Background

Maternal obesity increases offspring risk for several metabolic diseases. We previously demonstrated that the offspring of obese dams are predisposed to obesity and associated co-morbidities. However, the effect of maternal obesity on the programing of brown adipose tissue (BAT) is poorly understood. Here we examine the hypothesis that in utero exposure to high-fat diet (HFD) alters BAT transcriptome and pathways responsible for energy homeostasis.

Methods

Female C57BL6/J mice were fed diets with either low (10%) or HFD (45% of calories) for 12 wk starting at 5 wk of age. Dams were bred with males on control diets and provided access to respective diets during pregnancy and lactation. At weaning, offspring were weaned onto control and HFD. Male offspring from the four groups were followed till 20 wk of age on control and HFD diet.

Results

Twenty weeks of HFD lead to significantly increased weight gain in HFD fed offspring of obese dams. The transcriptome analysis of BAT revealed that maternal HFD altered expression of 219 genes (±1.5-fold change, adj. p<0.05), which affected pathways related to cellular metabolic process, response to stress, chemical, temperature stimulus, and heat. Among genes reduced due to maternal obesity, homeobox gene expressed in ES cells (Hesx1) was identified in offspring of obese dams, which was also confirmed by RT-PCR. Hesx1 was also found to be expressed at a higher level in differentiating brown adipocytes (BMC-WT cell line), whereas, in 3T3L1 cell line which is white adipogenic cell line, Hesx1 expression was minimal. Classic BAT-specific proteins such as Ucp1, Dio2 and Cidea were also lower in BAT of offspring of HFD fed dams. In addition, protein kinases such as AMPK as well as ERK1/2 were also downregulated in BAT of offspring of HFD fed dams.

Conclusions

In conclusion, our results indicate that maternal obesity programs BAT transcriptome and may influence pathways regulating energy expenditure, metabolism, and susceptibility to obesity.