Seeking to understand how a mother’s health and diet during pregnancy can affect the children, researchers discovered, in mice, that a maternal high-fat diet disrupts the wiring of brain circuitry and fuels the development of excess body fat and other metabolic conditions in the offspring.
The researchers first pinpointed a critical time for the dietary effects by feeding mice either standard chow or a high-fat diet during pregnancy and lactation. A high-fat diet was most detrimental to the mouse pups when given to their mothers exclusively during lactation, a stage similar to the third trimester of human pregnancy. Within a few weeks, mice born to mothers on this unhealthy diet developed excess body fat along with signs of prediabetes and type 2 diabetes (insulin resistance and glucose intolerance). Based on clues from prior studies, the scientists then traced the connections among cells in a region of the brain called the hypothalamus, which plays a key role in regulating metabolism. In the offspring of mothers fed the high-fat diet during this stage of development, brain cells did not branch out normally to build a dense network of connections. Instead, these mice had many fewer fibers linking different areas of the hypothalamus. From additional experiments, the scientists found that the adverse dietary effects result, in part, from elevated signaling by the hormone insulin in the brains of the young mice. Other biologic pathways, yet to be defined, also play a role.
Because diabetes and obesity in women during pregnancy are known to increase risk for diabetes and obesity in their children, this study of a high fat diet in mice may have implications for human health. Further research may lead to improved strategies for healthy eating and other interventions during pregnancy, to benefit women and their children.
Vogt MC, Paeger L, Hess S, Steculorum SM, Awazawa M, Hampel B, Neupert S, Nicholls HT, Mauer J, Hausen AC, Predel R, Kloppenburg P, Horvath TL, Brüning JC. Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high-fat feeding. Cell 156:495-509, 2014.