Too Fat? No More Excuses

Research is revealing how very damaging extra baggage is.

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You may think your jiggling spare tire is just along for the ride, an inert mass that slows you down and forces a slackened belt. But far from just sitting there quietly, your body fat is talking. And what it's saying—in a constant stream of messages to your brain, liver, muscles, and points in between—amounts to an urgent reason to finally follow through on that New Year's resolution.

Researchers worried about the obesity epidemic are furiously studying body fat in an effort to decode its effect on health. And they have discovered that fat is as active and important an endocrine organ as the thyroid or reproductive glands. In healthy amounts, it tightly regulates the amount of energy burned or stored by releasing a cadre of hormones. In excess, the fat cells swell and multiply, and their functioning overwhelms the system: Nasty inflammatory factors spew into the bloodstream, and the delicate balance of hormones becomes skewed, altering the brain's normal response to fat's signals. The result: a much-elevated risk of diabetes, cardiovascular disease, cancer, and liver disease. Plus metabolic changes that make losing weight—and keeping it off—seem impossibly tough.

"People think obesity is two behaviors: gluttony and sloth," says Robert Lustig, director of the Weight Assessment for Teen and Child Health Clinic at the University of California-San Francisco Children's Hospital. "That's not what it is. Obesity is a manifestation of a biochemical problem." Excessive fat strengthens the dysfunction, too, trapping the body in a vicious cycle. Even slightly overweight people can be on the path to a disturbed physiology—no matter that their clothes can still disguise a paunch.

For evidence, look no further than the recent surge in type 2 diabetes, which correlates in near lockstep with Americans' expanding waistlines. As fat stores go up, so does the pancreas's production of insulin, the hormone that helps usher glucose out of the bloodstream and into cells where it's used for fuel. So people with too many extra pounds end up with a glut of the stuff, typically leading to "insulin resistance"—and too much glucose in the blood. Meantime, the excess insulin sends energy into the fat cells, causing them to plump up and multiply ad infinitum—and end up in places fat shouldn't be, like muscles, the liver, and deep in the gut, wrapped around vital organs.

Discipline. Insulin resistance has been Jesse Manek's nemesis. Now 15, Manek was told three years ago that—seriously overweight at 283 pounds and prediabetic—he would very likely have full-blown diabetes or a heart attack by the time he reached his 20s. Manek, who lives in Novato, Calif., sought help from Lustig and the watch clinic and has managed to drop more than 75 pounds and bring his body-mass index, a number that relates weight to height, from 41.6 to a closer-to-normal 29.9. His regimen has been ultradisciplined: at least four classes per week at Marin Mixed Martial Arts, weekly sessions of strength training with a personal trainer, and a diet nearly devoid of fructose (found in table sugar and high-fructose corn syrup) and chock-full of fruits, vegetables, and whole grains. Lustig also has treated Manek with metformin, a diabetes drug, to rein in his insulin-gone-haywire. "It really comes down to a mental battle," Manek says of his struggle. "Do you want to be healthy?" He's now safely out of the prediabetic zone.

Besides upsetting the insulin balance, too much fat seems to unleash a flood of molecules called cytokines that trigger systemwide inflammation. "Obesity is a pro-inflammatory state," says Michael Charlton, medical director of liver transplantation at the Mayo Clinic in Rochester, Minn. Normally, inflammation is a healthy immune response, critical to fighting off infection. But chronic inflammation causes widespread tissue damage. The plumper and more abundant a person's fat cells, the greater the number of cytokine-releasing macrophage cells in the fat tissue. "It's these macrophages that are causing a lot of the trouble," says Rudolph Leibel, a Columbia University geneticist and noted obesity researcher. "They make mischief related to how fat you are."

Corrected on 1/9/07: An earlier version of this article misstated the name of the American Institute for Cancer Research.