Obesity in mothers alters babies' weight through brain rewiring

January 23, 2014, Cell Press

Obese mothers are more likely to have children with metabolic disorders such as diabetes compared with thin mothers, but the underlying molecular and cellular reasons for this effect have been unclear. A study published by Cell Press on January 23rd in the journal Cell reveals that the offspring of mouse mothers on a high-fat diet are predisposed to obesity and diabetes because of abnormal neuronal circuits in the hypothalamus—a key brain region that regulates metabolism. The findings suggest 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 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," says study author Tamas Horvath of the Yale University School of Medicine.

More than one-third of children and adolescents are overweight or obese and thus are at risk for long-term health problems such as type 2 diabetes. Studies in humans have shown that mothers who are obese or have diabetes put their children at risk for metabolic problems, but researchers have not previously identified the exact brain circuits mediating this effect, known as metabolic programming. Moreover, past studies failed to pinpoint the most critical stage of pregnancy during which maternal nutrition has the greatest impact on offspring health.

To address these questions, Horvath teamed up with Jens Brüning of the Max Planck Institute for Neurological Research and the University of Cologne to develop a mouse model of metabolic programming. 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 signaling in this brain circuit. As a result, the offspring remained overweight and had abnormalities in glucose metabolism throughout their adult life.

Because of developmental differences between species—neural circuits in the continue to develop after birth in mice but are fully developed before birth in humans—the 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 offspring'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," Brüning says.

Explore further: Fathers' diet, bodyweight and health at conception may contribute to obesity in offspring

More information: Cell, Vogt et al.: "Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high fat feeding." dx.doi.org/10.1016/j.cell.2014.01.008

Related Stories

Fathers' diet, bodyweight and health at conception may contribute to obesity in offspring

January 16, 2014
Research involving rats suggests that there is a biological link between paternal diet, bodyweight and health at the time of conception and the health of his offspring. In a new research report published online in The FASEB ...

Obese mums may pass health risks on to grandchildren

June 5, 2013
Health problems linked to obesity—like heart disease and diabetes—could skip an entire generation, a new study suggests.

Obese dads pass on predisposition to obesity and metabolic disorders to their kids

July 11, 2013
If you are obese and hope to be a father, here's another reason to lose weight: your children and grandchildren may inherit your waistline or metabolic disorders. That's because scientists have discovered in mice that obese ...

Exercise can reverse negative effects of maternal obesity

February 9, 2012
(Medical Xpress) -- Exercise is the key to overcoming the adverse metabolic effects passed on to offspring by their overweight mothers, with research showing for the first time these effects can be almost completely reversed ...

How women achieve a healthier weight may impact long-term health of offspring

August 21, 2013
New research from the University of Cincinnati (UC) suggests that the healthy weight and glucose control women achieve through weight-loss surgery don't necessarily translate into health benefits for their future children.

Recommended for you

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.