Obesity partly in genes

With the holiday season in full swing, it can be hard not to put on weight with all the festive treats and high-calorie foods on offer. A number of genetic factors may make this even harder for some people, according to research published in the journal Obesity.

Up to two thirds of American adults are already overweight, and a third are classed as obese; for these people, maintaining weight can be a major challenge.

The advance of the obesity epidemic has coincided with the abundance of palatable, highly processed, energy-dense foods and reduced physical activity levels, suggesting that environmental factors play a major role.

However, the fact that some people do not become obese in this environment, and that responses to treatment approaches vary between individuals, suggests that genetic factors may also have an impact.

To find out more about why avoiding weight gain is so difficult, the National Institutes of Health (NIH) Committee on Genes, Behavior and Response to Weight Loss Interventions created a Working Group to examine how genes affect weight, both at behavioral and biological levels.

The group focused on genetic factors leading to weight loss and weight regain and identified future research directions and opportunities for incorporating new weight-loss treatment strategies.

Variation in individual response to weight-loss strategies has already been documented, as has the likelihood that genetics plays a key role in the effectiveness of treatments.

Previous studies have identified 150 genetic variants tied to body mass index (BMI), waist circumferences or obesity risk. However, little is known about the genes that determine why some people lose weight more easily than others.

Which genetic contributors affect weight gain and loss?

The team wanted to study the genetics of weight loss and weight maintenance in order to understand the biology that underlies body weight regulation. This, they hoped, could lead to more efficient and targeted intervention strategies and medication.

The Working Group identified many potential genetic contributors to weight loss and recommended further research.

The factors identified include the following:

• Manifestation of an individual’s genes: weight loss interventions may not affect overall body weight or BMI, but they may improve fat distribution, increase lean mass or reduce diabetes and cancer risk, suggesting that different types of measurements may provide insight into the process of weight loss
• Genetic variants as predictors of obesity treatment response: some genetic variants appear to make particular treatments more successful for certain individuals. For example, those with a certain allele on the MTIF3 gene may find it easier to lose weight through intensive lifestyle interventions with a focus on diet and physical activity, while a specific FTO variation may lead to greater weight loss following bariatric surgery
• Biological systems that influence food intake and physical activity: epigenetics (chemical modifications of genes that may be the result of exposures to certain environments) and the gut microbiome (microorganisms that naturally live in our stomach and help with balancing metabolic function) have been shown to have lasting effects on weight
• Genetic impact on food preferences, eating and drinking behavior and physical activity: certain genes may lead to a greater preference for and consumption of high-calorie foods
• Genetics of physical activity: genetic differences have been linked to both those who exercise and those who do not, as well as adherence to an exercise plan and exercise tolerance.

Lead author Dr. Molly Bray, professor of nutrition sciences at the University of Texas-Austin, says:

“It’s easy to get frustrated, especially during the holiday season. After the New Year, losing those extra few pounds gained over the holidays is not the biggest challenge; it is maintaining that weight loss over the long term that can be the most difficult.”

Leveraging these findings, she says, and expanding research could help to provide personalized medicine for obesity.

A better understanding of these factors could lead to precision weight-loss treatments with dietary, physical activity and other methods customized to each individual.

Dr. Bray concludes that we now understand much more about what drives eating behavior, how fat cells are formed and how metabolism changes before and after obesity sets in.

The next step is to apply this data more effectively to treat obesity and related conditions, including diabetes, cardiovascular disease and cancer.