Window of Opportunity: Targeting ANGPTL4 Improves Triglyceride Levels in Maternal Obesity During Pregnancy.

Abstract

During pregnancy, maternal dyslipidemia is a physiological response that provides fuel and nutrients for both the placenta and the developing fetus (1). Although less appreciated than glucose and amino acids, maternal lipids promote fetal growth and are essential for normal development (2). During the first and second trimester of pregnancy, fat accumulates in maternal tissues, and by the third trimester of pregnancy, maternal hyperlipidemia, defined here as increased serum triglycerides (TG) and total cholesterol (TC), is significantly elevated due to moderately increased maternal insulin resistance and lipolysis of lipids in adipose tissues as well as attenuated lipid uptake by peripheral tissues (Fig. 1 A ). Both TG and TC are taken up by the placenta, and placental lipases can hydrolyze TG to free fatty acids for fetal-placental availability (3). It is important to note that while both TG and TC levels rise throughout pregnancy, the TG increase is disproportionately higher in comparison with other lipid fractions and subsequently falls precipitously to prepregnancy levels following delivery (4). Figure 1 Physiological elevation in maternal blood TG in pregnancy is regulated by increased ANGPTL4 expression in mice. A : During normal pregnancy, maternal blood TG concentrations are increased in part by insulin resistance in peripheral tissues to ensure TG supply for the placenta and fetus. These alterations result in increased adipose tissue lipolysis, increasing the release of free fatty acids (FAs) and glycerol from adipose tissue and their transfer to the liver and the placenta. During pregnancy, increased expression of ANGPTL4 inhibits LPL, regulating TG clearance from the blood serum. ANGPTL4 expression is increased during pregnancy in inguinal …