To examine the pups’ response to the mothers’ diets, brain samples and peripheral tissue (fat, blood, and liver) were collected at one day after birth, at weaning (20 days after birth), and in early adulthood (days 60 to 90). The investigators tested immune system functioning in the liver and in the brain, as well as behavioral measures of anxiety and the ability to learn and remember a maze.
Inflammatory response was tested in the pups after weaning (day 20) and in adulthood (days 60 to 90) by comparing immune response four hours after injections of dead bacteria. This procedure activates the immune system without causing an infection that would have a negative impact on an animal’s health.
The researchers observed clear evidence of brain inflammation in the pups born to mothers on high-fat diets. From birth through adulthood, there was evidence of low-level inflammation in brain samples from high-fat groups, including activation of microglia (immune cells) in the hippocampus of the brain. Inflammation also was present outside the brain as evidenced by increased C-reactive protein in the liver.
Most striking was the difference in response to immune challenge. Adult animals whose mothers had been on high-fat diets had a greatly exaggerated inflammatory response in these same areas, compared with low-fat control animals.
“It was absolutely one of the largest responses we have ever seen,” said Dr. Bilbo. In response to anxiety and cognition tests, adult animals whose mothers were given the high-fat diets were considerably more anxious than adult animals from the low-fat group. However, no negative impact was noted on cognition as a consequence of mothers’ high-fat diets.
“Dietary fats are critical to a healthy pregnancy, so we were unsure if the placenta would serve as a protector from the negative effects of the fats, but it seems this is not the case,” said Dr. Bilbo. “The mothers’ diet during pregnancy determines a lifelong neuroinflammatory condition for the fetus that cannot be reversed with low-fat diet alone.”
Dr. Bilbo emphasized that while these findings are noteworthy, this is the first look at the effects of mothers’ obesity on the fetal brain. More research is needed on the composition of the diet before drawing inferences for humans.
The next step in Dr. Bilbo’s research will be to look at the success of reversing the impact of the mothers’ diet of brain inflammation through interventions that target the fetal immune response.
Eating Disorders Linked With Disrupted Rewards Process in the Brain
New findings on eating disorders, including obesity and anorexia nervosa, demonstrate the influence the brain has on appetite and weight control.
Obesity and anorexia, often considered metabolic in nature, appear to also reflect brain functions involving reward and inhibition. Past studies have shown that individual differences may predispose a person to undereat or overeat. These behaviors are influenced by the pleasure derived from eating and drinking, sensory properties of food and a person’s prior experiences, current internal state, expectations, beliefs, and genes.
Multiple studies examined several of these factors and the brain activity associated with them. They revealed a complex, integrated system in which signals from the body interact with brain circuitry to control eating behavior. Desensitization to these signals may lead to pathologic eating. As in other addictions, the dopamine reward system is critically involved. The similarities hold implications for potential treatment and prevention of obesity, according to Nora D. Volkow, MD, Director of the National Institute on Drug Abuse in Bethesda, Maryland.
“The brain is a complicated, integrated system whose responses are linked to changes in the body, as well as predisposing factors associated with a person’s experiences with food,” said Dr. Volkow. “When the brain senses the need for food, the reward system is activated. But the more a person overeats, the more insensitive to food rewards they may become, potentially causing a need to increase stimuli, which in this case is more food intake.”
Examining the brain’s response to certain foods, Dana M. Small, PhD, of the John B. Pierce Laboratory and Yale University in New Haven, Connecticut, found an inverse relationship between a person’s BMI and the brain’s response to a milkshake. Obese persons experienced much less activation of reward centers as they ate the food. The study determined that the response of the caudate to a milkshake was a better predictor of future weight gain than many traditional measures.
Cary R. Savage, PhD, of the University of Kansas Medical Center in Kansas City, conducted a study of food motivation using fMRI. He and his colleagues found that individuals who were obese differed from healthy-weight participants in the way that the brain responded to anticipated food or monetary rewards and punishments. Obese individuals showed greater brain sensitivity to anticipated rewards and less sensitivity to anticipated negative consequences than did healthy-weight individuals.