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Weight Loss for Obesity Linked to Genetics

In a new study, scientists have revealed that the outcome of treatment for obesity can be affected by a person’s genetic make-up, finding that patients with severe and complicated obesity respond differently to a dietary weight loss programme based on their genes.

In the single-centre prospective cohort study, published in the Journal of Personalized Medicine, the authors highlighted that a better understanding of the influence of genetic factors on the response to lifestyle interventions in people with obesity may allow the development of more "personalised, effective, and efficient" therapeutic strategies.

Alex Blakemore, professor in human genomics at Brunel University London, said: "No-one chooses their genes, so, as a society, we need to recognise that when it comes to maintaining a healthy weight, the challenge is greater for some people than for others."

Finding Contributory Genes a 'Challenge'

The researchers set out to determine the influence of six obesity-related genetic risk scores on the magnitude of weight lost by patients with severe obesity who completed a dietary intervention. 

For the collaboration between University of Galway and Brunel University London, and as part of the GERONIMO project, 93 patients were monitored with severe and complicated obesity who were attending an obesity clinic and taking part in a 24-week milk-based meal replacement programme to try to reverse some of the medical problems with severe obesity. After completing the meal replacement programme, study participants were genotyped to detect the frequency of common risk alleles for obesity and type 2 diabetes-related traits.

Professor Francis Finucane, senior lecturer at the School of Medicine at the University of Galway and consultant endocrinologist at Galway University Hospitals, who led the study, said: "We know that in general, heritability and 'genetics' play a huge role in influencing body weight and the risk of obesity-related complications like diabetes, but finding the genes that account for this risk has been a challenge."

In those participants who were not carrying a known obesity-related gene mutation, 35.5% had diabetes, 53.8% were female, and the mean age was 51.4 years. The average body mass index at the start of the study was 52. After 24-weeks of the meal replacement programme participants lost an average of 16% of their body weight, equivalent to 21 kg. 

Waist-Hip Ratio Genetic Risk Score Influential

The scientists analysed small variations in hundreds of genes known to be associated with obesity, and by combining the gleaned information, calculated a genetic risk score for six different obesity-related traits - body mass index, body fat percentage, favourable adiposity, waist-hip ratio (adjusted for BMI), adiponectin, and type 2 diabetes - for each phenotype.

The researchers discovered that the waist-hip ratio genetic risk score - an individual's genetic tendency to hold on to central or abdominal fat - was associated with less weight loss after the intervention. However, there was no evidence of influence from the five other obesity-related genetic risk scores on the response to dietary restriction.

"The waist-hip ratio genetic risk score was inversely associated with percentage total weight loss at 24 weeks, and patients in the lowest tertile of waist–hip ratio genetic risk score lost more weight," reported the authors. They added that the inverse association between waist-hip ratio genetic risk score and weight loss persisted after adjusting for age, sex, and diabetes medication usage.

This suggested, they surmised, that "people with severe obesity who have a genetic tendency to store fat centrally respond less well to intensive dietary restriction".

Professor Blakemore conjectured that the study revealed "just a small part of the picture" of how genes can help or hinder in reaching health goals.

However, he emphasised that: "Mechanistic studies like these, which help us to understand why some people respond better than others to the same intervention, are really important in providing more personalised and effective treatments for people with obesity."

Dale Handley and Hasnat Amin receive financial support from the College of Health, Medicine, and Life Sciences at Brunel University London, UK. Sumaya Almansoori was funded by the Ministry of Higher Education, United Arab Emirates. Francis Finucane was funded by a Clinical Research Career Development Award from the Saolta University Healthcare Group and by a CURAM project grant from Science Foundation Ireland. The authors declare no conflict of interest.