Word: leptin
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...Because leptin is produced in fat tissue, the fatter an animal is, the more leptin its cells should make. Normal mice then respond to weight gain by turning out more leptin. As a result, their appetites slacken and their energy consumption speeds up. But the obese mice cannot produce leptin, so their brains never receive this vital message. "These animals," marvels Friedman, "get fat because they think they're starving, and then when we give them the protein, they get thin because they think they...
Defects in the ob gene are not likely to be a major reason for obesity in people, most experts concur. But that does not mean leptin might not be therapeutically useful for many other overweight people. In last week's Science, for example, a team of researchers from the pharmaceutical company Hoffmann-LaRoche described how they plumped up lean mice by giving them unrestricted access to high-fat food. Then they administered leptin. The mice responded by cutting their food intake and shedding the extra ounces, suggesting leptin may have value in reversing more typical cases of weight gain...
What about side effects? Injections of leptin do not, as one might fear, turn lean mice into starving wretches. After losing weight, researchers from Amgen reported, normal mice stabilize both their food intake and their metabolism. Obese mice likewise reach an optimal leanness, then stop losing weight. The pattern of weight loss is also encouraging. For unlike extreme calorie restriction, which can weaken muscle, leptin appears to dissolve fat while leaving lean tissue intact. On the basis of such data, Amgen (which paid Rockefeller University $20 million for patent rights to make products based on the ob gene) has announced...
Many experts find these plans too optimistic. Just because researchers have not noted worrisome side effects yet, critics say, does not mean that none will emerge. Leptin, they point out, is a serious drug, not the easy-to-swallow "thin pill" dieters have dreamed of for so long. To do its work, leptin would probably have to be either injected daily, like insulin, or implanted under the skin for the rest of one's life. In the laboratory experiments reported last week, the obese mice started regaining weight as soon as the injections stopped. Even with a boost from something...
Regardless of what eventually happens in the marketplace, the discovery of leptin is occasion for celebration. It has provided scientists with a new avenue for exploring a still poorly understood metabolic pathway, one that probably consists of many other equally powerful compounds, each of which could lead to new drugs...