| Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance. | |
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MedLine Citation:
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PMID: 23291629 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Obesity develops as a result of altered energy homeostasis favoring fat storage. Here we describe a new transcription co-regulator for adiposity and energy metabolism, SERTA domain containing 2 (TRIP-Br2, also called SERTAD2). TRIP-Br2-null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of these knockout mice showed greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and β3-adrenergic (Adrb3) receptors. The knockout mice also have higher energy expenditure because of increased adipocyte thermogenesis and oxidative metabolism caused by upregulating key enzymes in their respective processes. Our data show that a cell-cycle transcriptional co-regulator, TRIP-Br2, modulates fat storage through simultaneous regulation of lipolysis, thermogenesis and oxidative metabolism. These data, together with the observation that TRIP-Br2 expression is selectively elevated in visceral fat in obese humans, suggests that this transcriptional co-regulator is a new therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia. |
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Authors:
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Chong Wee Liew; Jeremie Boucher; Jit Kong Cheong; Cecile Vernochet; Ho-Jin Koh; Cristina Mallol; Kristy Townsend; Dominique Langin; Dan Kawamori; Jiang Hu; Yu-Hua Tseng; Marc K Hellerstein; Stephen R Farmer; Laurie Goodyear; Alessandro Doria; Matthias Blüher; Stephen I-Hong Hsu; Rohit N Kulkarni |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2013-01-06 |
Journal Detail:
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Title: Nature medicine Volume: 19 ISSN: 1546-170X ISO Abbreviation: Nat. Med. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-02-07 Completed Date: 2013-04-17 Revised Date: 2013-06-06 |
Medline Journal Info:
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Nlm Unique ID: 9502015 Medline TA: Nat Med Country: United States |
Other Details:
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Languages: eng Pagination: 217-26 Citation Subset: IM |
Affiliation:
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Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3T3-L1 Cells Adipocytes / pathology Adolescent Adult Aged Aged, 80 and over Animals Dietary Fats / administration & dosage Female Humans Insulin Resistance* Lipolysis* Male Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Obesity / prevention & control* Oxidation-Reduction Receptors, Adrenergic, beta-3 / physiology Sterol Esterase / physiology Thermogenesis* Transcription Factors / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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1RL9EB008539-01/EB/NIBIB NIH HHS; DK51586/DK/NIDDK NIH HHS; DK58825/DK/NIDDK NIH HHS; K99 DK090210/DK/NIDDK NIH HHS; K99DK090210/DK/NIDDK NIH HHS; P30 DK36836/DK/NIDDK NIH HHS; R00 DK090210/DK/NIDDK NIH HHS; R00 DK090210/DK/NIDDK NIH HHS; R01 DK 67536/DK/NIDDK NIH HHS; R01 HL073168/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dietary Fats; 0/Receptors, Adrenergic, beta-3; 0/SERTAD2 protein, human; 0/Sertad2 protein, mouse; 0/Transcription Factors; EC 3.1.1.13/Sterol Esterase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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