Adipokines: New Potential Therapeutic Target for Obesity and Metabolic, Rheumatic, and Cardiovascular Diseases

Abstract

Besides its role as an energy storage organ, adipose tissue can be viewed as a dynamic and complex endocrine organ, which produces and secretes several adipokines, including hormones, cytokines, extracellular matrix (ECM) proteins, and growth and vasoactive factors. A wide body of evidence showed that adipokines play a critical role in various biological and physiological functions, among which feeding modulation, inflammatory and immune function, glucose and lipid metabolism, and blood pressure control. The aim of this review is to summarize the effects of several adipokines, including leptin, diponectin, resistin, chemerin, lipocalin-2 (LCN2), vaspin, omentin, follistatin-like 1 (FSTL1), secreted protein acidic and rich in cysteine (SPARC), secreted frizzled-related protein 5 (SFRP5), C1q/TNF-related proteins (CTRPs), family with sequence similarity to 19 member A5 (FAM19A5), wingless-type inducible signaling pathway protein-1 (WISP1), progranulin (PGRN), nesfatin-1 (nesfatin), visfatin/PBEF/NAMPT, apelin, retinol binding protein 4 (RPB4), and plasminogen activator inhibitor-1 (PAI-1) in the regulation of insulin resistance and vascular function, as well as many aspects of inflammation and immunity and their potential role in managing obesity-associated diseases, including metabolic, osteoarticular, and cardiovascular diseases.

Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions

“…Lipocalin 2 (LCN2), also associated with neutrophil gelatinase-associated lipocalin (NGAL), is a glycoprotein identified as the cytokine of adipose tissue present in low-level systemic inflammation in obese patients with metabolic syndrome. Its receptors, the megalin/glycoprotein GP330 and SLC22A17 or 24p3R, the solute carrier family 22 members 17 binding mouse LCN2, are involved in regulating inflammation and the transport of fatty acids and iron [ 23 ]. High levels of LCN2 are associated with CVD, vascular remodeling, and instability of atherosclerotic plaques by regulating the metalloproteinase activity (MMP-9) [ 22 ].…”

“…The secreted acidic protein rich in cysteine (SPARC), known as BM40 or osteonectin, modulates the expression of pro-inflammatory cytokines involved in insulin resistance and adipogenesis [ 23 ]. Although initially found in bone tissue, SPARC is expressed in most tissues, being one of the proteins in the extracellular matrix of adipose tissue.…”

“…Its action occurs through several receptors, including adipoR1 and adipoR2. Studies in mice have demonstrated that the expression of CTRP6, regulated for adipose tissue in obesity and diabetes, is secreted by stromal vascular cells and macrophages, and its increased expression substantially compromised the disposal of glucose in peripheral tissues [ 23 ]. On the other hand, the family with sequence similarity to 19 member A5 (FAM19A5), initially demonstrated in mice, is released by adipose tissue, and its expression is reduced in obesity.…”

“…In rodents, injections of nesfatin-1 inhibit food intake, and its lack in the brain causes an increase in appetite, fat, and body weight. In addition, nesfatin-1 can regulate gastric distension and motility via the melanocortin pathway in the central nucleus of the amygdala [ 23 ].…”

Exploring the Crosstalk between Hydrostatic Pressure and Adipokines: An In Vitro Study on Human Osteoarthritic Chondrocytes

“…Interestingly, obesity induces a low-grade chronic inflammatory state mainly through the production of inflammatory mediators, such as adipokines, cytokines, chemokines, and complement factors by white adipose tissue [ 17 ]. Adipokines, including adiponectin, leptin, resistin, chemerin, and visfatin, are metabolically active proteins that emerged as crucial regulators of immune system response and chronic inflammation [ 18 , 19 ]. Their critical role in the pathogenesis of immune-mediated rheumatic diseases and degenerative OA has been amply demonstrated [ 20 , 21 , 22 , 23 ].…”