Membrane transport of long-chain fatty acids: evidence for a facilitated process

Abumrad, Nada A.; Harmon, Carroll M.; Ibrahimi, Azeddine

doi:10.1016/s0022-2275(20)33310-1

Cited by 286 publications

(27 citation statements)

References 100 publications

(118 reference statements)

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“…Thus, the most parsimonious explanation for impaired NEFA oxidation in aging is a block in mitochondrial β‐oxidation. Additional factors affecting NEFA oxidation include fatty acid translocase CD36 regulated cellular entry of NEFA (Abumrad et al ., ; Febbraio et al ., ) and regulation by PPARα and PGC1α. Hepatic Cd36 transcripts were lower in O‐CON mice (with higher hepatic fat) and higher in O‐RX mice (with lower hepatic fat).…”

Section: Discussionmentioning

confidence: 98%

Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione

et al. 2013

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SummaryAging is associated with impaired fasted oxidation of nonesterified fatty acids (NEFA) suggesting a mitochondrial defect. Aging is also associated with deficiency of glutathione (GSH), an important mitochondrial antioxidant, and with insulin resistance. This study tested whether GSH deficiency in aging contributes to impaired mitochondrial NEFA oxidation and insulin resistance, and whether GSH restoration reverses these defects. Three studies were conducted: (i) in 82-week-old C57BL/6 mice, the effect of naturally occurring GSH deficiency and its restoration on mitochondrial 13 C 1 -palmitate oxidation and glucose metabolism was compared with 22-week-old C57BL/6 mice; (ii) in 20-week C57BL/6 mice, the effect of GSH depletion on mitochondrial oxidation of 13 C 1 -palmitate and glucose metabolism was studied; (iii) the effect of GSH deficiency and its restoration on fasted NEFA oxidation and insulin resistance was studied in GSHdeficient elderly humans, and compared with GSH-replete young humans. Chronic GSH deficiency in old mice and elderly humans was associated with decreased fasted mitochondrial NEFA oxidation and insulin resistance, and these defects were reversed with GSH restoration. Acute depletion of GSH in young mice resulted in lower mitochondrial NEFA oxidation, but did not alter glucose metabolism. These data suggest that GSH is a novel regulator of mitochondrial NEFA oxidation and insulin resistance in aging. Chronic GSH deficiency promotes impaired NEFA oxidation and insulin resistance, and GSH restoration reverses these defects. Supplementing diets of elderly humans with cysteine and glycine to correct GSH deficiency could provide significant metabolic benefits.

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Section: Discussionmentioning

confidence: 98%

Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione

et al. 2013

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“…Unlike the vascular wall, where the overexpression of scavenger receptors favors the atherosclerotic process, in nonvascular cells of distant tissues it could help lower plasma lipids, as CD36/FAT mediates the uptake of long-chain fatty acids [ 144 , 145 ]. However, although several independent studies have reported reduced lipid levels in the plasma of transgenic mice overexpressing CD36 [ 37 , 146 , 147 , 148 , 149 , 150 , 151 ], a larger analysis clearly suggests that CD36 and oxLDLs form a pathogenic pair in different tissues.…”

Section: The Oxldl Signalingmentioning

confidence: 99%

Oxidized LDLs as Signaling Molecules

2021

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Levels of oxidized low-density lipoproteins (oxLDLs) are usually low in vivo but can increase whenever the balance between formation and scavenging of free radicals is impaired. Under normal conditions, uptake and degradation represent the physiological cellular response to oxLDL exposure. The uptake of oxLDLs is mediated by cell surface scavenger receptors that may also act as signaling molecules. Under conditions of atherosclerosis, monocytes/macrophages and vascular smooth muscle cells highly exposed to oxLDLs tend to convert to foam cells due to the intracellular accumulation of lipids. Moreover, the atherogenic process is accelerated by the increased expression of the scavenger receptors CD36, SR-BI, LOX-1, and SRA in response to high levels of oxLDL and oxidized lipids. In some respects, the effects of oxLDLs, involving cell proliferation, inflammation, apoptosis, adhesion, migration, senescence, and gene expression, can be seen as an adaptive response to the rise of free radicals in the vascular system. Unlike highly reactive radicals, circulating oxLDLs may signal to cells at more distant sites and possibly trigger a systemic antioxidant defense, thus elevating the role of oxLDLs to that of signaling molecules with physiological relevance.

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“…Additional arguments for existence of receptor mediated NEFA uptake are based on experimental evidence. Studies of long chain FA uptake kinetics in intact cells [77,78], reviewed in [74,79,80], documented saturation of uptake at <10 nM unbound FA with competitive inhibition between different FAs [77] and suggested receptor-mediated uptake for FAs with hydrocarbon chains of more than 8 carbons. Similar conclusions were reached in a study of FA transfer using real time fluorescence microscopy that tested FA transfer inhibitors and long versus short chain FAs [81].…”

Section: Cellular Uptake Of Fatty Acidsmentioning

confidence: 99%

Lipolytic enzymes and free fatty acids at the endothelial interface

et al. 2021

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Lipids released from circulating lipoproteins by intravascular action of lipoprotein lipase (LpL) reach parenchymal cells in tissues with a non-fenestrated endothelium by transfer through or around endothelial cells. The actions of LpL are controlled at multiple sites, its synthesis and release by myocytes and adipocytes, its transit and association with the endothelial cell luminal surface, and finally its activation and inhibition by a number of proteins and by its product non-esterified fatty acids. Multiple pathways mediate endothelial transit of lipids into muscle and adipose tissues. These include movement of fatty acids via the endothelial cell fatty acid transporter CD36 and movement of whole or partially LpL-hydrolyzed lipoproteins via other apical endothelial cell receptors such as SR-B1and Alk1. Lipids also likely change the barrier function of the endothelium and operation of the paracellular pathway around endothelial cells. This review summarizes in vitro and in vivo support for the key role of endothelial cells in delivery of lipids and highlights incompletely understood processes that are the focus of active investigation.

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Membrane transport of long-chain fatty acids: evidence for a facilitated process

Cited by 286 publications

References 100 publications

Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione

Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione

Oxidized LDLs as Signaling Molecules

Lipolytic enzymes and free fatty acids at the endothelial interface

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