Adipose tissue, adipokines, and inflammation

Adipose tissue: cellular components and molecules produced. Adipose tissue is composed of adipocytes and the stromovascular fraction, which includes macrophages. Left, Adipocytes produce leptin, adiponectin, visfatin, IL-6, MCP-1, and other factors. Macrophages produce TNF-α, IL-5, MCP-1, and other cytokines and chemokines. In human subjects the ultimate cellular source of adipsin and resistin seems to be the macrophage. Right, In obesity leptin and possibly other factors produced by adipocytes, macrophages, or both upregulate adhesion molecules on endothelial cells, leading to transmigration of bone marrow–derived monocytes and thus an increase in WAT-resident macrophages, some of which fuse to generate giant multinucleated cells. Macrophages present in the WAT of obese individuals produce higher levels of TNF-α, IL-6, and chemokines compared with those in lean persons. At the same time, adiponectin production by adipocytes is reduced, possibly through upregulated local TNF-α levels.

Effects of leptin on immunity and inflammation. Leptin is produced by adipocytes and acts on the long isoform of its receptor, which is expressed by many cell types, including lymphocytes, monocytes, and endothelial cells. Leptin protects T lymphocytes from apoptosis and modulates T-cell proliferation, increasing the proliferation of naive T cells while reducing the proliferation of memory T cells. Leptin modulates T cell–derived cytokine production and increases expression of the activation markers CD25 and CD71 in CD4⁺ and CD8⁺ cells. In monocytes leptin increases the expression of various activation markers and upregulates phagocytosis and cytokine production. In endothelial cells leptin upregulates the expression of adhesion molecules and induces oxidative stress. Many of the modulating activities of leptin in immune and inflammatory responses are observed only when a costimulus is present.

Adiponectin: structure and anti-inflammatory effects. Left, Adiponectin is composed of a collagenous and a globular domain. Adiponectin monomers trimerize through tight interactions in the collagenous domain. Trimers can then oligomerize. Both trimers and oligomers are present in the circulation and might have different effects on insulin sensitivity. Leukocyte elastase released by activated immune cells cleaves the globular domain of adiponectin, which might have activities distinct from those of the full-length molecule. Right, Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1 receptor antagonist in monocytes-macrophages, while inhibiting IL-6 and TNF-α levels. Adiponectin also inhibits the biologic activity of TNF-α. In endothelial cells adiponectin downregulates the expression of adhesion molecules, thus contrasting the effect of resistin.