Despite the widespread belief that obesity is the result of poor choices, a growing body of evidence indicates that lifestyle factors are only one of many complex causes of excess weight gain and fat storage. Now, researchers have uncovered strong new evidence pointing to a genetic reason for a tendency to put on weight.
The research, involving more than 400 researchers in two dozen countries who studied the genomes of 340,000 people, provides the most comprehensive picture to date of the genetic contributors to obesity.
Two new papers in the journal Nature describe the results of two studies that connected the obesity-related factors of body mass index (the ratio between height and weight) and fat distribution to their potential genetic drivers. The studies did not isolate specific genes—at least not yet—but identified areas in the human genome where people with different BMIs and different patterns of fat distribution varied in their genetic code. Those variants will lead scientists to the genes they code for, and eventually to how those genes influence susceptibility to obesity.
Those genetic clues may yield new weight-management treatments that are both more powerful and more personalized. “Our work clearly shows that predisposition to obesity and increased body mass index is not due to a single gene or genetic change,” senior study author Elizabeth Speliotes, M.D., Ph.D., M.P.H, assistant professor of internal medicine and computational medicine and bioinformatics at the University of Michigan Health System, said in a statement.
“The large number of genes makes it less likely that one solution to beat obesity will work for everyone and opens the door to possible ways we could use genetic clues to help defeat obesity,” she said.
Currently, however, all obesity is treated pretty much the same way. With a better understanding of the genetic underpinnings of different types of obesity, that may change.
Brain findings suggest obesity is a ‘neurobehavioral disorder’
In the study involving factors contributing to BMI, Speliotes and her team discovered 97 genetic regions, or loci that account for nearly 3% of the variation among people on BMI. Of those, 56 are entirely new. Many of the regions are in areas that code for nervous system functions, or brain systems. Some aren’t so surprising—they confirm previous studies that have implicated genetic regulators of areas that control appetite, for example—but others were more unexpected. They involved regions responsible for learning, memory and even emotional regulation, hinting that some of weight and obesity may be tied to the addiction and reward pathways that help to reinforce behaviors like eating with feelings of pleasure and satisfaction.
That makes obesity much more of a neurobehavioral disorder than a simple disruption of fat cell growth and storage, said the researchers, and it also supports other recent findings that have uncovered similarities between the brains of people with obesity and those with addiction.
The study also revealed a few very interesting links between some genetic variants that contributed to higher BMI and lower risk of diabetes, heart disease and triglyceride levels. That suggests that there may be some protective genetic factors that counteract the effects of higher BMI, and exploiting these may be an entirely new way of treating obesity.
The group that looked at the genetic factors driving body fat distribution had similar findings. Mohlke and her colleagues looked at the waist-hip ratio and found 49 areas in the genome that varied among the participants, 33 of which were entirely new. Most of the variants involved logical processes such as the formation of HDL and LDL cholesterol, triglycerides and processing of insulin.
What was interesting, however, was the fact that many of these exerted much more power on women than on men, suggesting the need to recognize gender-based differences as a critical factor in future obesity therapies.
Personalized obesity treatment
The findings, the authors stress, are just the beginning of a deeper understanding of what is driving obesity in its many forms, and how best to intervene with more personalized and potentially more effective treatments.
“We are realizing that many of the common diseases we aim to treat are caused by multiple different underlying causes,” Speliotes told Michigan Daily. “So now we can understand what those causes are and better define them. And then hopefully in the future we can sub-classify people into what they are at risk for versus what the general population is at risk for.”
Genes, they say, only play a part in obesity, but these studies are the first step toward a better appreciation of how genes are involved in behaviors that influence what and how much we eat, and our bodies process and store that food as energy and fat. “We envision using these [findings] to help doctors decide which treatments would work best to keep patients healthy,” adds Speliotes .