Genetics

Body size is determined by both genetic and environmental factors. Genetic background may explain 40% or more of the variance in body mass in humans. The genetics of obesity are complex and likely involve the interaction between multiple genes. Through a number of studies, over 250 genes, markers, and chromosomal regions have been identified and associated with human obesity. The clinical importance of these associations is still under investigation. In rare cases, monogenic causes of obesity have been identified in humans. These mutations include the genes for leptin, leptin receptor, prohormone convertase, proopiomelanocortin, melanocortin-4 receptor, and SIM1. While these rare mutations have not provided a solution to the obesity epidemic, they have been critical to enabling our understanding the etiology of the disorder.

It is highly unlikely that the increase in prevalence of obesity in the past 20 years can be attributed to genetic changes. It is much more likely that this is the result of environmental influences. The most likely cause of the obesity epidemic is a combination of the increase in energy intake coupled with a decline in physical activity. In recent years, there has been a greater availability of highly palatable and convenient food. In addition, more meals are eaten outside the home and serving sizes are generally larger. At the same time, a large portion of the population has decreased daily physical activity due to sedentary work and social activities as well as a proliferation of mass and individual motorized transportation. When placed in a modern lifestyle, individuals with susceptible genetic backgrounds are particularly predisposed to increased adiposity. Perhaps the best studied example is the Pima Indians. Those Pima Indians, who live in the Sierra Madre mountains of northern Mexico, eat a traditional diet with 15% of their intake as fat. They also labor at physically demanding occupations such as farming or working in a sawmill. On the other hand, the Pima Indians living in Arizona, US, are much more sedentary and eat a high-fat diet, consisting of 50% of their calories as fat that is provided by government surplus commodities. The latter environment has led to a dramatic increase in obesity and diabetes within this Indian population. Similar examples have been described in the aboriginal population of northern Australia and in natives of Papua New Guinea. Urbanization of these populations has also led to a dramatic increase in obesity, type 2 diabetes, and hypertriglyceridemia.

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