Posts Tagged ‘Thermo burn’

Molecular switch found in mice could lead to future obesity treatments, scientists say

A surprise discovery — that calorie-burning brown fat can be produced experimentally from muscle precursor cells in mice — raises the prospect of new ways to fight obesity and overweight, say scientists from Dana-Farber Cancer Institute.

Reporting in the Aug. 21 issue of the journal Nature, the researchers demonstrated that brown fat, which is known as the “good” form of fat — so called because it burns calories and releases energy, unlike “bad” white fat that simply stores extra calories — can be generated from unspecialized precursors that routinely spawn skeletal muscle.

The team led by Dana-Farber’s Bruce Spiegelman, PhD, showed that a previously known molecular switch, PRDM16, regulates the creation of brown fat from immature muscle cells. They also determined that the process is a two-way street: Knocking out PRDM16 in brown fat cells can convert them into muscle cells. However, Spiegelman called the latter an “experimental lab trick” for which he currently envisions no practical applications.

The “huge surprise” of the study results, he said, was that muscle precursor cells known as “satellite cells” are able to give birth to brown fat cells under the control of PRDM16.

Spiegelman said the finding confirms that PRDM16 is the “master regulator” of brown fat development. The confirmation will spur ongoing research in his laboratory, he said, to see if drugs that rev up PRDM16 in mice — and potentially, in people — could convert white fat into brown fat and thereby treat obesity. Another strategy, he said, might be to transplant brown fat cells into an overweight person to turn on the calorie-burning process.

“I think we now have very convincing evidence that PRDM16 can turn cells into brown fat cells, with the possibility of combating obesity,” said Spiegelman, the senior author of the paper. The lead author is Patrick Seale, PhD, a postdoctoral fellow in the Spiegelman lab.

Another paper in the same issue of Nature described a different trigger of brown fat production, a molecule called BMP7. A commentary in the journal by Barbara Cannon, an internationally recognized researcher in the biology of fat cells at the University of Stockholm, said that the two reports “take us a step closer to the ultimate goal of promoting the brown fat lineage as a potential way of counteracting obesity.”

The Spiegelman group has long studied fat cells both as a model for normal and abnormal cell development, which relates to cancer, and also because fat cells play such a key role in the growing epidemics of obesity and diabetes.

There is much interest in brown fat’s role in regulating metabolism. Rodents and human infants have abundant brown fat that dissipates food energy as heat to protect against the cold. Though human adults have little brown fat, it apparently does have a metabolic function, including the potential to be amplified in some way to combat obesity.

In 2007, Spiegelman and colleagues reported they had inserted PRDM16 genes into white fat precursors, which they implanted under the skin of mice. The PRDM16 switch coaxed the white fat precursors to produce brown fat cells instead of white. To Spiegelman, this suggested the possibility of transplanting PRDM16-equipped white fat precursors into people who are at high risk of becoming obese, to shift their metabolism slightly into a calorie-burning mode.

The new research adds another potential source of brown fat — the muscle cell progenitors, or myoblasts, that exist in the body to replace mature muscle cells as needed. The progenitors, which can be thought of as “adult stem cells,” are committed to becoming specialized muscle cells when activated by appropriate signals, or, as the study revealed, brown fat cells when PDRM16 is turned on. The PRDM16 trigger “is very powerful at what it does,” said Spiegelman, who is also a professor of cell biology at Harvard Medical School.

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Article adapted by MD Sports from original press release.
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Contact: Bill Schaller
Dana-Farber Cancer Institute 

Other authors of the paper include Bryan Bjork, PhD, and David R. Beier, PhD, MD, of Brigham and Women’s Hospital; Michael Rudnicki, PhD, of the Ottawa Health Research Institute; and Hediye Erdjument-Bromage, PhD, and Paul Tempst, PhD, of Memorial Sloan-Kettering Cancer Center.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

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Consuming caffeine, whether in coffee of soft drinks, has been shown to delay fatigue during prolonged exercise. Studies have shown, for example, that ingesting three to nine mg/kg of caffeine can increase the amount of exercise time to achieve by as much as 50 percent. How caffeine achieves this effect has not been fully determined.

Caffeine and the Central Nervous System (CNS) Study

No previous research effort has examined the possible direct central nervous system (CNS) effects of caffeine on fatigue during prolonged exercise. Now, a team of researchers from the University of South Carolina has hypothesized that the blockade of adenosine receptors by caffeine may be the most likely mechanism of CNS stimulation and delayed fatigue.

Their theory is based on the fact that adenosine is produced within the body and inhibits neuronal excitability and synapse transmission. Adenosine also inhibits the release of most brain excitatory neurotransmitters, particularly dopamine (DA), and may reduce DA synthesis. Decreases in dopamine (DA), along with increases in 5-HT (serotonin, which is generally associated with behavioral suppression), have been linked to central fatigue during exercise. In addition, adenosine has been shown to reduce arousal, induce sleep, and suppress spontaneous activity, which are all behaviors associated with increases in 5-HT.

The researchers’ hypothesis is the foundation of a new study to determine the effects of intracerebroventricular injection of caffeine and the adenosine A1 and A2 receptor agonist 5′-N-ethylcarboxamidoadenosine (NECA) on treadmill run time to fatigue in rats. NECA was chosen for the study because caffeine is a nonselective adenosine receptor antagonist, and it is not known which of the four subtypes of adenosine receptors may be involved in an effect of caffeine on fatigue. However, A2b and A3 receptors are relatively less active than A1 and A2a receptors under normal physiological conditions. If the researchers were correct, the CNS administration of caffeine will increase run time to fatigue, whereas NECA will reduce run time to fatigue. Furthermore, pretreatment with caffeine before NECA will weaken the fatigue-inducing effects of NECA.

The authors of “Central Nervous System Effects of Caffeine and Adenosine on Fatigue,” are J. Mark Davis, Zuowei Zhao, Howard S. Stock, Kristen A. Mehl, James Buggy, and Gregory A. Hand, all from the Schools of Public Health and Medicine, University of South Carolina, Columbia, SC. Their findings appear in the February 2003 edition of the American Journal of Physiology –Regulatory, Integrative and Comparative Physiology. The journal is one of 14 peer-reviewed publications produced monthly by the American Physiological Society (APS).

Methodology

Male Wistar rats, five weeks old and weighing 200-250 grams, were used in this study, and randomly assigned to intracerebroventricular or intraperitoneal injection groups. Rats were given two weeks of treadmill acclimation of running for 15 minutes a day. The treadmill speed was slowly increased from eight meters a minute, 7.5 percent grade at the beginning, progressing to 20 meters a minute at the end of the acclimation period. Gentle hand prodding and mild electric shock were combined to encourage the animals to run throughout the study.

After the first two weeks of acclimation, rats assigned to the intracerebroventricular group were anesthetized with pentobarbital sodium, and tubes were implanted bilaterally into the lateral ventricles. After seven days of recovery from surgery, the rats were again acclimated to treadmill running for another one to two weeks, until they were able to run easily for at least 15 minutes per day for 5 consecutive days at a speed of 20 meters a minute at a 7.5 percent grade. Animals that were unable to run at that pace were excluded.

Four drug treatments were used in the study: NECA, caffeine, caffeine plus NECA, and a vehicle solution (Normosol-R). The vehicle solution has been used as a control solution in other studies involving intracerebroventricular infusions of drugs and tissue microdialysis. In the CNS groups (n = 10), each rat was injected intracerebroventricularly with one of the four drugs (NECA, caffeine, caffeine plus NECA, or vehicle) in one testing session. The other drugs were then given in successive testing sessions at one-week intervals to allow full recovery from the exercise bout and washout of the drugs. On two days during the recovery period, all rats were exercised for 15 minutes to maintain acclimation to the treadmill protocol. All rats received all four-drug treatments in a randomized and counterbalanced design to minimize possible order effects.

Results
The major findings of this study revealed that:

  • CNS administration of caffeine at a dose of 200 µg/rat (0.6 mg/kg), which is much less than the effective dose given peripherally (6 mg/kg), does increase treadmill run time to fatigue in rats by approximately 60 percent;
  • the same dose of caffeine given peripherally (intraperitoneally) is ineffective.
  • the results supported the researchers’ hypothesis that intracerebroventricular CNS administration of the selective adenosine A1 and A2 receptor agonist NECA significantly reduced run time to fatigue, whereas intracerebroventricular caffeine increased run time to fatigue.
  • inhibitory effects of NECA on run time to fatigue were also reversed by intracerebroventricular pretreatment with caffeine, suggesting that the ergogenic effects of intracerebroventricular caffeine are mediated through blockade of the adenosine receptors.
  • CNS administration of the adenosine receptor agonist NECA inhibited treadmill run time to fatigue and spontaneous locomotor activity in rats.
  • pretreatment with caffeine blocked the inhibitory effects of NECA on exercise performance, although not on spontaneous behavioral activity.
  • peripheral (intraperitoneal) administration of the same drugs at the same doses had no effect on treadmill run time to fatigue.

Conclusions

These results indicate that caffeine can act specifically within the CNS to delay fatigue, at least in part by blocking adenosine receptors. Because caffeine easily crosses the BBB, these results also suggest that the CNS also plays an important role in the ergogenic effect of caffeine ingestion.

The precise independent contribution of caffeine at the central (behavioral) and peripheral (metabolic) levels awaits further research. The researchers argue that some interaction at both levels is likely.

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Article adapted by MD Only Sports Weblog from original press release.
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Contact: Donna Krupa
American Physiological Society

Source: February 2003 edition of the American Journal of Physiology– Regulatory, Integrative and Comparative Physiology

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

Although it’s too soon to recommend dropping by Starbucks before hitting the gym, a new study suggests that caffeine can help reduce the post-workout soreness that discourages some people from exercising.In a study to be published in the February issue of The Journal of Pain, a team of University of Georgia researchers finds that moderate doses of caffeine, roughly equivalent to two cups of coffee, cut post-workout muscle pain by up to 48 percent in a small sample of volunteers.

Lead author Victor Maridakis, a researcher in the department of kinesiology at the UGA College of Education, said the findings may be particularly relevant to people new to exercise, since they tend to experience the most soreness.

“If you can use caffeine to reduce the pain, it may make it easier to transition from that first week into a much longer exercise program,” he said.

Maridakis and his colleagues studied nine female college students who were not regular caffeine users and did not engage in regular resistance training. One and two days after an exercise session that caused moderate muscle soreness, the volunteers took either caffeine or a placebo and performed two different quadriceps (thigh) exercises, one designed to produce a maximal force, the other designed to generate a sub-maximal force. Those that consumed caffeine one-hour before the maximum force test had a 48 percent reduction in pain compared to the placebo group, while those that took caffeine before the sub-maximal test reported a 26 percent reduction in pain.

Caffeine has long been known to increase alertness and endurance, and a 2003 study led by UGA professor Patrick O’Connor found that caffeine reduces thigh pain during moderate-intensity cycling. O’Connor, who along with professors Kevin McCully and the late Gary Dudley co-authored the current study, explained that caffeine likely works by blocking the body’s receptors for adenosine, a chemical released in response to inflammation.

Despite the positive findings in the study, the researchers say there are some caveats. First, the results may not be applicable to regular caffeine users, since they may be less sensitive to caffeine’s effect. The researchers chose to study women to get a definitive answer in at least one sex, but men may respond differently to caffeine. And the small sample size of nine volunteers means that the study will have to be replicated with a larger study.

O’Connor said that despite these limitations, caffeine appears to be more effective in relieving post-workout muscle pain than several commonly used drugs. Previous studies have found that the pain reliever naproxen (the active ingredient in Aleve) produced a 30 percent reduction in soreness. Aspirin produced a 25 percent reduction, and ibuprofen has produced inconsistent results.

“A lot of times what people use for muscle pain is aspirin or ibuprofen, but caffeine seems to work better than those drugs, at least among women whose daily caffeine consumption is low,” O’Connor said.

Still, the researchers recommend that people use caution when using caffeine before a workout. For some people, too much caffeine can produce side effects such as jitteriness, heart palpitations and sleep disturbances.

“It can reduce pain,” Maridakis said, “but you have to apply some common sense and not go overboard.”

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Article adapted by MD Only Sports Weblog from original press release.
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Contact: Sam Fahmy
University of Georgia

The serious athlete knows better than to rely just on a famous cereal to provide additional energy in preparation of a sporting event. Supplements have assumed an important role in today’s training regimen. Some – such as anabolic steroids — have been deemed illegal by most sports authorities. Others – such as caffeine and creatine — are controversial yet presently allowed.Background
Caffeine, the primary ingredient of coffee, is used as a central nervous system stimulant, diuretic, circulatory and respiratory stimulant, and as an adjunct in the treatment of headaches. Evidence shows that caffeine intensifies muscle contractions, masks the discomfort of physical exertion, and even speeds up the use of the muscles’ short-term fuel stores. Some exercise physiologists believe that caffeine might improve performance by increasing fat oxidation and conserving muscle glycogen.

Creatine is used by athletes to increase lean body mass and improve performance in single and repetitive high-intensity, short-duration exercise tasks such as weightlifting, sprinting, and cycling. It is a popular nutritional supplement that is used by physically active people – from recreational exercisers to Olympic and professional athletes. According to a recent survey, 28 percent of athletes in an NCAA Division IA program reported using creatine. The creatine that is normally present in human muscle may come from two potential sources: dietary (animal flesh) and internally manufactured.

The purpose of creatine supplementation is to increase either total creatine stores or phosphocreatine (PCr) stores within muscle. Supplementation increases the rate of resynthesis of creatine phosphate following exercise. Various studies have shown increased muscle PCr levels after supplementing with 20-30 grams of creatine monohydrate daily.

Creatine supplementation has also been known to shorten relaxation time during intermittent maximal iosometric muscle contraction. This shortened time, coupled with a creatine loaded muscle facilitates calcium absorption into the sarcoplasmic reticulum (the endoplasmic reticulum of skeletal and cardiac muscle). However, some believe that caffeine intake enhances calcium release from the sarcoplasmic reticulum.

The Study
This has lead a research team from Belgium to suggest that the combined effects of creatine and caffeine supplementation may be counterproductive to creatine’s effect on muscle relaxation time. The authors of the study, “Opposite Actions of Caffeine and Creatine on Muscle Relaxation Time in Humans” are P. Hespel, B. Op ‘T Eijnde, and M. Van Leemputte, all from the Department of Kinesiology, Katholieke Universiteit Leuven, Leuven, Belgium. Their findings appear in the February 2002 edition of the Journal of Applied Physiology.

Methodology
Ten physical education students (nine men and one woman) participated in the study. They were told to abstain from medication and caffeine intake one week prior to the experiment. The subjects were additionally asked to avoid changes in their level of physical activity and diet during the 25-week duration of the study. In this double blind experiment, the subjects performed the exercise test before and after creatine supplementation, short-term caffeine intake, creatine supplementation in the short term, acute caffeine intake, or a placebo.

This study required the random assignment of the students into five experimental protocols, each lasting eight days. Three elements were measured during an experiment consisting of 30 intermittent contractions of quadriceps entailing two seconds of stimulation and two seconds of rest. Measurements included maximum torque (Tmax), contraction time (CT) from 0.25 to 0.75 of Tmax, and relaxation time (RT) from 0.75 to 0.25 of max.

Results
Key findings of this study included:

· a confirmation of the fact that oral creatine supplementation shortens muscle relaxation time in humans: relation time was reduced by five percent and was significantly shorter than after the placebo;

· discovery that the intake of caffeine, combined with a daily creatine supplement, counteracted the beneficial effects of creatine intake on relaxation time and fatigue enhanced this inhibitory effect; and

· the observation that caffeine reduces the functional capacity of sacroplasmic reticulum calcium ATPase.

Conclusion The researchers believe that the findings from this experiment offer indirect evidence that suggests that facilitation of muscle relaxation may be important to the ergogenic action of creatine supplementation as well as power production during sprint exercises.

However, for the athlete in training, the key finding is that sustained caffeine intake, over a three-day period, negates the benefits of creatine supplements.

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Article adapted by MD Only Sports Weblog from original press release.
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Contact: Donna Krupa
American Physiological Society