Adipose acyl-CoA synthetase-1 directs fatty acids toward beta-oxidation and is required for cold thermogenesis.
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.
Ellis
Jessica M
JM
Department of Nutrition, 2301 MHRC, Dauer Drive, University of North Carolina, Chapel Hill, NC 27599, USA.
Li
Lei O
LO
Wu
Pei-Chi
PC
Koves
Timothy R
TR
Ilkayeva
Olga
O
Stevens
Robert D
RD
Watkins
Steven M
SM
Muoio
Deborah M
DM
Coleman
Rosalind A
RA
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
D000322:Adrenergic Agonists; D005227:Fatty Acids; C544400:ACSL1 protein, mouse; D003066:Coenzyme A Ligases