Adipokine

Adipokines are a group of peptide hormones (polypeptides) that are predominantly produced and secreted in the adipocytes of adipose tissue. Currently, more than 600 adipokines have been described in the human body with different biological properties. In the general classifications, a distinction is made between pro-inflammatory and anti-inflammatory adipokines. The upregulation of pro-inflammatory adipokines leads to the development of a chronic, low-grade inflammatory state and contributes to metabolic dysfunction (Kovács D et al. 2020).

Many adipins transmit their signals via specific receptors. Others, however, act via receptors of various cytokines and hormones Kovács D et al. 2020). Adiponectin, for example, exerts its effect via two receptors: AdipoR1 is expressed by skeletal muscle and other tissues, AdipoR2 by hepatocytes. Leptin, for example, exerts its biological effect via the leptin receptor (Ob-R), which belongs to the type I cytokine receptor family (Gorska E et al. 2010). The receptors for chemerin, monocyte chemoattractant protein-1 (MCP-1) and apelin are G protein-coupled receptors/GPRs (Kovács D et al. 2020), while the effects of resistin, visfatin and fetuin-A are mediated via the insulin receptor and a pattern recognition receptor (Toll-like receptor /TLR) (Fasshauer, M et al. 2015).

Adiponectin receptors are the members of the progestin and AdipoQ receptor family, while the zinc-α2-glycoprotein (ZAG) is a β2-adrenoreceptor agonist. SERPINE1 binds to the urokinase receptor, lipocalin 2 (LCN2) may act via its own specific 24p3 receptor, and in the case of omentin-1, no specific receptor has yet been identified.

The best-researched adipokines to date include:

• Adiponectin (CTRP-1)
• apelin
• Asprosin
• chemerin
• CTRP-3/CTRP-4 (C1q/TNF-related proteins) (see CTRP family below)
• Interleukin-6
• leptin
• Monocyte chemotactic protein-1 (MCP-1/CCL2)
• omentin
• Plasminogen activator inhibitor-1 (PAI-1)
• Progranulin
• Retinol-binding protein 4 (RBP4)
• Tumor necrosis factor-alpha
• vaspin
• visfatin
• Zinc-alpha-2-glycoprotein (ZAG)

Adipokines are involved in important physiological functions such as carbohydrate and fat metabolism, insulin sensitivity, appetite regulation, inflammatory processes and cardiac functions. Adipokines act as signaling molecules. In the case of severe obesity, adipocyte function is deregulated and adipokines are produced in altered quantities. A diabetogenic, pro-inflammatory and atherogenic adipokine pattern often develops with the increase in adipose tissue in obesity. Indirect evidence of the importance of adipokines for energy and glucose homeostasis is also provided by the fact that insulin-sensitizing drugs such as thiazolidinediones and metformin on the one hand and insulin resistance-inducing hormones such as catecholamines and glucocorticoids on the other influence the regulation of adipokines.

Rosacea: Both metabolic syndrome and insulin resistance can be associated with rosacea. Leptin, adiponectin, resistin, SERPINE1 and visfatin were detectable in the sebaceous glands of rosacea skin, suggesting that sebaceous glands may contribute to the development of the characteristic inflammatory milieu in rosacea through the secretion of these adipokines.

Acne vulgaris: Although some papers showed that there was no significant difference between circulating leptin, adiponectin and RBP4 levels in patients with acne vulgaris, others found higher leptin and lower adiponectin serum concentrations. Interestingly, isotretinoin increased adiponectin levels (Tsai TY et al. 2019) and decreased leptin levels, which are already significantly lower at basal levels in acne patients compared to the control group (Kovács D et al. 2020). Remarkably, isotretinoin therapy for acne has no significant effect on the degree of insulin resistance.

Psoriasis: The role of adipokines in psoriasis has not yet been definitively clarified. As far as the anti-inflammatory adipokines are concerned, serum levels of adiponectin and omentin were significantly lower in psoriatic patients compared to healthy controls. Studies have found a negative correlation with the severity of the disease (Kovács D et al. 2020). RBP-4(retinol-binding protein 4) levels were significantly higher in patients. Systemic treatment can lower these levels. RBP-4 could thus serve as an important indicator for diagnosis and efficacy evaluation in these patients (Gao G et al. 2023).

Systemic scleroderma: The adipokines chemerin and visfatin are proinflammatory cytokines and could serve as novel markers of inflammation in systemic scleroderma. Chemerin could also establish a link between inflammation and skin and lung fibrosis (Sawicka K et al. 2019).

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