Research Paper Advance Articles
Depletion of the TRF1 telomere-binding protein leads to leaner mice with altered metabolic profiles
- 1 Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid E-28029, Spain
- 2 Bioinformatics Unit, Spanish National Cancer Centre (CNIO), Madrid E-28029, Spain
- 3 Animal Surgery and Medicine Department, Faculty of Veterinary Science, Complutense University of Madrid, Madrid, Spain
- 4 Confocal Microscopy Unit, Spanish National Cancer Centre (CNIO), Madrid E-28029, Spain
Received: October 21, 2024 Accepted: August 18, 2025 Published: September 17, 2025
https://doi.org/10.18632/aging.206320How to Cite
Copyright: © 2025 Louzame et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
TRF1, a component of the telomere shelterin complex, plays crucial roles in telomere protection, telomere length regulation, and stemness. Here, we describe a previously unknown connection between TRF1 and metabolism. Telomere attrition has been linked to obesity. Our study reveals that Trf1-deficient mice exhibit a leaner phenotype, reduced adiposity, and improved glucose tolerance, even when subjected to a high-fat diet, independently of telomere shortening. These findings uncover a previously unknown role of TRF1 in regulating metabolism.
Abbreviations
TERT: telomerase reverse transcriptase; TRF1: telomeric repeat binding factor 1; TRF2: telomeric repeat binding factor 2; TIN2: TRF1-interacting nuclear factor 2; POT1: protection of telomeres 1; TPP1: the POT1-TIN2 organizing protein 1; RAP1: repressor/activator protein 1; Q-FISH: Quantitative telomere Fluorescence In Situ Hybridization; DEXA: Dual-energy X-ray absorptiometry; HDL: High-density lipoprotein cholesterol; LDL: low-density lipoprotein cholesterol; HOMA-IR: homeostatic model assessment; QUICKI: quantitative insulin sensitivity check index; VCO2: volume of dioxide; RQ: the respiratory quotient; VO2: volume of oxygen; EE: energy expenditure; GSEA: Gene set enrichment analysis; TCA: the citric acid; H2AX: H2A histone family member X; HSCs: Hepatic stellate cells; ECM: the extracellular matrix; PAS: Periodic acid-Schiff; ALT: alanine transaminase; ALP: alkaline phosphatase; TGC: triglycerides..