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

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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)
JournalAmerican Journal of Obstetrics and Gynecology
Volume207
Issue number4
DOIs
StatePublished - Oct 2012
Externally publishedYes

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AMP-Activated Protein Kinases
Food
Liver
Lipogenesis
Fetus
Lipids
Histone Deacetylases
Lipolysis
Malnutrition
NAD
Fats
Non-alcoholic Fatty Liver Disease
Parturition
Pregnancy
Proteins

Keywords

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

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Nutrient sensor-mediated programmed nonalcoholic fatty liver disease in low birthweight offspring. / Wolfe, Diana S.; Gong, Ming; Han, Guang; Magee, Thomas R.; Ross, Michael G.; Desai, Mina.

In: American Journal of Obstetrics and Gynecology, Vol. 207, No. 4, 10.2012.

Research output: Contribution to journalArticle

Wolfe, Diana S. ; Gong, Ming ; Han, Guang ; Magee, Thomas R. ; Ross, Michael G. ; Desai, Mina. / Nutrient sensor-mediated programmed nonalcoholic fatty liver disease in low birthweight offspring. In: American Journal of Obstetrics and Gynecology. 2012 ; Vol. 207, No. 4.
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