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The regulation of body weight: lessons from the seasonal animal

Published online by Cambridge University Press:  28 February 2007

Peter J. Morgan  and
Julian G. Mercer
Peter J. Morgan*
Affiliation:
Aberdeen Centre for Energy Regulation and Obesity (ACERO), Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
Julian G. Mercer
Affiliation:
Aberdeen Centre for Energy Regulation and Obesity (ACERO), Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
*
*Corresponding author: Professor Peter J. Morgan, fax +44 1224 716698, email p.morgan@rri.sari.ac.uk
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Abstract

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The hypothalamus is a major regulatory centre involved in the control of many important physiological axes. One of these axes is the regulation of ingestive behaviour. Recent work using a combination of genetic-mutant mouse models together with targeted gene deletions has contributed much to our understanding of how neural pathways of the hypothalamus are involved in the regulation of energy balance in animals. These pathways are also relevant to human energy homeostasis, as mutations in key genes are correlated with obesity. Many of the genes identified mediate the effects of leptin, and are therefore primarily involved in sensing and responding to peripheral signals. In seasonal animals, such as the Siberian hamster (Phodopus sungorus), there is evidence for a higher level of regulation. The systems involved regulate body weight around an apparent 'set-point' through the action of photoperiod via the neurohormone, melatonin. The ability to manipulate energy balance through photoperiod (and melatonin) in the seasonal-animal model offers novel opportunities to identify further fundamental aspects of the control mechanisms involved in the central control of energy homeostasis and body weight.

Keywords

Energy balanceMelatoninHypothalamusGene expression
Type
Nutrition and Behaviour Group Symposium on ‘Future Perspectives in Nutrition and Behaviour Research’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 1 , February 2001 , pp. 127 - 134
Copyright
Copyright © The Nutrition Society 2001

References

Boss-Williams, KA & Bartness, TJ (1996) NPY stimulation of food intake in Siberian hamsters is not photoperiod dependent. Physiology and Behavior 59, 157–164.CrossRefGoogle Scholar
Broberger, C, Johansen, J, Johansson, C, Schalling, M & Hokfelt, T (1998) The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proceedings of the National Academy of Sciences USA 95, 15043–15048.CrossRefGoogle ScholarPubMed
Chemelli, RM, Willie, JT, Sinton, CM, Elmquist, JK, Scammell, T, Lee, C, Richardson, JA, Williams, SC, Xiong, Y, Kisanuki, Y, Fitch, TE, Nakazato, M, Hammer, RE, Saper, CB & Yanagisawa, M (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98, 437–451.CrossRefGoogle ScholarPubMed
Chen, H, Charlat, O, Tartaglia, LA, Woolf, EA, Weng, X, Ellis, SJ, Lakey, ND, Culpepper, J, Moore, KJ, Breitbart, RE, Duyk, GM, Tepper, RI & Morgenstern, JP (1996) Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84, 491–495.CrossRefGoogle ScholarPubMed
Cheung, CC, Clifton, DK & Steiner, RA (1997) Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138, 4489–4492.CrossRefGoogle ScholarPubMed
Cone, RD, Lu, D, Koppula, S, Vage, DI, Klungland, H, Boston, B, Chen, W, Orth, DN, Pouton, C & Kesterson, RA (1996 a) The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Recent Progress in Hormone Research 51, 287–317.Google ScholarPubMed
Cone, RD, Lu, D, Koppula, S, Vage, DI, Klungland, H, Boston, B, Chen, W, Orth, DN, Poulton, C & Kesterson, RA (1996 b) The melanocortin receptors: agonists, antagonists, and hormonal control of pigmentation. Discussion. Recent Progress in Hormone Research 51, 318.Google Scholar
Cowley, MA, Pronchuk, N, Fan, W, Dinulescu, DM, Colmers, WF & Cone, RD (1999) Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron 24, 155–163.CrossRefGoogle ScholarPubMed
de Lecea, L, Kilduff, TS, Peyron, C, Gao, X, Foye, PE, Danielson, PE, Fukuhara, C, Battenberg, EL, Gautvik, VT, Bartlett, FS II, Frankel, WN, van den Pol, AN, Bloom, FE, Gautvik, KM & Sutcliffe, JG (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proceedings of the National Academy of Sciences USA 95, 322–327.CrossRefGoogle ScholarPubMed
Ebling, FJ, Arthurs, OJ, Turney, BW & Cronin, AS (1998) Seasonal neuroendocrine rhythms in the male Siberian hamster persist after monosodium glutamate-induced lesions of the arcuate nucleus in the neonatal period. Journal of Neuroendocrinology 10, 701–712.CrossRefGoogle ScholarPubMed
Elias, CF, Lee, C, Kelly, J, Aschkenasi, C, Ahima, RS, Couceyro, PR, Kuhar, MJ, Saper, CB & Elmquist, JK (1998) Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron 21, 1375–1385.CrossRefGoogle ScholarPubMed
Erickson, JC, Clegg, KE & Palmiter, RD (1996 a) Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature 381, 415–421.CrossRefGoogle ScholarPubMed
Erickson, JC, Hollopeter, G & Palmiter, RD (1996 b) Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274, 1704–1707.CrossRefGoogle Scholar
Fan, W, Boston, BA, Kesterson, RA, Hruby, VJ & Cone, RD (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385, 165–168.CrossRefGoogle ScholarPubMed
Garrow, J (1999) Significance of within person weight variation. Obesity. British Nutrition Foundation Report, pp. 132–138. Oxford: Blackwell Science.Google Scholar
Hahn, TM, Breininger, JF, Baskin, DG & Schwartz, MW (1998) Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nature Neuroscience 1, 271–272.CrossRefGoogle ScholarPubMed
Hardie, LJ, Rayner, DV, Holmes, S & Trayhurn, P (1996) Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. Biochemical and Biophysical Research Communications 223, 660–665.CrossRefGoogle Scholar
Huszar, D, Lynch, CA, Fairchild-Huntress, V, Dunmore, JH, Fang, Q, Berkemeier, LR, Gu, W, Kesterson, RA, Boston, BA, Cone, RD, Smith, FJ, Campfield, LA, Burn, P & Lee, F (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–141.CrossRefGoogle ScholarPubMed
Jackson, RS, Creemers, JW, Ohagi, S, Raffin-Sanson, ML, Sanders, L, Montague, CT, Hutton, JC & O'Rahilly, S (1997) Obesity and impaired prohormone processing associated with mutations in the human prohomone convertase 1 gene. Nature Genetics 16, 303–306.CrossRefGoogle Scholar
Kalra, SP, Dube, MG, Pu, S, Xu, B, Horvath, TL & Kalra, PS (1999) Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocrine Reviews 20, 68–100.Google ScholarPubMed
Klingenspor, M, Dickopp, A, Heldmaier, G & Klaus, S (1996) Short photoperiod reduces leptin gene expression in white and brown adipose tissue of Djungarian hamsters. FEBS Letters 399, 290–294.CrossRefGoogle Scholar
Klingenspor, M, Niggemann, H & Heldmaier, G (2000) Modulation of leptin sensitivity by short photoperiod acclimation in the Djungarian hamster, Phodopus sungorus. Journal of Comparative Physiology 170B, 37–43.CrossRefGoogle Scholar
Levin, BE & Dunn-Meynell, AA (2000) Defense of body weight against chronic caloric restriction in obesity-prone and -resistant rats. American Journal of Physiology 278, R231–R237.Google ScholarPubMed
Levin, BE & Keesey, RE (1998) Defense of differing body weight set points in diet-induced obese and resistant rats. American Journal of Physiology 274, R412–R419.Google ScholarPubMed
Masuda, A & Oishi, T (1995) Effects of restricted feeding on the light-induced body weight change and locomotor activity in the Djungarian hamster. Physiology and Behavior 58, 153–159.CrossRefGoogle ScholarPubMed
Mela, D, Ritson, C & Kuznesof, S (1999) Aetiology of obesity X: Food policy and eating patterns Obesity. British Nutrition Foundation Report, pp. 101–115. Oxford: Blackwell Science.Google Scholar
Mercer, JG (1998) Regulation of appetite and body weight in seasonal mammals. Comparative Biochemistry and Physiology 119C, 295–303.Google Scholar
Mercer, JG, Adam, CL & Morgan, PJ (2000 a) Towards an understanding of physiological body mass regulation: seasonal animal models. Nutritional Neuroscience 3, 307–320.CrossRefGoogle ScholarPubMed
Mercer, JG, Hoggard, N, Williams, LM, Lawrence, CB, Hannah, LT, Morgan, PJ & Trayhurn, P (1996) Coexpression of leptin receptor and preproneuropeptide Y mRNA in arcuate nucleus of mouse hypothalamus. Journal of Neuroendocrinology 8, 733–735.CrossRefGoogle ScholarPubMed
Mercer, JG, Moar, KM, Rayner, DV, Trayhurn, P & Hoggard, N (1997) Regulation of leptin receptor and NPY gene expression in hypothalamus of leptin-treated obese (ob/ob) and cold-exposed lean mice. FEBS Letters 402, 185–188.CrossRefGoogle ScholarPubMed
Mercer, JG, Moar, KM, Ross, AW, Hoggard, N & Morgan, PJ (2000 b) Photoperiod regulates arcuate nucleus POMC, AGRP, and leptin receptor mRNA in Siberian hamster hypothalamus. American Journal of Physiology 278, R271–R281.Google ScholarPubMed
Mercer, JG, Moar, KM, Ross, AW & Morgan, PJ (2000 c) Regulation of leptin receptor, POMC and AGRP gene expression by photoperiod and food deprivation in the hypothalamic arcuate nucleus of the male Siberian hamster (Phodopus sungorus). Appetite 34, 109–111.CrossRefGoogle ScholarPubMed
Messager, S, Ross, AW, Barren, P & Morgan, PJ (1999) Decoding photoperiodic time through Perl and ICER gene amplitude. Proceedings of the National Academy of Sciences USA 96, 9938–9943.CrossRefGoogle Scholar
Miller, MW, Duhl, DM, Vrieling, H, Cordes, SP, Ollmann, MM, Winkes, BM & Barsh, GS (1993) Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation. Genes and Development 7, 454–467.CrossRefGoogle ScholarPubMed
Montague, CT, Farooqi, IS, Whitehead, JP, Soos, MA, Rau, H, Wareham, NJ, Sewter, CP, Digby, JE, Mohammed, SN, Hurst, JA, Cheetham, CH, Earley, AR, Barnett, AH, Prins, JB & O'Rahilly, S (1997) Congenital leptin deficiency is associated with early-onset obesity in humans. Nature 387, 903–908.CrossRefGoogle ScholarPubMed
Morgan, PJ, Barrett, P, Howell, HE & Helliwell, R (1994) Melatonin receptors: localization, molecular pharmacology and physiological significance. Neurochemistry International 24, 101–146.CrossRefGoogle ScholarPubMed
Morgan, PJ, Ross, AW, Graham, ES, Adam, C, Messager, S & Barrett, P (1998) oPerl is an early response gene under photoperiodic regulation in the ovine pars tuberalis. Journal of Neuroendocrinology 10, 319–323.CrossRefGoogle ScholarPubMed
Mountjoy, KG, Mortrud, MT, Low, MJ, Simerly, RB & Cone, RD (1994) Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Molecular Endocrinology 8, 1298–1308.Google ScholarPubMed
Ollmann, MM, Wilson, BD, Yang, YK, Kerns, JA, Chen, Y, Gantz, I & Barsh, GS (1997) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278, 135–138.CrossRefGoogle ScholarPubMed
Qu, D, Ludwig, DS, Gammeltoft, S, Piper, M, Pelleymounter, MA, Cullen, MJ, Mathes, WF, Przypek, R, Kanarek, R & Maratos-Flier, E (1996) A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature 380, 243–247.CrossRefGoogle ScholarPubMed
Reddy, AB, Cronin, AS, Ford, H & Ebling, FJ (1999) Seasonal regulation of food intake and body weight in the male Siberian hamster: studies of hypothalamic orexin (hypocretin), neuropeptide Y (NPY) and pro-opiomelanocortin (POMC). European Journal of Neuroscience 11, 3255–3264.CrossRefGoogle ScholarPubMed
Rosenbaum, M, Leibel, RL & Hirsch, J (1997) Obesity. New England Journal of Medicine 337, 396–407.CrossRefGoogle ScholarPubMed
Rossi, M, Kim, MS, Morgan, DG, Small, CJ, Edwards, CM, Sunter, D, Abusnana, S, Goldstone, AP, Russell, SH, Stanley, SA, Smith, DM, Yagaloff, K, Ghatei, MA & Bloom, SR (1998) A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. Endocrinology 139, 4428–4431.CrossRefGoogle ScholarPubMed
Sakurai, T, Amemiya, A, Ishii, M, Matsuzaki, I, Chemelli, RM, Tanaka, H, Williams, SC, Richardson, JA, Kozlowski, GP, Wilson, S, Arch, JR, Buckingham, RE, Haynes, AC, Carr, SA, Annan, RS, McNulty, DE, Liu, WS, Terrett, JA, Elshourbagy, NA, Bergsma, DJ & Yanagisawa, M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573–585.CrossRefGoogle Scholar
Schwartz, MW, Erickson, JC, Baskin, DG & Palmiter, RD (1998) Effect of fasting and leptin deficiency on hypothalamic neuropeptide Y gene transcription in vivo revealed by expression of a lacZ reporter gene. Endocrinology 139, 2629–2635.CrossRefGoogle ScholarPubMed
Schwartz, MW, Seeley, RJ, Woods, SC, Weigle, DS, Campfield, LA, Burn, P & Baskin, DG (1997) Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 46, 2119–2123.CrossRefGoogle ScholarPubMed
Schwartz, MW, Woods, SC, Porte, D Jr, Seeley, RJ & Baskin, DG (2000) Central nervous system control of food intake. Nature 404, 661–671.CrossRefGoogle ScholarPubMed
Shimada, M, Tritos, NA, Lowell, BB, Flier, JS & Maratos-Flier, E (1998) Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396, 670–674.CrossRefGoogle ScholarPubMed
Shutter, JR, Graham, M, Kinsey, AC, Scully, S, Luthy, R & Stark, KL (1997) Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes and Development 11, 593–602.CrossRefGoogle ScholarPubMed
Stanley, BG, Kyrkouli, SE, Lampert, S & Leibowitz, SF (1986) Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 7, 1189–1192.CrossRefGoogle ScholarPubMed
Steinlechner, S, Heldmaier, G & Becker, H (1983) The seasonal cycle of body weight in the Djungarian hamster: photoperiod control and influence of starvation and melatonin. Oecologia 60, 401–405.CrossRefGoogle ScholarPubMed
Stellar, E (1954) The physiology of motivation. Psychological Reviews 61, 5–22.CrossRefGoogle ScholarPubMed
Thornton, JE, Cheung, CC, Clifton, DK & Steiner, RA (1997) Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology 138, 5063–5066.CrossRefGoogle ScholarPubMed
Vaisse, C, Clement, K, Guy-Grand, B & Froguel, P (1998) A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nature Genetics 20, 113–114.CrossRefGoogle ScholarPubMed
Wardle, JS (1999) Aetiology of obesity VIII: Psychological factors Obesity. British Nutrition Foundation Report, pp. 83–91. Oxford: Blackwell Science.Google Scholar
Yeo, GS, Farooqi, IS, Aminian, S, Halsall, DJ, Stanhope, RG & O'Rahilly, S (1998) A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nature Genetics 20, 111–112.CrossRefGoogle ScholarPubMed
Zhang, Y, Proenca, R, Maffei, M, Barone, M, Leopold, L & Friedman, JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432.CrossRefGoogle ScholarPubMed