Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Figure 1. Adipose tissue resident and infiltrating immune cells activity in health and disease. Significant crosstalk exists among adipocytes, adipokines, and resident and infiltrating, innate and adaptive immune cells. Metabolic disease conditions modulate the adipokine profile and immune cell activity leading to the observed chronic low-grade inflammation. Pathways involved in AT homeostasis are depicted in black arrows, while those activated by metabolic dysfunction are shown in red. B Cell, B Lymphocyte; Breg Cells, Regulatory B Lymphocyte; CCL11, C-C motif chemokine 11; CD1d, Cluster of Differentiation 1d; cDC, Conventional Dendritic Cell; FFA, Free Fatty Acids; IFNγ, Interferon Gamma; IgG, Immunoglobulin G; IL, Interleukin; ILC, Innate Lymphoid Cell; iNKT Cell, Invariant Natural Killer T Cell; LTB4, Leukotriene B4; NET, Neutrophil Extracellular Trap; NF-κB, Nuclear Factor Kapp-light-chain-enhancer of Activated B cells; NLRP3, NLR Family Pyrin Domain Containing 3; NO, Nitric Oxide; pDC, Plasmacytoid Dendritic Cell; ROS, Reactive Oxygen Species; T Cell, T Lymphocyte; TGF-β, Transforming Growth Factor Beta; Th Cell, Helper T Lymphocyte; TLR, Toll Like Receptor; TNFα, Tumor Necrosis…

Figure 2. Perivascular and epicardiac adipose tissue dysfunction: the emerging role of immune cell and adipokine profile dysregulation. Metabolic impairment triggers changes in PVAT (left) and EpiCAT (right) adipokine environment and immune cell activity. Inflammation has a direct effect on the neighboring vascular and cardiac tissue. Changes in UCP1 expression were reported to have opposite effects in either depot. Pathways active in basal PVAT and EpiCAT homeostasis are depicted in black arrows, while those activated during inflammation are shown in red. ADM2, Adrenomedullin-2; eNOS, Endothelial Nitric Oxide Synthase; EpiCAT, Epicardial Adipose Tissue; ER Stress, Endoplasmic Reticulum Stress; HIF-1α, Hypoxia-induced Factor 1 Alpha; IL, Interleukin; MCP-1, Monocyte Chemoattractant Protein 1; NF-κB, Nuclear Factor Kapp-light-chain-enhancer of Activated B cells; NLRP3, NLR Family Pyrin Domain Containing 3; O2, Oxygen; PVAT, Perivascular Adipose Tissue; RAS, Renin Angiotensin System; ROS, Reactive Oxygen Species; TGF-β, Transforming Growth Factor Beta; TNFα, Tumor Necrosis Factor Alpha; UCP1, Uncoupling Protein 1.

Figure 3. Immune cells-mediated regulation of adaptive thermogenesis. Different types of immune cells exert various modes of control on thermogenesis by either directly modulating the adipocyte function or affecting sympathetic nerve activity and norepinephrine turn-over. Pathways promoting thermogenesis are depicted in black, while inhibitory pathways are shown in red. ADM2, Adrenomedullin-1; β3-AR, Beta 3-adrenergic Receptor; CCL11, C-C motif chemokine 11; FGF21, Fibroblast Growth Factor 21; H2R, Histamine 2 Receptor; γGalCer, Alpha-galactosylceramide; IL, Interleukin; ILC, Innate Lymphoid Cell; MAO, Monoamine Oxidase; NE, Norepinephrine; Opioid R, Opioid Receptor; SCL6A2, Solute Carrier Family 6 Member 2; TGF-β, Transforming Growth Factor Beta; Treg, Regulatory T Lymphocyte.