Insights into how muscle adapts to endurance

Duke University Medical Center researchers have identified the skeletal muscle changes that occur in response to endurance exercise and have better defined the role of vascular endothelial growth factor (VEGF) in creating new blood vessels, known as angiogenesis, in the process.

VEGF is a protein known to trigger blood vessel growth by activating numerous genes involved in angiogenesis.

The researchers’ new insights could provide a roadmap for medical investigators as they seek to use VEGF in treating human conditions characterized by lack of adequate blood flow, such as coronary artery disease or peripheral arterial disease.

Using mice as animal models, the researchers found that exercise initially stimulates the production of VEGF, which then leads to an increase in the number of capillaries within a specific muscle fiber type, ultimately leading to an anaerobic to aerobic change in the muscle fibers supplied by those vessels. The VEGF gene produces a protein that is known to trigger blood vessel growth.

The results of the Duke experiments were presented by cardiologist Richard Waters, M.D., Nov. 8, 2004, at the American Heart Association’s annual scientific sessions in New Orleans.

“It is known that exercise can improve the symptoms of peripheral arterial disease in humans and it has been assumed that angiogenesis played a role in this improvement,” Waters said. “However, the clinical angiogenesis trials to date utilizing VEGF have been marginally successful and largely disappointing, so we felt it would be better at this point to return to animal studies in an attempt to better understand the angiogenic process.”

The Duke team performed their experiments using a mouse model of voluntary exercise. This experimental approach is important, they explained, because most skeletal muscle adaptation studies utilize electrical stimulation of the muscle, which is much less physiologic and does not as closely mimic what would be expected in human exercise.

When placed in the dark with a running wheel, mice will instinctively run, the researchers said. In the Duke experiments, 41 out of 42 mice “ran” up to seven miles each night. At regular intervals over a 28-day period, the researchers then performed detailed analysis of capillary growth and the subsequent changes in muscle fiber type and compared these findings to sedentary mice.

Mammalian muscle is generally made up of two different fiber types – slow-twitch fibers requiring oxygen to function, and the fast-twitch fibers, which function in the absence of oxygen by breaking down glucose. Because of their need for oxygen, slow-twitch fibers tend to have a higher density of capillaries.

“Exercise training is probably the most widely utilized physiological stimulus for skeletal muscle, but the mechanisms underlying the adaptations muscle fibers make in response to exercise is not well understood,” Waters said. “What we have shown in our model is that increases in the capillary density occur before a significant change from fast-twitch to slow-twitch fiber type, and furthermore, that changes in levels of the VEGF protein occur before the increased capillary density.”

“Interestingly, capillary growth appears to occur preferentially among fast-twitch fibers, and it is these very fibers that likely change to slow-twitch fibers,” Waters said. “Since exercise has the potential to impact an enormous number of clinical conditions, therapeutic manipulations intended to alter the response to exercise would benefit from a more detailed understanding of what actually happens to muscle as a result of exercise.”

The exact relationship between VEGF, exercise induced angiogenesis, and muscle fiber type adaptation is still not clear and will become the focus of the group’s continuing research. The findings from the current study, however, are providing important temporal and spatial clues to the adaptability process.

“Our data suggests that angiogenesis is one of the key early steps in skeletal muscle adaptation and may be an essential step in the adaptability process,” Waters continued. “This understanding could be crucial for designing new studies that can be performed to inhibit the angiogenic response to exercise in order to directly test the links between angiogenesis and skeletal muscle plasticity.”

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The research team was supported by grants from the American Heart Association and the U.S. Department of Veterans Affairs.

Other members of the Duke team were Ping Li, Brian Annex, M.D., and Zhen Yan, Ph.D. Svein Rotevatn, Haukeland University Hospital, Bergen, Norway, was also a member of the team.

Duke University Medical Center researchers have identified the skeletal muscle changes that occur in response to endurance exercise and have better defined the role of vascular endothelial growth factor (VEGF) in creating new blood vessels, known as angiogenesis, in the process.

VEGF is a protein known to trigger blood vessel growth by activating numerous genes involved in angiogenesis.

The researchers’ new insights could provide a roadmap for medical investigators as they seek to use VEGF in treating human conditions characterized by lack of adequate blood flow, such as coronary artery disease or peripheral arterial disease.

Using mice as animal models, the researchers found that exercise initially stimulates the production of VEGF, which then leads to an increase in the number of capillaries within a specific muscle fiber type, ultimately leading to an anaerobic to aerobic change in the muscle fibers supplied by those vessels. The VEGF gene produces a protein that is known to trigger blood vessel growth.

The results of the Duke experiments were presented by cardiologist Richard Waters, M.D., Nov. 8, 2004, at the American Heart Association’s annual scientific sessions in New Orleans.

“It is known that exercise can improve the symptoms of peripheral arterial disease in humans and it has been assumed that angiogenesis played a role in this improvement,” Waters said. “However, the clinical angiogenesis trials to date utilizing VEGF have been marginally successful and largely disappointing, so we felt it would be better at this point to return to animal studies in an attempt to better understand the angiogenic process.”

The Duke team performed their experiments using a mouse model of voluntary exercise. This experimental approach is important, they explained, because most skeletal muscle adaptation studies utilize electrical stimulation of the muscle, which is much less physiologic and does not as closely mimic what would be expected in human exercise.

When placed in the dark with a running wheel, mice will instinctively run, the researchers said. In the Duke experiments, 41 out of 42 mice “ran” up to seven miles each night. At regular intervals over a 28-day period, the researchers then performed detailed analysis of capillary growth and the subsequent changes in muscle fiber type and compared these findings to sedentary mice.

Mammalian muscle is generally made up of two different fiber types – slow-twitch fibers requiring oxygen to function, and the fast-twitch fibers, which function in the absence of oxygen by breaking down glucose. Because of their need for oxygen, slow-twitch fibers tend to have a higher density of capillaries.

“Exercise training is probably the most widely utilized physiological stimulus for skeletal muscle, but the mechanisms underlying the adaptations muscle fibers make in response to exercise is not well understood,” Waters said. “What we have shown in our model is that increases in the capillary density occur before a significant change from fast-twitch to slow-twitch fiber type, and furthermore, that changes in levels of the VEGF protein occur before the increased capillary density.”

“Interestingly, capillary growth appears to occur preferentially among fast-twitch fibers, and it is these very fibers that likely change to slow-twitch fibers,” Waters said. “Since exercise has the potential to impact an enormous number of clinical conditions, therapeutic manipulations intended to alter the response to exercise would benefit from a more detailed understanding of what actually happens to muscle as a result of exercise.”

The exact relationship between VEGF, exercise induced angiogenesis, and muscle fiber type adaptation is still not clear and will become the focus of the group’s continuing research. The findings from the current study, however, are providing important temporal and spatial clues to the adaptability process.

“Our data suggests that angiogenesis is one of the key early steps in skeletal muscle adaptation and may be an essential step in the adaptability process,” Waters continued. “This understanding could be crucial for designing new studies that can be performed to inhibit the angiogenic response to exercise in order to directly test the links between angiogenesis and skeletal muscle plasticity.”

 

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Article adapted by MD Sports from original press release.
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Contact: Richard Merritt
Duke University Medical Center 

The research team was supported by grants from the American Heart Association and the U.S. Department of Veterans Affairs

Health Benifits Of Weight Lifting For Elderly

ATHENS, Ohio – Men over 60 may be able to increase their strength by as much as 80 percent by performing intense weight training exercises, according to physiologists involved in studies of the health benefits of weight lifting. The researchers also have found that older men gain strength at the same rate as men in their 20s.

In a study of 18 men ages 60 to 75, Ohio University physiologists found that subjects who participated in a 16-week, high-intensity resistence training program on average were 50 percent to 80 percent stronger by the end of the study. None of the participants had engaged in weight lifting prior to the study. Researchers also observed improvements in the seniors’ muscle tone, aerobic capacity and cholesterol profile.

These are some of the latest findings from a decades-long examination of the impact of exercise on the health of men and women of all ages. When researchers compared the strength gains of the elderly participants in this study to findings from other studies they’ve done of college-age men, they found that changes in strength and muscle size were similar in both age groups. The findings were published in a recent issue of the Journal of Gerontology.

“There have been a number of research projects that have come out over the years that suggest there is no age limitation to getting stronger from resistance training,” said Robert Staron, co-author of this study and an associate professor of anatomy in the university’s College of Osteopathic Medicine. “It’s become obvious that it’s important to maintain a certain amount of muscle mass as we age.”

This new study also suggests that elderly men can handle heavy workloads over a long period of time. Participants – who all were in good health and closely monitored during testing and training – performed leg presses, half squats and leg extensions twice a week to exercise the lower body. When the men began the study, they were able to leg press about 375 pounds on average. After the 16-week period, they could take on about 600 pounds. Studies elsewhere have involved low-intensity exercises over a shorter term.

In addition to the increase in strength, researchers found that weight lifting had a beneficial impact on the participants’ cardiovascular system. Tests on an exercise treadmill showed that their bodies used oxygen more efficiently after weight training.

“The individuals run until they are completely exhausted, and it took longer for them to reach that point after resistance training,” Staron said.

Blood samples taken before and after weight training also showed favorable changes in participants’ overall cholesterol profiles, he said, including increases in HDL cholesterol levels and decreases in LDL cholesterol levels.

Losing muscle tone and strength is not uncommon for many senior citizens, Staron said, but this research suggests that a lack of physical exercise can contribute to the problem.

“Certainly, inactivity does play a role in contributing to the decrease in muscle mass,” Staron said. “If we can maintain a certain level of strength through exercise, our quality of life should be better as we age.”

Before beginning a weight lifting regimen, it’s a good idea to consult a physician, Staron advised, adding that it’s also important to learn proper weight lifting techniques. Staron and his colleagues now have turned their attention to how certain weight training routines impact young people.

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Article adapted by MD Sports from original press release.
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Contact: Andrea Gibson
Ohio University

Collaborators on this project are Fredrick Hagerman, Robert Hikida and Thomas Murray of the College of Osteopathic Medicine, former graduate student Seamus Walsh, Roger Gilders of the College of Health and Human Services, Kumika Toma of the College of Arts and Sciences and Kerry Ragg of the Student Health Service.

New Fat Fighting Process Controls Fat Storage

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered a process that controls the amount of fat that cells store for use as a back-up energy source. Disruption of this process allows cellular fat to accumulate — a key factor in age-related metabolic diseases such as obesity and type 2 diabetes. The study is published today in the online version of Nature.

Discovery of this previously unknown fat-fighting pathway could lead to novel drugs for the treatment of metabolic syndrome (characterized by obesity, blood lipid disorders, and insulin resistance) and for a common liver disease known as “fatty liver” or steatohepatitis. Nonalcoholic steatohepatitis (NASH) is a common, often “silent” liver disease. Although NASH resembles alcoholic liver disease, it occurs in people who drink little or no alcohol. NASH affects 2 to 5 percent of Americans, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

All cells store lipids, a type of fat, in the form of small droplets that can be broken down for energy when needed. In situations of excessive food intake or in certain diseases such as diabetes or obesity, these lipid droplets become so large that they interfere with normal cell function.

“In this study, we found that the amount of fat stored in these intracellular lipid droplets is controlled through autophagy, a process until now thought to help primarily in digesting and recycling damaged cellular structures,” says Mark Czaja, M.D., professor of medicine at Einstein whose team worked collaboratively on the research with the laboratory of Ana Maria Cuervo, M.D., Ph.D., associate professor of developmental & molecular biology, medicine, and anatomy & structural biology at Einstein.

Autophagy, or “self-eating,” is carried out by lysosomes, which function as the cell’s recycling center. In studies of liver cells in culture and in live animals, Dr. Czaja and his colleagues discovered that lysosomes do something never before observed: continuously remove portions of lipid droplets and process them for energy production.

“When food is scarce, autophagy becomes a main source of energy for the cells and this process of digesting lipid droplets is accelerated,” says Dr. Cuervo. “If autophagy slows down, as occurs in aging, the lipid droplets stored in cells keep growing and eventually become so big that they can no longer be degraded.”

This slowdown in fat control appears to trigger a vicious cycle in which the enlarging fat droplets impair autophagy, allowing even more fat to accumulate, and so on, which could eventually contribute to diseases such as diabetes. The researchers noted that therapies aimed at helping autophagy operate more efficiently might prevent disease by keeping fat droplets under control.

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Article adapted by MD Sports from original press release.
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Contact: Deirdre Branley
Albert Einstein College of Medicine

Drs. Cuervo and Czaja’s paper, “Autophagy regulates lipid metabolism” is published in the April 1 online version of Nature. Their co-authors at Einstein include Rajat Singh and Susmita Kaushik (primary co-authors), Yongjun Wang, Youqing Xiang, and Inna Novak; as well as Masaaki Komatsu and Keiji Tanaka of the Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo, Japan.

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About Albert Einstein College of Medicine of Yeshiva University

Albert Einstein College of Medicine of Yeshiva University is one of the nation’s premier centers for research, medical education and clinical investigation. It is the home to some 2,000 faculty members, 750 M.D. students, 350 Ph.D. students (including 125 in combined M.D./Ph.D. programs) and 380 postdoctoral investigators. Last year, Einstein received more than $130 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five hospital centers in the Bronx, Manhattan and Long Island – which includes Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein – the College runs one of the largest post-graduate medical training program in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit http://www.aecom.yu.edu.

Endorphins and opioids released during running protect against Heart Attacks

Endorphins and other morphine-like substances known as opioids, which are released during exercise, don’t just make you feel good — they may also protect you from heart attacks, according to University of Iowa researchers.

It has long been known that the so-called “runner’s high” is caused by natural opioids that are released during exercise. However, a UI study, which is published in the online edition of the American Journal of Physiology’s Heart and Circulatory Physiology, suggests that these opioids may also be responsible for some of exercise’s cardiovascular benefits.

Working with rats, UI researchers showed that blocking the receptors that bind morphine, endorphins and other opioids eliminates the cardiovascular benefits of exercise. Moreover, the UI team showed that exercise was associated with increased expression of several genes involved in opioid pathways that appear to be critical in protecting the heart.

“This is the first evidence linking the natural opioids produced during exercise to the cardio-protective effects of exercise,” said Eric Dickson, M.D., UI associate professor and head of emergency medicine in the Roy J. and Lucille A. Carver College of Medicine and the study’s lead investigator. “We have known for a long time that exercise is great for the heart. This study helps us better understand why.”

Studies have shown that regular vigorous exercise reduces the risk of having a heart attack and improves survival rates following heart attack, even in people with cardiovascular disease. In addition, exercise also decreases the risk of atherosclerosis, stroke, osteoporosis and even depression. However, despite these proven health benefits, much less is understood about how exercise produces these benefits.

The UI study investigated the idea that the opioids produced by exercise might have a direct role in cardio-protection. The researchers compared rats that exercised with rats that did not. As expected, exercised rats sustained significantly less heart damage from a heart attack than non-exercised rats. The researchers then showed that blocking opioid receptors completely eliminated these cardio-protective effects in exercising rats, suggesting that opioids are responsible for some of the cardiac benefits of exercise.

The UI team also showed that exercise was associated with transient increases in expression of several opioid system genes in heart muscle, and changes in expression of other genes that are involved in inflammation and cell death. The researchers plan to investigate whether these altered gene expression patterns reveal specific cardio-protective pathways.

A better understanding of how exercise protects the heart may eventually allow scientists to harness these protective effects for patients with decreased mobility.

“Hopefully this study will move us closer to developing therapies that mimic the benefits of exercise,” Dickson said. “It also serves as a reminder of how important it is to get out and exercise every day.”

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Article adapted by MD Only Weblog from original press release.
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Contact: Jennifer Brown
University of Iowa

In addition to Dickson, the UI research team included Christopher Hogrefe, Paula Ludwig, Laynez Ackermann, Lynn Stoll, Ph.D., and Gerene Denning, Ph.D.

STORY SOURCE: University of Iowa Health Science Relations, 5135, Westlawn, Iowa City, Iowa 52242-1178

ORIGINAL ARTICLE: Abstract is available Click here