Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions
Abstract
:1. Introduction
2. Discussion
2.1. Adipokines
2.2. Myokines
2.3. Hepatokines
2.4. Adipokines, Myokines and Hepatokines: Crosstalk and Metabolic Repercussions
3. Methods
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Adipokine | Stimulation for Its Increase | Metabolic Action | Reference |
---|---|---|---|
Leptin | Increase in fat mass. | In the immune system, it acts to increase pro-inflammatory cytokines. In the CNS, it promotes a decrease in food intake and an increase in global energy expenditure. In skeletal muscle, it acts in the absorption and oxidation of glucose and FFA. In the liver it increases the oxidation of fatty acids and reduces the accumulation of lipids. | [11] |
Adiponectina | Adrenergic beta signaling; increase in FGF21, IL-15, and irisin induced by physical exercise. | In the immune system it has anti-inflammatory actions. In the CNS it promotes an increase in food intake and a reduction in hypothalamic inflammation. In the liver and skeletal muscle, it increases fatty acid oxidation and insulin sensitivity. | [11] |
Resistin | Increase in fat mass. | Immune system: pro-inflammatory actions. It acts in endothelial dysfunction, CVD and inhibition of insulin signaling through the suppressor of cytokine signaling 3 (SOCS3). | [14,15] |
IL-6 | Activation of the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB). | Adipose tissue: proinflammatory action, and acts in inhibiting the expression of insulin receptor substrate 1 (IRS1) and glucose transporter type 4 GLUT4) in adipocytes. | [14] |
Asprosin | Induced by fasting and produced by white adipose tissue in obese people with DM2. | It increases food consumption and body weight and accelerates the production of liver glucose. | [16,17] |
Chemerin | Inflammatory and coagulation serine proteases. | It accentuates glucose intolerance and makes insulin signaling difficult. | [18] |
Omentin | Increase in FGF21 and dexamethasone. | Optimizes the action of insulin and, consequently, the absorption of glucose. It also acts as an anti-atherosclerotic factor. | [19] |
FGF21 | Exposure to cold and physical exercise. | It acts in the browning of WAT, lipid oxidation and thermogenesis, and stimulates the expression of adiponectin in the bloodstream. | [20] |
SFRP5 | Induced during the proliferation, differentiation and maturation of pre-adipocytes. | Regulates the expression of pro-inflammatory cytokines by inhibiting the Wingless-type family member 5a signaling (Wnt5a), non-canonical Wnt family. | [14,21] |
Lipocalin 2 | Low-level systemic inflammation in obese patients with metabolic syndrome. | Regulation of inflammation and the transport of fatty acids and iron. It is associated with CVD, vascular remodeling and instability of atherosclerotic plaques. | [22,23] |
Vaspin | Increase in fat mass. | Reduces the synthesis of pro-inflammatory cytokines. It improves glucose intolerance and insulin sensitivity and protects the vascular tissues from fatty acid-induced apoptosis. | [24,25] |
FSTL1 | It is expressed in large quantities by adipose tissue in the state of low-grade chronic inflammation. | Lower levels of FSTL1 are associated with super obesity due to loss of adipogenesis, increased maturated adipocytes, cellular senescence and anti-apoptotic FSLT1 reduction. It has a pro-inflammatory action and possible relationship with overweight and obesity. | [26] |
Sparc | Secreted by adipocytes, promoted adipose tissue fibrosis and inhibited adipogenesis. | Responsible for modulating the expression of pro-inflammatory cytokines that act on insulin resistance; and inhibits adipogenesis. | [23,27] |
CTRPs | Expressed in conditions of adiponectin and leptin deficiency and high body mass index. | Regulation of inflammatory processes of adipose tissue. Regulation of glucose and fat metabolism in peripheral tissues and food intake. | [23,28] |
FAM19A5 | Increase in fat mass. | Inhibits the proliferation and inflammation of vascular smooth muscle cell related to cardiovascular diseases through obesity. | [29] |
WISP1 | Obesity, adipogenesis and visceral fat abnormalities. | Stimulates the cytokine response in macrophages associated with tissue adipose; induces the proliferation of mesenchymal stem cells, which increases tissue adipose. | [30] |
Progranulin | Increase in fat mass associated with obesidade visceral, DM2 and dislipidemia. | It has anti-inflammatory properties. Hyper-progranulinemia is associated with insulin resistance and deficient insulin signaling. | [31,32] |
Nesfatin-1 | Unclear | Induces satiety, which promotes body weight reduction. It can also regulate gastric distension and motility via the melanocortin pathway in the central nucleus of amygdala. | [23] |
Visfatin | Increase in fat mass. | It produces adipocyte inflammation, insulin resistance and pancreatic beta cell dysfunction. | [33,34] |
Fetuin-A | Increase in fat mass. | Associated to insulin resistance and inflammation. | [35] |
ZAG | PPARγ, glucocorticoids, certain β3-adrenergic receptor agonists, thyroid hormones, and growth hormone (GH). | It acts in the acceleration of lipid metabolism, regulating enzymes of lipogenesis and lipolysis and stimulating production of adiponectin and BAT. | [36,37,38] |
Myokine | Stimulation for Its Increase | Metabolic Action | Reference |
---|---|---|---|
Irisin | Physical exercise. | Darkening of WAT, increases energy expenditure, improves insulin sensitivity and induces weight loss. | [8] |
BAIBA | Aerobic exercise | It acts in the Browning of adipose tissue, lipid oxidation and reduces insulin resistance. | [11] |
Myostatin | Sedentary lifestyle | Induces muscle mass loss associated with insulin resistance and fat accumulation in the liver. Facilitates body fat accumulation. | [45] |
Follistatin | Expressed in the context of physical activity, especially aerobic, resistance or high intensity training. | Inhibits the actions of myostatin, contributing to hypertrophy of skeletal muscle and reduction in fat mass, with consequent optimization of glucose uptake. | [13] |
FGF21 | Physical exercise. | Increases insulin sensitivity, reduces plasma glucose and acts on lipolysis. | [57] |
Apelin | Resistance exercises. | Anti-inflammatory role. It acts in the formation of new vessels and in the control of cardiac muscles and blood pressure. | [58] |
Myonectin | Resistance exercises. | Increases the uptake of lipids by adipose tissue and liver, decreasing the plasma concentration of FFA. | [20] |
IL-6 | Physical exercise. | Pro-inflammatory cytokine associated with insulin resistance in obesity. | [59] |
IL-15 | Released after acute episodes of aerobic exercise. | Anti-inflammatory properties by inhibiting TNF-α expression; contributes to muscle hypertrophy, reduction in visceral adipose tissue and optimizes insulin action. | [14] |
Sparc | Resistance exercises and muscle hypertrophy. | Inhibition of adipose tissue formation, increased insulin release and optimization of glucose uptake. | [60] |
BDNF | Muscle and brain induced after exercise. | When produced by muscle, it increases sensitivity to insulin. | [61] |
METRNL | Resistance exercises. | Anti-inflammatory role. Contributes to the browning of WAT and energy expenditure through the oxidation of glucose and FFA. | [62] |
Decorin | Expressed in response to acute or chronic endurance training | Binds to myostatin by inhibiting its actions. As a consequence, it induces hypertrophy in the skeletal muscle. | [63] |
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] |
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de Oliveira dos Santos, A.R.; de Oliveira Zanuso, B.; Miola, V.F.B.; Barbalho, S.M.; Santos Bueno, P.C.; Flato, U.A.P.; Detregiachi, C.R.P.; Buchaim, D.V.; Buchaim, R.L.; Tofano, R.J.; et al. Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions. Int. J. Mol. Sci. 2021, 22, 2639. https://doi.org/10.3390/ijms22052639
de Oliveira dos Santos AR, de Oliveira Zanuso B, Miola VFB, Barbalho SM, Santos Bueno PC, Flato UAP, Detregiachi CRP, Buchaim DV, Buchaim RL, Tofano RJ, et al. Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions. International Journal of Molecular Sciences. 2021; 22(5):2639. https://doi.org/10.3390/ijms22052639
Chicago/Turabian Stylede Oliveira dos Santos, Ana Rita, Bárbara de Oliveira Zanuso, Vitor Fernando Bordin Miola, Sandra Maria Barbalho, Patrícia C. Santos Bueno, Uri Adrian Prync Flato, Claudia Rucco P. Detregiachi, Daniela Vieira Buchaim, Rogério Leone Buchaim, Ricardo José Tofano, and et al. 2021. "Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions" International Journal of Molecular Sciences 22, no. 5: 2639. https://doi.org/10.3390/ijms22052639