Table 3.
Main characteristics of the hepatokines.
| Hepatokine | Stimulation for Its Increase | Metabolic Action | Reference |
|---|---|---|---|
| Fetuin A | Related to obesity, especially NAFLD and the increase in VAT. | It causes injury to the pancreas B cells and insulin resistance and works as a predictor of DM2. | [59,65] |
| Fetuin B | Increased in humans with steatosis and is related to insulin resistance. | Promotes insulin resistance and the development of diabetes. | [66] |
| Adropin | Regulated positively with food intake and weight reduction. | Stimulates lipolysis throughout the body, reducing weight gain and hepatic steatosis, optimizing the action of insulin and preventing the progression of atherosclerosis. | [67] |
| Activin E | High with obesity and NAFLD. | Reduces lipolysis and increase fat accumulation in adipocytes. | [68,69] |
| SHBG | Weight reduction and healthy lifestyle. | Transport of sex steroids to its target tissues. The increase in insulin sensitivity, stimulated by SHBG, is not yet fully cleared. | [70,71] |
| Chemerin | Produced in a state of obesity, dyslipidemia, metabolic syndrome and DM2. | Impairment of glucose homeostasis, increases insulin resistance and fat accumulation in the liver. | [14,72] |
| Selenoprotein | Associated with metabolic diseases, insulin resistance and hypoxia. | Attenuates fat loss induced by exercise. In hypoxia, insulin resistance and fat accumulation in adipose tissue increases. | [11,73] |
| Folistatin | It increases when the glucagon-to-insulin ratio rises in situations of aerobic exercise and resistance. | Actions on skeletal muscle hypertrophy, which increases glucose capture, and on the expression of thermogenic genes in murine adipocytes. | [11,74] |
| FGF21 | Aerobic exercises | It increases the sensitivity to insulin, the oxidation of fatty acids in the liver, decreases the production of glucose and the development of hepatic steatosis. | [11] |
| ANGPTL4 | Physical exercise | Stimulates lipolysis and decreases the action of the LPL enzyme on white adipose tissue. Inhibits pancreatic lipase and consequently decreases fat absorption. | [11,75] |
| ANGPTL4 | Food signals | Mediates food-driven resetting of circadian clock in mice liver; associated with regulation of inflammation, lipid metabolism, cancer cell invasion, and hematopoietic stem activity | [76] |
| LECT2 | Associated with metabolic stress | Impairment of insulin signal transduction and increases the appearance of pro-inflammatory cytokines. | [67] |
| Hepassocin | Elevated in pre-diabetes, DM2, and NAFLD. | Participates in the regulation of hepatocyte proliferation and liver regeneration. | [67,77] |
| Tsukushi | In response to NAFLD. | Reduces HDL-c cholesterol; reduced cholesterol efflux capacity, and reduces cholesterol-to–bile acid conversion in the liver. | [78] |
ANGPTL4: angiopoietin-like 4; DM2: diabetes mellitus typo 2; FGF21: fibroblast growth factor 21; LPL: lipoprotein lipase; LECT2: leukocyte cell-derived chemotaxin 2; NAFLD: nonalcoholic fatty liver disease; SHBG: sex hormone-binding globulin; VAT: visceral adipose tissue.