Animal study shows high-fat diet is more harmful to males than females

Male and female brains are not equal when it comes to the biological response to a high-fat diet. Cedars-Sinai Diabetes and Obesity Research Institute scientist Deborah Clegg, PhD, and a team of international investigators found that the brains of male laboratory mice exposed to the same high-fat diet as their female counterparts developed brain inflammation and heart disease that were not seen in the females.

"For the first time, we have identified remarkable differences in the sexes when it comes to how the body responds to high-fat diets," said Clegg. "In the study, the mice were given the equivalent of a steady diet of hamburgers and soda. The brains of the male mice became inflamed and their hearts were damaged. But the female mice showed no brain inflammation and had normal hearts during the diet."

The study was funded by the National Institutes of Health and the findings are published today in the journal Cell Reports.

According to Clegg, the females in the study apparently had a strong protection against the ravages of a high-fat, high-sugar diet that can cause brain inflammation and heart disease. Researchers have linked brain inflammation to overeating, harmful changes in blood sugar levels and to changes in fat tissue composition that can lead to obesity.

"It is as if the brains of females had a chemical force field that kept the dangers of fats and sugars from harming them," said Clegg. "Our data in this study also adds to the growing body of evidence that brain inflammation may be a key factor in the obesity epidemic. These negative brain changes can occur even over a short period of eating fatty and sugary food and clearly affected males much more than females."

Clegg said the research suggests that one size may not fit all when it comes to nutritional guidance aimed at keeping patients from becoming dangerously overweight. An occasional high-fat meal may be OK for women, but something men at risk for obesity will need to avoid always.

"These findings on how the brains and bodies of males and females respond so differently to nutrients suggests we have to reconsider whether the diets and drugs we recommend for managing obesity may need to be sex-specific to be more effective," said Richard Bergman, PhD, director of the Diabetes and Obesity Research Institute.

Investigators discovered one encouraging sign for males: They could manipulate the brain of the mice in such a way they would develop the anti-inflammation characteristics of the female brain.

"When we caused the male brain to resemble the female brain in chemical composition, it was protected from the dangerous inflammatory effects a high-fat diet created in the normal male brain," said Clegg. "It provided more proof that the female brain inherently possesses certain chemical qualities that protects her from the dangers of a high-fat diet."

Clegg said the next step in the research of sex differences and nutrition is to investigate these initial findings in humans. Identifying which factors appear to protect female brains from high-fat diet inflammation, and their hearts from disease, could significantly impact the future treatment of obesity and diabetes for all patients.