Tom's Life Bits

Monday, October 29, 2012 As of 3:32 PM EDT

By SHIRLEY S. WANG

Researchers are discovering more ways that obesity can damage the body. These include altering a person's ability to smell, disrupting sleep and sexual function, and accelerating cancerous tumor growth.

“Obesity is a complex condition,” said Mikhail Kolonin, a professor at the University of Texas Health Science Center in Houston. “Many, many things change in the body.”

Fat produces numerous hormones, inflammatory molecules and other chemicals that can act directly on nearby organs or travel to wreak havoc in other areas of the body. Better understanding how this works might eventually open new avenues for treatment of obesity and linked conditions, experts say.

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Debra Ann Fadool/Florida State University Bred with a supersensitive sense of smell, the bottom mouse appeared in the lab to be more resistant to obesity than normal mice

Weighty Findings

Excess weight doesn't just raise the risk of heart disease and diabetes. Researchers are finding it affects other bodily functions and diseases in surprising ways.

SMELL

Obese mice appear to have reduced sense of smell compared with those of normal weight. Mice with a super sense of smell appear resistant to obesity. SLEEP

Obesity is linked with people feeling greater (daytime) sleepiness and fatigue, independent of conditions like sleep apnea. Losing weight appears to decrease sleepiness. FERTILITY

Obese teenage males appear to have substantially decreased testosterone compared with normal-weight males. Obese females have a greater risk of polycystic ovarian syndrome and high levels of testosterone. CANCER

Obese people have higher rates and faster progression of certain types of cancer. Tumor cells appear to recruit fat cells to help cancer grow Researchers are increasingly interested in understanding the role of the olfactory bulb, which relays smell information from the nose to the brain, and contains one of the densest collections of insulin receptors outside the pancreas. The production of insulin, which is used to turn sugar into energy, is often impaired in obese people.

Debra Ann Fadool, a professor at Florida State University in the program in neuroscience and molecular biophysics, and Kristal Tucker, a research associate in pharmacology and chemical biology at the University of Pittsburgh School of Medicine, were studying the role of insulin in the olfactory system when they bred genetically modified “super-smeller” mice that could discriminate odors better than normal mice.

They observed that these modified mice were thinner than normal mice and appeared resistant to obesity, perhaps because the modified mice metabolized the fat differently. Even when they were fed a high-fat diet, they didn't put on extra fat. They also exhibited lower levels of insulin, glucose and leptin—chemicals that are usually elevated in obesity, said Dr. Fadool.

This observation led the scientists to remove the super-smeller mice's olfactory bulbs. When they did this, the mice ceased to remain resistant to obesity, Dr. Fadool said.

Further investigation found that the neurons in the bulbs of obese mice fired less frequently than in lean mice, suggesting that these mice didn't decipher odors as well, and they couldn't adapt well to different situations, such as an influx of insulin.

In another study, published last month in the Public Library of Medicine, they found that mice made obese on a high-fat diet also exhibited damped responses in their olfactory bulbs, suggesting obesity can disrupt the bulb's functioning.

It isn't clear how olfaction and body weight are linked. One theory: Excess fat and related hormonal changes could trigger changes in the olfactory system.

Another is that olfactory dysfunction comes first, and can cause or contribute to obesity, according to Dr. Tucker. In the future, targeting smell could be another approach to addressing obesity, she added.

“If you can modulate your olfactory function, it's possible it could be a future target for controlling food intake and metabolism,” she said.

Obesity also influences sleepiness. Obese people often report feeling sleepier than their leaner counterparts. For a long time it was believed this was due to sleep apnea, a condition—common in the overweight—in which a person stops breathing repeatedly while sleeping.

But Alexandros Vgontzas, a sleep specialist at Penn State University, and others have found that the obese sleep worse and report being sleepy in the daytime—to the point of falling asleep at work or while driving—regardless of whether they have sleep apnea.

At the Associated Professional Sleep Society in Boston this summer, they presented data on 1,700 people they followed for 7½ years, studying the factors at work in those who reported significant sleepiness. Obesity, weight gain and depression were the biggest risk factors, they found. In addition, weight loss appeared to make people less sleepy.

“The weight gain and weight loss findings tell us it's indeed the obesity that makes you complain about sleepiness, not the other way around,” said Dr. Vgontzas. This makes sense because fat produces certain molecules that are known to be sleep factors, he said.

These results could help clinicians treating patients with sleep problems, Dr. Vgontzas says. Rather than immediately treating an overweight person with what is known as a CPAP machine, a mask that forces air up the nose to improve breathing, the doctor should consider intervening to encourage weight loss instead, he said.

“It's a bad practice for sleep medicine physicians if someone comes with mild or moderate sleep apnea to stuff them with mask instead of [change] lifestyle,” said Dr. Vgontzas.

Fertility is another area that obesity seems to disrupt. In a recent study of teenage boys, obese males had half the level of testosterone of lean ones, suggesting they could have problems with impotence and fertility later on, said Paresh Dandona, a professor and head of endocrinology, diabetes and metabolism at the University of Buffalo in New York state.

“It is still not fully appreciated that obesity could be a cause of sexual dysfunction and infertility,” said Dr. Dandona. “It's a public health issue.”

It isn't clear why there is a link, though it seems likely that the hormones produced by fat disrupt the typical balance of sex hormones, said Dr. Dandona.

Excess fat doesn't just disrupt normal bodily function; it can make other diseases worse.

For instance, a study published earlier this month in the journal Cancer Research demonstrated that, in mice, cancer-tumor cells appear to recruit fat stem cells to help them grow. Fat releases molecules that induce new blood vessels to grow, which then feed the tumor. Some fat stem cells also travel to the site of the tumor and merge with it.

Earlier research has suggested that obese people are more likely to get cancer, or see some cancers progress faster, but it wasn't clear whether the excess fat or lifestyle issues were to blame, said the University of Texas' Dr. Kolonin, an author of last week's paper.

Although several studies have linked obesity and cancer, this study was the first to demonstrate that fat tissue itself enhances tumor growth.

Tumors grew faster in obese mice, even those eating a healthy diet, than in lean mice.

Tumors appear to “scream for help” and emit signals that activate cells in other parts of body, Dr. Kolonin said. They recruit stem cells from bone marrow and body fat. Since there is a lot more fat tissue in obese individuals, such cells are recruited in higher levels.

“Essentially we've proven that fat tissue works not only from the distance, but also from within the tumor by contributing cells to the tumor microenvironment,” said Dr. Kolonin.

Write to Shirley S. Wang at shirley.wang@wsj.com