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Published on: November 28, 2015
Hyperactivated glycolysis drives spatially patterned Kupffer cell depletion in MASLD
1Yunnan Key Laboratory of Cell Metabolism and Diseases, Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China.
Elife
|May 26, 2026
Summary
Kupffer cell (KC) loss in metabolic dysfunction-associated steatotic liver disease (MASLD) is driven by increased glucose metabolism. Targeting these pathways may preserve KC function and reduce liver disease severity.
Area of Science:
- Hepatology
- Immunology
- Metabolic Diseases
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) involves liver inflammation and cell death.
- Mechanisms of Kupffer cell (KC) loss during MASLD progression are not well understood.
Purpose of the Study:
- To investigate the metabolic drivers of KC death in early MASLD.
- To establish a causal link between metabolic alterations and KC loss.
Main Methods:
- Metabolomics, immunostaining, and flow cytometry were used to assess metabolic changes and KC death.
- Biochemical agonists, isotope tracing, and primary KC cultures were employed for in vitro studies.
- Studies utilized Chi3l1-deficient mice to investigate KC death in vivo.
Main Results:
- KC death is an early feature of MASLD, with a distribution suggesting KC zonation.
- KCs exhibit increased glucose utilization during MASLD development, correlating with KC death.
- Augmented glycolytic metabolism was shown to directly cause KC death in vitro and in vivo.
Conclusions:
- Glycolytic activation causally links to KC loss during MASLD progression.
- Glucose metabolic pathways represent potential therapeutic targets for preserving KC homeostasis in MASLD.
