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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]
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“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]
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Štofková, A., Škurlová, M., Kiss, A., Železná, B., Zórad, Š., & Jur̀čovičová, J. (2009) · PubMed · Cited by 33
Reynolds, C. M., Perry, J. K., & Vickers, M. H. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081729 · Cited by 32
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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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