Staying Trim When Fat Runs in the Family
Just in time for Thanksgiving, a major new study offers some hopeful news about fat and fate, as well as about the consequences of the choices we make.
For the research, investigators tallied the results of dozens of studies about the effects of exercise on the so-called fat gene, which is believed to increase the risk that carriers will be overweight or obese by 12 percent or more. Scientists first identified this gene, called the "fat mass and obesity-associated" gene, or FTO gene, several years ago, and as it turns out, itís distressingly common. By most estimates, about 65 percent of people of European or African descent and perhaps 44 percent of Asians carry some version of the FTO gene.
These findings would seem to suggest that most of us are doomed to be tubby, an enervating idea ó and one that may even be self-fulfilling. In a study published in the New England Journal of Medicine, volunteers who learned that they carried the FTO gene or similar fat-promoting genes frequently turned afterward to heedless binging, consuming more fatty foods in the next 90 days than they had in the preceding months, presumably because they believed that their fate, at least in terms of weight, was sealed.
But the new report, published this month in the journal PLoS Medicine, emphatically suggests otherwise. It found that physical activity, even in small doses, may subvert genetic destiny.
"Soon after FTO was discovered in 2007, studies showed that physical activity attenuates" the effect of the gene on body weight gain, said Ruth Loos, a program leader at the Institute of Metabolic Science in Cambridge, England, and senior author of the study. "However, these were followed by studies that could not convincingly confirm this interaction or that did not find an interaction at all."
Hoping to reduce the scientific confusion about the role that exercise might play in the geneís activity, she and her colleagues contacted the studiesí many authors in the United States and Europe and asked them, as a professional courtesy, to reanalyze their data. They suspected that part of the reason for the varying results was that individual research teams had employed widely different methods to quantify and define physical activity levels. So for the most part they defined what constitutes a physically active person as someone who engaged in at least an hour of moderate to vigorous physical activity per week.
Even by this very generous standard, only 25 percent of the 218,000 FTO carriers who had been studied in the various experiments to date qualified as active.
But those people, the newly reanalyzed data showed, had managed to partly thwart their genetic heritage. Being physically active, in the new analysis, "reduced the effect of FTO by about 30 percent," Dr. Loos says. While that still leaves 70 percent of the potentially fat-encouraging effect of the gene intact, she adds, the consequences of physical activity on the workings of this single gene seem to be substantial enough to perhaps allow someone who otherwise would become seriously overweight to maintain a normal waistline.
Scientists still donít understand how the FTO gene promotes weight gain, although they suspect that it affects appetite and behavior. "Though there are only limited functional data, it appears that the gene is highly expressed in the brain," says Dr. Lu Qi, an assistant professor in the department of nutrition at the Harvard School of Public Health and one of the dozens of scientists who agreed to re-examine his past data for this new analysis. It is especially active in "the regions that regulate the balance of energy intake and expenditure," he continues. "The loss of energy balance is the basis of development of obesity."
By implication, physical activity may have countervailing effects in the brain and on energy output. "Physical activity is among the most important parts of energy expenditure," Dr. Qi says. "Biologically, it is possible these two factors, genes and physical activity, may interact in affecting energy balance."
Itís also possible that exercise might directly change how the FTO gene works, altering whether it expresses certain proteins or remains quiet. But all such explanations are "speculative" at the moment, Dr. Loos says, and require more experimentation.
Already, though, the implications of the new analysis are guardedly encouraging. "Often people feel that obesity runs in the family or that obesity is in their genes, and therefore feel they have no control over their weight issues," Dr. Loos says. "Our study shows that physical activity plays a role in weight control, even in those who are genetically predisposed."
And the amount of activity required seems to be slight, she adds. "You donít have to run marathons or work out in the gym," she says. "Walking the dog, cycling to work, weeding the garden ó those all count" and should help to counter the FTO geneís effects.
"We hope," Dr. Loos concludes, "that our message empowers people who may have given up hope to try to control their weight."
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