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.
Highlights
ACAT (Acyl-CoA cholesterol acyl transferase) related enzyme 2 required for viability 1 (ARV1) is a transmembrane protein of the endoplasmic reticulum (ER) that is conserved between plants, yeast and mammals.[1,2]
The cDNA products were counts were corrected for the specific activity of the total [3H] in the diluted 1:20 into a final reaction volume of 12.5 μl in the wells of a 384-well plasma and normalized to the fasting body weight of each animal, reaction plate containing 300 nM of each forward and reverse primer, and reported as microgram oleate oxidized per kilogram body weight per hour
TGs were solubilized with the addition of 20 μl of RNA was present at a low level in all the tissues with greatest expression observed in the kidney, testes and brown adipose tissue (BAT) (Figure 1b, Supplementary Figure 1)
Summary
ACAT-related enzyme 2 required for viability 1 (ARV1) is a putative lipid transporter of the endoplasmic reticulum that is conserved across eukaryotic species. Animals were examined for alterations in lipid and lipoprotein levels, body weight, body composition, glucose tolerance and energy expenditure. RESULTS: Global loss of Arv[1] significantly decreased total cholesterol and high-density lipoprotein cholesterol levels in the plasma. Arv[1] 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 Arv[1] as an important player in mammalian lipid metabolism and whole-body energy homeostasis. Nutrition & Diabetes (2015) 5, e181; doi:10.1038/nutd.2015.32; published online 19 October 2015
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