title: Deletion of murine Arv1 results in a lean phenotype with increased energy expenditure.
abstract: BACKGROUND
  ACAT-related enzyme 2 required for viability 1 (ARV1) is a putative lipid transporter of the endoplasmic reticulum that is conserved across eukaryotic species. The ARV1 protein contains a conserved N-terminal cytosolic zinc ribbon motif known as the ARV1 homology domain, followed by multiple transmembrane regions anchoring it in the ER. Deletion of ARV1 in yeast results in defective sterol trafficking, aberrant lipid synthesis, ER stress, membrane disorganization and hypersensitivity to fatty acids (FAs). We sought to investigate the role of Arv1 in mammalian lipid metabolism.
  
  
  METHODS
  Homologous recombination was used to disrupt the Arv1 gene in mice. Animals were examined for alterations in lipid and lipoprotein levels, body weight, body composition, glucose tolerance and energy expenditure.
  
  
  RESULTS
  Global loss of Arv1 significantly decreased total cholesterol and high-density lipoprotein cholesterol levels in the plasma. Arv1 knockout mice exhibited a dramatic lean phenotype, with major reductions in white adipose tissue (WAT) mass and body weight on a chow diet. This loss of WAT is accompanied by improved glucose tolerance, higher adiponectin levels, increased energy expenditure and greater rates of whole-body FA oxidation.
  
  
  CONCLUSIONS
  This work identifies Arv1 as an important player in mammalian lipid metabolism and whole-body energy homeostasis.
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: W R
authors.initials: WR
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authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.initials: F
authors.lastname: Tong
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
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authors.initials: KE
authors.lastname: Jarrett
authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.initials: DM
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authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.lastname: Smith
authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.initials: DW
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authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: O'Neill
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
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authors.initials: R
authors.lastname: Gupta
authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.initials: A
authors.lastname: Kumaravel
authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Redon
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Ahima
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Sturley
authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.initials: JT
authors.lastname: Billheimer
authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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authors.initials: DJ
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