Maternal Caloric Restriction Effect on Brown Adipose Tissue Development and Thermogenic Capacity in Mouse Offspring

Abstract

Background: Animal studies have shown that maternal calorie restriction during pregnancy can increase the risk of adult obesity and metabolic disorders. Brown adipose tissue (BAT) is the main source of non-shivering thermogenesis and could be target to treat obesity. This study aimed to investigate whether maternal calorie restriction during pregnancy affect BAT development and thermogenic capacity in mouse offspring. Methods: Female Institute of Cancer Research (ICR) mice were fed a normal diet prior to gestation and were randomly assigned to either a normal calorie (NC) diet group or a 50% calorie restricted (CR) diet at 12.5 days of gestation, lasting until 18.5 days of gestation group. The offspring in the NC and CR groups were breast feeding for 3 weeks. After weaning, the mice were fed with high-fat diet (HFD) for four months. Then mice in the NC and CR groups were named the NCH (normal calorie with high-fat diet) and CRH (calorie restricted with high-fat diet) groups, respectively. Body weight (BW), thermogenesis-related gene expression, and protein expression of uncoupling protein 1 (Ucp1) were measured in interscapular BAT (iBAT). Results: The CRH group had a lower birth weight than the NCH group (p < 0.01). However, there was no significant weight difference between the two groups after weaning. There were no significant differences in total calorie intake and body weight between the NCH and CRH groups after four months of HFD (p > 0.05). mRNA expression of iBAT, Ucp1 and Adrb3 mRNA levels were significantly higher in the NCH group than those in CRH mice (p < 0.05). In addition, the mRNA levels of fatty acid oxidation-related genes (Pgc1α, Cpt1b, Cox8b, and Cox5b) were significantly higher in the NCH group than those in the CRH group (p < 0.05). Conclusions: Severe maternal calorie restriction during late gestation could adversely affect offspring iBAT development and thermogenic capacity when challenged with a HFD. This may be related to damaged fatty acid oxidation.