Abstract
Adipose tissue is an immunologically active organ that controls host physiology, partly through the release of mediators termed adipokines. In obesity, adipocytes and infiltrating leukocytes produce adipokines, which include the hormones adiponectin and leptin and cytokines such as tumour necrosis factor and IL-1β. These adipokines orchestrate immune responses that are collectively referred to as metabolic inflammation. Consequently, metabolic inflammation characterizes metabolic disorders and promotes distinct disease aspects, such as insulin resistance, metabolic dysfunction-associated liver disease and cardiovascular complications. In this unifying concept, adipokines participate in the immunological cross-talk that occurs between metabolically active organs in metabolic diseases, highlighting the fundamental role of adipokines in obesity and their potential for therapeutic intervention. Here, we summarize how adipokines shape metabolic inflammation in mice and humans, focusing on their contribution to metabolic disorders in the setting of obesity and discussing their value as therapeutic targets.
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Acknowledgements
T.E.A. received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant 101039320), the Austrian Science Fund (FWF P33070 and FG15) and the MYCOS consortium of the Medical University of Innsbruck. Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.
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Glossary
- CANTOS trial
-
A landmark randomized, double-blind clinical trial in which 10,061 participants with previous myocardial infarction and a high-sensitivity C-reactive protein (hsCRP) level ≥2 mg l–1 received canakinumab, a therapeutic monoclonal antibody neutralizing IL-1β, over 48 months. Primary efficacy end-points were non-fatal myocardial infarction, non-fatal stroke or cardiovascular death.
- Ciliary neurotrophic factor
-
(CNTF). A polypeptide hormone and neurotrophic factor and member of the IL-6 cytokine family that is able to interact with the IL-6 receptor (IL-6R).
- gp130 receptor
-
A common receptor subunit of the IL-6 cytokine family.
- HbA1c levels
-
Glycated haemoglobin levels chemically linked to a sugar (glucose) and reflecting circulating (serum) glucose levels within the past 3 months, therefore being an excellent indicator of euglycaemia/dysglycaemia.
- High-sensitivity C-reactive protein (hsCRP) test
-
A test assessing in a very sensitive manner minimal/moderate elevated levels of CRP, which is one of the most important human acute -phase proteins reflecting systemic activity of pro-inflammatory cytokines such as tumour necrosis factor (TNF), IL-1β or IL-6.
- Leukaemia inhibitory factor
-
(LIF). An IL-6 cytokine member which has main functions in the regulation of cell growth and differentiation.
- M2-like macrophage phenotype
-
Macrophages are either classified as M1, a more pro-inflammatory phenotype, or M2, a phenotype dominated by the synthesis of more anti-inflammatory cytokines such as IL-10 to block T helper 1 cell (TH1 cell)-type immunity.
- Metabolic dysfunction-associated steatotic liver disease
-
(MASLD). Previously called non-alcoholic fatty liver disease (NAFLD), one of the most common metabolic disorders in the world affecting almost a third of the world’s population.
- Monosodium urate crystals
-
Crystals reflecting potent pro-inflammatory agents causing potent upregulation of various inflammasomes (including NLR family pyrin containing domain 3 (NLRP3)) and pro-inflammatory cytokines such as IL-1β.
- Pathobionts
-
Members of the gut microbiota (mainly bacteria) which over time/life, especially in the context of various diseases – for example, chronic liver disease or colorectal cancer – develop the potential to become pathogenic and induce various diseases.
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Tilg, H., Ianiro, G., Gasbarrini, A. et al. Adipokines: masterminds of metabolic inflammation. Nat Rev Immunol (2024). https://doi.org/10.1038/s41577-024-01103-8
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DOI: https://doi.org/10.1038/s41577-024-01103-8