Why are some obese people healthy, apparently protected from the damaging effects of excess fat on the liver and other organs?

interfere with:干涉,妨碍,打扰    metabolism:新陈代谢    obese:肥胖的,过胖的    liver:肝脏

Scientists are investigating this question as they look to understand how obesity disrupts normal organ function and causes inflammation, insulin resistance, diabetes and other metabolic abnormalities.

inflammation:炎症,燃烧    insulin:胰岛素    diabetes:糖尿病

Understanding the different ways in which fat tissue causes disease throughout the body could yield new insights for treatment. New research on the subject was presented in Atlanta last week at Obesity Week, a major conference of weight-loss surgeons and other health professionals.

tissue:组织,纸巾    surgeon:外科医生

Much of the new research centers on how some fat tissue becomes unable to do its job of storing new fat cells and instead shunts them off to be stored in places where they don't belong, like liver and muscle tissue.

shunt:使分流,转轨

Another line of inquiry examines how different types of fat in the body exhibit different behaviors, with some serving a more useful function than others. Other work has examined the role of viruses and gut bacteria in contributing to body weight and disease.

viruses:病毒    gut bacteria:肠道细菌

Some of the most recent research, conducted by Evan Nadler, co-director of the Obesity Institute at Children's National Medical Center in Washington, D.C., suggests yet a new mechanism for how obesity causes disease all over the body: Small sacs, called exosomes, are produced by fat cells and sent off carrying disruptive disease-causing signals to organs.

sac:液囊    exosome:外来体    

Though the negative health effects of obesity are well known, scientists have observed that not all obese individuals are unhealthy. Experts at the Atlanta conference said an estimated 10% to 30% of the obese population appears immune to the negative health effects of excess fat and remains metabolically normal—meaning without inflammation, diabetes or any hint of insulin resistance. For instance, while more than 60% of U.S. adults are overweight or obese, only about 10% are diabetic.

immune to:不受...感染

In the laboratory, scientists including Philip Schauer, professor of surgery at the Cleveland Clinic, have genetically engineered mice that become obese but metabolically remain perfectly healthy. Obese mice typically exhibit insulin resistance.

What's more, scientists say that for obese individuals who are metabolically normal, health doesn't improve significantly with weight loss.

Samuel Klein, director of the Center for Human Nutrition at the Washington University School of Medicine in St. Louis, recently conducted a randomized controlled study in which researchers asked 22 obese individuals to eat more calories, inducing a 6% weight gain.

The subjects who were metabolically normal at the start didn't show any ill effects from the weight gain. But those who started out metabolically abnormal experienced worsened insulin sensitivity after the weight gain. When participants were then induced to lose the weight, only the health of the metabolically abnormal group improved.

"A critical question is, Why are some people predisposed to the metabolic dysfunction and others resistant to it?" Dr. Klein says.

predispose to:易受感染    dysfunction:功能紊乱,机能障碍

The answer is a work in progress. The type of excess fat, as well as the amount and the location of it, plays an important role. Belly fat, or visceral fat, which sits around the organs in the abdomen, is considered particularly unhealthy because it doesn't help store new fat cells. Instead, it redirects the cells to other organs for storage, most notably to the liver, and produces damaging inflammatory proteins that can even reach the brain.

belly:腹部,胃,胀满,鼓起    visceral:内脏的    abdomen:腹部,腹腔

Fat cells sitting under the skin's surface, known as subcutaneous fat—particularly in the thighs, legs and lower body—"suck up energy, store it avidly and protect the liver," says Steven R. Smith, a professor at Sanford Burnham Medical Research Institute in Orlando, Fla. Dr. Smith and his group are studying the molecular programming of lower-body fat in an effort to change other types of fat into this subcutaneous fat.

subcutaneous:皮下的    thigh:大腿    avidly:贪心地,热心地    molecular:分子的

Both visceral and subcutaneous fat are made of white adipose tissue and are thought to be less healthy than the type of fat known as brown fat. Brown fat has a darker appearance because the tissue is metabolically active—which means it burns energy and calories, in contrast with white fat, which just sits.

white adipose tissue:白色脂肪组织

Scientists have been trying for years to figure out how to create more brown fat. Recently, researchers at Harvard University discovered that with exercise, something called the "beiging" of fat can occur. Subcutaneous white fat becomes more metabolically active, according to work presented in Atlanta by Bruce Spiegelman, a professor of cell biology at Harvard.

Another line of study examined how individuals infected with a virus called adenovirus Ad36 not only gain weight but also become more resistant to diabetes, apparently because it causes the redistribution of fat. Instead of being stored in the liver, fat is stored in subcutaneous tissue. "The fat gets stored in the right place," says Nikhil Dhurandhar, professor in health promotion at Pennington Biomedical Research Center in Baton Rouge, La., whose group has studied the virus for years.、

adenovirus:腺病毒

The infected individuals' fat cells increase production of a hormone called adiponectin, known to help increase insulin sensitivity, a protective factor against developing diabetes. "We want to harness the ability of the virus so we can use it to treat diabetes," Dr. Dhurandhar says.

hormone:荷尔蒙,激素    adiponectin:脂肪连接蛋白    harness:治理,利用

While infecting people with the actual virus is out of the question, Dr. Dhurandhar's group recently identified a gene that appears to be responsible for the virus's antidiabetic effect and found a way to deliver the gene into animals. In preliminary work, the researchers injected various doses of the gene into obese mice, which were fed a high-fat diet to impair blood-sugar control.

out of the question:不可能的    antidiabetic:抗糖尿病的    impair:损害,削弱,减小

Each exhibited a temporary improvement of one to two weeks in its ability to regulate blood sugar without dieting, though the effect seemed to shorten as the mice aged, according to Vijay Hegde, a Pennington researcher who presented the research at Obesity Week.

The newest but least-studied factor in how obesity causes disease are exosomes, sacs that have been implicated in contributing to cancer because they contain bad-acting DNA modifiers that become incorporated into the cells of other organs. Independent experts say exosomes could be important, but urge caution in interpreting the findings in obesity.

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