With commentary by Sebastien Bouret, PhD, the lead author of the study and associate professor of pediatrics at the Keck School of Medicine, University of Southern California.
A new animal study found that having an excess of the hormone leptin while pregnant could be one of the reasons why children born to obese women are at a higher risk of type 2 diabetes. The study, conducted by researchers at The Saban Research Institute of Children’s Hospital Los Angeles, found that leptin, which is important in maintaining energy balance, inhibits the development of neuron connections between the brain and pancreas in a developing fetus. People who are obese have higher levels of leptin, which is excreted by fat cells.
The findings were published in the online version of the journal Cell Reports [in advance of print publication on April 5].
Studies have shown a strong association between maternal obesity and a child’s predisposition to diabetes. “We know that the baby born to an obese mother is at higher risk to develop diabetes in life, but we don’t know how this happens, how obesity programs your baby to become obese,” says Sebastien Bouret, PhD, the lead author of the study and associate professor of pediatrics at the Keck School of Medicine, University of Southern California. They homed in on leptin because research has shown that obesity in pregnancy is associated with higher levels of leptin in both the mother and the fetus.
Insulin and blood glucose levels are partly regulated by hormones, including leptin. The researchers had previously looked at what factors influenced the direct connections between the brain and pancreatic cells, and found that leptin receptors were turned on during this period. In this study, they exposed the embryonic mouse brain to one dose of leptin during a key developmental period—the middle of gestation.
They found that this one-time exposure caused permanent alternations in the growth of neurons from the brain stem to the pancreas. Leptin led to reduced neural connections, which resulted in abnormal insulin levels and impaired glucose regulation in the adult mouse. “The blood glucose levels were abnormally high in those animals exposed to high levels of leptin,” says Bouret. They performed a glucose tolerance test, and when the mice exposed to leptin were given glucose, they had a hard time bringing glucose back down to normal, suggesting that the pancreas was not functioning normally.
Obese people have two or three times higher levels of leptin than average weight people, and sometimes even more. The more obese you are, the higher your leptin.
The best way to reduce the risk of passing down diabetes to your children is to lose weight. “Women do all sorts of things to protect their babies. They stop smoking, eat organic food. Losing weight is just as important,” says Bouret.
Babies born to obese women carry higher levels of leptin as well, but the damage could potentially be minimized if parents keep an eye on the infant’s weight and try to prevent the baby from becoming overweight. “All the organs—the brain, the pancreas—are still developing and are highly plastic,” says Bouret. It’s likely that an intervention could act on the brain and have effects on the pancreas,” he says.