Immunometabolic Interactions in Adipose Tissue and Metabolic Disorders

Adipose tissue functions not only as an energy reservoir but also as a dynamic immunological organ in which adipocytes, stromal cells and resident immune populations form integrated networks that regulate systemic metabolism. In states of caloric excess, hypertrophic white adipocytes release pro-inflammatory adipokines and chemokines that recruit macrophages, T cells and neutrophils, driving a shift towards chronic low-grade inflammation. This immunometabolic imbalance contributes to insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular complications. Conversely, brown and beige adipocytes engage in reciprocal crosstalk with anti-inflammatory M2-polarised macrophages and sympathetic nerves to sustain adaptive thermogenesis and energy expenditure. Ageing and obesity perturb these circuits through senescent immune cell infiltration and fibrotic remodelling, impairing adipose plasticity. Elucidation of the molecular mediators and cell-cell dialogues within distinct fat depots offers avenues for targeted interventions to restore metabolic homeostasis.

Research from Nature Portfolio

Recent studies have shown that bone marrow-derived senescent T cells and neutrophils infiltrate brown adipose tissue during ageing, secreting S100A8 to downregulate axon guidance genes and disrupt sympathetic innervation. Pharmacological blockade of senescence-associated factors reconstitutes neural networks and revives thermogenic capacity in aged rodents, highlighting senescent immune cells as therapeutic targets to counteract metabolic decline. Foundational work in human adipose depots has further delineated how immune cell-derived cytokines orchestrate tissue dysfunction: IL-1β and IL-17 provoke robust inflammatory transcriptional programmes in pre-adipocytes and endothelial cells and suppress lipid storage genes in mature adipocytes, whereas TGF-β1 chiefly induces extracellular matrix production and fibrogenesis. These insights underscore the dual roles of cytokines in driving inflammation and metabolic dysregulation.

Immunometabolic Interactions in Adipose Tissue and Metabolic Disorders publication trend

The graph below shows the total number of articles in immunometabolic interactions in adipose tissue and metabolic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Adipocyte: A specialised cell that stores energy as fat within adipose tissue.

Macrophage polarisation: The process by which macrophages adopt distinct functional phenotypes, notably pro-inflammatory (M1) or anti-inflammatory (M2).

Cytokine: A soluble protein released by immune cells that modulates inflammation, cell growth and tissue remodelling.

Thermogenesis: The production of heat by metabolic processes, principally occurring in brown and beige adipocytes.

Senescence: A stable state of cell cycle arrest in which cells secrete pro-inflammatory factors and contribute to tissue dysfunction.

References

1. Regulation of systemic metabolism by tissue-resident immune cell circuits. Immunity (2023).
2. Senescent immune cells accumulation promotes brown adipose tissue dysfunction during aging. Nature Communications (2023).
3. Thermogenic Adipocytes Promote M2 Macrophage Polarization through CNNM4‐Mediated Mg Secretion. Advanced Science (2024).
4. Immune cell-derived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue. Scientific Reports (2017).