Living Large: What Mouse Models Reveal about Growth Hormone and Obesity

Abstract

Growth hormone (GH) regulates a broad spectrum of biological processes in addition to promoting longitudinal growth. As such, GH influences most organ and cellular systems in the body with adipose tissue being one of its well-established targets. This chapter will describe mouse lines with specific alteration in GH action. Mice with increased, decreased, and absence of GH action have a unique phenotype for which clinical equivalents exist (acromegaly, GH deficiency, and Laron syndrome, respectively). Interestingly, these mouse lines demonstrate adiposity profiles that are counterintuitive to health and longevity. That is, mice with excess GH action are lean but insulin resistant, prone to cancer, and short-lived (or ``unhealthy lean{''}). On the other hand, mice with no GH action are obese but insulin sensitive, resistant to cancer, and long-lived (or ``healthy obesity{''}). These extremes in GH action provide fascinating mouse strains with which to study the features of fat that are responsible for metabolic dysfunction and to explore traits that are obligatory for cancer or lifespan.