Role of Early Hormonal and Nutritional Experiences in Shaping Feeding Behavior and Hypothalamic Development1, 2, 3

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Abstract

Obesity in adults and children is increasingly becoming a major health problem worldwide. However, the precise biological mechanisms governing this disease have not been fully elucidated. Obesity involves the complex interaction of a wide range of environmental and genetic factors. Additionally, there is now a growing body of evidence suggesting that alterations in metabolic environment during important periods of organ development can predispose individuals to later development of obesity and diabetes. Maternal obesity or malnutrition during pregnancy increases the risk for metabolic disorders (including obesity) in the offspring. Similarly, early postnatal overnutrition also predisposes offspring to adult obesity. The hypothalamus appears to play an essential role in controlling appetite. It undergoes a tremendous growth beginning early in gestation and continuing during the postnatal period. These developmental windows represent periods of sensitivity for hypothalamic development during which alterations in the nutritional and/or hormonal environment may perturb hypothalamic development and subsequent function.

Abbreviations used:

AgRP
agouti-related peptide
ARH
arcuate nucleus of the hypothalamus
DMH
dorsomedial nucleus of the hypothalamus
E
embryonic day
Lepob/Lepob
leptin-deficient
LHA
lateral hypothalamic area
NPY
neuropeptide Y
P
postnatal day
POMC
proopiomelanocortin
PVH
paraventricular nucleus of the hypothalamus;
VMH
ventromedial nucleus of the hypothalamus

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1

Presented as part of the symposium entitled “Nutritional Experiences in Early Life as Determinants of the Adult Metabolic Phenotype” at the Experimental Biology 2009 meeting, April 20, 2009, in New Orleans, LA. This symposium was sponsored by the ASN and supported by an unrestricted educational grant from the ASN Nutritional Sciences Council and Milk Specialties Global. The Guest Editor for this symposium publication was Marta Fiorotto. Guest Editor disclosure: no conflicts of interest.

2

Supported by grants from the March of Dimes, Agence National de la Recherche (grant ANR-08-JCJC-0055-01), and Fondation pour la Recherche Medicale.

3

Author disclosures: S. G. Bouret, no conflicts of interest.