Sanchez-Feutrie 2017 Abstract MITOEAGLE Barcelona

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COST Action MITOEAGLE
RAP250 deficiency protects from obesity, and enhances mitochondrial metabolism in adipose depots.

Link: MitoEAGLE

Sanchez-Feutrie M, Zorzano A (2017)

Event: MitoEAGLE Barcelona 2017

COST Action MITOEAGLE

RAP250 is a nuclear co-activator that potentiates the activity of nuclear hormone receptors and other transcription factors and it participates in the H3K4 methyltransferases MLL3/MLL4. We report that RAP250+/- mice are lean, and show enhanced energy expenditure, and improved glucose tolerance and insulin sensitivity. In addition, RAP250+/- mice were resistant to high-fat diet-induced obesity. The increased energy expenditure of RAP250 deficient mice was a consequence of enhanced oxidative activity of brown and white adipose tissues. Brown adipose tissue from RAP250 deficient mice showed enhanced glucose oxidation activity parallel to enhanced UCP1 expression. White adipose tissue switched to an oxidative transcriptional programme upon RAP250 gene inactivation, and that was characterized by an increased expression of key oxidative elements such as PGC-1α. We also demonstrate that RAP250 deficient cells show higher PKA activity, which explains the enhanced PGC-1α and increased oxidative activity in adipose tissue. Our results indicate that the nuclear co-factor RAP250 exerts a key role in glucose handling, energy expenditure, and adiposity. Protection from adiposity and insulin resistance is mediated by the control of oxidative metabolism in adipose depots. Our data suggest that inhibition of RAP250 may provide a healthy metabolic state under obesogenic conditions.


Bioblast editor: Kandolf G O2k-Network Lab: ES Barcelona Zorzano A


Labels: MiParea: nDNA;cell genetics, Exercise physiology;nutrition;life style, Pharmacology;toxicology  Pathology: Obesity 

Organism: Mouse  Tissue;cell: Fat 




Event: A3 


Affiliations

Sánchez-Feutrie M(1,2,3) Zorzano A(1,2,3)
  1. Inst Research Biomedicine (IRB Barcelona), Barcelona Inst Science Technol, Barcelona, Spain
  2. Dept Bioquímica Biomedicina Molecular, Fac Biologia, Univ Barcelona, Barcelona, Spain
  3. CIBER de Diabetes Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III