Working Group identifies many potential genetic contributors to weight loss

In the midst of the holiday season, celebratory get-togethers can mean overindulging on treats and high-calorie foods, leaving many of us struggling to keep off the extra pounds. With as many as two-thirds of American adults already carrying excess weight, and one third with obesity, maintaining weight can be the biggest challenge, say researchers.

"It's easy to get frustrated, especially during the holiday season," said Molly Bray, PhD, professor of nutrition sciences at the University of Texas at Austin. "After the New Year, losing those extra few pounds gained over the holidays is not the biggest challenge - it's maintaining that weight loss over the long term that can be the most difficult."

To create a more complete picture of "why" keeping the weight off is so difficult, the Trans-National Institutes of Health (NIH) Committee on Genes, Behavior and Response to Weight Loss Interventions (National Cancer Institute; National Health Lung and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Office of Behavioral and Social Sciences Research) created a Working Group to better understand how genes affect weight, both at behavioral and biological levels. The Working 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. The group summarized their findings in a review published in the January 2016 issue of Obesity, the official journal of The Obesity Society.

Why genes? Previously, researchers identified that response to weight-loss strategies varies widely among individuals, and that genetics may play a key role in the effectiveness of various treatments. Further, 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. The main reason to study the genetics of weight loss and weight maintenance is to understand the biology that underlies body weight regulation, which is needed to develop more efficient and targeted intervention strategies and medication.

"Leveraging these findings - and expanding the research in this area - could help bring us closer to providing personalized medicine for obesity," continued Dr. Bray, who was the lead author of the Working Group review.

The Working Group identified many potential genetic contributors to weight loss and recommended further research. Here are a few examples:

•Manifestation of an individual's genes: Research shows that while weight loss interventions may not affect overall body weight/BMI, they may improve fat distribution, increase lean mass or reduce diabetes and cancer risk, suggesting that different types of measurements may be more informative in our understanding of the process of weight loss.
•Genetic variants as predictors of obesity treatment response: Research has identified genetic variants that make certain individuals more likely to succeed with some treatments over others. For example, those with a certain allele on the MTIF3 gene may be more likely to achieve weight-loss success through intensive lifestyle interventions with a focus on diet and physical activity, while those with a specific FTO variation may achieve greater weight loss following bariatric surgery.
•Biological systems at work 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, ingestive behavior and physical activity: Research has shown that certain genes expressed in the brain may lead to a greater preference for and consumption of high-calorie foods. Other studies tie genes to both those who exercise and those who don't, as well as adherence to an exercise plan and exercise tolerance.

Researchers continue to explore the benefits of integrating what we know about genes and weight change into the clinical setting. For clinicians, better understanding of the genetic underpinnings for individual patients could aid in the development of precision weight-loss treatments with dietary, physical activity and other methods customized to each individual.

Researchers in the Working Group agreed: more research is needed to give us a better understanding of how precision medicine in obesity treatment can present new avenues to tackle the epidemic.

"Our hope is that by acquiring more advanced insights in the biology of body weight regulation combined with the ability to take into account multiple forms of data simultaneously, we may greatly improve the efficacy of weight loss and weight maintenance," said Ruth Loos, PhD, FTOS, spokesperson for The Obesity Society and co-author of the paper.

Dr. Bray concludes, "Obesity researchers have made tremendous strides in our understanding of what drives eating behavior, how fat cells are formed and how metabolism is altered prior to and after the onset of obesity. The time is ripe to take this wealth of data and find out ways to apply it more effectively for treatments for obesity and other related conditions, including diabetes, cardiovascular disease and cancer."

Source The Obesity Society