Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-6bf8c574d5-685pp Total loading time: 0 Render date: 2025-03-09T15:59:34.422Z Has data issue: false hasContentIssue false

6 - Diet-induced obesity in animal models and what they tell us about human obesity

Published online by Cambridge University Press:  15 September 2009

By
Barry E. Levin  and
Alison M. Strack
Edited by
Jenni Harvey  and
Dominic J. Withers
Barry E. Levin
Affiliation:
Neurology Service (127C) Veterans Affairs, Medical Center, 385, Tremont Avenue, East Orange, New Jersey 07018–1095, USA
Alison M. Strack
Affiliation:
Neurology Service (127C) Veterans Affairs, Medical Center, 385, Tremont Avenue, East Orange, New Jersey 07018–1095, USA
Jenni Harvey
Affiliation:
University of Dundee
Dominic J. Withers
Affiliation:
Imperial College of Science, Technology and Medicine, London
Get access

Summary

Introduction

Animals have been used extensively as surrogates for the study of factors that contribute to the development and persistence of obesity in human beings. Each model has its own set of advantages and disadvantages in relation to its similarities and differences from humans. In fact, obesity rarely occurs in feral animals outside of the pre-hibernating period. For the majority of individuals obesity is a relatively recent event in human history because food availability was generally limited and a relatively high degree of physical activity was required to procure sufficient food to maintain survival. The switch from hunter-gatherer to agricultural societies has allowed increasing numbers of individuals to obtain food with reduced expenditure of energy. In the developed world, the prevalence of obesity has increased precipitously in the last 20–30 years as the availability of cheap, highly palatable, energy-dense food has become more widely available and physical activity has declined (Popkin & Doak, 1999). Clearly, the gene pool has not changed substantially over such a short period of time to explain the rapid increase in obesity prevalence. Thus, environmental factors must be the critical variable which has promoted the current epidemic of human obesity. Animal models of obesity have become a useful tool in our quest to understand the factors contributing to the recent obesity epidemic in humans. Although other animals differ from humans in many ways, they share many common physiological properties that assure their survival during periods of famine.

Type
Chapter
Information
Neurobiology of Obesity , pp. 164 - 195
Publisher: Cambridge University Press
Print publication year: 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abou, M. J., Yakubu, F., Lin, D., Peters, J. C., Atkinson, J. B. & Hill, J. O. (1992). Skeletal muscle composition in dietary obesity-susceptible and dietary obesity-resistant rats. Am. J. Physiol. 262, 1–8.Google Scholar
Adachi, A., Shimizu, N., Oomura, Y. & Kobashi, M. (1984). Convergence of heptoportal glucose-sensitive afferent signals to glucose-sensitive units within the nucleus of the solitary tract. Neurosci. Lett. 46, 215–18.CrossRefGoogle ScholarPubMed
Altmann, J., Schoeller, D., Altmann, S. A., Muruthi, P. & Sapolsky, R. M. (1993). Body size and fatness of free-living baboons reflect food availability and activity levels. Am. J. Primatol. 30, 149–61.CrossRefGoogle Scholar
Anand, B. K., Chhina, G. S., Sharma, K. N., Dua, S. & Singh, B. (1964). Activity of single neurons in the hypothalamus feeding centers: effect of glucose. Am. J. Physiol. 207, 1146–54.Google ScholarPubMed
Archer, Z. A., Rayner, D. V., Rozman, J., Klingenspor, M. & Mercer, J. G. (2003). Normal distribution of body weight gain in male Sprague–Dawley rats fed a high-energy diet. Obes. Res. 11, 1376–83.CrossRefGoogle ScholarPubMed
Bai, F., Sozen, M. A., Lukiw, W. J. & Argyropoulos, G. (2005). Expression of AgRP, NPY, POMC and CART in human fetal and adult hippocampus. Neuropeptides 39, 439–43.CrossRefGoogle ScholarPubMed
Balkan, B., Strubbe, J. H., Bruggink, J. E. & Steffens, A. B. (1993). Overfeeding-induced obesity in rats: insulin sensitivity and autonomic regulation of metabolismMetabolism. 42, 1509–18.CrossRefGoogle ScholarPubMed
Banks, W. A. & Farrell, C. L. (2003). Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible. Am. J. Physiol. 285, E10–15.Google ScholarPubMed
Banks, W. A., DiPalma, C. R. & Farrell, C. L. (1999). Impaired transport of leptin across the blood–brain barrier in obesity. Peptides 20, 1341–5.CrossRefGoogle ScholarPubMed
Banks, W. A., Altmann, J., Sapolsky, R. M., Phillips-Conroy, J. E. & Morley, J. E. (2003). Serum leptin levels as a marker for a syndrome X-like condition in wild baboons. J. Clin. Endocrinol. Metab. 88, 1234–40.CrossRefGoogle ScholarPubMed
Bellinger, L. L. & Bernardis, L. L. (2002). The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation: lessons learned from lesioning studies. Physiol Behav. 76, 431–42.CrossRefGoogle ScholarPubMed
Bergman, R. N. & Ader, M. (2000). Free fatty acids and pathogenesis of type 2 diabetes mellitus. TEM 11, 351–6.Google ScholarPubMed
Berthoud, H. -R. (1985). Cephalic phase insulin response as a predictor of body weight gain and obesity induced by a palatable cafeteria diet. J. Obes. Weight Reg. 4, 120–8.Google Scholar
Bickel, P. E. (2002). Lipid rafts and insulin signaling. Am. J. Physiol. Endocrinol. Metab. 282, E1–10.CrossRefGoogle ScholarPubMed
Bjorntorp, P. (1991). Metabolic implications of body fat distribution. Diabetes Care 14, 1132–43.CrossRefGoogle ScholarPubMed
Bodkin, N. L.Hannah, J. S., Ortmeyer, H. K. & Hansen, B. C. (1993). Central obesity in rhesus monkeys: association with hyperinsulinemia, insulin resistance and hypertriglyceridemia? Int. J. Obes. Relat. Metab. Disord. 17, 53–61.Google ScholarPubMed
Boozer, C. N. & Lauterio, T. J. (1998). High initial levels of plasma leptin predict diet-induced obesity in rat?. Int. J. Ob. 22, S166.Google Scholar
Bouchard, C. & Perusse, L. (1993). Genetics of obesit?. Ann. Rev. Nutr. 13, 337–54.CrossRefGoogle Scholar
Burcelin, R., Crivelli, V., Dacosta, A., Roy-Tirelli, A. & Thorens, B. (2002). Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat die?. Am. J. Physiol. 282, E834–42.Google Scholar
Butterwick, R. F. & Hawthorne, A. J. (1998). Advances in dietary management of obesity in dogs and cat?. J. Nutr. 128, 2771s–5s.CrossRefGoogle Scholar
Cai, G., Cole, S. A., Tejero, M. E.et al. (2004). Pleiotropic effects of genes for insulin resistance on adiposity in baboon?. Obes. Res. 12, 1766–72.CrossRefGoogle Scholar
Camacho, R. E., Forrest, M. J., MacIntyre, D. E. & Strack, A. M. (1999). Increased sensitivity to dexfenfluramine in rats on high fat die?. FASEB J. 13, A751.Google Scholar
Caro, J. F., Kolaczynski, J. W., Nyce, M. R.et al. (1996). Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistanc?. Lancet 348, 159–61.CrossRefGoogle Scholar
Chandler, P., Viana, J., Oswald, K., Wauford, P. & Boggiano, M. (2005). Feeding response to melanocortin agonist predicts preference for and obesity from a high-fat die?. Physiol. Behav. 85, 221–30.CrossRefGoogle Scholar
Chang, S., Graham, B., Yakubu, F., Lin, D., Peters, J. C. & Hill, J. O. (1990). Metabolic differences between obesity-prone and obesity-resistant rat?. Am. J. Physiol. Regul. Integr. Comp. Physiol. 259, R1103–10.CrossRefGoogle Scholar
Clark, F. M., Yeomans, D. C. & Proudfit, H. K. (1991). The noradrenergic innervation of the spinal cord: differences between two substrains of Sprague-Dawley rats determined using retrograde tracers combined with immunocytochemistr?. Neurosci. Lett. 125, 155–8.CrossRefGoogle Scholar
Clegg, D. J., Riedy, C. A., Smith, K. A., Benoit, S. C. & Woods, S. C. (2003). Differential sensitivity to central leptin and insulin in male and female rat?. Diabetes 52, 682–7.CrossRefGoogle Scholar
Clegg, D. J., Benoit, S. C., Reed, J. A., Woods, S. C. & Levin, B. E. (2005). Reduced anorexic effects of insulin in obesity-prone rats and rats fed a moderate fat die?. Am. J. Physiol. 288, R981–6.Google Scholar
Cohn, C., Joseph, D. & Shrago, E. (1957). Effect of diet on body composition. I. The production of increased body fat without overweight (nonobese obesity) by force feeding the normal ra?. Metabolism 6, 381–7.Google Scholar
Cole, S. A., Martin, L. J., Peebles, K. W.et al. (2003). Genetics of leptin expression in baboon?. Int. J. Obes. 27, 778–83.CrossRefGoogle Scholar
Commerford, S. R., Pagliassotti, M. J., Melby, C. L., Wei, Y., Gayles, E. C. & Hill, J. O. (2000). Fat oxidation, lipolysis, and free fatty acid cycling in obesity-prone and obesity-resistant rat?. Am. J. Physiol. 279, E875–85.Google Scholar
Comuzzie, A. G., Cole, S. A., Martin, L.et al. (2003). The baboon as a nonhuman primate model for the study of the genetics of obesit?. Obes. Res. 11, 75–80.CrossRefGoogle Scholar
Corbett, S. W., Stern, J. S. & Keesey, R. E. (1986). Energy expenditure in rats with diet-induced obesit?. Am. J. Clin. Nutr. 44, 173–80.CrossRefGoogle Scholar
Dallaporta, M., Himmi, T., Perrin, J. & Orsini, J. C. (1999). Solitary tract nucleus sensitivity to moderate changes in glucose leve?. NeuroReport 10, 2657–60.CrossRefGoogle Scholar
Davies, A. D., Dobrian, R. L., Prewitt, R. L. & Lauterio, J. L. (1999). Metabolic syndrome in a diet-induced obesity mode?. Obes. Res. 7, 127S.Google Scholar
Davis, J. D. & Wirtshafter, D. (1978). Set points or settling points for body weight?: A reply to Mrosovsky and Powle?. Behav. Biol. 24, 405–11.CrossRefGoogle ScholarPubMed
Drewnowski, A., Cohen, A. E., Faust, I. M. & Grinker, J. A. (1984). Meal-taking behavior is related to predisposition to dietary obesity in the ra?. Physiol. Behav. 32, 61–7.CrossRefGoogle Scholar
Dunn-Meynell, A. A., Routh, V. H., Kang, L., Gaspers, L. & Levin, B. E. (2002). Glucokinase is the likely mediator of glucosensing in both glucose excited and glucose inhibited central neuron?. Diabetes 51, 2056–65.CrossRefGoogle Scholar
El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjorbaek, C. & Flier, J. S. (2000). Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesit?. J. Clin. Invest. 105, 1827–32.CrossRefGoogle Scholar
Farley, C., Cook, J. A., Spar, B. D., Austin, T. M. & Kowalski, T. J. (2003). Meal pattern analysis of diet-induced obesity in susceptible and resistant rat?. Obes. Res. 11, 845–51.CrossRefGoogle Scholar
Foster, D. O. & Frydman, M. L. (1978). Nonshivering thermogenesis in the rat. II. Measurement of blood flow with microspheres points to brown adipose tissue as the dominant site of calorigenesis induced by noradrenalin?. Can. J. Physiol. Pharmacol. 56, 110–22.CrossRefGoogle Scholar
Gayles, E. C., Pagliassotti, M. J., Prach, P. A., Koppenhafer, T. A. & Hill, J. O. (1997). Contribution of energy intake and tissue enzymatic profile to body weight in high-fat-fed rat?. Am. J. Physiol. 272, R188–94.Google Scholar
Grill, H. J., Schwartz, M. W., Kaplan, J. M., Foxhall, J. S., Breininger, J. & Baskin, D. G. (2002). Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intak?. Endocrinology 143, 239–46.CrossRefGoogle Scholar
Grinker, J. A. & Block, W. D. (1991). Sensory responses, dietary-induced obesity and biochemical values in Sprague–Dawley rat?. Brain Res. Bull. 27, 535–40.CrossRefGoogle Scholar
Guo, F. & Jen, K. -L. (1995). High-fat feeding during pregnancy and lactation affects offspring metabolism in rat?. Physiol. Behav. 57, 681–6.CrossRefGoogle Scholar
Hales, C. N. & Barker, D. J. (1992). Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesi?. Diabetologia 35, 595–601.CrossRefGoogle Scholar
Hall, J. E., Brands, M. W., Hildebrandt, D. A., Kuo, J. & Fitzgerald, S. (2000). Role of sympathetic nervous system and neuropeptides in obesity hypertensio?. Braz. J. Med. Biol. Res. 33, 605–18.CrossRefGoogle Scholar
Hamilton, C. L., Kuo, P. T. & Fenge, L. Y. (1972). Experimental production of syndrome of obesity, hyperinsulinemia and hyperlipidemia in monkey?. Proc. Soc. Exp. Biol. Med. 140, 1005–8.CrossRefGoogle Scholar
Hansen, B. C., Bodkin, N. L. & Ortmeyer, H. K. (1999). Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortalit?. Toxicol. Sci. 52, 56–60.CrossRefGoogle Scholar
Harrold, J. A., Williams, G. & Widdowson, P. S. (2000). Early leptin response to a palatable diet predicts dietary obesity in rats: key role of melanocortin-4 receptors in the ventromedial hypothalamic nucleu?. J. Neurochem. 74, 1224–8.CrossRefGoogle Scholar
Hassanain, M. & Levin, B. E. (2002). Dysregulation of hypothalamic serotonin turnover in diet-induced obese rat?. Brain Res. 929, 175–80.CrossRefGoogle Scholar
Helies, J. M., Diane, A., Langlois, A.et al. (2005). Comparison of fat storage between Fischer 344 and obesity-resistant Lou/C rats fed different diet?. Obes. Res. 13, 3–10.CrossRefGoogle Scholar
Hill, J. O., Fried, S. K. & Digirolamo, M. (1983). Effects of a high-fat diet on energy intake and expenditure in rat?. Life Sci. 33, 141–9.CrossRefGoogle Scholar
Hill, J. O., Dorton, J., Sykes, M. N. & Digirolamo, M. (1989). Reversal of dietary obesity is influenced by its duration and severit?. Int. J. Obes. 13, 711–22.Google Scholar
Hollifield, G. & Parson, W. (1962). Metabolic adaptations to a “stuff and starve” feeding program. II. Obesity and the persistence of adaptive changes in adipose tissue and liver occurring in rats limited to a short daily feeding perio?. J. Clin. Invest. 41, 250–3.CrossRefGoogle Scholar
Ingle, D. J. (1949). A simple means of producing obesity in the ra?. Proc. Soc. Exp. Biol. Med. 72, 604.CrossRefGoogle Scholar
Jeusette, I. C., Detilleux, J., Shibata, H.et al. (2005). Effects of chronic obesity and weight loss on plasma ghrelin and leptin concentrations in dog?. Res. Vet. Sci. 79, 169–75.CrossRefGoogle Scholar
Jones, A. P., Simson, E. L. & Friedman, M. I. (1984). Gestational undernutrition and the development of obesity in rat?. J. Nutr. 114, 1484–92.Google Scholar
Kaiyala, K. J., Prigeon, R. L., Kahn, S. E., Woods, S. C., Porte, D. & Schwartz, M. W. (1999). Reduced β-cell function contributes to impaired glucose tolerance in dogs made obese by high-fat feedin?. Am. J. Physiol. 277, E659–67.Google Scholar
Kaiyala, K. J., Prigeon, R. L., Kahn, S. E., Woods, S. C. & Schwartz, M. W. (2000). Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dog?. Diabetes 49, 1525–33.CrossRefGoogle Scholar
Kang, L., Routh, V. H., Kuzhikandathil, E. V., Gaspers, L. & Levin, B. E. (2004). Physiological and molecular characteristics of rat hypothalamic ventromedial nucleus glucosensing neuron?. Diabetes 53, 549–59.CrossRefGoogle Scholar
Keesey, R. E., Mitchel, J. S. & Kemnitz, J. W. (1979). Body weight and body composition of male rats following hypothalamic lesion?. Am. J. Physiol. 237, R68–73.Google Scholar
Kemnitz, J. W., Goy, R. W., Flitsch, T. J., Lohmiller, J. J. & Robinson, J. A. (1989). Obesity in male and female rhesus monkeys: fat distribution, glucoregulation, and serum androgen level?. J. Clin. Endocrinol. Metab. 69, 287–93.CrossRefGoogle Scholar
Kennedy, G. C. (1953). The role of depot fat in the hypothalamic control of food intake in the ra?. Proc. R. Soc. Lond. B. Biol. Sci. 611, 221–35.Google Scholar
Kennedy, G. C. (1957). The development with age of hypothalamic restraint upon the appetite of the ra?. J. Endocrinol. 16, 9–17.CrossRefGoogle Scholar
King, B. M.Kass, J. M., Neville, K. L., Sam, H., Tatford, A. C. I. & Zansler, A. C. (1993). Abnormal weight gain in rats with amygdaloid lesion?. Physiol. Behav. 54, 467–70.CrossRefGoogle Scholar
Kowalski, T. J., Houpt, T. A., Jahng, J., Okada, N., Chua, S. C. Jr. & Smith, G. P. (1998). Ontogeny of neuropeptide Y expression in response to deprivation in lean Zucker rat pup?. Am. J. Physiol. 275, R466–70.Google Scholar
Kramer, F. M., Jeffery, R. W., Forster, J. L. & Snell, M. K. (1989). Long-term follow-up of behavioral treatment for obesity: patterns of weight regain among men and wome?. Int. J. Obes. 13, 123–36.Google Scholar
Landerholm, T. E. & Stern, J. S. (1992). Adipose tissue lipolysis in vitro: a predictor of diet-induced obesity in female rat?. Am. J. Physiol. Regul. Integr. Comp. Physiol. 263, R1248–53.CrossRefGoogle Scholar
Lane, M. A., Ingram, D. K. & Roth, G. S. (1999). Calorie restriction in nonhuman primates: effects on diabetes and cardiovascular disease ris?. Toxicol. Sci. 52, 41–8.CrossRefGoogle Scholar
Lauterio, T. J. & Perez, F. M. (1997). Growth hormone secretion and synthesis are depressed in obesity-susceptible compared with obesity-resistant rat?. Metabolism 46, 210–16.CrossRefGoogle Scholar
Leibel, R. L. & Hirsch, J. (1984). Diminished energy requirements in reduced-obese patient?. Metabolism 33, 164–70.CrossRefGoogle Scholar
Levin, B. E. (1990a). Obesity-prone and -resistant rats differ in their brain 3H paraminoclonidine bindin?. Brain Res. 512, 54–9.CrossRefGoogle Scholar
Levin, B. E. (1990b). Increased brain 3H paraminoclonidine (α2-adrenoceptor) binding associated with perpetuation of diet-induced obesity in rat?. Int. J. Obes. 14, 689–700.Google Scholar
Levin, B. E. (1991a). Defective cerebral glucose utilization in diet-induced obese rat?. Am. J. Physiol. 261, R787–92.Google Scholar
Levin, B. E. (1991b). Spontaneous motor activity during the development and maintenance of diet-induced obesity in the ra?. Physiol. Behav. 50, 573–81.CrossRefGoogle Scholar
Levin, B. E. (1992). Intracarotid glucose-induced norepinephrine response and the development of diet-induced obesit?. Int. J. Obesity. 16, 451–7.Google Scholar
Levin, B. E. (1994). Diet cycling and age alter weight gain and insulin levels in rat?. Am. J. Physiol. 267, R527–35.Google Scholar
Levin, B. E. (1995). Reduced norepinephrine turnover in organs and brains of obesity-prone rat?. Am. J. Physiol. 268, R389–94.Google Scholar
Levin, B. E. (1996). Reduced paraventricular nucleus norepinephrine responsiveness in obesity-prone rat?. Am. J. Physiol. 270, R456–61.Google Scholar
Levin, B. E. (1999). Arcuate NPY neurons and energy homeostasis in diet-induced obese and resistant rat?. Am. J. Physiol. 276, R382–7.Google Scholar
Levin, B. E. (2000). Metabolic imprinting on genetically predisposed neural circuits perpetuates obesit?. Nutrition. 16, 909–15.CrossRefGoogle Scholar
Levin, B. E. (2001). Glucosensing neurons do more than just sense glucos?. Int. J. Obes. Relat. Metab. Disord. 25, S68–72.CrossRefGoogle Scholar
Levin, B. E. (2002a). Glucosensing neurons: the metabolic sensors of the brai?? Diab. Nutr. Metab. 15, 274–80.Google Scholar
Levin, B. E. (2002b). Metabolic sensors: viewing glucosensing neurons from a broader perspectiv?. Physiol. Behav. 76, 397–401.CrossRefGoogle Scholar
Levin, B. E. (2004). The drive to regain is mainly in the brai?. Am. J. Physiol. 287, R1297–300.Google Scholar
Levin, B. E. & Dunn-Meynell, A. A. (1997a). In vivo and in vitro regulation of [3H]glyburide binding to brain sulfonylurea receptors in obesity-prone and resistant rats by glucos?. Brain Res. 776, 146–53.CrossRefGoogle Scholar
Levin, B. E. & Dunn-Meynell, A. A. (1997b). Dysregulation of arcuate nucleus preproneuropeptide Y mRNA in diet-induced obese rat?. Am. J. Physiol. 272, R1365–70.Google Scholar
Levin, B. E. & Dunn-Meynell, A. A. (2000). Defense of body weight against chronic caloric restriction in obesity-prone and -resistant rat?. Am. J. Physiol. 278, R231–7.Google Scholar
Levin, B. E. & Dunn-Meynell, A. A. (2002a). Reduced central leptin sensitivity in rats with diet-induced obesit?. Am. J. Physiol. 283, R941–8.Google Scholar
Levin, B. E. & Dunn-Meynell, A. A. (2002b). Defense of body weight depends on dietary composition and palatability in rats with diet-induced obesit?. Am. J. Physiol. 282, R46–54.Google Scholar
Levin, B. E. & Dunn-Meynell, A. A. (2002c) Maternal obesity alters adiposity and monoamine function in genetically predisposed offsprin?. Am. J. Physiol. 283, R1087–93.Google Scholar
Levin, B. E. & Dunn-Meynell, A. A. (2005). Differential effects of exercise on body weight gain in obesity-prone and -resistant rat?. Int. J. Obes. 30, 722–7.CrossRefGoogle Scholar
Levin, B. E. & Govek, E. (1998). Gestational obesity accentuates obesity in obesity-prone progen?. Am. J. Physiol. 275, R1374–9.Google Scholar
Levin, B. E. & Hamm, M. W. (1994). Plasticity of brain α-adrenoceptors during the development of diet-induced obesity in the ra?. Obes Res. 2, 230–8.CrossRefGoogle Scholar
Levin, B. E. & Keesey, R. E. (1998). Defense of differing body weight set-points in diet-induced obese and resistant rat?. Am. J. Physiol. 274, R412–19.Google Scholar
Levin, B. E. & Planas, B. (1993). Defective glucoregulation of brain α2-adrenoceptors in obesity-prone rat?. Am. J. Physiol. 264, R305–11.Google Scholar
Levin, B. E. & Sullivan, A. C. (1987). Glucose-induced norepinephrine levels and obesity resistanc?. Am. J. Physiol. 253, R475–81.Google Scholar
Levin, B. E. & Sullivan, A. C. (1989a). Glucose-induced sympathetic activation in obesity-prone and resistant rat?. Int. J. Obesity. 13, 235–46.Google Scholar
Levin, B. E. & Sullivan, A. C. (1989b). Differences in saccharin-induced cerebral glucose utilization between obesity-prone and resistant rat?. Brain Res. 488, 221–32.CrossRefGoogle Scholar
Levin, B. E., Triscari, J. & Sullivan, A. C. (1982). Sympathetic activity in thyroid–treated Zucker rat?. Am. J. Physiol. 243, R170–8.Google Scholar
Levin, B. E., Triscari, J. & Sullivan, A. C. (1983). Relationship between sympathetic activity and diet-induced obesity in two rat strain?. Am. J. Physiol. 245, R367–71.Google Scholar
Levin, B. E., Finnegan, M., Triscari, J. & Sullivan, A. C. (1985). Brown adipose and metabolic features of chronic diet-induced obesit?. Am. J. Physiol. 248, R717–23.Google Scholar
Levin, B. E., Triscari, J. & Sullivan, A. C. (1986). The effect of diet and chronic obesity on brain catecholamine turnover in the ra?. Pharmacol. Biochem. Behav. 24, 299–304.CrossRefGoogle Scholar
Levin, B. E., Brown, K. L. & Vincent, D. G. (1994). Increased potency and binding of mazindol to putative brain anorectic receptors in obesity-prone rat?. Brain Res. 668, 171–9.CrossRefGoogle Scholar
Levin, B. E., Brown, K. L. & Dunn-Meynell, A. A. (1996). Differential effects of diet and obesity on high and low affinity sulfonylurea binding sites in the rat brai?. Brain Res. 739, 293–300.CrossRefGoogle Scholar
Levin, B. E., Dunn-Meynell, A. A., Balkan, B. & Keesey, R. E. (1997). Selective breeding for diet-induced obesity and resistance in Sprague–Dawley rat?. Am. J. Physiol. 273, R725–30.Google Scholar
Levin, B. E., Govek, E. K. & Dunn-Meynell, A. A. (1998). Reduced glucose-induced neuronal activation in the hypothalamus of diet-induced obese rat?. Brain Res. 808, 317–19.CrossRefGoogle Scholar
Levin, B. E., Richard, D., Michel, C. & Servatius, R. (2000). Differential stress responsivity in diet-induced obese and resistant rat?. Am. J. Physiol. 279, R1357–64.Google Scholar
Levin, B. E., Dunn-Meynell, A. A. & Banks, W. A. (2003a). Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling prior to obesity onse?. Am. J. Physiol. 286, R143–50.Google Scholar
Levin, B. E., Dunn-Meynell, A. A., McMinn, J. E., Cunningham-Bussel, A. & Chua, S. C. Jr. (2003b). A new obesity-prone, glucose intolerant rat strain (F.DIO?. Am. J. Physiol. 285, R1184–91.Google Scholar
Levin, B. E., Dunn-Meynell, A. A., Ricci, M. R. & Cummings, D. E. (2003c). Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rat?. Am. J. Physiol. 285, E949–57.Google Scholar
Levin, B. E., Routh, V. H., Kang, L., Sanders, K. L. & Dunn-Meynell, A. A. (2004). Neuronal glucosensing: what do we know after 50 year?? Diabetes 53, 2521–8.CrossRefGoogle Scholar
Levin, B. E., Magnan, C., Migrenne, S., Chua, S. C. Jr. & Dunn-Meynell, A. A. (2005). The F-DIO obesity-prone rat is insulin resistant prior to obesity onse?. Am. J. Physiol. 289, R704–11.Google Scholar
Lewis, D. S., Coelho, A. M. J. & Jackson, E. M. (1991). Maternal weight and sire group, not caloric intake, influence adipocyte volume in infant female baboon?. Pediatr. Res. 30, 534–40.CrossRefGoogle ScholarPubMed
Lewis, D. S., Jackson, E. M. & Mott, G. E. (1992). Effect of energy intake on postprandial plasma hormones and triglyceride concentrations in infant female baboons (Papio species?. J. Clin. Endocrinol. Metab. 74, 920–6.CrossRefGoogle ScholarPubMed
Li, A. J. & Ritter, S. (2004). Glucoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate the hypothalamu?. Eur. J. Neurosci. 19, 2147–54.CrossRefGoogle Scholar
Lin, X., Chavez, M. R., Bruch, R. C.et al. (1998). The effects of a high fat diet on leptin mRNA, serum leptin and the response to leptin are not altered in a rat strain susceptible to high fat diet–induced obesit?. J. Nutr. 128, 1606–13.CrossRefGoogle ScholarPubMed
Lindblad-Toh, T. K., Wade, C. M., Mikkelsen, T. S.et al. (2005). Genome sequence, comparative analysis and haplotype structure of the domestic do?. Nature 438, 803–19.CrossRefGoogle Scholar
MacLean, P. S., Higgins, J. A., Johnson, G. C.et al. (2004). Enhanced metabolic efficiency contributes to weight regain after weight loss in obesity-prone rat?. Am. J. Physiol. 287, R1306–15.Google Scholar
Mahankali, S., Liu, Y., Pu, Y.et al. (2000). In vivo fMRI demonstration of hypothalamic function following intraperitoneal glucose administration in a rat mode?. Magn. Reson. Med. 43, 155–9.3.0.CO;2-5>CrossRefGoogle Scholar
Marriott, B. M., Roemer, J. & Sultana, C. (1989). An overview of the food intake patterns of the Cayo Santiago rhesus monkeys (Macaca mulatta): report of a pilot stud?. P R Health Sci. J. 8, 87–94.Google Scholar
Matsuda, M., Liu, Y., Mahankali, S.et al. (1999). Altered hypothalamic function in response to glucose ingestion in obese human?. Diabetes 48, 1801–6.CrossRefGoogle Scholar
Mayer, J., Marshall, N. B., Vitale, J. J., Christensen, J. H., Mashayekhi, M. B. & Stare, F. J. (1954). Exercise, food intake and body weight in normal rats and genetically obese adult mic?. Am. J. Physiol. 177, 544–8.Google Scholar
Michel, C., Levin, B. E. & Dunn-Meynell, A. A. (2003). Stress facilitates body weight gain in genetically predisposed rats on medium fat die?. Am. J. Physiol. 285, R791–9.Google Scholar
Michel, C., Dunn-Meynell, A. A. & Levin, B. E. (2004). Reduced brain CRH and GR mRNA expression precedes obesity in juvenile rats bred for diet-induced obesit?. Behav. Brain Res. 154, 511–17.CrossRefGoogle Scholar
Minami, T., Shimizu, N., Duan, S. & Oomura, Y. (1990). Hypothalamic neuronal activity responses to 3-hydroxybutyric acid, an endogenous organic aci?. Brain Res. 509, 351–4.CrossRefGoogle Scholar
Mittelman, S. D., Citters, V. W., Kirkman, E. L. & Bergman, R. N. (2002). Extreme insulin resistance of the central adipose depot in vivo?. Diabetes 51, 755–61.CrossRefGoogle ScholarPubMed
Mohan, P. F., Ihnen, J. S., Levin, B. E. & Cleary, M. P. (1990). Effects of dehydroepiandrosterone treatment in rats with diet-induced obesit?. J. Nutr. 120, 1103–14.CrossRefGoogle Scholar
Mrad, J. A., Yakubu, F., Lin, D., Peters, J. C., Atkinson, J. B. & Hill, J. O. (1992). Skeletal muscle composition in dietary obesity-susceptible and dietary obesity-resistant rat?. Am. J. Physiol. 262, R684–8.Google Scholar
Nagase, H., Bray, G. A. & York, D. A. (1996). Pyruvate and hepatic pyruvate dehydrogenase levels in rat strains sensitive and resistant to dietary obesit?. Am. J. Physiol. 270, R485–95.Google Scholar
Neel, V. (1962). In diabetes mellitus: a “thrifty” genotype rendered detrimental by progres?. Am. J. Hum. Genet. 14, 353–62.Google Scholar
Niijima, A. (1969). Afferent impulse discharges from glucoreceptors in the liver of the guinea pi?. Ann. N.Y. Acad. Sci. 157, 690–700.CrossRefGoogle Scholar
Oomura, Y., Kimura, K., Ooyama, H., Maeo, T., Iki, M. & Kuniyoshi, N. (1964). Reciprocal activities of the ventromedial and lateral hypothalamic area of cat?. Science 143, 484–5.CrossRefGoogle Scholar
Oomura, Y., Nakamura, T., Sugimori, M. & Yamada, Y. (1975). Effect of free fatty acid on the rat lateral hypothalamic neuron?. Physiol. Behav. 14, 483–6.CrossRefGoogle Scholar
Pagliassotti, M. J., Shahrokhi, K. A. & Hill, J. O. (1993). Skeletal muscle glucose metabolism in obesity-prone and obesity-resistant rat?. Am. J. Physiol. 264, R1224–8.Google Scholar
Pagliassotti, M. J., Knobel, S. M., Shahrokhi, K. A., Manzo, A. M. & Hill, J. O. (1994). Time course adaptation to a high-fat diet in obesity-resistant and obesity-prone rat?. Am. J. Physiol. 267, R659–64.Google Scholar
Pagliassotti, M. J., Pan, D. A., Prach, P. A., Koppenhafer, T. A., Storlien, L. H. & Hill, J. O. (1995). Tissue oxidative capacity, fuel stores and skeletal muscle fatty acid composition in obesity-prone and obesity-resistant rat?. Obes. Res. 3, 459–64.CrossRefGoogle Scholar
Pagliassotti, M. J., Horton, T. J., Gayles, E. C., Koppenhafer, T. A., Rosenzweig, T. D. & Hill, J. O. (1997). Reduced insulin suppression of glucose appearance is related to susceptibility to dietary obesity in rat?. Am. J. Physiol. 272, R1264–70.Google Scholar
Pelat, M., Verwaerde, P., Tran, M. -A., Montastruc, J. -L. & Senard, J. M. (2002). Alpha2-adrenoceptor function in arterial hypertension associated with obesity in dogs fed a high-fat die?. J Hypertens. 20, 957–64.CrossRefGoogle Scholar
Philip-Couderc, P., Smih, F., Hall, J. E.et al. (2004). Kinetic analysis of cardiac transcriptome regulation during chronic high-fat diet in dog?. Physiol. Genomics. 19, 32–40.CrossRefGoogle Scholar
Plagemann, A., Heidrich, I., Gotz, F., Rohde, W. & Dorner, G. (1992). Lifelong enhanced diabetes susceptibility and obesity after temporary intrahypothalamic hyperinsulinism during brain organizatio?. Exp. Clin. Endocrinol. 99, 91–5.CrossRefGoogle Scholar
Popkin, B. M. & Doak, C. M. (1999). The obesity epidemic is a worldwide phenomeno?. Nutr. Rev. 56, 106–14.CrossRefGoogle Scholar
Porte, D. Jr. (1969). Sympathetic regulation of insulin secretion. Its relation to diabetes mellitu?. Arch. Intern. Med. 123, 252–60.CrossRefGoogle Scholar
Ramirez, I. (1987). Feeding a liquid diet increases energy intake, weight gain and body fat in rat?. J. Nutr. 117, 2127–34.CrossRefGoogle Scholar
Reaven, G. M. (1988). Banting Lecture 1988: role of insulin resistance in human diseas?. Diabetes 37, 1595–607.CrossRefGoogle Scholar
Reifsnyder, P. C., Churchill, G. & Leiter, E. H. (2000). Maternal environment and genotype interact to establish diabesity in mic?. Genome Res. 10, 1568–78.CrossRefGoogle Scholar
Ricardo, J. A. & Koh, E. T. (1978). Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the ra?. Brain Res. 153, 1–26.CrossRefGoogle Scholar
Ricci, M. M. & Levin, B. E. (2003). Ontogeny of diet-induced obesity in selectively-bred Sprague–Dawley rat?. Am. J. Physiol. 285, R610–18.Google Scholar
Ritter, S., Dinh, T. T. & Zhang, Y. (2000). Localization of hindbrain glucoreceptive sites controlling food intake and blood glucos?. Brain Res. 856, 37–47.CrossRefGoogle Scholar
Ritter, S., Bugarith, K. & Dinh, T. T. (2001). Immunotoxic destruction of distinct catecholamine subgroups produces selective impairment of glucoregulatory responses and neuronal activatio?. J. Comp. Neurol. 432, 197–216.CrossRefGoogle Scholar
Rolls, B. A. & Rowe, E. A. (1979). Exercise and the development and persistence of dietary obesity in male and female rat?. Physiol. Behav. 23, 241–7.CrossRefGoogle Scholar
Rolls, B. A., Rowe, E. A. & Turner, R. C. (1980). Persistent obesity in rats following a period of consumption of a mixed, high energy die?. J. Physiol. 298, 415–27.CrossRefGoogle Scholar
Routh, V. H., Levin, B. E. & McArdle, J. J. (1998). Defective ATP-sensitive K+ (KATP) channel in ventromedial hypothalamic nucleus (VMN) of obesity-prone (DIO) rat?. FASEB J. 12, A864.Google Scholar
Rowland, N. E. & Carlton, J. (1986). Tolerance to fenfluramine anorexia: fact or fictio??. Appetite. 7, Suppl. 71–83.CrossRefGoogle ScholarPubMed
Sanders, N. M., Dunn-Meynell, A. A. & Levin, B. E. (2004). Third ventricular alloxan reversibly impairs glucose counterregulatory response?. Diabetes 53, 1230–6.CrossRefGoogle Scholar
Schemmel, R., Mickelsen, O. & Tolgay, Z. (1969). Dietary obesity in rats: influence of diet, weight, age, and sex on body compositio?. Am. J. Physiol. 216, 373–9.Google Scholar
Schemmel, R., Mickelsen, O. & Gill, J. L. (1970). Dietary obesity in rats: body weight and body fat accretion in seven strains of rat?. J. Nutr. 100, 1041–8.CrossRefGoogle Scholar
Schwartz, M. W., Baskin, D. G., Bukowski, T. R.et al. (1996). Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mic?. Diabetes 45, 531–5.CrossRefGoogle Scholar
Schwartz, S. M. (1989). Characteristics of spontaneous obesity in the Cayo Santiago rhesus macaque: preliminary repor?. P. R. Health Sci. J. 8, 103–6.Google Scholar
Schwartz, S. M., Kemnitz, J. W. & Howard, C. F. J. (1993). Obesity in free–ranging rhesus macaque?. Int. J. Obes. 17, 1–9.Google Scholar
Sclafani, A. & Springer, D. (1976). Dietary obesity in adult rats: similarities to hypothalamic and human obesity syndrome?. Physiol. Behav. 17, 461–71.CrossRefGoogle Scholar
Shor-Posner, G., Ian, C., Brennan, G.et al. (1991). Self-selecting albino rats exhibit differential preferences for pure macronutrient diets: characterization of three subpopulation?. Physiol. Behav. 50, 1187–95.CrossRefGoogle Scholar
Sims, E. A. H., Danforth, E. Jr., Bray, G. A., Glennon, J. A. & Salans, L. B. (1973). Endocrine and metabolic effects of experimental obesity in ma?. Recent Progr. Horm. Res. 29, 457–87.Google Scholar
Smith, B. K., Kelly, L. A., Pina, R., York, D. A. & Bray, G. A. (1998). Preferential fat intake increases adiposity but not body weight in Sprague–Dawley rat?. Appetite 31, 127–39.CrossRefGoogle ScholarPubMed
Song, Z. & Routh, V. H. (2005). Differential effects of glucose and lactate on glucosensing neurons in the ventromedial hypothalamic nucleu?. Diabetes 54, 15–22.CrossRefGoogle Scholar
Song, Z., Levin, B. E., McArdle, J. J., Bakhos, N. & Routh, V. H. (2001). Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus (VMN?. Diabetes 50, 2673–81.CrossRefGoogle Scholar
Spanswick, D., Smith, M. A., Groppi, V. E., Logan, S. D. & Ashford, M. L. (1997). Leptin inhibits hypothalamic neurons by activation of ATP- sensitive potassium channel?. Nature 390, 521–5.CrossRefGoogle Scholar
Stunkard, A. J. (1982). Anorectic agents lower a body weight set poin?. Life Sci. 30, 2043–55.CrossRefGoogle Scholar
Stunkard, A. J., Harris, J. R., Pedersen, N. L. & McClearn, G. E. (1990). The body-mass index of twins who have been reared apar?. N. Engl. J. Med. 322, 1483–7.CrossRefGoogle Scholar
Surwit, R. S., Petro, A. E., Parekh, P. & Collins, S. (1997). Low plasma leptin in response to dietary fat in diabetes- and obesity-prone mic?. Diabetes 46, 1516–20.CrossRefGoogle Scholar
Taghibiglou, C., Bradley, C. A., Wang, Y. & Wang, Y. (2004). High cholesterol levels in neuronal cells impair the insulin signaling pathway and interfere with insulin's neuromodulatory actio?. Soc. Neurosci. Abst. 24, 633.13.Google Scholar
Tang-Christensen, M., Larsen, P. J., Thulesen, J., Romer, J. & Vrang, N. (2000). The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intak?. Nat. Med. 6, 802–7.CrossRefGoogle Scholar
Tkacs, N. C. & Levin, B. E. (2004). Obesity-prone rats have pre-existing defects in their counterregulatory response to insulin-induced hypoglycemi?. Am. J. Physiol. 287, R1110–15.Google Scholar
Triscari, J., Nauss-Karol, C., Levin, B. E. & Sullivan, A. C. (1985). Changes in lipid metabolism in diet-induced obesit?. Metabolism 34, 580–7.CrossRefGoogle Scholar
Truett, A. A., Borne, A. T., Monteiro, M. P. & West, D. B. (1998). Composition of dietary fat affects blood pressure and insulin responses to dietary obesity in the do?. Obes. Res. 6, 137–46.CrossRefGoogle Scholar
Tschop, M., Weyer, C., Tataranni, P. A., Devanarayan, V., Ravussin, E. & Heiman, M. L. (2001). Circulating ghrelin levels are decreased in human obesit?. Diabetes 50, 707–9.CrossRefGoogle Scholar
Vainio, S., Heino, S., Mansson, J. E.et al. (2002). Dynamic association of human insulin receptor with lipid rafts in cells lacking caveola?. EMBO Rep. 3, 95–100.CrossRefGoogle Scholar
VandeBerg, J. L. & Williams-Blangero, S. (1997). Advantages and limitations of nonhuman primates as animal models in genetic resesarch on complex disease?. J. Med. Primatol. 26, 113–19.CrossRefGoogle Scholar
Heek, M., Compton, D. S., France, C. F.et al. (1997). Diet-induced obese mice develop peripheral, but not central, resistance to lepti?. J. Clin. Invest. 99, 385–90.CrossRefGoogle ScholarPubMed
Vliet, B. N., Hall, J. E., Mizelle, H. L., Montani, J. P. & Smith, M. J. Jr. (1995). Reduced parasympathetic control of heart rate in obese dog?. Am. J. Physiol. 269, H629–37.Google Scholar
Verwaerde, P., Senard, J. M., Galinier, M.et al. (1999). Changes in short-term variability of blood pressure and heart rate during the development of obesity-associated hypertension in high-fat fed dog?. J. Hypertens. 17, 1135–43.CrossRefGoogle Scholar
Vilberg, T. R. & Keesey, R. E. (1990). Ventromedial hypothalamic lesions abolish compensatory reduction in energy expenditure to weight los?. Am. J. Physiol. 258, R476–80.Google Scholar
Wang, R., Liu, X., Hentges, S. T.et al. (2004). The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptide?. Diabetes 53, 1959–65.CrossRefGoogle Scholar
Wang, R., Cruciani-Guglielmacci, C., Migrenne, S., Magnan, C., Cotero, V. & Routh, V. H. (2005). The effects of oleic-acid (OA) on distinct populations of neurons in the hypothalamic arcuate nucleus (ARC) are dependent on extracellular glucose level?. J. Neurophysiol. 95, 1491–8.CrossRefGoogle Scholar
Weigle, D. S. & Levin, B. E. (2000). Defective dietary induction of uncoupling protein 3 in skeletal muscle of obesity-prone rat?. Obes. Res. 8, 385–91.CrossRefGoogle Scholar
Weinsier, R. L., Nelson, K. M., Hensrud, K. M., Darnell, B. E., Hunter, G. R. & Schutz, Y. (1995). Metabolic predictors of obesity: contribution of resting energy expenditure, thermic effect of food, and fuel utilization to four-year weight gain of post-obese and never-obese wome?. J. Clin. Invest. 95, 980–5.CrossRefGoogle Scholar
West, D. B., Moody, D. L., Boozer, C. N., Atkinson, R. L. & Levin, B. E. (1991). Differential catecholamine response to intraperitoneal glucose injection in inbred mice susceptible or resistant to dietary obesit?. Int. J. Obes. 15, 16.Google Scholar
West, D. B., Boozer, C. N., Moody, D. L. & Atkinson, R. L. (1992). Dietary obesity in nine inbred mouse strain?. Am. J. Physiol. 262, R1025–32.Google Scholar
West, D. B., Goudey-Lefevre, J., York, B. & Truett, G. E. (1994). Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse mode?. J. Clin. Invest. 94, 1410–16.CrossRefGoogle Scholar
Will, M. J., Franzblau, E. B. & Kelley, A. E. (2003). Nucleus accumbens mu-opioids regulate intake of a high-fat diet via activation of a distributed brain networ?. J. Neurosci. 23, 2882–8.CrossRefGoogle Scholar
Williams, T., Berelowitz, M., Joffe, S. N.et al. (1984). Impaired growth hormone responses to growth hormone-releasing factor in obesit?. N. Engl. J. Med. 311, 1403–7.CrossRefGoogle Scholar
Wilmot, C. A., Sullivan, A. C. & Levin, B. E. (1988). Effects of diet and obesity on brain α1- and α2-noradrenergic receptors in the ra?. Brain Res. 453, 157–66.CrossRefGoogle Scholar
Wolden-Hanson, T., Davis, G. A., Baum, S. T. & Kemnitz, J. W. (1993). Insulin levels, physical activity, and urinary catecholamine excretion of obese and non-obese rhesus monkey?. Obes. Res. 1, 5–17.CrossRefGoogle Scholar
Woods, S. C., Seeley, R. J., Rushing, P. A., D'Alessio, D. & Tso, P. (2003). A controlled high-fat diet induces an obese syndrome in rat?. J. Nutr. 133, 1081–7.CrossRefGoogle Scholar
Yang, X., Kow, L. M., Funabashi, T. & Mobbs, C. V. (1999). Hypothalamic glucose sensor. Similarities to and differences from pancreatic β-cell mechanism?. Diabetes 48, 1763–72.CrossRefGoogle Scholar
Yang, X. J., Kow, L. M., Pfaff, D. W. & Mobbs, C. V. (2004). Metabolic pathways that mediate inhibition of hypothalamic neurons by glucos?. Diabetes 53, 67–73.CrossRefGoogle Scholar
Yoshida, T., Fisler, J. S., Fukushima, M., Bray, G. A. & Schemmel, R. A. (1987). Diet, lighting, and food intake affect norepinephrine turnover in dietary obesit?. Am. J. Physiol. 252, R402–8.Google Scholar
Zamboni, M., Armellini, F., Turcato, E.et al. (1994). Relationship between visceral fat, steroid hormones and insulin sensitivity in premenopausal obese wome?. J. Intern. Med. 236, 521–7.CrossRefGoogle Scholar
Zierath, J. R., Livingston, J., Thorne, A., Bolinder, J. & Reynisdottir, S. (1998). Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathwa?. Diabetologia 41, 1343–54.CrossRefGoogle Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×