Overexpression of interleukin-15 in mice promotes resistance to diet-induced obesity, increased insulin sensitivity, and markers of oxidative skeletal muscle metabolism
Open accessAbstract
Interleukin-15 (IL-15) is a cytokine that is highly expressed in skeletal muscle. In addition to its well-characterized effects on innate immunity, IL-15 has been proposed to modulate skeletal muscle and adipose tissue mass, as well as insulin sensitivity. In the present study, an IL-15 gain-of-function model, transgenic mice with skeletal muscle-specific oversecretion of IL-15 (IL-15 Tg mice), was utilized to test the hypotheses that IL-15 promotes insulin sensitivity and resistance to diet-induced obesity (DIO) by increasing circulating adiponectin levels, and that IL-15 regulates skeletal muscle metabolism without inducing overt muscle hypertrophy. Compared to closely related control mice, IL-15 Tg mice exhibited lower total body fat following high-fat feeding, lower intra-abdominal fat following both low- and high-fat feeding, and greater insulin sensitivity. However, this was not accompanied by increased total or high molecular weight serum adiponectin levels in IL-15 Tg mice. While overall lean body mass did not differ, IL-15 Tg mice exhibited increased mass of the oxidative soleus muscle, and increased expression of mRNA encoding the slow isoform of troponin I (TnnI 1) in the predominately glycolytic extensor digitorum longus muscle. Skeletal muscle tissue from IL-15 Tg mice also exhibited alterations in the expression of several genes associated with fatty acid metabolism, such as SIRT1, SIRT4, and uncoupling protein 2 (UCP2). These findings suggest changes in oxidative metabolism, rather than induction of adiponectin expression, appear to be responsible for the DIO-resistant and more insulin-sensitive phenotype of IL-15 Tg mice.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IL-15 is directly related to muscle metabolism, diet-induced obesity, and insulin sensitivity.
“In addition, IL-15 is directly related to muscle metabolism, or even diet-induced obesity and insulin sensitivity (Quinn et al., 2011, 2013).”
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., 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Bulfone‐Paus, S., Bulanova, E., Pohl, T., Budagian, V., Dürkop, H., Ruckert, R., Kunzendorf, U., Paus, R., & Krause, H. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.12.1575 · Cited by 152 · see citing works
RetractedAdipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518 · see citing works
Mechanisms linking obesity to insulin resistance and type 2 diabetes
Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006) · Nature · doi:10.1038/nature05482 · Cited by 5,448 · see citing works
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139 · see citing works
Harris, M. I., Flegal, K. M., Cowie, C. C., Eberhardt, M. S., Goldstein, D. E., Little, R. R., Wiedmeyer, H.-M., & Byrd-Holt, D. D. (1998) · Diabetes Care · doi:10.2337/diacare.21.4.518 · Cited by 2,703 · see citing works
Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546 · see citing works
Obesity and the Environment: Where Do We Go from Here?
Hill, J. O., Wyatt, H. R., Reed, G. W., & Peters, J. C. (2003) · Science · doi:10.1126/science.1079857 · Cited by 2,180 · see citing works
Mitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107 · see citing works
Maeda, N., Takahashi, M., Funahashi, T., Kihara, S., Nishizawa, H., Kishida, K., Nagaretani, H., Matsuda, M., Komuro, R., Ouchi, N., et al. (2001) · Diabetes · doi:10.2337/diabetes.50.9.2094 · Cited by 1,659 · see citing works
Cloning of a T Cell Growth Factor that Interacts with the β Chain of the Interleukin-2 Receptor
Grabstein, K. H., Eisenman, J. R., Shanebeck, K. D., Rauch, C. T., Srinivasan, S., Fung, V., Beers, C., Richardson, J. S., Schoenborn, M. A., Ahdieh, M., et al. (1994) · Science · doi:10.1126/science.8178155 · Cited by 1,422 · see citing works
Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC‐1α
Gerhart‐Hines, Z., Rodgers, J. T., Bare, O., Lerin, C., Kim, S., Mostoslavsky, R., Alt, F. W., Wu, Z., & Puigserver, P. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601633 · Cited by 1,294 · see citing works
Visser, M., Pahor, M., Taaffe, D. R., Goodpaster, B. H., Simonsick, E. M., Newman, A. B., Nevitt, M., & Harris, T. B. (2002) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/57.5.m326 · Cited by 1,294 · see citing works
Interleukin 15: biology and relevance to human disease
Fehniger, T. A., & Caligiuri, M. A. (2001) · Blood · doi:10.1182/blood.v97.1.14 · Cited by 976 · see citing works
Cantó, C., Jiang, L. Q., Deshmukh, A. S., Mataki, C., Coste, A., Lagouge, M., Zierath, J. R., & Auwerx, J. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.02.006 · Cited by 921 · see citing works
Minireview: Lipid Metabolism, Metabolic Diseases, and Peroxisome Proliferator-Activated Receptors
Lee, C., Olson, P., & Evans, R. M. (2003) · Endocrinology · doi:10.1210/en.2003-0288 · Cited by 891 · see citing works
Fulco, M., Cen, Y., Zhao, P., Hoffman, E. P., McBurney, M. W., Sauve, A. A., & Sartorelli, V. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.02.004 · Cited by 821 · see citing works
Feige, J. N., Lagouge, M., Canto, C., Strehle, A., Houten, S. M., Milne, J. C., Lambert, P. D., Mataki, C., Elliott, P. J., & Auwerx, J. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.017 · Cited by 719 · see citing works
The diseasome of physical inactivity – and the role of myokines in muscle–fat cross talk
Pedersen, B. K. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.179515 · Cited by 631 · see citing works
Adipose Tissue-Derived Factors: Impact on Health and Disease
Trujillo, M. E., & Scherer, P. E. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0033 · Cited by 611 · see citing works
Srikanthan, P., Hevener, A. L., & Karlamangla, A. S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010805 · Cited by 600 · see citing works
Sir2 Regulates Skeletal Muscle Differentiation as a Potential Sensor of the Redox State
Fulco, M., Schiltz, R. L., Iezzi, S., King, M. T., Zhao, P., Kashiwaya, Y., Hoffman, E. P., Veech, R. L., & Sartorelli, V. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00226-0 · Cited by 590 · see citing works
Tumor necrosis factor-α and muscle wasting: a cellular perspective
Reid, M. B., & Li, Y. (2001) · Respiratory Research · doi:10.1186/rr67 · Cited by 458 · see citing works
IL-15/IL-15 receptor biology: A guided tour through an expanding universe
Budagian, V., BULANOVA, E., Paus, R., & Bulfone‐Paus, S. (2006) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2006.05.001 · Cited by 386 · see citing works
Arany, Z., Lebrasseur, N., Morris, C., Smith, E., Yang, W., Ma, Y., Chin, S., & Spiegelman, B. M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2006.12.003 · Cited by 370 · see citing works
SIRT4 Regulates Fatty Acid Oxidation and Mitochondrial Gene Expression in Liver and Muscle Cells
Nasrin, N., Wu, X.-P., Fortier, E., Feng, Y., Bare, O., Chen, S., Ren, X., Wu, Z., Streeper, R. S., & Bordone, L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.124164 · Cited by 323 · see citing works
Interleukin-15: a novel anabolic cytokine for skeletal muscle.
Quinn, L. S., Haugk, K. L., & Grabstein, K. H. (1995) · Endocrinology · doi:10.1210/endo.136.8.7628408 · Cited by 270 · see citing works
Self-citationOversecretion of interleukin-15 from skeletal muscle reduces adiposity
Quinn, L. S., Anderson, B. G., Strait-Bodey, L., Stroud, A. M., & Argilés, J. M. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90506.2008 · Cited by 267 · cited 5× · see citing works
“22 In the present study, mice were group-housed in order to minimize stress as a variable; therefore, food intake could not be assessed.”
InfluentialEvaluation of a Quantitative Magnetic Resonance Method for Mouse Whole Body Composition Analysis
Tinsley, F. C., Taicher, G. Z., & Heiman, M. L. (2004) · Obesity Research · doi:10.1038/oby.2004.20 · Cited by 244 · see citing works
Quinn, L. S., Anderson, B. G., Drivdahl, R. H., Alvarez, B., & Argilés, J. M. (2002) · Experimental Cell Research · doi:10.1006/excr.2002.5624 · Cited by 226 · see citing works
Skeletal muscle lipid accumulation in obesity, insulin resistance, and type 2 diabetes
Goodpaster, B. H., & Wolf, D. L. (2004) · Pediatric Diabetes · doi:10.1111/j.1399-543x.2004.00071.x · Cited by 206 · see citing works
Hughes, S. M., Chi, M. M.-Y., Lowry, O. H., & Gundersen, K. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.3.633 · Cited by 202 · see citing works
QUINN, L., STRAITBODEY, L., ANDERSON, B., ARGILES, J., & HAVEL, P. (2005) · Cell Biology International · doi:10.1016/j.cellbi.2005.02.005 · Cited by 199 · see citing works
Association between Interleukin-15 and Obesity: Interleukin-15 as a Potential Regulator of Fat Mass
Nielsen, A. R., Højman, P., Erikstrup, C., Fischer, C. P., Plomgaard, P., Mounier, R., Mortensen, O. H., Broholm, C., Taudorf, S., Krogh‐Madsen, R., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2561 · Cited by 194 · see citing works
McGuinness, O. P., Ayala, J. E., Laughlin, M. R., & Wasserman, D. H. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90996.2008 · Cited by 190 · see citing works
Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats
Carbó, N., López‐Soriano, J., Costelli, P., Busquets, S., Alvarez, B., Baccino, F. M., Quinn, L. S., López-Soriano, F. J., & Argilés, J. M. A. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1299 · Cited by 181 · see citing works
Self-citationCarbó, N., López-Soriano, J., Costelli, P., Alvarez, B., Busquets, S., Baccino, F. M., Quinn, L. S., López-Soriano, F. J., & Argilés, J. M. (2001) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(00)00188-4 · Cited by 174 · see citing works
Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function
Krause, M. P., Liu, Y., Vu, V., Chan, L., Xu, A., Riddell, M. C., Sweeney, G., & Hawke, T. J. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00030.2008 · Cited by 168 · see citing works
Interleukin-15 contributes to the regulation of murine adipose tissue and human adipocytes
Barra, N. G., Reid, S., MacKenzie, R., Werstuck, G., Trigatti, B. L., Richards, C., Holloway, A. C., & Ashkar, A. A. (2010) · Obesity · doi:10.1038/oby.2009.445 · Cited by 116 · see citing works
Marzetti, E., Carter, C. S., Wohlgemuth, S. E., Lees, H. A., Giovannini, S., Anderson, B., Quinn, L. S., & Leeuwenburgh, C. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.12.008 · Cited by 113 · see citing works
Self-citationHull, R. L., Andrikopoulos, S., Verchere, C. B., Vidal, J., Wang, F., Cnop, M., Prigeon, R. L., & Kahn, S. E. (2003) · Diabetes · doi:10.2337/diabetes.52.2.372 · Cited by 109 · see citing works
Alvarez, B., Carbó, N., López‐Soriano, J., Drivdahl, R. H., Busquets, S., López-Soriano, F. J., Argilés, J. M. A., & Quinn, L. S. (2002) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(02)00148-4 · Cited by 108 · see citing works
Self-citationFigueras, M., Busquets, S., Carbó, N., Barreiro, E., Almendro, V., Argilés, J. M. A., & López-Soriano, F. J. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.05.066 · Cited by 108 · see citing works
Busquets, S., Figueras, M., Almendro, V., López-Soriano, F. J., & Argilés, J. M. A. (2006) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2006.09.001 · Cited by 92 · see citing works
Liu, Y., Chewchuk, S., Lavigne, C., Brûlé, S., Pilon, G., Houde, V. P., Xu, A., Marette, A., & Sweeney, G. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00186.2009 · Cited by 86 · see citing works
Degens, H., Turek, Z., Hoofd, L. J. C., et al. (1992) · PubMed · Cited by 84 · see citing works
Uncoupling Proteins: Role in Insulin Resistance and Insulin Insufficiency
B.Chan, C., & Harper, M.-E. (2006) · Current Diabetes Reviews · doi:10.2174/157339906777950660 · Cited by 71 · see citing works
Pistilli, E. E., Devaney, J. M., Gordish‐Dressman, H., Bradbury, M. K., Seip, R. L., Thompson, P. D., Angelopoulos, T. J., Clarkson, P. M., Moyna, N. M., Pescatello, L. S., et al. (2008) · Cytokine · doi:10.1016/j.cyto.2008.04.008 · Cited by 71 · see citing works
Large Copy-Number Variations Are Enriched in Cases With Moderate to Extreme Obesity
Wang, K., Li, W., Glessner, J., Grant, S. F. A., Hakonarson, H. H., & Price, R. A. (2010) · Diabetes · doi:10.2337/db10-0192 · Cited by 67 · see citing works
SirT1 in muscle physiology and disease: lessons from mouse models
Vinciguerra, M., Fulco, M., Ladurner, A. G., Sartorelli, V., & Rosenthal, N. A. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.004655 · Cited by 66 · see citing works
Direct regulation of lipolysis by interleukin-15 in primary pig adipocytes
Ajuwon, K. M., & Spurlock, M. E. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00192.2004 · Cited by 64 · see citing works
Harcourt, L. J., Holmes, A. G., Gregorevic, P., Schertzer, J. D., Stupka, N., Plant, D. R., & Lynch, G. S. (2005) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62333-4 · Cited by 63 · see citing works
Interleukin-15: a novel anabolic cytokine for skeletal muscle
Quinn, L. S. (1995) · Endocrinology · doi:10.1210/en.136.8.3669 · Cited by 56 · see citing works
Self-citationEffects of interleukin-15 on lipid oxidation
Almendro, V., Busquets, S., Ametller, E., Carbó, N., Figueras, M., Fuster, G., Argilés, J. M. A., & López-Soriano, F. J. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.12.006 · Cited by 55 · see citing works
Renzo, L. D., Bigioni, M., Bottini, F. G., Gobbo, V. D., Premrov, M. G., Cianci, R., & LORENZO, A. D. (2006) · PubMed · Cited by 54 · see citing works
Differential effects of GLUT-1 or GLUT-4 overexpression on insulin responsiveness in transgenic mice
Marshall, B. A., & Mueckler, M. M. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.267.5.e738 · Cited by 49 · see citing works
Pistilli, E. E., & Alway, S. E. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.05.188 · Cited by 42 · see citing works
Feige, J. N., Lagouge, M., Cantó, C., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.01.005 · Cited by 38 · see citing works
Role of fatty acids in the development of insulin resistance and type 2 diabetes mellitus
Wolf, G. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2008.00110.x · Cited by 34 · see citing works
Role of UCP2 and UCP3 in nutrition and obesity
Nagy, T. R., Blaylock, M. L., & Garvey, W. T. (2003) · Nutrition · doi:10.1016/j.nut.2003.09.024 · Cited by 34 · see citing works
Sir2 Regulates Skeletal Muscle Differentiation as a Potential Sensor of the Redox State
Fulco, M., Schiltz, R. L., Iezzi, S., King, M., Zhao, P., Kashiwaya, Y., Hoffman, E. P., Veech, R. L., & Sartorelli, V. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.10.032 · Cited by 33 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Leal, L. G., Lopes, M. A., & Batista, M. L. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01307 · Cited by 382 · see citing works
Myokines and Adipokines: Involvement in the Crosstalk between Skeletal Muscle and Adipose Tissue
Li, F., Li, Y., Duan, Y., Hu, C.-A. A., Tang, Y., & Yin, Y. (2017) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.10.003 · Cited by 288 · see citing works
Quinn, L. S., Anderson, B. G., Conner, J. D., & Wolden-Hanson, T. (2013) · Endocrinology · doi:10.1210/en.2012-1773 · Cited by 102 · see citing works
Sarcopenic obesity: Myokines as potential diagnostic biomarkers and therapeutic targets?
Guo, A., Li, K., & Xiao, Q. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.111022 · Cited by 83 · see citing works
Interleukin-15 as a myokine: Mechanistic insight into its effect on skeletal muscle metabolism
Nadeau, L., & Aguer, C. (2019) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2018-0022 · Cited by 83 · see citing works
Quinn, L. S., Anderson, B. G., Conner, J. D., Wolden-Hanson, T., & Marcell, T. J. (2014) · Endocrinology · doi:10.1210/en.2013-1645 · Cited by 40 · see citing works
Self-citation
- Authors
- Quinn, L., Anderson, Conner, Pistilli, & Wolden-Hanson
- Affiliations
- University of Washington (US)
- VA Puget Sound Health Care System (US)
- University of Pennsylvania (US)
- Venue
- International Journal of Interferon Cytokine and Mediator Research
- Publisher
- Informa UK Limited
- Published
- 2011-04
- Volume
- 3
- Pages
- 29
- ISSN
- 1179-139X (ISSN-L)
- PMC
- PMC5605924
- OpenAlex
- W2077817563
- Cited by
- 47
- References
- 60
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 1 · 2020: 9 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 1 · 2012: 3
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- International Journal of Interferon Cytokine and Mediator Research (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc)
- PubMed Central (acceptedVersion, cc-by-nc)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- University of Washington
- National Institutes of Health
- National Institute on Aging (R01AG024136, RO1AG024136, P01AG001751, P30AG013280)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK017047)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32AR053461)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- IL-15, diet-induced obesity, insulin sensitivity, skeletal muscle metabolism, oxidative metabolism, adiponectin, transgenic mice, soleus muscle, extensor digitorum longus, troponin I isoforms, fatty acid metabolism, SIRT1, SIRT4, UCP2, high-fat diet, intra-abdominal fat
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 ›
Are you an author, or do you see a problem with this page? Request a review
