E-GEOD-43658 - Transcriptional co-factor TBLR1 controls lipid mobilization in white adipose tissue
Released on 1 April 2013, last updated on 2 June 2014
Lipid mobilization (lipolysis) in white adipose tissue (WAT) critically controls lipid turnover and adiposity in humans. While the acute regulation of lipolysis has been studied in detail, the transcriptional determinants of WAT lipolytic activity remain still largely unexplored. Here we show that the genetic inactivation of transcriptional co-factor transducin beta-like-related (TBLR) 1 blunts the lipolytic response of white adipocytes through the impairment of cAMP-dependent signal transduction. Indeed, mice lacking TBLR1 in adipocytes are defective in fasting-induced lipid mobilization and when placed on a high fat diet show aggravated adiposity, glucose intolerance and insulin resistance. TBLR1 levels are found to increase under lipolytic conditions in WAT of both human patients and mice, correlating with serum free fatty acids (FFA). As a critical regulator of WAT cAMP signaling and lipid mobilization, proper activity of TBLR1 in adipocytes may thus represent a critical molecular checkpoint for the prevention of metabolic dysfunction in subjects with obesity-related disorders. We used microarrays to identify global gene expression in 3T3-L1 adipocytes lacking TBLR1 and compared gene expression to control shRNA treated cells in both basal and isoproterenol stimulated states. We analyzed 12 RNA samples extracted from 3T3-L1 adipocytes that were treated with either control or TBLR1 specific shRNAs and with or without 10 µM isoproterenol for 3 hrs. Three replicates of each condition.
transcription profiling by array
Carsten Sticht <email@example.com>, Alexandros Vegiopoulos, Allan Jones, Anke Sommerfeld, Christian Wolfrum, Daniela Strzoda, Gottfried Rudofsky, Lukas Leitner, Maria Rohm, Mauricio Berriel Diaz, Maximilian Zeyda, Norbert Gretz, Peter Nawroth, Stephan Herzig, Thomas Stulnig, Tjeerd Sijmonsma