Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Am J Obstet Gynecol. 2012 Oct;207(4):308.e1-6. doi: 10.1016/j.ajog.2012.07.033. Epub 2012 Jul 31.
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).
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).
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.
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.
我们假设低出生体重儿的妊娠期程序性非酒精性脂肪肝是通过营养传感器烟酰胺腺嘌呤二核苷酸依赖性组蛋白去乙酰化酶（SIRT1）和 AMP 激活蛋白激酶（AMPK）介导的。
从妊娠第 10-21 天起，给予妊娠母鼠自由进食或 50%食物限制，分别产生对照和低出生体重新生仔鼠。所有幼鼠均由对照母鼠哺乳，并断奶至自由进食。我们测定了低出生体重和对照胎儿、新生儿和成年仔鼠（3 个月）肝脏中的 SIRT1 和 AMPK 活性以及脂质靶点的蛋白表达。
低出生体重胎儿表现出产前肝 SIRT1 活性增加，尽管脂生成增加。出生后，低出生体重新生儿仔鼠的肝 SIRT1 和 AMPK 活性受到抑制，同时伴有脂生成增加、脂肪分解减少和脂肪储存增加。
这些发现表明，宫内营养不足可能会使肝脏营养传感器编程，将正常的产后营养感知为营养过剩状态，从而诱导肝脏脂质储存。
