TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator
Open accessAbstract
The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1(-/-)) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1(-/-) mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1(-/-) mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage.
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GDF-15 knockout mice weigh more and have increased adiposity associated with increased food intake.
“Tsai et al. (107) reported that GDF-15 gene knockout mice (Gdf-15 (-/-)) weighed more and had increased adiposity, which was associated with increased food intake, and that infusion of human recombinant GDF-15 was sufficient to raise serum levels in Gdf-15 (-/-) mice to within the normal human range, reducing body weight and food intake.”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [107]
Exogenous administration of recombinant murine or human GDF-15 induces weight loss in different animal models.
“In line with these studies, exogenous administration of recombinant murine or human GDF-15 induced weight loss in different animal models (26, 32, 40, 41, 107).”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [107]
Infusion of human recombinant GDF-15 into Gdf-15(-/-) mice raises serum levels to within the normal human range and reduces body weight and food intake.
“Tsai et al. (107) reported that GDF-15 gene knockout mice (Gdf-15 (-/-)) weighed more and had increased adiposity, which was associated with increased food intake, and that infusion of human recombinant GDF-15 was sufficient to raise serum levels in Gdf-15 (-/-) mice to within the normal human range, reducing body weight and food intake.”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [107]
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- Authors
- Tsai, V. W.-W., Macia, L., Johnen, H., Kuffner, T., Manadhar, R., Jørgensen, S. B., Lee-Ng, K. K. M., Zhang, H. P., Wu, L., Marquis, C. P., Jiang, L., Husaini, Y., Lin, S., Herzog, H., Brown, D. A., Sainsbury, A., & Breit, S. N.
- Affiliations
- UNSW Sydney (AU)
- Garvan Institute of Medical Research (AU)
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Breit, Samuel N.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-02-28
- Volume
- 8
- Issue
- 2
- Pages
- e55174
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3585300
- OpenAlex
- W1983011875
- Cited by
- 188
- References
- 42
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 20 · 2023: 20 · 2022: 17 · 2021: 18 · 2020: 24 · 2019: 24 · 2018: 9 · 2017: 12 · 2016: 10 · 2015: 7 · 2014: 8 · 2013: 1
- FWCI
- 4.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (acceptedVersion, cc-by)
- The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Keywords
- appetite regulation, body weight regulation, basal metabolic rate, energy expenditure, dietary intake, adiposity, lean body mass, knockout mice, energy storage
- MeSH terms
- Adipose Tissue, Animals, Appetite, Body Weight, Eating, Energy Metabolism, Female, Genotype, Humans, Male, Organ Size, Sex Factors, Signal Transduction, Weight Gain, Mice, Knockout, Mice, Growth Differentiation Factor 15
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