Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation

Abstract

Chronic low-grade inflammation in adipose tissue (AT) is a hallmark of obesity and contributes to various metabolic disorders, such as type 2 diabetes and cardiovascular diseases. Inflammation in ATs is characterized by macrophage infiltration and the activation of inflammatory pathways mediated by NF-κB, JNK, and NLRP3 inflammasomes. Adipokines, hepatokines and myokines - proteins secreted from AT, the liver and skeletal muscle play regulatory roles in AT inflammation via endocrine, paracrine, and autocrine pathways. For example, obesity is associated with elevated levels of pro-inflammatory adipokines (e.g., leptin, resistin, chemerin, progranulin, RBP4, WISP1, FABP4, PAI-1, Follistatin-like1, MCP-1, SPARC, SPARCL1, and SAA) and reduced levels of anti-inflammatory adipokines such as adiponectin, omentin, ZAG, SFRP5, CTRP3, vaspin, and IL-10. Moreover, some hepatokines (Fetuin A, DPP4, FGF21, GDF15, and MANF) and myokines (irisin, IL-6, and DEL-1) also play pro- or anti-inflammatory roles in AT inflammation. This review aims to provide an updated understanding of these organokines and their role in AT inflammation and related metabolic abnormalities. It serves to highlight the molecular mechanisms underlying the effects of these organokines and their clinical significance. Insights into the roles and mechanisms of these organokines could provide novel and potential therapeutic targets for obesity-induced inflammation.

Keywords: adipokines; adipose tissue; hepatokines; inflammation; myokines.

Figure 1

Summarized mechanisms of the organokines in regulation of adipose tissue inflammation under obesity condition. Adipocytes (A) and macrophages (B) are the primary target cells. Red colors symbols reflect pro-inflammatory organokines, blue symbols reflect anti-inflammatory organokines. Red upward arrows reflect an increase of the organokines in obesity and blue downward arrows reflect decreased level of organokines in obesity. The overall roles of organokines has been categorized into 3 groups: chemokine, regulation of macrophage polarization and regulation of inflammatory pathways (Fig 1, box 1). CTRP3: C1q/TNF-related proteins; DEL-1: Developmental endothelial locus-1; DPP4: Dipeptidyl peptidase 4; FABP4: Fatty acid binding protein 4; FFA: Free Fatty Acids; FGF21: Fibroblast growth factor-21; GDF15: Growth differentiation factor 15; LCN2: Lipocalin-2; MCP-1: Monocyte chemoattractant protein-1; PAI-1: Plasminogen activator inhibitor 1; RBP4: Retinol-binding protein-4; SAA: serum amyloid A; SFRP5: Secreted frizzled-related protein 5; SPARC: Secreted protein acidic and rich in cysteine; WISP1: Wingless‐type (Wnt)-inducible signaling pathway protein-1.