Genetic Variants Influence Waist Circumference Regain after a Weight Loss

Posted on 06.02.2024

Nearly all individuals who intentionally lose weight experience weight regain – but a recent study finds that some people are genetically predisposed to regain more weight around the waist after a weight loss.

Obesity is a major contributor to the worldwide increasing incidence of type 2 diabetes, but maintaining weight loss is hard – and for some more than others.

A recent study found that people with a genetic predisposition for abdominal adiposity regained more weight around their waist after a weight loss than other people.

The study, Abdominal Obesity Genetic Variants Predict Waist Circumference Regain After Weight Loss, was published in Diabetes in October.

The article’s first author is Malene Revsbech Christiansen, who finished her PhD last June with a grant from the former Danish Diabetes Academy.

Advancing the Understanding of Genetics and Weight Change

Having an article published in Diabetes is no small feat. The journal has existed since 1952, and it maintains a high impact factor. It is one of the biggest journals in its field.

I am very honored and proud that Diabetes accepted our study. It was a lot of work, and it is gratifying to see our work published in such an esteemed journal. By publishing in Diabetes, I hope that our findings can reach a broad audience who can use them to advance the field of genetics and weight change,” says Malene Revsbech Christiansen.

The study aimed to discover whether the genetics of obesity traits (abdominal and overall obesity) influence weight regain after weight loss, and thereby potentially explain why it is more difficult for some people to maintain weight loss over time.

“Our co-author, Associate Professor Jeanne McCaffery, led a previous meta-analysis study to which we contributed. This meta-analysis explored whether genetic variants could influence weight loss in short- and long-term weight loss interventions. As the findings were promising, showing that variants associated with abdominal obesity were associated with weight loss, we decided to take this to the next level and look at the recurring issue of weight regain which affects up to 80 % of people who previously lost weight,” explains Malene Revsbech Christiansen.

New Strategies for the Obesity Pandemic

It is widely known that genes associated with fat deposition are different from the ones associated with overall obesity, and Malene and her co-authors made some new findings on the genetic effects of abdominal obesity.

The study found that people with a genetic predisposition for abdominal adiposity regained more weight around their waist after a weight loss than other people.

“We were quite amazed to find that only the genetic background of waist circumference adjusted for BMI, an indicator for abdominal fat, seemed to influence weight change. This finding was consistent across all our sensitivity analyses. We did not find any influence from the variants associated with overall adiposity on weight regain or weight loss. This leads us to our next research question: which pathways are affected by these abdominal fat variants and how do they differ from those involved in overall obesity? We hope that by uncovering the mechanisms at work in adipose tissue during weight change, we may find potential targets for preventing weight regain,” says Malene Revsbech Christiansen.

As ‘genetic profiling’ in medicine becomes more viable and more affordable, Malene and her co-authors hope that their findings might be a catalyst to help people who possess these genetic variants maintain their weight loss.

Many people are successful in losing weight. However, as the majority tend to regain weight within 5 years, these efforts can seem futile. I hope our findings can guide future research on the prevention of weight regain after weight loss. By doing so, I hope to contribute to potential strategies for addressing the obesity pandemic,” says Malene Revsbech Christiansen.

The Look AHEAD trial

Malene and her co-authors used data from the Look AHEAD trial – a massive study with data from more than 16 centers in the US and involving almost 5,000 participants who were followed up for 9.6 years on average.

“It is important to note, however, that all participants of the Look AHEAD trial had type 2 diabetes and obesity, and the average age was 60 at the start of the intervention.  Given these demographics, it would be interesting to replicate our findings in a diverse study population,” explains Malene Revsbech Christiansen.

Malene Revsbech Christiansen did her PhD in genetic epidemiology with the Kilpeläinen group at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen.

She is currently a postdoctoral fellow in the Kilpeläinen group.

Publication

Abdominal Obesity Genetic Variants Predict Waist Circumference Regain After Weight Loss

Malene Revsbech Christiansen, Tuomas O. Kilpeläinen, Jeanne M. McCaffery
Diabetes 2023;72(10):1424–1432
https://doi.org/10.2337/db23-0131

Contact Information

Malene Revsbech Christiansen
Postdoc, Kilpeläinen group at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen
malene.christiansen@sund.ku.dk

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