In This Issue of Diabetes


By Max Bingham, PhD

Prepregnancy High-Fat Feeding Reduces Offspring Blood Glucose Levels via Increased β-Cell Development

The effects of maternal obesity on the development of offspring are explored by Qiao et al. (p. 1604) revealing that, at least in mouse models, a prolonged high-fat diet prior to pregnancy reduces blood glucose concentrations in both newborn offspring and fetuses in late pregnancy. Significantly, however, the authors also explore the potential underlying mechanisms that might be involved. The relationship between maternal obesity and neonatal hypoglycemia is well established, with concern pointing toward developmental issues, but why the phenomenon occurs is relatively unexplored. The authors explain that identifying the mechanisms underlying the relationship could unlock diagnostic and therapeutic options that might improve pregnancy outcomes. Using a series of mouse models, they report that feeding prepregnant and pregnant mice a high-fat diet did result in reduced blood glucose in both neonates and fetuses in late pregnancy and also resulted in increased blood insulin concentrations and pancreatic β-cell mass. They also found hyperactivation in a series of metabolically active tissues, which they suggest explains the reduction in offspring blood glucose concentrations. While they did not find an increase in placenta cross-sectional area or GLUT1 expression, there was a significantly enhanced expression of genes that control placental fatty acid supply. Turning to a mouse model with placenta-specific knockout of adipose triglyceride lipase, they found it had a reduced fetal β-cell area and blood insulin concentrations and also attenuated the reductions in offspring blood glucose concentrations due to maternal high-fat feeding and obesity. Author Jianhua Shao told Diabetes: “This is the first animal study that reveals the significance of prepregnant maternal obesity, but not dietary fat during pregnancy, in offspring islet development and glucose metabolism. This study also demonstrates that fetal glucose metabolism is not simply and passively controlled by placental glucose supply but is …

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