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

Authors: Ellis, Jessica M; Li, Lei O; Wu, Pei-Chi; Koves, Timothy R; Ilkayeva, Olga; Stevens, Robert D; Watkins, Steven M; Muoio, Deborah M; Coleman, Rosalind A

Published In Cell Metab, (2010 Jul 7)

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.

PubMed ID: 20620995

MeSH Terms: No MeSH terms associated with this publication