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Morser, J. Chemerin Forms and Disease. Encyclopedia. Available online: https://encyclopedia.pub/entry/26835 (accessed on 17 July 2025).
Morser J. Chemerin Forms and Disease. Encyclopedia. Available at: https://encyclopedia.pub/entry/26835. Accessed July 17, 2025.
Morser, John. "Chemerin Forms and Disease" Encyclopedia, https://encyclopedia.pub/entry/26835 (accessed July 17, 2025).
Morser, J. (2022, September 02). Chemerin Forms and Disease. In Encyclopedia. https://encyclopedia.pub/entry/26835
Morser, John. "Chemerin Forms and Disease." Encyclopedia. Web. 02 September, 2022.
Chemerin Forms and Disease
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This entry is adapted from the peer-reviewed paper 10.3390/biomedicines10082018

Since chemerin was first identified, investigators have shown in longitudinal, cross-sectional, and case control studies, as well as a few prospective studies, that there are differences in chemerin levels between patients with disease and normal samples. The studies have been able to show a correlation between chemerin levels and disease incidence, severity, or progression. That correlation between chemerin and disease does not prove that chemerin is causing the disease as, alternatively, the change in chemerin levels could be caused by the disease, or an independent unknown factor could be causing both the disease and the changes in chemerin levels.

chemerin obesity diabetes

1. Introduction

Single nucleotide polymorphisms (SNP) have been identified in the RARRES2 gene but none of the ones used in studies investigating the association with disease so far has been an informative SNP that alters the encoded amino acid sequence. The association studies have in some cases shown a positive association with various phenotypes, for example with regional body fat disposition [1], gestational diabetes [2], or serum chemerin levels [3]. Other studies failed to find an association between RARRES2 SNPs and type-2 diabetes (T2D) [4]. These differences found in the effect of SNPs within the RARRES2 gene on diseases might be due to the different populations studied or the definitions of the indications.
There is a lack of information about the normal variation in chemerin levels in individuals, with the levels reported in research papers varying from median levels of <10 ng/mL to ones reporting median levels of >100 ng/mL [5][6]. The field needs to develop a method to normalize these data, such as creating an international standard for chemerin ELISAs and activity assays in order to improve the comparability of results from different laboratories.
Chemerin levels did not change in post-prandial plasma samples compared with fasting samples in a small study which also showed no changes in the levels of the different forms [5]. In contrast, a drop in total chemerin levels was found following feeding with a larger reduction in people with obesity [6].
Diurnal variation in total serum chemerin levels has been observed in mice with differences in the diurnal rhythm found in wild type and obese mice [7], but no comparable studies have been reported for humans.
There are limited comparative data on any potential differences in circulating chemerin levels in men and women; some studies have shown that women have higher chemerin levels than men [8][9], but other studies have reached the opposite conclusion [10]. Although reports are available on chemerin levels in different racial or ethnic groups, the influence of this factor on circulating chemerin has not been formally compared within a single study to the knowledge. Information and an agreed consensus about these baseline parameters would improve the interpretation of studies investigating chemerin in disease.

2. Cardiovascular Disease

A role for chemerin in hypertension has been shown in rats and humans [11], while atherogenesis is also affected by chemerin [12]. The mechanism by which chemerin in hypertension regulates blood pressure has been explored in rats, as mice do not show the same response to chemerin in aorta and arteries as humans, while rats do [13]. The chemerin is produced by the peri-vascular adipose tissue and causes contraction by acting on vascular smooth muscle cells via chem1. Despite the lack of effect reported on arterial contraction by the nonapeptide, mice given chemerin (6 μg/kg/day) intraperitoneally had elevated systolic blood pressure [14]. These mechanistic studies and model organism experiments show that chemerin affects blood pressure, but unfortunately association studies on human hypertension and the levels of different forms of chemerin are currently lacking.
In a study on a large cohort derived from the European prospective investigation into nutrition and cancer (EPIC), chemerin levels in plasma were measured by ELISA. Participants in the quartile with the highest chemerin levels had a hazard ratio of 3.57 compared to the those in the lowest quartile for the development of myocardial infarction, stroke, and type 2 diabetes (T2D) [15]. Importantly, this was a prospective study in which the incident cases occurred after the acquisition of the samples. When the data were adjusted for body mass index (BMI) and waist circumference, the hazard ratio was not significantly changed. It was suggested that plasma chemerin levels could be a biomarker for cardiovascular risk.
A recent meta-analysis that included five independent studies confirmed that in patients with diagnosed acute coronary syndrome (ACS), chemerin levels were higher than in controls [16]. This was not found for patients with stable angina pectoris. In two studies that investigated T2D in patients with ACS, levels of chemerin were higher in T2D patients than those without.
In patients with congestive heart failure (CHF), serum chemerin levels were measured while outcomes were investigated prospectively [17]. CHF patients whose chemerin levels were in the top quartile had more major adverse cardiac events than those with chemerin levels in the bottom quartile, with a hazard ratio of 3.25, while the hazard ratio for all cause mortality was 3.06. Analysis of Kaplan–Meier event-free survival curves showed that high chemerin levels were a predictor of major adverse cardiac events irrespective of the level of N-terminal prohormone of brain natriuretic peptide (BNPT), a well-documented predictive biomarker in CHF.

3. Chemerin in Obesity and Diabetes

Data from cell and animal studies have documented that chemerin is involved in energy balance and metabolism with implications for obesity, diabetes, and metabolic syndrome in adults [18][19][20][21]. The role of chemerin in pediatric and gestational diabetes will not be discussed here, although there is good evidence of its involvement [22][23]. There are many reports describing chemerin levels along with other adipokines in various cohorts showing that chemerin levels are associated with disorders involved with energy balance [9][24][25][26]. Those reports are in agreement that levels of circulating chemerin are higher in people with obesity.
In patients about to undergo bariatric surgery, there are higher levels of total chemerin in their circulation, with data suggesting that those levels are reduced at 6 or 12 months after surgery [27][28][29][30][31]. In contrast, in the days immediately after the surgery, there are inconsistent data on chemerin levels.
In one report, the levels of chemerin isoforms in plasma were also investigated. In a cohort that was 80% male, total chemerin was increased in plasma from patients with obesity compared to lean controls. The use of ELISAs specific for different chemerin forms showed that the level of the precursor, chem163S, was reduced and that the increase was due to chemerin degraded to a smaller size than chem155A [5]. One form of that degraded chemerin was identified as chem144D. In a study investigating a small number of female patients with obesity, the bioactivity of serum samples was measured [32]. Compared to normal BMI controls, patients with obesity had higher levels of total chemerin, which was more bioactive than the chemerin from controls. Both of these studies show that in patients with obesity, circulating chemerin levels are increased, with more processing occurring.
These results are similar to those obtained in a model of obesity in mice in which plasma chemerin forms were determined by specific ELISAs [33]. Those results were confirmed in a study in which the bioactivity of chemerin samples was assayed in serum from murine models of obesity [34].
In rodent animal models, the status of the chemerin system affects energy metabolism and the development of insulin resistance [35]. In rodents, loss- or gain-of-function mutations in the chemerin gene or either of its two receptors leads to changes in adipogenesis, food intake, glucose homeostasis, and inflammation both in control animals and in animals challenged with interventions such as a high fat diet [13][19][36][37]. These data support the hypothesis that chemerin is involved in the development of T2D.
That concept has been investigated in human clinical samples, and in numerous studies an association has been found between chemerin levels and diabetic and obesity-related comorbidities (summarized in [38]). For example, serum levels of total chemerin have been found to be positively associated with levels of hemoglobin A1c (Hb A1c) in a large population of relatively healthy Taiwanese [9]. Herein, a small difference was detected in chemerin levels between men and women. Multivariate analysis showed that several markers of metabolic disease, such as blood pressure, cholesterol, and triglyceride levels, were correlated positively with serum chemerin levels, while HDL levels were negatively correlated with chemerin levels. Both BMI and Hb A1c were independent predictors of chemerin levels, suggesting that obesity and glucose homeostasis were affecting chemerin levels by different mechanisms.
Some studies have presented data that are not in agreement with the idea that T2D and metabolic syndrome patients have increased chemerin levels. For example, in a study in which Japanese with T2D or metabolic syndrome were compared to controls, men but not women were found to have lower chemerin levels than either people with metabolic syndrome or controls [10]. The disagreements between studies could arise from differences in which factors, such as age or sex, if any, were taken into account in the statistical analysis.

References

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  2. Hasanvand, Z.; Sadeghi, A.; Rezvanfar, M.R.; Goodarzi, M.T.; Rahmannezhad, G.; Mashayekhi, F.J. Association between chemerin rs17173608 and rs4721 gene polymorphisms and gestational diabetes mellitus in Iranian pregnant women. Gene 2018, 649, 87–92.
  3. Tonjes, A.; Scholz, M.; Breitfeld, J.; Marzi, C.; Grallert, H.; Gross, A.; Ladenvall, C.; Schleinitz, D.; Krause, K.; Kirsten, H.; et al. Genome wide meta-analysis highlights the role of genetic variation in RARRES2 in the regulation of circulating serum chemerin. PLoS Genet. 2014, 10, e1004854.
  4. Huang, H.W.; Liang, B.Y.; Li, Y.X. Association of Polymorphisms in STRA6 and RARRES2 Genes with Type 2 Diabetes in Southern Han Chinese. BioMed Res. Int. 2016, 2016, 6589793.
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  19. Zhang, Y.; Shen, W.J.; Qiu, S.; Yang, P.; Dempsey, G.; Zhao, L.; Zhou, Q.; Hao, X.; Dong, D.; Stahl, A.; et al. Chemerin regulates formation and function of brown adipose tissue: Ablation results in increased insulin resistance with high fat challenge and aging. FASEB J. 2021, 35, e21687.
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