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Contempo 1999 |

Recent Advances in Basic Obesity Research

Jack A. Yanovski, MD, PhD; Susan Z. Yanovski, MD
JAMA. 1999;282(16):1504-1506. doi:10.1001/jama.282.16.1504.
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More than 50% of US adults are overweight, with a body mass index of more than 25 kg/m2 (calculated as weight in kilograms divided by the square of height in meters).1 Even more concerning, the percentage of Americans who are obese (body mass index ≥30 kg/m2) has increased by more than 50% in the past 20 years, and the number of overweight children has doubled.2 Most overweight individuals can successfully lose some of the weight, but the majority regain that weight within 5 years.3

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Figure 1. Daily Energy Expenditure
Graphic Jump Location
Adapted from Ravussin and Bogardus, Am J Clin Nutr. 1989;49:968-975.
Figure 2. A Simplified Model of Human Body Weight Regulation
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Leptin is produced by adipocytes and acts primarily by binding to hypothalamic leptin receptors. Known second messenger systems include neurons coexpressing neuropeptide y (NPY) and agouti-related peptide (AGRP), neurons expressing the products of proopiomelanocortin (POMC), including α-melanocyte stimulating hormone (MSH), and other systems not shown. Acute administration of leptin suppresses NPY/AGRP, and stimulates POMC secretion. The MSH is believed to act via melanocortin-4 (MC-4) receptors, and NPY through a family of NPY receptors to modulate energy intake and to affect energy expenditure via regulation of autonomic nervous system activity. Autonomic nervous system activity may regulate energy expenditure in both skeletal muscle and adipose tissues, perhaps in part via the activity of uncoupling protein (UCP) 2 and UCP 3. The number of mature adipocytes available to store lipid may in part be determined by γ-2 type peroxisome proliferator-activating receptor (PPAR-γ2) activity.

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