Health At Every Size: The Surprising Truth About Your Weight by Linda Bacon Read Free Book Online Page A

experiment called parabiosis), allowing the mice to share the same blood. The result was that the fat mouse returned to average weight, suggesting that something in the blood of the thinner mouse played a role in weight regulation.
     
    Suspecting that few humans would want to be stitched to a thinner human to lose weight, scientists set their sights on isolating the gene that kept the thin mice thin. In 1995, Jeffrey Friedman and colleagues at Rockefeller University in New York located the gene. Turns out this gene was responsible for the production of a hormone called leptin. 18 Mice that lacked the gene—and didn’t make leptin—were extremely fat.
     
    Friedman hypothesized that the hypothalamus was sensitive to leptin and that when the mouse reached an appropriate weight, leptin traveled to the brain and either turned on the LH or turned off the VMH, causing a release of chemicals that helped maintain the setpoint.
     
    The initial research was exhilarating. When the fat mice were injected with leptin, they lost 30 percent of their body weight in two weeks with no apparent side effects. Their metabolism sped up, they ate less, and they ran around more, suggesting that leptin affected many aspects of the energy balance equation simultaneously. When average-sized mice were given extra leptin, they also lost weight.
     
    Since then, we’ve learned that when fat cells increase in size in a healthy person, they produce more leptin, signaling the hypothalamus to do what it needs to do to slow your eating, increase your activity level and metabolism, and return your fat cells to their previous size.
     
    In other words, leptin acted as the “fat meter” fantasized about in the beginning of this chapter.
     
    As you might imagine, the weight-loss industry went wild over the leptin research, certain that a weight-loss pill was finally within reach. Hello leptin, goodbye dieting.
     
    After all, it made sense: If mice got fat because they didn’t make enough leptin, and mice are genetically similar to humans, then wouldn’t it stand to reason that fat humans also didn’t make enough leptin? Inject them with leptin, the thought went, and the fat would melt away.
     
    The biotech firm Amgen quickly bought the rights to Friedman’s discovery for more than $20 million, with the promise of subsequent payments if leptin proved to be the magic bullet some anticipated. The day after announcing the acquisition, Amgen’s stock sky-rocketed.
     
    Scientists in the know were amazed at this reckless cash outlay as it hadn’t been determined—and didn’t seem likely—that many humans had a gene mutation similar to the ob/ob mice. As any scientist worth her rat pellets can tell you, what’s true in mice isn’t always true in humans.
     
    The clinical trials on leptin were disappointing to say the least. In one, for example, seventy-three fat volunteers injected themselves with leptin or a placebo for twenty-four weeks. 19 Nearly everyone experienced skin irritation and swelling, and many withdrew from the study because of these problems, leaving just forty-seven to complete the study. Although there was an extreme amount of individual variability, of those who stayed in the study, the eight receiving the highest dose of leptin (which also caused the greatest irritation and swelling) lost an average of 16 pounds (though some individuals actually gained weight), while the twelve taking the placebo lost an average of 3 pounds. Low doses had virtually no effect.
     
    Further studies in both rats and humans showed that weight returned to baseline levels after the leptin injections ended. The euphoria over leptin crashed like a lead balloon.
     
    Yes, leptin is produced in humans, and yes, just as in the mice, leptin travels to the brain where it triggers the release of various chemicals to turn down your appetite, speed up your metabolism, and get you moving more. But, researchers learned, fat people were already producing plenty of