Newly discovered endocrine functions of the liver

Abstract

The liver, the largest solid visceral organ of the body, has numerous endocrine functions, such as direct hormone and hepatokine production, hormone metabolism, synthesis of binding proteins, and processing and redistribution of metabolic fuels. In the last 10 years, many new endocrine functions of the liver have been discovered. Advances in the classical endocrine functions include delineation of mechanisms of liver production of endocrine hormones [including 25-hydroxyvitamin D, insulin-like growth factor 1 (IGF-1), and angiotensinogen], hepatic metabolism of hormones (including thyroid hormones, glucagon-like peptide-1, and steroid hormones), and actions of specific binding proteins to glucocorticoids, sex steroids, and thyroid hormones. These studies have furthered insight into cirrhosis-associated endocrinopathies, such as hypogonadism, osteoporosis, IGF-1 deficiency, vitamin D deficiency, alterations in glucose and lipid homeostasis, and controversially relative adrenal insufficiency. Several novel endocrine functions of the liver have also been unraveled, elucidating the liver’s key negative feedback regulatory role in the pancreatic α cell-liver axis, which regulates pancreatic α cell mass, glucagon secretion, and circulating amino acid levels. Betatrophin and other hepatokines, such as fetuin-A and fibroblast growth factor 21, have also been discovered to play important endocrine roles in modulating insulin sensitivity, lipid metabolism, and body weight. It is expected that more endocrine functions of the liver will be revealed in the near future.

Keywords: Liver; Endocrine function; Hormone; Amino acids; Hepatokine; Fibroblast growth factor 21

Core Tip: The liver has many newly discovered endocrine functions, most of which are in regulating metabolism, underscoring the functioning of the liver as a major metabolic organ. Convincing evidence has shown that the liver regulates endocrine functions in mineral and fuel metabolism, especially in the metabolism of glucose and lipids via hepatokines and amino acids via negative feedback on pancreatic α cells. As research into the endocrine function of the liver is a rapidly evolving field, controversial findings often exist; caution needs to be taken when interpreting novel findings to avoid over-simplification of complex metabolic processes and premature allocation of research resources.