Transcriptional Cofactor TBLR1 Controls Lipid Mobilization in White Adipose Tissue

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• 作者：Maria Rohm¹ ; Anke Sommerfeld¹ ; Daniela Strzoda¹ ; Allan Jones¹ ; Tjeerd P. Sijmonsma¹ ; Gottfried Rudofsky² ; Christian Wolfrum³ ; Carsten Sticht⁴ ; Norbert Gretz⁴ ; Maximilian Zeyda⁵ ; Lukas Leitner⁵ ; Peter P. Nawroth² ; Thomas M. Stulnig⁵ ; Mauricio Berriel Diaz¹ ; Alexandros Vegiopoulos¹ ; Stephan Herzig¹ ; ^{s.herzig@dkfz.de}
• 刊名：Cell Metabolism
• 出版年：2013
• 出版时间：2 April, 2013
• 年：2013
• 卷：17
• 期：4
• 页码：575-585
• 全文大小：1077 K

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Summary

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 cofactor transducin beta-like-related 1(TBLR1) 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 (FFAs). As a critical regulator of WAT cAMP signaling and lipid mobilization, proper activity of TBLR1 in adipocytes might thus represent a critical molecular checkpoint for the prevention of?metabolic dysfunction in subjects with obesity-related disorders.