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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In a murine model overexpressing IL-15, the percentage of visceral fat mass measured by DEXA was approximately half compared with controls.
“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]
The Results (page unavailable) report that DEXA-measured percentage body fat was lower in IL-15-secreting transgenic mice, and total fat mass was approximately 50% lower in males than in controls. They do not report that DEXA-measured visceral fat mass was halved; a separate Results passage says visceral fat cell area was approximately half that of controls in males. (LLM, conf=0.91)
Experimental — accuracy not yet measuredInterleukin-15 exerts local anabolic/anti-catabolic effects and increases glucose uptake, thus inhibiting lipid deposition.
“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]
The Abstract reports anti-atrophic effects in muscle, increased glucose uptake, and reduced fat deposition. It does not establish that increased glucose uptake causes the reduction in lipid deposition; the Discussion says the mechanism remains to be explored and suggests a possible direct effect on adipose tissue. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIL-15 overexpression is related to reduced adiposity.
“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
The Abstract reports reduced body fat in mice with elevated circulating IL-15, supporting the link to reduced adiposity. It also reports that IL-15 overexpression in muscle without increased secretion produced no difference in body composition; the citing sentence omits that important condition. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn transgenic animals overexpressing IL-15 in skeletal muscle, only the group with increased levels of IL-15 from muscle in circulation had a reduction in adiposity, due to greater targeting of substrate for energy generation.
“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
The Abstract and Discussion report that only the transgenic mouse line with elevated circulating muscle-derived IL-15 had reduced adiposity. They do not establish that the reduction was due to greater targeting of substrate for energy generation; the Discussion instead proposes a direct endocrine effect on adipose tissue. (LLM, conf=0.88)
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2 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
RetractedBulanova, E., Budagian, V., Duitman, E. H., Orinska, Z., Krause, H., Rückert, R., Reiling, N., & Bulfone‐Paus, S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610036200 · Cited by 63 · see citing works
RetractedAnalysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041 · see citing works
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199 · see citing works
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760 · 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
Regulation of skeletal muscle mass in mice by a new TGF-p superfamily member
McPherron, A. C., Lawler, A. M., & Lee, S.-J. (1997) · Nature · doi:10.1038/387083a0 · Cited by 4,013 · see citing works
Mechanisms linking obesity with cardiovascular disease
Van Gaal, L. F., Mertens, I. L., & De Block, C. E. (2006) · Nature · doi:10.1038/nature05487 · Cited by 2,814 · 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
Adipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170 · cited 1× · see citing works
“Conversely, serum levels of adiponectin, an insulinsensitizing adipokine that has direct effects on skeletal muscle, are lower in obese subjects than in lean animals and humans (17, 60, 68, 70).”
BackgroundDouble muscling in cattle due to mutations in the myostatin gene
McPherron, A. C., & Lee, S.-J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.23.12457 · Cited by 2,039 · see citing works
Reversible Defects in Natural Killer and Memory Cd8 T Cell Lineages in Interleukin 15–Deficient Mice
Kennedy, M. K., Glaccum, M. B., Brown, S. N., Butz, E. A., Viney, J. L., Embers, M. E., Matsuki, N., Charrier, K., Sedger, L. M., Willis, C. R., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.5.771 · Cited by 1,635 · 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
Advances in Male Contraception
Page, S. T., Amory, J. K., & Bremner, W. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0041 · Cited by 1,134 · see citing works
Mechanisms of Disease: is osteoporosis the obesity of bone?
Rosen, C. J., & Bouxsein, M. (2006) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0070 · Cited by 961 · see citing works
Induction of Cachexia in Mice by Systemically Administered Myostatin
Zimmers, T. A., Davies, M. V., Koniaris, L. G., Haynes, P. A., Esquela‐Kerscher, A., Tomkinson, K. N., McPherron, A. C., Wolfman, N. M., & Lee, S. (2002) · Science · doi:10.1126/science.1069525 · Cited by 908 · see citing works
Interleukin-6 Is an Essential Regulator of Satellite Cell-Mediated Skeletal Muscle Hypertrophy
Serrano, A. L., Baeza-Raja, B., Perdiguero, E., Jardí, M., & Muñoz-Cánoves, P. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.011 · Cited by 873 · cited 1× · see citing works
“However, IL-6 also has paracrine muscle hypertrophic actions via stimulation of satellite cell proliferation (62); paradoxically, systemic IL-6 also stimulates muscle atrophy and muscle protein degradation (21, 69).”
BackgroundRole of Myokines in Exercise and Metabolism
Pedersen, B. K., Åkerström, T. C. A., Nielsen, A. R., & Fischer, C. P. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00080.2007 · Cited by 841 · 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
Suppression of body fat accumulation in myostatin-deficient mice
McPherron, A. C., & Lee, S.-J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0213562 · Cited by 505 · see citing works
Direct effects of sex steroid hormones on adipose tissues and obesity
Mayes, J., & Watson, G. (2004) · Obesity Reviews · doi:10.1111/j.1467-789x.2004.00152.x · Cited by 502 · 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
Conditional Activation of Akt in Adult Skeletal Muscle Induces Rapid Hypertrophy
Lai, K.-M. V., Gonzalez, M., Poueymirou, W. T., Kline, W. O., Na, E., Zlotchenko, E., Stitt, T. N., Economides, A. N., Yancopoulos, G. D., & Glass, D. J. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.21.9295-9304.2004 · Cited by 442 · see citing works
Tagaya, Y., Bamford, R. N., DeFilippis, A. P., & Waldmann, T. A. (1996) · Immunity · doi:10.1016/s1074-7613(00)80246-0 · Cited by 440 · see citing works
Cesari, M., Kritchevsky, S. B., Baumgartner, R., Atkinson, H. H., Penninx, B. W. J. H., Lenchik, L., Palla, S. L., Ambrosius, W. T., Tracy, R. P., & Pahor, M. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn.82.2.428 · Cited by 422 · see citing works
Leptin, from fat to inflammation: old questions and new insights
Otero, M., Lago, R., Lago, F., Casanueva, F. F., Diéguez, C., Gómez-Reino, J. J., & Gualillo, O. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.11.024 · Cited by 407 · 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
Fehniger, T. A., Suzuki, K., Ponnappan, A., VanDeusen, J. B., Cooper, M. A., Florea, S. M., Freud, A. G., Robinson, M. L., Durbin, J. E., & Caligiuri, M. A. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.2.219 · Cited by 373 · see citing works
Cesari, M., Kritchevsky, S. B., Baumgartner, R., et al. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/82.2.428 · Cited by 345 · see citing works
Pischon, T., Nöthlings, U., & Boeing, H. (2008) · Proceedings of The Nutrition Society · doi:10.1017/s0029665108006976 · Cited by 320 · see citing works
Interleukin-6 Induces Skeletal Muscle Protein Breakdown in Rats
Goodman, M. N. (1994) · Experimental Biology and Medicine · doi:10.3181/00379727-205-43695 · Cited by 296 · see citing works
Nagy, T. R., & Clair, A. (2000) · Obesity Research · doi:10.1038/oby.2000.47 · Cited by 293 · see citing works
Interleukin-6 depletion selectively improves hepatic insulin action in obesity.
Klover, P. J., Clementi, A. H., & Mooney, R. A. (2005) · Endocrinology · doi:10.1210/en.2004-1468 · Cited by 273 · see citing works
Dyck, D. J., Heigenhauser, G. J. F., & Bruce, C. R. (2005) · Acta Physiologica · doi:10.1111/j.1748-1716.2005.01502.x · Cited by 272 · see citing works
Nielsen, A. R., Mounier, R., Plomgaard, P., Mortensen, O. H., Penkowa, M., Speerschneider, T., Pilegaard, H., & Pedersen, B. K. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.139618 · Cited by 266 · see citing works
Cauley, J. A., Danielson, M. E., Boudreau, R. M., Forrest, K. Y. Z., Zmuda, J. M., Pahor, M., Tylavsky, F. A., Cummings, S. R., Harris, T. B., & Newman, A. B. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070409 · Cited by 262 · see citing works
Evaluation 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
Riechman, S. E., Balasekaran, G., Roth, S. M., & Ferrell, R. E. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00491.2004 · Cited by 228 · see citing works
Physiological roles of muscle-derived interleukin-6 in response to exercise
Pedersen, B. K., & Fischer, C. P. (2007) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e3280ebb5b3 · Cited by 227 · 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
Crawford, G. E., Faulkner, J. A., Crosbie, R. H., Campbell, K. P., Froehner, S. C., & Chamberlain, J. S. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.150.6.1399 · Cited by 222 · see citing works
Phylogeny and evolution of class-I helical cytokines
Huising, M. O., Kruiswijk, C. P., & Flik, G. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06591 · Cited by 219 · see citing works
The role of interleukin‐6 in insulin resistance, body fat distribution and energy balance
Hoene, M., & Weigert, C. (2007) · Obesity Reviews · doi:10.1111/j.1467-789x.2007.00410.x · Cited by 218 · see citing works
Kelley, K. W., Weigent, D. A., & Kooijman, R. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.11.010 · Cited by 217 · see citing works
Tagaya, Y., Kurys, G., Thies, T. A., Losi, J. M., Azimi, N., Hanover, J. A., Bamford, R. N., & Waldmann, T. A. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14444 · Cited by 210 · see citing works
Gosset, M., Berenbaum, F., Salvat, C., Sautet, A., Pigenet, A., Tahiri, K., & Jacques, C. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23431 · 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
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
Carbó, 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
Quantitative analysis of the human alpha-skeletal actin gene in transgenic mice.
Brennan, K., & Hardeman, E. C. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54211-3 · Cited by 169 · see citing works
Bergamaschi, C., Rosati, M., Jalah, R., Valentin, A., Kulkarni, V., Alicea, C., Zhang, G., Patel, V. V., Felber, B. K., & Pavlakis, G. N. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705725200 · Cited by 169 · see citing works
Tsujinaka, T., Ebisui, C., Fujita, J., Kishibuchi, M., Morimoto, T., Ogawa, A., Katsume, A., Ohsugi, Y., Kominami, E., & Monden, M. (1995) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1006/bbrc.1995.1168 · Cited by 159 · see citing works
Sun, X., & Zemel, M. B. (2007) · Lipids · doi:10.1007/s11745-007-3029-5 · Cited by 126 · see citing works
Lebrun, C. E. I., van der Schouw, Y. T., de Jong, F. H., Grobbee, D. E., & Lamberts, S. W. J. (2006) · Menopause The Journal of The North American Menopause Society · doi:10.1097/01.gme.0000222331.23478.ec · Cited by 112 · see citing works
Expression of drug resistance proteins in breast cancer, in relation to chemotherapy
Linn, S. C., Pinedo, H. M., van Ark-Otte, J., van der Valk, P., Hoekman, K., Honkoop, A. H., Vermorken, J. B., & Giaccone, G. (1997) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19970529)71:5 · Cited by 112 · 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
Figueras, 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
Radioimmunoassay of rat leptin: sexual dimorphism reversed from humans
Landt, M., Gingerich, R. L., Havel, P. J., Mueller, W. M., Schoner, B. E., Hale, J. E., & Heiman, M. L. (1998) · Clinical Chemistry · doi:10.1093/clinchem/44.3.565 · Cited by 96 · see citing works
Skeletal muscle cytokines: regulation by pathogen-associated molecules and catabolic hormones
Frost, R. A., & Lang, C. H. (2005) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/01.mco.0000165003.16578.2d · Cited by 93 · 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
Interleukin-15: A muscle-derived cytokine regulating fat-to-lean body composition1,2
Quinn, L. S. (2008) · Journal of Animal Science · doi:10.2527/jas.2007-0458 · Cited by 91 · see citing works
The roles of interleukin-15 receptor α: Trans-presentation, receptor component, or both?
Schluns, K. S., Stoklasek, T. A., & Lefrançois, L. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.02.017 · Cited by 85 · see citing works
Interleukin-15 decreases proteolysis in skeletal muscle: A direct effect
Busquets, S., Figueras, M., Meijsing, S. H., Carbó, N., Quinn, L. S., Almendro, V., Argilés, J. M. A., & López-Soriano, F. J. (2005) · International Journal of Molecular Medicine · doi:10.3892/ijmm.16.3.471 · Cited by 85 · see citing works
Increased IL-15 production of muscle cells in polymyositis and dermatomyositis
Sugiura, T. (2002) · International Immunology · doi:10.1093/intimm/dxf062 · Cited by 73 · 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
Nishimura, H., Fujimoto, A., Tamura, N., Yajima, T., Wajjwalku, W., & Yoshikai, Y. (2005) · The FASEB Journal · doi:10.1096/fj.04-2633com · Cited by 65 · 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
Effects 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
Jacobi, S. K., Gabler, N. K., Ajuwon, K. M., Davis, J. E., & Spurlock, M. E. (2006) · Journal of Animal Science · doi:10.2527/2006.8413_supple140x · 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
Interleukin-15 and interleukin-2 enhance non-REM sleep in rabbits
Kubota, T., Brown, R. A., Fang, J., & Krueger, J. M. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.281.3.r1004 · Cited by 51 · see citing works
Mauban, J. R. H., & Wier, W. G. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01084.2003 · Cited by 46 · see citing works
Yang, J., & Zhao, B. (2006) · Molecular Reproduction and Development · doi:10.1002/mrd.20452 · Cited by 38 · see citing works
Cundy, C., & Weekes, C. E. (2008) · Proceedings of The Nutrition Society · doi:10.1017/s002966510800760x · Cited by 23 · see citing works
Alternative splicing of mouse IL-15 is due to the use of an internal splice site in exon 5
Prinz, M., Hanisch, U., Kettenmann, H., & Kirchhoff, F. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00284-8 · Cited by 16 · see citing works
Lambert, C. P., Flynn, M. G., Sullivan, D. H., & Evans, W. J. (2004) · The Journals of Gerontology Series A · doi:10.1093/gerona/59.8.m855 · Cited by 15 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [22]Gosset M, Berenbaum F, Salat C, Sautet A, Pigenet A, Tahiri K, Jacques C. Crucial role of visfatin/pre-B cell colony-enhancing factor in matrix degradation and prostaglandin E2 synthesis in chrondrocytes. Arthr Rheum 58: 1399–1409, 2008. [DOI] [PubMed] [Google Scholar]
- [40]Lollini PL, Palmieri G, De Giovanni C, Landuzzi L, Nicoletti G, Rossi I, Griffoni C, Frabetti F, Scotland K, Benini S, Baldini N, Santoni A, Nanni P. Expression of interleukin 15 (IL-15) in human rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma. Intl J Cancer 71: 732–736, 1997. [DOI] [PubMed] [Google Scholar]
Cited by
Sorted by citations
Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training
Roberts, C. K., Hevener, A. L., & Barnard, R. J. (2012) · Comprehensive physiology · doi:10.1002/cphy.c110062 · Cited by 919 · see citing works
“Muscle-derived factors including IL-6 (100, 101, 492, 493) IL-15 (514), BNDF (365, 424, 520), FGF21 (29, 64, 132, 164, 311, 349), and Follistatin-like 1 (482, 484), and SPARC (466) are a few putative myokines currently under investigation.”
Moreno-Navarrete, J. M., Ortega, F., Serrano, M., Guerra, E., Pardo, G., Tinahones, F., Ricart, W., & Fernández-Real, J. M. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2749 · Cited by 788 · see citing works
“IL-15 leads to reduced adipogenesis and increased fatty acid mobilization from adipose tissue depots (8, 9).”
BackgroundExercise is the real polypill.
Fiuza-Luces, C., Garatachea, N., Berger, N. A., & Lucia, A. (2013) · Physiology · doi:10.1152/physiol.00019.2013 · Cited by 791 · see citing works
Pedersen, B. K. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.048074 · Cited by 668 · see citing works
“THE JOURNAL OF EXPERIMENTAL BIOLOGY 342 increased bone mineral content, without appreciably affecting lean body mass or levels of other cytokines (Quinn et al., 2009).”
BackgroundSkeletal muscle: A review of molecular structure and function, in health and disease
Mukund, K., & Subramaniam, S. (2019) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1462 · Cited by 680 · 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
“Quinn et al. (2009) found that 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.”
BackgroundRole of Inflammation in Muscle Homeostasis and Myogenesis
Costamagna, D., Costelli, P., Sampaolesi, M., & Penna, F. (2015) · Mediators of Inflammation · doi:10.1155/2015/805172 · Cited by 390 · see citing works
Pedersen, B. K. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120033 · Cited by 516 · see citing works
Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake
Merz, K. E., & Thurmond, D. C. (2020) · Comprehensive Physiology · doi:10.1002/cphy.c190029 · Cited by 494 · see citing works
The Role of Exercise-Induced Myokines in Muscle Homeostasis and the Defense against Chronic Diseases
Brandt, C., & Pedersen, B. K. (2010) · BioMed Research International · doi:10.1155/2010/520258 · Cited by 426 · see citing works
“found that 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 [37].”
BackgroundMyonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis
Seldin, M. M., Peterson, J. M., Byerly, M. S., Wei, Z., & Wong, G. W. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.336834 · Cited by 406 · see citing works
“reduce fat mass and decrease adiposity in response to high-fat feeding (13).”
BackgroundMuscle and bone, two interconnected tissues
Tagliaferri, C., Wittrant, Y., Davicco, M.-J., Walrand, S., & Coxam, V. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.03.002 · Cited by 394 · see citing works
Skeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations
Hoffmann, C., & Weigert, C. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029793 · Cited by 393 · see citing works
“Conversely, transgenic mice with skeletal muscle overexpression of IL-15 also have a high endurance capacity (Quinn et al. 2013).”
InfluentialLeal, L. G., Lopes, M. A., & Batista, M. L. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01307 · Cited by 382 · see citing works
Exercise-induced myokines and their role in chronic diseases
Pedersen, B. K. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.02.010 · Cited by 358 · see citing works
“affecting lean body mass or levels of other cytokines (Quinn et al., 2009).”
Bone and muscle: Interactions beyond mechanical
Brotto, M. A. P., & Bonewald, L. F. (2015) · Bone · doi:10.1016/j.bone.2015.02.010 · Cited by 347 · see citing works
“Mice with elevated circulating levels of IL-15 show increased bone mineral content(13).”
BackgroundLutz, C. T., & Quinn, L. S. (2012) · Aging · doi:10.18632/aging.100482 · Cited by 338 · see citing works
“Consistent with these findings, high IL-15 levels caused lean body type, decreased white adipose tissue, and increased adipose tissue NK cell number [102, 112, 117].”
ResultMuscle as a paracrine and endocrine organ
Giudice, J., & Taylor, J. M. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.05.005 · Cited by 331 · see citing works
“Notably, transgenic mice that ectopically express IL15 under the control of a skeletal muscle-specific promoter exhibit significantly elevated circulating IL15 accompanied by reduced body fat and increased bone mineral content (see below for further discussion) [23].”
Inter-tissue communication in cancer cachexia
Argilés, J. M. A., Stemmler, B., López-Soriano, F. J., & Busquets, S. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0123-0 · Cited by 305 · 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
Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake
Merz, K. E., & Thurmond, D. C. (2020) · Comprehensive physiology · doi:10.1002/j.2040-4603.2020.tb00136.x · Cited by 283 · see citing works
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278 · see citing works
“The global effect of IL-15 on fat mass appears to be significant, 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].”
BackgroundChristiansen, T., Paulsen, S. K., Bruun, J. M., Pedersen, S. B., & Richelsen, B. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00574.2009 · Cited by 255 · see citing works
“IL-15 has been found to be highly expressed in muscle tissue, and it is suggested to have regulatory effects on the amount of body fat, maybe particularly through a reduction of the trunk fat mass that has been found at least in mice overexpressing IL-15 in skeletal muscle (44).”
BackgroundBilski, J., Pierzchalski, P., Szczepanik, M., Bonior, J., & Zoladz, J. A. (2022) · Cells · doi:10.3390/cells11010160 · Cited by 262 · see citing works
Pathophysiology and mechanisms of primary sarcopenia (Review)
Nishikawa, H., Fukunishi, S., Asai, A., Yokohama, K., Nishiguchi, S., & Higuchi, K. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.4989 · Cited by 235 · see citing works
“IL‐15 is a cytokine that is abundantly expressed in skeletal muscle and is recognized as a myokine that acts endocrinologically on adipose tissue and regulates whole body energy metabolism (73).”
BackgroundMyokines in insulin resistance and type 2 diabetes
Eckardt, K., Görgens, S. W., Raschke, S., & Eckel, J. (2014) · Diabetologia · doi:10.1007/s00125-014-3224-x · Cited by 221 · see citing works
“Overexpression of IL-15 in skeletal muscle resulted in reduced body fat, suggesting a potential role in the regulation of fat mass [6, 45].”
BackgroundEdward F. Adolph Distinguished Lecture: Muscle as an endocrine organ: IL-6 and other myokines
Pedersen, B. K. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00734.2009 · Cited by 214 · see citing works
“(96) found that elevated circulating levels of IL-15 in mice resulted in significant reductions in body fat and increased bone mineral content, without appreciably affecting lean body mass or levels of other cytokines.”
BackgroundMetabolic adaptation in obesity and type ii diabetes: myokines, adipokines and hepatokines
Oh, K.-J., Lee, D., Kim, W., Han, B., Lee, S., & Bae, K.-H. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms18010008 · Cited by 210 · see citing works
Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training
Roberts, C. K., Hevener, A. L., & Barnard, R. J. (2013) · Comprehensive physiology · doi:10.1002/j.2040-4603.2013.tb00484.x · Cited by 184 · see citing works
Crane, J. D., MacNeil, L. G., Lally, J. S., Ford, R. J., Bujak, A. L., Brar, I. K., Kemp, B. E., Raha, S., Steinberg, G. R., & Tarnopolsky, M. A. (2015) · Aging Cell · doi:10.1111/acel.12341 · Cited by 179 · see citing works
Muscle–bone interactions: basic and clinical aspects
Cianferotti, L., & Brandi, M. L. (2013) · Endocrine · doi:10.1007/s12020-013-0026-8 · Cited by 168 · see citing works
Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis
Li, G., Zhang, L., Wang, D., AIQudsy, L., Jiang, J. X., Xu, H., & Shang, P. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28946 · Cited by 166 · see citing works
Cellular models for understanding adipogenesis, adipose dysfunction, and obesity
Armani, A., Mammi, C., Marzolla, V., Calanchini, M., Antelmi, A., Rosano, G. M. C., Fabbri, A., & Caprio, M. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22598 · Cited by 166 · see citing works
“Interestingly, it is known that skeletal muscle can influence adipose tissue formation by secretion/expression of interleukin-15 (IL-15) [Quinn et al., 2009], whose expression is abundant in muscle.”
BackgroundInfluentialKaji, H. (2016) · BoneKEy Reports · doi:10.1038/bonekey.2016.48 · Cited by 162 · see citing works
Myokines mediate the cross talk between skeletal muscle and other organs
Chen, W., Wang, L., You, W., & Shan, T. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30033 · Cited by 162 · see citing works
“Fat mass is closely correlated with circulating IL‐15 expression in humans (Carbo et al., 2001; Nielsen et al., 2008; Quinn et al., 2009, 2005), which implies that IL‐15 may be involved in the regulation of lipid deposition.”
BackgroundMuscle-bone interactions: From experimental models to the clinic? A critical update
Laurent, M. R., Dubois, V., Claessens, F., Verschueren, S., Vanderschueren, D., Gielen, E., & Jardí, F. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.10.017 · Cited by 152 · see citing works
“IL-15 overexpression in muscle reduced body fat and increased bone mass in transgenic mice, although only when systemic IL-15 levels were increased as well (Quinn et al., 2009).”
BackgroundExercise therapy for people with sarcopenic obesity: myokines and adipokines as effective actors
Alizadeh Pahlavani, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.811751 · Cited by 145 · see citing works
“Elevated plasma IL-15 is involved in stimulating the expression of mitochondrial-related factors, such as PPARs and SIRT1, and with increasing circulating IL-15, endurance capacity increases (37, 38).”
BackgroundThe skeletal muscle secretome: an emerging player in muscle–bone crosstalk
Hamrick, M. W. (2012) · BoneKEy Reports · doi:10.1038/bonekey.2012.60 · Cited by 145 · see citing works
Tamura, Y., Watanabe, K., Kantani, T., Hayashi, J., Ishida, N., & Kaneki, M. (2011) · Endocrine Journal · doi:10.1507/endocrj.k10e-400 · Cited by 137 · see citing works
“Recently, the functional role of IL-15 in the regulation of fat mass and energy expenditure has been highlighted [6-9].”
BackgroundRole of interleukins in obesity: implications for metabolic disease
Febbraio, M. A. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.02.004 · Cited by 130 · see citing works
The Role of Physical Exercise in Inflammatory Bowel Disease
Bilski, J., Brzozowski, B., Mazur-Biały, A. I., Śliwowski, Z., & Brzozowski, T. (2014) · BioMed Research International · doi:10.1155/2014/429031 · Cited by 133 · see citing works
Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives
Das, D. K., Graham, Z. A., & Cardozo, C. P. (2020) · Acta Physiologica · doi:10.1111/apha.13367 · Cited by 129 · see citing works
Systemic Nutrient and Stress Signaling via Myokines and Myometabolites
Rai, M., & Demontis, F. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105305 · Cited by 123 · see citing works
Exercise-induced myokines and their effect on prostate cancer
Kim, J., Galvao, D. A., Newton, R. U., Gray, E. S., & Taaffe, D. R. (2021) · Nature Reviews Urology · doi:10.1038/s41585-021-00476-y · Cited by 126 · see citing works
Maurel, D. B., Jähn, K., & Lara-Castillo, N. (2017) · Biomedicines · doi:10.3390/biomedicines5040062 · Cited by 122 · see citing works
“Such “uncoupling” of muscle and bone is also found in transgenic mice overexpressing interleukin-15 (IL15) in the skeletal muscle [10].”
BackgroundInfluentialBeta-Aminoisobutyric Acid as a Novel Regulator of Carbohydrate and Lipid Metabolism
Tanianskii, D. A., Jarzebska, N., Birkenfeld, A. L., O’Sullivan, J. F., & Rodionov, R. N. (2019) · Nutrients · doi:10.3390/nu11030524 · Cited by 121 · see citing works
“Elevation of IL-15 leads to a decline of fat mass in mice [20], and recently discovered myokine irisin induces “browning” of white adipose tissue (the differentiation of resident progenitor cells in white adipose tissue into morphologically and physiologically distinct brown-like adipocytes) and results in increased e…”
BackgroundEngineered skeletal muscles for disease modeling and drug discovery
Wang, J., Khodabukus, A., Rao, L., VanDusen, K. W., Abutaleb, N. O., & Bursac, N. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119416 · Cited by 117 · see citing works
Endocrine Crosstalk Between Muscle and Bone
Brotto, M. A. P., & Johnson, M. L. (2014) · Current Osteoporosis Reports · doi:10.1007/s11914-014-0209-0 · Cited by 118 · see citing works
Characterization and Regulation of Mechanical Loading‐Induced Compensatory Muscle Hypertrophy
Adams, G. R., & Bamman, M. M. (2012) · Comprehensive physiology · doi:10.1002/cphy.c110066 · Cited by 114 · see citing works
Aging and the Muscle-Bone Relationship
Novotny, S. A., Warren, G. L., & Hamrick, M. W. (2015) · Physiology · doi:10.1152/physiol.00033.2014 · Cited by 103 · see citing works
“The effect of myokines on bone may be systemic as well as local, since elevated secretion of muscle-derived IL-15 not only decreases body fat but also increases whole-body bone mineral content (59).”
BackgroundQuinn, 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
Endurance training enhances skeletal muscle interleukin-15 in human male subjects
Rinnov, A., Yfanti, C., Nielsen, S., Åkerström, T. C. A., Peijs, L., Zankari, A., Fischer, C. P., & Pedersen, B. K. (2014) · Endocrine · doi:10.1007/s12020-013-9969-z · Cited by 103 · see citing works
IL-15 activates the Jak3/STAT3 signaling pathway to mediate glucose uptake in skeletal muscle cells
Krolopp, J. E., Thornton, S. M., & Abbott, M. J. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00626 · Cited by 104 · see citing works
“Many cytokines secreted from skeletal muscle, termed “myokines,” have been identified and muscle contraction appears to be a major stimulator of their release (Pedersen, 2013; Raschke and Eckel, 2013; Catoire et al., 2014; Eckardt et al., 2014).”
BackgroundHow does the skeletal muscle communicate with the brain in health and disease?
Isaac, A. R., Lima‐Filho, R. A. S., & Lourenco, M. V. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108744 · Cited by 94 · see citing works
The Role of Exercise, Diet, and Cytokines in Preventing Obesity and Improving Adipose Tissue
ATAKAN, M. M., Koşar, Ş. N., Güzel, Y., Tin, H. T., & Yan, X. (2021) · Nutrients · doi:10.3390/nu13051459 · Cited by 94 · see citing works
“Conversely, mice with the IL15 gene deleted in cultured adipocytes showed higher amounts of BF than control mice [292], whereas transgenic mice with elevated circulating levels of IL-15 had lower levels of BF and were resistant to diet-induced obesity [286].”
BackgroundMicroRNA-Regulated Proinflammatory Cytokines in Sarcopenia
Fan, J., Kou, X., Yang, Y., & Chen, N. (2016) · Mediators of Inflammation · doi:10.1155/2016/1438686 · Cited by 86 · see citing works
“Moreover, IL-15 [61] is usually mentioned among paracrine effectors, while cytokines such as irisin [62] and myonectin [63] are able to induce anti-inflammatory cytokines (IL-1 receptor antagonist and IL-10), especially during contraction and aging conditions [64].”
BackgroundShi, H., Munk, A., Nielsen, T. S., Daughtry, M. R., Larsson, L., Li, S., Høyer, K. F., Geisler, H. W., Sulek, K., Kjøbsted, R., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.02.010 · Cited by 85 · see citing works
“These findings supported our thesis, as those mice over-expressing IL-15 are also protected from this type of induced obesity [62].”
BackgroundResultMuscle-derived follistatin-like 1 functions to reduce neointimal formation after vascular injury
Miyabe, M., Ohashi, K., Shibata, R., Uemura, Y., Ogura, Y., Yuasa, D., Kambara, T., Kataoka, Y., Yamamoto, T., Matsuo, K., et al. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu105 · Cited by 86 · see citing works
Myokines, physical activity, insulin resistance and autoimmune diseases
Díaz, B. B., González, D. A., Gannar, F., Pérez, M. C. R., & de León, A. C. (2018) · Immunology Letters · doi:10.1016/j.imlet.2018.09.002 · Cited by 82 · see citing works
Carson, B. P. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00097 · Cited by 83 · see citing works
“Overexpression and oversecretion of IL-15 in a transgenic mouse model resulted in decreased total body and visceral fat (66).”
BackgroundMolecular insights of exercise therapy in disease prevention and treatment
Walzik, D., Chirino, T. Y. W., Zimmer, P., & Joisten, N. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01841-0 · Cited by 89 · see citing works
“163 In humans, plasma IL-15 levels were negatively associated with fat mass, 164 however, a mechanistic connection between exercise, IL-15 secretion, and reduction of fat mass is still lacking.”
BackgroundPistilli, E. E., Bogdanovich, S., Garton, F. C., Yang, N., Gulbin, J. P., Conner, J. D., Anderson, B. G., Quinn, L. S., North, K. N., Ahima, R. S., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44945 · Cited by 83 · see citing works
“HSA-IL-15TG mice overexpress IL-15 from a skeletal muscle–specific promoter, as previously described (34).”
InfluentialInterleukin-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
Myonectin deletion promotes adipose fat storage and reduces liver steatosis
Little, H. C., Rodriguez, S., Lei, X., Tan, S. Y., Stewart, A. N., Sahagun, A., Sarver, D. C., & William Wong, G. (2019) · The FASEB Journal · doi:10.1096/fj.201900520r · Cited by 78 · see citing works
“Of the hundreds of proteins secreted by skeletal muscle (7–9), only a few have been functionally characterized, includingmyostatin (10–12), IL-6 (13), fibroblast growth factor 21 (14, 15), insulin-like 6 (16), follistatinlike 1 (17), leukemia inhibitory factor (18), IL-7 (19), IL-15 (20), musclin (21, 22), and irisin…”
BackgroundEffect of Various Exercise Regimens on Selected Exercise-Induced Cytokines in Healthy People
Domin, R., Dadej, D., Pytka, M., Zybek-Kocik, A., Ruchała, M., & Guzik, P. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18031261 · Cited by 79 · see citing works
“Interleukin 15 Immune cell proliferation, differentiation and maturation [58,59] Immune response regulation [60] Muscle protein synthesis [61] Adipose tissue reduction [62,63].”
BackgroundCell Types Used for Cultured Meat Production and the Importance of Myokines
Shaikh, S., Lee, E. J., Ahmad, K., Ahmad, S. S., Chun, H.-J., Lim, J. H., Lee, Y., & Choi, I. (2021) · Foods · doi:10.3390/foods10102318 · Cited by 77 · see citing works
“In cultured skeletal myotubes, IL-15 stimulated protein synthesis while inhibiting protein degradation [55,56], while IL-15 secreted by myotubes, derived from human SM, promoted human myotube development by increasing the expression levels of myogenic marker genes [57].”
BackgroundInfluentialBone and muscle crosstalk in ageing and disease
Kirk, B., Lombardi, G., & Duque, G. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01088-x · Cited by 81 · see citing works
“Both factors are believed to strongly stimulate oste-oclastogenesis and bone resorption, primarily via RANκL stimulation, but conflicting evidence has emerged for the role of IL-15, such as the correlation between its circulating level, adipose tissue mass (negatively) and BMC (positively) 106 .”
Quinn, L. S., & Anderson, B. G. (2011) · Journal of Obesity · doi:10.1155/2011/456347 · Cited by 73 · see citing works
“Conversely, transgenic mice which were engineered for elevated circulating levels of IL-15 (IL-15 Tg mice), expressed from a skeletal muscle-specific promoter, exhibited lower levels of body fat than closely related controls, and were resistant to diet-induced obesity [42].”
BackgroundInfluentialYe, J. (2015) · Frontiers of Medicine · doi:10.1007/s11684-015-0377-z · Cited by 66 · see citing works
“In 2009, it was reported that elevation of plasma IL-15 by overexpression of IL-15 in muscle led to a lean phenotype in transgenic mice [38].”
Regulation of tissue crosstalk by skeletal muscle-derived myonectin and other myokines
Seldin, M. M., & Wong, G. W. (2012) · Adipocyte · doi:10.4161/adip.20877 · Cited by 70 · see citing works
The role of pro-inflammatory cytokines in lipid metabolism of metabolic diseases
Chen, Y., Yu, C., & Deng, W. (2019) · International Reviews of Immunology · doi:10.1080/08830185.2019.1645138 · Cited by 68 · see citing works
“In normal and obese rodents, IL-15 reduces fat deposition by inhibiting lipogenesis in liver and adipose tissue [136], while in vitro, IL-15 can directly inhibit preadipocyte differentiation and lipogenesis, thus stimulating lipolysis [133, 137, 138].”
BackgroundQuinn, L. S., Anderson, B. G., Strait‐Bodey, L., & Wolden‐Hanson, T. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.10.012 · Cited by 68 · see citing works
“…experiments (not shown), this assay was compared to a similar LINCOplex bead-based immunoassay performed in the same instrument and utilized previously in publications from this laboratory describing serum and muscle IL-15 concentrations in IL-15 overexpressing transgenic mice (Quinn et al., 2009).”
BackgroundMethodResultInfluentialFactors mediating exercise‐induced organ crosstalk
Sabaratnam, R., Wojtaszewski, J. F. P., & Højlund, K. (2022) · Acta Physiologica · doi:10.1111/apha.13766 · Cited by 69 · see citing works
Altered Myokine Secretion Is an Intrinsic Property of Skeletal Muscle in Type 2 Diabetes
Ciaraldi, T. P., Ryan, A. J., Mudaliar, S. R., & Henry, R. R. (2016) · PLOS ONE · doi:10.1371/journal.pone.0158209 · Cited by 66 · see citing works
“impaired fatty acid oxidation, would seem to be in conflict with studies in transgenic mice, where muscle-specific overexpression of IL15 [59] and CXCL1 [60] (the rodent homologue of GROa) each resulted in improved fat metabolism.”
BackgroundType I IFN Substitutes for T Cell Help during Viral Infections
Wiesel, M., Kratky, W., & Oxenius, A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1003166 · Cited by 65 · see citing works
“The following mouse strains were kept and bred in a specific pathogen-free (SPF) facility at the Institute of Microbiology: C57BL/6 (wild type [WT]), CD4 (17), IL-15 (18), CD8 (19), and IL-2 (20).”
MethodBoa, B. C. S., Yudkin, J. S., van Hinsbergh, V. W. M., Bouskela, E., & Eringa, E. C. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13732 · Cited by 64 · see citing works
“Although IL-15 is considered a pro-inflammatory cytokine, the fact that its circulating levels are negatively related to obesity, WAT mass and type 2 diabetes is also consistent with a role as a myokine (Quinn et al., 2009).”
BackgroundTherapeutic potential of interleukin-15: a myokine involved in muscle wasting and adiposity
Argilés, J. M. A., López-Soriano, F. J., & Busquets, S. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.10.010 · Cited by 64 · see citing works
“Rheumatology 47, 1269–1277 10 Quinn, L.S. et al. (1995) Interleukin-15: a novel anabolic cytokine for skeletal muscle.”
BackgroundInfluentialInterplay of adipokines and myokines in cancer pathophysiology: Emerging therapeutic implications
Dalamaga, Μ. (2013) · World Journal of Experimental Medicine · doi:10.5493/wjem.v3.i3.26 · Cited by 64 · see citing works
Chang, K. C., Wu, W., Chen, Y., Chen, L.-R., Hsu, W., Lin, Y., & Han, D. (2023) · Aging · doi:10.18632/aging.205254 · Cited by 65 · see citing works
Pierce, J. R., Maples, J. M., & Hickner, R. C. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00575.2014 · Cited by 60 · see citing works
Nadeau, L., Patten, D. A., Caron, A., Garneau, L., Pinault-Masson, É., Foretz, M., Haddad, P., Anderson, B. G., Quinn, L. S., Jardine, K. E., et al. (2018) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2018.10.021 · Cited by 60 · see citing works
“In order to determine whether the muscle of mice that are chronically exposed to very high levels of IL-15 show similar alterations, we measured ETC supercomplex formation and PAMPK and P-ACC levels in muscle samples from IL-15 Tg mice [31].”
BackgroundMethodInfluentialMyokines as possible therapeutic targets in cancer cachexia
Manole, E., Ceafalan, L. C., Popescu, B. O., Dumitru, C., & Bastian, A. E. (2018) · Journal of Immunology Research · doi:10.1155/2018/8260742 · Cited by 60 · see citing works
Pedersen, B. K. (2013) · Comprehensive physiology · doi:10.1002/j.2040-4603.2013.tb00522.x · Cited by 59 · see citing works
The 2009 Stock Conference Report: Inflammation, Obesity and Metabolic Disease
Hevener, A. L., Febbraio, M. A., & the Stock Conference Working Group (2009) · Obesity Reviews · doi:10.1111/j.1467-789x.2009.00691.x · Cited by 59 · see citing works
“What is the role of IL-6, IL-15, IL-10, IL-1 antagonist, and IL-4 in regulating whole body metabolism?”
BackgroundInfluentialBiomarkers in the field of obesity and its related comorbidities
Katsareli, E. A., & Dedoussis, G. V. (2014) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.882321 · Cited by 59 · see citing works
“8 Interleukin-15 While best known as a key regulator of immune natural killer cell function and development [196,197], it is reported that reduced expression of the IL-15 cytokine is closely linked with increased body weight and adiposity in both mice and humans [198-200].”
BackgroundBilski, J., Mazur-Biały, A. I., Wierdak, M., & Brzozowski, T. (2013) · PubMed · Cited by 55 · see citing works
Yang, H., Chang, J.-R., Chen, W.-J., Zhao, L., Qu, B., Tang, C., Qi, Y., & Zhang, J. (2012) · Endocrine · doi:10.1007/s12020-012-9809-6 · Cited by 56 · see citing works
Bohlen, J. F., McLaughlin, S. L., Hazard-Jenkins, H. W., Infante, A. M., Montgomery, C., Davis, M. C., & Pistilli, E. E. (2018) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12294 · Cited by 55 · see citing works
“skeletal muscle, which results in greater circulating levels of this cytokine.(30) Female IL15TG (n = 19) and B6 littermate”
BackgroundThe Importance of Biophysical and Biochemical Stimuli in Dynamic Skeletal Muscle Models
Maleiner, B., Tomasch, J., Heher, P., Oliver Spadiut, A., Rünzler, D., & Fuchs, C. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01130 · Cited by 56 · see citing works
“IL-15 as well as IL-15 receptor alpha are involved in anabolic/catabolic regulation of skeletal muscle tissue (Quinn et al., 1995; Quinn, 2002; Furmanczyk and Quinn, 2003; Riechman et al., 2004; Busquets et al., 2005; Pistilli et al., Frontiers in Physiology | www.frontiersin.org 11 August 2018 | Volume 9 | Article 11…”
BackgroundInfluentialBiomarkers for Cancer Cachexia: A Mini Review
Cao, Z., Zhao, K., Jose, I., Hoogenraad, N. J., & Osellame, L. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094501 · Cited by 55 · see citing works
“Brown adipose tissue was shown to induce muscle atrophy via secretion of myostatin [87], while muscle-derived IL-15 was able to modulate adipose tissue deposition [88].”
BackgroundMyokine-mediated muscle-organ interactions: Molecular mechanisms and clinical significance
Yi, J., Chen, J., Yao, X., Zhao, Z., Niu, X., Li, X., Sun, J., Ji, Y., Shang, T., Gong, L., et al. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117326 · Cited by 59 · see citing works
Ryu, J. Y., Choi, H. M., Yang, H.-I., & Kim, K. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186887 · Cited by 51 · see citing works
A new look at an old drug for the treatment of cancer cachexia: Megestrol acetate
Argilés, J. M. A., Anguera, A., & Stemmler, B. (2013) · Clinical Nutrition · doi:10.1016/j.clnu.2013.01.004 · Cited by 49 · see citing works
Mou, K., Chan, S. M. H., & Vlahos, R. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108635 · Cited by 50 · see citing works
Granados, N., Amengual, J., Ribot, J., Palou, A., & Bonet, M. L. (2011) · British Journal Of Nutrition · doi:10.1017/s0007114510004885 · Cited by 49 · see citing works
“In addition to antidiabetogenic effects, anti-adiposity effects have been proposed for muscle-derived IL-15 acting on multiple target tissues including adipose tissue((38,39)).”
BackgroundCancer cachexia: molecular basis and therapeutic advances
Tan, Y., Xue, R., Pan, Y., he, Z., Hu, X., Li, Y., Li, K., Zhang, X., Bian, X.-W., & Wang, B. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02331-7 · Cited by 48 · see citing works
Interleukin‐15 in obesity and metabolic dysfunction: current understanding and future perspectives
Duan, Y., Li, F., Wang, W., Guo, Q., Wen, C., Li, Y., & Yin, Y. (2017) · Obesity Reviews · doi:10.1111/obr.12567 · Cited by 47 · see citing works
“In addition, experiments using animal and cell models indicate that IL-15 is secreted from skeletal muscle and plays roles in adipose tissue lipolysis through a skeletal muscle–blood–adipose tissue endocrine axis (17,22,46).”
BackgroundQuinn, L., Anderson, Conner, Pistilli, & Wolden-Hanson (2011) · International Journal of Interferon Cytokine and Mediator Research · doi:10.2147/ijicmr.s19007 · Cited by 47 · 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.”
InfluentialEvidence for acute contraction-induced myokine secretion by C2C12 myotubes
Furuichi, Y., Manabe, Y., Takagi, M., Aoki, M., & FUJII, N. L. (2018) · PLoS ONE · doi:10.1371/journal.pone.0206146 · Cited by 46 · see citing works
Matthews, I., Birnbaum, A., Gromova, A., Huang, A., Liu, K.-L., Liu, E. A., Coutinho, K., McGraw, M., Patterson, D., Banks, M. T., et al. (2023) · bioRxiv · doi:10.1016/j.celrep.2023.113436 · Cited by 34 · see citing works
- 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 › 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, 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
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