ANN ARBOR—Is obesity all in your head?

New research suggests that genes that predispose people to obesity act in the brain, and that perhaps some people are simply hardwired to overeat. An international research team co-led by the University of Michigan found six new genes that help explain body mass index and obesity, and all but one of the genes are tied to the brain rather than to metabolic functions, such as fat storage and sugar metabolism.

In addition to the six new genes, the study also confirmed the role of two other genes previously associated with obesity, said co-principal investigator Goncalo Abecasis, an associate professor at the University of Michigan School of Public Health who helped direct and write the paper. The study will appear online Dec. 14 in advance of print publication in the journal Nature Genetics.

It’s significant that five of the six new genes also impact brain function, because the findings suggest people could simply be programmed to overeat, said Cristen Willer, a postdoctoral researcher at University of Michigan, and first author on the paper. The brain, she said, has two main functions related to weight: appetite control and the regulation of one’s total energy balance (whether you burn more calories or conserve more energy.)

“This research tells you a little about what kinds of drugs you want to develop and where you want them to act,” Abecasis said.

Unfortunately, society is often particularly unforgiving of overweight people, assuming them weak or lacking in discipline.

“If you just want to think about how you react to these people who are obese, they can just be wired differently, so you have to be respectful of that,” Abecasis said.

“It’s different if you know that overeating is about biology, and it takes a major effort to overcome that biology,” Willer said. “Clearly this suggests that some aspects of eating behavior may be something you’re born with.”

For example one of the genes, NEGR1, controls how your brain is wired as it’s developing by regulating neuronal growth, Abecasis said.

“In younger children ages 5-10 we found that with three of (the genes) the children were already heavier at that young age, and with the other three genes, we saw that there was no effect on children” Abecasis said. “For those, we only saw an effect in much older individuals. This points to different mechanisms influencing your weight at different ages.”

Another example is SH2B1, which was first discovered by U-M researchers studying the mouse, Abecasis said. Researchers created an obese mouse then returned the mouse to a normal weight by turning on the SH2B1 gene in the brain.

The international team analyzed 32,387 individuals of European ancestry from 15 large scale genetic association studies. The findings were confirmed in more than 50,000 additional individuals. The study collaborators included researchers from the Oxford and Cambridge, UK, the National Institutes of Health in the U.S., and the Broad Institute of Harvard and MIT, as well as many other members of the Genetic Investigation of Anthropometric Traits (GIANT) consortium.

The University of Michigan School of Public Health has been working to promote health and prevent disease since 1941, and is consistently ranked among the top five public health schools in the nation. Faculty and students in the school’s five academic departments and dozens of collaborative centers and initiatives are forging new solutions to the complex health challenges of today, including chronic disease, health care quality and finance, emerging genetic technologies, climate change, socioeconomic inequalities and their impact on health, infectious disease, and the globalization of health. Whether making new discoveries in the lab or researching and educating in the field, our faculty, students, and alumni are deployed around the globe to promote and protect our health.

Related Links:

• Abecasis
• More on Abecasis
• Willer
• Department of Biostatistics