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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Endocrinology of Aging
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1539983
This article is part of the Research Topic The Crosstalk Between Metabolism and Inflammation in Aging and Longevity View all articles

Metabolically healthy across body mass index categories in relation to serum Klotho levels: A population-based study

Provisionally accepted
Yanling Shu Yanling Shu 1Junfan Yang Junfan Yang 2Linfei Dou Linfei Dou 2Mingyang Wu Mingyang Wu 2*
  • 1 Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • 2 School of Public Health, Central South University, Changsha, China

The final, formatted version of the article will be published soon.

    Background: Metabolic health status and body mass index (BMI) are both key predictors of aging-related diseases and premature mortality. However, the relationship between metabolically distinct phenotypes, classified by BMI categories, and serum Klotho levels—a biomarker of aging—remains poorly understood. This study aimed to investigate the association between metabolically healthy phenotypes and serum Klotho levels among middle and aged adults.Methods: A total of 11,413 participants were included in this study. Participants were categorized into phenotypes according to metabolic disorders and BMI: metabolically healthy and normal weight (MH-NW), metabolically healthy and overweight (MH-OW), metabolically healthy and obesity (MHO), metabolically unhealthy and normal weight (MU-NW), metabolically unhealthy and overweight (MU-OW), and metabolically unhealthy and obesity (MUO). Weighted multivariate linear regression models were performed to estimate the association between metabolically healthy phenotypes and Klotho levels.Results: After adjusting for potential confounders, participants in the MH-OW, MU-OW, and MUO groups had significantly lower Klotho levels compared to the MH-NW group, with estimated percentage changes (95%CIs) at -5.4% (-9.2% to -1.4%), -5.0% (-8.3% to -1.5%), and -5.7% (-8.7% to -2.5%), respectively. Additionally, reduced Klotho levels were more pronounced among females with MU-OW and MUO phenotypes, showing estimated percentage changes of -6.6% (-11.1% to -1.9) and -8.4% (-12.7% to -3.8%), respectively.Conclusion: This large population-based study found that Klotho levels vary according to metabolically healthy status across BMI categories, with metabolically unhealthy phenotypes exhibiting notably lower levels. These findings highlight the influence of metabolic abnormalities and body fatness on the aging process.

    Keywords: NHANES, Klotho, Metabolically healthy, phenotypes, Obesity

    Received: 05 Dec 2024; Accepted: 31 Jan 2025.

    Copyright: © 2025 Shu, Yang, Dou and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mingyang Wu, School of Public Health, Central South University, Changsha, China

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