title: Increase of long-term 'diabesity' risk, hyperphagia, and altered hypothalamic neuropeptide expression in neonatally overnourished 'small-for-gestational-age' (SGA) rats.
abstract: BACKGROUND
  Epidemiological data have shown long-term health adversity in low birth weight subjects, especially concerning the metabolic syndrome and 'diabesity' risk. Alterations in adult food intake have been suggested to be causally involved. Responsible mechanisms remain unclear.
  
  
  RESULTS
  By rearing in normal (NL) vs. small litters (SL), small-for-gestational-age (SGA) rats were neonatally exposed to either normal (SGA-in-NL) or over-feeding (SGA-in-SL), and followed up into late adult age as compared to normally reared appropriate-for-gestational-age control rats (AGA-in-NL). SGA-in-SL rats displayed rapid neonatal weight gain within one week after birth, while SGA-in-NL growth caught up only at juvenile age (day 60), as compared to AGA-in-NL controls. In adulthood, an increase in lipids, leptin, insulin, insulin/glucose-ratio (all p<0.05), and hyperphagia under normal chow as well as high-energy/high-fat diet, modelling modern 'westernized' lifestyle, were observed only in SGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (p<0.05). Lasercapture microdissection (LMD)-based neuropeptide expression analyses in single neuron pools of the arcuate hypothalamic nucleus (ARC) revealed a significant shift towards down-regulation of the anorexigenic melanocortinergic system (proopiomelanocortin, Pomc) in SGA-in-SL rats (p<0.05). Neuropeptide expression within the orexigenic system (neuropeptide Y (Npy), agouti-related-peptide (Agrp) and galanin (Gal)) was not significantly altered. In essence, the 'orexigenic index', proposed here as a neuroendocrine 'net-indicator', was increased in SGA-in-SL regarding Npy/Pomc expression (p<0.01), correlated to food intake (p<0.05).
  
  
  CONCLUSIONS
  Adult SGA rats developed increased 'diabesity' risk only if exposed to neonatal overfeeding. Hypothalamic malprogramming towards decreased anorexigenic activity was involved into the pathophysiology of this neonatally acquired adverse phenotype. Neonatal overfeeding appears to be a critical long-term risk factor in 'small-for-gestational-age babies'.
authors.affiliation: Clinic of Obstetrics, Division of 'Experimental Obstetrics', Charité - University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Schellong
authors.forename: Uta
authors.initials: U
authors.lastname: Neumann
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Rancourt
authors.forename: Andreas
authors.initials: A
authors.lastname: Plagemann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism* / Q000473:pathology; D001481:Basal Metabolism; D001724:Birth Weight; D001823:Body Composition; D048909:Diabetes Complications / Q000150:complications*; D005260:Female; D005786:Gene Expression Regulation; D005865:Gestational Age; D005951:Glucose Tolerance Test; D006963:Hyperphagia / Q000150:complications* / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012306:Risk; D015430:Weight Gain
chemical_list: D009479:Neuropeptides