ABSTRACT
The World Health Organization recently estimated that 1.4 billion people in the world are overweight and over 500 million of them are obese.1 Epidemiological data indicate that obesity is associated with premature death through increased risk from chronic disease.2-4 Obesity is the product of a chronic positive energy balance, and the resulting accumulation of excess adipose tissue is strongly linked to disordered lipid metabolism, development of insulin resistance, and a cluster of comorbidities called the metabolic syndrome. Obesity is viewed as the seminal event in disease progression, but the underlying mechanisms that link development of obesity to metabolic disease are less well understood. This is partly because of the chronic nature of the progressive deterioration in responsiveness of multiple, highly integrated organ systems to endocrine signals, which function to compartmentalize substrate utilization and maintain energy balance. However, given the growing impact of obesity on public health and the recognition that obesity is a precipitating event in the development of essentially all forms of metabolic disease, coordinated efforts of scientists from around the world have been devoted to understanding the genes, molecules, and systems biology involved in energy homeostasis.
