Understanding adipose tissue development from transgenic animal models

Abstract

The World Health Organization has recognized obesity as a health problem of pandemic proportions. Recent work led to major breakthroughs in the understanding of the molecular basis of adipose tissue development with the cloning and characterization of numerous genes involved in fat cell differentiation and metabolism. Transgenesis has proved very useful in establishing the physiological roles of these genes. Here we review transgenic models made to study adipose tissue's metabolic and trophic responses. Genetic modifications unexpectedly associated to alterations of adipose tissue development are also examined because of their potential involvement in obesity and energy balance regulation. After a description of the methodologies commonly used, we review the data obtained on transcription factors, metabolism, signal transduction, secreted products, and models of lipodystrophy. An overview of such integrative studies leads to a better understanding of the physiology of adipose tissue development.Alterations in expression levels of proteins involved at different steps of a regulatory pathway highlight the complementary roles of genes in the regulation of adipose tissue development. However, lack of phenotypes also illustrates the capacity of animals to set up adaptive mechanisms.

Keywords

• fat cell
• obesity
• gene invalidation
• additive or random insertional transgenesis
• targeted transgenesis