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:
- The Plvap gene helps the liver recognize when the body is fasting.
- When the researchers turned off Plvap, the liver did not switch to burning fat during fasting as it normally would. Instead, it kept burning sugar.
- This tricked the body into continuing to burn calories as if it were not in a fasting state.
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:
- The liver did not recognize fasting and continued burning sugar instead of switching to fat-burning.
- Fat that was released from storage was redirected to muscles instead of the liver.
- The mice had improved insulin sensitivity and lower blood sugar levels—potential benefits for people with diabetes.
- Despite changes in metabolism, the mice remained healthy with no negative effects.
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.
- Most studies focus on hepatocytes, the liver’s main cells that process nutrients.
- But this research shows that stellate cells send important signals that control how the liver switches between burning sugar and fat.
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:
- Weight-loss drugs could be made more effective by blocking Plvap to prevent the body from slowing metabolism.
- Type 2 diabetes treatments could improve by helping the body burn sugar more efficiently.
- New therapies for fatty liver disease could be developed, as fat was redirected to muscles instead of accumulating in the liver.
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.
If you care about diabetes, please read studies about diabetes and vitamin B12, and the right diet for people with type 2 diabetes.
For more health information, please see recent studies about how to eat smart with diabetes, and turmeric and vitamin D: a duo for blood pressure control in diabetic patients.
The research findings can be found in Cell Metabolism.
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