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Oversecretion of interleukin-15 from skeletal muscle reduces adiposity
Open accessAbstract
Obesity is a risk factor for development of insulin resistance, type 2 diabetes, cardiovascular disease, osteoarthritis, and some forms of cancer. Many of the adverse health consequences of excess fat deposition are caused by increased secretion of proinflammatory adipokines by adipose tissue. Reciprocal muscle-to-fat signaling factors, or myokines, are starting to be identified. Interleukin-15 (IL-15) is a cytokine that is highly expressed in muscle tissue and that, on the basis of cell culture experiments, has been proposed to act as a circulating myokine that inhibits adipose tissue deposition. To test this hypothesis in vivo, two lines of transgenic mice that overexpressed IL-15 mRNA and protein in skeletal muscle tissue were constructed. By substitution of the inefficient native IL-15 signal peptide with a more efficient signal peptide, one of the transgenic mouse lines also exhibited elevated secretion of IL-15 in the circulation. Overexpression of IL-15 in muscle tissue without secretion in the bloodstream resulted in no differences in body composition. Elevated circulating levels of IL-15 resulted in significant reductions in body fat and increased bone mineral content, without appreciably affecting lean body mass or levels of other cytokines. Elevated circulating levels of IL-15 also inhibited adiposity induced by consumption of a high-fat/high-energy diet in male, but not female, transgenic mice. Female mice with elevated serum IL-15 exhibited increased deposition of lean body mass on a low-fat/low-energy diet and a high-fat/high-energy diet. These findings indicate that muscle-derived circulating IL-15 can modulate adipose tissue deposition and support addition of IL-15 to the growing list of potential myokines that are increasingly being implicated in regulation of body composition.
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“as exemplified in a murine model overexpressing IL-15 in which the percentage of visceral fat mass, measured by DEXA, was approximately half when compared with controls [88].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [88]
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“Interleukin-15 exerts local anabolic/anti-catabolic effects [10] and increases glucose uptake, thus inhibiting lipid deposition [10, 11].”
From β-hydroxy-β -methylbutyrate supplementation benefits the effects of resistance training on body fat reduction via increased irisin expression in white adipose tissue (2021) · cites this paper as [11]
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“The ability of IL-15 to act on muscle- adipose tissue crosstalk was investigated by the same group, showing IL-15 overexpression in relation to reduced adiposity.”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Quinn et al., 2009
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“Only the group that had the increased levels of IL-15 from the muscle in circulation had a reduction in adiposity due to the greater targeting of this substrate for energy generation (Quinn et al., 2009).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Quinn et al., 2009
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Metadata
- Authors
- Quinn, L. S., Anderson, B. G., Strait-Bodey, L., Stroud, A. M., & Argilés, J. M.
- Affiliations
- VA Puget Sound Health Care System (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2009-01
- Volume
- 296
- Issue
- 1
- Pages
- E191-E202
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC2636988
- OpenAlex
- W2167204431
- Cited by
- 267
- References
- 78
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 10 · 2023: 12 · 2022: 21 · 2021: 18 · 2020: 16 · 2019: 16 · 2018: 24 · 2017: 21 · 2016: 14 · 2015: 21 · 2014: 16 · 2013: 16 · 2012: 21
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG024136, P30AG013280)
- National Institute of Diabetes and Digestive and Kidney Diseases (5-P30-DK-17047, P30DK017047)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- IL-15, myokines, skeletal muscle, adiposity, fat deposition, transgenic mice, bone mineral content, high-fat diet, sex differences, body composition, obesity
- MeSH terms
- Animals, Body Composition, Crosses, Genetic, Dietary Fats, Female, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, RNA, Messenger, Specific Pathogen-Free Organisms, Muscle, Skeletal, Interleukin-15, Reverse Transcriptase Polymerase Chain Reaction, Adiposity, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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