, E. A. H. Storage and expenditure of energy in obesity and their implications for management. Med. Clin. North Am. 73: 97–110, 1989.
 250. Skaggs, S. R., and D. M. Crist. Exogenous human growth hormone reduces body fat in obese women. Horm. Res. 35: 19–24, 1991.
 251. Smolin, L. A., M. B. Grosvenor, D. J. Handelsmand, and J. Brasel. Diet composition and lipoprotein lipase activity in human obesity. Br. J. Nutr. 58: 13–21, 1987.
 252. Snyder, D. K., D. R. Clemmons, and L. E. Underwood. Dietary carbohydrate content determines responsiveness to growth hormone in energy‐restricted humans. J. Clin. Endocrinol. Metab. 69: 745–752, 1989.
 253. Snyder, D. K., L. E. Underwood, and D. R. Clemmons. Anabolic effects of growth hormone in obese diet‐restricted subjects are dose dependent. Am. J. Clin. Nutr. 52: 431–437, 1990.
 254. Sobal, J., and A. J. Stunkard. Socioeconomic status and obesity: a review of the literature. Psychol. Bull. 105: 260–275, 1989.
 255. Sorensen, T. I. A. Genetic epidemiology utilizing the adoption method: studies of obesity and of premature deaths in adults. Scand. J. Soc. Med. 19: 14–19, 1991.
 256. Sorensen, T. I. A., and R. A. Price. Secular trends in body mass index among Danish young men. Int. J. Obes. 14: 411–419, 1990.
 257. Steffens, A. B., A. J. W. Scheurink, P. G. M. Luiten, and B. Bohus. Hypothalamic food intake regulating areas are involved in the homeostasis of blood glucose and plasma FFA levels. Physiol. Behav. 44: 581–589, 1988.
 258. Steinbeck, K., I. D. Caterson, L. Astbury, and J. R. Turtle. The effect of diet composition on weight gain and pyruvate dehydrogenase activity in heart muscle in the gold thioglucose obese mouse. Int. J. Obes. 11: 507–518, 1987.
 259. Stern, J. S., and P. R. Johnson. Size and number of adipocytes and their implications. In: Advances in Modern Nutrition, Diabetes, Obesity and Vascular Disease. edited by H. M. Katzen and R. J. Mahler. Washington, DC: Hemisphere, 1977, vol. 2, p. 303–341.
 260. Stevenson, J. A. F., and R. H. Rixon. Environmental temperature and deprivation of food and water on spontaneous activity of rats. Yale J. Biol. Med. 29: 575–584, 1957.
 261. Stone, M., R. A. Schemmel, and D. M. Czajka‐Narins. Growth and development of kidneys, heart and liver in S 5B/P1 and Osborne‐Mendel rats fed high or low‐fat diets. Int. J. Obes. 4: 65–78, 1980.
 262. Tanaka, K., S. Inoue, J. Shiraki, T. Shishido, M. Saito, K. Numata, and Y. Takamura. Age‐related decrease in plasma growth hormone: response to growth hormone‐releasing hormone, arginine, and L‐dopa in obesity. Metabolism 40: 1257–1262, 1991.
 263. Thomas, J. D., D. C. Thomas, M. M. Doucette, and J. D. Stoeckle. Disease, lifestyle, and consanguinity in 58 American gypsies. Lancet 2: 377–379, 1987.
 264. Timmers, K., D. L. Coleman, N. R. Voyles, A. M. Powell, A. Rokaeus, and L. Recant. Neuropeptide content in pancreas and pituitary of obese and diabetes mutant mice: strain and sex differences. Metabolism 39: 378–383, 1990.
 265. Timmers, K., N. R. Voyles, C. Zalenski, S. Wilkins, and L. Recant. Altered β‐endorphin, met‐ and leu‐enkephalins, and enkephalin‐containing peptides in pancreas and pituitary of genetically obese diabetic (db/db) mice during development of diabetic syndrome. Diabetes 35: 1143–1151, 1986.
 266. Tokunaga, K., M. Fukushima, J. W. Kemnitz, and G. A. Bray. Comparison of ventromedial and paraventricular lesions in rats that become obese. Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 22): R1221–R1227, 1986.
 267. Trayhurn, P. Energy expenditure and thermogenesis: animal studies on brown adipose tissue. Int. J. Obes. 14 (suppl. 1): 17–29, 1990.
 268. Trayhurn, P., and W. P. T. James. Thermoregulation and non‐shivering thermogenesis in the genetically obese (ob/ob) mouse. Pflugers Arch. 373: 189–193, 1978.
 269. Triandafillou, J., and J. Himms‐Hagen. Brown adipose tissue in genetically obese (fa/fa) rats: response to cold and diet. Am. J. Physiol. 244 (Endocrinol. Metab. 7): E145–E150, 1983.
 270. Troisi, R. J., S. T. Weiss, D. R. Parker, D. Sparrow, J. B. Young, and L. Landsberg. Relation of obesity and diet to sympathetic nervous system activity. Hypertension 17: 669–677, 1991.
 271. Turula, M., J. Kaprio, A. Rissanen, and M. Koskenvuo. Body weight in the Finnish twin cohort. Diabetes Res. Clin. Pract. 10: S33–S36, 1990.
 272. Vague, J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am. J. Clin. Nutr. 4: 20–34, 1956.
 273. Van, R. L. R., C. E. Bayliss, and D. A. K. Roncari. Cytological and enzymological characterization of adult human adipocyte precursors in culture. J. Clin. Invest. 58: 699–704, 1976.
 274. Van Dale, D., and V. H. M. Saris. Repetitive weight loss and weight regain: effects on weight reduction, resting metabolic rate, and lipolytic activity before and after exercise and/or diet treatment. Am. J. Clin. Nutr. 49: 409–416, 1989.
 275. Vander Tuig, J. G., J. Kerner, and D. R. Romsos. Hypothalamic obesity, brown adipose tissue, and sympathoadrenal activity in rats. Am. J. Physiol. 248 (Endocrinol. Metab. 11): E607–E617, 1985.
 276. Van Itallie, T. B. The glucostatic theory 1953‐1988: roots and branches. Int. J. Obes. 14 (suppl. 3): 1–10, 1990.
 277. Vannucci, S. J., C. M. Klim, K. F. LaNoue, and L. F. Martin. Regulation of fat cell adenylate cyclase in young Zucker (fa/fa) rats: alterations in GTP sensitivity of adenosine A1 mediated inhibition. Int. J. Obes. 14 (suppl. 3): 125–134, 1990.
 278. Vitale, P. M., J. M. Darrow, M. J. Duncan, C. A. Shustak, and B. D. Goldman. Effects of photoperiod, pinealectomy and castration on body weight and daily torpor in Djungarian hamsters. J. Endocrinol. 106: 367–375, 1985.
 279. Wade, G. N., and T. J. Bartness. Effects of photoperiod and gonadectomy on food intake, body weight, and body composition in Siberian hamsters. Am. J. Physiol. 246 (Regulatory Integrative Comp. Physiol. 17): R26–R30, 1984.
 280. Walberg, J. L., D. Upton, and J. S. Stern. Exercise training improves sensitivity in the obese Zucker rat. Metabolism 33: 1075–1079, 1984.
 281. Weinsier, R. L., L. D. James, B. E. Darnell, H. P. Dustan, R. Birch, and G. R. Hunter. Obesity‐related hypertension: evaluation of the separate effects of energy restriction and weight reduction on hemodynamic and neuroendocrine status. Am. J. Med. 90: 460–468, 1991.
 282. Weststrate, J. A., J. Dekker, M. Stoel, L. Begheijn, P. Deurenberg, and J. G. A. J. Hautvast. Resting energy expenditure in women: impact of obesity and body‐fat distribution. Metabolism 39: 11–17, 1990.
 283. Williams, P. T. Weight set‐point theory predicts HDL‐cholesterol levels in previously obese long‐distance runners. Int. J. Obes. 14: 421–427, 1990.
 284. Williams, R. R., S. C. Hunt, S. J. Hasstedt, P. N. Hopkins, L. L. Wu, T. D. Berry, B. M. Stults, G. K. Barlow, M. C. Schumacher, R. P. Lifton, and J. M. Lalouel. Are there interactions and relations between genetic and environmental factors predisposing to high blood pressure? Hypertension 18 (suppl. I): I29–I37, 1991.
 285. Wing, R. R., E. H. Blair, L. H. Epstein, and M. D. McDermott. Psychological stress and glucose metabolism in obese and normal‐weight subjects: a possible mechanism for differences in stress‐induced eating. Health Psychol. 9: 693–700, 1990.
 286. Woods, S. C., D. P. F. Lattemann, M. W. Schwartz, and D. Porte, Jr. A re‐assessment of the regulation of adiposity and appetite by the brain insulin system. Int. J. Obes. 14 (suppl. 3): 69–76, 1990.
 287. Wu, S. Y., J. S. Stern, D. A. Fisher, and Z. Glick. Cold‐induced increase in brown fat thyroxine 5‐monodeiodinase is attenuated in Zucker obese rat. Am. J. Physiol. 252 (Endocrinol. Metab. 15): E63–E67, 1987.
 288. Xu, X., and P. Bjorntorp. The effects of steroid hormones on adipocyte development. Int. J. Obes. 14 (suppl. 3): 159–163, 1990.
 289. York, D. A. Neural activity in hypothalamic and genetic obesity. Proc. Nutr. Soc. 46: 105–117, 1987.
 290. Zador, D. A., and A. S. Truswell. Nutritional status on admission to a general surgical ward in a Sydney hospital. Aust. N. Z. J. Med. 17: 234–240, 1987.
 291. Zawadzki, J. K., R. R. Wolfe, D. M. Mott, S. Lillioja, B. V. Howard, and C. Bogardus. Increased rate of Cori Cycle in obese subjects with NIDDM and effect of weight reduction. Diabetes 37: 154–159, 1988.
 292. Zinder, O., M. Hamosh, T. R. C. Fleck, and R. O. Scow. Effect of prolactin on lipoprotein lipase in mammary gland and adipose tissue of rats. Am. J. Physiol. 226: 744–748, 1974.
 293. Zurlo, F., S. Lillioja, A. Esposito‐Del Puente, B. L. Nyomba, I. Raz, M. F. Saad, B. A. Swinburn, W. C. Knowler, C. Bogardus, and E. Ravussin. Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24‐h RQ. Am. J. Physiol. 259 (Regulatory Integrative Comp. Physiol. 30): E650–E657, 1990.

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Vanessa H. Routh, Judith S. Stern, Barbara A. Horwitz. Physiological Responses of Mammals to Overnutrition. Compr Physiol 2011, Supplement 14: Handbook of Physiology, Environmental Physiology: 1411-1435. First published in print 1996. doi: 10.1002/cphy.cp040262