chapter  11
8 Pages

Leptin and Insulin Resistance in Rodent Models

WithKevin L. Stark

In recent years, the knowledge of the molecular mechanisms controlling body weight has exploded (for a recent review, see Spiegelman and Flier, 2001), due in large measure to the techniques of molecular biology. However, the concept of an endocrine feedback system controlling body fat was presciently suggested in 1953 based upon data from classical experiments (Kennedy, 1953). Since body fat tends to be stable over long periods of time, the proposed regulatory system maintained a balance between energy consumption and expenditure. The presence of a blood-borne hormone released from adipose tissue which sends a negative feedback signal to the central nervous system (CNS) was then confirmed with parabiosis experiments in which animals made hyperphagic and obese by hypothalamic lesions induced dramatic weight loss in normal animals (Hervey, 1958). The application of this parabiosis technique to mouse models of obesity resulted in the identification of strains of mice which genetically lacked either the postulated hormone (ob/ob) or the response to the hormone (db/db) (Coleman and Hummel, 1969; Coleman, 1973). Both strains of mice exhibited hyperphagia, decreased energy expenditure, and early onset obesity.