title: Adipose acyl-CoA synthetase-1 directs fatty acids toward beta-oxidation and is required for cold thermogenesis.
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.
authors.affiliation: Department of Nutrition, 2301 MHRC, Dauer Drive, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Ellis
authors.forename: Lei O
authors.initials: LO
authors.lastname: Li
authors.forename: Pei-Chi
authors.initials: PC
authors.lastname: Wu
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Koves
authors.forename: Olga
authors.initials: O
authors.lastname: Ilkayeva
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.forename: Steven M
authors.initials: SM
authors.lastname: Watkins
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Muoio
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Coleman
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism*; D003080:Cold Temperature; D018752:Diet, Fat-Restricted; D005227:Fatty Acids / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D022722:Thermogenesis
chemical_list: D000322:Adrenergic Agonists; D005227:Fatty Acids; C544400:ACSL1 protein, mouse; D003066:Coenzyme A Ligases