A Potential Role of Adropin in Inflammatory Rheumatic Diseases-What Do We Know So Far?

Abstract

Adropin is a regulatory peptide hormone involved in metabolic homeostasis, cardiovascular protection, and immune modulation. Recent evidence suggests that adropin plays a role in the pathophysiology of autoimmune rheumatic diseases (ARDs) by influencing key processes such as endothelial function, oxidative stress, tissue fibrosis, and immune cell regulation. This review summarizes current knowledge on adropin's biological functions and its relevance in conditions including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren's syndrome, osteoarthritis, psoriasis, Behçet's disease, and Kawasaki disease. We discuss how adropin interacts with various signaling pathways and highlight its potential role in macrophage polarization, regulatory T cell activity, and fibrotic remodeling. Although data remain limited and sometimes conflicting, altered adropin levels have been observed across several ARDs, suggesting potential utility as a biomarker or therapeutic target. Further research is needed to clarify its clinical significance and translational potential in immune-mediated diseases.

Keywords: adropin; autoimmune diseases; biomarker; cardiovascular diseases; endothelial dysfunction; metabolic homeostasis; oxidative stress.

Figure 1

Structural schematic of adropin peptide. The Enho precursor protein consists of 76 amino acids. The N-terminal region (1–33 aa) forms the signal peptide, while the C-terminal region (34–76 aa) represents the functional adropin peptide (43 aa). The C-terminal part contains the putative receptorbinding region, implicated in interactions with GPR19, VEGFR2, and NB-3/Notch. Abbreviations: Enho: energy homeostasis-associated gene; aa: amino acids; GPR19: G-protein coupled receptor 19; VEGFR2: vascular endothelial growth factor receptor 2; NB-3/Notch: neuroblastoma suppressor of tumorigenicity 1/Notch signaling pathway.

Figure 2

Schematic representation of adropin’s biological functions in immune regulation, cardiovascular protection, and metabolic homeostasis. Adropin promotes polarization of macrophages toward the anti-inflammatory M2 phenotype and suppresses pro-inflammatory cytokine production by M1 macrophages. In the cardiovascular system, adropin enhances angiogenesis, improves blood flow, and inhibits TNF-α-induced endothelial cell apoptosis. In liver and adipose tissue, it improves glucose tolerance and insulin sensitivity, reduces hepatic glucose production and lipogenic gene expression, and decreases secretion of inflammatory mediators. Adropin also exerts antioxidant effects by limiting ROS-induced apoptosis of regulatory Tregs. Abbreviations: IL-10: interleukin 10; IL-6: interleukin 6; IL-12: interleukin 12; IL-23: interleukin 23; ROS: reactive oxygen species; TGF-β: transforming growth factor beta; TNF-α: tumor necrosis factor alpha; Treg: regulatory T cell.

Figure 3

Disease-specific pathways in autoimmune rheumatic diseases (ARDs). The schematic highlights key molecular and cellular mechanisms implicated in the pathogenesis of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Behçet’s disease (BD), primary Sjögren’s syndrome (pSjS), and Kawasaki disease (KD). Upward arrows (↑) indicate upregulation or increase, while downward arrows (↓) indicate downregulation or decrease. Abbreviations: AKT: protein kinase B; BD: Behçet’s disease; ERK1/2: extracellular signal-regulated kinase ½; ECs: endothelial cells; IL: interleukin; KD: Kawasaki disease; MPO-ANCA: myeloperoxidase anti-neutrophil cytoplasmic antibodies; NF-κB: nuclear factor kappa B; NO: nitric oxide; PPAR-γ: peroxisome proliferator activated receptor-γ; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus; SSc: systemic sclerosis; TNF-α: tumor necrosis factor α; Tregs: regulatory T cells; VEGFR2: vascular endothelial growth factor receptor 2; eNOS: endothelial nitric oxide synthase; pSjS—primary Sjögren’s syndrome; NLRP3: NOD-like receptor family pyrin domain-containing 3; CALs: coronary artery lesions; GLI1: glio-ma-associated oncogene homolog 1; Th17: T helper 17 cells.