Genetics of human obesity: research directions

Rapid strides in understanding the physiology controlling energy or nutrient intake and energy expenditure have complemented the search for the genetic basis of obesity. Several single gene defects are known that produce obesity in animals. All of these have been cloned within the past 4 years, providing a rich new base for understanding obesity. Since obesity is likely to be "multifactorial," a number of laboratories have used the quantitative trait locus (QTL) technique of genome scanning to identify candidate genomic regions and, eventually, genes that may influence body weight and body fat. So far, 18 QTLs have been identified in association with crossbreeding strains of mice or rats with variable susceptibility to obesity. A number of mendelian disorders are known to exist in humans, but no specific genes have yet been identified for them. The potential for inserting new genetic material into mammals has produced numerous transgenic mice with increased or decreased quantities of body fat. These models will provide a continuing source of new insights into obesity. Several areas in the human genome have been linked to the development of obesity. Among the candidate genes with evidence of linkage to body fat are TNF-alpha, adenosine deaminase, and melanocortin-3 receptor. The new insights described above have invigorated the pharmaceutical industry to increase their efforts for new drug development aimed at the growing problem of obesity.