Summary: Early overnutrition rewires brain development to crave unhealthy food and increases the risk for obesity late in life in children born to mothers who were overweight during pregnancy.
Source: Rutgers University
People whose mothers are overweight during pregnancy and nursing may become obese as adults because early overnutrition rewires developing brains to crave unhealthy food, according to a Rutgers study in Molecular Metabolism.
Rutgers researchers traced this link from mother to child in mice with an experiment that began by letting some mice get obese on unlimited high-fat food during pregnancy and breastfeeding while keeping others slim on limitless healthy food.
They found that mice born to obese mothers stay slim in adulthood on unlimited healthy food but overeat more than mice born to lean mothers when given access to unhealthy food.
The findings indicate that while people whose mothers were overweight during pregnancy and nursing may struggle to moderate their consumption of treats, they could safely eat their fill of healthy foods.
The study may also help inform the development of brain-altering drugs that reduce cravings for unhealthy food.
“People born to overweight or obese mothers tend to be heavier in adulthood than people born to leaner mothers, and experiments like this suggest that the explanation goes beyond environmental factors such as learning unhealthy eating habits in childhood,” said Mark Rossi, a professor of psychiatry at Rutgers Robert Wood Johnson Medical School and senior author of the study.
“Overnutrition during pregnancy and nursing appears to rewire the brains of developing children and, possibly, future generations.”
In the experiment, researchers gave the high-fat food to three sister mice and the healthy chow to another three of their sisters. Once breastfeeding was complete, the researchers turned their attention to the nearly 50 pups—who predictably started at heavier or lighter weights, depending on their mom’s diet.
Their weights converged (at healthy levels) after all the pups received several weeks of unlimited healthy chow, but they diverged again when the researchers offered them constant access to the high-fat diet. All the mice overate, but the offspring of overweight mothers overate significantly more than the others.
Further analysis indicated that the differing behaviors probably stemmed from differing connections between two parts of the brain—the hypothalamus and the amygdala—that arose because of differing maternal nutrition during pregnancy and breastfeeding.
The study has mixed implications for people born to overweight mothers who struggle with their own weight. On the one hand, it suggests the possibility of staying lean while eating healthy food to satiety and avoiding junk entirely. On the other hand, it suggests that efforts to eat moderate quantities of unhealthy treats may spur overconsumption and obesity.
Looking forward, the study’s finding about disrupted brain circuits in the two groups of mice may help inform the creation of drugs that would block the excess desire to consume unhealthy foods.
“There’s still more work to do because we don’t yet fully understand how these changes are happening, even in mice,” Rossi said.
“But each experiment tells us a little more, and each little bit we learn about the processes that drive overeating may uncover a strategy for potential therapies.”
Maternal overnutrition is associated with altered synaptic input to lateral hypothalamic area
Maternal overnutrition is associated with adverse outcomes in offspring, including increased risk for obesity and diabetes. Here, we aim to test the effects of maternal obesity on lateral hypothalamic feeding circuit function and determine the relationship with body weight regulation.
Using a mouse model of maternal obesity, we assessed how perinatal overnutrition affected food intake and body weight regulation in adult offspring. We then used channelrhodopsin-assisted circuit mapping and electrophysiological recordings to assess the synaptic connectivity within an extended amygdala-lateral hypothalamic pathway.
We show that maternal overnutrition during gestation and throughout lactation produces offspring that are heavier than controls prior to weaning. When weaned onto chow, the body weights of over-nourished offspring normalize to control levels. However, when presented with highly palatable food as adults, both male and female maternally over-nourished offspring are highly susceptible to diet-induced obesity. This is associated with altered synaptic strength in an extended amygdala-lateral hypothalamic pathway, which is predicted by developmental growth rate. Additionally, lateral hypothalamic neurons receiving synaptic input from the bed nucleus of the stria terminalis have enhanced excitatory input following maternal overnutrition which is predicted by early life growth rate.
Together, these results demonstrate one way in which maternal obesity rewires hypothalamic feeding circuits to predispose offspring to metabolic dysfunction.