The study aimed to shed further light on the molecular processes underlying the previously reported phenomenon that 'heavy mothers have heavy babies' - also referred to as metabolic programming .
"We aimed to establish a mouse model of metabolic programming that would allow us to identify the most sensitive period of hypothalamic neurocircuit development in response to maternal HFD [high-fat diet] feeding," explained the research team, led by Professor Jens Brüning of the Max Planck Institute for Neurological Research and Professor Tamas Horvath of the Yale University School of Medicine in the US.
The study, published in Cell, suggests that mothers who consume a large amount of fat during the third trimester may be putting their children at risk for lifelong obesity and related metabolic disorders.
"Our study suggests that expecting mothers can have major impact on the long-term metabolic health of their children by properly controlling nutrition during this critical developmental period of the offspring," said Horvath.
The team noted that previous studies in humans have shown that mothers who are obese or have diabetes put their children at risk for metabolic problems. However, the exact mechanisms and brain circuits mediating this effect are still unknown, while past studies failed to pinpoint the most critical stage of pregnancy during which maternal nutrition has the greatest impact on children's health.
To address these questions the authors used a mouse model to examine and identify the periods of hypothalamic neurocircuit development that are most strongly affected by a high fat diet in mothers.
They found that mouse mothers fed a high fat diet during lactation had offspring with abnormal neuronal connections in the hypothalamus, as well as altered insulin signalling in this brain circuit. As a result, the offspring remained overweight and had abnormalities in glucose metabolism throughout their adult life.
"Our study not only shows that the lactation period in rodents is most sensitive to the altered developmental environment in response to maternal HFD feeding, predisposing the offspring for metabolic diseases as described before, but importantly demonstrates that the short exposure to HFD during this distinct developmental phase is sufficient to predispose the offspring for metabolic disorders," wrote Hovarth, Brüning and colleagues.
Because of developmental differences between species - neural circuits in the hypothalamus continue to develop after birth in mice but are fully developed before birth in humans - the authors noted that their findings suggest that the third trimester of pregnancy in humans is the most critical time window for a mother's nutrition to have long-lasting effects on her child's health.
"Given that gestational diabetes frequently manifests during the third trimester, our results point toward the necessity of more intensified screening of mothers for altered glucose metabolism, as well as tightly controlled antidiabetic therapy if any alterations are detected during this critical period," commented Brüning.
"Mothers can control or even reverse their offspring's predisposition to obesity and resulting diseases by altering their food intake," added Horvath.
Published online ahead of print, doi: 10.1016/j.cell.2014.01.008
"Neonatal Insulin Action Impairs Hypothalamic Neurocircuit Formation in Response to Maternal High-Fat Feeding"
Authors: Merly C. Vogt, Lars Paeger, et al