Nuclear receptors, gestational metabolism and maternal metabolic disorders

Normal pregnancy is characterised by a gradual alteration in metabolism that results in elevated serum bile acids, dyslipidaemia and impaired glucose tolerance in the third trimester. Nuclear receptors play important roles in regulating metabolic pathways that influence alterations in these parameters. There is evidence for altered function of FXR and LXR in gestation; these nuclear receptors play an integral role in bile acid and lipid homeostasis. There is some evidence for influence of clock genes in late pregnancy metabolic changes, and this may be linked to alterations in placental gene expression and function, thereby influencing fetal growth. This article will review the current data from human studies and investigation of animal models to illustrate the role of nuclear receptors (namely LXR, FXR, PPARs and clock genes) in gestational alterations in metabolism and the ways this may influence susceptibility to metabolic disorders of pregnancy such as gestational diabetes mellitus and intrahepatic cholestasis of pregnancy.