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Sanford-Burnham Science Blog

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Differences between “marathon mice” and “couch potato mice” reveal key to muscle fitness

by Heather Buschman, Ph.D. on May 8, 2013 at 2:41 pm | 0 Comments
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Muscle from normal mice (left) and a mouse model lacking ERRgamma and ERRbeta (right) differ in muscle fiber-type, as indicated by immunofluorescence staining (green = myosin heavey chain 1, blue = myosin heavy chain 2a)

Muscle from normal mice (left) and a mouse model lacking ERRgamma and ERRbeta (right) differ in muscle fiber-type, as indicated by immunofluorescence staining (green = myosin heavey chain 1, blue = myosin heavy chain 2a)

Sanford-Burnham researchers identify microRNAs as the missing link between the two defining features of muscle fitness—fuel-burning and fiber-type switching—providing a potential new target for interventions that boost fitness in people with chronic illness or injury.

Researchers discovered that small pieces of genetic material called microRNAs link the two defining characteristics of fit muscles: the ability to burn sugar and fat and the ability to switch between slow- and fast-twitch muscle fibers. The team used two complementary mouse models—the “marathon mouse” and the “couch potato mouse”—to make this discovery. But what’s more, they also found that active people have higher levels of one of these microRNAs than sedentary people. These findings, published May 8 in The Journal of Clinical Investigation, suggest microRNAs could be targeted for the development of new medical interventions aimed at improving muscle fitness in people with chronic illness or injury.

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White blood cell enzyme contributes to inflammation and obesity

by Heather Buschman, Ph.D. on April 2, 2013 at 12:02 pm | 1 comment
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Left: In fat tissue from a lean mouse, neutrophil elastase and a1-antitrypsin levels are balanced. Right: In fat tissue from an obese mouse, they are imbalanced—neutrophil elastase levels are high (dark staining) and a1-antitrypsin levels are low.

Left: In fat tissue from a lean mouse, neutrophil elastase and a1-antitrypsin levels are balanced. Right: In fat tissue from an obese mouse, they are imbalanced—neutrophil elastase levels are high (dark staining) and a1-antitrypsin levels are low.

Imbalance between an enzyme called neutrophil elastase and its inhibitor causes inflammation, obesity, insulin resistance, and fatty liver in mice and humans—providing a new therapeutic target for these health conditions

Many recent studies have suggested that obesity is associated with chronic inflammation in fat tissues. In a new study, researchers discovered that an imbalance between an enzyme called neutrophil elastase and its inhibitor causes inflammation, obesity, insulin resistance, and fatty liver disease. This enzyme is produced by white blood cells called neutrophils, which play an important role in the body’s immune defense against bacteria.

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First five organizations selected for Florida Translational Research Program

by Patrick Bartosch on April 2, 2013 at 6:00 am | 0 Comments
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The Florida Translational Research Program provides Florida-based scientists with access to Sanford-Burnham's drug-discovery technology and expertise.

The Florida Translational Research Program provides Florida-based scientists with access to Sanford-Burnham's drug-discovery technology and expertise.

We announced today the selection of the first five research organizations that will participate in the Florida Translational Research Program (FTRP) to advance drug discovery in the state. The projects focus on cancer, diabetes, and obesity, and are led by scientists from the University of Central Florida, the University of Florida, the University of Miami, Scripps Florida, and a team of our own Lake Nona scientists.  The Florida Department of Health and Sanford-Burnham established the FTRP as a competitive grant program that provides funding for collaborative drug discovery projects. The overall goal of the program is to translate research discoveries made in Florida laboratories into the medicines of tomorrow.

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Type 2 diabetes: a cellular metabolism problem

by Heather Buschman, Ph.D. on January 10, 2013 at 12:27 pm | 2 Comments
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Left: healthy beta cells.  Right: type 2 diabetic beta cells lose their glucose-sensing capability as glucose transporters (green) are internalized due to environmental disturbances brought about by fat and obesity.

Left: healthy beta cells. Right: type 2 diabetic beta cells lose their glucose-sensing capability as glucose transporters (green) are internalized due to environmental disturbances brought about by fat and obesity.

A new computational model of sugar transport in the pancreas reveals a metabolic “tipping point” in type 2 diabetes—a discovery that may form the basis for new efforts to prevent and treat the disease.

Changes in cellular metabolism play a bigger role in the development of type 2 diabetes than previously thought—perhaps an even larger part than genetic predisposition plays in the disease. That’s what Sanford-Burnham and UC Santa Barbara researchers concluded in a study published recently in the journal PLOS ONE. The team, including Jamey Marth, Ph.D., developed a computational model to better understand the underlying causes and progression of type 2 diabetes. The model revealed a metabolic “tipping point” that, when crossed, prevents the pancreas from adequately sensing blood sugar and secreting insulin. The team expects the discovery will form the basis for new efforts to prevent and treat type 2 diabetes.

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How belly fat differs from thigh fat—and why it matters

by Heather Buschman, Ph.D. on January 9, 2013 at 6:20 am | 4 Comments
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Obesity-waist_circumference

Researchers discover that the genes active in a person’s belly fat are significantly different from those in his or her thigh fat, a finding that could shift the way we approach unwanted belly fat—from banishing it to relocating it.

Men tend to store fat in the abdominal area, but don’t usually have much in the way of hips or thighs. Women, on the other hand, are more often pear-shaped—storing more fat on their hips and thighs than in the belly.

Why are women and men shaped differently?

The answer still isn’t clear, but it’s an issue worth investigating, says Steven Smith, M.D., director of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes. That’s because belly fat is associated with higher risks of heart disease and diabetes. On the other hand, hip and thigh fat don’t seem to play a special role in these conditions.

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Shifting the balance between good fat and bad fat

by Bruce Lieberman on January 4, 2013 at 10:39 am | 3 Comments
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Moscat_Diaz-Meco

Sanford-Burnham Professors Jorge Moscat, Ph.D., and Maria Diaz-Meco, Ph.D. co-authored a study on p62's role in fat metabolism

Sanford-Burnham researchers show that protein p62 balances metabolism in fat tissue—making it an attractive target for anti-obesity therapies

In many cases, obesity is caused by more than just overeating and a lack of exercise. Something in the body goes haywire, causing it to store more fat and burn less energy. But what is it? Sanford-Burnham researchers have a new theory—a protein called p62. According to a study the team published December 21 in the Journal of Clinical Investigation, when p62 is missing in fat tissue, the body’s metabolic balance shifts—inhibiting “good” brown fat, while favoring “bad” white fat. These findings indicate that p62 might make a promising target for new therapies aimed at curbing obesity.

“Without p62 you’re making lots of fat but not burning energy, and the body thinks it needs to store energy,” said Jorge Moscat, Ph.D., Sanford-Burnham professor. “It’s a double whammy.” Moscat led the study with collaborators at Helmholtz Zentrum München in Germany and the University of Cincinnati.

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