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Minireview: Leptin and Development of Hypothalamic Feeding Circuits
Abstract
The arcuate nucleus of the hypothalamus (ARH) is a critical component of the forebrain pathways that regulate energy homeostasis, and it plays a particularly important role in relaying leptin signal to other part of the hypothalamus. However, until recently, little was known about the development of these critical pathways. Recent work investigating the development of leptin-sensitive hypothalamic pathways suggests possible developmental mechanisms that may contribute to obesity later in life. Anatomic findings indicate that ARH circuits are structurally and functionally immature until the third week of postnatal life in mice. Recent data also suggest that leptin is required for normal development of ARH pathways and that this developmental activity of leptin is restricted to a neonatal window of maximum sensitivity that corresponds to a period of elevated leptin secretion. Thus, leptin may function to organize formation of hypothalamic circuitry in much the same way that sex steroids act on sexually dimorphic circuits. Perturbations in perinatal nutrition that alter leptin levels may, therefore, have enduring consequences for the formation and function of circuits regulating food intake and body weight.
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“GDM exposure disrupts fetal hypothalamic development, impairing appetite regulation.”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [68]
In the citing paper
“Recently, compromised development of hypothalamic circuits due to maternal hyperglycemia and impaired development and axonal growth of ARH neurons has been demonstrated [66,67,68,69,70].”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [68]
Citations
Cites
Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451
Childhood obesity: public-health crisis, common sense cure
Ebbeling, C. B., Pawlak, D. B., & Ludwig, D. S. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09678-2 · Cited by 2,980
Congenital leptin deficiency is associated with severe early-onset obesity in humans
Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J. A., et al. (1997) · Nature · doi:10.1038/43185 · Cited by 2,936
Morgan, J., & Curran, T. (1991) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.14.030191.002225 · Cited by 2,689
Years of Life Lost Due to Obesity
Fontaine, K. R., Redden, D. T., Wang, C., Westfall, A. O., & Allison, D. B. (2003) · JAMA · doi:10.1001/jama.289.2.187 · Cited by 2,551
Brain Lesions, Obesity, and Other Disturbances in Mice Treated with Monosodium Glutamate
Olney, J. (1969) · Science · doi:10.1126/science.164.3880.719 · Cited by 1,885
Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding
Bouret, S. G., Draper, S. J., & Simerly, R. B. (2004) · Science · doi:10.1126/science.1095004 · Cited by 1,247
Self-citationElmquist, J. K., Elias, C. F., & Saper, C. B. (1999) · Neuron · doi:10.1016/s0896-6273(00)81084-3 · Cited by 1,160
Saper, C. B., Chou, T. C., & Elmquist, J. K. (2002) · Neuron · doi:10.1016/s0896-6273(02)00969-8 · Cited by 1,120
Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice.
Vaisse, C., Halaas, J. L., Horvath, C. M., Darnell, J. E., Stoffel, M., & Friedman, J. M. (1996) · Nature Genetics · doi:10.1038/ng0996-95 · Cited by 1,086
Critical periods in childhood for the development of obesity
Dietz, W. H. (1994) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/59.5.955 · Cited by 1,072
Vickers, M. H., Breier, B. H., Cutfield, W. S., Hofman, P. L., & Gluckman, P. D. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.279.1.e83 · Cited by 999
Leptin Differentially Regulates NPY and POMC Neurons Projecting to the Lateral Hypothalamic Area
Elias, C. F., Aschkenasi, C., Lee, C., Kelly, J., Ahima, R. S., Bjorbæk, C., Flier, J. S., Saper, C. B., & Elmquist, J. K. (1999) · Neuron · doi:10.1016/s0896-6273(01)80035-0 · Cited by 924
Broberger, C., Johansen, J., Johansson, C., Schalling, M., & Hökfelt, T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.15043 · Cited by 798
Fei, H., Okano, H. J., Li, C., Lee, G.-H., Zhao, C., Darnell, R., & Friedman, J. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.7001 · Cited by 766
Leptin Receptor Immunoreactivity in Chemically Defined Target Neurons of the Hypothalamus
Håkansson, M., Brown, H., Ghilardi, N., Skoda, R. C., & Meister, B. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-01-00559.1998 · Cited by 741
Simerly, R. B. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142745 · Cited by 723
Self-citationShutter, J. R., Graham, M., Kinsey, A. C., Scully, S. A., Lüthy, R., & Stark, K. L. (1997) · Genes & Development · doi:10.1101/gad.11.5.593 · Cited by 672
Ahima, R. S., Prabakaran, D., & Flier, J. S. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1176 · Cited by 643
The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis
Cone, R. D., Cowley, M. A., Butler, A. A., Fan, W., Dl, M., & Low, M. J. (2001) · International Journal of Obesity · doi:10.1038/sj.ijo.0801913 · Cited by 591
Bouret, S. G., Draper, S. J., & Simerly, R. B. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5369-03.2004 · Cited by 584
Self-citationEarly Life Origins of Insulin Resistance and Type 2 Diabetes in India and Other Asian Countries
Yajnik, C. S. (2004) · Journal of Nutrition · doi:10.1093/jn/134.1.205 · Cited by 491
Leptin Activates Neurons in Ventrobasal Hypothalamus and Brainstem
Elmquist, J. K., Ahima, R. S., Maratos–Flier, E., Flier, J. S., & Saper, C. B. (1997) · Endocrinology · doi:10.1210/endo.138.2.5033 · Cited by 438
Bagnol, D., Lu, X.-Y., Kaelin, C. B., Day, H. E. W., Ollmann, M., Gantz, I., Akil, H., Barsh, G. S., & Watson, S. J. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-18-j0004.1999 · Cited by 425 · cited 1×
“are generally believed to originate exclusively from NPY containing neurons in the ARH (24, 25).”
Mizuno, T. M., & Mobbs, C. V. (1999) · Endocrinology · doi:10.1210/endo.140.2.6491 · Cited by 406
Minireview: From Anorexia to Obesity—The Yin and Yang of Body Weight Control
Zigman, J. M., & Elmquist, J. K. (2003) · Endocrinology · doi:10.1210/en.2003-0241 · Cited by 382
Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei
Elmquist, J. K., Ahima, R. S., Elias, C. F., Flier, J. S., & Saper, C. B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.2.741 · Cited by 376
Regulation of Neuronal and Glial Proteins by Leptin: Implications for Brain Development
Ahima, R. S., Bjørbæk, C., Osei, S. Y., & Flier, J. S. (1999) · Endocrinology · doi:10.1210/endo.140.6.6774 · Cited by 337
Mushroom bodies of the cockroach: Their participation in place memory
Mizunami, M., Weibrecht, J. M., & Strausfeld, N. J. (1998) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19981228)402:4 · Cited by 289
Proulx, K., Richard, D., & Walker, C. (2002) · Endocrinology · doi:10.1210/en.2002-220593 · Cited by 211
Obesity and Adipocyte Abnormalities in Offspring of Rats Undernourished During Pregnancy
Jones, A. P., & Friedman, M. I. (1982) · Science · doi:10.1126/science.7063860 · Cited by 208
Brain Stem Is a Direct Target for Leptin’s Action in the Central Nervous System
Hosoi, T., Kawagishi, T., Okuma, Y., Tanaka, J., & Nomura, Y. (2002) · Endocrinology · doi:10.1210/en.2002-220077 · Cited by 204
Baker, R. A., & Herkenham, M. A. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903580405 · Cited by 200
Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice
Mistry, A. M., Swick, A. G., & Romsos, D. R. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.3.r742 · Cited by 193
Hübschle, T., Thom, E., Watson, A. M. D., Roth, J., Klaus, S., & Meyerhof, W. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-07-02413.2001 · Cited by 191
Gestational obesity accentuates obesity in obesity-prone progeny
Levin, B. E., & Govek, E. K. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.4.r1374 · Cited by 179
A Role for Leptin in Brain Development
Steppan, C. M., & Swick, A. G. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0382 · Cited by 164
Ahima, R. S., & Hileman, S. M. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00142-7 · Cited by 149
Circumventricular organs and body fluids
Gross, P. M. (1987) · CRC Press eBooks · Cited by 147
Bereiter, D. A., & Jeanrenaud, B. (1979) · Brain Research · doi:10.1016/0006-8993(79)90557-2 · Cited by 145
Engelbregt, M. J. T., van Weissenbruch, M. M., Popp‐Snijders, C., Lips, P. T. A. M., & de Waal, H. A. D. (2001) · Pediatric Research · doi:10.1203/00006450-200110000-00009 · Cited by 144
Rhees, R. W., Shryne, J. E., & Gorski, R. A. (1990) · Developmental Brain Research · doi:10.1016/0165-3806(90)90217-m · Cited by 139
Postnatal development of the hypothalamic neuropeptide Y system
Grove, K. L., Allen, S. E., Grayson, B. E., & Smith, M. S. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00668-1 · Cited by 136
Transsynaptic Control of Gene Expression
Armstrong, R. C., & Montminy, M. (1993) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.16.030193.000313 · Cited by 124
Developmental Changes inobGene Expression and Circulating Leptin Peptide Concentrations
Devaskar, S. U., Ollesch, C., Rajakumar, R. A., & Rajakumar, P. A. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7237 · Cited by 121
Leptin Signaling in the Hypothalamus of Normal Rats in Vivo
McCowen, K. C., Chow, J. C., & Smith, R. J. (1998) · Endocrinology · doi:10.1210/endo.139.11.6301 · Cited by 113
The Obesity Epidemic: Metabolic Imprinting on Genetically Susceptible Neural Circuits
Levin, B. E. (2000) · Obesity Research · doi:10.1038/oby.2000.41 · Cited by 109
Gu, G., Cornea, A., & Simerly, R. (2003) · The Journal of comparative neurology · doi:10.1002/cne.10677 · Cited by 103
Self-citationWatts, A. G. (2000) · Hormones and Behavior · doi:10.1006/hbeh.2000.1581 · Cited by 98
Proulx, K., Clavel, S., Nault, G., Richard, D., & Walker, C. (2001) · Endocrinology · doi:10.1210/endo.142.11.8512 · Cited by 96
Ocular dominance development revisited
Crowley, J. C., & Katz, L. C. (2002) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(02)00297-0 · Cited by 95
Presynaptic NMDA receptor subunit immunoreactivity in GABAergic terminals in rat brain
Paquet, M., & Smith, Y. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20000724)423:2 · Cited by 95
The effect of leptin treatment on the development of obesity in overfed suckling Wistar rats
Schmidt, I., Fritz, A., Schölch, C., Schneider, D., Simón, E., & Plagemann, A. (2001) · International Journal of Obesity · doi:10.1038/sj.ijo.0801669 · Cited by 89
Dodson, R. E., & Gorski, R. A. (1993) · Journal of Neurobiology · doi:10.1002/neu.480240107 · Cited by 81
Brain myelin of genetically obese mice
Sena, A., Sarliève, L. L., & Rebel, G. (1985) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(85)90104-2 · Cited by 79
Udagawa, J., Hatta, T., Naora, H., & Otani, H. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02334-9 · Cited by 71
Developmental Changes in Long-Form Leptin Receptor Expression and Localization in Rat Brain
Matsuda, J., Yokota, I., Tsuruo, Y., Murakami, T., Ishimura, K., Shima, K., & Kuroda, Y. (1999) · Endocrinology · doi:10.1210/endo.140.11.7152 · Cited by 64
Altered dendritic orientation of hypothalamic neurons from genetically obese (ob/ob) mice
Bereiter, D. A., & Jeanrenaud, B. (1980) · Brain Research · doi:10.1016/s0006-8993(80)80046-1 · Cited by 63
Target-Dependent Sexual Differentiation of a Limbic–Hypothalamic Neural Pathway
Ibanez, M. A., Gu, G., & Simerly, R. B. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-15-05652.2001 · Cited by 59
Self-citationGarris, D. R. (1989) · Brain Research · doi:10.1016/0006-8993(89)91037-8 · Cited by 34
Maternal hormone manipulations and the development of obesity in rats
Jones, A. P., & Dayries, M. (1990) · Physiology & Behavior · doi:10.1016/0031-9384(90)90359-c · Cited by 27
Elmquist (1998) · doi:10.1002/(sici)1096-9861(19980615)395:4
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Metadata
- Authors
- Bouret, S. G., & Simerly, R. B.
- Affiliations
- Oregon National Primate Research Center, Division of Neuroscience and Oregon Health and Science University, Beaverton, Oregon 97006
- Oregon National Primate Research Center (US)
- ORCID
- Simerly, Richard B.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2004-06-01
- Volume
- 145
- Issue
- 6
- Pages
- 2621-2626
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2024116770
- Cited by
- 210
- References
- 62
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 8 · 2016: 10 · 2015: 10 · 2014: 12 · 2013: 11 · 2012: 16
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK055819, R01DK065900, DK055819, DK65900)
- National Institute of Neurological Disorders and Stroke (NS37952, R01NS037952)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, arcuate nucleus, energy homeostasis, postnatal development, obesity, perinatal nutrition, food intake regulation, body weight regulation
- MeSH terms
- Aging, Animals, Arcuate Nucleus of Hypothalamus, Brain, Eating, Hypothalamus, Neural Pathways, Synaptic Transmission, Signal Transduction, Leptin
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