Nutrient sensor-mediated programmed nonalcoholic fatty liver disease in low birthweight offspring

Diana Wolfe, Ming Gong, Guang Han, Thomas R. Magee, Michael G. Ross, Mina Desai

Research output: Contribution to journalArticle

20 Scopus citations

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). Study Design: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)308.e1-308.e6
JournalAmerican journal of obstetrics and gynecology
Volume207
Issue number4
DOIs
StatePublished - Oct 2012
Externally publishedYes

Keywords

  • lipogenesis
  • lipolysis
  • nutrient/metabolic sensors
  • programmed fatty liver

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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