Glucosamine increases macrophage lipid accumulation by regulating the mammalian target of rapamycin signaling pathway
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Elevated blood glucose is associated with an increased risk ofatherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosaminebiosynthetic pathway (HBP), promoted lipid accumulation inRAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced byGlcN in RAW264.7 cells, although there was no a significantchange in the rate of fatty acid uptake. GlcN increased acetylCoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory elementbinding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) andABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA bindingactivity. GlcN stimulated phosphorylation of mammalian targetof rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation inRAW264.7 cells. The GlcN-mediated increase in ACC and FASmRNA was suppressed, while the decrease in ABCA-1 andABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulationand further support a potential link between mTOR and HBPsignaling in lipogenesis.
Abstract
Elevated blood glucose is associated with an increased risk ofatherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosaminebiosynthetic pathway (HBP), promoted lipid accumulation inRAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced byGlcN in RAW264.7 cells, although there was no a significantchange in the rate of fatty acid uptake. GlcN increased acetylCoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory elementbinding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) andABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA bindingactivity. GlcN stimulated phosphorylation of mammalian targetof rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation inRAW264.7 cells. The GlcN-mediated increase in ACC and FASmRNA was suppressed, while the decrease in ABCA-1 andABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulationand further support a potential link between mTOR and HBPsignaling in lipogenesis.
참고문헌 (20)
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