Prenatal PPARa-dependent gene expression in fetal mouse liver just before birth (E19.5)

Inborn errors of lipid metabolism illustrate the importance of proper milk fat oxidation in newborn mammals. In the liver, a remarkable lipid catabolic competence is present at birth; however, it is unclear how this critical trait is acquired and regulated. In this work, we found that the genes required for milk lipid catabolism are already transcribed before birth in the term fetus (E19.5) and controlled by the peroxisome-proliferator activated receptor alpha (PPARalpha) in mouse liver. The developmental activity of PPARalpha strongly regulates fatty acid oxidation genes. Two days after birth (P2), during milk suckling, PPARalpha-null mice develop a congenital steatosis and milk protein oxidation is de-repressed to fuel an alternative energy pathway that maintains glucose homeostasis and postnatal growth. Our results demonstrate for the first time, the developmental role of PPARalpha in regulating the metabolic ability to use maternal milk as fuel in the early days of life. Expression profile difference between PPARalpha wild-type (n=6) and knock-out (n=6) mouse liver at fetal day E19.5. Term fetuses were collected by cesarean section, their liver promptly dissected and frozen in liquid nitrogen.先天性脂代谢异常（Inborn errors of lipid metabolism）阐明了新生哺乳动物乳汁脂肪正常氧化的重要性。肝脏在出生时即具备显著的脂类分解代谢能力，但目前尚不明确这一关键特性的获得与调控机制。本研究发现，乳汁脂类分解代谢所需的基因在足月胎鼠（E19.5）出生前即已完成转录，并在小鼠肝脏中受过氧化物酶体增殖物激活受体α（PPARalpha）的调控。过氧化物酶体增殖物激活受体α（PPARalpha）的发育活性可强力调控脂肪酸氧化相关基因的表达。出生后第2天（P2），在乳汁哺育阶段，PPARalpha敲除小鼠会出现先天性脂肪变性，同时乳汁蛋白氧化的阻遏被解除，从而为替代能量通路供能，以维持葡萄糖稳态与出生后生长。本研究首次证实了过氧化物酶体增殖物激活受体α（PPARalpha）在生命早期调控利用母体乳汁作为能量来源的代谢能力方面的发育调控作用。本数据集包含胎鼠E19.5时，PPARalpha野生型（n=6）与敲除型（n=6）小鼠肝脏的表达谱差异数据。实验通过剖宫产术采集足月胎鼠，迅速解剖其肝脏并以液氮冷冻保存。