Posts tagged science
Articles and news from the latest research reports.
Dark matter made visible before the final cut
Research findings from the University of North Carolina School of Medicine are shining a light on an important regulatory role performed by the so-called dark matter, or “junk DNA,” within each of our genes.
The new study reveals snippets of information contained in dark matter that can alter the way a gene is assembled.
“These small sequences of genetic information tell the gene how to splice, either by enhancing the splicing process or inhibiting it. The research opens the door for studying the dark matter of genes. And it helps us further understand how mutations or polymorphisms affect the functions of any gene,” said study senior author, Zefeng Wang, PhD, assistant professor of pharmacology in the UNC School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center.
The study is described in a report published in the January 2013 issue of the journal Nature Structural & Molecular Biology.
Cheap and easy technique to snip DNA could revolutionize gene therapy
A simple, precise and inexpensive method for cutting DNA to insert genes into human cells could transform genetic medicine, making routine what now are expensive, complicated and rare procedures for replacing defective genes in order to fix genetic disease or even cure AIDS.
Discovered last year by Jennifer Doudna and Martin Jinek of the Howard Hughes Medical Institute and University of California, Berkeley, and Emmanuelle Charpentier of the Laboratory for Molecular Infection Medicine-Sweden, the technique was labeled a “tour de force” in a 2012 review in the journal Nature Biotechnology.
That review was based solely on the team’s June 28, 2012, Science paper, in which the researchers described a new method of precisely targeting and cutting DNA in bacteria.
Two new papers published last week in the journal Science Express (1 , 2) demonstrate that the technique also works in human cells. A paper by Doudna and her team reporting similarly successful results in human cells has been accepted for publication by the new open-access journal eLife.
“The ability to modify specific elements of an organism’s genes has been essential to advance our understanding of biology, including human health,” said Doudna, a professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute Investigator at UC Berkeley. “However, the techniques for making these modifications in animals and humans have been a huge bottleneck in both research and the development of human therapeutics.
“This is going to remove a major bottleneck in the field, because it means that essentially anybody can use this kind of genome editing or reprogramming to introduce genetic changes into mammalian or, quite likely, other eukaryotic systems.”
“I think this is going to be a real hit,” said George Church, professor of genetics at Harvard Medical School and principal author of one of the Science Express papers. “There are going to be a lot of people practicing this method because it is easier and about 100 times more compact than other techniques.”
“Based on the feedback we’ve received, it’s possible that this technique will completely revolutionize genome engineering in animals and plants,” said Doudna, who also holds an appointment at Lawrence Berkeley National Laboratory. “It’s easy to program and could potentially be as powerful as the Polymerase Chain Reaction (PCR).”
The latter technique made it easy to generate millions of copies of small pieces of DNA and permanently altered biological research and medical genetics.
Stem cell materials could boost research into key diseases
Stem cell manufacturing for drug screening and treatments for diseases such as Huntington’s and Parkinson’s could be boosted by a new method of generating stem cells, a study suggests.
Scientists have developed a family of compounds that can support the growth of human embryonic stem cells on a large scale for use in drug testing or treatments.
The new materials, which are water-based gels, act as a tiny scaffold to which cells can cling as they grow. Normally cells must be grown on expensive biological surfaces that can carry pathogens and contaminate cells.
Once cells have multiplied sufficiently for their intended purpose, the gels can be cooled, enabling the stem cells to drop off the scaffold without becoming damaged.
The new approach surpasses existing techniques of separating cells by mechanical or chemical means, which carry a greater risk of damage to cells.
Scientists say the materials could offer a means of enabling the stem cells to be produced in large numbers efficiently and without the risk of inadvertent contamination, facilitating research, drug screening programmes and clinical applications that call for large numbers of cells.
Researchers at the University of Edinburgh developed the new materials by screening hundreds of potential compounds for their ability to support stem cell growth. From a shortlist of four, one has been found to be effective, and researchers say the remaining three show similar potential.
Stem cells provide a powerful tool for screening drugs as they can be used to show the effects of drugs on cells and systems within the body.
The study, published in Nature Communications, was supported by the European Union Framework 7 Grant Funding. The gels are being developed under licence by technology company Ilika.
Dr Paul de Sousa, of the University of Edinburgh’s Scottish Centre for Regenerative Medicine, said: “This development could greatly enhance automated production of embryonic stem cells, which would improve the efficiency and reduce the cost of stem cell manufacturing. We are also looking into whether this work could help develop pluripotent stem cells induced from adult cells.”
Does listening to Mozart really boost your brainpower?
It is said that classical music could make children more intelligent, but when you look at the scientific evidence, the picture is more mixed.
You have probably heard of the Mozart effect. It’s the idea that if children or even babies listen to music composed by Mozart they will become more intelligent. A quick internet search reveals plenty of products to assist you in the task. Whatever your age there are CDs and books to help you to harness the power of Mozart’s music, but when it comes to scientific evidence that it can make you more clever, the picture is more mixed.
The phrase “the Mozart effect” was coined in 1991, but it is a study described two years later in the journal Nature that sparked real media and public interest about the idea that listening to classical music somehow improves the brain. It is one of those ideas that feels plausible. Mozart was undoubtedly a genius himself, his music is complex and there is a hope that if we listen to enough of it, a little of that intelligence might rub off on us.
The idea took off, with thousands of parents playing Mozart to their children, and in 1998 Zell Miller, the Governor of the state of Georgia in the US, even asked for money to be set aside in the state budget so that every newborn baby could be sent a CD of classical music. It’s not just babies and children who were deliberately exposed to Mozart’s melodies. When Sergio Della Sala, the psychologist and author of the book Mind Myths, visited a mozzarella farm in Italy, the farmer proudly explained that the buffalos were played Mozart three times a day to help them to produce better milk.
I’ll leave the debate on the impact on milk yield to farmers, but what about the evidence that listening to Mozart makes people more intelligent? Exactly what was it was that the authors of the initial study discovered that took public imagination by storm?
When you look back at the original paper, the first surprise is that the authors from the University of California, Irvine are modest in their claims and don’t even use the “Mozart effect” phrase in the paper. The second surprise is that it wasn’t conducted on children at all: it was in fact conducted with those stalwarts of psychological studies – young adult students. Only 36 students took part. On three occasions they were given a series of mental tasks to complete, and before each task, they listened either to ten minutes of silence, ten minutes of a tape of relaxation instructions, or ten minutes of Mozart’s sonata for two pianos in D major (K448).
The students who listened to Mozart did better at tasks where they had to create shapes in their minds. For a short time the students were better at spatial tasks where they had to look at folded up pieces of paper with cuts in them and to predict how they would appear when unfolded. But unfortunately, as the authors make clear at the time, this effect lasts for about fifteen minutes. So it’s hardly going to bring you a lifetime of enhanced intelligence.
Brain arousal
Nevertheless, people began to theorise about why it was that Mozart’s music in particular could have this effect. Did the complexity of music cause patterns of cortical firing in the brain similar to those associated with solving spatial puzzles?
More research followed, and a meta-analysis of sixteen different studies confirmed that listening to music does lead to a temporary improvement in the ability to manipulate shapes mentally, but the benefits are short-lived and it doesn’t make us more intelligent.
Then it began to emerge that perhaps Mozart wasn’t so special after all. In 2010 a larger meta-analysis of a greater number of studies again found a positive effect, but that other kinds of music worked just as well. One study found that listening to Schubert was just as good, and so was hearing a passage read out aloud from a Stephen King novel. But only if you enjoyed it. So, perhaps enjoyment and engagement are key, rather than the exact notes you hear.
Although we tend to associate the Mozart effect with babies and small children, most of these studies were conducted on adults, whose brains are of course at a very different stage of development. But in 2006 a large study was conducted in Britain involving eight thousand children. They listened either to ten minutes of Mozart’s String Quintet in D Major, a discussion about the experiment or to a sequence of three pop songs: Blur’s “Country House,” “Return of the Mack,” by Mark Morrison and PJ and Duncan’s “Stepping Stone”. Once again music improved the ability to predict paper shapes, but this time it wasn’t a Mozart effect, but a Blur effect. The children who listened to Mozart did well, but with pop music they did even better, so prior preference could come into it.
Whatever your musical choice, it seems that all you need to do a bit better at predictive origami is some cognitive arousal. Your mind needs to get a little more active, it needs something to get it going and that’s going to be whichever kind of music appeals to you. In fact, it doesn’t have to be music. Anything that makes you more alert should work just as well – doing a few star jumps or drinking some coffee, for instance.
There is a way in which music can make a difference to your IQ, though. Unfortunately it requires a bit more effort than putting on a CD. Learning to play a musical instrument can have a beneficial effect on your brain. Jessica Grahn, a cognitive scientist at Western University in London, Ontario says that a year of piano lessons, combined with regular practice can increase IQ by as much as three points.
So listening to Mozart won’t do you or your children any harm and could be the start of a life-long love of classical music. But unless you and your family have some urgent imaginary origami to do, the chances are that sticking on a sonata is not going to make you better at anything.
(Source: bbc.com)
First Oral Drug for Spinal Cord Injury Improves Movement in Mice
An experimental oral drug given to mice after a spinal cord injury was effective at improving limb movement after the injury, a new study shows.
The compound efficiently crossed the blood-brain barrier, did not increase pain and showed no toxic effects to the animals.
“This is a first to have a drug that can be taken orally to produce functional improvement with no toxicity in a rodent model,” said Sung Ok Yoon, associate professor of molecular & cellular biochemistry at Ohio State University and lead author of the study. “So far, in the spinal cord injury field with rodent models, effective treatments have included more than one therapy, often involving invasive means. Here, with a single agent, we were able to obtain functional improvement.”
The small molecule in this study was tested for its ability to prevent the death of cells called oligodendrocytes. These cells surround and protect axons, long projections of a nerve cell, by wrapping them in myelin. In addition to functioning as axon insulation, myelin allows for the rapid transmission of signals between nerve cells.
The drug preserved oligodendrocytes by inhibiting the activation of a protein called p75. Yoon’s lab previously discovered that p75 is linked to the death of these specialized cells after a spinal cord injury. When they die, axons that are supported by them degenerate.
“Because we know that oligodendrocytes continue to die for a long period of time after an injury, we took the approach that if we could put a brake on that cell death, we could prevent continued degeneration of axons,” she said. “Many researchers in the field are focusing on regeneration of neurons, but we specifically targeted a different type of cells because it allows a relatively long therapeutic window.”
An additional benefit of targeting oligodendrocytes is that it can amplify the therapeutic effect because a single oligodendrocyte myelinates multiple axons.
A current acute treatment for humans, methylprednisolone, must be administered within eight but not more than 24 hours after the injury to be effective at all. An estimated 1.3 million people in the United States are living with spinal cord injuries, experiencing paralysis and complications that include bladder, bowel and sexual dysfunction and chronic pain.
The experimental drug, called LM11A-31, was developed by study co-author Frank Longo, professor of neurology and neurological sciences at Stanford University. The drug is the first to be developed with a specific target, p75, as a potential therapy for spinal cord injury.
The research is published in the Jan. 9, 2013, issue of The Journal of Neuroscience.
Researchers gave three different oral doses of LM11A-31, as well as a placebo, to different groups of mice beginning four hours after injury and then twice daily for a 42-day experimental period. The scientists analyzed the compound’s effectiveness at improving limb movement and preventing myelin loss.
The spinal cord injuries in mice mimicked those caused in humans by the application of extensive force and pressure, resulting in loss of hind-limb and bladder function andexperimentally calibrated baseline difficulty in walking and swimming.
The researchers determined that the mice did not experience more pain than the placebo group at all the doses tested, suggesting that LM11A-31 does not worsen nerve pain after spinal cord injury.
Analysis showed that the extent of myelin sparing was dependent on the dose of the drug. Each dose – 10, 25 or 100 milligrams per kilogram of body weight – led to increasing myelin sparing, with the highest dose demonstrating the greatest effect.
The injury in the animals caused a loss of about 75 percent of myelinated axons in the lesion area in the placebo group. This loss was reduced so that myelinated axons reached more than half of the normal levels with LM11A-31 at 100 mg/kg. That was correlated with about a 50 percent increase in surviving oligodendrotcytes compared to those in the placebo group, Yoon said.
In behavior tests, only the highest dose of the compound led to improvements in motor function. Mice were tested in both weight-bearing and non-weight-bearing activities over the 42 days to evaluate their functional recovery.
Mice receiving the highest dose could walk with well-coordinated steps. In swimming tests, scientists saw similar improvements, with mice receiving the highest dose most able to coordinate hind-limb crisscross movement. The other treatment groups exhibited difficulty in walking and swimming.
Yoon said the findings may suggest that myelin sparing needs to reach a threshold of roughly 50 percent of normal levels before motor function improvements become measurable.
“The cellular analysis of the myelin profile detects small changes. Behavior is more complex, and we don’t think functional behavior necessarily improves in a linear fashion,” she said. “Still, these results clearly show that this is the first oral drug in spinal cord injury that works alone to improve function.”
(Source: researchnews.osu.edu)
Study shows cogntive benefit of lifelong bilingualism
Seniors who have spoken two languages since childhood are faster than single-language speakers at switching from one task to another, according to a study published in the January 9 issue of The Journal of Neuroscience. Compared to their monolingual peers, lifelong bilinguals also show different patterns of brain activity when making the switch, the study found.
The findings suggest the value of regular stimulating mental activity across the lifetime. As people age, cognitive flexibility — the ability to adapt to unfamiliar or unexpected circumstances — and related “executive” functions decline. Recent studies suggest lifelong bilingualism may reduce this decline — a boost that may stem from the experience of constantly switching between languages. However, how brain activity differs between older bilinguals and monolinguals was previously unclear.
In the current study, Brian T. Gold, PhD, and colleagues at the University of Kentucky College of Medicine, used functional magnetic resonance imaging (fMRI) to compare the brain activity of healthy bilingual seniors (ages 60-68) with that of healthy monolingual seniors as they completed a task that tested their cognitive flexibility. The researchers found that both groups performed the task accurately. However, bilingual seniors were faster at completing the task than their monolingual peers despite expending less energy in the frontal cortex — an area known to be involved in task switching.
“This study provides some of the first evidence of an association between a particular cognitively stimulating activity — in this case, speaking multiple languages on a daily basis — and brain function,” said John L. Woodard, PhD, an aging expert from Wayne State University, who was not involved with the study. “The authors provide clear evidence of a different pattern of neural functioning in bilingual versus monolingual individuals.”
The researchers also measured the brain activity of younger bilingual and monolingual adults while they performed the cognitive flexibility task.
Overall, the young adults were faster than the seniors at performing the task. Being bilingual did not affect task performance or brain activity in the young participants. In contrast, older bilinguals performed the task faster than their monolingual peers and expended less energy in the frontal parts of their brain.
“This suggests that bilingual seniors use their brains more efficiently than monolingual seniors,” Gold said. “Together, these results suggest that lifelong bilingualism may exert its strongest benefits on the functioning of frontal brain regions in aging.”
(Image: Harriet Russell)
Simulated Mars Mission Reveals Body’s Sodium Rhythms
Clinical pharmacologist Jens Titze, M.D., knew he had a one-of-a-kind scientific opportunity: the Russians were going to simulate a flight to Mars, and he was invited to study the participating cosmonauts.
Titze, now an associate professor of Medicine at Vanderbilt University, wanted to explore long-term sodium balance in humans. He didn’t believe the textbook view – that the salt we eat is rapidly excreted in urine to maintain relatively constant body sodium levels. The “Mars500” simulation gave him the chance to keep salt intake constant and monitor urine sodium levels in humans over a long period of time.
Now, in the Jan. 8 issue of Cell Metabolism, Titze and his colleagues report that – in contrast to the prevailing dogma – sodium levels fluctuate rhythmically with 7-day and monthly cycles. The findings, which demonstrate that sodium is stored in the body, have implications for blood pressure control, hypertension and salt-associated cardiovascular risk.
Titze’s interest in sodium balance was sparked by human space flight simulation studies he conducted in the 1990s that showed rhythmic variations in sodium urine excretion.
“It was so clear to me that sodium must be stored in the body, but no one wanted to hear about that because it was so different from the textbook view,” he said.
He and his team persisted with animal studies and demonstrated that the skin stores sodium and that the immune system regulates sodium release from the skin.
In 2005, planning began for Mars500 – a collaboration between Russia, the European Union and China to prepare for manned spaceflight to Mars. Mars500 was conducted at a research facility in Moscow between 2007 and 2011 in three phases: a 15-day phase to test the equipment, a 105-day phase, and a 520-day phase to simulate a full-length manned mission.
Crews of healthy male cosmonauts volunteered to live and work in an enclosed habitat of sealed interconnecting modules, as if they were on an international space station. Titze and his colleagues organized the food for the mission and secured commitments from the participants to consume all of the food and to collect all urine each day. They studied twelve men: six for the full 105-day phase of the program, and six for the first 205 days of the 520-day phase.
“It was the participants’ stamina to precisely adhere to the daily menu plans and to accurately collect their urine for months that allowed scientific discovery,” Titze said. The researchers found that nearly all (95 percent) of the ingested salt was excreted in the urine, but not on a daily basis. Instead, at constant salt intake, sodium excretion fluctuated with a weekly rhythm, resulting in sodium storage. The levels of the hormones aldosterone (a regulator of sodium excretion) and cortisol (no known major role in sodium balance) also fluctuated weekly.
Changes in total body sodium levels fluctuated on monthly and longer cycles, Titze said. Sodium storage on this longer cycle was independent of salt intake and did not include weight gain, supporting the idea that sodium is stored without accompanying increases in water.
The findings suggest that current medical practice and studies that rely on 24-hour urine samples to determine salt intake are not accurate, he said. “We understand now that there are 7-day and monthly sodium clocks that are ticking, so a one-day snapshot shouldn’t be used to determine salt intake.”
Using newly developed magnetic resonance imaging (MRI) technologies to view sodium, Titze and his colleagues have found that humans store sodium in skin (as they found in their animal studies) and in muscle.
The investigators suspect that genes related to the circadian “clock” genes, which regulate daily rhythms, may be involved in sodium storage and release. “We find these long rhythms of sodium storage in the body particularly intriguing,” Titze said. “The observations open up entirely new avenues for research.”
In the first study of its kind, a team of researchers led by faculty at the Perelman School of Medicine at the University of Pennsylvania and the Baylor College of Medicine, has analyzed data on the impact of prolonged operational confinement on sleep, performance, and mood in astronauts from a groundbreaking international effort to simulate a 520-day space mission to Mars. The findings, published online-first in the Proceedings of the National Academy of Sciences, revealed alterations of life-sustaining sleep patterns and neurobehavioral consequences for crew members that must be addressed for successful adaption to prolonged space missions.
"The success of human interplanetary spaceflight, which is anticipated to be in this century, will depend on the ability of astronauts to remain confined and isolated from Earth much longer than previous missions or simulations," said David F. Dinges, PhD, professor and chief, Division of Sleep and Chronobiology in the Department of Psychiatry at the Perelman School of Medicine, and co-lead author of the new study. "This is the first investigation to pinpoint the crucial role that sleep-wake cycles will play in extended space missions."
The 520-day simulation, which was developed by the Institute for Biomedical Problems (IBMP) of the Russian Academy of Sciences, and sponsored in part by the European Space Agency (ESA), was initiated on June 3, 2010 when the hatches were closed on a 550-cubic-meter IBMP spacecraft-like confinement facility in Russia. The simulated mission, involving an international, six-man team of volunteers, involved more than 90 experiments and realistic scenarios to gather valuable psychological and medical data on the effects of a long-term deep space flight. The 520-day mission was broken into three phases: 250 days for the trip to Mars, 30 days on the surface, and 240 days for the return to Earth.
“As the only U.S. research team involved with the Mars 520-day simulation, the study required international coordination and strong collaborations to ensure that the experiments were conducted in a thorough and rigorous manner,” said Jeffrey P. Sutton, MD, PhD, professor and director, Center for Space Medicine at Baylor College of Medicine, and senior study author. The investigators monitored the crew’s rest-activity patterns, performance and psychological responses to determine the extent to which sleep loss, fatigue, stress, mood changes and conflicts occurred during the mission.
Measurements included continuous recordings of body movements using wrist actigraphy (a noninvasive means of estimating sleep and movement intensity), and light exposure and weekly computer-based neurobehavioral assessments to identify changes in the crew’s activity levels, sleep quantity and quality, sleep–wake intervals, alertness performance, and workload throughout the 17 months of mission confinement.
Data from the actigraph devices revealed that crew sedentariness increased across the mission, as illustrated by decreased waking movement and increased sleep and rest times. The majority of crewmembers also experienced one or more disturbances of sleep quality, alertness deficits, or altered sleep–wake intervals and timing, suggesting inadequate circadian synchronization.
"Taken together, these measurements point to the need to identify markers of differential vulnerability to abnormal decrease in muscular movement and sleep– wake changes in crew members during the prolonged isolation of exploration spaceflight and the need to ensure maintenance of the Earth’s natural circadian rhythm, sleep quantity and quality, and optimal activity levels during exploration missions," said Mathias Basner, MD, PhD, MSc, assistant professor of Sleep and Chronobiology in Psychiatry at Penn, and co-lead author.
The research team concludes that successful adaptation to such missions will require crews to transit in spacecraft and live in surface habitats that artificially mimic aspects of Earth’s sleep-wake activity cycles, such as appropriately timed light exposure, food intake, and exercise. This dynamic will be necessary to maintain neurocognition and human behavior throughout the flight.
The question ‘How do songbirds sing?’ is addressed in a study published in BioMed Central’s open access journal BMC Biology. High-field magnetic resonance imaging and micro-computed tomography have been used to construct stunning high resolution, 3D, images, as well as a data set “morphome” of the zebra finch (Taeniopygia guttata) vocal organ, the syrinx.
Like humans, songbirds learn their vocalizations by imitation. Since their songs are used for finding a mate and retaining territories, birdsong is very important for reproductive success.
The syrinx, located at the point where the trachea splits in two to send air to the lungs, is unique to birds and performs the same function as vocal cords in humans. Birds can have such a complete control over the syrinx, with sub-millisecond precision, that in some cases they are even able to mimic human speech.
Despite great inroads in uncovering the neural control of birdsong, the anatomy of the complex physical structures that generate sound have been less well understood.
The multinational team has generated interactive 3D PDF models of the syringeal skeleton, soft tissues, cartilaginous pads, and muscles affecting sound production. These models show in detail the delicate balance between strength, and lightness of bones and cartilage required to support and alter the vibrating membranes of the syrinx at superfast speeds.
Dr Coen Elemans, from the University of Southern Denmark, who led this study, explained, “This study provides the basis to analyze the micromechanics, and exact neural and muscular control of the syrinx. For example, we describe a cartilaginous structure which may allow the zebra finch to precisely control its songs by uncoupling sound frequency and volume.” In addition, the researchers found a previously unrecognized Y-shaped structure on the sternum which corresponds to the shape of the syrinx and could help stabilize sound production.
Study uncovers protein key to fighting and preventing obesity
University of Florida researchers and colleagues have identified a protein that, when absent, helps the body burn fat and prevents insulin resistance and obesity. The findings from the National Institutes of Health-funded study were published online ahead of print Sunday, Jan. 6, in the journal Nature Medicine.
The discovery could aid development of drugs that not only prevent obesity, but also spur weight loss in people who are already overweight, said Dr. Stephen Hsu, one of the study’s corresponding authors and a principal investigator with the UF Sid Martin Biotechnology Development Institute.
One-third of adults and about 17 percent of children in the United States are obese, according to the Centers for Disease Control and Prevention. Although unrelated studies have shown that lifestyle changes such as choosing healthy food over junk food and increasing exercise can help reduce obesity, people are often unable to maintain these changes over time, Hsu said.
“The problem is when these studies end and the people go off the protocols, they almost always return to old habits and end up eating the same processed foods they did before and gain back the weight they lost during the study,” he said. Developing drugs that target the protein, called TRIP-Br2, and mimic its absence may allow for the prevention of obesity without relying solely on lifestyle modifications, Hsu said.
First identified by Hsu, TRIP-Br2 helps regulate how fat is stored in and released from cells. To understand its role, the researchers compared mice that lacked the gene responsible for production of the protein, with normal mice that had the gene.
They quickly discovered that mice missing the TRIP-Br2 gene did not gain weight no matter what they ate — even when placed on a high-fat diet — and were otherwise normal and healthy. On the other hand, the mice that still made TRIP-Br2 gained weight and developed associated problems such as insulin resistance, type 2 diabetes and high cholesterol when placed on a high-fat diet. The normal and fat-resistant mice ate the same amount of food, ruling out differences in food intake as a reason why the mice lacking TRIP-Br2 were leaner.
“We had to explain why the animals eating so much fat were remaining lean and not getting high cholesterol. Where was this fat going?” Hsu said. “It turns out this protein is a master regulator. It coordinates expression of a lot of genes and controls the release of the fuel form of fat and how it is metabolized.”
When functioning normally, TRIP-Br2 restricts the amount of fat that cells burn as energy. But when TRIP-Br2 is absent, a fat-burning fury seems to occur in fat cells. Although other proteins have been linked to the storage and release of fat in cells, TRIP-Br2 is unique in that it regulates how cells burn fat in a few different ways, Hsu said. When TRIP-Br2 is absent, fat cells dramatically increase the release of free fatty acids and also burn fat to produce the molecular fuel called ATP that powers mitochondria — the cell’s energy source. In addition, cells free from the influence of TRIP-Br2 start using free fatty acids to generate thermal energy, which protects the body from exposure to cold.
“TRIP-Br2 is important for the accumulation of fat,” said Dr. Rohit N. Kulkarni, also a senior author of the paper and an associate professor of medicine at Harvard Medical School and the Joslin Diabetes Center. “When an animal lacks TRIP-Br2, it can’t accumulate fat.”
Because the studies were done mostly in mice, additional studies are still needed to see if the findings translate to humans.
“We are very optimistic about the translational promise of our findings because we showed that only human subjects who had the kind of fat (visceral) that becomes insulin-resistant also had high protein levels of TRIP-Br2,” Hsu said.
“Imagine you are able to develop drugs that pharmacologically mimic the complete absence of TRIP-Br2,” Hsu said. “If a patient started off fat, he or she would burn the weight off. If people are at risk of obesity and its associated conditions, such as type 2 diabetes, it would help keep them lean regardless of how much fat they ate. That is the ideal anti-obesity drug, one that prevents obesity and helps people burn off excess weight.”
(Source: news.ufl.edu)