Exercise, genetics and the fat gene

According to the World Health Organization, after high blood pressure, tobacco use and high blood sugar, physical inactivity is the fourth leading risk factor for global mortality. So it’s fitting a physically active lifestyle is promoted in global public health policies. But does physical activity confer the same benefits on everyone to the same extent?

In the early 1990s, five universities in the United States and Canada recruited 90 Caucasian families and 40 African-American families – including both parents and three or more biological adult offspring – to the Heritage Family Study. The study investigated the role of genetics in the cardiovascular, metabolic and hormonal responses to the same 20-week programme of aerobic exercise the families undertook.

Although age, sex and race had a minimal impact on the training responses, researchers noted in a 2007 report in the American Journal of Epidemiology that there are "marked inter-individual differences in the response . . . to regular exercise, and these differences are not randomly distributed but clearly aggregate in families."

For example, the heritability estimates for changes in cardiovascular and diabetes risk following a programme of endurance training ranged from 20 to 60 per cent.

And, this year, a review in the journal Sports Medicine concluded: "Shared familial factors, including genetics, are likely to be a significant contributor to the response of body composition and cardiorespiratory fitness following physical activity."

The study's lead author, Joshua Zadro, is a physiotherapist and PhD candidate at the University of Sydney, with an interest in researching the relationship between genetics, physical activity and low back pain.

"The results of our study demonstrate that our genes influence how well our bodies respond to increased physical activity," he told The Irish Times. "Moreover, our genes play a larger role in dictating changes in our body composition after a diet and exercise programme – such as our weight, body mass index, or percentage of body fat – compared to how our fitness changes after an exercise programme.

“This means some individuals who are physically active and have a calorie-restricted diet may not demonstrate significant improvements in their body composition or fitness, with genetics potentially being to blame for these disappointing results.”

FTO gene

With genetics playing an important part in exercise, what is the role of the recently identified fat mass and obesity-associated gene (FTO) in shaping our response? A leading Irish researcher is part of a team investigating the impact of personalised nutrition advice on healthy eating and lifestyle in the Food4 Me study.

Eileen Gibney, a lecturer/assistant professor in nutrition in the UCD Institute of Food and Health, and School of Agriculture and Food Science, explained what is meant by the so-called obesity gene."The term refers to variations within our genetic make-up that may predispose an individual – and by this I mean make someone more susceptible to to obesity."

Dr Gibney said that for certain diseases, the variation and incidence of the disease is direct. For example, with cystic fibrosis a defect in one gene causes one disease. Obesity, however, is caused by many factors that vary from one individual to another.

“With respect to obesity,” she said, “there are some genetic variations, which are rare but do have a direct impact on risk of obesity. Take, for example, the metabolism of leptin, a hormone secreted by our fat cells, and which influences weight control. However, most other obesity-associated genetic variations so far discovered are more subtle, and present a ‘risk’ that is small.”

Ongoing research in may reveal more variations within our genes that are potentially obesity-associated,” she said. “If we can bring these all together, then together they may explain some of the risk of obesity. But it is important to note this is a risk or risk of increased predisposition; it is not a determinant. So it’s not as if obesity is unavoidable. It may simply mean you need to work harder; exercise more and be more vigilant with your diet. Even individuals with a genetic predisposition to obesity can and should maintain a healthy weight through healthy eating and exercise.”

Food and genetics

The emerging field of “nutrigenomics” investigates the relationship between food and genetics, with a view to devise diets based on an individual’s genetic profile.

Dr Gibney is one of a team of international experts engaged in the European Food4Me project, which aimed to explore the applications of personalised nutrition. She was co-author of a recent Food4Me study published in the journal Obesity, which investigated the effect of physical activity levels on obesity traits among European adults with a variant of the FTO gene.

"Within the Food4Me study, over 1,600 individuals across Europe took part in a six-month personalised nutrition study," she said. "One area of investigation, led by Drs Celis-Morales and Marsaux, was to examine the FTO gene, where there is a known variant associated with risk of obesity. By this we mean that if someone has this specific genetic variant, they are more likely to be overweight than someone without this variation."

Researchers within the Food4Me team measured physical activity in the study group and allocated these individuals into three groups: low, medium and high.

“Drs Celis-Morales and Marsaux then looked to see if there was a difference in weight/obesity in each of these groups between those who had the genetic variant or not,” she said. “They showed in the low-exercise group that those with the FTO variant were more obese than those without, as expected. But in the high-exercise group there was no difference in obesity between those with the risky genetic variation and those without.

“This means that being active – as recommended in many healthy eating and lifestyle campaigns – removed the risk of obesity.”

With the World Health Organization implicating physical inactivity in 21-25 per cent of cases of breast and colon cancer, 27 per cent of diabetes and 30 per cent of ischaemic heart disease, there is no doubting the importance of exercise, irrespective of one’s genetic profile.