Coleman and Friedman revealed the existence of the genes involved in the regulation of appetite and body weight, and in so doing discovered a new hormone pathway critical for human pathologies such as obesity.
From their work it is clear that leptin is the hormone made by fat and other peripheral tissues, that acts as a negative feedback signal on the leptin receptor in the hypothalamus in the brain to maintain control of food intake, energy expenditure and the amount of fat that accumulates.
The absence of leptin or its receptor leads to obesity. This pathway also links changes in nutrition to adaptive responses in other physiologic systems. Initially identified in the mouse, this system holds true for humans, and is therefore of obvious clinical importance. The work also resulted in a massive expansion of new research in endocrinology and metabolism, and how these are related to circuits in the nervous system that regulate feeding behavior and energy balance.
This discovery turned opinion from one that obesity was largely a problem of inappropriate behavior to one where it is the consequence of imbalance in a hormone driven process, where appetite is determined by sensitivity to the levels of leptin. Obesity is an increasingly significant burden on healthcare systems, especially with its additional impacts on cardiovascular disease, diabetes and cancer.