title: Transcriptional cofactor TBLR1 controls lipid mobilization in white adipose tissue.
abstract: 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.
authors.affiliation: Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Rohm
authors.forename: Anke
authors.initials: A
authors.lastname: Sommerfeld
authors.forename: Daniela
authors.initials: D
authors.lastname: Strzoda
authors.forename: Allan
authors.initials: A
authors.lastname: Jones
authors.forename: Tjeerd P
authors.initials: TP
authors.lastname: Sijmonsma
authors.forename: Gottfried
authors.initials: G
authors.lastname: Rudofsky
authors.forename: Christian
authors.initials: C
authors.lastname: Wolfrum
authors.forename: Carsten
authors.initials: C
authors.lastname: Sticht
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.forename: Maximilian
authors.initials: M
authors.lastname: Zeyda
authors.forename: Lukas
authors.initials: L
authors.lastname: Leitner
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
authors.forename: Mauricio
authors.initials: M
authors.lastname: Berriel Diaz
authors.forename: Alexandros
authors.initials: A
authors.lastname: Vegiopoulos
authors.forename: Stephan
authors.initials: S
authors.lastname: Herzig
mesh_terms: D041721:3T3-L1 Cells; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D059305:Diet, High-Fat; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007333:Insulin Resistance; D008053:Lipid Mobilization / Q000502:physiology*; D008066:Lipolysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011941:Receptors, Adrenergic; D018160:Receptors, Cytoplasmic and Nuclear; D000242:Cyclic AMP