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-55f67697df-sqlfs Total loading time: 0 Render date: 2025-05-11T13:56:33.255Z Has data issue: false hasContentIssue false

3 - Hypothalamic control of energy homeostasis

Published online by Cambridge University Press:  15 September 2009

By
Neel S. Singhal  and
Rexford S. Ahima
Edited by
Jenni Harvey  and
Dominic J. Withers
Neel S. Singhal
Affiliation:
University of Pennsylvania, School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism Philadelphia, Pennsylvania 19104, USA
Rexford S. Ahima
Affiliation:
University of Pennsylvania, School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism Philadelphia, Pennsylvania 19104, USA
Jenni Harvey
Affiliation:
University of Dundee
Dominic J. Withers
Affiliation:
Imperial College of Science, Technology and Medicine, London
Get access

Summary

Introduction

The hypothalamus is a critical integrator of peripheral and central signals that mediate energy homeostasis. Over the last two decades, substantial progress has been made in elucidating the details of how neural, hormonal and nutrient signals from the gut and adipose tissue act on specific hypothalamic pathways to control energy balance and various physiologic processes. These hypothalamic circuits affect not only appetite, but through their diverse projections to the autonomic nervous system, brainstem and higher centers also influence motivational and motor function, and the endocrine system via the pituitary gland. Although the details of the interacting factors and effector mechanisms remain an area of active research, it is clear that neuropeptides at the level of the hypothalamus modulate key aspects of feeding behavior, energy expenditure and neuroendocrine function (Grill & Kaplan, 2002). In this chapter, we provide an overview of the hypothalamic circuitry within a framework for understanding its role as a sensor, integrator and effector of energy homeostasis and diverse physiologic processes.

Classical role of the hypothalamus in feeding regulation

A crucial involvement of the base of the diencephalon in energy homeostasis was first suggested by clinical observations in patients with pituitary tumors associated with excessive fat deposition and hypogonadism (Bramwell, 1888; Frolich, 1901). Several animal studies confirmed the importance of this region in body weight regulation, but it was not until the experiments of Hetherington and Ranson that the role of the hypothalamus rather than that of the pituitary gland was firmly established.

Type
Chapter
Information
Neurobiology of Obesity , pp. 52 - 82
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.)

Book purchase

Temporarily unavailable

References

Acuna-Goycolea, C. & Pol, A. N. (2005). Peptide YY(3–36) inhibits both anorexigenic proopiomelanocortin and orexigenic neuropeptide Y neurons: implications for hypothalamic regulation of energy homeostasis. J. Neurosci. 25, 10 510–19.CrossRefGoogle ScholarPubMed
Adrian, T. E., Allen, J. M., Bloom, S. R.et al. (1983). Neuropeptide Y distribution in human brain. Nature 306, 584–6.CrossRefGoogle ScholarPubMed
Ahima, R. S., Bjorbaek, C., Osei, S. & Flier, J. S. (1999). Regulation of neuronal and glial proteins by leptin: implications for brain development. Endocrinology 140, 2755–62.CrossRefGoogle ScholarPubMed
Ammar, A. A., Sederholm, F., Saito, T. R., Scheurink, A. J., Johnson, A. E. & Sodersten, P. (2000). NPY-leptin: opposing effects on appetitive and consummatory ingestive behavior and sexual behavior. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278, R1627–33.CrossRefGoogle ScholarPubMed
Anand, B. K. & Brobeck, J. R. (1951). Localization of a “feeding center” in the hypothalamus of the rat. Proc. Soc. Exp. Biol. Med. 77, 323–4.CrossRefGoogle ScholarPubMed
Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B. & Maness, L. M. (1996). Leptin enters the brain by a saturable system independent of insulin. Peptides 17, 305–11.CrossRefGoogle ScholarPubMed
Bannon, A. W., Seda, J., Carmouche, M.et al. (2000). Behavioral characterization of neuropeptide Y knockout mice. Brain Res. 868, 79–87.CrossRefGoogle ScholarPubMed
Berridge, K. C. (1991). Modulation of taste affect by hunger, caloric satiety, and sensory-specific satiety in the rat. Appetite 16, 103–20.CrossRefGoogle ScholarPubMed
Billington, C. J., Briggs, J. E., Grace, M. & Levine, A. S. (1991). Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am. J. Physiol. 260, R321–7.Google ScholarPubMed
Borg, M. A., Sherwin, R. S., Borg, W. P., Tamborlane, W. V. & Shulman, G. I. (1997). Local ventromedial hypothalamus glucose perfusion blocks counterregulation during systemic hypoglycemia in awake rats. J. Clin. Invest. 99, 361–5.CrossRefGoogle ScholarPubMed
Borg, W. P., Sherwin, R. S., During, M. J., Borg, M. A. & Shulman, G. I. (1995). Local ventromedial hypothalamus glucopenia triggers counterregulatory hormone release. Diabetes 44, 180–4.CrossRefGoogle ScholarPubMed
Borowsky, B., Durkin, M. M., Ogozalek, K.et al. (2002). Antidepressant, anxiolytic and anorectic effects of a melanin concentrating hormone-1 receptor antagonist. Nat. Med. 8, 825–30.CrossRefGoogle ScholarPubMed
Bouret, S. G., Draper, S. J. & Simerly, R. B. (2004). Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304, 108–10.CrossRefGoogle ScholarPubMed
Bramwell, B. (1888). Intracranial Tumours. Edinburgh: Pentland.Google Scholar
Broadwell, R. D. & Brightman, M. W. (1976). Entry of peroxidase into neurons of the central and peripheral nervous systems from extracerebral and cerebral blood. J. Comp. Neurol. 166, 257–83.CrossRefGoogle ScholarPubMed
Broberger, C., Lecea, L., Sutcliffe, J. G. & Hokfelt, T. (1998). Hypocretin/orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene-related protein systems. J. Comp. Neurol. 402, 460–74.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
Burdakov, D., Luckman, S. M. & Verkhratsky, A. (2005). Glucose-sensing neurons of the hypothalamus. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 360, 2227–35.CrossRefGoogle ScholarPubMed
Clark, G., Magoun, H. W. & Ranson, S. W. (1939). Hypothalamic regulation of body temperature. J. Neurophysiol. 2, 61–80.CrossRefGoogle Scholar
Cowley, M. A., Smart, J. L., Rubinstein, M.et al. (2001). Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411, 480–4.CrossRefGoogle ScholarPubMed
Critchley, H. D. & Rolls, E. T. (1996). Hunger and satiety modify the responses of olfactory and visual neurons in the primate orbitofrontal cortex. J. Neurophysiol. 75, 1673–86.CrossRefGoogle ScholarPubMed
Di Marzo, V. & Matias, I. (2005). Endocannabinoid control of food intake and energy balance. Nat. Neurosci. 8, 585–9.CrossRefGoogle ScholarPubMed
Di Marzo, V., Goparaju, S. K., Wang, L.et al. (2001). Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410, 822–5.CrossRefGoogle ScholarPubMed
DiRocco, R. J. & Grill, H. G. (1979). The forebrain is not essential for sympathoadrenal hyperglycemic response to glucoprivation. Science 204, 1112–14.CrossRefGoogle Scholar
Douglass, J., McKinzie, A. A. & Couceyro, P. (1995). PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine. J. Neurosci. 15, 2471–81.CrossRefGoogle ScholarPubMed
Egawa, M., Yoshimatsu, H. & Bray, H. G. (1991). Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats. Am. J. Physiol. 260, R328–34.Google ScholarPubMed
Elias, C. F., Aschkenasi, C., Lee, C.et al. (1999). Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23, 775–86.CrossRefGoogle ScholarPubMed
Elmquist, J. K., Ahima, R. S., Elias, C. F., Flier, J. S. & Saper, C. B. (1998a). Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei. Proc. Natl. Acad. Sci. USA 95, 741–6.CrossRefGoogle Scholar
Elmquist, J. K., Bjorbaek, C., Ahima, R. S., Flier, J. S. & Saper, C. B. (1998b). Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol. 395, 535–47.3.0.CO;2-2>CrossRefGoogle Scholar
Erickson, J. C., Hollopeter, G. & Palmiter, R. D. (1996). Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274, 1704–7.CrossRefGoogle Scholar
Farooqi, I. S., Yeo, G. S., Keogh, J. M.et al. (2000). Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J. Clin. Invest. 106, 271–9.CrossRefGoogle ScholarPubMed
Fekete, C., Legradi, G., Mihaly, E.et al. (2000). Alpha-melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. J. Neurosci. 20, 1550–8.CrossRefGoogle ScholarPubMed
Fekete, C., Sarkar, S., Rand, W. M.et al. (2002). Neuropeptide Y1 and Y5 receptors mediate the effects of neuropeptide Y on the hypothalamic-pituitary-thyroid axis. Endocrinology 143, 4513–19.CrossRefGoogle ScholarPubMed
Fekete, C., Marks, D. L., Sarkar, S.et al. (2004). Effect of agouti-related protein in regulation of the hypothalamic pituitary-thyroid axis in the melanocortin 4 receptor knockout mouse. Endocrinology 145, 14 816–21.CrossRefGoogle ScholarPubMed
Fekete, C., Sarkar, S. & Lechan, R. M. (2005). Relative contribution of brainstem afferents to the cocaine- and amphetamine-regulated transcript (CART) innervation of thyrotropin-releasing hormone synthesizing neurons in the hypothalamic paraventricular nucleus (PVN). Brain Res. 1032, 171–5.CrossRefGoogle Scholar
Frolich, A. (1901). Ein fall von tumor der hypophysis cerebri ohne akromegalie. Rundsch 15, 883–6.Google Scholar
Fulton, S., Woodside, B. & Shizgal, P. (2000). Modulation of brain reward circuitry by leptin. Science 287, 125–8.CrossRefGoogle ScholarPubMed
Gold, R. M. (1973). Hypothalamic obesity: the myth of the ventromedial nucleus. Science 182, 488–90.CrossRefGoogle ScholarPubMed
Gomez, R., Navarro, M., Ferrer, B.et al. (2002). A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J. Neurosci. 22, 9612–17.CrossRefGoogle ScholarPubMed
Gooley, J. J., Schomer, A. & Saper, C. B. (2006). The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms. Nat. Neurosci. 9, 398–407.CrossRefGoogle ScholarPubMed
Grill, H. J. & Kaplan, J. M. (2002). The neuroanatomical axis for control of energy balance. Front. Neuroendocrinol. 23, 2–40.CrossRefGoogle ScholarPubMed
Harris, G. C. & Aston-Jones, G. (2006). Arousal and reward: a dichotomy in orexin function. Trends Neurosci. 29, 571–7.CrossRefGoogle ScholarPubMed
Harrold, J. A. & Williams, G. (2003). The cannabinoid system: a role in both the homeostatic and hedonic control of eating? Br. J. Nutr. 90, 729–34.CrossRefGoogle ScholarPubMed
Haynes, A. C., Jackson, B., Overend, P.et al. (1999). Effects of single and chronic intracerebroventricular administration of the orexins on feeding in the rat. Peptides 20, 1099–105.CrossRefGoogle ScholarPubMed
Hetherington, A. W. & Ranson, S. W. (1940). Hypothalamic lesions and adiposity in the rat. Anat. Rec., 78, 149–72.CrossRefGoogle Scholar
Howard, J. K., Cave, B. J., Oksanen, L. J., Tzameli, I., Bjorbaek, C. & Flier, J. S. (2004). Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nat. Med. 10, 734–8.CrossRefGoogle ScholarPubMed
Huang, X. F., Han, M., South, T. & Storlien, L. (2003). Altered levels of POMC, AgRP and MC4 R mRNA expression in the hypothalamus and other parts of the limbic system of mice prone or resistant to chronic high energy diet-induced obesity. Brain Res. 992, 9–19.CrossRefGoogle ScholarPubMed
Kahn, B. B., Alquier, T., Carling, D. & Hardie, D. G. (2005). AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 1, 15–25.CrossRefGoogle Scholar
Kalra, S. P., Dube, M. G., Sahu, A., Phelps, C. P. & Kalra, P. S. (1991). Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food. Proc. Natl. Acad. Sci. USA, 88, 10 931–5.CrossRefGoogle Scholar
Kastin, A. J., Akerstrom, V. & Pan, W. (2002). Interactions of glucagon-like peptide-1 (GLP-1) with the blood–brain barrier. J. Mol. Neurosci. 18, 7–14.CrossRefGoogle ScholarPubMed
Kim, M. S., Small, C. J., Stanley, S. A.et al. (2000). The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin. J. Clin. Invest. 105, 1005–11.CrossRefGoogle ScholarPubMed
Kirkham, T. C., Williams, C. M., Fezza, F. & Di Marzo, V. (2002). Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. Br. J. Pharmacol. 136, 550–7.CrossRefGoogle ScholarPubMed
Kitamura, T., Feng, Y., Kitamura, Y. I.et al. (2006). Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake. Nat. Med. 12, 534–40.CrossRefGoogle ScholarPubMed
Knigge, K. M. & Scott, D. E. (1970). Structure and function of the median eminence. Am. J. Anat. 129, 223–43.CrossRefGoogle ScholarPubMed
Kohno, D., Gao, H. Z., Muroya, S., Kikuyama, S. & Yada, T. (2003). Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin. Diabetes 52, 948–56.CrossRefGoogle ScholarPubMed
Kristensen, P., Judge, M. E., Thim, L.et al. (1998). Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 393, 72–6.CrossRefGoogle ScholarPubMed
Krude, H., Biebermann, H., Luck, W., Horn, R., Brabant, G. & Gruters, A. (1998). Severe early onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat. Genet. 19, 155–7.CrossRefGoogle ScholarPubMed
Krugel, U., Schraft, T., Kittner, H., Kiess, W. & Illes, P. (2003). Basal and feeding-evoked dopamine release in the rat nucleus accumbens is depressed by leptin. Eur. J. Pharmacol. 482, 185–7.CrossRefGoogle ScholarPubMed
Kuhar, M. J., Jaworski, J. N., Hubert, G. W., Philpot, K. B. & Dominguez, G. (2005). Cocaine- and amphetamine-regulated transcript peptides play a role in drug abuse and are potential therapeutic targets. AAPS J. 7, E259–65.CrossRefGoogle ScholarPubMed
Lam, T. K., Gutierrez-Juarez, R., Pocai, A. & Rossetti, L. (2005). Regulation of blood glucose by hypothalamic pyruvate metabolism. Science 309, 943–7.CrossRefGoogle ScholarPubMed
Lambert, P. D., Couceyro, P. R., McGirr, K. M., Vechia, Dall S. E., Smith, Y. & Kuhar, M. J. (1998). CART peptides in the central control of feeding and interactions with neuropeptide Y. Synapse 29, 293–8.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
Landree, L. E., Hanlon, A. L., Strong, D. W.et al. (2004). C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism. J. Biol. Chem. 279, 3817–27.CrossRefGoogle ScholarPubMed
Lapchak, P. A. & Hefti, F. (1992). BDNF and NGF treatment in lesioned rats: effects on cholinergic function and weight gain. Neuroreport 3, 405–8.CrossRefGoogle ScholarPubMed
Lechan, R. M. & Fekete, C. (2006). Chapter 12: The TRH neuron: a hypothalamic integrator of energy metabolism. Prog. Brain Res. 153C, 209–35.CrossRefGoogle Scholar
Levine, J. A. (2002). Non-exercise activity thermogenesis (NEAT). Best Pract. Res. Clin. Endocrinol. Metab. 16, 679–702.CrossRefGoogle Scholar
Lin, S., Boey, D. & Herzog, H. (2004). NPY and Y receptors: lessons from transgenic and knockout models. Neuropeptides 38, 189–200.CrossRefGoogle Scholar
Loftus, T. M., Jaworsky, D. E., Frehywot, G. L.et al. (2000). Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 288, 2379–81.CrossRefGoogle ScholarPubMed
Lu, X. Y., Barsh, G. S., Akil, H. & Watson, S. J. (2003). Interaction between alpha-melanocyte stimulating hormone and corticotropin-releasing hormone in the regulation of feeding and hypothalamo-pituitary-adrenal responses. J. Neurosci. 23, 7863–72.CrossRefGoogle ScholarPubMed
Lutz, T. A. (2006). Amylinergic control of food intake. Physiol. Behav. doi:10.1016/j.physbeh.2006.04.001.CrossRefGoogle ScholarPubMed
Marsh, D. J., Weingarth, D. T., Novi, D. E.et al. (2002). Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc. Natl. Acad. Sci. USA, 99, 3240–5.CrossRefGoogle ScholarPubMed
Masaki, T., Yoshimichi, G., Chiba, S.et al. (2003). Corticotropin-releasing hormone-mediated pathway of leptin to regulate feeding, adiposity, and uncoupling protein expression in mice. Endocrinology 144, 3547–54.CrossRefGoogle ScholarPubMed
Matochik, J. A., London, E. D., Yildiz, B. O.et al. (2005). Effect of leptin replacement on brain structure in genetically leptin deficient adults. J. Clin. Endocrinol. Metab. 90, 2851–4.CrossRefGoogle ScholarPubMed
McCrimmon, R. J., Fan, X., Ding, Y., Zhu, W., Jacob, R. J. & Sherwin, R. S. (2004). Potential role for AMP-activated protein kinase in hypoglycemia sensing in the ventromedial hypothalamus. Diabetes 53, 1953–8.CrossRefGoogle ScholarPubMed
Mieda, M., Williams, S. C., Richardson, J. A., Tanaka, K. & Yanagisawa, M. (2006). The dorsomedial hypothalamic nucleus as a putative food-entrainable circadian pacemaker. Proc. Natl. Acad. Sci. USA, 103, 12 150–5.CrossRefGoogle ScholarPubMed
Miller, J. C., Gnaedinger, J. M. & Rapoport, S. I. (1987). Utilization of plasma fatty acid in rat brain: distribution of [14C]palmitate between oxidative and synthetic pathways. J. Neurochem. 49, 1507–14.CrossRefGoogle ScholarPubMed
Minokoshi, Y., Alquier, T., Furukawa, N.et al. (2004). AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428, 569–74.CrossRefGoogle ScholarPubMed
Mori, H., Hanada, R., Hanada, T.et al. (2004). Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat. Med. 10, 739–43.CrossRefGoogle ScholarPubMed
Morton, G. J., Gelling, R. W., Niswender, K. D., Morrison, C. D., Rhodes, C. J. & Schwartz, M. W. (2005). Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab. 2, 411–20.CrossRefGoogle ScholarPubMed
Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B. & Cone, R. D. (1994). Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol. Endocrinol. 8, 1298–308.Google Scholar
Murphy, K. G., Abbott, C. R., Mahmoudi, M.et al. (2000). Quantification and synthesis of cocaine- and amphetamine-regulated transcript peptide (79–102)-like immunoreactivity and mRNA in rat tissues. J. Endocrinol. 166, 659–68.CrossRefGoogle ScholarPubMed
Nakazato, M., Murakami, N., Date, Y.et al. (2001). A role for ghrelin in the central regulation of feeding. Nature 409, 194–8.CrossRefGoogle ScholarPubMed
Nichols, C. G. (2006). KATP channels as molecular sensors of cellular metabolism. Nature 440, 470–6.CrossRefGoogle ScholarPubMed
Niswender, K. D. & Schwartz, M. W. (2003). Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities. Front. Neuroendocrinol. 24, 1–10.CrossRefGoogle ScholarPubMed
Niswender, K. D., Baskin, D. G. & Schwartz, M. W. (2004). Insulin and its evolving partnership with leptin in the hypothalamic control of energy homeostasis. Trends Endocrinol. Metab. 15, 362–9.CrossRefGoogle ScholarPubMed
Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G. & Rossetti, L. (2002a). Central administration of oleic acid inhibits glucose production and food intake. Diabetes 51, 271–5.CrossRefGoogle Scholar
Obici, S., Feng, Z., Karkanias, G., Baskin, D. G. & Rossetti, L. (2002b). Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat. Neurosci. 5, 566–72.CrossRefGoogle Scholar
Obici, S., Feng, Z., Arduini, A., Conti, R. & Rossetti, L. (2003). Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat. Med. 9, 756–61.CrossRefGoogle ScholarPubMed
Oomura, Y., Ono, T., Ooyama, H. & Wayner, M. J. (1969). Glucose and osmosensitive neurones of the rat hypothalamus. Nature 222, 282–4.CrossRefGoogle ScholarPubMed
Peyron, C., Tighe, D. K., Pol, A. N.et al. (1998). Neurons containing hypocretin (orexin) project to multiple neuronal systems. J. Neurosci. 18, 9996–10 015.CrossRefGoogle ScholarPubMed
Plum, L., Ma, X., Hampel, B.et al. (2006). Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. J. Clin. Invest. 116, 1886–901.CrossRefGoogle ScholarPubMed
Pinto, S., Roseberry, A. G., Liu, H.et al. (2004). Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 304, 110–15.CrossRefGoogle ScholarPubMed
Qu, D., Ludwig, D. S., Gammeltoft, S.et al. (1996). A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature 380, 243–7.CrossRefGoogle ScholarPubMed
Rapoport, S. I. (1999). In vivo fatty acid incorporation into brain phospholipids in relation to signal transduction and membrane remodeling. Neurochem. Res. 24, 1403–15.CrossRefGoogle ScholarPubMed
Raptis, S., Fekete, C., Sarkar, S.et al. (2004). Cocaine- and amphetamine-regulated transcript co-contained in thyrotropin-releasing hormone (TRH) neurons of the hypothalamic paraventricular nucleus modulates TRH-induced prolactin secretion. Endocrinology 145, 1695–9.CrossRefGoogle ScholarPubMed
Trillou, Ravinet C., Delgorge, C., Menet, C., Arnone, M. & Soubrie, P. (2004). CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int. J. Obes. Relat. Metab. Disord. 28, 640–8.CrossRefGoogle Scholar
Richard, D., Huang, Q. & Timofeeva, E. (2000). The corticotropin-releasing hormone system in the regulation of energy balance in obesity. Int. J. Obes. Relat. Metab. Disord. 24 (Suppl. 2), S36–9.CrossRefGoogle ScholarPubMed
Rios, M., Fan, G., Fekete, C.et al. (2001). Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol. Endocrinol. 15, 1748–57.CrossRefGoogle ScholarPubMed
Rossi, M., Kim, M. S., Morgan, D. G.et al. (1998). A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. Endocrinology 139, 4428–31.CrossRefGoogle ScholarPubMed
Routh, R. E., Johnson, J. H. & McCarthy, K. J. (2002). Troglitazone suppresses the secretion of type I collagen by mesangial cells in vitro. Kidney Int. 61, 1365–76.CrossRefGoogle ScholarPubMed
Routh, V. H. (2003). Glucosensing neurons in the ventromedial hypothalamic nucleus (VMN) and hypoglycemia-associated autonomic failure (HAAF). Diabetes Metab. Res. Rev. 19, 348–56.CrossRefGoogle Scholar
Russo, V. C., Metaxas, S., Kobayashi, K., Harris, M. & Werther, G. A. (2004). Antiapoptotic effects of leptin in human neuroblastoma cells. Endocrinology 145, 4103–12.CrossRefGoogle ScholarPubMed
Sakurai, T., Amemiya, A., Ishii, M.et al. (1998). Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573–85.CrossRefGoogle Scholar
Sarkar, S. & Lechan, R. M. (2003). Central administration of neuropeptide Y reduces alpha melanocyte-stimulating hormone-induced cyclic adenosine 5′-monophosphate response element binding protein (CREB) phosphorylation in pro-thyrotropin-releasing hormone neurons and increases CREB phosphorylation in corticotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus. Endocrinology 144, 281–91.CrossRefGoogle ScholarPubMed
Sarkar, S., Legradi, G. & Lechan, R. M. (2002). Intracerebroventricular administration of α-melanocyte stimulating hormone increases phosphorylation of CREB in TRH- and CRH-producing neurons of the hypothalamic paraventricular nucleus. Brain Res. 945, 50–9.CrossRefGoogle ScholarPubMed
Sawchenko, P. E. & Swanson, L. W. (1983). The organization of forebrain afferents to the paraventricular and supraoptic nuclei of the rat. J. Comp. Neurol. 218, 121–44.CrossRefGoogle ScholarPubMed
Schwartz, M. W., Seeley, R. J., Woods, S. C.et al. (1997). Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 46, 2119–23.CrossRefGoogle ScholarPubMed
Schwartz, M. W., Woods, S. C., Porte, D. Jr, Seeley, R. J. & Baskin, D. G. (2000). Central nervous system control of food intake. Nature 404, 661–71.CrossRefGoogle ScholarPubMed
Segal-Lieberman, G., Bradley, R. L., Kokkotou, E.et al. (2003). Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Proc. Natl. Acad. Sci. USA 100, 10 085–90.CrossRefGoogle ScholarPubMed
Sena, A., Sarlieve, L. L. & Rebel, G. (1985). Brain myelin of genetically obese mice. J. Neurol. Sci. 68, 233–43.CrossRefGoogle ScholarPubMed
Shyng, S. L. & Nichols, C. G. (1998). Membrane phospholipid control of nucleotide sensitivity of KATP channels. Science 282, 1138–41.CrossRefGoogle ScholarPubMed
Small, C. J., Liu, Y. L., Stanley, S. A.et al. (2003). Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure. Int. J. Obes. Relat. Metab. Disord. 27, 530–3.CrossRefGoogle ScholarPubMed
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 channels. Nature 390, 521–5.CrossRefGoogle ScholarPubMed
Spanswick, D., Smith, M. A., Mirshamsi, S., Routh, V. H. & Ashford, M. L. (2000). Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat. Neurosci. 3, 757–8.CrossRefGoogle Scholar
Stanley, B. G. & Leibowitz, S. F. (1985). Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior. Proc. Natl. Acad. Sci. USA 82, 3940–3.CrossRefGoogle ScholarPubMed
Stanley, B. G., Magdalin, W., Seirafi, A., Thomas, W. J. & Leibowitz, S. F. (1993). The perifornical area: the major focus of (a) patchily distributed hypothalamic neuropeptide Y sensitive feeding system(s). Brain Res. 604, 304–17.CrossRefGoogle Scholar
Stanley, S. A., Small, C. J., Murphy, K. G.et al. (2001). Actions of cocaine- and amphetamine-regulated transcript (CART) peptide on regulation of appetite and hypothalamo-pituitary axes in vitro and in vivo in male rats. Brain Res. 893, 186–94.CrossRefGoogle ScholarPubMed
Stellar, E. (1954). The physiology of motivation. Psychol. Rev. 61, 5–22.CrossRefGoogle ScholarPubMed
Swanson, L. W. & Sawchenko, P. E. (1980). Paraventricular nucleus: a site for the integration of neuroendocrine and autonomic mechanisms. Neuroendocrinology 31, 410–17.CrossRefGoogle ScholarPubMed
Takahashi, K. A. & Cone, R. D. (2005). Fasting induces a large, leptin-dependent increase in the intrinsic action potential frequency of orexigenic arcuate nucleus neuropeptide Y/Agouti-related protein neurons. Endocrinology 146, 1043–7.CrossRefGoogle ScholarPubMed
Takahashi, N., Okumura, T., Yamada, H. & Kohgo, Y. (1999). Stimulation of gastric acid secretion by centrally administered orexin-A in conscious rats. Biochem. Biophys. Res. Commun. 254, 623–7.CrossRefGoogle ScholarPubMed
Tannenbaum, G. S., Lapointe, M., Beaudet, A. & Howard, A. D. (1998). Expression of growth hormone secretagogue-receptors by growth hormone-releasing hormone neurons in the mediobasal hypothalamus. Endocrinology 139, 4420–3.CrossRefGoogle ScholarPubMed
Tartaglia, L. A. (1997). The leptin receptor. J. Biol. Chem. 272, 6093–6.CrossRefGoogle ScholarPubMed
Thompson, R. H. & Swanson, L. W. (1998). Organization of inputs to the dorsomedial nucleus of the hypothalamus: a reexamination with Fluorogold and PHAL in the rat. Brain Res. Rev. 27, 89–118.CrossRefGoogle ScholarPubMed
Ungerstedt, U. (1970). Is interruption of the nigro-striatal dopamine system producing the “lateral hypothalamus syndrome”?Acta Physiol. Scand. 80, 35A–6A.CrossRefGoogle ScholarPubMed
Top, M., Lee, K., Whyment, A. D., Blanks, A. M. & Spanswick, D. (2004). Orexigen sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus. Nat. Neurosci. 7, 493–4.Google ScholarPubMed
Vrang, N., Tang-Christensen, M., Larsen, P. J. & Kristensen, P. (1999). Recombinant CART peptide induces c-Fos expression in central areas involved in control of feeding behaviour. Brain Res. 818, 499–509.CrossRefGoogle ScholarPubMed
Wang, C., Billington, C. J., Levine, A. S. & Kotz, C. M. (2000). Effect of CART in the hypothalamic paraventricular nucleus on feeding and uncoupling protein gene expression. Neuroreport 11, 3251–5.CrossRefGoogle ScholarPubMed
Wittmann, G., Liposits, Z., Lechan, R. M. & Fekete, C. (2004). Medullary adrenergic neurons contribute to the cocaine- and amphetamine-regulated transcript-immunoreactive innervation of thyrotropin-releasing hormone synthesizing neurons in the hypothalamic paraventricular nucleus. Brain Res. 1006, 1–7.CrossRefGoogle ScholarPubMed
Xu, B., Goulding, E. H., Zang, K.et al. (2003). Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat. Neurosci 6, 736–42.CrossRefGoogle ScholarPubMed
Yamanaka, A., Sakurai, T., Katsumoto, T., Yanagisawa, M. & Goto, K. (1999). Chronic intracerebroventricular administration of orexin-A to rats increases food intake in daytime, but has no effect on body weight. Brain Res. 849, 248–52.CrossRefGoogle ScholarPubMed
Yoshida, K., Konishi, M., Nagashima, K., Saper, C. B. & Kanosue, K. (2005). Fos activation in hypothalamic neurons during cold or warm exposure: projections to periaqueductal gray matter. Neuroscience 133, 1039–46.CrossRefGoogle ScholarPubMed
Yoshimatsu, H., Niijima, A., Oomura, Y., Yamabe, K. & Katafuchi, T. (1984). Effects of hypothalamic lesion on pancreatic autonomic nerve activity in the rat. Brain Res. 303, 147–52.CrossRefGoogle ScholarPubMed
Yura, S., Itoh, H., Sagawa, N.et al. (2005). Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell Metab. 1, 371–8.CrossRefGoogle ScholarPubMed

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.

  • Hypothalamic control of energy homeostasis
    • By Neel S. Singhal, University of Pennsylvania, School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism Philadelphia, Pennsylvania 19104, USA, Rexford S. Ahima, University of Pennsylvania, School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism Philadelphia, Pennsylvania 19104, USA
  • Edited by Jenni Harvey, University of Dundee, Dominic J. Withers, Imperial College of Science, Technology and Medicine, London
  • Book: Neurobiology of Obesity
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541643.004
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.

  • Hypothalamic control of energy homeostasis
    • By Neel S. Singhal, University of Pennsylvania, School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism Philadelphia, Pennsylvania 19104, USA, Rexford S. Ahima, University of Pennsylvania, School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism Philadelphia, Pennsylvania 19104, USA
  • Edited by Jenni Harvey, University of Dundee, Dominic J. Withers, Imperial College of Science, Technology and Medicine, London
  • Book: Neurobiology of Obesity
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541643.004
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.

  • Hypothalamic control of energy homeostasis
    • By Neel S. Singhal, University of Pennsylvania, School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism Philadelphia, Pennsylvania 19104, USA, Rexford S. Ahima, University of Pennsylvania, School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism Philadelphia, Pennsylvania 19104, USA
  • Edited by Jenni Harvey, University of Dundee, Dominic J. Withers, Imperial College of Science, Technology and Medicine, London
  • Book: Neurobiology of Obesity
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541643.004
Available formats
×