Endocrine Abstracts

Introduction: Pregnancy is associated with maternal metabolic adaptations (increased cholesterol and triglycerides) that are essential for the development and maintenance of the fetus. Physiological and behavioural changes are driven via biological clocks entrained by the light–dark/rest–activity cycles that define feeding time and body temperature. A number of oscillators are present in the peripheral organs that are synchronised by cues from the suprachiasmatic nucleus. The core clock machinery drives rhythmic metabolic activities and receives feedback from intracellular metabolites.

Hypothesis: Maternal metabolic adaptations in pregnancy are a result of altered circadian rhythmicity of metabolism-associated genes.

Methods: C57BL6 mice were sacrificed in early pregnancy (day 7 post-coitum (pcm)-pre-placentation) and in the third trimester of pregnancy (day 14 pcm) at 4 h intervals over a 24 h light/dark cycle. Mice on day 2 pcm were used as controls.

Results and conclusions: Circadian rhythmicity of hepatic lipogenic genes (Fas, Scd-1, Scd-2, Lpl, and Hmgcr) was increased on day 7 pcm with a peak expression during the night and was blunted on day 14 pcm mice compared to controls. In gonadal fat of pregnant animals, there was a loss in circadian rhythmicity of lipogenic (Fas) and lipolytic (Hsl, Cd36, and Hadh) genes throughout pregnancy. In skeletal muscle, we demonstrated loss of rhythmicity of fatty acid oxidation-related genes (Cpt1β, Fatp1, and Glut4) on day 7 pcm that was restored on day 14 pcm with a peak expression during the light phase. We showed circadian rhythmicity in placental targets involved in lipid transport (Lxrβ, Abca1, Ldlr, pFabp-pm, and Fatp4) with a peak expression in the dark phase on day 14 pcm. These data suggest altered syncronisation of metabolic tissues at different stages of pregnancy. A shift from fat storage in early pregnancy (driven by a rhythmic liver) to energy mobilisation later in pregnancy (driven by a rhythmic muscle) appears essential for development and maintenance of the growing fetus.