Your diet may affect your risk for lung cancer. (WindNight/Shutterstock)
High-fat, high-carb regimen drives tumor growth in mice
In a nutshell
- Scientists discovered that a high-fat, high-sugar diet can lead to glycogen buildup in lung tissue, providing fuel for lung adenocarcinoma, the most common type of lung cancer.
- Higher levels of glycogen in lung cancer cells are linked to more aggressive tumors and poorer survival rates. Mice fed a Western-style diet developed larger, more numerous lung tumors.
- This research opens the door to dietary strategies and drug therapies that target glycogen metabolism, similar to how anti-smoking efforts helped reduce lung cancer risk in smokers.
GAINESVILLE, Fla. — Smoking isn’t the only lifestyle choice that might be damaging your lungs. Scientists have uncovered a surprising new villain in the fight against lung cancer: the combination of sugar and fat in your diet. This deadly duo triggers the buildup of glycogen, stored sugar, in lung tissue, creating what researchers call a “giant lollipop for cancer’s sweet tooth.”
Research published in Nature Metabolism shows that glycogen buildup plays a critical role in lung adenocarcinoma, an aggressive and common type of lung cancer. The study, led by University of Florida researchers, changes how we think about cancer and diet. Scientists have long known that cancer cells change how they use energy to fuel rapid growth, but the specific role of glycogen, the storage form of glucose that our bodies use for energy, has remained largely unexplored until now.
“Lung cancer has not traditionally been thought of as a dietary-related disease,” says study author Ramon Sun, Ph.D., from the University of Florida, in a statement. “Diseases like pancreatic cancer or liver cancer, yes. However, when it comes to lung cancer, the idea that diet could play a role is rarely discussed.”
The Western Diet Connection
A diet high in both fat and carbohydrates, similar to what many Americans eat daily, appears to trigger increased glycogen buildup specifically in lung tissue. The researchers found that glycogen essentially serves as a ready source of fuel for cancer cells.
The research team first analyzed tissue samples from cancer patients. They found that lung adenocarcinoma tumors contained significantly higher levels of glycogen compared to both normal lung tissue and other types of lung cancer. Higher glycogen levels in these tumors were linked to more advanced cancer and poorer survival rates.
The team conducted experiments using mice with altered genetics to directly control glycogen metabolism. By breeding mice lacking a key glycogen-regulating enzyme called laforin, they created animals that accumulated more glycogen.
For just two weeks, researchers fed mice either water (control), high-fructose corn syrup, corn oil, or a combination of both. Only the combination diet dramatically increased lung glycogen levels. When cancer was later initiated in these mice, those pre-treated with the combination diet developed more numerous and higher-grade tumors.
In experiments with mice, those given a high-fat, high-fructose “Western diet” experienced increased glycogen accumulation, which corresponded with accelerated lung tumor growth.
On the flip side, when researchers removed the gene for glycogen synthase, essentially shutting down the body’s ability to produce glycogen, tumor growth was dramatically reduced. This showed strong evidence that glycogen production is essential for lung adenocarcinoma tumor development.
The Western diet, rich in both fats and refined carbohydrates, may create conditions that make lung tissue more vulnerable to aggressive cancer growth.
What This Means for Cancer Prevention
This discovery opens new avenues for cancer prevention and treatment. Changes in diet or medications targeting glycogen metabolism could slow tumor progression in patients with lung adenocarcinoma or those at high risk.
This also builds on the research of a rare condition called Lafora disease, which has been a focus of the study authors for 20 years. This devastating neurological disorder causes patients to develop normally for about a decade and then develop epilepsy. Dementia follows, and most patients die before age 25. The disease is characterized by abnormal glycogen buildup in the brain.
“Prioritizing a nutrient-rich diet, maintaining an active lifestyle, and minimizing alcohol intake are foundational strategies for long-term health,” says study author Matthew Gentry, Ph.D., from the University of Florida College of Medicine.
For cancers of organs like the liver, the long-term impact of our diet has been well studied. Now we know that the lungs aren’t immune to dietary influences. That stockpile of glycogen is ready to feed cancer, and our Western diet might be supplying the fuel.
Paper Summary
Methodology
Researchers analyzed tissue samples from 276 lung cancer patients. They created mouse models where they could control glycogen levels through either dietary intervention or genetic modifications. Some mice were given different diets (water, high-fructose corn syrup, corn oil, or a combination) before cancer was initiated. They also bred mice lacking key enzymes involved in glycogen regulation. To understand how glycogen fuels cancer, they developed a specialized technique that could detect both glycogen and cellular metabolites in the same tissue section.
Results
Lung adenocarcinoma tumors contained significantly more glycogen than other lung cancer types or normal lung tissue. Higher glycogen levels correlated with advanced cancer and poorer survival. Mice fed a combined high-fat and high-carbohydrate diet for just two weeks before cancer initiation developed more numerous and larger tumors than control mice. Mice genetically prone to accumulate glycogen developed more aggressive tumors, while mice unable to make glycogen showed dramatically reduced tumor growth.
Limitations
The dietary studies in mice were short-term (only 2 weeks) and may not represent the effects of long-term poor diet in humans. The study focused primarily on specific genetic models of lung cancer which represent only a subset of human lung cancers. The human data came from a limited cohort of 276 patients. The study doesn’t prove whether dietary changes would be effective in patients who already have tumors, as the experiments focused on the effects of diet before cancer began.
Discussion and Takeaways
This research represents the first study of the association between lung cancer and poor diet at an NCI-designated cancer center. It identifies glycogen as a critical metabolic driver of lung adenocarcinoma and highlights potential new targets for prevention and treatment. The findings suggest that dietary choices may influence not just whether cancer develops but how aggressively it grows. From a therapeutic perspective, drugs that target glycogen metabolism might slow tumor progression in lung adenocarcinoma patients.
Funding and Disclosures
The study was supported by several grants from the National Institute of Health. Dr. Sun disclosed receiving research support and consultancy fees from Maze Therapeutics and is a member of the Medical Advisory Board for Little Warrior Foundation. Dr. Gentry reported research support from Maze Therapeutics, Valerion Therapeutics, and Ionis Pharmaceuticals, as well as consultancy fees from Maze Therapeutics, PTC Therapeutics, and the Glut1-Deficiency Syndrome Foundation.
Publication Information
The study, titled “Glycogen drives tumour initiation and progression in lung adenocarcinoma,” was published in Nature Metabolism on March 11, 2025. The collaboration was between the University of Florida and the University of Kentucky’s Markey Cancer Center, with corresponding authors Matthew S. Gentry and Ramon C. Sun from the University of Florida.
