Acyl-CoA synthetase 1 is induced by Gram-negative bacteria and
lipopolysaccharide and is required for phospholipid turnover in stimulated
Authors Rubinow KB, Wall VZ, Nelson J, Mar D, Bomsztyk K, Askari B, Lai MA, Smith KD,
Han MS, Vivekanandan-Giri A, Pennathur S, Albert CJ, Ford DA, Davis RJ,
Bornfeldt KE
Submitted By Submitted Externally on 5/5/2014
Status Published
Journal The Journal of biological chemistry
Year 2013
Date Published 4/5/2013
Volume : Pages 288 : 9957 - 9970
PubMed Reference 23426369
Abstract The enzyme acyl-CoA synthetase 1 (ACSL1) is induced by peroxisome
proliferator-activated receptor a (PPARa) and PPAR? in insulin target tissues,
such as skeletal muscle and adipose tissue, and plays an important role in
ß-oxidation in these tissues. In macrophages, however, ACSL1 mediates
inflammatory effects without significant effects on ß-oxidation. Thus, the
function of ACSL1 varies in different tissues. We therefore investigated the
signals and signal transduction pathways resulting in ACSL1 induction in
macrophages as well as the consequences of ACSL1 deficiency for phospholipid
turnover in LPS-activated macrophages. LPS, Gram-negative bacteria, IFN-?, and
TNFa all induce ACSL1 expression in macrophages, whereas PPAR agonists do not.
LPS-induced ACSL1 expression is dependent on Toll-like receptor 4 (TLR4) and its
adaptor protein TRIF (Toll-like receptor adaptor molecule 1) but does not
require the MyD88 (myeloid differentiation primary response gene 88) arm of TLR4
signaling; nor does it require STAT1 (signal transducer and activator of
transcription 1) for maximal induction. Furthermore, ACSL1 deletion attenuates
phospholipid turnover in LPS-stimulated macrophages. Thus, the regulation and
biological function of ACSL1 in macrophages differ markedly from that in insulin
target tissues. These results suggest that ACSL1 may have an important role in
the innate immune response. Further, these findings illustrate an interesting
paradigm in which the same enzyme, ACSL1, confers distinct biological effects in
different cell types, and these disparate functions are paralleled by
differences in the pathways that regulate its expression.

Investigators with authorship
Karol BomsztykUniversity of Washington