Ramon Sun, PhD
The long-term impact of diet on health has been well studied, leading to guidance about limiting the consumption of red meat, alcohol, and other foods associated with an increased risk of malignancies such as colorectal, breast, and liver cancers. Researchers at the University of Florida Health evaluated the association of poor diet and lung cancer in a National Institutes of Health–funded study and a collaboration between the University of Kentucky’s Markey Cancer Center and the University of Florida (UF) Health Cancer Center in Gainesville.1
“Lung cancer has not traditionally been thought of as a dietary-related disease,” said Ramon Sun, PhD, Associate Professor and Director of the UF Center for Advanced Spatial Biomolecule Research.
Glycogen as an Oncogenic Metabolite
Glycogen has been found to accumulate in high levels across a variety of cancers and other diseases. Through lab models and computer-guided models of glycogen stores in the lungs, the researchers showed that in lung cancer, glycogen acts as an oncogenic metabolite.
Researchers used advanced spatial screening techniques, which allowed for the detailed mapping of metabolites within tumor tissue at a microscopic level. These techniques enabled the analysis of lung cancer tissue samples in their native context, preserving the spatial relationships between different cell types and metabolites within the tumor microenvironment. The researchers found that glycogen accumulation in lung cancer samples from patients was linked to higher tumor grades and poorer survival outcomes.
Dietary Interventions
To further investigate the role of glycogen in tumor progression, investigators examined the effects of increasing glycogen levels using dietary interventions and genetic models. These approaches showed that elevated glycogen levels significantly accelerated tumor growth, leading to more aggressive cancer. In contrast, reducing glycogen production by targeting glycogen synthase slowed tumor growth. Additionally, they developed a new method to analyze glycogen and other key metabolites in tumor cells, revealing a strong connection between high glycogen levels and increased levels of central carbon metabolites.
The more glycogen in the cancer cells, the worse the tumor growth. When scientists fed mice a high-fat, high-fructose “Western diet” that supported more glycogen in the blood, lung tumors grew. When glycogen levels decreased, tumor growth did, too.
DISCLOSURE: For full disclosures of all study authors, visit nature.com.
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