Abstract 691: Arv1 Deletion Alters Fat Storage via Adipose-Extrinsic Mechanisms
ARE2 Required for Viability 1 (ARV1) is a transmembrane protein of the endoplasmic reticulum (ER) that is believed to promote intracellular sterol transport in yeast. Deletion of ARV1 in yeast causes lipid accumulation in the ER, altered membrane structure, and constitutive activation of the unfolded protein response. This protein is conserved in mammals, and human ARV1 is known to rescue the growth and viability defects in ARV1 deficient yeast. In previous work, we found that germline deletion of Arv1 in mice results in a 25% reduction in body weight, greatly reduced fat mass, increased energy expenditure, andimproved glucose tolerance. In the present work, we sought to test the hypothesis that loss of ARV1 activity in white and brown fat is responsible for the metabolic changes we observed. To test this, we utilized two different adipose-selective Cre drivers: Adiponectin-Cre and Ap2-Cre. Adiponectin-Cre mediated deletion was robust and highly specific to the white and brown fat, and had no impact on fat storage or blood glucose. In contrast, Ap2-Cre resulted in a substantial 53% decrease in Arv1 mRNA in the brain (p < 0.05), accompanied by reduced fat mass and markedly improved glucose tolerance. The data suggest that mammalian ARV1 controls metabolic rate and fat storage through non-adipocyte tissues, most likely involving the central nervous system.
Author Disclosures: K.E. Jarrett: None. R. Gupta: None. J.T. Billheimer: None. W.R. Lagor: None. D.J. Rader: None.
- © 2015 by American Heart Association, Inc.