Immunometabolic Profile in Overweight and Obesity: Circulating NLRP3, Cytokine Imbalance and Insulin Resistance
DOI:
https://doi.org/10.22317/jcms.v12i4.2231Keywords:
Overweight, Obesity, NLR Family, Pyrin Domain-Containing 3 Protein, Cytokines, Insulin Resistance, Inflammation, Metabolic DiseasesAbstract
Objective: This study compared inflammatory, metabolic, hormonal, lipid, hepatic and renal biomarkers between normal-weight controls and adults with overweight or obesity and assessed whether major differences persisted after adjustment for age, sex and glycaemic status.
Methods: This cross-sectional study analysed 108 participants: 22 normal-weight controls and 86 adults with overweight or obesity. Samples were collected after an 8–12-hour fast. Circulating NLRP3 was measured using ELK5399; control sera were analysed undiluted and overweight/obesity sera at 1:4 or 1:8 dilution when required. Correlations were evaluated with Spearman coefficients and Benjamini-Hochberg false-discovery-rate correction. Multivariable models adjusted for age, sex and HbA1c-defined glycaemic status.
Results: The pro-inflammatory cytokines such as TNF-α and IL-1β, circulating NLRP3 inflammasome were higher and anti-inflammatory cytokine such IL-10 was lower in the overweight/obesity group (all p<0.001) compared to normal controls. Vitamin D remained lower, while total cholesterol, triglycerides and corrected VLDL-C remained higher in overweight/obesity group compared to normal control. AST, ALT, blood urea and creatinine did not show independent adverse group differences. NLRP3 produced complete separation of the two groups (apparent AUC=1.000), which is considered exploratory and requires external validation.
Conclusion: Overweight and obesity were associated with a distinct circulating inflammatory-metabolic profile independent of major measured confounders. The cross-sectional design and absence of external validation preclude causal or diagnostic claims.
References
World Health Organization. Obesity and overweight [Internet]. Geneva: World Health Organization; 2025 [cited 2026 Aug 24]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
Rubino F, Cummings DE, Eckel RH, Cohen RV, Wilding JP, Brown WA, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025;13(3):221-262. doi:10.1016/S2213-8587(24)00316-4.
Kunz HE, Hart CR, Gries KJ, Parvizi M, Laurenti M, Dalla Man C, et al. Adipose tissue macrophage populations and inflammation are associated with systemic inflammation and insulin resistance in obesity. Am J Physiol Endocrinol Metab. 2021;321(1):E105-E121. doi:10.1152/ajpendo.00070.2021.
Oussaada SM, Kilicarslan M, de Weijer BA, et al. Tissue-specific inflammation and insulin sensitivity in subjects with obesity. Diabetes Res Clin Pract. 2024;211:111663. doi:10.1016/j.diabres.2024.111663.
Wu H, Ballantyne CM. Metabolic inflammation and insulin resistance in obesity. Circ Res. 2020;126(11):1549-1564. doi:10.1161/CIRCRESAHA.119.315896.
Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci. 2019;20(13):3328. doi:10.3390/ijms20133328.
Wu KKL, Cheung SWM, Cheng KKY. NLRP3 inflammasome activation in adipose tissues and its implications on metabolic diseases. Int J Mol Sci. 2020;21(11):4184. doi:10.3390/ijms21114184.
Unamuno X, Gómez-Ambrosi J, Ramírez B, et al. NLRP3 inflammasome blockade reduces adipose tissue inflammation and extracellular matrix remodeling. Cell Mol Immunol. 2021;18:1045-1057. doi:10.1038/s41423-019-0296-z.
Oliveira MS, Rheinheimer J, Moehlecke M, Rodrigues M, Assmann TS, Leitão CB, et al. UCP2, IL18, and miR-133a-3p are dysregulated in subcutaneous adipose tissue of patients with obesity. Mol Cell Endocrinol. 2020;509:110805. doi:10.1016/j.mce.2020.110805.
Cyr Y, Bissonnette S, Lamantia V, Wassef H, Loizon E, Ngo Sock ET, et al. White adipose tissue surface expression of LDLR and CD36 is associated with risk factors for type 2 diabetes in adults with obesity. Obesity (Silver Spring). 2020;28(12):2357-2367. doi:10.1002/oby.22985.
Meier DT, de Paula Souza J, Donath MY. Targeting the NLRP3 inflammasome-IL-1β pathway in type 2 diabetes and obesity. Diabetologia. 2025;68(1):3-16.
Alipourfard I, Datukishvili N, Mikeladze D. TNF-α downregulation modifies insulin receptor substrate 1 (IRS-1) in metabolic signaling of diabetic insulin-resistant hepatocytes. Mediators Inflamm. 2019;2019:3560819. doi:10.1155/2019/3560819.
Azizian M, Mahdipour E, Mirhafez SR, Shoeibi S, Nematy M, Esmaily H, et al. Cytokine profiles in overweight and obese subjects and normal weight individuals matched for age and gender. Ann Clin Biochem. 2016;53(6):663-668. doi:10.1177/0004563216629997.
Acosta JR, Tavira B, Douagi I, Kulyté A, Arner P, Rydén M, et al. Human-specific function of IL-10 in adipose tissue linked to insulin resistance. J Clin Endocrinol Metab. 2019;104(10):4552-4562. doi:10.1210/jc.2019-00341.
Poosri S, Vimaleswaran KS, Prangthip P. Dietary lipids shape cytokine and leptin profiles in obesity-metabolic syndrome implications: a cross-sectional study. PLoS One. 2024;19(12):e0315711. doi:10.1371/journal.pone.0315711.
Krajewska M, Witkowska-Sędek E, Rumińska M, Stelmaszczyk-Emmel A, Sobol M, Majcher A, et al. Vitamin D effects on selected anti-inflammatory and pro-inflammatory markers of obesity-related chronic inflammation. Front Endocrinol (Lausanne). 2022;13:920340. doi:10.3389/fendo.2022.920340.
Derbel S, Zarraa L, Assarrar I, Bouichrat N, Rouf S, Latrech H. Assessment of vitamin D status in obese and non-obese patients: a case-control study. Diabetes Epidemiol Manag. 2025;17:100237. doi:10.1016/j.deman.2024.100237.
Clarke SA, Eng PC, Comninos AN, Lazarus K, Choudhury S, Tsang C, et al. Current challenges and future directions in the assessment of glucocorticoid status. Endocr Rev. 2024;45(6):795-817. doi:10.1210/endrev/bnae016.
Nussbaumerova B, Rosolova H. Obesity and dyslipidemia. Curr Atheroscler Rep. 2023;25(12):947-955. doi:10.1007/s11883-023-01167-2.
Alcover S, Ramos-Regalado L, Girón G, Muñoz-García N, Vilahur G. HDL cholesterol and triglycerides dynamics: essential players in metabolic syndrome. Antioxidants (Basel). 2025;14(4):434. doi:10.3390/antiox14040434.
Luo Y, Lin H. Inflammation initiates a vicious cycle between obesity and nonalcoholic fatty liver disease. Immun Inflamm Dis. 2021;9(1):59-73. doi:10.1002/iid3.391.
Zhai Q, Dou J, Wen J, Wang M, Zuo Y, Su X, et al. Association between changes in lipid indexes and early progression of kidney dysfunction in participants with normal estimated glomerular filtration rate: a prospective cohort study. Endocrine. 2022;76:312-323. doi:10.1007/s12020-022-03012-z.
Zbrzeźniak-Suszczewicz J, Winiarska A, Perkowska-Ptasińska A, Stompor T. Obesity-related glomerulosclerosis-how adiposity damages the kidneys. Int J Mol Sci. 2025;26(13):6247. doi:10.3390/ijms26136247.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-419. doi:10.1007/BF00280883.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499-502. doi:10.1093/clinchem/18.6.499.
American Diabetes Association Professional Practice Committee for Diabetes. 2. Diagnosis and classification of diabetes: Standards of Care in Diabetes-2026. Diabetes Care. 2026;49(Suppl 1):S27-S49. doi:10.2337/dc26-S002.
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 1995;57(1):289-300. doi:10.1111/j.2517-6161.1995.tb02031.x.
Youden WJ. Index for rating diagnostic tests. Cancer. 1950;3(1):32-35. doi:10.1002/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3.
Xuan Y, Wu D, Zhang Q, Yu Z, Yu J, Zhou D. Elevated ALT/AST ratio as a marker for NAFLD risk and severity: insights from a cross-sectional analysis in the United States. Front Endocrinol (Lausanne). 2024;15:1457598. doi:10.3389/fendo.2024.1457598.
Zegeye MM, Nakka SS, Andersson JSO, Söderberg S, Ljungberg LU, Kumawat AK, et al. Soluble LDL-receptor is induced by TNF-α and inhibits hepatocytic clearance of LDL-cholesterol. J Mol Med (Berl). 2023;101(12):1615-1626. doi:10.1007/s00109-023-02379-4.
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Journal of Contemporary Medical Sciences

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

