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4 - OBESITY: NEW MECHANISMS AND TRANSLATIONAL PARADIGMS

Published online by Cambridge University Press:  04 April 2011

By
Gregory Gaich  and
David E. Moller
Edited by
Bruce H. Littman  and
Rajesh Krishna
Gregory Gaich
Affiliation:
Eli Lilly & Co.
David E. Moller
Affiliation:
Eli Lilly & Co.
Bruce H. Littman
Affiliation:
Translational Medicine Associates
Rajesh Krishna
Affiliation:
Merck Research Laboratories
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Summary

Introduction

Medical Need and History of Failure

From 1985 through 2005, the prevalence of obesity doubled in the United States. In 2005, only four states had obesity prevalence rates less than 20%, whereas 17 states had prevalence rates of at least 25%, with several exceeding 30% (Centers for Disease Control and Prevention's [CDC's] Behavioral Risk Factor Surveillance System [BRFSS]). Obesity is a growing health epidemic outside the United States as well. Conditions of overweight and obesity are the sixth most important risk factor contributing to the overall global disease burden. According to the International Obesity Task Force and the World Health Organization (WHO), globally more than 1.7 billion adults are overweight, including more than 312 million who are obese. The disease burden of excess adiposity contributes to increased risk of additional diseases, including hypertension, type 2 diabetes, atherosclerosis, osteoarthritis, and some cancers.

Lifestyle interventions are the first-line treatments for obesity, yet this precipitous increase in the prevalence of obesity has occurred despite many years of lifestyle intervention as the primary mode of therapy. The underlying reason may be that survival is dependent on avoiding a negative energy balance, and both eating and activity behaviors required to maintain a neutral or positive energy balance are regulated by hundreds of genes in scores of biochemical and neural pathways. The active regulation of energy balance of both energy intake and energy expenditure is extremely precise with the average adult maintaining energy balance to within 0.3% over several decades.

Type
Chapter
Information
Translational Medicine and Drug Discovery , pp. 89 - 114
Publisher: Cambridge University Press
Print publication year: 2011

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