Obesity: in the genes?

Claude Bouchard
, Ph.D.

Scientists studying the causes of human obesity are optimistic about their chances of identifying the genes associated with the predisposition to this disease. Our growing understanding of human gene structure, the similarities of the genes and chromosomes between humans and common laboratory animals, and the availability of a whole variety of tools to study and manipulate DNA are among the most important reasons for the present level of hope in the obesity research community.

How the genes that cause obesity are passed from generation to generation has been considered in a large number of twin, adoption and family studies. Studies have shown that the 'level of heritability' (the risk level for inheriting these genes) depends upon which relatives were used in the research. Recent studies using individuals with a wide range of Body Mass Indexes (BMIs) together with information obtained on their parents, siblings and spouses suggest that the genetic contribution to obesity may be about 25 to 40 percent of the individual differences in body mass or body fat.

It is commonly felt that severely obese people are, on average, about 10 to 12 BMI units heavier than their parents, brothers or sisters. A few studies have reported that a single major gene for high body mass was being passed from the parents to their children. From this small body of data, it seems a major 'recessive' or 'hidden' gene accounts for about 20 to 25 percent of the variance, but these results must be viewed with great caution as the gene(s) has(have) not yet been identified.

The risk of becoming obese.
A number of studies report that obese children have frequently obeseparents. In about 30 percent of the cases, both parents of obese children are obese themselves. It has also been estimated that about 25 to 35 percent of the obese cases occur in families with normal weight parents despite the fact that the risk of becoming obese is higher if the person has obese parents. The level of risk for a firstdegree relative (i.e., a son or daughter) of an overweight person is about two to three times higher than the general population.

It is generally recognized that there are some individuals who are prone to weight gain and for whom losing weight is a continuous battle. On the other hand, there are others who seem relatively well-protected against such a menace. Two experiments to examine whether such differences could be accounted for by genetic factors were conducted. How prone a person is to gain weight when continually exposed to a program that promotes it, or to loseweight under a prolonged program designed to promote loss of weight, was studied. The dependence or independence of these differences on subjects' complete genetic make-ups were also considered.

Twelve pairs of male identical twins* who consumed 1,000 calories more than usual per day, six days per week for 100 days, were studied. Significant gains in body weight and fat were noticed after the overfeeding. There were considerable differences in how each man's body adapted to the excess calories and a definite pattern was seen. For instance, there was at least three times more variance in response between pairs of twins than within the pairs. In other words, two brothers were more likely to respond to overfeeding in similar ways than when one brother from two different sets of twins were compared. The response between identical twin pairs suggests that the amount of fat stored is likely influenced by their body's entire genetic make-up.

In the second experiment, second pairs of young adult male identical twins exercised on cycle ergometers twice a day, nine out of 10 days, over a period of 93 days while being kept on a constant daily energy and nutrient intake. The average body weight loss was five kilograms and it was entirely accounted for by the loss of fat. Similarities were observed for the changes in body weight and body fat within pairs of twins, with about seven times more variance between pairs than within pairs in the response pattern. Even though there were large individual differences in response to the exercise, twins with the same set of genes were more alike in responses than subjects with different genes particularly for body fat loss and energy use. These results are remarkably similar to those of the overfeeding tests.

The complexity of human obesity.
Obesity is complex and is influenced by a variety of social, behavioral andphysical elements. Separation of the genes is not easy and whatever the influence of the gene pool on the development of obesity, it is generally by nongenetic factors. From the research currently available, a good number of genes seem to have the capacity to cause obesity or increase the likelihood of becoming obese. This may be a reflection of how most human obesity comes about. With the advent of a comprehensive human genetic linkage map, linkage studies with a large number of markers covering the complete set of genes in the human body, are likely to be helpful in the identification of obesity genes. The stage is now set for major advances in the understanding of the genetic and molecular basis of complex diseases such as human obesity.

Claude Bouchard PhD was the first Chairman of the Donald B. Brown Obesity Research Chair at Laval University from 1997 to 1999. 

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