Developmental programming of hypothalamic feeding circuits

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, l...

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Bibliographic Details
Published in:Clinical genetics 2006-10, Vol.70 (4), p.295-301
Main Authors: Bouret, SG, Simerly, RB
Format: Article
Language:English
Subjects:
Adiposity - physiology
Animals
Appetite Regulation - physiology
Arcuate Nucleus of Hypothalamus - growth & development
Arcuate Nucleus of Hypothalamus - physiology
Biological and medical sciences
brain
development
Feeding Behavior - physiology
General aspects. Genetic counseling
Genetics
Hormones
Humans
hypothalamus
Hypothalamus - growth & development
Hypothalamus - physiology
leptin
Leptin - physiology
Medical genetics
Medical sciences
Metabolic diseases
Metabolism
Mice
Neurosciences
Obesity
Obesity - pathology
Obesity - physiopathology
post-natal
programming
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Summary: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.
ISSN:0009-9163
1399-0004
DOI:10.1111/j.1399-0004.2006.00684.x