Adipose Acyl-CoA Synthetase-1 Directs Fatty Acids toward beta-Oxidation and Is Required for Cold Thermogenesis

作者：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^*

来源：Cell Metabolism, 2010, 12(1): 53-64.

DOI：10.1016/j.cmet.2010.05.012

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 Acsl1A(-/-) 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.

• 出版日期2010-7-7