New research from the UK suggests that living an active lifestyle can reduce people’s genetic predisposition to obesity by about 40 per cent, challenging a popular view that exercise doesn’t help people lose weight if they are genetically predisposed to obesity.

The study was the work of senior author Dr Ruth Loos, group leader in Genetics in the MRC Epidemiology Unit at the Institute of Metabolic Science, based at Addenbrooke’s Hospital in Cambridge, and colleagues, and was published online on 31 August in the journal PLoS Medicine.

Among the factors driving the worldwide obesity epidemic are a shift in diet as we eat more energy-dense foods high in fat and sugar, particularly in more westernised societies, and a tendency to be less active as our lifestyles become more and more sedentary.

However, scientists believe genes also play a role in that people with such a predisposition who live in an environment with easy access to labour-saving devices and energy-dense foods tend to be more prone to obesity.

Loos and colleagues wrote that while previous genetic studies have shown that a number of genes increase susceptibility to obesity, this is the first to examine the effect of a physically lifestyle on such a predisposition.

So far, recent genome-wide association studies have found 12 DNA variants or “snips” (SNPs, short for single-nucleotide polymorphisms), that are linked to increased BMI.

BMI is short for body mass index, which equals a person’s weight in kilos divided by the square of their height in metres. A BMI of 25 to 29.9 is classed as overweight, and a BMI of 30 or more is classed as obese.

For their study, Loos and colleagues looked for these same 12 variants in the genomes of over 20,000 people aged 39 to 79 years who were taking part in the European Prospective Investigation of Cancer (EPIC)-Norfolk study.

They worked out a “genetic predisposition score” for each person depending on how many of the 12 SNPs they found in his or her genome.

As part of the EPIC study the participants had filled in questionnaires about their lifestyle and from their responses the researchers were able to calculate how physically active each participant was.

They then used statistical models to look at how the interaction between the genetic predisposition scores and physical activity linked to BMI and obesity risk, assuming an “additive effect” for each “snip” or DNA variant.

The results showed that each additional BMI-increasing snip was linked to a 0.154 increase in BMI (equivalent to 445g or 1 lb in body weight for a person who is 1.70m or 5 ft 7 in tall).

However, the link was much stronger in inactive people than in active people (0.205 vs 0.131 increase in BMI per snip respectively, translating to an equivalent of 592 g per snip and 379 g per snip respectively for a 1.70 m tall person).

A similar pattern was found in obesity risk: taking the population as a whole, each snip increased the odds of obesity by 1.116-fold, but in physically inactive people, each snip increased the odds of obesity by 1.158-fold, whereas in their physically active counterparts, each snip only increased the obesity risk by 1.095-fold, representing a 40% lower increase.

The researchers also confirmed these cross-sectional observations (ie data based on a “single snapshot” of participants’ lives) by looked at trends over time, and established that over an average follow up of 3.6 years, “physical activity modified the association between the genetic predisposition score and change in BMI”.

Loos and colleagues concluded that, basing the estimates on how many of the known 12 recently identified “snips” people carry, living a physically active lifestyle is linked to a 40 per cent reduction in the genetic predisposition to common obesity.

These findings suggest that while increased physical activity benefits everyone in terms of reducing obesity risk, it would seem that the genetically predisposed benefit even more, challenging a widely held popular view that if you have obesity-related genes then there is no point in doing exercise because you will become obese anyway.

“Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study.”
Shengxu Li, Jing Hua Zhao, Jian’an Luan, Ulf Ekelund, Robert N. Luben, Kay-Tee Khaw, Nicholas J. Wareham, Ruth J. F. Loos.
PLoS Med 7(8): e1000332, Published online 31 August 2010.
DOI:10.1371/journal.pmed.1000332

Written by: Catharine Paddock, PhD