Estimation of Chemerin in Iraqi Diabetic Women Patients with Hypothyroidism

Hypothyroidism, characterised by insufficient production of Thyroid Hormones (THs), disrupts energy balance and metabolic homeostasis [1].

Thyroxine (T4) and Triiodothyronine (T3), two thyroid hormones, are important modulators of metabolic rate that affect the metabolism of proteins, fats, and carbohydrates [2]. Weight gain, insulin resistance, and dyslipidemia are just a few of the metabolic disorders that can result from thyroid hormone dysregulation [3].

Common symptoms of hypothyroidism are usually sluggish at onset and include fatigue, dry skin, cold susceptibility, hair loss, constipation, voice changes, and slower movement and thought [4].

Diagnosis

The symptoms of hypothyroidism can be different from person to person. And they often look like symptoms of other health issues. Because of that, a diagnosis of hypothyroidism doesn't rely on symptoms alone. It's usually based on the results of blood tests.

The first blood test typically done to diagnose hypothyroidism measures the level of Thyroid-Stimulating Hormone (TSH) in the blood. If it's high, the test is done again, along with a blood test for the thyroid hormone T-4. If the results show that TSH is high and T-4 is low, then the diagnosis is hypothyroidism.

The metabolic effects of chemerin, a newly identified adipokine produced from adipose tissue, have drawn attention. Adipose tissue, liver, kidney, pancreas, lungs, ovaries, and the pituitary gland are among the organs that express chemerin, which binds to the G-protein-coupled receptor CMKLR1, often referred to as ChemR23 or GPCR-DEZ [5]. Chemerin, which has paracrine and autocrine effects, is synthetized from adipose tissue. It activates lipolysis and metabolic pathways in an autocrine fashion.

It also plays a filament in the chronic low-grade inflammation associated with obesity through paracrine effects. [6]. Initially identified as a chemotactic protein, chemerin acts via its receptor CMKLR1, which is expressed on neutrophils as well as activated macrophages and dendritic cells. Chemerin has been involved with adipogenesis, osteoclastogenesis, angiogenesis, type 2 diabetes, Crohn's disease, Metabolic Syndrome (MetS), and arthritis [7]. Other functions of chemerin include tissue remodelling, cell proliferation and immune responses [8].

Differences in chemerin level of expression between cell types and tissue have an important influence on several illness problems (obesity, cancer, inflammation, heart disease and vascular diseases) [9-11].Several metabolic and inflammatory mediators, including glucose, fatty acids, insulin, immunoregulatory cytokines, and nuclear receptor activators, including glucocorticoids, retinoids, and vitamin D, have been suggested to have an impact on the regulation of chemerin expression, which is specific to various tissues [12,13].

Chemerin’s Role in Hypothyroidism

Chemerin’s role in hypothyroidism is emerging as a critical link to metabolic dysfunction. Studies have shown that people with thyroid dysfunction exhibit different patterns in their blood levels of chemerin, with hypothyroidism patients showing higher amounts of chemerin. Elevated chemerin in hypothyroidism correlates strongly with TSH and metabolic markers. There are multiple important links between chemerin and thyroid function: (1) an inverse relationship with HDL cholesterol (2) a positive correlation with TSH levels (3) a direct correlation with BMI and triglycerides and (4) a negative correlation with T3 and T4 levels [7].

Case controls study design, Between "1 June 2024-1 September 2024," 50 individuals who were at least 30 years old and had been diagnosed with diabetes mellitus and hypothyroidism by a specialist were recruited for the study from the Al-Yarmouk Teaching Hospital. Age and sex matching with patients were taken into account when recruiting apparently healthy controls from those who were not ill at the time “check by blood test” (all patients and controls are women).

Blood Analysis

Both patients' and controls' blood samples were taken. Serum was isolated, divided into aliquots, and utilized for thyroid function and chemerin tests. These tests relied on the use of enzyme-linked immune sorbent assay kits “the principle of kit is sandwich method also detected by pg./mL” , which were provided by My BioSource Company, USA.

Statistical Analysis Data

Statistical analysis data were examined using the SPSS-24 statistical software. The data was presented using the mean, standard deviation of the mean, and percentage once it was confirmed that the data was regularly distributed by use the normal distribution curve. The difference between two means was tested using the t-test. Statistical significance was defined as a p-value of "<0.05." ROC curve analysis measures the specificity and sensitivity of biomarker research also cutoff value by Youden index.

Table 1 displays the clinical features of the research participants. The age distribution of the patients and the controls were individually matched (Table 2,3 and Figures 1-3).

An adipokine called chemerin has gained a lot of attention due to its role in several physiological processes, including inflammation, adipogenesis, and energy metabolism [14]. While it has a reasonably well-established role in several metabolic illnesses, including type 2 diabetes and obesity [15], its possible significance in thyroid dysfunction, specifically hypothyroidism, is still being studied and discussed.

Studies have shown that people with thyroid dysfunction exhibit different patterns in their blood levels of chemerin, with hypothyroidism patients showing higher amounts of chemerin [16]. Elevated chemerin in hypothyroidism correlates strongly with TSH.

According to the outcome data, hypothyroid patients had a substantially greater (mean± SD) level of chemerin than the control group. These findings were consistent with a study by Edrees et al. [16] that found that patients with hypothyroidism had higher serum chemerin levels. Although chemerin has been connected to metabolic diseases [14], more research is necessary to determine its precise function in the aetiology of hypothyroidism and its related consequences. n addition, the level of chemerin is significantly associated with metabolic derangements and impaired energy homeostasis caused by low thyroid hormone levels in patients with hypothyroidism [17]. Al-Doghaither et al. [18] suggest that thyroid hormones, chemerin, and the regulation of metabolism has an intricate interaction which may play a role in contributing to the overall pathophysiology of hypothyroidism. Thyroid hormones (T3) mediate gene expression through nuclear receptor complex interactions with coactivators/corepressors that impact mRNA stability and translation [19]. Recent evidence indicates direct modulation of chemerin secretion by TSH through TSHR signalling in adipocytes, independent of T3/T4 [20]. In hypothyroidism, increased TSH stimulates cAMP-PKA-dependent signalling to enhance RARR ES2 (chemerin) transcription in adipocytes [20], fuelling CMKLR1 that aggravates inflammation.

Table 1: Laboratory Investigations of Subjects of Study

Figure 1: Chemerin (pg/mL) Levels in Patients and Controls

Figure 2: TSH mlU/L Levels in Patients and Controls

Table 2: Correlations between Study Biomarkers for Patients

**.Correlation is significant at the 0.01 level (2-tailed)

Table 3: ROC Curve Analysis between Patients and Controls

Figure 3: ROC Curve Analysis of Chemerin and TSH between Patients and Controls

In hypothyroidism, chemerin, an inflammatory marker, to be elevated and statistically significant. Further studies with larger sample sizes are needed to clarify the role of adipokine and inflammation in the development of hypothyroidism and to assess whether this parameter could serve as potential biomarker.

Conflicts of Interest

The writers did not disclose any conflicts of interest.

Ethical Statement

This study has been approved by the scientific committees of the local health care department in Al-Karkh, Baghdad province. Each patient was given an explanation of the study's objectives in order to gain their consent to participate.

1. Gatta, E. et al. “Differential association of hypothyroidism with cardiovascular events and cardiovascular mortality: A systematic review and meta-analysis.” Endocrine, vol. 91, no. 1, 2026, pp. 277.
2. Kumar, V. et al. “Effects of thyroid dysfunction on lipid profile.” International Journal of Medical and Biomedical Studies, vol. 3, no. 6, 2019, pp. 76-80.
3. Ozdemir, D. et al. “Serum adiponectin levels and changes in glucose metabolism before and after treatment for thyroid dysfunction.” Internal Medicine, vol. 54, no. 15, 2015, pp. 1849-1857.
4. Wilson, S.A. et al. “Hypothyroidism: Diagnosis and treatment.” American Family Physician, vol. 103, no. 10, 2021, pp. 605-613.
5. Wittamer, V. et al. “Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids.” Journal of Experimental Medicine, vol. 198, 2003, pp. 977-985.
6. Booth, A. et al. “Adipose tissue, obesity and adipokines: Role in cancer promotion.” Hormone Molecular Biology and Clinical Investigation, vol. 21, 2015, pp. 57-74.
7. Rourke, J.L. et al. “Towards an integrative approach to understanding the role of chemerin in human health and disease.” Obesity Reviews, vol. 14, 2013, pp. 245-262.
8. Kiezun, M. et al. “Chemerin affects the expression of angiogenesis-related factors in the porcine endometrium during early pregnancy and the oestrous cycle: An in vitro study.” Reproduction, Fertility and Development, vol. 35, no. 16, 2023, pp. 692-707.
9. Skrzeczyńska-Moncznik, J. et al. “Chemerin and the recruitment of NK cells to diseased skin.” Acta Biochimica Polonica, vol. 56, 2009, pp. 355–360.
10. Pachynski, R.K. et al. “Chemerin suppresses breast cancer growth by recruiting immune effector cells into the tumor microenvironment.” Frontiers in Immunology, vol. 10, 2019, p. 983.
11. Niklowitz, P. et al. “Link between chemerin, central obesity, and parameters of the metabolic syndrome: Findings from a longitudinal study in obese children participating in lifestyle intervention.” International Journal of Obesity, vol. 42, 2018, pp. 1743-1752.
12. Parlee, S.D. et al. “Serum chemerin levels vary with time of day and are modified by obesity and tumor necrosis factor-alpha.” Endocrinology, vol. 151, 2010, pp. 2590–2602.
13. Kwiecien, K. et al. “The methylation status of the chemerin promoter region located from −252 to +258 bp regulates constitutive but not acute-phase cytokine-inducible chemerin expression levels.” Scientific Reports, vol. 10, 2020, p. 13702.
14. Helfer, G. et al. “Chemerin: A multifaceted adipokine involved in metabolic disorders.” Journal of Endocrinology, vol. 238, no. 2, 2018, pp. R79-R94.
15. Chyra, A. et al. “Chemerin: A new regulator of metabolic and immune processes.” Postępy Biologii Komórki, vol. 38, no. 3, 2011, pp. 407–421.
16. Edrees, H.M. et al. “A study on serum level of chemerin in experimentally induced thyroid dysfunctions.” Basic Sciences and Medicine, vol. 7, no. 2, 2018, pp. 21–26.
17. Hu, S. et al. “Chemerin facilitates intervertebral disc degeneration via TLR4 and CMKLR1 and activation of NF-kB signaling pathway.” Aging, vol. 12, no. 12, 2020, pp. 11732–11753.
18. Al-Doghaither, H.A. et al. “Insulin resistance and its correlation with chemerin and visfatin in Saudi patients with hyperthyroidism.” International Journal of Health Sciences, vol. 13, no. 5, 2019, pp. 18-21.
19. Sinha, R. et al. “Cellular action of thyroid hormone.” Endotext, edited by K.R. Feingold et al., MDText.com, Inc., 2000.
20. Goralski, K.B. et al. “More than an adipokine: The complex roles of chemerin signaling in cancer.” International Journal of Molecular Sciences, vol. 20, no. 19, 2019, pp. 4778.