Most of the public, including doctors believe people are overweight
because they eat too much, eat the wrong foods, and exercise too little.
But there may be other reasons. Can people be genetically predisposed
to weight gain? Can one’s metabolism affect weight gain? Can drugs
or the environment change one’s metabolism and cause weight gain? The
links presented here may contain some useful answers to these questions.
Obesity and Genetics
Obesity as a major public health problem
Obesity is an increasingly important health problem in the United States and also worldwide. The rates of obesity (defined as body mass index (BMI) > 30.0) have nearly doubled in the U.S. population from approximately 15 percent in 1980 to an estimated 27 percent in 1999 (1). Although our society has made great strides in reducing other threats to health such as smoking, we have been unable to stem the rising tide of obesity in the population. This trend is particularly disturbing because obesity is central to the development of many chronic diseases such as type 2 diabetes, heart disease, hypertension and cancer. Clearly, the increase in rates of obesity is a matter of major public health concern.
Obesity as a complex metabolic condition
Obesity is characterized by an excessively high amount of body fat or adipose tissue. This condition is common, but the condition varies from individual to individual. At one end of the spectrum, a healthy weight can be attained by cutting down on certain foods, taking smaller portions, and embarking on a regimen of regular exercise. For individuals in this population, a moderate change in diet and exercise are the proper interventions because they work.
At the other end of the spectrum, there is another population of overweight people who do not respond as well to these interventions. Everyone knows someone who tries diligently to lose weight but who experiences limited success or loses weight only to gain it back over time. In fact, more than 80% of those who lose weight will gradually regain it unless a weight maintenance program is implemented over the long-term (2). What is different about these people compared to those who either stay thin or lose weight readily and keep it off with relatively minor lifestyle changes? One difference may be genetic risk factors that affect energy metabolism and result in an inborn susceptibility to gain weight.
Genetics as a risk factor for obesity
Obesity is a condition that results from an environment of caloric abundance and relative physical inactivity that is modulated by a susceptible genotype. Although rare obesity syndromes caused by mutations in single genes have been described, by far the greatest proportion of obesity in humans is not due to mutations in single genes. Genetic predisposition may not be health destiny, but studies indicate that inherited genetic variation is an important risk factor for obesity. Evidence from twin, adoption and family studies strongly suggests that biological relatives exhibit similarities in maintenance of body weight. Genetic factors also are beginning to be implicated in the degree of effectiveness of diet and physical activity interventions for weight reduction.
These genetic risk factors tend to be familial, but are not inherited in a simple manner; they may reflect many genetic variations, and each variation may contribute a small amount of risk and may interact with environmental elements to produce the clinical condition of obesity. An active area of research is determining associations between various obesity-related phenotypes with variations in candidate genes or through linkage studies with anonymous markers spread over the human genome. Learning how genetic variations affect susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and, hopefully, how better to prevent and treat this condition.
You can’t change your genes, but you can change your behavior
Does this mean that those with a susceptible genotype are destined to a life of futile efforts to achieve a healthy weight? This need not be the case. We can’t change our genes, but we can change our behavior. Small victories in weight loss—often as little as 10% of total body mass--can result in positive effects on health and well-being, even if an ideal weight remains elusive. Also, the positive effects of regular physical activity include lower blood pressure and increased cardiorespiratory fitness' even in people who are significantly overweight. In the longer term, understanding the genetic variations that influence energy metabolism may help us to understand the underlying biological factors that affect weight gain and energy expenditure and develop interventions that capitalize on these insights. Finally, to recognize that obesity may be due to a metabolic condition rather than a flaw in character is important both for the people who are affected and for society as a whole.
The public health messages to prevent overweight emphasize a nutritious diet and daily physical activity. Many who follow this advice from the outset are able to maintain a healthy weight, even with a genetic susceptibility to gain weight. However, these lifestyle interventions have a range of uptake and effectiveness, especially if obesity is already present. For people who are already overweight, the public health interventions aimed at the general population are not a complete solution. Insights from genetics and molecular biology in controlling appetite and activity may provide more effective drug therapies for treatment of affected individuals. As we continue to emphasize the importance of diet and exercise as major factors that affect long-term health, public health needs to also seek new approaches—such as considering genetic factors in risk factor assessment and intervention design--to more thoroughly address this complex problem.