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.

A Comparison of Gene Expression Profiles of Rat Tissues after Mild and Short-Term Calorie Restrictions

“…The liver, muscle, adipose tissue, intestine, and brain are main organs with pivotal roles in the metabolism and absorption of food and nutrients. These organs, which are known to communicate with each other [ 6 , 7 ], are significant for the regulation of homeostasis by nutrient sensing. In addition, all organs and tissues are affected by CR, a major protective factor for most age-related diseases in humans.…”

Beyond the Liver: Liver-Eye Communication in Clinical and Experimental Aspects

“…The interaction between the liver and the eye is reflected in the molecular communication by their secretory factors and their associated cytokines (Figure 1). "Hepatokines" are certain signaling proteins that are secreted exclusively or predominantly by the liver (Wang et al, 2021),which are mostly delivered to liver or other distant organs through the human circulation system, and are involved in regulating diseases such as metabolic, inflammatory disease (Meex and Watt, 2017). Similarly, some factors secreted by the eyes also remotely affect the state of the liver.…”

“…Angiopoietin-like proteins 4 (ANGPTL-4) and ANGPTL-8 are a class of proteins mainly secreted by the liver, and a very small part is produced by adipose tissue and muscle (Wang et al, 2021). ANGPTL4 transcript in adipose tissue accounts for only 10% of liver in human (Romeo et al, 2009).…”

“…With the development of modern medical physiology and pathology, it has been discovered that there are some communication links between the human body's organs and organs or tissues that are established with the help of endocrine, immune and other systems, which are considered to be important for maintaining homeostasis and achieving physiological functions. The connection between the eyes and the liver has been discovered and valued in many studies (Wang et al, 2021), which is achieved through a variety of pathways including metabolism, inflammation, oxidative stress, and immunity. In addition, clinically, some possible connections have been revealed in the occurrence, development and outcome of some liver diseases and ocular diseases, such as Nonalcoholic fatty liver disease (NAFLD) and Diabetic retinopathy (DR).…”

The Hepatic Stellate Cells (HSTCs) and Adipose-derived Mesenchymal Stem Cells (ASCs) Axis as a Potential Major Driver of Metabolic Syndrome – Novel Concept and Therapeutic Implications

“…Fibroblast growth factor-21 (FGF21) represents one of the most common liver-derived hormones, that positively regulate human metabolism and energy homeostasis. FGF21 predominantly acts on glucose and lipids metabolism by increasing the oxidation of fatty acids as well as insulin sensitivity, while decreasing gluconeogenesis in liver [11]. In adipose tissue, liver FGF21 has been demonstrated to substantially modulate lipolysis in both in vivo and in vitro models, whereas stimulating glucose uptake in human adipocytes through the GLUT1 and adiponectin expression increment.…”