Obesity Therapeutics Prospects and Perspectives

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David M. Duhl and Rustum S. Boyce Chiron Corporation, Emeryville, CA 94608

Introduction - The prevalence of obesity is rising at an alarming rate. When measured by Body Mass Index (BMI = weight in kilograms divided by the square of height in meters), a BMI of 30 is the threshold for obesity. In the United States alone, an analysis of the National Health and Nutrition Examination Survey (NHANES IV) data from 1999-2000 found that the age-adjusted prevalence of obesity was 30.5% and had increased by approximately 8% in just 5 years (NHANES III 1988-1994) (1). This shocking increase in obesity has been mirrored to varying degrees throughout the world.

Obesity is often mischaracterized as a cosmetic, or life style issue when in fact it is a devastating disease with tremendous health and financial consequences. In the US alone, it has been estimated that there are greater than 300,000 deaths per year (2). This distressing effect on life expectancy is largely related directly to the life threatening co-morbidities of obesity such as non-insulin-dependent diabetes, hypertension, coronary artery disease, and some forms of cancer (3). The less lethal comorbidities associated with obesity include gallstones, osteoarthritis, degenerative arthritis, and apnea. The financial consequences of obesity can be measured in multiple ways; as a total cost to society (direct and indirect), estimated percent of total medical cost, and direct value of obesity related medications (4-6). Whichever parameter is chosen to measure the financial impact of obesity, the cost is highly significant to our society.

Regulation of Obesity Through Multiple Integrated Pathways The Brain

Cannabinoid Receptors (?), Leptin Receptors, Melanocortin Receptors, NPY Receptors, CART, Corticotropin-Releasing Factor Receptors, Serotonin Receptors,

Cannabinoid Receptors (?), Leptin Receptors, Melanocortin Receptors, NPY Receptors, CART, Corticotropin-Releasing Factor Receptors, Serotonin Receptors,

The Adrenal Glands

The Adipocyte

Cortisol

Leptin, Uncoupling Proteins, B3-Adrenergic Receptors,

The Pancreas and Gastrointestinal Track

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