Targeted Deletion of Adipocyte Abca1 (ATP-Binding Cassette Transporter A1) Impairs Diet-Induced Obesity

Helen Cuffe, Mingxia Liu, Chia Chi C. Key, Elena Boudyguina, Janet K. Sawyer, Allison Weckerle, Alexander Bashore, Susan K. Fried, Soonkyu Chung, John S. Parks

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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 PPARγ (peroxisome proliferator-activated receptor γ) 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 PPARγ 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 PPARγ and SREBP1.

Original languageEnglish (US)
Pages (from-to)733-743
Number of pages11
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume38
Issue number4
DOIs
StatePublished - Apr 1 2018

Keywords

  • adipose tissue
  • animals
  • cholesterol
  • mice
  • obesity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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