2-Deoxy-D-glucose Alleviates Cancer Cachexia-Induced Muscle Wasting by Enhancing Ketone Metabolism and Inhibiting the Cori Cycle.
Level 5 - mechanism / opinion, no new human data
Preclinical animal study
PubMed 36230949 · doi:10.3390/cells11192987
What was done
Researchers evaluated the therapeutic effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on metabolic alterations and muscle wasting in a C26 adenocarcinoma mouse xenograft model of cancer cachexia. Following in vivo 2-DG administration, they assessed tumor-free lean mass, hindlimb muscle morphology, fiber-type composition, hepatic gluconeogenesis and ketogenesis, and activation of the ubiquitin-proteasome pathway (UPS) and autophagic-lysosomal pathway (ALP).
What was found
The abstract reports no specific quantitative values or effect sizes. Qualitatively, tumor-bearing cachectic mice exhibited altered glucose and lipid metabolism, decreased carbohydrate utilization, increased lipid beta-oxidation, increased hepatic gluconeogenesis, and decreased hepatic ketogenesis. Administration of 2-DG significantly attenuated cachexia-induced loss of lean mass and muscle fiber cross-sectional area. Mechanistically, 2-DG inhibited protein degradation via the UPS and ALP, stimulated liver ketogenesis, enhanced skeletal muscle ketone metabolism, and improved mitochondrial bioenergetic capacity by disrupting abnormal Cori cycle activity.
Why it matters
Targeting metabolic shifts such as hyperactive Cori cycling and altered substrate utilization with 2-DG provides a potential mechanistic rationale for preserving skeletal muscle mass and bioenergetics during cancer cachexia.
Limits
This is entirely preclinical research conducted in a single mouse xenograft model (C26 adenocarcinoma); findings cannot be directly applied to human patients. The abstract omits sample sizes, dosage, treatment duration, and exact quantitative data or confidence intervals. Potential systemic toxicities or tolerability issues associated with pharmacological glycolysis inhibition were not detailed.
Cited by
- supports 2-deoxyglucose administration increases ketone levels because cells experience perceived glucose deprivation.