| Ablation of the cholesterol transporter adenosine triphosphate-binding cassette transporter G1 reduces adipose cell size and protects against diet-induced obesity. | |
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MedLine Citation:
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PMID: 17194745 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The ATP-binding cassette transporter G1 (ABCG1) catalyzes export of cellular cholesterol from macrophages and hepatocytes. Here we identify an additional function of ABCG1 in the regulation of adiposity in screens of the Drosophila melanogaster and the New Zealand obese (NZO) mouse genomes. Insertion of modified transposable elements of the P-family upstream of CG17646, the Drosophila ortholog of Abcg1, generated lines of flies with increased triglyceride stores. In NZO mice, an Abcg1 variant was identified in a suggestive adiposity quantitative trait locus and was associated with higher expression of the gene in white adipose tissue. Targeted disruption of Abcg1 in mice resulted in reduced body weight gain (8.42+/-0.6 g in Abcg1-/- vs. 13.07+/-1.1 g in Abcg1+/+ mice) and adipose tissue mass gain (3.78+/-1.3 g in Abcg1-/- vs. 9.39+/-1.6 g in Abcg1+/+ mice) detected over a period of 12 wk. The reduction of adipose tissue mass in Abcg1-/- mice was associated with markedly decreased size of the adipocytes. In contrast to their wild-type littermates, male Abcg1-/- mice exhibited no high-fat diet-induced impairment of glucose tolerance and fatty liver. Furthermore, Abcg1-/- mice possess decreased food intake and elevated total energy expenditure (Abcg1-/- mice, 748.1+/-5.4 kJ/kg metabolic body mass; Abcg1+/+ mice, 684.3+/-5.0 kJ/kg metabolic body mass; P=0.011), body temperature (Abcg1-/- mice, 37.82+/-0.29 C; Abcg1+/+ mice, 36.83+/-0.24 C; P<0.05), and locomotor activity (Abcg1-/- mice, 3655+/-189 counts/12 h during dark phase; Abcg1+/+ mice, 2445+/-235 counts/12 h during dark phase; P<0.01). Our data indicate a previously unrecognized role of ABCG1 in the regulation of energy balance and triglyceride storage. |
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Authors:
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Jana Buchmann; Christoph Meyer; Susanne Neschen; Robert Augustin; Katja Schmolz; Reinhart Kluge; Hadi Al-Hasani; Hella Jürgens; Karsten Eulenberg; Roland Wehr; Cord Dohrmann; Hans-Georg Joost; Annette Schürmann |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-12-28 |
Journal Detail:
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Title: Endocrinology Volume: 148 ISSN: 0013-7227 ISO Abbreviation: Endocrinology Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-03-19 Completed Date: 2007-04-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 1561-73 Citation Subset: AIM; IM |
Affiliation:
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Department of Pharmacology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics*,
physiology Adipocytes / cytology* Adipose Tissue / metabolism Animals Body Weight Cell Size* Diet / adverse effects* Drosophila melanogaster Female Lipoproteins / genetics*, physiology Male Mice Mice, Inbred C57BL Mice, Inbred NZB Mice, Knockout Mice, Obese Obesity / etiology, genetics, prevention & control* |
| Chemical | |
Reg. No./Substance:
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0/ABCG1 protein, mouse; 0/ATP-Binding Cassette Transporters; 0/Lipoproteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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