Scientists have identified an important molecule that is critical to metabolism. Called sarcolipin, this peptide that is only present in muscles can promote energy expenditure and increase fat oxidation. Sarcolipin causes muscle to drive the cell’s power plants, mitochondria, to make more energy by burning fat. This work, by scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP), has been published in Cell Reports.
"This study shows a direct relationship between sarcolipin and energy metabolism," says Muthu Periasamy, Ph.D., senior author of the paper and professor at SBP Lake Nona. "This mechanism is intrinsic to muscle and generates heat at the expense of fat burning."
It’s known that cold temperatures and exercise increase the amount of energy that muscles burn. Sarcolipin makes that energy expenditure less efficient, burning more. It forces muscles to move calcium ions into an organelle called the sarcoplasmic reticulum with SERCA, a calcium ion transporter. The process needs a lot of energy, in the form of ATP, which SERCA uses to move the ions. But if sarcolipin binds to SERCA, activity is uncoupled; that increases ATP consumption and decreases efficiency.
"When you exercise, your muscle makes more mitochondria and oxidizes more fat. Sarcolipin is the missing link. It's recruited during exercise or cold exposure and alters calcium cycling to increase mitochondria biogenesis and fat burning," explained Periasamy.
The researchers manipulated sarcolipin levels in a mouse model and found that without sarcolipin, mice had cells with fewer mitochondria. The mice also had difficulty burning fat; there was more of it in their muscle, a disorder called lipotoxicity. Lipotoxicity is known to cause insulin resistance, which can result in type 2 diabetes. Animals with more sarcolipin had increased numbers of mitochondria and higher fat oxidation.
"When we feed mice with more sarcolipin a high-fat diet, they don't accumulate any fat in their muscle, and they don't develop insulin resistance and type 2 diabetes," said the first author of the report, Santosh Maurya, Ph.D., staff scientist at SBP Lake Nona.
It’s possible that sarcolipin may help people with metabolic disorders like diabetes or obesity, but more work will be necessary to know.
"Researchers have already shown that extreme obesity reduces sarcolipin function," noted Periasamy. "There might be a therapeutic window to increase sarcolipin recruitment to burn more energy. This strategy could help people with metabolic conditions, as well as those who have difficulty exercising.
"We have more SERCA pumps than we need. Some are bound by sarcolipin, but it only binds around 25 percent of SERCA pumps at any one time. We would need to find drugs that increase [the] efficiency of sarcolipin uncoupling SERCA."
Periasamy is featured discussing his work in the following video.
Sources: AAAS/Eurekalert! via Sanford Burnham Presbys Medical Discovery Institute, Cell Reports