The Roles of PPARs in the Fetal Origins of Metabolic Health and Disease

Beyond the short-term effects on fertility, there is increasing evidence that obesity or the consumption of an inappropriate diet by the mother during pregnancy adversely affects the long-term health of her offspring. PPAR and RXR isotypes are widely expressed in reproductive tissues and in the developing fetus. Through their interactions with fatty acids, they may mediate adaptive responses to the changes in the maternal diet. In the maturing follicle, PPAR- [Formula: see text] has an important role in the granulosa cells that surround the maturing oocyte. After fertilisation, PPAR- [Formula: see text] and PPAR- [Formula: see text] are essential regulators of placentation and the subsequent development of key metabolic tissues such as skeletal muscle and adipose cells. Activation of PPAR- [Formula: see text] and PPAR- [Formula: see text] during fetal development has the potential to modify the growth and development of these tissues. PPAR- [Formula: see text] is expressed at low levels in the fetal liver, however, this expression may be important, as changes in the methylation of DNA in its promoter region are reported to take place during this period of development. This epigenetic modification then programmes subsequent expression. These findings suggest that two separate PPAR-dependent mechanisms may be involved in the fetal adaptations to the maternal diet, one, mediated by PPAR- [Formula: see text] and PPAR- [Formula: see text] , regulating cell growth and differentiation; and another adapting long-term lipid metabolism via epigenetic changes in PPAR- [Formula: see text] to optimise postnatal survival.