TERT expression attenuates metabolic disorders in obese mice by promoting adipose stem and progenitor cell expansion and differentiation
Abstract
Obesity is linked to limited adipose tissue (AT) remodeling capacity, leading to hypertrophic adipocytes, senescence, and inflammation. We used a mouse model expressing mTert (p21 +/Tert ) from the Cdkn1a locus to investigate the role of mTERT in obesity-induced metabolic disorders. Conditional expression of mTERT reduces metabolic disorders associated with obesity. In AT, this is accompanied by a decrease in the number of senescent p21-positive cells, very short telomeres, and oxidative DNA damage. Single nucleus RNA-seq data reveal TERT expression attenuates senescence induced by HFD in particular in adipose stem and progenitor cells (ASPC). We show that ASPC expansion and differentiation are promoted in p21 +/Tert obese mice, thereby reducing metabolic disorders. We further report that mTERT remodels the landscape of macrophages in AT of obese mice. Strikingly, inactivation of mTERT catalytic activity in p21 +/Tert (p21 +/TertCi ) mice suppresses the promotion of adipocyte formation, but neither affects attenuation of senescence nor macrophage remodeling. These results highlight mTERT’s canonical and non-canonical functions in reducing obesity-associated metabolic disorders. Conditional expression of TERT thus appears as a potential therapeutic option for obesity.
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BibTeX
@article{braud2026tert,
title = {{TERT expression attenuates metabolic disorders in obese mice by promoting adipose stem and progenitor cell expansion and differentiation}},
author = {Laura Braud and Manuel Bernabe and Julien Vernerey and Antonio M.A. Miranda and Andrea Dominguez and Dmitri Churikov and Manon Richaud and Frédéric Jourquin and Liam Mc Allan and Christophe Lachaud and Jesus Gil and Will Scott and Vincent Géli},
journal = {Molecular metabolism},
year = {2026},
month = nov,
doi = {10.1016/j.molmet.2025.102262},
url = {https://hal.science/hal-05855011v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - TERT expression attenuates metabolic disorders in obese mice by promoting adipose stem and progenitor cell expansion and differentiation
AU - Laura Braud
AU - Manuel Bernabe
AU - Julien Vernerey
AU - Antonio M.A. Miranda
AU - Andrea Dominguez
AU - Dmitri Churikov
AU - Manon Richaud
AU - Frédéric Jourquin
AU - Liam Mc Allan
AU - Christophe Lachaud
AU - Jesus Gil
AU - Will Scott
AU - Vincent Géli
PY - 2026
DA - 2026/11/06
JO - Molecular metabolism
DO - 10.1016/j.molmet.2025.102262
UR - https://hal.science/hal-05855011v1
AB - Obesity is linked to limited adipose tissue (AT) remodeling capacity, leading to hypertrophic adipocytes, senescence, and inflammation. We used a mouse model expressing mTert (p21 +/Tert ) from the Cdkn1a locus to investigate the role of mTERT in obesity-induced metabolic disorders. Conditional expression of mTERT reduces metabolic disorders associated with obesity. In AT, this is accompanied by a decrease in the number of senescent p21-positive cells, very short telomeres, and oxidative DNA damage. Single nucleus RNA-seq data reveal TERT expression attenuates senescence induced by HFD in particular in adipose stem and progenitor cells (ASPC). We show that ASPC expansion and differentiation are promoted in p21 +/Tert obese mice, thereby reducing metabolic disorders. We further report that mTERT remodels the landscape of macrophages in AT of obese mice. Strikingly, inactivation of mTERT catalytic activity in p21 +/Tert (p21 +/TertCi ) mice suppresses the promotion of adipocyte formation, but neither affects attenuation of senescence nor macrophage remodeling. These results highlight mTERT’s canonical and non-canonical functions in reducing obesity-associated metabolic disorders. Conditional expression of TERT thus appears as a potential therapeutic option for obesity.
SN - 2212-8778
ER -