Crosstalk between Metabolic Disorders and Immune Cells

Abstract

Metabolic syndrome results from multiple risk factors that arise from insulin resistance induced by abnormal fat deposition. Chronic inflammation owing to obesity primarily results from the recruitment of pro-inflammatory M1 macrophages into the adipose tissue stroma, as the adipocytes within become hypertrophied. During obesity-induced inflammation in adipose tissue, pro-inflammatory cytokines are produced by macrophages and recruit further pro-inflammatory immune cells into the adipose tissue to boost the immune response. Here, we provide an overview of the biology of macrophages in adipose tissue and the relationship between other immune cells, such as CD4+ T cells, natural killer cells, and innate lymphoid cells, and obesity and type 2 diabetes. Finally, we discuss the link between the human pathology and immune response and metabolism and further highlight potential therapeutic targets for the treatment of metabolic disorders.

Keywords: 5-aminolevulinic acid; CD4+ T cells; M1/M2 macrophages; chronic inflammation; cytokine; innate lymphoid cells; mesenchymal stem cells; natural killer cells; non-obese metabolic disorder; obesity.

Figure 1

Schematic representation of the crosstalk between mesenchymal stem cells (MSCs) and macrophages. Pro-inflammatory cytokines such as TNF-α secreted by macrophages stimulate MSCs to produce and secrete prostaglandin E2 (PGE2). MSC-secreted PGE2 promotes lipid droplet biogenesis in macrophages and mediates macrophage polarization. PGE-2-mediated activation of the EP2 receptor induces additional COX-2 expression, further amplifying downstream PGE2 generation. The figure was created using BioRender.com (accessed on 14 September 2021).

Figure 2

Schematic representation of the function of NK cells in adipose tissue homeostasis. Both SAT and VAT express IL-15 and IL-15Rα, and IL-15 levels are higher in obese patients than in healthy patients. Obesity induces the upregulation of NKp46 (NCR1) ligand expression in adipocytes, which activates adipose tissue-resident NK cells to rapidly increase IFN-γ production, thereby promoting the accumulation of pro-inflammatory M1 macrophages and insulin resistance. Macrophages increase the production of chemokines and let them further enhance NK cells recruitment. The figure was created using BioRender.com (accessed on 14 September 2021).

Figure 3

Schematic representation of the link between innate lymphoid cells and the regulation of adipocyte thermogenesis and obesity in WAT. Tissue-resident ILC1 promotes macrophage activation and adipose fibrosis. ILC2 respond to epithelial cell-derived cytokine IL-33. Activated ILC2 enhances proliferation and commitment of beige adipocyte precursors, where IL-13 and eosinophil-derived IL-4 promote the growth of beige fat via IL-4 receptor signaling. Eosinophils are a major source of IL-4, and they migrate into adipose tissue and play a role in the maintenance of adipose M2 macrophages. The figure was created using BioRender.com (accessed on 14 September 2021).