People with obesity gene can still lose weight

 

People with a gene linked to weight gain are just as likely to benefit from weight loss programmes as those without, researchers have discovered.
The findings suggest diet, exercise and drug-based approaches to losing weight can be widely beneficial, even if some people may have a greater risk of piling on the pounds due to their genetics. In short, your DNA is not a barrier to weight loss.

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While many genes are believed to affect body weight, a particular version of the so-called FTO gene shows one of the strongest associations with fat gain. Those carrying two copies of the genetic variant – about 16% of the population – are on average 3kg heavier than those without, and 1.7 times more likely to be obese.
While it is not known exactly how the genetic variant promotes weight gain, it is believed to increase the appeal of high-calorie foods and reduce the feeling of fullness after a meal. But whether it also affects efforts to shed pounds has been a matter of debate.
“It has become clear that genetics play a part in the reason why some of us get fatter,” said John Mathers, lead author of the research from Newcastle University. “The one that has the biggest effect in most people is the FTO gene, so we wondered whether having the [high-risk version of the] FTO gene would affect how well you could lose weight.”
Writing in the British Medical Journal, Mathers and an international team of collaborators describe how they analysed eight previously published randomised control trials involving a total of more than 9,500 overweight or obese adults to investigate whether carrying the obesity-linked version of the FTO gene affects the ability to lose weight.
In all of the studies, the participants were tested to discover whether they carried the genetic variant, and whether they had one copy or two, but the results were not disclosed to the participants. The researchers found that for each copy of the high-risk gene the participants possessed, they were, on average, almost 0.9kg heavier.
The participants took part in a variety of weight-loss programmes, including diet-based, exercise-based and drug-based approaches. “To our surprise, we discovered that carrying the [high-risk] FTO gene made no difference to your ability to lose weight. So people lost weight at just the same rate if they had the [high-risk version of the] FTO gene as if they didn’t,” said Mathers.
“There was no link between the type of the intervention – so whether the people were losing weight through diet or physical activity – and the gene. It seemed to work equally well.”
Sex and ethnicity, the authors said, did not affect the rate of weight loss, although they noted there was a lack of participants of Asian descent.
The studies, added Mathers, did not show whether carrying the obesity-linked version of the FTO gene affects whether weight loss was sustained, as the longest follow-up time was three years.
Dr Jude Oben, co-founder of the Obesity Action Campaign and senior lecturer in hepatology at University College London, welcomed the results. “Obesity is costing the NHS £16bn a year. We at Obesity Action Campaign are alarmed by this. Obesity causes cancer, diabetes, heart disease and liver cirrhosis. It is the HIV of our age. It is killing millions of our patients,” he said.
“That this size of study and its robust statistical methodologies support common sense is great. It means that general weight loss strategies which must involve the psychological, nutritional, physical and policy changes should be developed.”
Andrew Hattersley, professor of molecular medicine at the University of Exeter and part of the team that discovered the influence of the FTO genetic variant on weight gain, said it was not surprising that those with the variant were as able to lose weight as those without.
“Part of [obesity] is environmental, part of it is genetic, part of the genetic component is the FTO gene,” he said. “This isn’t a group that is remarkably different genetically. It is a very minor change and it is only a minor part of their susceptibility.” 

A number of so-called obesity genes have recently been uncovered. Some researchers have associated these genes with an increased difficulty in losing weight; however, a new review of existing data, published in The BMJ, calls this conclusion into question.

Although a wealth of obesity-related genes have been described, how much difference do they make?

Obesity has increased sharply over recent decades. Globally, an estimated 2.1 billion adults are now overweight or obese.
In the United States, more than one third of adults are obese.
The estimated medical cost of obesity in the United States was $147 billion in 2008.
In the interest of stemming this tide, much research has been plowed into methods of reducing this burden.
As genetic profiling has grown in speed and accuracy, our knowledge of the influence of genes on our bodies has increased in line.
Recent research into the genetics of obesity has uncovered a range of gene loci associated with body mass index (BMI) and the distribution of body fat. In fact, no less than 97 loci have been shown to account for 2.7 percent of variation in BMI.
The obesity-associated FTO gene, MC4R, and TMEM18 have shown the greatest association. And, of those top three, the FTO gene has been found to explain the largest amount of genetic variance in obesity traits.
Individuals with two copies of the FTO minor allele weigh an average of 3 kilograms more and have a 1.7-fold increased chance of being obese, compared with those who have two copies of the lower risk allele.
A number of studies have investigated how carriers of the FTO minor alleles respond to weight loss interventions; however, to date, findings have been contradictory. Because the question carries a great deal of importance for public health, it deserves further study.

Reopening the obesity gene debate

An international team of investigators set out to examine the interaction of the FTO gene with weight loss interventions by reviewing currently available data. In total, the team analyzed almost 10,000 participants who took part in eight randomized control trials.
At the start of the trials, on average, FTO carriers were heavier than their non-FTO counterparts by 0.89 kilograms. The team took note of the participant's body weight, waist circumference, and BMI. These metrics were measured against the type of weight loss intervention, its duration, and the participants' ethnicity, gender, age, and baseline BMI.
By the end of the trials, the researchers found no relationship between the FTO carriers and a reduced ability to lose weight.
The authors conclude that "people who carry obesity risk FTO genotypes respond equally well to weight loss treatment."
Although the authors acknowledge certain limitations of the research, for instance, they only looked at the effects of the FTO gene, they believe that this is "an important finding for the development of effective weight loss interventions in the context of the global epidemic of obesity."

The future of weight loss

The team hopes that the results will increase the "focus on improving lifestyle behaviors, principally eating patterns and physical activity, since these will be effective in achieving sustained weight loss irrespective of FTO genotype."
The research, published this week, is accompanied by an editorial, written by Dr. Alison Tedstone, chief nutritionist at Public Health England. In the article - "Obesity treatment - are personalized approaches missing the point?" - she reminds us that the causes and solutions of obesity are varied and complex, but that the influence of gene profiles does not currently have the backing of evidence.

"Was it ever plausible that the FTO gene would have a noticeable influence on energy imbalance, and hence weight gain, compared with the influence of environmental factors such as food price, availability, and marketing?"

Dr. Alison Tedstone

Dr. Tedstone says that "a rebalancing of research towards whole systems approaches including environmental drivers may be of greater benefit to the population in the long term."
The results can be considered as positive for those who carry the obese genes; weight loss is still very much achievable. Genes certainly do appear to play a part in body shape and weight, but exercise and good diet should still be the primary concern when attempting to lose weight.
Dr. Tedstone rounds off her editorial by noting: "The solutions to the obesity crisis must be societal, as well as individual."
Read more about the discovery of the obesity gene.

Written by Tim Newman