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For some people, exercise alone may not help lose weight as fast as others, research indicates. Jaap Arriens/NurPhoto via Getty Images
  • Regular physical activity plays an important role in maintaining a healthy weight.
  • Some people lose more weight than others through exercise.
  • Researchers from Kobe University report that people who lose weight slower with regular physical activity may be lacking variants of a specific protein that helps regulate the body’s metabolism and response to short-term exercise.
  • Scientists believe this finding may open the doors for an entirely new class of weight loss medications.

Everyone knows that regular physical activity is important to maintaining a healthy weight. However, some people lose more weight than others through exercise.

Why is that?

Researchers from Kobe University in Japan say people who lose weight slower with regular physical activity may be lacking variants of the protein PGC-1α, which helps regulate the body’s metabolism and response to short-term exercise.

Scientists believe this finding may open the doors for an entirely new class of weight loss medication.

The study was recently published in the journal Molecular Metabolism.

For this study, researchers used both mouse and human models to look deeper into how the protein PGC-1α impacts exercise and its effects on the body.

“PGC-1α is a protein that falls under the category of ‘transcription coactivators,’ which have the function of inducing gene expression,” Wataru Ogawa, MD, PhD, professor and chair in the Division of Diabetes and Endocrinology in the Department of Internal Medicine at Kobe University Graduate School of Medicine in Japan and lead author of this study explained to Medical News Today. “PGC-1α enhances the expression of genes related to mitochondria, genes involved in fatty acid oxidation, and genes involved in thermogenesis, promoting efficient energy consumption in muscles.”

“When you exercise, the expression of PGC-1α in skeletal muscle increases, which in turn induces the expression of genes that promote efficient energy consumption,” Ogawa continued. “This is considered to be the mechanism by which energy is efficiently expended in muscles during exercise.”

Through previous research, scientists have identified there is not only the normal “a” version of the PGC-1α protein, but also “b” and “c” versions that are a bit different.

“These new PGC-1α versions, called ‘b’ and ‘c,’ have almost the same function as the conventional ‘a’ version, but they are produced in muscles more than tenfold more during exercise, while the ‘a’ version does not show such an increase,” Ogawa explains.

Using both a mouse model and human test subjects, Ogawa and his team found that not having “b” and “c” versions of PGC-1⍺ protein meant short-term activity had no impact on the body, causing less fat burn during and after a workout.

However, when human test subjects had both “b” and “c” versions of the protein, they consumed more oxygen and had a smaller percentage of body fat than those who did not. This was seen in humans who were both healthy and with type 2 diabetes.

“Mice lacking only PGC-1α b/c not only exhibited reduced energy expenditure during exercise but also gained weight even when housed under normal conditions,” Ogawa said. “The amount of food the mice consumed was not different from that of the control mice. We were surprised to find this strong phenotype; these mice became obese. While there are many model mice that become obese due to increased food intake, there are few model mice that gain weight due to reduced energy expenditure.”

“Additionally, there are mouse models that gain weight when fed a high-fat diet or other special diets, but a mouse model that gains weight simply by eating a normal diet is rare,” he added. “Our observations clearly support the hypothesis that ‘the efficiency of energy expenditure in muscles determines the tendency to gain weight.’”

With the current interest in weight loss drugs such as glucagon-like peptide-1 (GLP-1) receptor agonists, how might these findings be used to either change or develop weight loss medications in the future?

How this is different from drugs like Wegovy

“Recently, powerful anti-obesity drugs have been developed and are starting to be widely used around the world. These medications [GLP-1 agonists] work by suppressing appetite. In other words, they help people lose weight by reducing their food intake. A drug that increases the expression of PGC-1α b/c, unlike such appetite-suppressing medications, would promote weight loss regardless of diet. This represents an entirely new class of medication.”
— Wataru Ogawa, MD, PhD,

“As the saying goes, ‘exercise is medicine’ and exercise contributes to the cure and improvement of various conditions,” he continued. “In the treatment of diabetes, which is my expertise, exercise therapy is the most fundamental and effective treatment. If the mechanisms of weight loss through exercise become clear, it could lead to the development of better exercise therapies and, more importantly, drugs that mimic the effects of exercise.”

For the next steps in this research, Ogawa said they are conducting research on why the increase in PGC-1α b/c varies among individuals, and we are beginning to uncover some of the reasons.

“The phenomenon of DNA methylation seems to explain this variability,” he added. “Additionally, we have identified a substance that can increase PGC-1α b/c levels. Such a substance could potentially lead to the development of new anti-obesity drugs.”

After reviewing this study, Mir Ali, MD, a board certified bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA told MNT he found it to be very interesting.

“Obviously, we’ve known for a long time that genetics plays a big component in some of the weight gain and weight loss, so it was interesting to see that this shows a genetic component to exercise as well,” Ali said.

Although exercise does contribute to how well or quickly someone loses weight, Ali said he tells his patients the biggest factor in losing weight is their diet.

“Even if somebody exercises a lot but they’re choosing the wrong diet, they still are not going to see a lot of weight loss results,” he continued. “Exercise is an important adjunct to weight loss, also of course cardiovascular health and there’s a lot of other benefits to exercise. But for somebody trying to lose weight, the biggest thing is the actual diet that they’re eating.”