Immune Cell-Mediated Inflammation in Obesity: Mechanisms, Links with Inflammaging, and Therapeutic Implications: A Review

Chronic low-grade metabolic inflammation (metaflammation) is a hallmark of obesity and plays a role in adipose-tissue dysfunction, insulin resistance and metabolic comorbidities. Recruitment and activation of immune cells play a key role in this process, but their role is dependent on adipose tissue depot, disease stage and cellular phenotype. This review article focuses on the innate and adaptive immune cells such as macrophages, T cells, B cells, natural killer (NK) cells, natural killer T (NKT) cells, neutrophils, eosinophils and mast cells and their role in the inflammation associated with obesity. The evidence linking macrophage accumulation and activation, especially the interaction with T cells, to adipose metabolic dysfunction is more consistent, although evidence for other immune cells is more variable. Additionally, the link between metaflammation and inflammaging is also discussed. While they have common traits of immune dysregulation and inflammatory signaling, metaflammation is mostly triggered by nutrient excess and metabolic stress, and inflammaging by biological ageing and underlying cellular and molecular damage. There is a need for clinical translation of therapeutic targeting of inflammatory pathways, although this is not straightforward as these pathways are essential for host defense and tissue homeostasis. Human studies, understanding immune-cell heterogeneity and developing targeted approaches to inhibit pathological inflammation without affecting protective immune responses should be the focus of future research.