Organ-organ communication: The liver's perspective

Abstract

Communication between organs participates in most physiological and pathological events. Owing to the importance of precise coordination among the liver and virtually all organs in the body for the maintenance of homeostasis, many hepatic disorders originate from impaired organ-organ communication, resulting in concomitant pathological phenotypes of distant organs. Hepatokines are proteins that are predominantly secreted from the liver, and many hepatokines and several signaling proteins have been linked to diseases of other organs, such as the heart, muscle, bone, and eyes. Although liver-centered interorgan communication has been proposed in both basic and clinical studies, to date, the regulatory mechanisms of hepatokine production, secretion, and reciprocation with signaling factors from other organs are obscure. Whether other hormones and cytokines are involved in such communication also warrants investigation. Herein, we summarize the current knowledge of organ-organ communication phenotypes in a variety of diseases and the possible involvement of hepatokines and/or other important signaling factors. This provides novel insight into the underlying roles and mechanisms of liver-originated signal transduction and, more importantly, the understanding of disease in an integrative view.

Keywords: Cytokine; Disease mechanism.; Hepatokine; Liver; Organ communication.

Figure 1

Effective communicating molecules, mostly hepatokines and cytokines, from the liver to other major distant organs under physiological and pathological conditions. AGT, angiotensinogen; AMBP, alpha-1-microglobulin; ANGPTL, angiopoietin-like protein; FGF, fibroblast growth factor; IGF, insulin growth factor; IGFBP, insulin growth factor binding protein (Created with BioRender.com).

Figure 2

Distant communicating mechanisms, including neuronal, hormonal, metabolic, and other factors, between major organs under pathological conditions. 5-HT, 5-hydroxytryptamine; AIH, auto-immune hepatitis; ANGPTL, angiopoietin-like protein; DILI, drug-induced liver injury; FFA, free fatty acids; GI, gastrointestinal; IgA, immunoglobulin A; I/R injury, ischemia/reperfusion injury; PBA, primary bile acids; RAS, renin-angiotensin system (Created with BioRender.com).