The link between maternal obesity and adverse pregnancy outcomes is well established; however the specific mechanisms behind obesity-induced pregnancy complications remain unclear. Circadian rhythms are integral to metabolic homeostasis and undergo substantial adaptations in both pregnancy and obesity. Disturbances in circadian rhythms may provide a mechanistic link between obesity and adverse pregnancy outcomes.
This study examined the impact of obesity on clock gene expression in maternal metabolic tissues. It was hypothesised that obesity disturbs clock gene expression and alters key maternal metabolic adaptations that normally occur in pregnancy.
Female Wistar rats were fed either a control diet of standard chow (CON) or chow supplemented with a cafeteria diet (CAF) for 8 weeks to induce obesity. Rats were then mated and maintained on the diets throughout gestation. Maternal liver and retroperitoneal (RP) adipose tissue samples were collected at four-hourly time points (ZT1, ZT5, ZT9, ZT13, ZT17, ZT21) across days 15 and 21 of gestation. Expression of core clock genes (Clock, Bmal1, Per, Cry, Reverb-α and Ror-α) 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 displayed rhythmic expression in liver and adipose tissue (each P<0.001) with CAF-induced changes more prominent in liver than RP. Dietary-induced obesity altered clock gene expression in a tissue, ZT and gestational day dependant manner. Amongst other changes, CAF consumption suppressed peak expression for Reverb-α in liver (P<0.001) and RP (P<0.005), Per1 and Per2 in liver (each P<0.01) as well as a prolonged suppression over consecutive time-points for Bmal1 in RP (P<0.001), Cry2 in liver (P<0.005).
Dietary-induced changes to clock gene expression in maternal metabolic tissues may lead to altered substrate supply to the fetus, which could act as a potential mechanism for altered fetal growth rates observed in obese pregnancy.