Anyone who has tried to lose weight by cutting calories knows the frustration -- after initial success, weight loss slows down or stops completely.
This happens because the body adapts to lower calorie intake by slowing metabolism, conserving energy as if it were facing starvation.
Now, researchers at the University of Southern Denmark have found a potential way to keep the body burning calories efficiently even when fewer calories are consumed.
Their study, published in Cell Metabolism, could help people using weight-loss medications like Wegovy and Ozempic, which often stop working after a certain point.
Why Weight Loss Slows Down
Many people using weight-loss drugs can lose 20-25% of their body weight, but their progress eventually stalls. This is because the body naturally lowers metabolism to match the new, lower weight.
"If we could develop a medication that helps maintain fat or sugar burning at its original high level, people could continue losing weight beyond the usual plateau," explains Kim Ravnskjaer, lead researcher and associate professor at the University of Southern Denmark.
While a breakthrough drug is still far away, this discovery could one day help extend the benefits of current weight-loss treatments.
A Surprising Gene Discovery
The research team was not initially studying weight loss. They were investigating a gene called Plvap in mouse liver cells. This gene is known to be involved in fat metabolism, but its exact function was unclear.
They made an unexpected discovery:
Essentially, the researchers found a way to override the body's natural response to calorie restriction, which could help people avoid weight-loss plateaus.
What Happens When Plvap is Turned Off?
The researchers found that when Plvap was turned off in mice:
This suggests that blocking Plvap might not only help with weight loss but also improve blood sugar control, which could be useful for treating type 2 diabetes and metabolic disorders.
A New Way the Liver Controls Metabolism
One of the most exciting findings was that stellate cells -- a type of liver cell not previously linked to metabolism -- were responsible for triggering these changes.
This discovery reveals a new way that cells in the liver communicate to regulate metabolism -- a breakthrough that could lead to new treatments for metabolic diseases.
Implications for Weight Loss and Diabetes
This research opens exciting possibilities for weight loss and metabolic health:
Challenges and Next Steps
While these findings are promising, they are currently based on mouse studies. It will take years of further research to determine whether blocking Plvap has the same effects in humans.
Still, researchers are hopeful.
"If we can control how the liver burns sugar and fat, we may be able to make weight-loss and diabetes treatments far more effective," says Ravnskjaer.
In the future, this research could lead to new medications that help people continue losing weight beyond the typical plateau and better treatments for metabolic diseases. For now, scientists will continue studying how Plvap works and how it can be safely targeted for medical use.
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