Postnatal PPARa-dependent gene expression in two-days old mouse liver

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 (3 males and 3 females) and knock-out (3 males and 3 females) mouse liver in suckling mice. Two days after birth, pups were killed and their liver promptly removed and frozen in liquid nitrogen.脂质代谢先天性异常阐明了乳脂氧化对新生哺乳动物的重要意义。肝脏在出生时即具备显著的脂质分解代谢能力，但目前尚未明确这一关键性状的获得与调控机制。本研究发现，乳脂分解代谢所需的基因在足月胎儿（E19.5）出生前即已转录，并在小鼠肝脏中受过氧化物酶体增殖物激活受体α（peroxisome-proliferator activated receptor alpha，PPARα）调控。PPARα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）进入哺乳阶段时，PPARα基因敲除小鼠会出现先天性肝脂肪变性，乳蛋白氧化通路被解除抑制，以此为替代能源通路供能，维持葡萄糖稳态与出生后生长。本研究首次证实了PPARα在生命早期调控利用母乳作为能源的代谢能力中的发育调控作用。本数据集涵盖哺乳阶段小鼠PPARα野生型（3只雄性、3只雌性）与基因敲除型（3只雄性、3只雌性）的肝脏组织表达谱差异数据。实验流程为：出生后第2天处死幼鼠，迅速摘取肝脏并置于液氮中速冻保存。