# Associations Between Klotho/FGF-Related Protein Expression in Peripheral Blood Mononuclear Cells, Inflammation, and Muscle Function in Middle-Aged Adults with Obesity: A Pilot Study

**Authors:** Diana G. Ariadel-Cobo, Brisamar Estébanez, Elena González-Arnáiz, María Pilar García-Pérez, Marta Rivera Viloria, Alejandra Villasante Santos, Begoña Pintor de la Maza, David Emilio Barajas-Galindo, Diana García-Sastre, María José Cuevas González, María D. Ballesteros-Pomar

PMC · DOI: 10.3390/ijms27041983 · International Journal of Molecular Sciences · 2026-02-19

## TL;DR

This study explores how Klotho and FGF proteins in blood cells relate to inflammation and muscle function in middle-aged people with obesity.

## Contribution

The study is the first to explore Klotho/FGF system associations with inflammation and muscle dysfunction in middle-aged adults with obesity.

## Key findings

- Obese individuals had lower Klotho levels and higher TNF-α compared to controls.
- Higher Klotho levels were linked to better muscle function and lower inflammation.
- Klotho/FGF system alterations may reflect aging-related biological processes in obesity.

## Abstract

This pilot study aimed to investigate the role of the Klotho/FGF (fibroblast growth factor) system in biological features associated with premature aging, particularly inflammation and muscle dysfunction, focusing on its association with inflammatory markers, body composition, and muscle function in middle-aged adults. A total of 45 participants aged 50–60 years were enrolled, including 30 patients with obesity (22F/8M) and 15 healthy controls (11F/4M). Comprehensive assessments were conducted, including body composition analysis and muscle function tests. Evaluations of protein expression of Klotho, β-Klotho, FGF19, FGF21, FGF23, TFN-α and IL-10 were assessed in peripheral blood mononuclear cells (PBMCs). A Principal Component Analysis (PCA) was carried out to explore the relationships among variables. Significant differences were observed between the obese and control groups, with obese individuals exhibiting lower levels of Klotho and higher levels of TFN-α. The PCA revealed that higher Klotho levels were positively associated with better muscle function and lower inflammatory markers. These associations suggest that Klotho-related alterations may reflect biological processes linked to inflammation and muscle dysfunction in obesity. These findings suggest that alterations in the Klotho/FGF system may reflect biological pathways commonly associated with aging-related phenotypes in obesity, rather than direct measures of chronological aging. Given the exploratory design and limited sample size, these findings should be interpreted as hypothesis-generating rather than evidence of causal mechanisms.

## Linked entities

- **Genes:** CG9701 (uncharacterized protein) [NCBI Gene 39872], FGF19 (fibroblast growth factor 19) [NCBI Gene 9965], FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], FGF23 (fibroblast growth factor 23) [NCBI Gene 8074]
- **Proteins:** CG9701 (uncharacterized protein), FGF19 (fibroblast growth factor 19), FGF21 (fibroblast growth factor 21), FGF23 (fibroblast growth factor 23), TNF (tumor necrosis factor), IL10 (interleukin 10)
- **Diseases:** obesity (MONDO:0011122)

## Full-text entities

- **Genes:** PCSK1 (proprotein convertase subtilisin/kexin type 1) [NCBI Gene 281967] {aka PC1, PC3}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, CRP (C-reactive protein) [NCBI Gene 527553], FGF23 (fibroblast growth factor 23) [NCBI Gene 8074] {aka ADHR, FGFN, HFTC2, HPDR2, HYPF, PHPTC}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, FGF19 (fibroblast growth factor 19) [NCBI Gene 9965], GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, PCSK1 (proprotein convertase subtilisin/kexin type 1) [NCBI Gene 5122] {aka BMIQ12, NEC1, PC1, PC1/3, PC3, SPC3}, KRT6B (keratin 6B) [NCBI Gene 3854] {aka CK-6B, CK6B, K6B, KRTL1, PC2, PC4}, KLB (klotho beta) [NCBI Gene 152831] {aka BKL}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, TNF (tumor necrosis factor) [NCBI Gene 280943] {aka TNF-a, TNF-alpha, TNFa}, GGTLC5P (gamma-glutamyltransferase light chain 5 pseudogene) [NCBI Gene 653590] {aka GGT}, KLB (klotho beta) [NCBI Gene 514925], IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, KL (klotho) [NCBI Gene 9365] {aka HFTC3, KLA}, FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, MYOG (myogenin) [NCBI Gene 4656] {aka MYF4, bHLHc3, myf-4}
- **Diseases:** Obesity (MESH:D009765), Adiposity (MESH:D018205), kidney disease (MESH:D007674), type 2 diabetes (MESH:D003924), cardiac or respiratory failure (MESH:D012131), ALM (MESH:D013851), osteopenia (MESH:D001851), overweight (MESH:D050177), anorexia nervosa (MESH:D000856), impaired muscle function (MESH:D009135), PCA (MESH:C566443), abdominal obesity (MESH:D056128), immune dysregulation (OMIM:614878), metabolic (MESH:D008659), hypertriglyceridemia (MESH:D015228), metabolic syndrome (MESH:D024821), injury to (MESH:D014947), vascular calcification (MESH:D061205), liver disease (MESH:D008107), sarcopenia (MESH:D055948), Inflammation (MESH:D007249), gastrointestinal symptoms (MESH:D012817), muscle wasting (MESH:D009133), hypertension (MESH:D006973), polycystic ovary syndrome (MESH:D011085), dyslipidemia (MESH:D050171), hyperinsulinemia (MESH:D006946), diabetes (MESH:D003920), immune system impairment (MESH:D007154), cancer (MESH:D009369), osteoporosis (MESH:D010024), Insulin Resistance (MESH:D007333), CF (MESH:D003550)
- **Chemicals:** lipid (MESH:D008055), sucrose (MESH:D013395), PVDF (MESH:C024865), SDS (MESH:D012967), KCl (MESH:D011189), calcium (MESH:D002118), Glucose (MESH:D005947), creatinine (MESH:D003404), cholesterol (MESH:D002784), magnesium (MESH:D008274), vitamin D (MESH:D014807), sodium deoxycholate (MESH:D003840), bile acid (MESH:D001647), PBS (-), phosphorus (MESH:D010758), phosphate (MESH:D010710), EDTA (MESH:D004492), NP-40 (MESH:C010615), polyacrylamide (MESH:C016679)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** PC3 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0035)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940495/full.md

## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940495/full.md

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Source: https://tomesphere.com/paper/PMC12940495