The Immune Landscape of Visceral Adipose Tissue During Obesity and Aging

Abstract

Obesity and aging represent major health burdens to the global adult population. Both conditions promote the development of associated metabolic diseases such as insulin resistance. The visceral adipose tissue (VAT) is a site that becomes dysfunctional during obesity and aging, and plays a significant role during their pathophysiology. The changes in obese and aging VAT are now recognized to be partly driven by a chronic local inflammatory state, characterized by immune cells that typically adopt an inflammatory phenotype during metabolic disease. Here, we summarize the current knowledge on the immune cell landscape of the VAT during lean, obese, and aged conditions, highlighting their similarities and differences. We also briefly discuss possible linked mechanisms that fuel obesity- and age-associated VAT dysfunction.

Keywords: aging; diabetes; immunology; immunometabolism; insulin resistance; metabolism; obesity; visceral adipose tissue.

Figure 1

Alterations in the visceral adipose tissue (VAT) immune cells during obesity and aging. In lean VAT, homeostasis is maintained via the secretion of anti-inflammatory cytokines by regulatory T cells (Tregs), T helper 2 (Th2) cells, tolerogenic macrophages, group 1 innate lymphoid cells (ILC1s), ILC2s, regulatory B cells (Bregs), B1 cells, and eosinophils. (Top) Obesity induces an expansion in adipocyte size and promotes a shift in the phenotype of local immune cells toward a pro-inflammatory state with increases in pro-inflammatory macrophages, NK Cells, B2 cells, Th1 CD4 cells, CD8+ T cells, and neutrophils. Inflammation of adipose tissue leads to tissue damage, cell death, and metabolic disturbances. (Bottom) During aging, the VAT is characterized by alterations in the immune cell environment. Emerging evidence indicates that these changes are associated with a shift in the phenotype of macrophages, expansion of B2 cells, age-associated B cells (AABs), CD8+ T cells and, paradoxically, regulatory T cells (Tregs). Changes in the composition of adipose tissue immune cells during aging may contribute to insulin resistance and ectopic lipid storage. Illustration created in the Mind the Graph platform: www.mindthegraph.com.