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Sanford-Burnham Science Blog

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Fighting fat with fat

by Heather Buschman, Ph.D. on October 4, 2011 at 9:00 am | 0 Comments
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Loss of orexin impairs brown fat function and promotes obesity in mice. The leaner mouse with functional brown fat (left) dissipates considerable amounts of energy as heat. The orexin-deficient mouse (right) lacks fat fuel and active mitochondria, thus storing energy as fat instead of burning it. (Image by Peter Allen, UCSB)

Loss of orexin impairs brown fat function and promotes obesity in mice. The leaner mouse with functional brown fat (left) dissipates considerable amounts of energy as heat. The orexin-deficient mouse (right) lacks fat fuel and active mitochondria, thus storing energy as fat instead of burning it. (Image by Peter Allen, UCSB)

The fat we typically think of as body fat is called white fat. But there’s another type—known as brown fat—that does more than just store fat. It burns fat. Scientists used to think that brown fat disappeared after infancy, but recent advances in imaging technology led to its rediscovery in adult humans. Because brown fat is so full of blood vessels and mitochondria—that’s what makes it brown—it’s very good at converting calories into energy, a process that malfunctions in obesity.

In a study published October 5 in Cell Metabolism, Sanford-Burnham researchers discovered that orexin, a hormone produced in the brain, activates calorie-burning brown fat in mice. Orexin deficiency is associated with obesity, suggesting that orexin supplementation could provide a new therapeutic approach for the treatment of obesity and other metabolic disorders. Most current weight loss drugs are aimed at reducing a person’s appetite. An orexin-based therapy would represent a new class of fat-fighting drugs—one that focuses on peripheral fat-burning tissue rather than the brain’s appetite control center.

“Our study provides a possible reason why some people are overweight or obese despite the fact that they don’t overeat—they might lack the orexin necessary to activate brown fat and increase energy expenditure,” explains Dr. Devanjan Sikder, senior author of the study and assistant professor in Sanford-Burnham’s Diabetes and Obesity Research Center, located in Orlando’s Medical City at Lake Nona.

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Glucose uptake relies on newly identified protein

by Heather Buschman, Ph.D. on September 7, 2011 at 10:50 am | 0 Comments
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Dr. Zhen Jiang

Dr. Zhen Jiang

All cells need glucose (sugar) to produce the energy they need to survive. High glucose levels in the bloodstream (such as occur after a meal), trigger the pancreas to produce insulin. In turn, muscle and fat cells respond to insulin by moving GLUT4, a glucose transporter, from intracellular storage out to the cell surface. There, GLUT4 can take up the glucose the cell needs from the bloodstream.

A team led by Dr. Zhen Jiang recently identified the protein—called CDP138—responsible for ensuring that GLUT4 is properly inserted in the cellular membrane. This finding provides a new understanding of glucose metabolism—an important finding considering that impaired insulin action and glucose metabolism contribute to the development of type 2 diabetes.

“This is a newly identified protein that’s involved in an important step in glucose uptake,” said Dr. Jiang, assistant professor in Sanford-Burnham’s Diabetes and Obesity Research Center, located in Orlando’s Medical City at Lake Nona.

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Taste receptors…in the gut?

by Bruce Lieberman on August 1, 2011 at 5:58 am | 0 Comments
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Dr. Tae-Il Jeon

Let’s suppose your summer backpacking trip takes a disastrous turn and you’re lost, out of food, and desperate. You think those berries look OK so you swallow them down—even though they’re as bitter as anything you’ve eaten before. It’s not long before you regret ignoring your taste buds and suspect you’ve eaten something poisonous.

Unless you’re a molecular biologist, you’re probably not thinking at that moment about the biochemistry churning in your gut. But a cacophony of cellular signals is actually assembling a second line of defense to keep your digestive system from absorbing toxins into your bloodstream.

Of course, your body doesn’t always win. But Dr. Timothy Osborne’s lab at Sanford-Burnham’s Lake Nona campus has outlined how bitter taste-sensing receptors on enteroendocrine cells in the gut, called T2Rs, automatically kick into gear when confronted with bitter-tasting substances. You might disregard the taste buds in your mouth, but your digestive system knows better and tries to make up for your recklessness.

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Why are we so fat?

by Heather Buschman, Ph.D. on July 11, 2011 at 2:33 pm | 0 Comments
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New report shows the percent of the population considered obese has increased over the past two decades.

New report shows the percent of the population considered obese has increased over the past two decades.

A new report released by the Trust for America’s Health and the Robert Wood Johnson Foundation held dire news about the state of America’s obesity epidemic. The report, aptly named “F as in Fat: How Obesity Threatens America’s Future 2011,” revealed several eye-opening statistics. Here are a few:

• Twenty years ago, no state had an obesity rate above 15 percent. Now every state does.
• Today, 12 states have obesity rates over 30 percent. Four years ago, only one did.
•  Since 1995, diabetes rates (long associated with obesity) have doubled in eight states. Then, only four states had diabetes rates above six percent.  Now, 43 states have diabetes rates over seven percent, and 32 have rates above eight percent.

To understand why the nation’s weight problem has ballooned over the past two decades, obesity researchers are increasingly looking to our environment. The Orlando Sentinel interviewed obesity expert Dr. Steven R. Smith, Sanford-Burnham professor and scientific director of the Translational Research Institute for Metabolism and Diabetes (TRI), a collaboration between Florida Hospital and Sanford-Burnham. He said:

“Our genes haven’t changed that much in thousands of years, but we have seen a rapid change in the environment, and that has interacted with our genetic propensity toward obesity.”

Read more in How fat is America? New report gives nation an F.

Coming soon: Medscape’s “Developments to Watch”

by Kristina Meek on July 1, 2011 at 7:08 am | 0 Comments
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Dr. Evan Snyder (right) interviews his colleague, Dr. Steven Smith, on the Medscape set.

Dr. Evan Snyder interviews his colleague, Dr. Steven Smith, on the Medscape set.

Last week, Sanford-Burnham’s Fishman Auditorium, on the Institute’s La Jolla campus, was transformed into a temporary television studio. It was hardly recognizable under the bright lights and set dressing. Medical website Medscape recorded interviews with three Sanford-Burnham researchers for a new video series called “Developments to Watch.” The talk show-like discussions were hosted by Dr. Evan Snyder, who directs the Stem Cells and Regenerative Biology Program at Sanford-Burnham. Dr. Snyder is both a medical doctor who regularly sees patients and a scientist who conducts research in his own lab – the perfect person to help explain how discoveries made today might one day help patients.

Medscape is part of the network of sites run by WebMD. With this newest video series, Sanford-Burnham scientists will be providing expert commentary and information to help keep Medscape’s audience – primary care physicians, specialists and other health professionals – up-to-date on the latest medical research and what it means for their patients.

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A different kind of dorm room

by Heather Buschman, Ph.D. on May 19, 2011 at 5:00 am | 3 Comments
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This calorimetry suite will be an important tool in the new Translational Research Institute facility, opening January 2012 (rendering by Flad Architects)

Calorimetry suite in the new Translational Research Institute facility, due to open January 2012 (artist's rendering by Flad Architects)

Obesity negatively affects the entire body – no organ system is left untouched. It increases a person’s risk of type 2 diabetes, high blood pressure, depression, certain cancers and many other conditions. If the current trend of expanding waistlines continues, the U.S. Centers for Disease Control and Prevention estimates that at least one in five Americans will be diabetic by the year 2050.

The goal of the Translational Research Institute for Metabolism and Diabetes (TRI), a collaboration between Florida Hospital and Sanford-Burnham, is to alter this course by translating basic scientific discoveries in the laboratory to usable information and products that improve the diagnosis and treatment of human diseases – especially obesity and diabetes.

“At the moment, there is a big gap between what we know and what we want to know about human metabolism, obesity and diabetes. Our ultimate goal in translational research is to bridge that gap,” says Dr. Steven R. Smith, TRI’s scientific director and professor at Sanford-Burnham. “As basic researchers continue to unravel the molecular underpinnings of these diseases, TRI will be conducting proof-of-concept experiments to validate new drug targets and test new therapies for safety and efficacy.”

When it opens in January 2012, the TRI’s new three-story facility in Orlando, Florida will contain a research clinic, imaging technology, a biorepository for sample collection and storage, and several other resources for metabolic studies. But the facility’s highlight will be the calorimeter rooms – small dormitory-style rooms outfitted with a bed, treadmill and toilet. These whole-room calorimeters will allow the TRI staff to measure fat and carbohydrate oxidation and energy expenditure as a person goes about his or her normal life – sleeping, eating, walking, etc. As the patient exercises on the treadmill, scientists will be able to measure his or her oxygen consumption and calories burned without using invasive tubing or sensors. This approach will provide superior comfort – and therefore generate more accurate data – during exercise.

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A medical revolution

by Josh Baxt on May 18, 2011 at 8:04 am | 1 comment
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Nanoparticles, like this micelle, may be the future of medicine. (Image by Peter Allen, UC Santa Barbara College of Engineering)

A syndicated article that recently appeared in the Orlando Sentinel, the Los Angeles Times and other outlets described several revolutionary technologies that will change medicine in the coming decade.

In particular, the piece highlighted how new genomic technologies can personalize treatment to individual patients; how robotic surgery will help surgeons perform complex procedures on people thousands of miles away; and how new classes of diagnostic tests will allow physicians to discover diseases earlier, when they are most treatable.

The article included insights from Dr. Ranjan Perera, associate professor at Sanford-Burnham’s Lake Nona campus, and Dr. Jamey Marth, who directs the U.C. Santa Barbara–Sanford-Burnham Center for Nanomedicine. Dr. Marth is particularly excited about nanomedicine’s potential to enhance both diagnosis and treatment:

“Today’s scientists work at the molecular and atomic level with nanoparticles, to harness these biomachines that detect and bind to diseased cells. The nanoparticle then fuses with that sick cell and delivers its cargo — drugs or imaging agents.”

Read ‘Revolution is at hand’ for breakthroughs in medicine.

Fat to the rescue

by Heather Buschman, Ph.D. on May 12, 2011 at 8:59 am | 0 Comments
Full Article
Timothy Osborne, Ph.D., professor and program director in Sanford-Burnham's Diabetes and Obesity Center, was recently appointed to the NIH’s Molecular and Cellular Endocrinology Study Section.

Dr. Timothy Osborne

When pathogenic invaders – bacteria, viruses, parasites – are detected by the body, things begin to happen in a hurry. Macrophages, a type of immune cell, are among the first to respond as the body starts mobilizing its defense. These are phagocytic cells, meaning they engulf microorganisms – digesting them, clearing them away and using them to prod other immune cells into action.

Scientists have studied these processes for a long time. And yet there are still surprises.

Dr. Timothy Osborne is interested in lipid (fat) metabolism – specifically the role of sterol regulatory element-binding proteins (SREBP). Members of this protein family sense changes in the environment and trigger the genes needed to adjust cellular fat and cholesterol levels.

But it turns out that SREBPs do more than just respond to nutrient levels. Dr. Osborne’s group and their collaborators recently determined that one SREBP, called SREBP-1a, directs macrophage lipid metabolism in a way that helps these immune cells fight infection.

“When macrophages engage their prey, they proliferate to generate more macrophages and they expand and contract their membranes as they engulf the invading microbes. Both of these responses require new lipids to generate and renew cellular membranes,” explains Dr. Osborne, professor and director of the Metabolic Signaling and Disease Program in Lake Nona, Orlando.

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Science, will power and weight loss

by Josh Baxt on April 15, 2011 at 2:36 pm | 0 Comments
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Dr. Sheila Collins

Dr. Sheila Collins

Dr. Sheila Collins studies fat. Specifically, as a professor at Sanford-Burnham’s Lake Nona campus she studies fat metabolism and other biochemical mechanisms that regulate body weight. However, prior to becoming a scientist, Dr. Collins was a fitness trainer.

On April 13, Dr. Collins combined her scientific and fitness expertise to answer questions about dieting, exercise and weight loss for a syndicated web chat sponsored by the Orlando Sentinel.

Dr. Collins offered some practical advice for maintaining motivation, including setting realistic goals and working out with a buddy.  Another tip was mixing up workouts to avoid boredom and stress new muscle groups. Maintaining a balance between calories consumed and fuel expenditure is a challenge rooted in our genetic history.

“The body is WIRED to store energy. We evolved in the cave days with little to eat – fruit maybe, an occasional successful hunt for meat or fish,” said Dr. Collins. “So when food was available, you had better well store it because it’s infrequent. Not able to gain weight or retain it…your genes are gone from the gene-pool. All the biochemistry of appetite and body fat metabolism and muscle tell us that this is true.”

Visit Can’t stick with your exercise program? to read the complete transcript.

Cellular feast or famine

by Heather Buschman, Ph.D. on April 5, 2011 at 9:38 am | 0 Comments
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Fat droplets (green) meet the autophagosome (red) and its arsenal of enzymes. (Image courtesy of the Osborne lab)

Autophagosome colocalization

Not all cholesterol is bad. Every cell requires it for growth – they either have to get cholesterol somewhere or they die. A sensor called sterol regulatory element-binding protein 2 (SREBP-2) monitors cellular cholesterol levels and responds to low levels by switching on genes that allow the cell to either 1) take up more from the bloodstream or 2) manufacture more from cholesterol building blocks inside the cell. Now, in a study published in the April 6 issue of the journal Cell Metabolism, Sanford-Burnham researchers and their collaborators uncover a third cholesterol source also controlled by SREBP-2: fat droplets stored inside the cell itself.

“We were searching the mouse liver cell genome to find DNA sequences specifically bound by SREBP-2,” explains Dr. Timothy Osborne, director of Sanford-Burnham’s Metabolic Signaling and Disease Program in Lake Nona, Orlando, and senior author of the study. “First we were surprised that SREBP-2 binds very close to the genes it regulates – that’s not typical. Second, we were surprised to find that in addition to genes related to fat metabolism and cholesterol balance, SREBP-2 also binds and activates genes responsible for autophagy.”

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Reining in melanoma with MicroRNA

by Heather Buschman, Ph.D. on November 1, 2010 at 2:12 pm | 2 Comments
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Dr. Ranjan Perera (left) with post-doctoral researcher Dr. Joseph Mazar

Dr. Ranjan Perera with post-doctoral researcher Dr. Joseph Mazar

Skin cancer is the most common cancer in the United States. Melanoma is one of the rarest forms of skin cancer, but it is also the most deadly. At Sanford-Burnham’s Lake Nona campus, Dr. Ranjan Perera’s lab is studying what causes melanocytes (pigment-producing skin cells) to divide abnormally, ultimately forming melanoma. In a study published today in the journal PLoS ONE, a team led by Dr. Perera and post-doctoral researcher Dr. Joseph Mazar show that melanocyte growth and the cancer’s ability to invade other tissue is at least partially controlled by abnormal expression of microRNAs (miRNAs) – small strands of genetic material that may play a major role in numerous diseases by interfering with proteinproduction.“We’ve identified one specific miRNA, called miR-211, that could be used not only as a novel diagnostic marker for early melanoma detection, but also as a therapeutic target,” explains Dr. Perera, associate professor in Sanford-Burnham’s RNA Biology Program and senior author of the study.

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