title: Nutrient sensor-mediated programmed nonalcoholic fatty liver disease in low birthweight offspring.
abstract: OBJECTIVE
  We hypothesized that gestationally programmed nonalcoholic fatty liver disease in low-birthweight offspring is mediated through nutrient sensors nicotinamide adenine dinucleotide+-dependent histone deacetylase (SIRT1) and AMP-activated protein kinase (AMPK).
  
  
  METHODS
  Pregnant dams received ad libitum food or were 50% food restricted from pregnancy days 10-21 to produce control and low-birthweight newborn offspring, respectively. All pups were nursed by control dams and weaned to ad libitum feed. We determined hepatic SIRT1 and AMPK activities and protein expression of lipid targets in low-birthweight and control fetuses, newborns, and adult offspring (3 months).
  
  
  RESULTS
  Low-birthweight fetuses demonstrated increased prenatal hepatic SIRT1 activity, although with increased lipogenesis. After birth, low-birthweight newborn offspring undergo postnatal suppression of hepatic SIRT1 and AMPK activities in conjunction with increased lipogenesis, decreased lipolysis, and increased fat stores.
  
  
  CONCLUSIONS
  These findings suggest that undernutrition stress in utero may program hepatic nutrient sensors to perceive normal postnatal nutrition as a state of nutrient excess with the induction of hepatic lipid storage.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Wolfe
authors.forename: Ming
authors.initials: M
authors.lastname: Gong
authors.forename: Guang
authors.initials: G
authors.lastname: Han
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Magee
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ross
authors.forename: Mina
authors.initials: M
authors.lastname: Desai
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005508:Food Deprivation / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D000263:Adenylate Kinase; C488368:Sirt1 protein, rat; D056564:Sirtuin 1