PMID- 17194745 OWN - NLM STAT- MEDLINE DCOM- 20070424 LR - 20181201 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 148 IP - 4 DP - 2007 Apr TI - Ablation of the cholesterol transporter adenosine triphosphate-binding cassette transporter G1 reduces adipose cell size and protects against diet-induced obesity. PG - 1561-73 AB - 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. FAU - Buchmann, Jana AU - Buchmann J AD - Department of Pharmacology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany. FAU - Meyer, Christoph AU - Meyer C FAU - Neschen, Susanne AU - Neschen S FAU - Augustin, Robert AU - Augustin R FAU - Schmolz, Katja AU - Schmolz K FAU - Kluge, Reinhart AU - Kluge R FAU - Al-Hasani, Hadi AU - Al-Hasani H FAU - Jurgens, Hella AU - Jurgens H FAU - Eulenberg, Karsten AU - Eulenberg K FAU - Wehr, Roland AU - Wehr R FAU - Dohrmann, Cord AU - Dohrmann C FAU - Joost, Hans-Georg AU - Joost HG FAU - Schurmann, Annette AU - Schurmann A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061228 PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (ABCG1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Lipoproteins) SB - IM MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/*genetics/physiology MH - Adipocytes/*cytology MH - Adipose Tissue/metabolism MH - Animals MH - Body Weight MH - *Cell Size MH - Diet/*adverse effects MH - Drosophila melanogaster MH - Female MH - Lipoproteins/*genetics/physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred NZB MH - Mice, Knockout MH - Mice, Obese MH - Obesity/etiology/genetics/*prevention & control EDAT- 2006/12/30 09:00 MHDA- 2007/04/25 09:00 CRDT- 2006/12/30 09:00 PHST- 2006/12/30 09:00 [pubmed] PHST- 2007/04/25 09:00 [medline] PHST- 2006/12/30 09:00 [entrez] AID - en.2006-1244 [pii] AID - 10.1210/en.2006-1244 [doi] PST - ppublish SO - Endocrinology. 2007 Apr;148(4):1561-73. doi: 10.1210/en.2006-1244. Epub 2006 Dec 28.