Reversing the Effects of Maternal Obesity

Obese women tend to give birth to overweight offspring who have a predisposition to metabolic disease and obesity. This effect has now been reversed in mice by infusing pregnant mothers with adiponectin, a hormone that helps manage metabolism [1]. The effects of maternal obesity on the fetus seem to be mediated mainly through the placenta, and include increased transport of nutrients across the placenta as a result of elevated insulin signaling, leading to excess fetal growth. There have been hints that adiponectin, which is produced by fat cells, might counteract some of these effects—for instance, circulating levels of adiponectin are low in mouse and human mothers who are obese or have gestational diabetes. Irving Aye et al. now report that restoring normal levels of adiponectin reverses the effects of maternal obesity in mice. Consistent with previous studies, the researchers found that overweight pregnant mice had a host of problems: elevated fasting serum insulin and leptin, elevated placental insulin signaling, activation of regulators such as mTORC1 that respond to insulin, increased expression of glucose and amino acid transporters in the placenta, and increased flux of these nutrients across the placenta. Their offspring were about 29 percent heavier than offspring from normal-weight mice and also had high blood sugar. Treatment with adiponectin reversed all of these effects, and resulted in offspring of normal weight with normal glucose levels. The researchers propose that adiponectin operates by restoring normal placental insulin signaling and fetal nutrient supply, leading to normal-weight offspring. These findings have the potential to be translated to humans, but one caveat is that that adiponectin treatment in mice can result in underweight offspring if given to normal-weight mothers. An intervention is urgently needed, as about two-thirds of mothers in the United States enter pregnancy being overweight or obese—contributing to a spiraling population-wide obesity epidemic. Future studies testing the value of this potential therapy may use an oral form of adiponectin, which recently has been developed.