title: Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin.
abstract: OBJECTIVE
  Excess nutrient supply and rapid weight gain during early life are risk factors for the development of obesity during adulthood. This metabolic malprogramming may be mediated by endocrine disturbances during critical periods of development. Ghrelin is a metabolic hormone secreted from the stomach that acts centrally to promote feeding behavior by binding to growth hormone secretagogue receptors in the arcuate nucleus of the hypothalamus. Here, we examined whether neonatal overnutrition causes changes in the ghrelin system.
  
  
  METHODS
  We used a well-described mouse model of divergent litter sizes to study the effects of postnatal overfeeding on the central and peripheral ghrelin systems during postnatal development.
  
  
  RESULTS
  Mice raised in small litters became overweight during lactation and remained overweight with increased adiposity as adults. Neonatally overnourished mice showed attenuated levels of total and acyl ghrelin in serum and decreased levels of Ghrelin mRNA expression in the stomach during the third week of postnatal life. Normalization of hypoghrelinemia in overnourished pups was relatively ineffective at ameliorating metabolic outcomes, suggesting that small litter pups may present ghrelin resistance. Consistent with this idea, neonatally overnourished pups displayed an impaired central response to peripheral ghrelin. The mechanisms underlying this ghrelin resistance appear to include diminished ghrelin transport into the hypothalamus.
  
  
  CONCLUSIONS
  Early postnatal overnutrition results in central resistance to peripheral ghrelin during important periods of hypothalamic development. Because ghrelin signaling has recently been implicated in the neonatal programming of metabolism, these alterations in the ghrelin system may contribute to the metabolic defects observed in postnatally overnourished mice.
authors: Inserm U1172, Jean-Pierre Aubert Research Center, University Lille 2, Lille 59045, France.
authors: Gustav
authors: G
authors: Collden
authors: Inserm U1172, Jean-Pierre Aubert Research Center, University Lille 2, Lille 59045, France.
authors: Eglantine
authors: E
authors: Balland
authors: Inserm U1172, Jean-Pierre Aubert Research Center, University Lille 2, Lille 59045, France.
authors: Jyoti
authors: J
authors: Parkash
authors: Inserm U1172, Jean-Pierre Aubert Research Center, University Lille 2, Lille 59045, France.
authors: Emilie
authors: E
authors: Caron
authors: Inserm U1172, Jean-Pierre Aubert Research Center, University Lille 2, Lille 59045, France.
authors: Fanny
authors: F
authors: Langlet
authors: Inserm U1172, Jean-Pierre Aubert Research Center, University Lille 2, Lille 59045, France.
authors: Vincent
authors: V
authors: Prevot
authors: The Saban Research Institute, Developmental Neuroscience Program, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA ; Inserm U1172, Jean-Pierre Aubert Research Center, University Lille 2, Lille 59045, France.
authors: Sebastien G
authors: SG
authors: Bouret
keywords: ARH, arcuate nucleus; AgRP, agouti-related peptide; DMH, dorsomedial nucleus; GHSR, growth hormone secretagogue receptor; GOAT, ghrelin O-acyltransferase; Ghrelin; HFHS, high-fat/high-sucrose diet; Hormone; Hypothalamus; LHA, lateral hypothalamic area; MBH, mediobasal hypothalamus; ME, median eminence; NL, normal litters; NPY, neuropeptide Y; Nutrition; P, postnatal day; POMC, pro-opiomelanocortin; PVH, paraventricular nucleus; Programming; SL, small litter; Tanycytes