Genes May Play Major Role in Long-term Weight Loss

Genes May Play Major Role in Long-term Weight Loss

Holidays and overeating — especially of rich meals and desserts — are known to go hand-in-hand, leaving many struggling to shed the extra pounds and, importantly, to maintain a better weight.

“It’s easy to get frustrated, especially during the holiday season,” said Dr. Molly Bray, professor of nutrition sciences at the University of Texas at Austin in a news release. “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 better understand how genes affect weight at the biological as well as behavioral levels — and so understand why it’s so difficult to keep from regaining lost weight — 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, Office of Behavioral and Social Sciences Research, National Institute of Diabetes and Digestive and Kidney Diseases) created a Working Group. The group’s focus was understanding the genetic risk factors that lead to weight loss and weight regain, and also to identify research opportunities and directions for integrating novel treatment methods for weight loss. Its findings were recently published in the journal Obesity.

Why the focus on genes? Earlier, scientists discovered that response to weight-loss methods usually differ among individuals, with genetics playing a vital role in the success of many treatments. Studies have identified 150 genetic variants associated with factors including obesity risk, body mass index (BMI), and waist circumference. Still, researchers are puzzled as to which genes work to help some individuals lose weight more effortlessly than others.

The purpose of studying the genetics of weight loss and weight maintenance is to comprehend the underlying biological mechanisms of body weight regulation, research that is necessary to developing more effective medications and intervention strategies.

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

Working Group researchers identified potential weight-loss genetic contributors and areas for future studies, including:

  • Genetic manifestation in individuals: Evidence has determined that while interventions targeting weight loss may not have an effect on overall body weight/BMI, they might improve the distribution of fat, and reduce the risk of cancer or diabetes. This suggests that different types of measurements may be important to understanding the weight loss process.
  • Genetic variants as obesity treatment response predictors: Scientists have discovered genetic variants that make some people more likely than others to succeed with certain treatment methods. As an example, people carrying a specific MTIF3 gene allele may be better suited to weight-loss interventions that involve intensive lifestyle changes like diet and exercise, while those carrying a FTO variation may be more successful in losing weight if they undergo bariatric surgery.
  • Influence of biological systems on physical activity and food intake: Research has shown that epigenetics and the gut microbiome play a role in the long-term effects of weight loss.
  • Genetics and physical activity, food preferences and ingestive behaviors: Studies have shown that particular genes expressed in the brain may lead to a predilection for, and greater intake of, food that is high in calories. Findings from other studies link genes to those who exercise and those who do not, and to better tolerance for and adherence to an exercise plan.

Scientists are still exploring the benefits of integrating existing knowledge on genetics and weight change into clinical practice. For doctors, a better comprehension here could assist in the creation of precision treatments to address weight loss, such as physical activity and diet, as well as other patient-customized methods.

Working Group researchers agreed that more studies are necessary to better understand how precision medicine might lead to novel avenues for treating the obesity 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 Dr. Ruth Loos, FTOS, spokesperson for The Obesity Society and a study co-author.

Dr. Bray concluded, “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.”

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