The regulatory role of metabolic organ-secreted factors in the nonalcoholic fatty liver disease and cardiovascular disease

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  Figure 1. Complex mechanism between metabolic organ-secreted factors and increased risk of NAFLD. Metabolic organ-secreted factors, such as hepatokines, adipokines, cytokines, chemokines, complements, extracellular vesicles and gut-derived factors, promote the pathogenesis of NAFLD via a variety of signaling pathways and mechanisms, including disturbance lipid and glucose metabolism, oxidative stress, chronic inflammation and so on. ACC, acetyl-CoA carboxylase; Akt, protein kinase B; AMPK, adenosine monophosphate-activated protein kinase; ANGPTLs, angiopoietin-like proteins; BBOX, γ-butyrobetaine hydroxylase; CCL2, chemokine ligand 2; CCL5, chemokine ligand 5; CCL20, chemokine ligand 20; CCN2, connective tissue growth factor; Col1α1, collagen type I α 1; ERK, extracellular signal-regulated kinase; EVs, extracellular vesicles; FGF21, fibroblast growth factor 21; FXR, farnesoid × receptor; GDF15, growth differentiation factor 15; GLP-1, glucagon-like peptide-1; GLUT4, glucose transport 4; GPCRs, G-protein-coupled receptors; GSH-Px, glutathione peroxidase; IL-6, interleukin-6; IR, insulin resistance; JAK2, Janus kinase 2; JNK, c-Jun N-terminal kinase; LAMP1, lysosomal associated membrane…

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  Figure 2. The regulatory roles of metabolic organ-secreted factors linking NAFLD and CVD. AF, atrial fibrillation; ANGPTLs, angiopoietin-like proteins; CCL2, chemokine ligand 2; CRP, C-reactive protein; CVD, cardiovascular disease; ERK, extracellular signal-regulated kinase; FGF21, fibroblast growth factor 21; JNK, c-Jun N-terminal kinase; GPCRs, G-protein-coupled receptors; ICAM-1, intercellular adhesion molecule-1; IL-1, interleukin-1; IL-1β, interleukin-1β; IL-6, interleukin-6; IR, insulin resistance; LDL, low-density lipoprotein; LECT2, leukocyte cell-derived chemotaxin 2; LPL, lipoprotein lipase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemotactic protein 1; NAFLD, nonalcoholic fatty liver disease; NLRP3, NOD-like receptor protein 3; PAI-1, plasminogen activator inhibitor-1; RAAS, renin-angiotensin system; RBP4, retinol binding protein-4; SCFAs, short-chain fatty acids; Sep, selenoprotein P; SERCA2a, sarco-endoplasmic reticulum Ca2+ ATPase 2a; SMC, smooth muscle cell; SNS, sympathetic nervous system; SREBP2, sterol regulatory element-binding protein-2; TGF-α, transforming growth factor-α; TMAO, trimethylamine N-oxide; VCAM-1, vascular cell…