Fig. 3

Overview of the communication network between the liver, bone, cardiovascular system, and gut mediated by EVs. (a) Within the liver-bone axis, EVs carry different substances to maintain bone health and influence hepatic metabolism. (b) The liver-cardiovascular axis focuses on revealing the effects of liver-derived EVs on the vascular endothelium and the heart, ranging from atherosclerosis and neovascularisation to cardiomyopathy. (c) The liver-gut axis unravels the role that gut microbiota-derived EVs play in the regulation of hepatic injury. Each axis represents a distinct spectrum of organ-liver interactions and provides a thorough understanding of the liver’s pivotal function in systemic physiology and pathology. Abbreviation: SIRT2: sirtuin 2; NF-κB: nuclear factor κB; LRG1: leucine-rich alpha-2-glycoprotein 1; HSP70: heat shock protein 70; HIRI: hepatic ischemia‒reperfusion injury; PI3K: phosphoinositide 3-kinase; mTOR: mammalian target of rapamycin; PDLCs: periodontal ligament cells; Fasn: fatty acid synthase; SCD-1: stearoyl-CoA desaturase 1; AMPK: adenosine monophosphate (AMP)-activated protein kinase; KLF4: kruppel-like factor 4; ABCA1: ATP-binding cassette transporter A1; LAMP1: lysosomal-associated membrane protein 1; NLRP3: NOD-like receptor pyrin domain-containing protein 3; AGPAT1: 1-acyl-sn-glycerol-3-phosphate acyltransferase; Arl2: ADP-ribosylation factor-like protein 2; TLR: toll-like receptor; PPAR: peroxisome proliferator-activated receptor; HSC: hepatic stellate cell; HFD: high-fat diet; cGAS: cyclic GMP–AMP synthase; STING: stimulator of interferon genes; NASH: nonalcoholic steatohepatitis; DIO: diet-induced obese; HMGB1: high-mobility group box protein 1