Leptin Physiology throughout the Life Cycle of the Frog

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

Leptin, the protein product of the obese gene, is a hormone secreted by fat cells that is integral to food intake regulation in mammals. Leptin signals to the brain information about long term energy balance, and thus influences critical aspects of the life cycle such as growth and reproduction in many species. Additionally, the prevalence of obesity in developed countries in recent years has focused intense interest on leptin and other factors that influence appetite and energy metabolism. Dr. Denver's lab reported the first definitive identification of the obese gene and the functional characterization of leptin in a nonmammalian species, the South African clawed frog, Xenopus laevis. Until now, virtually nothing was known about the biology of leptin outside of mammals. The overall goal of this research is to understand the functions of leptin in a cold blooded species, Xenopus laevis, whose lineage diverged from that of modern mammals over 200 million years ago. The frog has been, and continues to be an important model organism for the study of animal development. Using molecular, physiological and developmental approaches, the major questions to be addressed in this research are: 1) Does leptin play an evolutionarily conserved role in long term energy balance in frogs, and thereby influence critical aspects of the amphibian life history such as metamorphosis, growth and reproduction? 2) Where and when in the frog's body is leptin produced, and where are leptin's major sites of action? 3) Does leptin influence tadpole brain development, alter tadpole growth and the timing of metamorphosis? This project, which will offer unique training opportunities for undergraduate and graduate students, will provide a foundation for understanding the functional evolution of this important vertebrate hormone, and establish the frog as a model system for the study of leptin actions in early development. Basic research on the hormonal control of appetite and feeding is particularly timely given the global concern over the rising incidence of obesity and related disorders in humans.