Newly discovered endocrine functions of the liver

Table 1 Classic endocrine functions of the liver

Hormone	Liver function	Target organ	Action on target organ	Alteration in liver diseases
25-hydroxyvitamin D	Direct production	Gut	Prohormone of calcitriol which stimulates gut calcium absorption	Decreased production resulting in low bone density
Insulin-like growth factor 1	Direct production	Ubiquitous	Promoting growth and differentiation and regulating nutrients metabolism	Decreased production resulting in dysmetabolism
Angiotensinogen	Direct production	Cardiovascular system	Precursor of angiotensin II which regulates aldosterone level. Both regulate vascular tone, sodium retention, and cardiac remodeling	Near-normal function
Thyroid hormone	Activation through T4 to T3 conversion; inactivation through degradation; TBG production	Ubiquitous	Increasing metabolism and energy expenditure	Low T3 syndrome
Glucagon-like peptide 1 (GLP-1)	Metabolism of GLP-1 via dipeptidyl peptidase-4(DPPIV)	Pancreas, gut, and brain	Stimulating insulin production, decreasing gut motility, and suppressing appetite	Increased DPPIV expression resulting in higher risk of diabetes
Sex hormones	Hormone metabolism and SHBG production	Ubiquitous	Numerous (details beyond this review)	Hypogonadism
Glucocorticoids	Hormone metabolism and CBG production	Ubiquitous	Numerous (details beyond this review)	Relative adrenal insufficiency
Mineralocorticoids	Hormone metabolism	Cardiovascular system	Maintaining electrolyte balance and blood pressure	Largely intact

TBG: Thyroxine binding globulin; CBG: Cortisol binding globulin; SHBG: Sex hormone binding globulin.

Table 2 Novel endocrine functions of the liver

Liver hormone	Target organ	Action on target organ	Alteration in liver diseases
Amino acids	Pancreatic α cells	Stimulate cell proliferation and glucagon secretion	Not studied yet
Betatrophin	Pancreatic β cells (?)	Stimulate cell proliferation (?)	Increased in cirrhosis
Fetuin	Skeletal muscle; Adipose tissue	Decrease insulin sensitivity; Reduce adiponectin expression	Elevated in nonalcoholic fatty liver disease
FGF21	Adipose tissue; Brain	Increase insulin sensitivity; Reduce food intake	Elevated in nonalcoholic fatty liver disease
Activin E	Adipose tissue	Increase fat oxidation	Increased in nonalcoholic fatty liver disease
Tsukushi	Adipose tissue	Increase thermogenesis	Increased in nonalcoholic fatty liver disease
GPNMB	Adipose tissue	Increase lipogenesis	Increased in nonalcoholic fatty liver disease

FGF21: Fibroblast growth factor 21; GPNMB: Glycoprotein nonmetastatic melanoma protein B.