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Leucine supplementation attenuates macrophage foamâ cell formation: Studies in humans, mice, and cultured macrophages
dc.contributor.authorGrajeda‐iglesias, Claudia
dc.contributor.authorRom, Oren
dc.contributor.authorHamoud, Shadi
dc.contributor.authorVolkova, Nina
dc.contributor.authorHayek, Tony
dc.contributor.authorAbu‐saleh, Niroz
dc.contributor.authorAviram, Michael
dc.date.accessioned2018-07-13T15:47:30Z
dc.date.available2019-07-01T14:52:17Zen
dc.date.issued2018-05
dc.identifier.citationGrajeda‐iglesias, Claudia ; Rom, Oren; Hamoud, Shadi; Volkova, Nina; Hayek, Tony; Abu‐saleh, Niroz ; Aviram, Michael (2018). "Leucine supplementation attenuates macrophage foamâ cell formation: Studies in humans, mice, and cultured macrophages." BioFactors 44(3): 245-262.
dc.identifier.issn0951-6433
dc.identifier.issn1872-8081
dc.identifier.urihttps://hdl.handle.net/2027.42/144642
dc.description.abstractWhereas atherogenicity of dietary lipids has been largely studied, relatively little is known about the possible contribution of dietary amino acids to macrophage foamâ cell formation, a hallmark of early atherogenesis. Recently, we showed that leucine has antiatherogenic properties in the macrophage model system. In this study, an inâ depth investigation of the role of leucine in macrophage lipid metabolism was conducted by supplementing humans, mice, or cultured macrophages with leucine. Macrophage incubation with serum obtained from healthy adults supplemented with leucine (5 g/d, 3 weeks) significantly decreased cellular cholesterol mass by inhibiting the rate of cholesterol biosynthesis and increasing cholesterol efflux from macrophages. Similarly, leucine supplementation to C57BL/6 mice (8 weeks) resulted in decreased cholesterol content in their harvested peritoneal macrophages (MPM) in relation with reduced cholesterol biosynthesis rate. Studies in J774A.1 murine macrophages revealed that leucine doseâ dependently decreased cellular cholesterol and triglyceride mass. Macrophages treated with leucine (0.2 mM) showed attenuated uptake of very lowâ density lipoproteins and triglyceride biosynthesis rate, with a concurrent downâ regulation of diacylglycerol acyltransferaseâ 1, a key enzyme catalyzing triglyceride biosynthesis in macrophages. Similar effects were observed when macrophages were treated with αâ ketoisocaproate, a key leucine metabolite. Finally, both in vivo and in vitro leucine supplementation significantly improved macrophage mitochondrial respiration and ATP production. The above studies, conducted in human, mice, and cultured macrophages, highlight a protective role for leucine attenuating macrophage foamâ cell formation by mechanisms related to the metabolism of cholesterol, triglycerides, and energy production. © 2018 BioFactors, 44(3):245â 262, 2018
dc.publisherSpringer
dc.publisherWiley Periodicals, Inc.
dc.subject.otherleucine
dc.subject.other뱉 ketoisocaproate
dc.subject.othermacrophages
dc.subject.otherlipid metabolism
dc.subject.otherfoamâ cell formation
dc.titleLeucine supplementation attenuates macrophage foamâ cell formation: Studies in humans, mice, and cultured macrophages
dc.typeArticleen_US
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/144642/1/biof1415.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/144642/2/biof1415_am.pdf
dc.identifier.doi10.1002/biof.1415
dc.identifier.sourceBioFactors
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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