Archive for November 29, 2007

New research on the effects of the female sex hormone estrogen in the brain lend credence to what many women have suspected about the hormonal changes that accompany aging: Menopause can make you fat.Scientists long have sought to understand how changes in hormones during menopause could account for the increase in appetite and accompanying weight gain that often occurs among aging women.

In a series of animal experiments described today at the 234th national meeting of the American Chemical Society, the world’s largest scientific society, researchers showed how estrogen receptors located in the hypothalamus serve as a master switch to control food intake, energy expenditure and body fat distribution. When these receptors are destroyed, the animals immediately begin to eat more food, burn less energy and pack on pounds.

This research seems to support a link between estrogen and regulation of obesity, especially the dangerous accumulation of abdominal fat linked to heart disease, diabetes, and cancer, says Deborah J. Clegg, Ph. D., assistant professor of psychiatry at the University of Cincinnati Academic Health Center, who is directing the studies.

The findings may also help scientists develop more targeted hormone replacement therapies, capable of stimulating estrogen receptors in one part of the brain or body while dampening it in the next, Clegg says.

Estrogen receptors are located on cells throughout a woman’s body. Previous studies have shown that one type of estrogen receptor, known as estrogen receptor alpha or ER-alpha, plays a role in regulating food intake and energy expenditure. But scientists have been unable to pinpoint exactly where these fat-regulating receptors reside or how they work to govern these behaviors.

To determine the effect of dwindling estrogen levels in the brain, Clegg and her colleagues are focusing on two ER-alpha rich regions located in the hypothalamus, an area of the brain that controls body temperature, hunger and thirst. The first region, called the ventromedial nucleus or VMN, is a key center for energy regulation.

Using a relatively new gene-silencing technique called RNA interference, the researchers in earlier research deactivated the alpha-receptors in the VMN. The estrogen receptors in other regions of the brain maintained their normal capacity.

When estrogen levels in the VMN dipped, the animals’ metabolic rate and energy levels also plummeted. The findings show the animals quickly developed an impaired tolerance to glucose and a sizable weight gain, even when their caloric intake remained the same. What’s more, the excess weight went straight to their middle sections, creating an increase in visceral fat.

The findings suggested that the ER-alpha in this region plays an essential role in controlling energy balance, body fat distribution and normal body weight.

Clegg now plans to perform a similar experiment to deactivate ER-alpha in the arcuate nucleus region of the hypothalamus. This region contains two populations of neurons: one puts the brake on food intake and the other stimulates food intake. Clegg anticipates that a loss of estrogen in this region may create an increase in the animals’ appetites as well as their weight.

Clegg says her studies address an area that is sorely needed given the incidence and impact of gender differences in obesity and its complications.

“The accumulation of abdominal fat puts both men and women at a heightened risk of cardiovascular disease, diabetes, and insulin resistance,” she says. “Women are protected from these negative consequences as long as they carry their weight in their hips and saddlebags. But when they go through menopause and the body fat shifts to the abdomen, they have to start battling all of these medical complications.”

By identifying the critical brain regions that determine where body fat is distributed, Clegg says her findings may help scientists design hormone replacement therapies to better manage and manipulate estrogen levels.

“If we could target those critical regions and estrogen receptors associated with weight gain and energy expenditure, we could perhaps design therapies that help women sidestep many of the complications brought on by the onset of menopause,” she says.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Charmayne Marsh
American Chemical Society

 The American Chemical Society — the world’s largest scientific society — is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

Deborah J. Clegg, Ph.D., is assistant professor of psychiatry at the University of Cincinnati Academic Health Center in Cincinnati, Ohio.

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Female athletes often lose their menstrual cycle when training strenuously, but researchers have long speculated on whether this infertility was due to low body fat, low weight or exercise itself. Now, researchers have shown that the cause of athletic amenorrhea is more likely a negative energy balance caused by increasing exercise without increasing food intake.”A growing proportion of women are susceptible to losing their menstrual cycle when exercising strenuously,” says Dr. Nancy I. Williams, assistant professor of kineseology and physiology at Penn State. “If women go six to 12 months without having a menstrual cycle, they could show bone loss. Bone densities in some long distance runners who have gone for a prolonged time period without having normal menstrual cycles can be very low.”

In studies done with monkeys, which show menstrual cyclicity much like women, researchers showed that low energy availability associated with strenuous exercise training plays an important role in causing exercise-induced amenorrhea. These researchers, working at the University of Pittsburgh, published findings in the Journal of Clinical Endocrinology and Metabolism showing that exercise-induced amenorrhea was reversible in the monkeys by increasing food intake while the monkeys still exercised.

Williams worked with Judy L. Cameron, associate professor of psychiatry and cell biology and physiology at the University of Pittsburgh. Dana L. Helmreich and David B. Parfitt, then graduate students, and Anne Caston-Balderrama, at that time a post-doctoral fellow at the University of Pittsburgh, were also part of the research team. The researchers decided to look at an animal model to understand the causes of exercise-induced amenorrhea because it is difficult to closely control factors, such as eating habits and exercise, when studying humans. They chose cynomolgus monkeys because, like humans, they have a menstrual cycle of 28 days, ovulate in mid-cycle and show monthly periods of menses.

“It is difficult to obtain rigorous control in human studies, short of locking people up,” says Williams.

Previous cross-sectional studies and short-term studies in humans had shown a correlation between changes in energy availability and changes in the menstrual cycle, but those studies were not definitive.

There was also some indication that metabolic states experienced by strenuously exercising women were similar to those in chronically calorie restricted people. However, whether the increased energy utilization which occurs with exercise or some other effect of exercise caused exercise-induced reproductive dysfunction was unknown.

“The idea that exercise or something about exercise is harmful to females was not definitively ruled out,” says Williams. “That exercise itself is harmful would be a dangerous message to put out there. We needed to look at what it was about exercise that caused amenorrhea, what it was that suppresses ovulation. To do that, we needed a carefully controlled study.”

After the researchers monitored normal menstrual cycles in eight monkeys for a few months, they trained the monkeys to run on treadmills, slowly increasing their daily training schedule to about six miles per day. Throughout the training period the amount of food provided remained the standard amount for a normal 4.5 to 7.5 pound monkey, although the researchers note that some monkeys did not finish all of their food all of the time.

The researchers found that during the study “there were no significant changes in body weight or caloric intake over the course of training and the development of amenorrhea.” While body weight did not change, there were indications of an adaptation in energy expenditure. That is, the monkeys’ metabolic hormones also changed, with a 20 percent drop in circulating thyroid hormone, suggesting that the suppression of ovulation is more closely related to negative energy balance than to a decrease in body weight.

To seal the conclusion that a negative energy balance was the key to exercise-induced amenorrhea, the researchers took four of the previous eight monkeys and, while keeping them on the same exercise program, provided them with more food than they were used to. All the monkeys eventually resumed normal menstrual cycles. However, those monkeys who increased their food consumption most rapidly and consumed the most additional food, resumed ovulation within as little as 12 to 16 days while those who increased their caloric intake more slowly, took almost two months to resume ovulation.

Williams is now conducting studies on women who agree to exercise and eat according to a prescribed regimen for four to six months. She is concerned because recreational exercisers have the first signs of ovulatory suppression and may easily be thrust into amenorrhea if energy availability declines. Many women that exercise also restrict their calories, consciously or unconsciously.

“Our goal is to test whether practical guidelines can be developed regarding the optimal balance between calories of food taken in and calories expended through exercise in order to maintain ovulation and regular menstrual cycles,” says Williams. “This would then ensure that estrogen levels were also maintained at healthy levels. This is important because estrogen is a key hormone in the body for many physiological systems, influencing bone strength and cardiovascular health, not just reproduction.”

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Article adapted by MD Sports Weblog from original press release.
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Contact: A’ndrea Elyse Messer
Penn State

The old adage “use it or lose it” is truer than ever. People who maintain a vigorously active lifestyle as they age gain less weight than people who exercise at more moderate levels, according to a first-of-its-kind study that tracked a large group of runners who kept the same exercise regimen as they grew older. The study also found that maintaining exercise with age is particularly effective in preventing extreme weight gain, which is associated with high blood pressure, high cholesterol, diabetes, and other diseases.

The study, conducted by Paul Williams of the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), followed 6,119 men and 2,221 women who maintained their weekly running mileage (to within three miles per week) over a seven-year period. On average, the men and women who ran over 30 miles per week gained half the weight of those who ran less than 15 miles per week.

“To my knowledge, this is the only study of its type,” says Williams, a staff scientist in Berkeley Lab’s Life Sciences Division. “Other studies have tracked exercise over time, but the majority of people will have changed their exercise habits considerably.”

The research is the latest report from the National Runners’ Health Study, a 20-year research initiative started by Williams that includes more than 120,000 runners. It appears in the May issue of the journal Medicine and Science in Sports and Exercise.

Specifically, between the time subjects entered the study and when they were re-contacted seven years later, 25-to-34-year-old men gained 1.4 pounds annually if they ran less than 15 miles per week. In addition, male runners gained 0.8 pounds annually if they ran between 15 and 30 miles per week, and 0.6 pounds annually if they ran more than 30 miles per week.

This trend is mirrored in women. Women between the ages of 18 and 25 gained about two pounds annually if they ran less than 15 miles per week, 1.4 pounds annually if they ran 15 to 30 miles per week, and slightly more than three-quarters of a pound annually if they ran more than 30 miles per week. Other benefits to running more miles each week included fewer inches gained around the waist in both men and women, and fewer added inches to the hips in women.

“As these runners aged, the benefits of exercise were not in the changes they saw in their bodies, but how they didn’t change like the people around them,” says Williams.

Although growing older and gaining weight is something of a package deal, it isn’t the same in everyone. The lucky few remain lean as they age, most people pack on several pounds, and some people become obese. The latter group is particularly at risk for high blood pressure, high cholesterol, and diabetes. Fortunately, Williams’ results show that maintaining exercise can combat such extreme weight gain.

“Getting people to commit to a vigorously active lifestyle while young and lean will go a long way to reducing the obesity epidemic in this country,” says Williams.

Another paper published in the November 2006 issue of the journal Obesity by Williams and Paul Thompson of Hartford (CT) Hospital found that runners who increased their running mileage gained less weight than those who remained sedentary, and runners that quit running became fatter.

“The time to think about exercise is before you think you need it,” says Williams. “The medical journals are full of reports on how difficult it is to regain the slenderness of youth. The trick is not to get fat.”

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Article adapted by MD Sports Weblog from original press release.
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Contact: Dan Krotz
DOE/Lawrence Berkeley National Laboratory

Williams’ research was funded by the National Heart, Lung and Blood Institute. The study in the May issue of the journal Medicine and Science in Sports and Exercise is entitled Maintaining Vigorous Activity Attenuates 7-yr Weight Gain in 8,340 Runners.

Trained runners who severely limit the amount of fat in their diets may be suppressing their immune system and increasing their susceptibility to infections and inflammation, a University at Buffalo study has shown.In findings presented here today (May 22, 1999) at the fourth International Society for Exercise and Immunology Symposium, lead author Jaya T. Venkatraman, Ph.D., reported that running 40 miles per week on a diet composed of approximately 17 percent fat compromised the runners’ immune response.

The medium and high-fat diets, composed of approximately 32 and 41 percent fat respectively, left the immune system intact, and enhanced certain components, the findings showed.

“The data suggest that higher-fat diets may lower the proinflammatory cytokines, free radicals and hormones, and may enhance the levels of anti-inflammatory cytokines,” Venkatraman said.

Venkatraman is an associate professor of nutrition in the Department of Physical Therapy, Exercise and Nutrition Sciences in the UB School of Health Related Professions.

Earlier studies published by a UB research group headed by David Pendergast, Ed.D., professor of physiology and biophysics, reported that competitive runners who increased the proportion of fat in their diets improved their endurance with no negative effect on weight, body composition, blood pressure, pulse rate or total cholesterol. (See editor’s note)

However, since a high level of fat was thought to be immunosuppressive, the researchers sought to determine if increasing dietary fat would compromise various elements of the immune system, while improving performance.

“In general, moderate levels of exercise are known to enhance the immune system,” said Venkatraman. “But high-intensity exercise and endurance exercise produce excess levels of free radicals, which may place stress on the immune system.

“Since we have shown that athletes perform better on a higher-fat diet than on a low-fat diet, it was important to determine if the higher-fat diet would further compromise the immune system,” she said. “We found that it did not, but the very-low-fat diet did.”

The study involved six female and eight male competitive runners who trained at 40 miles a week and were part of a larger performance study. They spent a month on their normal diets, followed by a month each on diets composed of approximately 17 percent, 32 percent and 41 percent fat. Protein remained stable at 15 percent and carbohydrates made up the difference.

The immune status of the runners was obtained by analyzing concentrations of essential components of the immune system — leukocytes, cytokines and plasma cortisol — in blood samples taken before and after an endurance exercise test. The tests were conducted at the end of each four-week diet period.

Results showed that natural killer cells, a type of leukocyte and one of the body’s defense mechanisms marshaled to fight infection, were more than doubled in runners after the high-fat diet, compared to the low-fat regimen. Levels of PGE2, inflammation-causing prostaglandins, increased after the endurance test and were higher when the runners were on the low-fat diet.

This study is part of a larger investigation to determine the effects of dietary fat on performance, biochemical and nutritional status, and plasma lipids and lipoprotein profiles in distance runners being conducted by a study group composed of — in addition to Venkatraman and Pendergast — Peter Horvath, Ph.D., associate professor in the UB Department of Physical Therapy, Exercise and Nutrition Sciences, and John Leddy, M.D., clinical professor of orthopaedics and associate director of the UB Sports Medicine Institute.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Lois Baker
University at Buffalo

Marathon runners 50 and older, and female athletes in particular, are showing greater improvement in running times than younger runners, according to a study by a Yale professor.Peter Jokl, M.D., professor of orthopedics, and his co-authors, Paul Sethi, M.D., and Andrew Cooper, all of Yale School of Medicine, looked at the running time, age, and gender of all of the runners in the New York City Marathon from 1983 through 1999. They also evaluated the performances of the top 50 male and top 50 female finishers by age categories. There were 415,000 runners in all. Master athletes were classified as those 50 and older.

Jokl said women marathon runners 50-59 improved their average race time by 2.08 minutes per year, which was substantially greater than men runners of the same age, whose running time improved on average about eight seconds per year.

The older male runners, in turn, increased their running time at a much greater rate than younger male runners. The younger runners, male and female ages 20 to 30, did not significantly improve their running times during the period studied. The most significant trends in improved running times noted in the top 50 finishers in the male category occurred in age 60-69 and 70-79, and for women, in ages 50-59 and 60-69.

“Our data reflect the potential for improvement of the general health status of our aging population,” Jokl said. “It is not surprising that the number of participating master athletes continues to rise. There is a general trend towards increasing numbers of our aging population who are in good health and physically able to participate in these types of strenuous competitions.”

He said the performance limits of master athletes appear to be greater than predicted by previous physiologic studies.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Jacqueline Weaver
Yale University

Citation: British Journal of Sports Medicine, Vol. 38: pp 408-412, August 2004