title: Overfeeding can cause NEC-like enterocolitis in premature rat pups.
abstract: BACKGROUND
  Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature infants. The mortality rate associated with NEC is quite high and in most reports ranges from 20 to 30%. Despite extensive studies, the pathogenesis of NEC remains poorly understood.
  
  
  OBJECTIVE
  To investigate the mechanisms of NEC in terms of inflammatory signaling in the intestine.
  
  
  METHODS
  A new enterocolitis model was established and examined the expression of inflammatory and anti-inflammatory signals in the intestines of rat pups. The premature rat pups, delivered by abdominal incision on day 20 of gestation (day 21 is considered as full term), were divided into three groups, and they were given a single administration of 0.05, 0.1, and 0.15 ml of formula milk via an orogastric catheter. After 24 h, the development of enterocolitis was evaluated by the presence of hemorrhagic enterocolitis, and the expression of signaling molecules, inhibitor of nuclear factor-kappaB (IkappaB)-alpha/beta and peroxisome proliferator-activated receptor (PPAR)-gamma mRNA was examined by reverse transcription-polymerase chain reaction from inflamed and non-inflamed intestinal samples.
  
  
  RESULTS
  The incidence of enterocolitis increased with the volume of milk, and 50% of rat pups showed enterocolitis with a volume of 0.15 ml of milk. Expression of IkappaB-alpha/beta and PPAR-gamma mRNA increased in inflamed intestine.
  
  
  CONCLUSIONS
  Increased expression of IkappaB-alpha/beta suggested that the inflammatory mediator nuclear factor-kappaB is deeply involved in the pathogenesis of enterocolitis that can be easily introduced by overfeeding of milk ingestion in premature rat pups which mimic those seen in NEC. Increased expression of PPAR-gamma may possibly regulate further development of enterocolitis in this system.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Kyo
authors.initials: K
authors.lastname: Okada
authors.forename: Tohru
authors.initials: T
authors.lastname: Fujii
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ohtsuka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamakawa
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Izumi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamashiro
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D004195:Disease Models, Animal; D004760:Enterocolitis / Q000209:etiology / Q000473:pathology; D020345:Enterocolitis, Necrotizing / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha; D044343:Overnutrition / Q000150:complications* / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C083487:I kappa B beta protein; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D047495:PPAR gamma; D000072000:NF-KappaB Inhibitor alpha