Table 1.
Known hepatokines and their role in metabolism and disease.
| Hepatokine | Target organs | Metabolic roles | Human serum concentration in insulin resistance | Reference |
|---|---|---|---|---|
| Activin-E | Liver and adipose tissue | Increases energy expenditure and insulin sensitivity through brown and beige adipocyte activation | Increased | [[28], [29], [30]] |
| ANGPTL3 | Liver, adipose tissue, skeletal muscle, and brain cardiac tissue | Regulates plasma triglycerides by inhibiting LPL and increasing insulin resistance Dissociates active dimeric LPL to monomers |
Increased | [37,39,40,42,45,46] |
| ANGPTL4 | Liver, adipose tissue, skeletal muscle, and brain | Enhances hepatic glucose production and promotes disruption of glucose metabolism | Debated | [59,60,[67], [68], [69], [70], [71],74,75,78,83] |
| ANGPTL6 | Various peripheral tissues | Regulates glucose and lipid metabolism and insulin sensitivity | Increased | [89,91,92,94] |
| ANGPTL8 | Liver, adipose tissue, skeletal muscle, and brain cardiac tissue | Regulates plasma triglycerides by binding ANGPTL3, inhibiting LPL, and increasing insulin resistance Downregulates ANGPTL4 |
Debated | [38,59,81,100] |
| Fetuin-A | Liver and skeletal muscle | Promotes adipose tissue inflammation and insulin resistance Inhibits liver and skeletal muscle insulin receptor phosphorylation |
Increased | [12,[107], [108], [109], [110], [111], [112],117,119] |
| FGF21 | Adipose tissue and brain | Regulates energy homeostasis by increasing energy expenditure, improving insulin sensitivity, decreasing plasma triglycerides, and decreasing sugar intake | Increased | [129,[133], [134], [135], [136], [137], [138], [139], [140], [141], [142],169] |
| Follistatin | Various peripheral tissues | Serves as a novel energy deprivation signal | Increased | [177,182,[188], [189], [190]] |
| GDF15 | Adipose tissue, skeletal muscle, liver, and brain | Regulates energy homeostasis by mediating increased energy expenditure and reduced body weight gain | Increased | [195,199,200,[202], [203], [204], [205]] |
| Hepassocin | Liver, adipose tissue, and skeletal muscle | Promotes insulin resistance and hepatic lipid accumulation | Increased | [29,[208], [209], [210]] |
| IGF1 | Skeletal muscle | Improves insulin sensitivity in skeletal muscle | Decreased | [214,219,[225], [226], [227], [228], [229]] |
| LECT2 | Skeletal muscle, liver, and adipose tissue | Impairs insulin signaling and promotes hepatic lipid accumulation | Increased | [230,239,241] |
| Lipocalin 13 | Adipose tissue and liver | Regulates glucose metabolism by enhancing insulin sensitivity and regulating expression of gluconeogenic genes | Decreased | [245, 248, 249] |
| Selenoprotein-P | Various peripheral tissues | Impairs insulin signaling and augments glucose metabolism | Increased | [251,252] |
| SMOC1 | Liver and skeletal muscle | Improves glycemic control by suppressing hepatic glucose output and skeletal muscle glucose uptake and inhibiting hepatic glucagon-stimulated insulin signaling | Decreased | [257,259] |
| Tsukushi | Various peripheral tissues | Likely improves energy homeostasis by regulating thermogenesis Regulates cholesterol homeostasis |
Increased | [[260], [261], [262], [263]] |