Mom’s dietary fat rewires male and female brains differently: Excess fat triggers immune cells to overeat serotonin in the brain of developing male mice, leading to depression-like behavior

More than half of all women in the United States are overweight or obese when they become pregnant. While being or becoming overweight during pregnancy can have potential health risks for moms, there are also hints that it may tip the scales for their kids to develop psychiatric disorders like autism or depression, which often affects one gender more than the other.

What hasn’t been understood however is how the accumulation of fat tissue in mom might signal through the placenta in a sex-specific way and rearrange the developing offspring’s brain.

To fill this gap, Duke postdoctoral researcher Alexis Ceasrine, Ph.D., and her team in the lab of Duke psychology & neuroscience professor Staci Bilbo, Ph.D., studied pregnant mice on a high-fat diet. In findings appearing November 28 in the journal Nature Metabolism, they found that mom’s high-fat diet triggers immune cells in the developing brains of male but not female mouse pups to overconsume the mood-influencing brain chemical serotonin, leading to depressed-like behavior.

The researchers said a similar thing may be happening in humans, too.

People with mood disorders like depression often lose interest in pleasurable activities. For mice, one innately pleasurable activity is drinking sugar water. Since mice preferentially sip sugar water over plain tap when given the choice, Ceasrine measured their drink preference as an estimate for depression. Males, but not females, born by moms on a high-fat diet lacked a preference for simple syrup over tap water. This rodent-like depression suggested to Ceasrine that mom’s nutrition while pregnant must have changed their male offspring’s brain during development.

One immediate suspect was serotonin. Often called the “happy” chemical, serotonin is a molecular brain messenger that’s typically reduced in people with depression.

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