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Updated: Oct 30, 2025
08:55
The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
16.7K
A Metabolic Change towards Fermentation Drives Cancer Cachexia in Myotubes
Michele Mannelli1, Tania Gamberi1, Francesca Magherini1
1Dipartimento di Scienze Biomediche, Sperimentali e Cliniche "M. Serio", Università degli Studi di Firenze, Viale Morgagni 50, 50134 Firenze, Italy.
Biomedicines
|July 2, 2021
Summary
Cachexia involves a metabolic shift to fermentation in muscle cells. Inhibiting lactate production prevents this cachectic phenotype, offering a potential therapeutic target.
Area of Science:
- Biochemistry
- Cell Biology
- Pathology
Background:
- Cachexia is a complex metabolic disorder linked to various diseases, notably cancer.
- It significantly impacts muscle tissue, leading to loss of function and mass.
- Understanding the molecular mechanisms driving cachexia is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of metabolic shifts in cachexia induction in muscle cells (myotubes).
- To identify key molecular targets for preventing or reversing the cachectic phenotype.
- To explore the potential of inhibiting specific metabolic pathways as a therapeutic strategy.
Main Methods:
- Cachexia was induced in myotubes using conditioned media from cancer cell lines (CT26, HCT116, MIAPaCa-2).
- Metabolic changes, including glucose uptake, oxygen consumption, and lactate production, were analyzed.
- The effects of inhibiting glycolysis (2-deoxy-glucose) and lactate dehydrogenase (oxamate) were assessed.
- Mitochondrial function, including membrane potential and pyruvate dehydrogenase activity, was evaluated.
- The role of interleukin-6 in cachexia and metabolic alterations was examined.
Main Results:
- Cachectic myotubes exhibited increased glucose uptake, reduced oxygen consumption, and elevated lactate production, indicating a shift towards fermentation.
- Inhibition of glycolysis or lactate dehydrogenase activity prevented cachexia induction and restored mitochondrial function.
- Interleukin-6-induced cachexia also involved a fermentative metabolism, which was reversed by lactate dehydrogenase inhibition.
- The observed metabolic shift and its reversal were consistent across different cancer cell line-derived conditioned media.
Conclusions:
- Cachexia induction in myotubes is strongly associated with a metabolic shift towards fermentation.
- Inhibiting lactate formation, specifically by targeting lactate dehydrogenase, effectively impedes cachexia.
- Lactate dehydrogenase emerges as a potential therapeutic target for counteracting cachexia onset.
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