Depletion of the TRF1 telomere-binding protein leads to leaner mice with improved metabolism

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. Our research not only contributes to the understanding of obesity onset but also positions TRF1 as a potential therapeutic target for combating metabolic syndrome. Tamoxifen (TMX) (Sigma Aldrich, T-5648-1G) was intraperitoneally (i.p.) injected to fifeteen-week-old female Trf1+/+ Cre+/t and Trf1lox/lox Cre+/t mice for three times a week for 5 weeks until the sacrifice.