# Soluble alpha-klotho and 25-hydroxivitamin D are not associated with brown adipose tissue metabolism in young healthy adults

## TL;DR

This study found no link between soluble alpha-klotho and vitamin D levels and brown fat activity in young healthy adults.

## Contribution

The study is the first to show no association between S-αklotho, 25-OH-D, and BAT metabolism in young adults.

## Key findings

- S-αklotho levels were not associated with BAT volume or activity.
- 25-OH-D levels also showed no significant relationship with BAT variables.
- Results suggest these biomarkers may not influence BAT in healthy young individuals.

## Abstract

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.

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.

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.

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).

The online version contains supplementary material available at 10.1007/s13105-025-01072-z.