Adipose Tissue Macrophage Dynamics in Metabolic Health

Adipose tissue harbours a diverse population of macrophages that play central roles in energy homeostasis, tissue remodelling and immune surveillance. Under physiological conditions, resident macrophages contribute to lipid buffering, clearance of apoptotic cells and secretion of anti-inflammatory mediators, thereby supporting insulin sensitivity and healthy adipose expansion. In obesity and related metabolic disorders, the macrophage landscape shifts towards proinflammatory phenotypes characterised by enhanced glycolysis, cytokine production and recruitment from circulating monocytes. This transition fosters chronic low-grade inflammation, adipocyte dysfunction and systemic insulin resistance. Recent evidence indicates that both extrinsic monocyte infiltration and local proliferation of resident macrophages drive their accumulation during weight gain, while specialised subsets retain plasticity to adopt reparative or inflammatory functions. Metabolic reprogramming within adipose tissue macrophages—encompassing alterations in glycolysis, fatty acid oxidation and glutaminolysis—underpins their effector activities. Furthermore, lipid-handling macrophages engage in foam cell formation and orchestrate inflammasome activation, linking lipid overload to inflammatory signalling. A deeper understanding of macrophage heterogeneity, intercellular crosstalk and the molecular circuits governing phenotype switching is unlocking novel strategies to restore adipose tissue homeostasis and ameliorate insulin resistance on a global scale.

Research from Nature Portfolio

Recent studies have clarified how hormonal and environmental cues shape macrophage functions in adipose tissue. One investigation demonstrated that physiological glucocorticoid receptor signalling in myeloid cells promotes an anti-inflammatory macrophage subset that limits adipose inflammation, restrains excessive lipolysis and preserves systemic insulin sensitivity during diet-induced obesity. Loss of this receptor in macrophages intensified inflammatory cytokine release, aggravated hepatic steatosis and impaired glucose uptake by adipocytes, underscoring the importance of endogenous glucocorticoids in immunometabolic regulation. Another multiomic analysis employing single-cell transcriptomics and protein profiling revealed that obesity imprints a persistent immune signature in adipose tissue, even following weight loss. Weight cycling led to exaggerated antigen presentation, T cell exhaustion and enhanced lipid-handling programmes in macrophages, explaining the heightened metabolic risk associated with repeated weight gain and loss. These insights pave the way for interventions targeting macrophage memory and hormone-mediated regulatory pathways.

Adipose Tissue Macrophage Dynamics in Metabolic Health publication trend

The graph below shows the total number of articles in adipose tissue macrophage dynamics in metabolic health across all publications each year (not limited to Nature Index journals).

Technical terms

Adipose tissue macrophages (ATMs): Resident and recruited immune cells in fat tissue that clear debris, buffer lipids and modulate inflammation.

M1/M2 polarization: Functional classification of macrophages into proinflammatory (M1) or anti-inflammatory (M2) states based on metabolic and cytokine profiles.

Lipid-associated macrophages (LAMs): A subset of ATMs specialised in handling excess lipids, implicated in both metabolic disease aggravation and resolution.

Inflammasome: A multiprotein complex in macrophages that activates inflammatory cytokines such as IL-1β in response to cellular stress or lipid overload.

Metabolic reprogramming: The shift in cellular energy pathways (e.g., glycolysis, fatty acid oxidation) that underpins macrophage activation and function.

Crown-like structures: Aggregates of macrophages encircling dying or necrotic adipocytes, characteristic of inflamed obese adipose tissue.

References

1. Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses. Diabetologia (2018).
2. Local proliferation initiates macrophage accumulation in adipose tissue during obesity. Cell Death & Disease (2016).
3. Meta-Inflammation and Metabolic Reprogramming of Macrophages in Diabetes and Obesity: The Importance of Metabolites. Frontiers in Immunology (2021).
4. Exocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation[S]. Journal of Lipid Research (2016).
5. Glucocorticoid activation of anti-inflammatory macrophages protects against insulin resistance. Nature Communications (2023).
6. Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice. Nature Communications (2022).
7. Lipid-associated macrophages between aggravation and alleviation of metabolic diseases. Trends in Endocrinology and Metabolism (2024).
8. Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome. Molecular Biomedicine (2023).