Obesity Archives - Sanford Burnham Prebys
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Long-term exercise makes fat better at burning calories, but doesn’t turn it brown

AuthorJessica Moore
Date

November 15, 2016

Brown fat is good, white fat bad. That’s the impression given by recent metabolism research focused on how to make white fat, which stores energy, more like the rarer brown fat, which burns energy. However, a new study from the Florida Hospital Translational Research Institute for Metabolism and Diabetes (TRI-MD), an affiliate of Sanford Burnham Prebys Medical Discovery Institute (SBP), suggests that with regular exercise even white fat can be cajoled into burning more calories.

“Our findings reveal that even though exercise doesn’t turn white fat ‘beige’—that is, make some of it behave similarly to brown fat—it still has beneficial effects on metabolism in that tissue,” said Lauren M. Sparks, PhD, adjunct professor in the Integrative Metabolism Program at SBP in Lake Nona and an investigator at the TRI-MD. She led the research, recently published in the journal Obesity.

Prior to this investigation, not much was known about how exercise shapes the way human fat cells burn energy. One study suggested that endurance training does not change metabolism in white fat, but the experiments only assessed markers of ‘browning’. Sparks’ team aimed to examine the question more comprehensively by looking not only at browning markers, but also heat generation and the means by which most cells use energy—oxidizing fuels in mitochondria.

The researchers, including SBP’s Steven R. Smith, MD, scientific director of the TRI-MD, compared the abdominal fat of people who work out at least four hours per week at moderate to vigorous intensity to that of sedentary individuals. The levels of mitochondrial oxidation markers were higher in the fat of active people compared with the inactive group, the scientists found, However, markers of heat generation and conversion to ‘beige’ fat were similar between the groups.

“This work highlights the importance of studying metabolism in humans,” Smith said. “Because exercise training in rodents does cause white fat to burn calories as heat, these animals may not be ideal models for answering these kinds of questions.”

“Understanding the effects of exercise on metabolism at the molecular level is critical,” Sparks said. “It connects the dots between physical activity and disease, and it could help refine exercise programs that help people with metabolic problems such as type 2 diabetes and obesity get healthier.”

The paper is available online here.

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Muscle heat may hold key to promoting weight loss

AuthorJessica Moore
Date

July 6, 2016

If you’ve tried to lose weight, you may have wished for a pill that would help you burn calories with little or no exercise. Because such a drug could treat obesity, which affects over one-third of Americans, many researchers are working toward this goal. Treatments that boost calorie burning could enhance the limited efficacy of current weight-loss drugs that suppress appetite.

Most scientists in this field focus on brown adipose tissue, a type of fat that’s specialized to convert calories to heat to keep you warm in the cold. The challenge with that approach is that most adults have very little brown fat—therapies would have to first convert regular white fat to brown. Instead, the laboratory of Muthu Periasamy, PhD, professor in the Center for Metabolic Origins of Disease, is investigating how to stimulate another, more plentiful tissue—muscle—to do the same thing.

Periasamy and Naresh Bal, PhD, a staff scientist in his lab, got the idea that muscle could be important for generating heat from birds—they don’t have any brown fat, but they can still keep themselves warm without constant shivering. In a paper recently published in the Journal of Biological Chemistry, Bal removed the brown fat from mice to examine whether muscle can effectively generate heat in mammals.

“Not only did these mice maintain near-normal body temperatures when living in the cold,” said Bal, “but they burned more calories than mice whose brown fat remained intact—they lost three times as much fat after nine days at cold temperatures.” The extended exposure is required to eliminate the contribution of shivering, which stops after they become adapted to the cold, within the first few days.

“These results suggest that inducing muscle to generate heat could be an even more efficient way to treat obesity than doing the same in brown fat,” said Periasamy. “This is the first step toward drugs that activate this process, called nonshivering thermogenesis (NST).”

“Our next step is to determine which factors turn on NST in muscle,” added Bal.

The lab’s work so far has provided some clues. They have previously shown that the protein sarcolipin changes the way muscle cells use ATP, causing them to generate heat instead of contract. In this research, they observed much higher levels of sarcolipin in the muscles of cold-adapted mice who lack brown fat.

“Since sarcolipin acts by binding another protein, it probably wouldn’t be easy to block,” explains Bal. “To find better drug targets we plan to look at how it affects its target protein, a calcium pump, and how that changes calcium dynamics. Ultimately, we might be able to mimic those effects with a drug.”

The paper is available online here.

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Why the “Biggest Losers” don’t win

AuthorJessica Moore
Date

May 12, 2016

Following a recent publication on the long-term effects of participation in TV’s “Biggest Loser” competition, Steven Smith, MD, professor in SBP’s Integrative Metabolism Program and director of the Translational Research Institute for Metabolism and Diabetes at Florida Hospital, was interviewed by NBC WESH TV Orlando reporter Amanda Ober. Smith explained why nearly all of the “Biggest Losers” regained large proportions of the weight they had lost, and sometimes even more. Continue reading “Why the “Biggest Losers” don’t win”

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Peter Crawford, MD, PhD, elected to the American Society for Clinical Investigation

Authorjmoore
Date

April 19, 2016

The director of SBP’s Cardiovascular Metabolism Program was recently elected into a pre-eminent honor society for physician-scientists. Peter Crawford, MD, PhD, was one of 74 medical researchers whose nominations to the American Society for Clinical Investigation (ASCI) were accepted in 2016. This distinction is conferred only on investigators who have made significant scientific advances prior to the age of 50. Continue reading “Peter Crawford, MD, PhD, elected to the American Society for Clinical Investigation”

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How your organs ‘taste’ sugar

Authorjmoore
Date

April 18, 2016

You might be surprised to learn that the sensors for sweet-tasting molecules aren’t located only on your tongue—they’re also found in the gut, pancreas, fat tissue, and muscle. And new research from the laboratory of George Kyriazis, PhD, assistant professor in the Integrative Metabolism Program at Lake Nona, indicates just how important these sweet taste receptors are in regulating metabolism. Continue reading “How your organs ‘taste’ sugar”

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Generating good fat by pushing the right buttons

Authorjmoore
Date

March 30, 2016

Researchers at SBP have identified a protein complex that is required for conversion of “bad” white fat to “good” brown fat. The findings, published in the Journal of Clinical Investigation, could help treat metabolic disorders such as obesity. Continue reading “Generating good fat by pushing the right buttons”

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New links between heart hormones, obesity, and diabetes

AuthorGuest Blogger
Date

February 17, 2016

New research from SBP’s Sheila Collins, PhD, and Richard Pratley, MD, has revealed an important relationship between proteins secreted by the heart and obesity, glucose intolerance, and insulin resistance. The findings, published in Obesity, offer a new approach to treating metabolic disorders, including type 2 diabetes, by targeting the pathway that controls the proteins’ concentration in the blood. Continue reading “New links between heart hormones, obesity, and diabetes”

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New method to identify bacteria in the gut may facilitate development of probiotics

Authorjmoore
Date

January 19, 2016

The gut microbiome, the community of bacteria living in the intestines, has an enormous impact on human health, affecting risk for obesity, inflammatory bowel disease (IBD), neurological disorders, and even cancer. Accordingly, there has been an explosion of research in this area in the past ten years, with the long-term goal of developing ways to manipulate the microbiome to promote the survival of bacteria that promote health and/or eliminate those associated with disease. Continue reading “New method to identify bacteria in the gut may facilitate development of probiotics”

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Can your heart prevent diabetes?

AuthorGuest Blogger
Date

November 19, 2015

This article was written by guest blogger Crystal Woodard, PhD

Can your heart prevent diabetes? Being overweight or obese is currently deemed the single best predictor of type 2 diabetes. With the prevalence of obesity on the rise, estimates suggest that one in three American adults could have type 2 diabetes by 2050. Weight loss is key to preventing this epidemic. At SBP, scientists are investigating how hormones released by the heart may help the body burn more calories to prevent obesity and type 2 diabetes.

What color is your fat? All fat is not created equal. Excess weight is held in energy-storing fat cells called white adipose tissue as well as energy-burning fat cells called brown adipose tissue. Increasing a person’s brown fat could improve the risks associated with obesity.

Two compounds released by the heart in response to high blood pressure—human atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)—have been found to play a direct role in “browning” white adipose tissue. By browning, white fat starts to burn more calories, mimicking what occurs in brown fat. Sheila Collins, PhD, professor in the Integrative Metabolism Program and her research team, are investigating how these natriuretic peptides activate fat browning with the goal of tapping into the process to help promote weight loss and prevent diabetes.

In collaboration with Dr. Richard Pratley at the Florida Hospital – SBP Translational Research Institute for Metabolism and Diabetes, the teams are conducting clinical trials with obese and lean volunteers to test whether BNP can increase energy expenditure and improve glucose tolerance. Since recombinant human BNP is an FDA-approved drug prescribed for acute heart failure patients, the costs, and development and approval times for using BNP for these conditions may be reduced.

How does BNP work? Investigators in Italy almost 20 years ago discovered that binding sites for BNP, called natriuretic peptide receptors (NPRs), were expressed in human adipose tissue. The natriuretic peptide ‘signaling’ receptor, NPRA, binds the natriuretic peptides, while the natriuretic peptide ‘clearance’ receptor, NPRC, removes them from circulation. Since then, several studies have reported that BNP levels are lower in the blood of obese patients compared to their lean counterparts. Additional research suggests BNP can lead to increased release of adiponectin, an insulin-sensitizing hormone produced by fat cells and that low levels of BNP in the bloodstream might contribute to insulin resistance.

According to Collins, “Early studies proposed that increased clearance is responsible for the lower peptide levels observed in obese individuals in comparison to lean individuals; however, there are no definitive studies to actually prove this or not. Important efforts are currently underway to understand how NPRs are regulated and how the peptides can be best used for their fat-burning capacity.”

Dr. Sheila Collins is a professor at Sanford Burnham Prebys Medical Discovery Institute (SBP) in Lake Nona, Fla. and a recipient of an American Diabetes Association research award. Dr. Richard Pratley is a senior investigator at the Florida Hospital – SBP Translational Research Institute, Medical Director of the Florida Hospital Diabetes Institute, and adjunct professor at SBP in Lake Nona. This post was written by Crystal Woodard, PhD, a post-doctoral fellow in Dr. Collins’s lab.