RT Journal Article
T1 RAP1 Protects from Obesity through Its Extratelomeric Role Regulating Gene Expression
A1 Martínez, Paula
A1 Gómez-López, Gonzalo
A1 García, Fernando
A1 Mercken, Evi
A1 Mitchell, Sarah
A1 Flores Landeira, Juana María
A1 de Cabo, Rafael
A1 Blasco, Maria A.
AB RAP1 is part of shelterin, the protective complex at telomeres. RAP1 also binds along chromosome arms, where it is proposed to regulate gene expression. To investigate the nontelomeric roles of RAP1 in vivo, we generated a RAP1 whole-body knockout mouse. These mice show early onset of obesity, which is more severe in females than in males. Rap1-deficient mice show accumulation of abdominal fat, hepatic steatosis, and high-fasting plasma levels of insulin, glucose, cholesterol, and alanine aminotransferase. Gene expression analyses of liver and visceral white fat from Rap1-deficient mice before the onset of obesity show deregulation of metabolic programs, including fatty acid, glucose metabolism, and PPARα signaling. We identify Pparα and Pgc1α as key factors affected by Rap1 deletion in the liver. We show that RAP1 binds to Pparα and Pgc1α loci and modulates their transcription. These findings reveal a role for a telomere-binding protein in the regulation of metabolism
PB Cell Press
SN 2639-1856
YR 2013
FD 2013
LK https://hdl.handle.net/20.500.14352/131386
UL https://hdl.handle.net/20.500.14352/131386
LA eng
NO Martínez, P., Gómez-López, G., García, F., Mercken, E., Mitchell, S., Flores, J. M., de Cabo, R., & Blasco, M. A. (2013). RAP1 protects from obesity through its extratelomeric role regulating gene expression. Cell reports, 3(6), 2059–2074. https://doi.org/10.1016/j.celrep.2013.05.030
NO Author Contribution:M.A.B. conceived the original idea; M.A.B. and P.M. designed experiments and wrote the manuscript; P.M. performed most of the experiments; G.G.-L. performed the microarray analysis and FG de iTRAQ experiment; E.M., S.M., and R.d.C. carried out the indirect calorimetry measurements; and J.M.F. performed the pathology analyses.
NO European Commission
NO Ministerio de Economía, Comercio y Empresa (España)
NO Comunidad de Madrid
DS Docta Complutense
RD 18 mar 2026