Protein that prevents weight gain

| Written by sgammon
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Let’s face it: Exercise is not for everyone. Even though it has unquestionable health benefits, some people just can’t—or won’t—do it. A busy schedule, previous failed attempts, lack of results, injuries, or just plain boredom are common reasons why people find exercise hard. But when the amount of energy (calories) we take in exceeds the amount going out, our bodies experience an energy imbalance, and we become overweight and are at risk of obesity. And obesity comes with more than a social stigma, it’s associated with a myriad of health problems including heart disease, diabetes, and cancer.

Muthu Periasamy, Ph.D., professor in the Cardiovascular Pathobiology Program at Sanford-Burnham’s Lake Nona campus, is working on alternative solutions to help restore the energy imbalance that leads to weight gain and obesity. His research is revealing the mechanics of energy expenditure in muscles, which are the major site of burning energy. His recent study, published in the Journal of Biological Chemistry, describes how higher levels of a protein called sarcolipin increase the energy demand of muscles, lead to less fat deposits, and promote weight loss.

“Our research shows for the first time that sarcolipin in skeletal muscle is an important player in energy expenditure and whole-body metabolism," said Periasamy. “Based on our results, we propose that sarcolipin is a novel target for enhancing whole-body energy expenditure, and may potentially be used to prevent and/or treat obesity."

Resistant to weight gain The study, led by Santosh Maurya, Ph.D., a postdoctoral fellow in Periasamy’s Ohio State University lab, used two groups of mice and fed them either normal or high-fat diets. The first group was genetically engineered so that their skeletal muscle lacked sarcolipin, and the second group was engineered so that the protein was overexpressed in skeletal muscle. The researchers found that when given identical amounts of food, the mice with elevated levels of sarcolipin lost weight compared to mice without the protein. Moreover, on a high-fat diet, mice with high sarcolipin levels ate more calories but gained less weight compared to their counterparts. The researchers concluded that mice with high sarcolipin levels were burning more calories and therefore were essentially resistant to diet-induced obesity. This occurred in the absence of exercise.

How it works The obesity-resistant phenotype was found to be a result of increased oxygen consumption and fatty-acid oxidation due to energy demand. The authors suggest that increasing sarcolipin levels causes futile cycling of the SERCA pump—a structure in the sarcoplasmic reticulum of muscle cells that controls calcium transport. The pump uses ATP to transport calcium, and the excess sarcolipin increases ATP hydrolysis, thereby creating a chronic energy demand. At the same time, higher sarcolipin levels lead to increased cytosolic calcium that activates mitochondrial enzymes to increase oxidative phosphorylation and ATP synthesis.

“Although exercise is the best mechanism to increase energy expenditure and maintain weight, we believe that activating skeletal muscle through other means—such as novel drugs—is an attractive alternative for people who do not get sufficient exercise,” said Periasamy. “Our next step is to validate our findings in humans, and begin searching for molecules that can elevate the sarcolipin levels and its activity in muscle.”

To read the paper in full, click here.

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Journal of Biological Chemistry

Santosh Maurya

Ohio State University

SERCA pump

sarcoplasmic reticulum