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An Update on the Obesity Problem

We have all heard the statistics: 30% of U.S. adults are obese, and another 35% are overweight; 15% of children and adolescents weigh too much, and diseases of obesity, such as type 2 ("adult-onset") diabetes, now are appearing in children. Each year in the U.S., 300,000 people die of obesity-related diseases, and rates are similar in other developed nations and even in many developing nations. Three forces are driving this epidemic: our genes, an expanding food supply, and machines that do physical work for us.

Our understanding of the biology of weight control has expanded enormously during the past decade. The arcuate nucleus in the hypothalamus appears to be the master control center. One part of the arcuate nucleus sends signals that increase appetite and decrease metabolic rate; another part does the opposite. The balance between the activities of these 2 centers affects both short-term and long-term weight control. Specific hormones produced in the stomach, intestines, pancreas, and adipose tissue act on the arcuate nucleus, as do signals that travel up the vagus and spinal nerves. At least some of those molecular signals have been identified and have been targeted by drug developers. Some molecules (such as leptin and insulin) affect weight in the long term. Others (such as ghrelin and PYY) affect weight in the short term: Ghrelin levels increase when we awaken, at noontime, and at dinnertime and stimulate appetite, whereas PYY levels rise in response to eating and cause satiety. As we begin to understand the chemistry and nervous system "wiring diagram" that governs weight control, it appears that evolution has rigged our biology to protect us against starvation -- but it doesn't protect us against food abundance.

That protection was a good thing for our distant ancestors, but it isn't a good thing for most humans who are living today. In the U.S., the food industry produces 3800 kilocalories per person per day -- almost twice as much as we need. Our biology, and market forces, encourage us to consume this surfeit. And, although it's more common to see people jogging today than it was 40 years ago, overall, we're less physically active: We rely on machines to move us, to entertain us, and to do physical work for us.

Currently available obesity drugs are not very effective and are fraught with adverse effects. Leptin, discovered in 1994, has led to an explosion in our understanding of the biology of weight control. However, leptin has been a bust as a weight-control drug. Some very promising results in both animal and initial human trials have been reported with other new molecules that were identified by scientists in the emerging field of weight control; however, it is much too early to determine their efficacy or their adverse effects. Because the biology of weight control is complex, many investigators doubt that a pharmaceutical "silver bullet" will be found that will allow us all to achieve healthy weights. However, others point to animal experiments in which single molecules have profound effects on weight control, thereby reducing the burden of weight-related diseases and even extending the length of life.

For now, faced with a biological drive and a marketplace that encourage us to overeat and underexert, the best hope for dealing with the obesity epidemic might be political: restrictions on marketing junk foods, particularly to children; taxes and calorie labels on junk foods; and changes in the farm subsidy laws to encourage production and consumption of grains, fruits, and vegetables. One can assume that resistance to such changes will be enormous. Adapted from a series of articles in Science.

— Anthony L. Komaroff, MD

Published in Journal Watch General Medicine March 7, 2003

Citation(s):

Nestle M. The ironic politics of obesity. Science 2003 Feb 7; 299:781.

• Medline abstract (Free)

Kelner K and Helmuth L. Obesity -- What is to be done? Science 2003 Feb 7; 299:845.

Marx J. Cellular warriors at the battle of the bulge. Science 2003 Feb 7; 299:846-9.

• Original article (Subscription may be required)
• Medline abstract (Free)

Gura T. Obesity drug pipeline not so fat. Science 2003 Feb 7; 299:849-52.

• Original article (Subscription may be required)
• Medline abstract (Free)

Hill JO et al. Obesity and the environment: Where do we go from here? Science 2003 Feb 7; 299:853-5.

• Original article (Subscription may be required)
• Medline abstract (Free)

Friedman JM. A war on obesity, not the obese. Science 2003 Feb 7; 299:856-8.

• Original article (Subscription may be required)
• Medline abstract (Free)

Pi-Sunyer X. A clinical view of the obesity problem. Science 2003 Feb 7; 299:859-60.

• Original article (Subscription may be required)
• Medline abstract (Free)