Influence of maternal high-calorie diet feeding on offspring fat development
Pre-pregnancy obesity is associated with offspring overweight. Adipose tissue development in obesity-exposed offspring mice was previously found to be sex-specific and particularly impaired in females. However, mechanisms are poorly understood. We aimed to study the effect of intrauterine obesogenic exposure on female adipocyte development. Maternal overweight was induced by high-calorie diet (HCD) feeding of Naval Medical Research Institute (NMRI) dams before and during gestation. Mouse embryonic fibroblasts were isolated from females exposed to HCD at embryonic day 13.5 and differentiated into mature adipocytes ex vivo. RNA sequencing identified downregulation of aldehyde dehydrogenase family 1, subfamily A7 (Aldh1a7) and Aldh1a1, compared to adipocytes derived from control diet exposed fetuses, which appeared to persist in visceral adipose tissue into adulthood. In vitro, knocking down Aldh1a7 mRNA expression during 3T3-L1 preadipocyte differentiation inhibited lipid droplet formation at early differentiation stages and resulted in downregulation of adipogenic markers including fatty acid synthase. Thereby, Aldh1a7 emerged as an important regulator in early murine differentiation. We further demonstrate that expression of several aldehyde dehydrogenase family members is divergent during early and late human SGBS adipocyte differentiation. Our data contribute to identifying molecular targets in female offspring adipocytes that are particularly vulnerable to early-life obesogenic exposure, possibly linked to unfavorable adipose tissue development, requiring counteracting nutritional strategies.
Pre-pregnancy obesity is associated with offspring overweight. Adipose tissue development in obesity-exposed offspring mice was previously found to be sex-specific and particularly impaired in females. However, mechanisms are poorly understood. We aimed to study the effect of intrauterine obesogenic exposure on female adipocyte development. Maternal overweight was induced by high-calorie diet (HCD) feeding of Naval Medical Research Institute (NMRI) dams before and during gestation. Mouse embryonic fibroblasts were isolated from females exposed to HCD at embryonic day 13.5 and differentiated into mature adipocytes ex vivo. RNA sequencing identified downregulation of aldehyde dehydrogenase family 1, subfamily A7 (Aldh1a7) and Aldh1a1, compared to adipocytes derived from control diet exposed fetuses, which appeared to persist in visceral adipose tissue into adulthood. In vitro, knocking down Aldh1a7 mRNA expression during 3T3-L1 preadipocyte differentiation inhibited lipid droplet formation at early differentiation stages and resulted in downregulation of adipogenic markers including fatty acid synthase. Thereby, Aldh1a7 emerged as an important regulator in early murine differentiation. We further demonstrate that expression of several aldehyde dehydrogenase family members is divergent during early and late human SGBS adipocyte differentiation. Our data contribute to identifying molecular targets in female offspring adipocytes that are particularly vulnerable to early-life obesogenic exposure, possibly linked to unfavorable adipose tissue development, requiring counteracting nutritional strategies.
Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Childrens Hospital, Faculty of Medicine, Heinrich Heine University Duesseldorf