Obesity Gene Shows No Effect on Weight Loss, Review Suggests

Veronica Hackethal, MD

September 21, 2016

People who carry the fat mass and obesity associated (FTO) gene respond as well as the rest of the population to weight-loss treatments that use diet, physical activity, or medication, according to a systematic review and meta-analysis published online on September 20 in the BMJ.

"We found that the FTO genotype had no detectable effect on weight loss in overweight and obese adults in response to intervention," write Katherine Livingstone, PhD, of Newcastle University, Newcastle upon Tyne, United Kingdom, and Deakin University, Victoria, Australia, and colleagues.

"Importantly, our findings show that the genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through dietary, exercise, or drug-based weight-loss interventions and that those carrying the minor allele respond equally well to such interventions," they add.

Research has shown strong associations between the FTO gene and body mass index (BMI), with the gene's main effect thought to be on decreasing appetite control. People who carry two copies of the gene weigh about 3 kg more and have 1.7 times increased odds of being obese, compared with those who have one copy of the gene, the authors note.

However, the relative contribution of genes and environment to weight loss remains unclear. Over 2.1 billion people worldwide are overweight or obese, so the findings from this study may have important public-health implications.

"Future public-health strategies for the management of obesity should aim to induce long-term improvements in lifestyle behaviors, principally eating patterns and physical activity, since these will be effective in achieving sustained weight loss irrespective of FTO genotype," the authors emphasize.

In the systematic review and meta-analysis, Dr Livingstone and colleagues searched four databases from inception until November 2015 for randomized controlled trials published in English only.

They identified eight randomized controlled trials conducted in North and South America and Europe, which included 9563 participants with a mean age of 51.6 years and a mean BMI of 32.2. Follow-up ranged from 8 weeks to 3 years; only one study evaluated weight-loss medications.

At baseline, individuals who carried one copy of the gene had significantly increased BMI (0.31, P < .001), weight (0.89 kg, P < .001), and waistline circumference (0.63 cm, P < .001), compared with those without it.

However, results showed no overall significant differences in the ability to lose weight based on FTO gene status and type of intervention. Specifically, changes in BMI, body weight, and waist circumference were not significantly different in carriers of the FTO gene who had participated in weight-loss interventions using diet, exercise, or medication, compared with those without the gene.

Further analyses showed that these results were not affected by intervention type, study length, sex, race/ethnicity, or BMI.

The authors discussed several limitations of the study. While research suggests that multiple genes may play a role in obesity and weight loss, the study could not evaluate the effect of other obesity-related genes on weight loss. Also, because studies included mostly white participants, the study could not evaluate differences in weight loss based on FTO carrier status and ethnicity.

In a linked editorial, Alison Tedstone, PhD, chief nutritionist at Public Health England, London, United Kingdom, notes that this study represents a "substantial step toward" unraveling how FTO may influence weight loss.

"The causes of obesity are multiple and complex, but the study by Livingstone et al adds to the evidence suggesting that environmental factors might dominate over at least common obesity-linked genes," she observed.

Understanding how diet and lifestyle interact with genetic predisposition for obesity may help some people, especially those with a rare condition. However, weight-loss interventions based on an individual's genes may not be the answer for the larger population, she explained.

"Given that obesity and poor diet are leading causes of morbidity in Britain, a rebalancing of research toward whole systems approaches, including environmental drivers, may be of greater benefit to the population in the long term," she emphasized. "The solutions to the obesity crisis must be societal, as well as individual."

The authors report no relevant financial relationships. Dr Tedstone reports meeting regularly with charities, academics, food companies, and other commercial interests as part of her work with Public Health England, although she receives no remuneration from these meetings.

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BMJ. Published online September 20, 2106. Article, Editorial

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