Growth differentiation factor 15 (GDF15) also known as macrophage inhibitory cytokine-1 (MIC-1) is a member of the TGFβ superfamily. GDF15 decreases food intake via glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL) by a presumably central mechanism. GDF15 is induced under stress conditions to maintain homeostasis in obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, cardiovascular disease and cancer. Among these conditions, obesity is associated with adipose inflammation and dysregulated immune cell function. Metabolic syndrome causes an excess of M1 over M2 macrophages by CD8+ T cells in white adipose tissue. Adipose infiltrating macrophages secrete inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, leading to glucose intolerance and insulin insensitivity. Administration of recombinant IL-4, a Th2 cytokine, induces adipose tissue to secrete GDF15 and reduce weight gain. GDF15 also increases M2 macrophage polarization and limits adipose tissue inflammation. GDF15 reduces markers of inflammation in obese mice serum and white adipose tissue. GDF15 also reduces severe fibrosis and infiltration of inflammatory CD4+ and CD8+ T cells, monocytes and neutrophils in liver. GDF15 also limits inflammatory cells infiltration by interfering β2-integrin activation. Immune cells have low expression of GFRAL as a GDF15 receptor. GDF15 effect mechanism on immune cells to reduce inflammation is not elucidated. Understanding the relevant mechanism will be significant for the therapeutic potential of GDF15. Anti-inflammatory GDF15 effects on adipose inflammation and immune cells were summarized in this review.
Anahtar Kelimeler: Growth differentiation factor 15, Obesity, Macrophage, Inflammation
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