Editors' ChoiceMetabolism

Exercising for future generations

See allHide authors and affiliations

Science Signaling  27 Apr 2021:
Vol. 14, Issue 680, eabj1456
DOI: 10.1126/scisignal.abj1456

A placenta-to-fetus pathway transmits the benefits of maternal exercise on the metabolic health of offspring.

Maternal obesity is a risk factor for obesity in future generations. Conversely, maternal exercise improves the health of the offspring by affecting hepatic gene expression. Kusuyama et al. delineated a placenta-to–fetal liver signaling axis that mediated the beneficial effects of maternal exercise on the metabolic health of offspring. Voluntary maternal exercise in gestating mice resulted in increased hepatic expression of glucose and fatty acid metabolic genes in the fetus. This effect was mediated through vitamin D receptor–induced placental expression of Sod3. Circulating SOD3 activated the kinase AMPK in fetal liver, leading to increased expression of the genes encoding the DNA demethylases Tet1 and Tet2; increased production of α-ketoglutarate, which stimulates Tet activity, due to greater expression of the enzymes involved in α-ketoglutarate biosynthesis; and demethylation of hepatic metabolic genes. Application of SOD3 to hepatoblasts from the embryos of sedentary dams attenuated the suppression of metabolic gene expression caused by feeding the dams a high-fat diet. The beneficial effect of maternal exercise on fetal glucose metabolic gene expression or glucose metabolism in offspring was ablated by placenta-specific deficiency or pharmacological inhibition of SOD3 and enhanced by vitamin D supplementation. Identification of this pathway may enable therapeutic intervention to limit the transmission of metabolic disease from mother to offspring.

Highlighted Article

Stay Connected to Science Signaling

Navigate This Article