Biochemistry of liver development in the perinatal period

Abstract

Just before birth, changes occur in the metabolic capacities of rat liver so that the animal can adapt to changes in the substrate supply. In utero, glucose is the main energy-generating fuel and the liver metabolism is directed towards glucose degradation. The activities of the rate-limiting enzymes of glycolysis, hexokinase and phosphofructokinase, are high. In preparation for post-natal life, when the continuous glucose supply from the mother is interrupted, very large amounts of glycogen are stored in the late fetal liver. With the intake of the fat-rich and carbohydrate-poor milk diet, the animal develops the ability to synthesize glucose de novo from non-carbohydrate precursors. During suckling, metabolic energy is derived mainly from the beta-oxidation of fatty acids, which in turn is an essential prerequisite for the high rate of gluconeogenesis, by yielding acetyl-CoA for the activation of pyruvate carboxylase and by generating a high NADH/NAD ratio for the shift of the glyceraldehyde 3-phosphate dehydrogenase reaction in the direction of glucose formation.--The developmental adaptation of metabolism and the process of enzymatic differentiation are closely connected with the maturation of the endocrine system and the changes in the concentration of circulating hormones. The neonatal regulation of phosphoenolpyruvate carboxykinase and of tyrosine aminotransferase by variations in the hormonal milieu around birth, and also the interaction of hormonal and nutritional factors in the induction of serine dehydratase and glucokinase at the end of the suckling period, will be discussed in detail.

Vitamin K-Dependent Carboxylation in the Developing Rat: Evidence for a Similar Mechanism of Action of Warfarin in Fetal and Adult Livers

“…Although there was no significant change in carboxylase activity in the mothers, the prothrombin precursor concentration revealed a transient increase at that time. Inasmuch as the appearance of many enzymes in the developing liver has been shown (28) to be closely related to changes in the hormonal environment, these data are interesting in light of the profound hormonal changes that occur around birth (28). Our data may indeed reflect hormonal control of maturation of the vitamin Kdependent carboxylation system.…”

High-resolution mapping of transcriptional dynamics across tissue development reveals a stable mRNA–tRNA interface

“…For example, the molecular landscape within the liver is known to undergo radical changes during development in response to shifts in the liver's physiological functions during embryogenesis. During early development, the embryonic liver is a haematopoetic organ; at birth, the neonatal liver becomes the primary metabolic and detoxification organ (Si-Tayeb et al 2010); at weaning, further metabolic pathways are up-regulated (Bohme et al 1983;Girard et al 1992). In the developing brain, coordinated gene expression changes in a heterogeneous collection of diverse cell types shape the functional specialization of specific regions in both embryonic and postnatal brains (Liscovitch and Chechik 2013;Sunkin et al 2013).…”

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

“…Chronic maternal HFD feeding reprograms the fetal hepatic gluconeogenic pathway. Hepatic gluconeogenesis is normally absent during fetal development, which is primarily attributed to the appearance of the rate-limiting enzyme phosphoenolpyruvate carboxykinase (PCK1) at the time of birth (58)(59)(60)(61)(62). Quantitative PCR demonstrated increased expression in 4 key enzymes in the gluconeogenic pathway in the O-HFD group: glucose 6 phosphatase (G6P), fructose 1,6-bisphosphatase 1 (FBP1), PPARγ coactivator 1α (PGC1A, which encodes PGC1α), and PCK1 (2-tailed Student's t test, Figure 4, A-D).…”