Hydrodynamic delivery of interleukin 15 gene promotes resistance to high fat diet-induced obesity, fatty liver and improves glucose homeostasis
Abstract
The objective of this study is to examine the effect of hydrodynamic delivery of plasmid containing Il-15 gene on high fat diet-induced obesity and obesity-associated metabolic disorders. We demonstrate that Il-15 gene transfer results in multiple beneficial effects, including blockade of weight gain, alleviation of fatty liver and improvement in glucose homeostasis in mice. These effects are accompanied by suppressed expression of genes involved in lipogenesis and gluconeogenesis including Scd-1, Fas, Pdk4, Pepck and G6p, and enhanced expression of genes responsible for lipolysis and glucose metabolism such as Cpt1-α, Cpt1-β, Acadm, Acadl and Glut-4. Collectively, our results suggest that Il-15 gene transfer is an effective approach in preventing diet-induced obesity and obesity-associated complications.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IL-15 augments glucose uptake in skeletal muscle by increasing transcription and membrane translocation of GLUT4 via JAK3/STAT3 signaling.
“IL-15 augments glucose uptake in SkM by increasing transcription [124] and membrane translocation of GLUT4 via JAK3/STAT3 signaling [125]”
Cites
Analysis 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
A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189 · see citing works
‘Small Changes' to Diet and Physical Activity Behaviors for Weight Management
Hills, A. P., Byrne, N. M., Lindstrom, R. C., & Hill, J. O. (2013) · Obesity Facts · doi:10.1159/000345030 · Cited by 9,526 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Muscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909 · 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
Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA
Liu, F., Song, Y. K., & Liu, D. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300947 · Cited by 1,728 · see citing works
Self-citationLi, A., Dubey, S., Varney, M. L., Davé, B. J., & Singh, R. K. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.6.3369 · Cited by 1,324 · see citing works
IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans
Steensberg, A., Fischer, C. P., Keller, C., Møller, K., & Pedersen, B. K. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00074.2003 · Cited by 1,135 · see citing works
Hydrodynamic Gene Delivery: Its Principles and Applications
Suda, T., & Liu, D. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300314 · Cited by 349 · see citing works
Self-citationOversecretion of interleukin-15 from skeletal muscle reduces adiposity
Quinn, L. S., Anderson, B. G., Strait-Bodey, L., Stroud, A. M., & Argilés, J. M. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90506.2008 · Cited by 267 · see citing works
A review of the effects of exercise on appetite regulation: an obesity perspective
Martins, C., Morgan, L., & Truby, H. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.98 · Cited by 254 · see citing works
The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15
Nielsen, A. R., & Pedersen, B. K. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h07-054 · Cited by 239 · 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
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
Obesity Prevalence in the United States — Up, Down, or Sideways?
Yanovski, S. Z., & Yanovski, J. A. (2011) · New England Journal of Medicine · doi:10.1056/nejmp1009229 · Cited by 173 · see citing works
Interleukin-15 contributes to the regulation of murine adipose tissue and human adipocytes
Barra, N. G., Reid, S., MacKenzie, R., Werstuck, G., Trigatti, B. L., Richards, C., Holloway, A. C., & Ashkar, A. A. (2010) · Obesity · doi:10.1038/oby.2009.445 · Cited by 116 · see citing works
Quinn, L. S., Anderson, B. G., Conner, J. D., & Wolden-Hanson, T. (2013) · Endocrinology · doi:10.1210/en.2012-1773 · Cited by 102 · see citing works
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
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
Interleukin‐15 treatment improves glucose homeostasis and insulin sensitivity in obese mice
Barra, N. G., Chew, M. V., Holloway, A. C., & Ashkar, A. A. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01495.x · Cited by 59 · 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
Hydrodynamic delivery of FGF21 gene alleviates obesity and fatty liver in mice fed a high-fat diet
Gao, M., Ma, Y., Cui, R., & Liu, D. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.03.047 · Cited by 48 · see citing works
Self-citationInterleukin‐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 · see citing works
Interleukin-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 · see citing works
López-Soriano, F. J. (2009) · International Journal of Molecular Medicine · doi:10.3892/ijmm_00000252 · Cited by 31 · see citing works
Rat liver lipogenesis is modulated by interleukin-15
López‐Soriano, J., Carbó, N., Almendro, V., Figueras, M., Ribas, V., Busquets, S., López-Soriano, F. J., & Argilés, J. M. A. (2004) · International Journal of Molecular Medicine · doi:10.3892/ijmm.13.6.817 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kalinkovich, A., & Livshits, G. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.008 · Cited by 882 · see citing works
Cytokines and abnormal glucose and lipid metabolism
Shi, J., Fan, J., Su, Q., & Yang, Z. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00703 · Cited by 282 · see citing works
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278 · see citing works
Gut microbiota influence in type 2 diabetes mellitus (T2DM)
Cunningham, A., Stephens, J. W., & Harris, D. A. (2021) · Gut Pathogens · doi:10.1186/s13099-021-00446-0 · Cited by 279 · 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
Mechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance
Balakrishnan, R., & Thurmond, D. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094636 · Cited by 132 · see citing works
Pallister, T., Jennings, A., Mohney, R. P., Yarand, D., Mangino, M., Cassidy, A., MacGregor, A. J., Spector, T. D., & Menni, C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158568 · Cited by 117 · 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
Interleukin-15 as a myokine: Mechanistic insight into its effect on skeletal muscle metabolism
Nadeau, L., & Aguer, C. (2019) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2018-0022 · Cited by 83 · see citing works
Effect 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
“Glucose metabolism regulation [64,65] Skeletal and heart muscle Placenta Monocytes/macrophages Bone marrow Thymus Lung Liver Kidney”
BackgroundHénin, G., Loumaye, A., Leclercq, I. A., & Lanthier, N. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100963 · Cited by 70 · 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
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
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 42 · see citing works
Inflammatory and Oxidative Stress Markers in Skeletal Muscle of Obese Subjects
Catalán, V., Frühbeck, G., & Gómez‐Ambrosi, J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812504-5.00008-8 · Cited by 43 · see citing works
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 · see citing works
Thornton, S. M., Krolopp, J. E., & Abbott, M. J. (2016) · PPAR Research · doi:10.1155/2016/5465804 · Cited by 31 · see citing works
Hydrodynamic delivery of IL-38 gene alleviates obesity-induced inflammation and insulin resistance
Xu, K., Sun, J., Chen, S., Li, Y., Peng, X., Li, M., & Yan, L. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.11.114 · Cited by 28 · see citing works
Pérez‐López, A., Encabo, P. G., Pérez‐Köhler, B., García‐Honduvilla, N., & Valadés, D. (2021) · European Journal of Sport Science · doi:10.1080/17461391.2021.1939430 · Cited by 28 · see citing works
IL-15/sIL-15Rα gene transfer induces weight loss and improves glucose homeostasis in obese mice
Sun, H. Y., Ma, Y., Gao, M., & Liu, D. (2016) · Gene Therapy · doi:10.1038/gt.2016.4 · Cited by 26 · see citing works
Self-citationWang, S., Guo, C., Xing, Z., Li, M., Yang, H., Zhang, Y., Ren, F., Chen, L., & Mi, S. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.664976 · Cited by 24 · see citing works
Yu, D., Li, H., Wang, Y., Li, C., You, D., Jiang, L., Song, Y., & Li, X. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s171963 · Cited by 24 · see citing works
Kado, A., Tsutsumi, T., Enooku, K., Fujinaga, H., Ikeuchi, K., Okushin, K., Moriya, K., Yotsuyanagi, H., & Koike, K. (2019) · Journal of Gastroenterology · doi:10.1007/s00535-019-01565-x · Cited by 23 · see citing works
Role of Protein Arginine Methyltransferases and Inflammation in Muscle Pathophysiology
So, H.-K., Kim, S., Kang, J., & Lee, S.-J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.712389 · Cited by 22 · see citing works
Wang, Y.-Q., Ma, Z., Jiang, L.-H., Bojan, N., Sha, Y.-W., Huang, B.-Y., Ming, L., Shen, J.-N., & Pang, W.-J. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03225-0 · Cited by 18 · see citing works
Weber, S. R., Zhao, Y., Ma, J., Gates, C., Leprevost, F. D. V., Basrur, V., Nesvizhskii, A., Gardner, T., & Sundstrom, J. (2021) · Clinical Proteomics · doi:10.1186/s12014-021-09328-8 · Cited by 15 · see citing works
Remodeling p38 signaling in muscle controls locomotor activity via IL-15
Folgueira, C., Herrera‐Melle, L., López, J. A., Galván-Álvarez, V., Martín-Rincón, M., Cuartero, M. I., García‐Culebras, A., Dumesic, P. A., Rodríguez, E., Leiva‐Vega, L., et al. (2024) · Science Advances · doi:10.1126/sciadv.adn5993 · Cited by 18 · see citing works
Li, L., Wang, L., Wang, T.-L., & Zheng, F.-M. (2023) · Medical Oncology · doi:10.1007/s12032-023-01978-y · Cited by 17 · see citing works
Antioxidants Facilitate High–intensity Exercise IL–15 Expression in Skeletal Muscle
Pérez‐López, A., Martín-Rincón, M., Santana, A., Pérez-Suárez, I., Dorado, C., Calbet, J. A. L., & Morales‐Álamo, D. (2018) · International Journal of Sports Medicine · doi:10.1055/a-0781-2527 · Cited by 17 · see citing works
Baik, M., Lee, M. S., Kang, H. J., Park, S. J., Piao, M. Y., Nguyen, T. H., & Hennighausen, L. G. (2015) · European Journal of Nutrition · doi:10.1007/s00394-015-1101-0 · Cited by 16 · see citing works
Choi, M. S., Kim, H.-J., Ham, M., Choi, D., Lee, T. R., & Shin, D. W. (2016) · Scientific Reports · doi:10.1038/srep28476 · Cited by 13 · see citing works
Lim, J. Y., & Kim, E. (2023) · Metabolites · doi:10.3390/metabo13090979 · Cited by 13 · see citing works
Jakubowicz, D. J., Matz, Y., Landau, Z., Rosenblum, R. C., Twito, O., Wainstein, J., & Tsameret, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212355 · Cited by 12 · see citing works
Loro, E., Jang, C., Quinn, W. J., Baur, J. A., Arany, Z. P., & Khurana, T. S. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01439 · Cited by 8 · see citing works
ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity
Chen, K., Hong, C., Kong, W., Li, G., Liu, Z., Zhu, K., Lu, C., Si, P., Gao, P., Ning, G., et al. (2024) · Cancer Cell International · doi:10.1186/s12935-024-03276-7 · Cited by 7 · see citing works
Cell-cell crosstalk between fat cells and immune cells
Liu, J., & Chen, Y. (2024) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00024.2024 · Cited by 7 · see citing works
Orsatti, C. L., Orsatti, F. L., Bezerra, T. G., Quevedo, A. L., & Nahás, E. A. P. (2022) · Gynecological Endocrinology · doi:10.1080/09513590.2022.2105832 · Cited by 6 · see citing works
Protective Effects of Interleukin-37 Expression against Acetaminophen-Induced Hepatotoxicity in Mice
Xu, Z., Li, K., Pan, X., Tan, J., Li, Y., & Li, M. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/6468299 · Cited by 2 · see citing works
Interleukin-15 based maintenance of metabolic homeostasis and treatment of lung cancer
Sun, H. (2016)
Self-citationLiver Gene Therapy: Employing Surgery and Radiology for Translational Research
Sendra, L., Herrero, M. J., Martí‐Bonmatí, L., Montalvá, E. M., López‐Andújar, R., Frasson, M., García‐Granero, E., & Pellicer, S. F. A. (2018) · InTech eBooks · doi:10.5772/intechopen.72665
Additional file 1 of ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity
Chen, K., Hong, C., Kong, W., Li, G., Liu, Z., Zhu, K., Lu, C., Si, P., Gao, P., Ning, G., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26685309
Kabakchieva, P., Gateva, A., Assyov, Y. S., Velikova, T. V., Kamenov, Z. A., & Georgiev, T. (2026) · SN Comprehensive Clinical Medicine · doi:10.1007/s42399-026-02512-7
- Authors
- Sun, H., & Liu, D.
- Affiliations
- University of Georgia (US)
- Corresponding author
- Liu, D
- Venue
- Gene Therapy
- Published
- 2014-12-11
- Volume
- 22
- Issue
- 4
- Pages
- 341-347
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- OpenAlex
- W2070098610
- Cited by
- 43
- References
- 27
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 1 · 2019: 4 · 2018: 7 · 2017: 2 · 2016: 7 · 2015: 2
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Georgia
- National Heart, Lung, and Blood Institute (R01HL098295)
- National Institute of Biomedical Imaging and Bioengineering (R01EB007357)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- IL-15, hydrodynamic gene delivery, plasmid DNA, high-fat diet-induced obesity, hepatic steatosis, glucose homeostasis, lipogenesis, gluconeogenesis, lipolysis, adipose tissue metabolism
- MeSH terms
- Animals, Fatty Liver, Glucose, Hyperglycemia, Hyperinsulinism, Insulin Resistance, Male, Mice, Inbred C57BL, Obesity, Gene Expression, Adipocytes, Gene Transfer Techniques, Interleukin-15, Lipid Metabolism, Hydrodynamics, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
