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Developmental programming of hypothalamic feeding circuits
Abstract
The hypothalamus plays a critical role in the regulation of food intake and body weight, and recent work has defined a core circuitry in the hypothalamus that appears to mediate many of the effects of the adipocyte‐derived hormone leptin on feeding and glucose homeostasis. However, until recently, little was known about the development of these critical pathways. This review summarizes recent advances regarding the post‐natal development of ‘metabolic’ projections from the arcuate nucleus of the hypothalamus. Evidence accumulated primarily in mice indicates that these circuits develop after birth and remain both structurally and functionally immature until the second week of life. Recent studies have begun to identify cues governing development of these pathways, and leptin appears to play a crucial neurotrophic role in the development of the hypothalamic circuits regulating food intake and adiposity. The neurodevelopmental actions of leptin appear specifically to be restricted to a neonatal critical period that coincides with the naturally occurring surge in leptin. In addition, the timing and amplitude of the post‐natal leptin surge has important consequences for normal body weight regulation and glucose homeostasis later in life. Ultimately, these data promise to provide new insight into the mechanisms by which alteration of perinatal nutrition may have long‐term consequences on body weight regulation and adiposity in the offspring.
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“Besides classical genetic, epigenetic and nongenetic mechanisms ([23](#B23), [34](#B34), [36](#B36), [37](#B37), [62](#B62), [67](#B67), [126](#B126), [155](#B155), [176](#B176), [184](#B184)) could also be potentially responsible for differences in neural reward circuitry and reward behaviors at a young age, predisposing to hyperphagia and obesity later in life.”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [23]
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Metadata
- Authors
- Bouret, S., & Simerly, R.
- Venue
- Clinical Genetics
- Publisher
- Wiley
- Published
- 2006-08-21
- Volume
- 70
- Issue
- 4
- Pages
- 295-301
- ISSN
- 0009-9163 (ISSN-L)
- 1399-0004
- OpenAlex
- W2048819152
- Cited by
- 227
- References
- 45
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 10 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 14 · 2016: 25 · 2015: 12 · 2014: 11 · 2013: 14 · 2012: 14
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065900, DK65900)
- 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 › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- hypothalamic development, arcuate nucleus, leptin, postnatal development, food intake regulation, body weight regulation, glucose homeostasis, adiposity, perinatal nutrition, developmental programming, neurotrophic signaling
- MeSH terms
- Animals, Appetite Regulation, Arcuate Nucleus of Hypothalamus, Feeding Behavior, Humans, Hypothalamus, Obesity, Leptin, Adiposity, Mice
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