title: Obesity and weight loss result in increased adipose tissue ABCG1 expression in db/db mice.
abstract: The prevalence of obesity has reached epidemic proportions and is associated with several co-morbid conditions including diabetes, dyslipidemia, cancer, atherosclerosis and gallstones. Obesity is associated with low systemic inflammation and an accumulation of adipose tissue macrophages (ATMs) that are thought to modulate insulin resistance. ATMs may also modulate adipocyte metabolism and take up lipids released during adipocyte lipolysis and cell death. We suggest that high levels of free cholesterol residing in adipocytes are released during these processes and contribute to ATM activation and accumulation during obesity and caloric restriction. Db/db mice were studied for extent of adipose tissue inflammation under feeding conditions of ad libitum (AL) and caloric restriction (CR). The major finding was a marked elevation in epididymal adipose ABCG1 mRNA levels with obesity and CR (6-fold and 16-fold, respectively) over that seen for lean wild-type mice. ABCG1 protein was also elevated for CR as compared to AL adipose tissue. ABCG1 is likely produced by cholesterol loaded ATMs since this gene is not highly expressed in adipocytes and ABCG1 expression is sterol mediated. Our data supports the concept that metabolic changes in adipocytes due to demand lipolysis and cell death lead to cholesterol loading of ATMs. Based on finding cholesterol-loaded peritoneal leukocytes with elevated levels of ABCG1 in CR as compared to AL mice, we suggest that pathways for cholesterol trafficking out of adipose tissue involve ATM egress as well as ABCG1 mediated cholesterol efflux. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).
authors.affiliation: Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, and the Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98109, USA. Kimberly.edgel@med.navy.mil
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Edgel
authors.forename: Timothy S
authors.initials: TS
authors.lastname: McMillen
authors.forename: Hao
authors.initials: H
authors.lastname: Wei
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pamir
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Houston
authors.forename: Mark T
authors.initials: MT
authors.lastname: Caldwell
authors.forename: Phuong-Oanh T
authors.initials: PO
authors.lastname: Mai
authors.forename: John F
authors.initials: JF
authors.lastname: Oram
authors.forename: Chongren
authors.initials: C
authors.lastname: Tang
authors.forename: Renée C
authors.initials: RC
authors.lastname: Leboeuf
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D050153:Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D052438:Adipocytes, White / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D031204:Caloric Restriction; D002465:Cell Movement; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D008066:Lipolysis; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy / Q000378:metabolism* / Q000503:physiopathology; D014280:Triglycerides / Q000378:metabolism; D015431:Weight Loss; D000097382:CD68 Molecule
chemical_list: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002784:Cholesterol; D008074:Lipoproteins; D052247:Nitric Oxide Synthase Type II; D014280:Triglycerides; C487540:ABCG1 protein, mouse; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C496317:Nos2 protein, mouse