Diet and Exercise Work Despite Genetic Obesity Risk


Obese and overweight individuals with genetic risk factors for obesity respond as well as anybody else to diet and exercise, according to a meta-analysis of clinical trials evaluating weight-loss interventions.

In trial participants with the high-risk FTO (fat mass and obesity associated) genotype, changes in body-mass index (BMI), body weight, and waist circumference with interventions were not significantly different from participants with the low-risk genotype, reported John Mathers, PhD, of Newcastle University in the United Kingdom, and colleagues.

Previous research has shown that individuals with the high-risk FTOgenotype weigh 3 kg more on average and have a 1.7-fold increased odds of being obese compared to those with the low-risk genotype, Mathers and colleagues noted in The BMJ.

Across eight weight-loss trials including more than 9,500 participants, the mean difference in BMI between high-risk and low-risk individuals at the end of each trial was -0.02 (95% CI -0.13 to 0.09; P=0.69), the study found.

The mean difference in body weight was -0.04 kg (95% CI -0.34 to 0.26; P=0.78) and the mean difference in waist circumference was -0.06 cm (95% CI -0.43 to 0.31; P=0.75), Mathers and colleagues reported.

“We found that the FTO genotype had no detectable effect on weight loss in overweight and obese adults in response to intervention. Importantly, our findings show that the genetic predisposition to obesity associated with theFTO 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,” Mathers and colleagues said.

“Moreover, our results suggest that screening for the FTO genotype in routine clinical work would not predict weight loss success,” the investigators said.

One of England’s top nutritionists, Alison Tedstone, PhD, of Public Health England, agreed with that assessment in an editorial. “At least for FTO, genes do not appear to affect our ability to lose weight,” Tedstone wrote.

She added that the meta-analysis “adds to the evidence suggesting that environmental factors might dominate over at least common obesity-liked genes.

“If we are to turn back the tide of obesity, an understanding of how diet and lifestyle interact with the genome might help some people, particularly those with rare conditions that cause devastating levels of weight gain in early life,” Tedstone said. “It is increasingly evident, however, that the idea that personalized interventions based on the genome will yield population benefit may not pay off, at least in the short term.”

The eight studies included in the meta-analysis were randomized, controlled trials of weight loss interventions in overweight or obese individuals (BMI of 25 or higher) that reported changes in body mass, body weight, or waist circumference by FTO genotype. The interventions included diet, exercise, drugs, or some combination of the three. The shortest trial was 8 weeks and the longest trials were 3 years.

The current meta-analysis expands on another published earlier this year in the American Journal of Clinical Nutrition, Mathers and colleagues noted. However, “Unlike Xiang et al, we included only randomized controlled trials, which provide stronger evidence than non-randomized trials and limited within-study bias and between-study heterogeneity,” the investigators wrote.

The current meta-analysis included two major studies, Look AHEAD and the Diabetes Prevention Program, which together contributed 67% of the total sample. “Independently, neither study identified any association between FTOgenotype and weight loss, which was consistent with parallel and pooled analysis of both studies and with our overall findings. In our sensitivity analyses, omission of the largest study (Look AHEAD) did not change the pattern of results,” Mathers and colleagues said.

An important limitation of the study is that it evaluated the effect of FTOgenotype only, the investigators noted. “Given that obesity risk and weight loss is influenced by multiple genes, the effect of other obesity related genes, such as MC4R and TMEM18, on weight loss in response to intervention remains to be determined,” they said.

The study was funded by an Alfred Deakin postdoctoral research fellowship and the U.K. Department of Health.

Mathers and Tedstone reported no financial relationships with industry.

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