Of mice and mass: fat rodents offered the first clue to a link between leptin and obesity. Here, the latest on how that translates to us humans

A FEW YEARS BACK, doctors at the University of Cambridge treated a pair of cousins from Pakistan who suffered from what could only be described as a pathological case of gluttony. The 8-year-old girl weighed nearly 190 pounds, and, despite liposuction and surgery, could no longer walk. The 2-year-old already tipped the scales at 65 pounds. Despite a padlocked fridge and well-guarded cupboards, the children would eat everything they could get their hands on, even scavenging through the trash for soggy french fries and gnawed-upon fish sticks.

One of the doctors wondered if the children could have something in common with a group of red-haired, obese mice he had read about. It seemed these mice were lacking in a recently discovered hormone called leptin, and this caused them to eat uncontrollably.

THE THIN HORMONE?

Leptin (from the Greek word leptos, meaning thin) is released by fat cells and is one of the body's chemicals responsible for controlling appetite, storing fat and regulating the body's ability to burn fat. Investigators at Rockefeller University in New York found that some mice predisposed to super-obesity had a genetic defect preventing leptin production. When the mice were injected with leptin, they experienced dramatic weight loss virtually overnight.

In fact, much like the mice, when the Pakistani cousins received similar treatment they quickly slimmed down to normal weight. The leptin curbed their appetites and kick-started their sluggish metabolisms. Naturally, this caused great excitement in the medical community. Was it possible that leptin therapy could be an effective new obesity treatment for humans?

Alas, no such luck. Scientists have since found that leptin deficiency in humans is quite rare. In fact, many overweight and obese people have a surplus of leptin in the bloodstream, suggesting that some sort of leptin resistance or malfunction may contribute to weight gain. Research indicates that while obese people have high leptin levels, their bodies seem unable to process it. No matter how much of the stuff the body pumps out, it's not enough to suppress appetite or accelerate metabolism.

THE OBESITY BATTLE

So where does that leave leptin research in the fight against obesity? Many medical experts believe the existence of leptin shows that, for some people, the drive to devour junk food may have a biological basis--it's not simply lack of willpower that makes some of us reach for chips, doughnuts and other high-fat, high-calorie foods.

Current leptin research is focused on how weight loss affects leptin levels and leptin resistance. Preliminary findings show that when people lose weight, their leptin levels return to normal and the body's ability to process leptin is restored. Exercise without weight loss also seems to enhance leptin balance, although at this point that's just a theory. Researchers still hope that studying leptin will offer a promising new direction for the development of obesity and weight-loss drugs. In the meantime, a sensible diet and plenty of exercise still seem to be the best, most effective weight loss remedies.

BY LIZ NEPORENT, MA, CSCS

COPYRIGHT 2003 Weider Publications
COPYRIGHT 2004 Gale Group