| First Author | Cuffe H | Year | 2018 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 38 |
| Issue | 4 | Pages | 733-743 |
| PubMed ID | 29348118 | Mgi Jnum | J:274837 |
| Mgi Id | MGI:6296397 | Doi | 10.1161/ATVBAHA.117.309880 |
| Citation | Cuffe H, et al. (2018) Targeted Deletion of Adipocyte Abca1 (ATP-Binding Cassette Transporter A1) Impairs Diet-Induced Obesity. Arterioscler Thromb Vasc Biol 38(4):733-743 |
| abstractText | OBJECTIVE: Adipose tissue cholesterol increases with adipocyte triglyceride content and size during development of obesity. However, how adipocyte cholesterol affects adipocyte function is poorly understood. The aim of this study was to evaluate the role of the cellular cholesterol exporter, Abca1 (ATP-binding cassette transporter A1), on adipose tissue function during diet-induced obesity. APPROACH AND RESULTS: Adiponectin Cre recombinase transgenic mice were crossed with Abca1(flox/flox) mice to generate ASKO (adipocyte-specific Abca1 knockout) mice. Control and ASKO mice were then fed a high-fat, high-cholesterol (45% calories as fat and 0.2% cholesterol) diet for 16 weeks. Compared with control mice, ASKO mice had a 2-fold increase in adipocyte plasma membrane cholesterol content and significantly lower body weight, epididymal fat pad weight, and adipocyte size. ASKO versus control adipose tissue had decreased PPARgamma (peroxisome proliferator-activated receptor gamma) and CCAAT/enhancer-binding protein expression, nuclear SREBP1 (sterol regulatory element-binding protein 1) protein, lipogenesis, and triglyceride accretion but similar Akt activation after acute insulin stimulation. Acute siRNA-mediated Abca1 silencing during 3T3L1 adipocyte differentiation reduced adipocyte Abca1 and PPARgamma protein expression and triglyceride content. Systemic stimulated triglyceride lipolysis and glucose homeostasis were similar between control and ASKO mice. CONCLUSIONS: Adipocyte Abca1 is a key regulator of adipocyte lipogenesis and lipid accretion, likely because of increased adipose tissue membrane cholesterol, resulting in decreased activation of lipogenic transcription factors PPARgamma and SREBP1. |
