metabolism Archives - Sanford Burnham Prebys
Institute News

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.

Institute News

SBP scientists reflect on progress in diabetes research

AuthorDeborah Robison
Date

June 23, 2016

“The most significant advances in diabetes treatment, which were underscored at the ADA meeting, is the clinical evidence that two newer classes of anti-diabetic drugs significantly improve cardiovascular outcomes and overall mortality. These drug families are insulin secretion enhancers such as liraglutide (LEADER trial) and drugs that promote glucose elimination in the urine, such as canagliflozin and empagliflozin (EMPA-REG OUTCOME trial). This has major impact because reducing the risk of heart disease is always the end goal in treating diabetes—the association with heart disease is what makes type 2 diabetes so serious. These trials also present a remarkable opportunity for basic researchers—many of us, including several here in Lake Nona, study how drugs in these classes affect metabolism. The answers to those questions should lead to new drug targets that are even more specific and precision-oriented.”

Peter Crawford, MD, PhD
Associate Professor and Director
Cardiovascular Metabolism Program

“From the sessions that I saw, there was a significant emphasis on combination treatments—either combining two or more already approved drugs that have related functions or generating fusions of multiple protein drugs. An example of the former is the combination of basal insulin and glucagon-like peptide-1 receptor agonists to control fasting and post-meal glucose levels, respectively. With regards to fusion proteins, there were many posters and presentations highlighting efforts to generate dual and triple combinations that would lower glucose and aid weight loss. These approaches may reduce the need for patients to take multiple drugs and therefore improve efficacy and patient adherence.”

Julio Ayala, PhD
Associate Professor
Integrative Metabolism Program
ADA Thomas R. Lee Career Development Award Recipient ’14

“During the ADA meeting two symposia and numerous other presentations examined evidence implicating gut microbiota in the development of type 1 and type 2 diabetes. I am personally enthusiastic about the potential of novel therapeutic strategies that either prevent harmful changes in gut microbiota or even directly transplant “therapeutic” microbial species. Nevertheless, our current understanding of the potential mechanisms is very limited due to the complex factors affecting the microbiome such as the host’s genetics and the environment (diet, antibiotic use, history of infections etc.).”

George Kyriazis, PhD
Assistant Professor
Integrative Metabolism Program

“Of particular interest to me were the symposia on experimental strategies for understanding how the brain controls metabolism. Specifically, optogenetics and magnetogenetics are emerging as two powerful research tools for this purpose, and involve genetically modifying neurons to express either light- or magnetic field-sensitive proteins so that their activity can be controlled with fiber optic light or magnets, respectively. These sophisticated techniques will help investigators delineate which regions in the brain play a critical role in regulating blood glucose, which could lead to more effective therapies for diabetes and obesity.”

Melissa Burmeister, PhD
Staff Scientist
Dr. Julio Ayala Lab

 

Institute News

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”

Institute News

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”

Institute News

Failing hearts switch fuels to generate energy

Authorsgammon
Date

January 27, 2016

More than 5 million people in the United States suffer from heart failure, according to the American Heart Association. Less than half of those with heart failure survive five years after diagnosis. New research from scientists at SBP published in the journal Circulation may lead to a new approach to help treat heart failure early in the disease. Continue reading “Failing hearts switch fuels to generate energy”