Adipose acyl-CoA synthetase-1 directs fatty acids toward beta-oxidation and is required for cold thermogenesis.

Cell Metabolism
Jessica M EllisRosalind A Coleman

Abstract

Long-chain acyl-CoA synthetase-1 (ACSL1) contributes 80% of total ACSL activity in adipose tissue and was believed to be essential for the synthesis of triacylglycerol. We predicted that an adipose-specific knockout of ACSL1 (Acsl1(A-/-)) would be lipodystrophic, but compared to controls, Acsl1(A-/-) mice had 30% greater fat mass when fed a low-fat diet and gained weight normally when fed a high-fat diet. Acsl1(A-/-) adipocytes incorporated [(14)C]oleate into glycerolipids normally, but fatty acid (FA) oxidation rates were 50%-90% lower than in control adipocytes and mitochondria. Acsl1(A-/-) mice were markedly cold intolerant, and beta(3)-adrenergic agonists did not increase oxygen consumption, despite normal adrenergic signaling in brown adipose tissue. The reduced adipose FA oxidation and marked cold intolerance of Acsl1(A-/-) mice indicate that normal activation of FA for oxidation in adipose tissue in vivo requires ACSL1. Thus, ACSL1 has a specific function in directing the metabolic partitioning of FAs toward beta-oxidation in adipocytes.

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Citations

Sep 17, 2013·Current Atherosclerosis Reports·Ira J Goldberg, Karin E Bornfeldt
Jun 2, 2011·Chemical Reviews·Rosalind A Coleman, Douglas G Mashek
Jul 7, 2012·Chemical Research in Toxicology·Herve AloysiusRichard A Tschirret-Guth
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Mar 20, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yongzhao ZhangDavid E Cohen
Feb 9, 2011·The Journal of Biological Chemistry·Ming XuHao Zhu
Feb 22, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hye Won KangDavid E Cohen
Jan 20, 2011·Molecular and Cellular Biology·Jessica M EllisRosalind A Coleman
Mar 6, 2013·Molecular and Cellular Biology·Jessica M EllisMichael J Wolfgang
Dec 18, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Xin LiKarin E Bornfeldt
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Jul 23, 2016·Frontiers in Endocrinology·Tiffany L MortonMaya Styner
Feb 11, 2015·International Immunopharmacology·Chengyan ZhouJun Yin

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