Obesity during pregnancy causes adverse outcomes for both mother and fetus, but the specific mechanisms behind these complications remain unclear. Circadian variation is an important feature of normal metabolic function and undergoes marked changes across pregnancy. Consequently, obesity-induced disruptions to the circadian system may drive adverse outcomes in obese pregnancy. We previously reported that obesity supresses clock gene expression in maternal liver and adipose tissue; this study investigated whether clock gene expression in fetal and placental tissues is also affected by maternal obesity.
Female Wistar rats were fed either chow (CON) or a cafeteria diet (CAF) for 8 weeks to induce obesity, then mated and maintained on the diets throughout gestation. Fetal liver and placental labyrinth zone (LZ) samples were collected at four-hourly time points across days 15 and 21 of gestation. Expression of clock genes was analysed by RT-qPCR.
CAF animals exhibited a 58% increase in body fat compared to CON as measured by DEXA analysis (P<0.001). All clock genes were expressed in fetal liver and LZ but their expression patterns did not follow the characteristic circadian profiles observed in maternal tissues. CAF consumption suppressed peak expression of Reverba in both fetal liver and LZ (P<0.05), similar to observations in maternal tissues. Cosinor analysis showed phase changes in Rora and Per1 in fetal liver and Rora and Per3 in LZ (all P<0.05). Unlike maternal tissues, there were no dietary effects on expression of Bmal1, Cry2 and Per2 in LZ or fetal liver.
In summary, obesity-induced changes to clock gene expression extend to the fetal and placental compartments, although to a lesser extent than in maternal tissues. Reverb-a suppression may be particularly significant given its direct role in adipogenesis and lipid metabolism and could thus be a potential mechanism for programming effects in offspring of obese mothers.