This preview shows pages 1–2. Sign up to view the full content.
This preview has intentionally blurred sections. Sign up to view the full version.View Full Document
Unformatted text preview: Leptin at 14 y of age: an ongoing story 14 Jeffrey M Friedman ABSTRACT The cloning of the ob gene and its gene product leptin has led to the elucidation of a robust physiologic system that maintains constancy of fat stores. Leptin is a peptide hormone secreted by adipose tissue and regulates adipose tissue mass and energy balance. Recessive mutations in the leptin gene are associated with massive obesity in mice and in some humans, which establishes a genetic basis for obesity. Leptin circulates in blood and acts on the brain to regulate food intake and energy expenditure. When fat mass decreases, plasma leptin concentrations decrease, which stimulates appetite and suppresses energy expenditure until fat mass is restored. When fat mass increases, leptin concentrations increase, which suppresses appetite until weight is lost. This system maintains homeostatic control of adipose tissue mass. Am J Clin Nutr 2009; 89(suppl):973S9S. INTRODUCTION The cloning of the ob gene and hormone leptin has led to several new insights. The identification of leptin has uncovered a new endocrine system regulating body weight. This system provides a means by which changes in nutritional state regulate other physiologic systems. A number of leptin deficiency syn- dromes that are treatable with leptin replacement have been identified. The majority of obese subjects are leptin resistant, which establishes that obesity is the result of hormone re- sistance. Leptin treatment results in weight loss in a subset of obese patients and can also synergize with other antiobesity agents to reduce weight. Leptin provides an entry point for studying a complex human behavior. Finally, there is a powerful biological basis for obesity, a fact that is (correctly) changing public perception about this medical condition. The ob gene was cloned in 1994, and leptin was identified in 1995 as the product of the ob gene and a hormonal signal that regulates energy balance (14). The passage of nearly 15 y of research and 26,880 articles on leptin provide an opportunity to assess, with some hindsight, what has been learned in the interim (S Korres, personal communication, 2008). What follows is an attempt to do sowith relevant conclusions that have emerged from the cloning of the ob gene and the discovery of leptin. CLONING OF THE ob GENE AND IDENTIFICATION OF LEPTIN The first law of thermodynamics applies similarly to inanimate and biological systems. The elaboration of this principle by the Prussian surgeon Hermann von Helmholtz and others made it clear that, to explain the striking stability of weight in living organisms in a stable environment, organisms would need a means for main- taining a constancy of energy stores (5). For example, a remarkable stability of weight has been noted in patients monitored over long periods of times considering the large numbers of calories con- sumed in that interval. In addition, a precise balance between energy intake and energy expenditure has been noted over even a 2-...
View Full Document
This note was uploaded on 04/21/2011 for the course BIO 105 taught by Professor Staff during the Winter '08 term at Grand Valley State University.
- Winter '08