Source: iStock/danr13
Source: iStock/danr13

It’s a common New Year’s resolution: exercise more and lose weight. Like many New Year’s resolutions, it often fails, but in this case there’s no scientific reason to doubt the weight-loss benefit of adopting a more physically active lifestyle—even for people who have a genetic predisposition to obesity.

Several studies have suggested that a physically active lifestyle can blunt the effect of inherited obesity genes, but most such studies have had their limitations. They’ve tended to use cross-sectional designs, which produce snapshot views of studied populations, potentially missing temporal relationships. They’ve tended to rely on imprecise self-report measurements of physical activity instead of more precise, rigorous quantitative measures. They’ve tended to emphasize the body mass index (BMI) as an outcome measure, even though it can fail to account for different body compositions. And they’ve tended to neglect populations of non-European ancestry.

To overcome these limitations and produce more compelling results, scientists at McMaster University conducted their own study. Led by David Meyre, Ph.D., associate professor of clinical epidemiology and biostatistics, the McMaster team found that a physically active lifestyle can substantially decrease the genetic effect of the major obesity gene FTO on body weight in a multiethnic population.

The McMaster scientists reported their results January 4 in the journal Scientific Reports in an article entitled, “Physical activity and genetic predisposition to obesity in a multiethnic longitudinal study.” The article describes how the scientists looked at data from 17,423 people from six ethnic groups (South Asian, East Asian, European, African, Latin American, Native North American) who they followed for more than three years.

The researchers indicated that they analyzed physical activity using not only basic (low-moderate-high) measures, but also quantitative measures, specifically the metabolic equivalent (MET) score. In addition, the scientists used both the body mass index and the body adiposity index (BAI) to measure obesity.

“Both basic and quantitative [physical activity] measures attenuated the association between FTO rs1421085 risk allele and BMI/BAI at baseline and follow-up,” wrote the authors. “Our results show that physical activity can blunt the genetic effect of FTO rs1421085 on adiposity by 36–75% in a longitudinal multiethnic cohort.”

“This provides a message of hope for people with obesity predisposing genes that they can do something about it. Our body weight destiny is not only written in our genetic blueprint,” said Dr. Meyre. “These promising results encourage us to investigate how additional lifestyle factors, such as diet, stress, and sleep patterns, may impact the genetic predisposition to obesity.”

In the Scientific Reports article, Dr. Meyre and colleagues noted that their results were consistent with a plausible underlying biological process. They pointed out that FTO is a nucleic acid demethylase, and that FTO intron 1 variation is associated with different methylation profiles and BMI variance. Since methylation of DNA is sensitive to environmental changes (such as physical activity and diet), the scientists reasoned, there is a strong biological rationale to identify GEI with FTO.

“Two studies have shown that [physical activity] can change the methylation and mRNA expression pattern of genes, including FTO, in both muscle and adipose tissue,” the authors detailed. “A more recent analysis demonstrated that variation at the FTO locus represses mitochondrial thermogenesis in adipocyte precursor cells and causes a shift from energy-dissipating beige (brite) to energy-storing white adipocytes, which is accompanied by increased lipid storage and weight gain.”

Exercise training could increase the expression of the brown adipocyte marker uncoupling protein (UCP1) in both visceral and subcutaneous white adipose tissue—changes that are associated with increases in brown-like adipocytes (browning or beiging), particularly in subcutaneous white adipose tissue. “The combined role of FTO and physical activity in obesity and adipocyte browning, in conjunction with epigenetic mechanisms,” the authors suggested, “strengthen the biological rationale and confidence in the statistical interaction.”

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