Tumor-induced anorexia and weight loss are mediated by the TGF-β superfamily cytokine MIC-1
Open accessAbstract
Anorexia and weight loss are part of the wasting syndrome of late-stage cancer, are a major cause of morbidity and mortality in cancer, and are thought to be cytokine mediated. Macrophage inhibitory cytokine-1 (MIC-1) is produced by many cancers. Examination of sera from individuals with advanced prostate cancer showed a direct relationship between MIC-1 abundance and cancer-associated weight loss. In mice with xenografted prostate tumors, elevated MIC-1 levels were also associated with marked weight, fat and lean tissue loss that was mediated by decreased food intake and was reversed by administration of antibody to MIC-1. Additionally, normal mice given systemic MIC-1 and transgenic mice overexpressing MIC-1 showed hypophagia and reduced body weight. MIC-1 mediates its effects by central mechanisms that implicate the hypothalamic transforming growth factor-beta receptor II, extracellular signal-regulated kinases 1 and 2, signal transducer and activator of transcription-3, neuropeptide Y and pro-opiomelanocortin. Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity.
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In mice, GDF-15 increases satiety and reduces food intake through actions in the central nervous system.
“In mice, GDF-15 increases satiety and reduces food intake through actions in the central nervous system [99].”
From What is the pipeline for future medications for obesity? (2025) · cites this paper as [99]
The use of GDF-15 RA as a potential treatment for obesity stems from observations that elevated tumour-secreted GDF-15 is correlated with weight loss.
“The GDF-15 RA use as a potential treatment for obesity stems from observations that elevated tumour-secreted GDF-15 is correlated with WL [99].”
From What is the pipeline for future medications for obesity? (2025) · cites this paper as [99]
Overexpressing GDF-15 decreases body weight, fat mass and food intake, and improves glucose tolerance in mouse models.
“On the contrary, overexpressing GDF-15 led to decreased body weight, fat mass and food intake, improving the glucose tolerance in mouse models (83, 108–110).”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [108]
Experimental and clinical data support a role for GDF15 in regulating body weight and energy homeostasis.
“Experimental and clinical data have supported its role in regulating body weight and energy homeostasis [[210], [211], [212], [213]] (Figure 2).”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [211]
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References 25 · Cited by 612
Research works printed but not linked: 1
- [13]13. Johnen et al.: Tumor-induced anorexia and weight loss are mediated by the TGF-β superfamily cytokine MIC-1 Nature Medicine 13(11): 1333-1340, 2007
- Authors
- Johnen, H., Lin, S., Kuffner, T., Brown, D. A., Tsai, V. W.-W., Bauskin, A. R., Wu, L., Pankhurst, G., Jiang, L., Junankar, S., Hunter, M., Fairlie, W. D., Lee, N. J., Enriquez, R. F., Baldock, P. A., Corey, E., Apple, F. S., Murakami, M. M., Lin, E.-J., Wang, C., During, M. J., Sainsbury, A., Herzog, H., & Breit, S. N.
- Affiliations
- UNSW Sydney (AU)
- Garvan Institute of Medical Research (AU)
- University of Washington (US)
- University of Minnesota (US)
- The Ohio State University (US)
- Corresponding author
- Breit, Samuel N
- ORCID
- Venue
- Nature Medicine
- Published
- 2007-11
- Volume
- 13
- Issue
- 11
- Pages
- 1333-1340
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1975913194
- Cited by
- 612
- References
- 25
- Citations by year
- 2026: 34 · 2025: 52 · 2024: 53 · 2023: 44 · 2022: 62 · 2021: 53 · 2020: 55 · 2019: 37 · 2018: 25 · 2017: 29 · 2016: 20 · 2015: 19 · 2014: 23 · 2013: 20 · 2012: 17
- FWCI
- 7.35
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
- Funders
- Lucas Foundation
- University of Queensland
- NSW Ministry of Health
- Medical Research Council
- National Health and Medical Research Council
- Cancer Council NSW
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- MIC-1, tumor-induced anorexia, cachexia, prostate cancer, TGF-beta superfamily, TGF-βRII, ERK1/2, STAT3, neuropeptide Y, proopiomelanocortin, hypothalamus, appetite regulation, dietary intake, obesity
- MeSH terms
- Animals, Anorexia, Antibodies, Multigene Family, Humans, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Mice, Transgenic, Prostatic Neoplasms, Weight Loss, Cytokines, Transforming Growth Factor beta, Cell Line, Tumor, Mice, Growth Differentiation Factor 15
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