Cell metabolism, 2013-04, Vol.17 (4), p.575-585
2013
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Details
- Autor(en) / Beteiligte
- Titel
- Transcriptional Cofactor TBLR1 Controls Lipid Mobilization in White Adipose Tissue
- Ist Teil von
- Cell metabolism, 2013-04, Vol.17 (4), p.575-585
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2013
- Quelle
- Elektronische Zeitschriftenbibliothek (Open access)
- Beschreibungen/Notizen
- 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. [Display omitted] ► TBLR1 controls cAMP-dependent lipolysis in adipocytes ► Adipocyte-specific deletion of TBLR1 in mice impairs fasting-induced lipolysis ► Lack of TBLR1 in adipocytes aggravates diet-induced obesity and metabolic dysfunction ► TBLR1 mRNA levels in WAT are elevated under lipolytic conditions in mice and humans
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1550-4131eISSN: 1932-7420DOI: 10.1016/j.cmet.2013.02.010Titel-ID: cdi_proquest_miscellaneous_1324957564
- Format
- –
- Schlagworte
- 3T3-L1 Cells, Adipose Tissue, White - metabolism, Animals, Cyclic AMP - metabolism, Diet, High-Fat, Fatty Acids, Nonesterified - blood, Humans, Insulin Resistance, Lipid Mobilization - physiology, Lipolysis, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Obese, Obesity - metabolism, Obesity - pathology, Receptors, Adrenergic - genetics, Receptors, Adrenergic - metabolism, Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors, Receptors, Cytoplasmic and Nuclear - genetics, Receptors, Cytoplasmic and Nuclear - metabolism, RNA Interference, RNA, Messenger - metabolism, RNA, Small Interfering - metabolism, Signal Transduction