Language
English
Publication Date
3-1-2025
Journal
Aging Cell
DOI
10.1111/acel.14499
PMID
39932851
PMCID
PMC11896407
PubMedCentral® Posted Date
3-1-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Inactivation of telomerase (TERT) in adipocyte progenitor cells (APC) expedites telomere attrition, and the onset of diabetes in mice fed high-fat diet (HFD), which promotes APC over-proliferation and replicative senescence. Here, we show that time-restricted feeding or caloric restriction in the postnatal development of mice subsequently subjected to HFD prevents telomere attrition but not glucose intolerance. This metabolic effect of dietary intervention was not observed for mice with TERT KO in endothelial or myeloid cells. To characterize the telomere-independent effects of TERT in the APC lineage, we analyzed mice with TERT knockout in mature adipocytes (AD-TERT-KO), which do not proliferate and avoid telomere attrition. Analysis of adipocytes from AD-TERT-KO mice indicated reliance on glycolysis and decreased mitochondrial oxidative metabolism. We show that AD-TERT-KO mice have reduced cold tolerance and metabolism abnormality indicating a defect in adaptive thermogenesis, characteristic of aging. Conversely, ectopic TERT expression in brown adipocytes-induced mitochondrial oxidation and thermogenic gene expression. We conclude that TERT plays an important non-canonical function in the mitochondria of adipocytes.
Keywords
Animals, Telomerase, Mice, Caloric Restriction, Telomere, Mitochondria, Mice, Knockout, Adipocytes, Stem Cells, Mice, Inbred C57BL, Male, Diet, High-Fat, adipocyte, mitochondria, progenitor, senescence, telomerase, telomere, TERT
Published Open-Access
yes
Recommended Citation
Gao, Zhanguo; Yu, Yongmei; Eckel-Mahan, Kristin; et al., "Caloric Restriction and Telomere Preservation in TERT Knockout Adipocyte Progenitors Does Not Rescue Mice From Metabolic Dysfunction due to a TERT Function in Adipocyte Mitochondria." (2025). The Brown Foundation: Institute of Molecular Medicine. 25.
https://digitalcommons.library.tmc.edu/molecular_med/25