RAP1 protects from obesity through its extratelomeric role regulating gene expression

2015-01-13

RAP1 protects from obesity through its extratelomeric role regulating gene expression

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Abstract
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 PPARa signaling. We identify Ppara and Pgc1a as key factors affected by Rap1 deletion in the liver. We show that RAP1 binds to Ppara and Pgc1a loci and modulates their transcription. These findings reveal a role for a telomere-binding protein in the regulation of metabolism.

Some notes
mouse.
which is more severe in females than in males
a telomere-binding protein in the regulation of
metabolism.
of Obesity
Tissues and Show Signs of Liver Steatosis and
In?ammation
Some Signs of Metabolic Syndrome
in Rap1 -De?cient Females
in the Absence of Changes in Telomere Length and in
the Absence of Telomere Damage
Networks before the Onset of Obesity
Pgc1a in Rap1 -De?cient Livers
De?cient Livers upon Fasting
transcriptional regulator that controls the capacity of down-
stream metabolic pathways critical for metabolic maturation