Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions

Abstract

Adipose, skeletal, and hepatic muscle tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines. These biomarkers can be harmful or beneficial to an organism and still perform crosstalk, acting through the endocrine, paracrine, and autocrine pathways. This study aims to review the crosstalk between adipokines, myokines, and hepatokines. Far beyond understanding the actions of each biomarker alone, it is important to underline that these cytokines act together in the body, resulting in a complex network of actions in different tissues, which may have beneficial or non-beneficial effects on the genesis of various physiological disorders and their respective outcomes, such as type 2 diabetes mellitus (DM2), obesity, metabolic syndrome, and cardiovascular diseases (CVD). Overweight individuals secrete more pro-inflammatory adipokines than those of a healthy weight, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases. Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), resistin, and chemerin. Fibroblast growth factor FGF21 acts as a beta-oxidation regulator and decreases lipogenesis in the liver. The crosstalk mentioned above can interfere with homeostatic disorders and can play a role as a potential therapeutic target that can assist in the methods of diagnosing metabolic syndrome and CVD.

Keywords: adipokines; cardiovascular diseases; hepatokines; metabolism; myokines.

Figure 1

Effects of leptin and adiponectin on the metabolism of the central nervous system, skeletal muscle, and liver. Black arrows represent the flow in metabolism; blue arrow represents increased action; red arrow represents decreased action; + represents activation; x represents inhibition. FFA: free fatty acid; NPY: neuropeptide Y; SkM: skeletal muscle; WAT: white adipose tissue.

Figure 2

General actions of the main myokines in the metabolism. Physical exercise is the stimulus for the release of most myokines, while it inhibits myostatin release. The actions of these myokines are outlined as shown in the figure above. + represents activation; − represents inhibition; blue arrows reflect the actions of myokines stimulated by exercise; red arrows reflect the actions of myostatin; black arrows represent stimulation of physical exercises on skeletal muscle and the release of myokines. IL-6: interleukin-6; IL-15: interleukin-15; BDNF: brain-derived neurotrophic factor; FGF-21: fibroblast growth factor-21; SkM: Skeletal Muscle; WAT: White adipose tissue.

Figure 3

Main functions of hepatokines and their respective activities. [↓] represents the decrease and [↑] represents the increase; black arrows represent the release of hepatokines and their actions on each specified target. FGF-21: fibroblast growth factor-21; ANGPTL4: Angiopoietin-Like 4; LECT2: Leukocyte cell-derived chemotaxin 2; SkM: Skeletal Muscle; WAT: white adipose tissue; CVD: Cardiovascular disease e IR: Insulin Resistance.

Figure 4

An overview of the crosstalk between adipokines, myokines and hepatokines. Adipokines are represented in brown, myokines in green and hepatokines in blue. The arrows that are indicating upward indicate an increase and downward decrease. (x) represents inhibition and (+) activation. Blue arrows are associated with benefits, while red arrows are associated with harm aspects. IL: interleukin; BDNF: brain-derived neurotrophic factor; FGF-21: fibroblast growth factor-21; SkM: skeletal muscle; WAT: white adipose tissue; CVD: cardiovascular disease; LECT2: leukocyte cell-derived chemotaxin 2; FFA: free fatty acid.