title: Adipocyte ATP-binding cassette G1 promotes triglyceride storage, fat mass growth, and human obesity.
abstract: The role of the ATP-binding cassette G1 (ABCG1) transporter in human pathophysiology is still largely unknown. Indeed, beyond its role in mediating free cholesterol efflux to HDL, the ABCG1 transporter equally promotes lipid accumulation in a triglyceride (TG)-rich environment through regulation of the bioavailability of lipoprotein lipase (LPL). Because both ABCG1 and LPL are expressed in adipose tissue, we hypothesized that ABCG1 is implicated in adipocyte TG storage and therefore could be a major actor in adipose tissue fat accumulation. Silencing of Abcg1 expression by RNA interference in 3T3-L1 preadipocytes compromised LPL-dependent TG accumulation during the initial phase of differentiation. Generation of stable Abcg1 knockdown 3T3-L1 adipocytes revealed that Abcg1 deficiency reduces TG storage and diminishes lipid droplet size through inhibition of Pparγ expression. Strikingly, local inhibition of adipocyte Abcg1 in adipose tissue from mice fed a high-fat diet led to a rapid decrease of adiposity and weight gain. Analysis of two frequent ABCG1 single nucleotide polymorphisms (rs1893590 [A/C] and rs1378577 [T/G]) in morbidly obese individuals indicated that elevated ABCG1 expression in adipose tissue was associated with increased PPARγ expression and adiposity concomitant to increased fat mass and BMI (haplotype AT>GC). The critical role of ABCG1 in obesity was further confirmed in independent populations of severe obese and diabetic obese individuals. This study identifies for the first time a major role of adipocyte ABCG1 in adiposity and fat mass growth and suggests that adipose ABCG1 might represent a potential therapeutic target in obesity.
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Frisdal
authors.affiliation: INSERM, U1063, Angers, France.
authors.forename: Soazig
authors.initials: S
authors.lastname: Le Lay
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France INSERM, U872, Nutriomique Team 7, Cordeliers Research Center, Paris, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Hooton
authors.affiliation: Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Poupel
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Olivier
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France INSERM, U872, Nutriomique Team 7, Cordeliers Research Center, Paris, France.
authors.forename: Rohia
authors.initials: R
authors.lastname: Alili
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Patumwan, Bangkok, Thailand.
authors.forename: Wanee
authors.initials: W
authors.lastname: Plengpanich
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Elise F
authors.initials: EF
authors.lastname: Villard
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gilibert
authors.affiliation: Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lhomme
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Superville
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France.
authors.forename: Lobna
authors.initials: L
authors.lastname: Miftah-Alkhair
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: Laboratory of Vascular Medicine, AMC Amsterdam, Amsterdam, the Netherlands.
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France INSERM, U872, Nutriomique Team 7, Cordeliers Research Center, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Venteclef
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France INSERM, U872, Nutriomique Team 7, Cordeliers Research Center, Paris, France Heart and Metabolism, Assistance-Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Poitou
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France INSERM, U872, Nutriomique Team 7, Cordeliers Research Center, Paris, France.
authors.forename: Joan
authors.initials: J
authors.lastname: Tordjman
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesnik
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Huby
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France INSERM, U872, Nutriomique Team 7, Cordeliers Research Center, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dugail
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France INSERM, U872, Nutriomique Team 7, Cordeliers Research Center, Paris, France Heart and Metabolism, Assistance-Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Clement
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Maryse
authors.initials: M
authors.lastname: Guerin
authors.affiliation: INSERM, UMR_S1166, Team 4, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France wilfried.le_goff@upmc.fr.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Le Goff
mesh_terms: D041721:3T3-L1 Cells; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics / Q000502:physiology; D000328:Adult; D000818:Animals; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009767:Obesity, Morbid / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D034741:RNA, Small Interfering; D014280:Triglycerides / Q000378:metabolism*; D015430:Weight Gain / Q000235:genetics / Q000502:physiology
chemical_list: C419353:ABCG1 protein, human; C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D034741:RNA, Small Interfering; D014280:Triglycerides