Soluble alpha‑klotho and 25‑hydroxivitamin D are not associated with brown adipose tissue metabolism in young healthy adults Amaro Gahete, Francisco José Vázquez Lorente, Héctor Sánchez Delgado, Guillermo Ruiz Ruiz, Jonatan Klotho protein 25-Hydroxyvitamin D Ageing Brown adipose tissue This study was supported by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), and PTA-12264, Retos de la Sociedad (DEP2016-79512-R), Spain and European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU13/04365 and FPU14/04172); the Fundación Iberoamericana de Nutrición (FINUT), Spain; the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), Spain; the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016—Excellence actions: Unit of Excellence on Exercise and Health (UCEES) -, the Plan Propio de Investigación 2018—Programa Contratos-Puente, Spain; the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades, the Fundación Alfonso Martin Escudero and by the CIBEROBN, Centro de Investigación Biomédica en Red (CB22/03/00058), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – European Regional Development Fund. Universidad de Granada/CBUA Background Soluble Alpha-Klotho (S-αklotho) protein and 25-Hydroxyvitamin D (25-OH-D) have emerged as potential modulators for activating and recruiting Brown Adipose Tissue (BAT). The present study aimed to investigate whether circulating S-αklotho and 25-OH-D levels are related to BAT volume, 18Fluorine-Fluorodeoxyglucose (18F-FDG) uptake, and BAT radiodensity in young healthy adults. Methods A total of 128 participants (68% women) aged 18–25 years old participated in this cross-sectional study. Serum levels of S-αklotho were determined by a solid-phase sandwich enzyme-linked immunosorbent assay kit and 25-OH-D serum levels were analyzed using a competitive chemiluminescence immunoassay, both in blood samples collected after an overnight fast. All participants underwent a personalized cold exposure to determine their BAT volume, 18F-FDG uptake, and radiodensity, using a static positron emission tomography combined with computed tomography scan. Results After adjusting for multiple covariates, serum levels of S-αklotho (all R2 ≤ 0.228 and P ≥ 0.364), 25-OH-D as continuous (all R2 ≤ 0.242 and P ≥ 0.088) or by vitamin D status (all R2 ≤ 0.767 and P ≥ 0.061) were not associated with either BAT volume and 18F-FDG uptake, or BAT radiodensity. Conclusion Serum S-αklotho and 25-OH-D levels within the physiological range are not related to BAT-related variables in young healthy adults. Further studies are needed to fully understand the underlying mechanisms involved in BAT metabolism in humans. (ACTIBATE; ClinicalTrials.gov identifier: not applicable). 2025-04-30T11:44:31Z 2025-04-30T11:44:31Z 2025-03-11 journal article Amaro-Gahete, F.J., Vázquez-Lorente, H., Sanchez-Delgado, G. et al. Soluble alpha-klotho and 25-hydroxivitamin D are not associated with brown adipose tissue metabolism in young healthy adults. J Physiol Biochem (2025). https://doi.org/10.1007/s13105-025-01072-z https://hdl.handle.net/10481/103873 10.1007/s13105-025-01072-z eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Springer Nature