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

SummaryLong-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 (Acsl1A−/−) would be lipodystrophic, but compared to controls, Acsl1A−/− mice had 30% greater fat mass when fed a low-fat diet and gained weight normally when fed a high-fat diet. Acsl1A−/− adipocytes incorporated [14C]oleate into glycerolipids normally, but fatty acid (FA) oxidation rates were 50%–90% lower than in control adipocytes and mitochondria. Acsl1A−/− mice were markedly cold intolerant, and β3-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 β-oxidation in adipocytes.

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► Adipose knockout of long-chain acyl-CoA synthetase-1 decreases ACS activity 80%
► Mice lacking ACSL1 are cold intolerant
► ACSL1 activates fatty acids that are directed toward β-oxidation