Heart hormone helps shape fat metabolism

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It’s well known that exercising reduces body weight because it draws on fat stores that muscle can burn as fuel. But a new study at Sanford-Burnham suggests that the heart also plays a role in breaking down fat. In their study, published February 6 in the Journal of Clinical Investigation, Sheila Collins, Ph.D. and colleagues detail how hormones released by the heart stimulate fat cell metabolism. These hormones turn on a molecular mechanism similar to what’s activated when the body is exposed to cold and burns fat to generate heat. This study adds another dimension to our understanding of how the body regulates fat tissue and may someday lead to new ways to manipulate the process with drugs to reduce weight in obese patients or maintain it in individuals who experience pathological weight loss during chronic heart failure.

“Exercise is always going to raise your blood pressure some, so there’s the potential that these heart hormones—called cardiac natriuretic peptides—are being released and contributing to the breakdown of fats,” said Collins, professor in the Diabetes and Obesity Research Center at Sanford-Burnham’s Lake Nona campus in Orlando and senior author of the study. “Over a period of time, natriuretic peptides could also be leading to an increase in the numbers of brown fat cells, which we know are very important for protection against diet-induced obesity, at least in laboratory experiments.”

Sanford-Burnham experts talk about why Americans are fat

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New Year’s resolutions and dieting seem to go hand-in-hand. Setting a personal goal to lose weight and exercise more may jump-start the New Year but “February frustration” can derail even the most determined. Scientists in Sanford-Burnham’s Diabetes and Obesity Research Center recently shared their expertise on the causes of weight gain and the metabolic challenges that make it so hard to keep off the extra pounds. Their insights on genetics, diet, metabolism and lifestyle were included in a four-part series called “What’s making Americans so fat?” that ran in the Orlando Sentinel beginning January 1. Medical reporter Marni Jameson spoke with national obesity experts to compile a list of 40 reasons for why 60 percent of U.S. adults are obese or overweight.

“It’s not gluttony, and it’s not lack of willpower,” says Dr. Steven Smith, scientific director of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes. “No scientist in the field will say the problem is strictly one of willpower,” he says. “It’s a result of the way our genes are interacting with an environment that is stacked against them.”

Here’s an excerpt of how the experts weighed in:

Science, will power and weight loss

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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.

Spotlight on disease: type 2 diabetes

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Diabetes results from a lack of insulin, a hormone that stimulates cells to take up glucose (a type of sugar) from the bloodstream. Cells need glucose as fuel to produce energy. Type 1 diabeticslack insulin because their immune systems destroy the pancreatic cells that produce it. Type 2 diabetics progress through two stages of the disease. In the first stage, called “insulin resistance”, cells no longer respond to insulin.  The pancreas compensates for this resistance by producing more insulin. As insulin resistance persists, the pancreas cannot make enough insulin to keep up with the increased demand. The pancreas eventually shuts down insulin production altogether, resulting in type 2 diabetes.Without sugar that can be converted to energy, cells starve and glucose levels build up in the blood, which can lead to life-threatening complications such as cardiovascular disease. Since fat interferes with the body’s ability to process insulin and overweight people are at increased risk for the disease, type 2 diabetes is sometimes called “obesity-related” diabetes. Type 2 diabetics are encouraged to carefully monitor their diet and exercise in order to prevent dangerous fluctuations in blood sugar levels.

Targeting mitochondria to combat obesity

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How is fat tissue from an obese person different from a thin person’s fat tissue? Dr. Sheila Collins and her colleagues at Sanford-Burnham’s Diabetes and Obesity Research Centerrecently discovered one major distinguishing feature – fat tissue from obese people doesn’t oxidize fatty acids as well as that from thinner people.Fat cells use fatty acids for energy. But in response to adrenaline, fat tissue can also release fatty acids into the bloodstream for use by other tissues, such as heart and muscle. This latest study, published in the journal Diabetes, revealed that obese fat tissue was not as good as non-obese fat tissue at consuming fatty acids for energy. This might be one of the reasons why obese fat tissue releases more fatty acids into the bloodstream.  And although fatty acids are an important source of energy for other tissues, too much of it in the blood – a condition frequently seen in obesity – is believed to lead to type 2 diabetes and cause detrimental heart problems.

Brown fat: not just for babies and bears

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Sanford-Burnham’s Dr. Sheila Collins recently returned from Stockholm, where she attended a meeting on brown fat (also called brown adipose tissue) and obesity, held in conjunction with the XI International Congress on Obesity. Brown fat, which helps generate heat, was historically thought to be limited to small mammals such as rodents, newborns of larger mammals (including humans), and hibernators – in order for them to stay warm. Scientists used to think that brown fat disappeared after infancy, but recent advances in imaging technology led to a rediscovery of brown fat in adult humans. This meeting brought together scientists studying the basic biology of brown fat tissue and its possible role in adults in order to figure out how all this information can be applied to fight obesity.

Diabetes meeting adds a human element to research

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This week in Orlando, Fla., the American Diabetes Association (ADA) gathered doctors and scientists from all over the world to drive its mission “to prevent and cure diabetes and to improve the lives of all people affected by diabetes.”  Many of Sanford-Burnham’s Lake Nona researchers attended the ADA’s annual meeting, including Dr. Sheila Collins, professor in the Diabetes and Obesity Research Center, and post-doctoral researchers Dr. Zhenji Gan and Dr. Rita Luther.“By bringing together scientists and clinical doctors, large interdisciplinary meetings like this help us to think more broadly about how our research impacts diabetes patients,” said Dr. Collins, whose work has been funded by the ADA in the past. “Clinical doctors attending the basic research sessions will sometimes ask a question that brings a different perspective to those of us working in the lab.”

Dr. Luther, who studies inflammation in Dr. Philip Wood’s laboratory, agreed, saying that the ADA meeting was very different from other scientific conferences she has attended. “Clinical lectures and chance meetings with nurses and doctors were eye-opening,” she commented.  “Learning about what patients need provides a human element to research.”

Researchers receive $3.5 million in NIH grants

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Two researchers at Sanford-Burnham at Lake Nona have received grants to study  heart disease and how fat cells function in the body.Lake Nona Scientific Director Dr. Daniel Kelly will be collaborating with Dr. Deborah M. Muoio of the Stedman Center at Duke University to investigate the metabolic basis of heart failure. The $2.9 million, four-year grant will help researchers better understand the mechanisms that cause heart disease and identify potential drug targets for heart failure.

Dr. Sheila Collins received a $525,000, two-year grant to study how beta-adrenergic receptors on fat cells regulate growth. This research will enhance our understanding of how fat cells contribute to metabolic syndrome and could also lead to new drug targets.

There’s more to fat

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Sheila Collins, Ph.D., recently joined Sanford-Burnham at Lake Nona as a professor in the Metabolic Signaling and Disease program. Her lab is interested in fat metabolism. Until the mid-1990s, adipose (fat) tissue had been largely considered an inert storage depot for excess metabolic fuel, much like a savings bank. There is now a better understanding of how fat cells secrete key hormones that play help regulate body weight and insulin sensitivity.