Too Fat? No More Excuses
Research is revealing how very damaging extra baggage is
Corrected on 1/9/07: An earlier version of this article misstated the name of the American Institute for Cancer Research.
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 transplanta-tion 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."
The cardiovascular system appears to be one victim. Macrophages play an important role in the development of the fatty plaques that lead to atherosclerosis. And cytokines can make tissues resistant to the effects of insulin and cause inflammation in the blood vessels. Meantime, too much insulin can promote salt retention—and soaring blood pressure. "If I hadn't lost the weight when I did, they say [I'd have had] a heart attack or stroke," says Sheri Fanning, 41, a geriatric care manager and now weight-loss coach in Sparta, Wis., who has heart disease in her family and recently experienced a dangerous blood pressure spike.
Five years ago, Fanning tipped the scale at 192 pounds, and her doctor delivered an ultimatum: Go on hypertension meds for life. Instead, Fanning credits a physician-directed program that offered thrice-weekly weigh-ins, counseling, and a calorie-restricted diet for helping her to get down to a healthy 130 pounds. Taking up marathoning, triathlon, and competitive road biking certainly did its part, too. Though she's been on blood pressure medication since her recent crisis, she was able to keep her numbers down for years without drugs; her doctors say that shedding those pounds and keeping them off probably saved her life.
Cancer experts, too, now strongly advise burning excess fat. In fact, the top recommendation in the new cancer prevention guidelines issued by the American Institute for Cancer Research and the World Cancer Research Fund puts it this way: "Be as lean as possible within the normal range of body weight." That means keeping your body-mass index between 21 and 23—or, for someone who is 5 foot 4, staying between 122 and 134 pounds. "A BMI of 25 increases the risk of postmenopausal breast cancer more than [a BMI] of 21," says Meir Stampfer, who researches nutrition and epidemiology at the Harvard School of Public Health. Extra fat is strongly believed to raise the risk of six types of cancer—esophageal, pancreatic, colorectal, breast (in postmenopausal women), endometrial, and kidney—and possibly gallbladder cancer, too.
The mechanisms that link obesity and cancer are not known, but the usual suspects—insulin resistance and inflammation—are likely players. Research released at December's American Association for Cancer Research conference on cancer prevention found that women with diabetes are 1.5 times more likely to develop colorectal cancer than those who aren't diabetic. "It's possible that fairly high levels of insulin—higher than seen in the prediabetics—are necessary to encourage cancer growth," says Andrew Flood, an epidemiologist at the University of Minnesota. And cytokines released from fat tissue are known to promote tumor growth and cell death.
Fatty liver. The workhorse of the body takes a beating, too. For example, when a person carries a surplus of fat, the liver—which is responsible for the breakdown of insulin, sugars, hormones, and lipids—less effectively produces a protein that helps move fat out. So most chronic overeaters end up with fat stored in this organ. Nonalcoholic fatty liver disease, when severe, results in rampant inflammation and scarring and is projected to be the most common reason for liver transplant by 2020.
"I probably had a week to live," says Bill Mackey, an engineer in Rochester, Minn., who once weighed 350 pounds and got a transplant in 2003 after developing liver failure. Through a yearlong recovery and adjustment to antirejection drugs, Mackey, 60, dropped down to 225 pounds, though he has crept back up to 275 these days. His doctor says this is typical in such patients, as is some reaccumulation of fat in the liver. "That tells you this is not a liver problem," explains Mayo's Charlton. "It's a whole-body problem, an endocrine problem associated with hormones, overnutrition, and some susceptibility factor we're still trying to identify."
Deep belly fat, also known as visceral fat, may especially endanger the liver. "Having fat in that visceral area can potentially increase the flow of fatty acids to the liver and have a next-door-neighbor effect," says Elizabeth Parks, associate professor and expert on liver metabolism at ut-Southwestern Medical Center in Dallas. And "maybe the visceral fat is releasing more cytokines [than fat stored elsewhere]." Genes seem to determine—at least in part—where a person stores fat, so lean people aren't necessarily off the hook if they don't exercise or eat a healthful diet.
All this new research on the workings of body fat also has revealed why it's so hard to lose weight and keep it off: As you eat more, exercise less, and ratchet upward on the scale, your hormones adjust and fiercely guard the new status quo. For example, the amount of leptin—a hormone secreted by fat that regulates food intake and energy expenditure—circulating in your blood is proportional to the amount of fat you've got stored, says Christopher Newgard, director of the Sarah Stedman Nutrition and Metabolism Center at Duke University. When the hypothalamus of a person at a healthy weight sees a higher level of leptin than it expects, it tells the body to ease up on food intake and boost energy burning. Sounds great—perhaps you'd like to sprinkle some on your morning cereal? But researchers tested the supplement idea after leptin was discovered in 1994 and found that chronically high levels seem to desensitize the brain, so that leptin's ability to reduce food intake all but disappears.
Fat cells, moreover, don't seem to go away; while other cells are programmed to die, "you've bought them for life," says Robert Kushner, professor of medicine and obesity-care specialist at Northwestern University Feinberg School of Medicine. Thus, the goal of shedding pounds really is about slimming fat cells down, then keeping them from packing in triglycerides again.
The obvious question: How much work is necessary to succeed at trimming the fat? The American Heart Association and the American College of Sports Medicine issued an updated, joint set of guidelines in August on physical activity. To "promote and maintain health," 30 minutes of moderate activity five days per week will do the job. But to prevent weight gain or shed pounds, "more is better." In fact, much more is called for: from 60 to 90 minutes of physical activity on most days.
The amount and type of food you take in matter, too, of course—although researchers don't yet understand how (or how well) various diets and interventions work. At Duke, for example, multiple ways of shedding pounds are being studied—from the Atkins Diet to bariatric surgery to drug treatments—to clarify what they do to a person biochemically and why certain people have success and others flounder. The one trick that researchers can agree upon so far is both simple and painfully familiar: Eat less and move more.
For Jesse Manek, that meant ditching what he craved most: fast food, ice cream, and sugary foods. In his doctor's mind, the ever present sweetener fructose, which shows up in everything from pasta to sports drinks to soda to breads, is the refined carbohydrate most culpable in the rise of obesity. Its breakdown in the liver, says Lustig, promotes inflammation, hypertension, and insulin resistance. The extra fiber Manek gets by stocking up on fruits, vegetables, and whole grains helps control his insulin levels and makes him feel fuller, longer. Thanks to his vigorous exercise regimen, he says, an irony has unfolded: "I actually eat more now."
With Katherine Hobson
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