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Systemic administration of ciliary neurotrophic factor induces cachexia in rodents
J T Henderson1, N A Seniuk, P M Richardson
1Samuel Lunenfeld Research Institute, Division of Neurobiology and Molecular Immunology, Mount Sinai Hospital, Toronto, Ontario, Canada.
The Journal of Clinical Investigation
|June 1, 1994
Summary
Ciliary neurotrophic factor (CNTF) causes rapid weight loss and death in mice, affecting fat and muscle tissue. This potent extra-neural effect is distinct from its known neurological roles.
Area of Science:
- Neuroscience
- Endocrinology
- Molecular Biology
Background:
- Ciliary neurotrophic factor (CNTF) is known for promoting neuron and glial cell survival.
- Its role in extra-neural tissues remains largely unexplored.
Purpose of the Study:
- To investigate the effects of CNTF on extra-neural tissues.
- To characterize the physiological consequences of systemic CNTF administration.
Main Methods:
- Engineered C6 glioma cells secreting CNTF were implanted subcutaneously or intraperitoneally in mice.
- Purified recombinant rat or human CNTF was administered systemically.
- Weight loss, food intake, body composition, and acute phase protein synthesis were analyzed.
Main Results:
- CNTF administration induced a rapid wasting syndrome, leading to death within 7-10 days.
- Weight loss involved significant reduction in fat and skeletal muscle mass, independent of food intake.
- CNTF stimulated the synthesis of acute phase proteins like haptoglobin.
Conclusions:
- CNTF exhibits potent, detrimental effects on extra-neural tissues, causing a wasting syndrome.
- The observed effects share similarities with cachectins but do not involve the induction of common inflammatory cytokines.
- CNTF represents a novel target for understanding metabolic dysregulation and wasting diseases.

