Endocrine Abstracts

Pregnancy is associated with increased maternal plasma lipid levels, an important physiological response to support the nutritional demand of the developing fetus and mother. The homeostatic controls of metabolically active organs are known to change in response to pregnancy signals. We hypothesised that pregnancy affects brown adipose tissue (BAT) phenotype and function and as a consequence plays a role in the regulation of fetal development and growth.

Using mice at gestational day 14 of pregnancy (GD14) or non-pregnant controls, we showed that the interscapular BAT (iBAT) was hypertrophied and exhibited a loss of BAT phenotypic markers (e.g. Ucp1) at GD14. In parallel, the expression of white adipose markers was increased at GD14, accompanied by lipid droplet accumulation. At a functional level, norepinephrine-mediated energy expenditure and increase in respiratory quotient observed in terminally anaesthetised non-pregnant mice were both abrogated in GD14 mice. This suggests that inducible thermogenesis and fuel utilisation in thermogenic tissue are modified by pregnancy.

To study the impact of the pregnancy-dependent phenotypic change on maternal and fetal parameters during the growth phase of the fetus (GD14-GD19), the iBAT was surgically ablated in female mice prior to mating and the mice were sacrificed at GD18. Ablation of iBAT resulted in a significant increase at GD18 in: i) normalised maternal body weight, ii) fetal weight, iii) placental weight, and iv) fetal serum FFA and hepatic cholesterol concentrations. This indicates that the removal of the main BAT depot results in the dysregulation of fetal lipid metabolism and growth.

These data shed new light on a pregnancy-brown adipose tissue axis that appears to play a role in the regulation of fetal growth driven by a gestational reduction in classical BAT phenotype.