# Adipolin, Chemerin, Neprilysin and Metabolic Disorders Associated with Obesity
## 1 Introduction  
Obesity disrupts the homeostasis of the secretion of adipokines, which are biologically active molecules secreted by adipose tissue. Adipokines have many essential functions in the human body--among others, they regulate metabolic and inflammatory processes and participate in adipogenesis [1; 2; 3]. The number of newly discovered adipokines is systematically increasing, and due to their pleiotropic effects, they have become an interesting research area. High hopes lie in their use as early biomarkers associated with the development of metabolic syndrome in overweight individuals.  
The adipokines analyzed in this study--adipolin, chemerin, and neprilysin--were chosen due to their impact on tissue metabolism and insulin sensitivity [3; 4]. Their mechanisms of action are not fully understood, and the results of studies determining the relationships between their blood concentrations and anthropometric and metabolic parameters in humans are inconclusive. According to scientific reports, adipolin has potentiallybeneficial metabolic effects, while the other two--neprilysin and chemerin--show adverse metabolic effects.  
Adipolin is one of the few adipokines with anti-inflammatory and insulin resistance-reducing effects. The FAM132A gene encodes adipolin (C1q/TNF-related protein 12, CTRP12). Overexpression of the FAM132A gene in obese mice improves insulin sensitivity, as reflected by a reduction in fasting glucose levels, a decrease in the Homeostasis Model Assessment--Insulin Resistance (HOMA-IR) score, or improved glucose tolerance [5]. In contrast, gene ablation increases body weight and insulin resistance in male mice with high-fat diets. For females, the opposite effect--a decrease in body weight despite a high-fat diet--has been observed [6]. Humans with a fragment of chromosome 1 (1p36.33) that includes the FAM132A locus deletion developed hyperplasia, obesity, hyperinsulinemia, and impaired glucose tolerance [7].  
Chemerin (Retinoic Acid Receptor Responder Protein 2), encoded by the RARRES2 gene, is a protein primarily synthesized by visceral adipose tissue cells [8]. Chemerin can modulate insulin action and glucose consumption. Administration of chemerin worsens glucose tolerance and reduces cellular glucose uptake in obese mice. Decreased blood levels of this adipokine are linked with improved insulin sensitivity as expressed by the Insulin Sensitivity Index (ISI) [9]. The results of this study suggest the effect of elevated chemerin concentration on the development of health dysfunctions accompanying visceral obesity. The adipokine in question may be a predictive factor for developing insulin resistance, hypertension, atherosclerosis, and numerous cardiovascular complications [10].  
Neprilysin is a conserved zinc metalloproteinase that hydrolyses oligopeptides by cleaving on the N-terminal side of hydrophobic amino acid residues [11]. Recent studies have shown that neprilysin is involved in the development of obesity and its metabolic consequences. In in vivo analyses using an experimental mouse model, several times higher neprilysin levels were observed in the blood of mice with obesity relative to normal-weight animals [12]. Neprilysin-deficient mice were also characterized by increased islet \(\beta\)-cell mass when fed a high-fat diet, suggesting neprilysin's role in modulating this cell type's metabolism [13].  
The aim of the study was to look for the relationships between adipolin, chemerin, and neprilysin levels and anthropometric and metabolic parameters, as well as blood pressure values, taking into account the influence of gender and age of the participants.