ACSL1 is a key regulator of inflammatory and macrophage foaming induced by short-term palmitate exposure or acute high-fat feeding.
ACSL1 is a key regulator of inflammatory and macrophage foaming induced by short-term palmitate exposure or acute high-fat feeding.
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DOI：
10.1016/j.isci.2023.107145
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发表时间：
2023-07-21
期刊：
影响因子：
5.8
通讯作者：
Ahmad, Rasheed
中科院分区：
文献类型：
--
作者：
Al-Rashed, Fatema;Haddad, Dania;Al Madhoun, Ashraf;Sindhu, Sardar;Jacob, Texy;Kochumon, Shihab;Obeid, Lina M.;Al-Mulla, Fahd;Hannun, Yusuf A.;Ahmad, Rasheed
Foamy and inflammatory macrophages play pathogenic roles in metabolic disorders. However, the mechanisms that promote foamy and inflammatory macrophage phenotypes under acute-high-fat feeding (AHFF) remain elusive. Herein, we investigated the role of acyl-CoA synthetase-1 (ACSL1) in favoring the foamy/inflammatory phenotype of monocytes/macrophages upon short-term exposure to palmitate or AHFF. Palmitate exposure induced a foamy/inflammatory phenotype in macrophages which was associated with increased ACSL1 expression. Inhibition/knockdown of ACSL1 in macrophages suppressed the foamy/inflammatory phenotype through the inhibition of the CD36-FABP4-p38-PPARδ signaling axis. ACSL1 inhibition/knockdown suppressed macrophage foaming/inflammation after palmitate stimulation by downregulating the FABP4 expression. Similar results were obtained using primary human monocytes. As expected, oral administration of ACSL1 inhibitor triacsin-C in mice before AHFF normalized the inflammatory/foamy phenotype of the circulatory monocytes by suppressing FABP4 expression. Our results reveal that targeting ACSL1 leads to the attenuation of the CD36-FABP4-p38-PPARδ signaling axis, providing a therapeutic strategy to prevent the AHFF-induced macrophage foaming and inflammation. Short-term palmitate exposure induces ACSL1 ACSL1 activates the CD36/p38/PPARδ axis to induce macrophage foaming and inflammation ACSL1 is necessary for PPARs-induced CD36 activation involving FABP4 ACSL1 inhibition suppresses AHFF-induced inflammatory and foamy monocytes in mice Physiology; Cellular physiology; Immunology
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