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Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: a potential role in body weight control
Abstract
Interleukin (IL)-15 is a cytokine which is highly expressed in skeletal muscle. Cell culture studies have indicated that IL-15 may have an important role in muscle fiber growth and anabolism. However, data concerning the metabolic effects of this cytokine in vivo are lacking. In the present study, IL-15 was administered to adult rats for 7 days. While IL-15 did not cause changes in either muscle mass or muscle protein content, it induced significant changes in the fractional rates of both muscle protein synthesis and degradation, with no net changes in protein accumulation. Additionally, IL-15 administration resulted in a 33% decrease in white adipose tissue mass and a 20% decrease in circulating triacylglycerols; this was associated with a 47% lower hepatic lipogenic rate and a 36% lower plasma VLDL triacylglycerol content. The decrease in white fat induced by IL-15 was in adipose tissue. No changes were observed in the rate of lipolysis as a result of cytokine administration. These findings indicate that IL-15 has significant effects on both protein and lipid metabolism, and suggest that this cytokine may participate in reciprocal regulation of muscle and adipose tissue mass.
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“while others such as irisin [65], IL-15 [90], and BAIBA [113] have been found to inhibit hepatic lipogenesis (7).”
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“Interleukin-15 exerts local anabolic/anti-catabolic effects [10] and increases glucose uptake, thus inhibiting lipid deposition [10, 11].”
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Argilés, J. M. A., López-Soriano, F. J., & Busquets, S. (2012) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2012.04.011 · Cited by 64
The relationship between plasma interleukin-15 levels and sarcopenia in outpatient older people
Yalçın, A., Sılay, K., Balik, A. R., Avcıoğlu, G., & Şenat, A. (2017) · Aging Clinical and Experimental Research · doi:10.1007/s40520-017-0848-y · Cited by 64
“In another study, administration of IL-15 for 7 days resulted in a decrease in white adipose tissue without affecting food intake in older rats [28].”
BackgroundAjuwon, K. M., Jacobi, S. K., Kuske, J. L., & Spurlock, M. E. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00585.2003 · Cited by 63
“However, in rodent models, IL-15 also promotes muscle growth (4, 23) and decreases adipose mass (4).”
BackgroundScheel, A. K., Espelage, L., & Chadt, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094759 · Cited by 68
“In rodents, administration of IL-15 led to a 35% reduction in WAT mass and a 20% decline in plasma triglycerides, indicating that IL-15 additionally exerts a regulatory role in lipid metabolism [135].”
BackgroundPierce, 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
Myokines 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
Biomarkers 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
“Previous work has shown that IL-15 treatment causes a significant decrease in AT mass in normal weight [201,202] and obese rodents.”
BackgroundRingleb, M., Javelle, F., Haunhorst, S., Bloch, W., Fennen, L., Baumgart, S., Drube, S., Reuken, P. A., Pletz, M. W., Wagner, H., et al. (2024) · The FASEB Journal · doi:10.1096/fj.202301619r · Cited by 73
“6,29 Furthermore, immune-related myokines are IL-7, 30 which is, for example, essential for T-and B-cell development, 31,32 and IL-15, 33 which reduces adipose tissue by stimulating lipolysis, 34,35 therefore exerting indirect anti-inflammatory effects by reducing cardiovascular risk factors.”
BackgroundEffects 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 57
Renzo, L. D., Bigioni, M., Bottini, F. G., Gobbo, V. D., Premrov, M. G., Cianci, R., & LORENZO, A. D. (2006) · PubMed · Cited by 54
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
Effects of IL-15 on rat brown adipose tissue: Uncoupling proteins and PPARs
Almendro, V., Fuster, G., Busquets, S., Ametller, E., Figueras, M., Argilés, J. M., & López‐Soriano, F. J. (2008) · Obesity · doi:10.1038/oby.2007.47 · Cited by 49
“In the course of in vivo studies regarding the effects of IL-15 on skeletal muscle, a 33% decrease in WAT was observed in rats, with no changes in food intake (20).”
BackgroundMethodInfluentialQuinn, L., Anderson, Conner, Pistilli, & Wolden-Hanson (2011) · International Journal of Interferon Cytokine and Mediator Research · doi:10.2147/ijicmr.s19007 · Cited by 47
“A number of in vivo studies using both laboratory rodents and human subjects have confirmed the negative association of IL-15 with adiposity, 19–22, 30, 31 and have suggested relationships The present study was undertaken to test three hypotheses: first, IL-15 inhibits diet-induced obesity (DIO)…”
Self-citationInsulin-like 6 Is Induced by Muscle Injury and Functions as a Regenerative Factor
Zeng, L., Akasaki, Y., Sato, K., Ouchi, N., Izumiya, Y., & Walsh, K. X. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.160879 · Cited by 49
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
“Overall, the roles of IL-15 in adipose tissue lipid metabolism include inhibition of LPL activity, lipid uptake and lipogenesis, and promotion of lipolysis, FA oxidation and thermogenesis (17,19,37).”
BackgroundInfluentialSun, 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
Serum IL ‐15 and IL ‐15Rα levels are decreased in lean and obese physically active humans
Pérez‐López, A., Valadés, D., Martínez, C. V., Blanco, A. I. D. C., Buján, J., & García‐Honduvilla, N. (2017) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.12983 · Cited by 40
López‐Soriano, J., Chiellini, C., Maffei, M., Grimaldi, P. A., & Argilés, J. M. A. (2006) · Endocrine Reviews · doi:10.1210/er.2005-0012 · Cited by 40
Wilhelmsen, A., Tsintzas, K., & Jones, S. W. (2021) · GeroScience · doi:10.1007/s11357-021-00322-4 · Cited by 42
Bisphenol A promotes hepatic lipid deposition involving Kupffer cells M1 polarization in male mice
Lv, Q., Gao, R., Peng, C., Yi, J., Liu, L., Yang, S., Li, D., Hu, J., Luo, T., Mei, M., et al. (2017) · Journal of Endocrinology · doi:10.1530/joe-17-0028 · Cited by 38
Interleukin‐15 Affects Differentiation and Apoptosis in Adipocytes: Implications in Obesity
Fuster, G., Almendro, V., de Oliveira, C. C. F., Toledo, M., Costelli, P., Busquets, S., López-Soriano, F. J., & Argilés, J. M. A. (2011) · Lipids · doi:10.1007/s11745-011-3594-5 · Cited by 33
“Taking this into consideration, IL-15 is a cytokine of special interest because it causes an important reduction of WAT weight by altering several important processes within this tissue, for example lipogenesis [9, 15], LPL activity, or lipid uptake [5, 10].”
BackgroundInfluentialInterleukin-15 Treatment Induces Weight Loss Independent of Lymphocytes
Barra, N. G., Chew, M. V., Reid, S., & Ashkar, A. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039553 · Cited by 31
“Previous work has shown that IL-15 treatment causes a significant decrease in adipose tissue mass in normal weight [19,20] and obese rodents [18], reduces lipoprotein lipase expression [18], and may play a role in lipid oxidation [21,22].”
BackgroundKim, H., Park, J. Y., Oh, S. L., Kim, Y.-A., So, B., Seong, J. K., & Song, W. J. (2013) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2013.37.5.358 · Cited by 31
Argilés, J. M. A. (2016) · Clinical Nutrition · doi:10.1016/j.clnu.2016.05.010 · Cited by 31
Exercise‐Induced cytokines, diet, and inflammation and their role in adipose tissue metabolism
Al‐Ibraheem, A. M. T., Hameed, A. A. Z., Marsool, M. D. M., Jain, H., Prajjwal, P., Khazmi, I., Nazzal, R., Al-Najati, H. M. H., Al‐Zuhairi, B. H. Y. K., Razzaq, M., et al. (2024) · Health Science Reports · doi:10.1002/hsr2.70034 · Cited by 33
“12,13 The observed pathway in these samples showed that IL ‐ 15 up-regulates PPAR δ in brown adipose tissue (BAT) in rats.”
BackgroundExercise-regulated lipolysis: Its role and mechanism in health and diseases
Zhu, J., & Guo, L. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.11.031 · Cited by 33
“Continuous subcutaneous injection of IL-15 at a dose of 100 l g/kg for seven days in rats was found to reduce white adipose tissue mass [59].”
Shin, K. O., Bae, J. Y., Woo, J., Jang, K. S., Kim, K. S., Park, J. S., Kim, I. K., & Kang, S. (2015) · Physical Activity and Nutrition · doi:10.5717/jenb.2015.15061006 · Cited by 32
“confirmed that IL-15 has a role of inducing the growth of muscles and reducing the adipose tissue; their studies reported that white adipose tissue was reduced by 33% when IL-15 was administered to adults rats for 7 days [12].”
Background
Metadata
- Authors
- Carbó, N., López-Soriano, J., Costelli, P., Alvarez, B., Busquets, S., Baccino, F. M., Quinn, L. S., López-Soriano, F. J., & Argilés, J. M.
- Affiliations
- Universitat de Barcelona (ES)
- University of Turin (IT)
- University of Washington (US)
- Corresponding author
- Argilés, Josep M
- Venue
- Biochimica et Biophysica Acta (BBA) - General Subjects
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 1526
- Issue
- 1
- Pages
- 17-24
- ISSN
- 0304-4165 (ISSN-L)
- OpenAlex
- W2040190888
- Cited by
- 174
- References
- 42
- Citations by year
- 2024: 7 · 2023: 6 · 2022: 11 · 2021: 4 · 2020: 6 · 2019: 8 · 2018: 11 · 2017: 12 · 2016: 10 · 2015: 11 · 2014: 10 · 2013: 10 · 2012: 7
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- IL-15, white adipose tissue, skeletal muscle mass, weight management, muscle protein synthesis, muscle protein degradation, hepatic lipogenesis, triglyceride metabolism, lipolysis
- MeSH terms
- Adipose Tissue, Animals, Body Weight, Eating, Lipolysis, Lipoproteins, VLDL, Male, Muscle Proteins, Organ Size, Triglycerides, Rats, Wistar, Muscle, Skeletal, Interleukin-15, Rats
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