Time for a détente in the war on the mechanism of cellular fatty acid uptake

Glatz, Jan F. C.; Luiken, Joost J. F. P.

doi:10.1194/jlr.6192020lte

Cited by 27 publications

(28 citation statements)

References 24 publications

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“…Independent of its physiological function, it is obvious that CD36 may participate in abnormal FA utilization and its deleterious consequences during insulin resistance and obesity (reviewed in Refs. [ 26 , 27 , 28 , 29 , 30 , 31 ]).…”

Section: Comment On Cd36-assisted Fatty Acid Uptakementioning

confidence: 99%

CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting

Karunakaran

Elumalai

Moon

et al. 2021

Cells

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The cluster of differentiation 36 (CD36) is a scavenger receptor present on various types of cells and has multiple biological functions that may be important in inflammation and in the pathogenesis of metabolic diseases, including diabetes. Here, we consider recent insights into how the CD36 response becomes deregulated under metabolic conditions, as well as the therapeutic benefits of CD36 inhibition, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with metabolic diseases. To facilitate this process further, it is important to pinpoint regulatory mechanisms that are relevant under physiological and pathological conditions. In particular, understanding the mechanisms involved in dictating specific CD36 downstream cellular outcomes will aid in the discovery of potent compounds that target specific CD36 downstream signaling cascades.

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Section: Comment On Cd36-assisted Fatty Acid Uptakementioning

confidence: 99%

CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting

Karunakaran

Elumalai

Moon

et al. 2021

Cells

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“…Other findings indicate that a membrane transporter and cytosolic fatty acid-binding protein are required for fatty acid uptake [ 35 , 36 ]. An integrated mechanism that involves diffusion across the lipid bilayer combined with targeting and desorption by binding proteins has been proposed recently [ 37 ]. However, further studies will be necessary to resolve this uncertainty regarding the mechanism of plasma unesterified DHA uptake by the brain.…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of N-Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal Cells

Kevala

Lagarde

Spector

et al. 2020

IJMS

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We investigated the synthesis of N-docosahexaenoylethanolamine (synaptamide) in neuronal cells from unesterified docosahexaenoic acid (DHA) or DHA-lysophosphatidylcholine (DHA-lysoPC), the two major lipid forms that deliver DHA to the brain, in order to understand the formation of this neurotrophic and neuroprotective metabolite of DHA in the brain. Both substrates were taken up in Neuro2A cells and metabolized to N-docosahexaenoylphosphatidylethanolamine (NDoPE) and synaptamide in a time- and concentration-dependent manner, but unesterified DHA was 1.5 to 2.4 times more effective than DHA-lysoPC at equimolar concentrations. The plasmalogen NDoPE (pNDoPE) amounted more than 80% of NDoPE produced from DHA or DHA-lysoPC, with 16-carbon-pNDoPE being the most abundant species. Inhibition of N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD) by hexachlorophene or bithionol significantly decreased the synaptamide production, indicating that synaptamide synthesis is mediated at least in part via NDoPE hydrolysis. NDoPE formation occurred much more rapidly than synaptamide production, indicating a precursor–product relationship. Although NDoPE is an intermediate for synaptamide biosynthesis, only about 1% of newly synthesized NDoPE was converted to synaptamide, possibly suggesting additional biological function of NDoPE, particularly for pNDoPE, which is the major form of NDoPE produced.

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“…Despite many years of research, the protein structure and membrane topology were only elucidated in 2016. The fatty acid facilitator function of CD36 involves its interaction with other membranes and cytoplasmic proteins (Figure 1) [14].…”

Section: Cd36 Functions In Myocardial Fatty Acid Uptake and In Lipid Signalingmentioning

confidence: 99%

CD36 as a target for metabolic modulation therapy in cardiac disease

Glatz

Wang

Nabben

et al. 2021

Expert Opinion on Therapeutic Targets

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Introduction: Disturbances in myocardial lipid metabolism are increasingly being recognized as drivers of the development and progression of heart disease. Therefore, there is a need for treatments that can directly target lipid metabolic defects in heart failure. The membrane-associated glycoprotein CD36 plays a pivotal role in governing myocardial lipid metabolism by mediating lipid signaling and facilitating the cellular uptake of long-chain fatty acids. Emerging evidence suggests that CD36 is a prominent target in the treatment of heart failure.Areas covered: This article provides an overview of the key role of CD36 for proper contractile functioning of a healthy heart, its implications in the development of cardiac disease (ischemia/ reperfusion, cardiac hypertrophy, and diabetic cardiomyopathy), and its application as a target to normalize cardiac metabolism as part of so-called metabolic modulation therapy. Expert opinion: CD36 appears a promising and effective therapeutic target in the treatment of heart failure. Natural compounds and chemical agents known to alter the amount or subcellular distribution of CD36 or inhibit its functioning, should be evaluated for their potency to correct cardiac metabolism and cure heart disease.

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Time for a détente in the war on the mechanism of cellular fatty acid uptake

Abstract: This is an open access article under the CC BY license.

Cited by 27 publications

References 24 publications

CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting

CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting

Biosynthesis of N-Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal Cells

CD36 as a target for metabolic modulation therapy in cardiac disease

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