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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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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
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
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
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
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199
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
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
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
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
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
Research works printed but not linked: 1
- 10.1016/j.cyto.2008.04.008.PMID18514540.2008 · DOI
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 966
“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
“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
Pedersen, B. K. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.048074 · Cited by 668
“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 805
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
“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 554
Pedersen, B. K. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120033 · Cited by 516
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
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 443
“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
“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 406
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
“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
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 370
“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 360
“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 339
“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
“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 317
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
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278
“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
“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 271
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 256
“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 234
“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 221
“(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
Exercise‐stimulated interleukin‐15 is controlled by AMPK and regulates skin metabolism and aging
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
Muscle–bone interactions: basic and clinical aspects
Cianferotti, L., & Brandi, M. L. (2013) · Endocrine · doi:10.1007/s12020-013-0026-8 · Cited by 170
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
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
“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 161
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
“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 156
“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
“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
Tamura, Y., Watanabe, K., Kantani, T., Hayashi, J., Ishida, N., & Kaneki, M. (2011) · Endocrine Journal · doi:10.1507/endocrj.k10e-400 · Cited by 137
“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 134
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 142
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
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 131
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
Maurel, D. B., Jähn, K., & Lara-Castillo, N. (2017) · Biomedicines · doi:10.3390/biomedicines5040062 · Cited by 127
“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
“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 125
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 120
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 123
“IL-15 in muscle tissue in vivo had a number of biological impacts but did not result in muscle hypertrophy (385).”
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 110
“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
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
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
“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 99
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 96
“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 98
“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 87
“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 87
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
Carson, B. P. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00097 · Cited by 86
“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 95
“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 86
“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
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
“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
“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 81
“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 89
“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
“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
“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 69
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 71
“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
“…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 70
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
“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 69
“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 65
“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
“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 66
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
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
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 62
“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
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 60
“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 60
“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
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
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 56
“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 60
“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
“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 68
Ryu, J. Y., Choi, H. M., Yang, H.-I., & Kim, K. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186887 · Cited by 52
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
Mou, K., Chan, S. M. H., & Vlahos, R. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108635 · Cited by 53
Granados, N., Amengual, J., Ribot, J., Palou, A., & Bonet, M. L. (2011) · British Journal Of Nutrition · doi:10.1017/s0007114510004885 · Cited by 51
“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)).”
BackgroundQuinn, L., Anderson, Conner, Pistilli, & Wolden-Hanson (2011) · International Journal of Interferon Cytokine and Mediator Research · doi:10.2147/ijicmr.s19007 · Cited by 47
“22 In the present study, mice were group-housed in order to minimize stress as a variable; therefore, food intake could not be assessed.”
InfluentialSelf-citationCancer 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 57
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
“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).”
BackgroundEvidence 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 47
Matthews, I., Birnbaum, A., Gromova, A., Huang, A. W., Liu, K., Liu, E. A., Coutinho, K., McGraw, M., Patterson, D. C., Banks, M. T., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113436 · Cited by 49
Secretomics for skeletal muscle cells: A discovery of novel regulators?
Yoon, J. H., Kim, J., Song, P., Lee, T. G., Suh, P., & Ryu, S. H. (2012) · Advances in Biological Regulation · doi:10.1016/j.jbior.2012.03.001 · Cited by 44
Sun, H., & Liu, D. (2015) · Gene Therapy · doi:10.1038/gt.2014.114 · Cited by 43
Zamboni, M. M., Mazzali, G., Brunelli, A., Saatchi, T., Urbani, S., Giani, A., Rossi, A. P., Zoico, E., & Fantin, F. (2022) · Cells · doi:10.3390/cells11213361 · Cited by 47
“Moreover, IL-15 inhibits the accumulation of lipids in preadipocytes and stimulates the secretion of adiponectin, which indirectly reduces WAT mass [170].”
Background
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
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