Compared with slim mothers, children born to obese mothers are more likely to suffer from metabolic diseases such as diabetes. However, the underlying molecular and cellular mechanisms of this influence have been unclear. A new study published in the journal Cell reveals that due to abnormalities in some neuronal circuits in the hypothalamus (an important brain region that regulates metabolism), offspring born to mothers on high-fat diet mice are more likely to suffer Obesity and diabetes. The results of these studies indicate that pregnant women who consume large amounts of fat during the last three months of pregnancy may expose their children to lifelong obesity and related metabolic diseases.
"Our research shows that by properly controlling nutrition during this critical period of future generations, expectant mothers can have a significant impact on the child's long-term metabolic health," said Tamas Horvath, author of the paper and Yale University School of Medicine.
More than one-third of children and adolescents are currently overweight or obese, and therefore at risk of long-term health problems such as type 2 diabetes. Some human studies have confirmed that mothers who are too obese or suffer from diabetes put their children at risk of metabolic problems. However, in the past, researchers have not identified the precise brain circuits that mediate this metabolic reprogramming effect. In addition, past studies have not accurately found the most critical stage in maternal nutrition that has the greatest impact on the health of future generations during pregnancy.
To answer these questions, Horvath collaborated with the Max Planck Institute of Neurology and Jens Brüning of the University of Cologne to develop a mouse metabolic reprogramming model. They found that the mothers of mice fed a high-fat diet during lactation had abnormal neuronal connections in the hypothalamus, and the insulin signaling pathway in this brain circuit was changed. Therefore, the offspring are still overweight and have abnormal glucose metabolism in adulthood.
Due to some developmental differences between humans and mice: mice continue to develop hypothalamic neural circuits after birth, and humans have fully developed hypothalamic neural circuits before birth. These findings indicate that the third trimester of human pregnancy Months are the most critical time window for a mother ’s nutrition to have a long-term impact on the health of future generations.
"Because gestational diabetes often occurs in the third month of pregnancy, our results indicate that it is necessary to screen the mother for changes in glucose metabolism more closely during this critical period, and to strictly control anti-diabetic treatment "Brüning said.
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