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Liu, X. ; Khalil, A. ; Muthukumarasamy, U.* ; Onogi, Y. ; Yan, X. ; Singh, I. ; Lopez Gonzales, E. ; Israel, A. ; Cebrian Serrano, A. ; Strowig, T.* ; Ussar, S.

Reduced intestinal lipid absorption improves glucose metabolism in aged G2-Terc knockout mice.

BMC Biol. 21:150 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
Background: Biological aging is an important factor leading to the development of pathologies associated with metabolic dysregulation, including type 2 diabetes, cancer, cardiovascular and neurodegenerative diseases. Telomere length, a central feature of aging, has additionally been identified as inversely associated with glucose tolerance and the development of type 2 diabetes. However, the effects of shortened telomeres on body weight and metabolism remain incompletely understood. Here, we studied the metabolic consequences of moderate telomere shortening using second generation loss of telomerase activity in mice. Results: Aged male and female G2 Terc-/- mice and controls were characterized with respect to body weight and composition, glucose homeostasis, insulin sensitivity and metabolic activity. This was complemented with molecular and histological analysis of adipose tissue, liver and the intestine as well as microbiota analysis. We show that moderate telomere shortening leads to improved insulin sensitivity and glucose tolerance in aged male and female G2 Terc-/- mice. This is accompanied by reduced fat and lean mass in both sexes. Mechanistically, the metabolic improvement results from reduced dietary lipid uptake in the intestine, characterized by reduced gene expression of fatty acid transporters in enterocytes of the small intestine. Furthermore, G2-Terc-/- mice showed significant alterations in the composition of gut microbiota, potentially contributing to the improved glucose metabolism. Conclusions: Our study shows that moderate telomere shortening reduces intestinal lipid absorption, resulting in reduced adiposity and improved glucose metabolism in aged mice. These findings will guide future murine and human aging studies and provide important insights into the age associated development of type 2 diabetes and metabolic syndrome.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Adipose Tissue ; Aging ; Glucose Tolerance ; Insulin Sensitivity ; Lipid Absorption ; Microbiota ; Obesity ; Telomerase; Sexual-dimorphism; Insulin Sensitivity; Hyperglycemia; Association; Telomerase; Tolerance
e-ISSN 1741-7007
Zeitschrift BMC Biology
Quellenangaben Band: 21, Heft: 1, Seiten: , Artikelnummer: 150 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Förderungen China Scholarship Council
Alexander von Humboldt-Stiftung, Germany
Uehara Memorial Foundation, Japan
Helmholtz Zukunftsthema Aging and Metabolic Programming (AMPro)
Projekt DEAL