In a breakthrough that could reshape how we understand fat, scientists have found that endosomes—tiny compartments in cells known for recycling molecules—also play a direct role in breaking down fat.
The findings, published in “Nature Communications,” offer fresh insights that could help treat diseases tied to fat imbalance, such as obesity, diabetes, Alzheimer’s and cancer.
The study was led by Professor of Biology Jianbo Yue at Duke Kunshan University. His team studied how cells store and use fat and discovered that endosomes engage in fat breakdown—something scientists hadn’t expected.
Unexpected behavior inside cells
Using a new fluorescent probe called AP1‑coumarin, the researchers watched tiny fat-storage spheres called lipid droplets inside live cells. To their surprise, they saw endosomes surround and swallow these droplets.
The team nicknamed the glowing endosomes “fat-eating Pac‑Men.” At first, the unexpected process seemed like an error, but after careful checks, they realized it was a genuine discovery.
Further tests showed that blocking the formation of lipid droplets disrupted endosome function and impaired the cell’s ability to absorb nutrients. According to Yue, this suggests that the interaction between lipid droplets and endosomes is essential for maintaining energy balance and cell health.
Broader health implications
Fat metabolism plays a central role in a range of diseases. Excess fat accumulation causes obesity, diabetes and fatty liver disease. Neurodegenerative diseases such as Alzheimer’s and Parkinson’s often show fat buildup in neurons. In cancer, tumor cells frequently rewire their metabolism to extract energy from fat, especially during metastasis.
Yue said the study could help scientists better understand these conditions and develop treatments by controlling how fat is processed inside cells. Boosting endosomal activity, for example, could help remove excess fat, while reducing it might slow fat loss in muscle-wasting diseases.
“People were skeptical,” Yue said. “Lipid metabolism has usually been explained through lysosomes and autophagosomes. We had to work hard to prove endosomes were in on the action.”
Future directions: drugs and diagnostics
The research team is now investigating key molecular “switches” that control the endosome–lipid droplet interaction. Their goal is to explore whether the process can be targeted to develop anti-cancer drugs, particularly to prevent tumor spread.
They also plan to expand the use of the AP1-coumarin probe as a commercial product, offering customizable imaging tools for live-cell research and drug screening.
The study was led by Yue and his Ph.D. student Wang Peng, with contributions from research assistant Jingyu Ma, postdoctoral fellows Naixin Lin and Jinchao Xing, and scientists from City University of Hong Kong, Southern University of Science and Technology, the Guangzhou Institute of Biomedicine and Health, the Chinese Academy of Sciences, and Cornell University.
The full, open-access study is available in “Nature Communications” at: https://rdcu.be/ea3Tx
