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. 2024 Nov 5;23(1):360.
doi: 10.1186/s12944-024-02339-y.

Systemic immune-inflammation mediates the association between Klotho protein and metabolic syndrome: findings from a large-scale population-based study

Yongzhou Liang #  1   2 , Ying Liu #  1   2 , Qin Tan  3 , Kaiyu Zhou  1   2 , Yurong Wu  4 , Li Yu  5   6
Affiliations

Systemic immune-inflammation mediates the association between Klotho protein and metabolic syndrome: findings from a large-scale population-based study

Yongzhou Liang et al. Lipids Health Dis. .

Abstract

Background: This study utilized large-scale population data from the National Health and Nutrition Examination Survey (NHANES) to elucidate the relationship between the Klotho protein and metabolic syndrome along with its components. We further investigated the possible mediating effect of inflammation on these relationships. Our objective was to identify biomarkers for risk stratification and potential therapeutic targets for metabolic syndrome.

Methods: This study enrolled 13,119 participants aged 40-79 years, spanning five NHANES cycles from 2007 to 2016, with complete information on metabolic syndrome and the Klotho protein. The definition of metabolic syndrome followed the criteria of the National Cholesterol Education Program-Adult Treatment Panel III. Survey-weighted logistic regression and subgroup analysis were used to explore the associations between serum Klotho protein levels and metabolic syndrome, along with its components. Mediation analysis was performed to investigate the mediating effects of inflammation-related markers, including white blood cells, neutrophils, lymphocytes, monocytes, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) and the monocyte-to-HDL ratio (MHR), with the aim of elucidating how the Klotho protein influences the onset and progression of metabolic syndrome.

Results: The study participants had an average age of 56.06 years (95% CI: 55.76-56.37), with a Klotho protein concentration of 798.10 pg/ml (95% CI: 656.50-980.50) and a 43.77% prevalence of metabolic syndrome (n = 5742). In the crude model, Klotho was negatively correlated with metabolic syndrome and its components, including central obesity, hypertension, and hypertriglyceridemia. After adjusting for all confounding factors, Klotho was demonstrated to be negatively associated only with metabolic syndrome (OR: 0.82, 95% CI: 0.70-0.97), hypertension (OR: 0.83, 95% CI: 0.70-0.98), and hypertriglyceridemia (OR: 0.78, 95% CI: 0.67-0.91). Subgroup and interaction analyses revealed significant interactions between age, sex, race/ethnicity, body mass index, and Klotho. Additionally, mediation analysis demonstrated that leukocytes, neutrophils and monocytes accounted for 34.78%, 31.91% and 7.13%, respectively, of the associations between Klotho and metabolic syndrome.

Conclusion: The serum concentration of Klotho protein was negatively associated with metabolic syndrome, with the relationship being partly mediated by systemic immune inflammation. The findings of this research revealed that the Klotho protein may be a valuable biomarker for risk stratification and a potential therapeutic target for metabolic syndrome.

Keywords: Biomarkers; Inflammation; Klotho; Metabolic syndrome; National Health and Nutrition Examination Survey.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The restricted cubic spline curves for the association between Klotho concentrations and metabolic syndrome and its components. A, metabolic syndrome; B, central obesity; C, hypertension; D, hypertriglyceridemia; E, low HDL-C; F, hyperglycemia
Fig. 2
Fig. 2
Subgroup analysis of the association between Klotho protein and metabolic syndrome. Abbreviations: PIR, family poverty income ratio; BMI, body mass index; eGFR, estimated glomerular filtration rate
Fig. 3
Fig. 3
The estimated proportion of the correlation between Klotho concentration and metabolic syndrome mediated by systemic inflammation. A, leukocyte; B, neutrophil
See this image and copyright information in PMC

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