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Interplay between the immune system and adipose tissue in obesity
Open accessAbstract
Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. Alongside its major role in energy storage, WAT is an important endocrine organ, producing many bioactive molecules, termed adipokines, which not only serve as regulators of systemic metabolism, but also possess immunoregulatory properties. Furthermore, WAT contains a unique immune cell repertoire, including an accumulation of leukocytes that are rare in other locations. These include alternatively activated macrophages, invariant natural killer T cells, and regulatory T cells. Disruption of resident adipose leukocyte homeostasis contributes to obesity-associated inflammation and consequent metabolic disorder. Despite many recent advances in this new field of immuno-metabolism, fundamental questions of why and how inflammation arises as obesity develops are not yet fully understood. Exploring the distinct immune system of adipose tissue is fundamental to our understanding of the endocrine as well as immune systems. In this review, we discuss the roles of adipose tissue leukocytes in the transition to obesity and progression of inflammation and highlight potential anti-inflammatory therapies for combating obesity-related pathology.
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“Obesity promotes inflammatory pathways in visceral fat through adipocyte hypertrophy and hyperplasia and the accumulation of immune cells including macrophages, mast cells, and T lymphocytes producing pro-inflammatory cytokines (148–150).”
From Health Consequences of Sarcopenic Obesity: A Narrative Review (2020) · cites this paper as [149]
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Agnese, M., Toia, P., Sollami, G., Militello, C., Rundo, L., Vitabile, S., Maffei, E., Agnello, F., Gagliardo, C., Grassedonio, E., et al. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e15984 · Cited by 7
Margiotta, D. P. E., Vadacca, M., Navarini, L., Basta, F., & Afeltra, A. (2016) · Lupus Open Access · doi:10.35248/2684-1630.16.1.107 · Cited by 7
“Adipokines are involved in metabolism, appetite and energy balance, insulin sensitivity, endocrine and reproductive function, bone metabolism, atherogenesis and immunity [1,2].”
BackgroundInfluentialOnmus, M. Y., Avcu, E. C., & Saklamaz, A. (2016) · doi:10.12691/jfnr-4-1-1 · Cited by 6
“In surveys conducted in recent years, it has reached the conclusion that obesity is an inflammatory disease and the weight loss has been shown to decrease the inflammation [7,8,10,11,23,24].”
BackgroundKrysiak, R. G., Żmuda, W., Marek, B., & Okopień, B. (2015) · Endokrynologia Polska · doi:10.5603/ep.a2016.0019 · Cited by 6
“A crosstalk between adipocytes and macrophages, being the most abundant immune cells in adipose tissue, allows the coordination of available energy stores for survival during times of starvation and pathogen challenge [30].”
BackgroundVitamin D, Obesity, and the Metabolic Syndrome
Hyppönen, E., & Boucher, B. J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809963-6.00078-x · Cited by 6
The Pivotal Role of Macrophages in Metabolic Distress
Roberts, J., Fallon, P. G., & Hams, E. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.86474 · Cited by 8
Adnan, A., Juntunen, M., Tyrväinen, T., Kelloniemi, M., Kummola, L., Autio, R., Patrikoski, M., & Miettinen, S. (2025) · Stem Cells International · doi:10.1155/sci/1212255 · Cited by 5
“…the immunomodulatory capacity of ASCs, macrophages were polarized and activated toward the M1 and M2 phenotypes from peripheral blood mononuclear cells (PBMCs) and studied in direct cocultures with ASCs to mimic the environment of adipose tissue where cells are in contact with each other [22, 23].”
InfluentialHeifner, J. J., Pannu, T. S., Gomez, O., Sakalian, P. A., & Corces, A. (2024) · The Journal of Arthroplasty · doi:10.1016/j.arth.2024.08.020 · Cited by 5
NKT-dependent B-cell activation in Gaucher disease
Salio, M., & Cerundolo, V. (2015) · Blood · doi:10.1182/blood-2014-12-617514 · Cited by 5
CD40 signaling and hepatic steatosis: Unanticipated links
Lepreux, S., Villeneuve, J., Dewitte, A., Bérard, A. M., Desmoulière, A., & Ripoche, J. (2016) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2016.11.002 · Cited by 6
Chilukuri, B., Saranya, C., Mahendran, B., Ramamoorthy, R., Sriram, S., & Rajeswari, S. (2020) · Indian Journal of Rheumatology · doi:10.4103/injr.injr_6_20 · Cited by 5
“[1] Adipocytes in the adipose tissue secrete adipokines, cytokines, and chemokines.”
Ohm, H., & Abdel-Rahman, O. M. (2023) · Current Oncology · doi:10.3390/curroncol30010060 · Cited by 5
“iNKT cells have mechanisms to activate anti-tumoral T helper cells rapidly [18].”
BackgroundInfluentialBakondi, E., Jung, T., Marg, S., Schnell, V., Weber, D., Schulz, T. J., Grune, T., & Höhn, A. (2024) · Redox Report · doi:10.1080/13510002.2024.2430882 · Cited by 6
“During obesity-induced inflammation and related disorders, the white adipose tissue (WAT) is assumed to be the most important organ regarding the regulation of immunological changes [11,12].”
Assessment of Oxidative Stress Markers in Obese Patients with Community-Acquired Pneumonia
Dumitraș, T., Fetco-Mereuță, D., Caproş, N., Chihai, V., Terna, E., Matcovschi, S., & Cascaval, V. (2023) · World Congress on Medical Physics and Biomedical Engineering, September 7 - 12, 2009, Munich, Germany · doi:10.1007/978-3-031-42782-4_41 · Cited by 5
Immune Response and Oxidative Stress in Obesity-Induced Cancer
Jaiswara, P. K., Sonker, P., & Kumar, A. (2021) · Springer eBooks · doi:10.1007/978-981-16-1846-8_6 · Cited by 3
Afroz, S., Parhin, A., Shamima Akter Somi, S., Munir, T. Y., & Khan, S. (2023) · Gynecology & Reproductive Health · doi:10.33425/2639-9342.1213 · Cited by 3
“The adipose tissue is present 10% of those in the omentum and 85% in the subcutaneous space [70].”
BackgroundObesity, Cancer and the Immune System: Cross Talks and Complex Interplay
Kamel, H. F. M., Al-Amodi, H. S. A. B., & Abdelsattar, S. (2022) · Springer eBooks · doi:10.1007/978-3-030-80962-1_105-1 · Cited by 3
Sarcopenia and the inflammatory cytokines
Orzechowski, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822146-4.00008-9 · Cited by 2
Immune regulation in obesity: a narrative review
Manuaba, I. B. P., & Sindhughosa, D. A. (2023) · Indonesia Journal of Biomedical Science · doi:10.15562/ijbs.v17i1.459 · Cited by 2
Effects of NKT Cells on Metabolic Disorders Caused by High-Fat Diet Using CD1d-Knockout Mice
Ishikawa, H., Nagashima, R., Kuno, Y., Sasaki, H., Kohda, C., & Iyoda, M. (2023) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s428190 · Cited by 2
“Discussion In the present study, we evaluated whether or not HFD feeding affects the progression of metabolic diseases in CD1dKO mice in comparison to WT mice, because controversy remains in relation to the clinical conditions caused by HFD feeding, such as obesity, dyslipidemia, type 2 diabetes and non-alcoholic fatt…”
BackgroundResultElliott, J. A., & Reynolds, J. V. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91707-0.00013-9 · Cited by 2
Metabolic Syndrome. Particularities During SARS-CoV-2 Infection
Cioti, A.-M., Grăjdeanu, I. V., SIMIONESCU, A. A., Bejan, G. C., & Stănescu, A. M. A. (2021) · Medicina Moderna - Modern Medicine · doi:10.31689/rmm.2021.28.2.119 · Cited by 3
Myeloid-resident neuropilin-1 influences brown adipose tissue in obesity
Diaz-Marin, R., Crespo‐Garcia, S., Wilson, A. M., Buscarlet, M., Dejda, A., Fournier, F., Juneau, R., Alquier, T., & Sapieha, P. S. (2021) · Scientific Reports · doi:10.1038/s41598-021-95064-w · Cited by 2
Sengupta, S., & Avtanski, D. B. (2023) · Contemporary Endocrinology · doi:10.1007/978-3-031-39721-9_2 · Cited by 3
Adipocyte-derived extracellular vesicles: characterisation and function
Connolly, K. D. (2016) · ORCA Online Research @Cardiff (Cardiff University) · Cited by 2
Liu, Y., Hu, G., Jia, Y., Qin, L., Xu, L., Chang, Y., Li, B., & Li, H. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09249-3 · Cited by 1
“It has been evidenced that there is a strong mutual cross - talk between the immune system and fat metabolism [ 20].”
Wang, R., Goruk, S., Chan, C. B., & Field, C. J. (2026) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2026.110288 · Cited by 1
Obesity, inflammation, and cancer immunotherapy: The adipose–immune axis as a therapeutic frontier
Gupta, A. K. (2026) · International Journal of Molecular and Immuno Oncology · doi:10.25259/ijmio_35_2025 · Cited by 1
Esteves, E. A., & Dias‐Peixoto, M. F. (2015) · doi:10.5348/n09-2015-2-ed-1 · Cited by 1
“Altered expression of pro- and anti-inflammatory factors produced by leukocytes acts reciprocally on adipocytes, perpetuating inflammation and dysfunction [12].”
BackgroundThrum, S. (2017) · Zeitschrift für Rheumatologie · doi:10.1007/s00393-017-0298-0 · Cited by 1
Obesity, Adipokines, and Gynecologic Cancer
Connor, E. V., Reizes, O., & Saygin, C. (2017) · Energy balance and cancer · doi:10.1007/978-3-319-63483-8_6 · Cited by 1
An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes
Sbierski‐Kind, J., Schmidt‐Bleek, K., Streitz, M., Kath, J., Spranger, J., & Volk, H. (2019) · Journal of Visualized Experiments · doi:10.3791/59470 · Cited by 1
Effects of Exercise Training on Vascular Inflammatory Markers in High-fat Diet-induced Obese Rats
Kim, K. (2020) · The Asian Journal of Kinesiology · doi:10.15758/ajk.2020.22.2.30 · Cited by 1
“The expression level of TNF-α was significantly lower (p 0.05) in the HFD and Chow groups than in the non-exercise group.”
BackgroundInfluentialVasomotor Symptoms, Cardiovascular Risk and the Role of Physical Activity in Midlife Women
Nilsson, S. (2023) · Linköping University medical dissertations · doi:10.3384/9789180752619 · Cited by 1
Impact of COVID-19 Pandemic and Lockdown Measures on the Nutrition Plan Service Cohort
Lorenzo, M. D., Mascolo, S., & Romanelli, A. (2021) · Iranian journal of diabetes and obesity · doi:10.18502/ijdo.v13i3.7183 · Cited by 1
IMPACTO DA OBESIDADE NO SISTEMA IMUNOLÓGICO
Marcondes, E. F., Schuh, K., Tavares, M. T., Centa, A., Pont, G. C. D., & Assolini, J. P. (2023) · Simpósio Internacional Interdisciplinar dos Cursos da Área da Saúde · doi:10.17648/siics-2022-159561 · Cited by 1
COVID-19 and metabolic disorders: focus on the implicated molecular pathwaysPreprint
Nigro, E., Perrotta, F., Polito, R., D’Agnano, V., Scialò, F., Bianco, A., & Daniele, A. (2020) · doi:10.22541/au.158880240.00304700
Role of Obesity and Mediators of Adipose Tissue in Renal Transplant and DiseasePreprint
Mota-Zamorano, S., García‐Pino, G., & Gervasini, G. (2024) · Preprints.org · doi:10.20944/preprints202401.0238.v1 · Cited by 1
Metadata
- Authors
- Exley, M. A., Hand, L., O'Shea, D., & Lynch, L.
- Affiliations
- University College Dublin (IE)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2014-09-16
- Volume
- 223
- Issue
- 2
- Pages
- R41-R48
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2145456795
- Cited by
- 242
- References
- 66
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 12 · 2023: 26 · 2022: 25 · 2021: 20 · 2020: 24 · 2019: 18 · 2018: 20 · 2017: 22 · 2016: 24 · 2015: 35
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- National Cancer Institute (P01CA017094, CA017094)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- obesity, white adipose tissue, adipose tissue inflammation, adipokines, M2 macrophages, invariant natural killer T cells, regulatory T cells, metabolic disorders, anti-inflammatory therapy
- MeSH terms
- Adipose Tissue, Animals, Eosinophils, Humans, Immune System, Inflammation, Lymphocytes, Macrophages, Obesity
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