ACSL1 is a key regulator of inflammatory and macrophage foaming induced by short-term palmitate exposure or acute high-fat feeding

Al-Rashed, Fatema; Haddad, Dania; Madhoun, Ashraf Al; Sindhu, Sardar; Jacob, Texy; Kochumon, Shihab; Obeid, Lina M.; Al‐Mulla, Fahd; Hannun, Yusuf A.; Ahmad, Rasheed

doi:10.1016/j.isci.2023.107145

Cited by 4 publications

(1 citation statement)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This hypothesis finds support in numerous studies demonstrating that diverse stimuli can modulate CD36 gene expression independently of receptor activity, often mediated by transcription factors such as PPARs. 32 , 33 , 34 …”

Section: Discussionmentioning

confidence: 99%

PPARdelta: A key modulator in the pathogenesis of diabetes mellitus and Mycobacterium tuberculosis co-morbidity

AlSaeed,

Haider,

Alzaid

et al. 2024

iScience

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

PPARdelta: A key modulator in the pathogenesis of diabetes mellitus and Mycobacterium tuberculosis co-morbidity

AlSaeed,

Haider,

Alzaid

et al. 2024

iScience

View full text Add to dashboard Cite

Type I IFN induces long-chain acyl-CoA synthetase 1 to generate a phosphatidic acid reservoir for lipotoxic saturated fatty acids

Barnhart,

Shimizu-Albergine,

Kedar

et al. 2024

Journal of Lipid Research

View full text Add to dashboard Cite

ABCA1 and apoA-I dependent 12-hydroxyeicosatetraenoic acid efflux regulates macrophage inflammatory signaling

Harsch,

Borkowski,

Walker

et al. 2024

Preprint

View full text Add to dashboard Cite

Aberrant high-density lipoprotein (HDL) function is implicated in inflammation-associated pathologies. While HDL ABCA1-mediated reverse cholesterol and phospholipid transport are well described, the movement of pro-/anti-inflammatory lipids has not been explored. HDL phospholipids are the largest reservoir of circulating arachidonic acid-derived oxylipins. Endotoxin-stimulation activates inflammatory cells leading to hydroxyeicosatetraenoic acid (HETE) production, oxylipins which are involved in inflammatory response coordination. Active signaling in the non-esterified (NE) pool is terminated by sequestration of HETEs as esterified (Es) forms and degradation. We speculate that an ABCA1-apoA-I-dependent efflux of HETEs from stimulated cells could regulate intracellular HETE availability. Here we test this hypothesis both in vitro and in vivo. In endotoxin-stimulated RAW-264.7 macrophages preloaded with d8-arachidonic acid we use compartmental tracer modeling to characterize the formation of HETEs, and their efflux into HDL. We found that in response to endotoxin: I) Cellular NE 12-HETE is positively associated with MCP-1 secretion (p<0.001); II) HETE transfer from NE to Es pools is ABCA1-depedent (p<0.001); III) Cellular Es HETEs are transported into media when both apoA-I and ABCA1 are present (p<0.001); IV) The stimulated efflux of HETEs >> arachidonate (p<0.001). Finally, in endotoxin challenged humans (n=17), we demonstrate that intravenous lipopolysaccharide (0.6 ng/kg body weight) resulted in accumulation of 12-HETE in HDL over a 168-hour follow-up. Therefore, HDL can suppress inflammatory responses in macrophages by regulating intracellular HETE content in an apoA-I/ABCA1 dependent manner. The described mechanism may apply to other oxylipins and explain anti-inflammatory properties of HDL. This newly defined HDL property opens new doors for the study of lipoprotein interactions in metabolic diseases.

show abstract

ACSL1 is a key regulator of inflammatory and macrophage foaming induced by short-term palmitate exposure or acute high-fat feeding

Cited by 4 publications

References 63 publications

PPARdelta: A key modulator in the pathogenesis of diabetes mellitus and Mycobacterium tuberculosis co-morbidity

PPARdelta: A key modulator in the pathogenesis of diabetes mellitus and Mycobacterium tuberculosis co-morbidity

Type I IFN induces long-chain acyl-CoA synthetase 1 to generate a phosphatidic acid reservoir for lipotoxic saturated fatty acids

ABCA1 and apoA-I dependent 12-hydroxyeicosatetraenoic acid efflux regulates macrophage inflammatory signaling

Contact Info

Product

Resources

About