Metabolic Reprogramming by Hexosamine Biosynthetic and Golgi N-Glycan Branching Pathways

doi:10.1038/srep23043

	Metabolic Reprogramming by Hexosamine Biosynthetic and Golgi N-Glycan Branching Pathways
	Chen, Rui 3,4; Ryczko, Michael C.1,2; Pawling, Judy 1; Rahman, Anas M. Abdel 1,5; Yau, Kevin 1; Copeland, Julia K.6; Zhang, Cunjie 1; Surendra, Anu 6; Guttman, David S.6; Figeys, Daniel 3,7
刊名	SCIENTIFIC REPORTS
	2016-03-14
卷号	6
ISSN号	2045-2322
DOI	10.1038/srep23043
文献子类	Article
英文摘要	De novo uridine-diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis requires glucose, glutamine, acetyl-CoA and uridine, however GlcNAc salvaged from glycoconjugate turnover and dietary sources also makes a significant contribution to the intracellular pool. Herein we ask whether dietary GlcNAc regulates nutrient transport and intermediate metabolism in C57BL/6 mice by increasing UDP-GlcNAc and in turn Golgi N-glycan branching. GlcNAc added to the drinking water showed a dose-dependent increase in growth of young mice, while in mature adult mice fat and body-weight increased without affecting calorie-intake, activity, energy expenditure, or the microbiome. Oral GlcNAc increased hepatic UDP-GlcNAc and N-glycan branching on hepatic glycoproteins. Glucose homeostasis, hepatic glycogen, lipid metabolism and response to fasting were altered with GlcNAc treatment. In cultured cells GlcNAc enhanced uptake of glucose, glutamine and fatty-acids, and enhanced lipid synthesis, while inhibition of Golgi N-glycan branching blocked GlcNAc-dependent lipid accumulation. The N-acetylglucosaminyltransferase enzymes of the N-glycan branching pathway (Mgat1,2,4,5) display multistep ultrasensitivity to UDP-GlcNAc, as well as branching-dependent compensation. Indeed, oral GlcNAc rescued fat accumulation in lean Mgat5(-/-) mice and in cultured Mgat5(-/-) hepatocytes, consistent with N-glycan branching compensation. Our results suggest GlcNAc reprograms cellular metabolism by enhancing nutrient uptake and lipid storage through the UDP-GlcNAc supply to N-glycan branching pathway.
WOS关键词	INSULIN-RESISTANCE ; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE ; TUMOR-CELLS ; F344 RATS ; GLYCOSYLATION ; OBESITY ; ACETYLGLUCOSAMINE ; MICE ; GLUCOSAMINE ; HOMEOSTASIS
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000371868700002
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/171064]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Dennis, James W.
作者单位	1.Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada 2.Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada 3.Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa Inst Syst Biol, Ottawa, ON K1H 8M5, Canada 4.Chinese Acad Sci, Dalian Inst Chem Phys, Natl Chromatog Res & Anal Ctr, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China 5.King Faisal Specialist Hosp & Res Ctr, Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia 6.Univ Toronto, Ctr Anal Genome Evolut & Funct, Toronto, ON M5S 3B2, Canada 7.Univ Ottawa, Fac Sci, Dept Chem, Ottawa, ON K1N 6N5, Canada 8.Univ Toronto, Dept Lab Med & Pathobiol, 100 Coll St, Toronto, ON M5S 1A8, Canada
推荐引用方式 GB/T 7714	Chen, Rui,Ryczko, Michael C.,Pawling, Judy,et al. Metabolic Reprogramming by Hexosamine Biosynthetic and Golgi N-Glycan Branching Pathways[J]. SCIENTIFIC REPORTS,2016,6.
APA	Chen, Rui.,Ryczko, Michael C..,Pawling, Judy.,Rahman, Anas M. Abdel.,Yau, Kevin.,...&Dennis, James W..(2016).Metabolic Reprogramming by Hexosamine Biosynthetic and Golgi N-Glycan Branching Pathways.SCIENTIFIC REPORTS,6.
MLA	Chen, Rui,et al."Metabolic Reprogramming by Hexosamine Biosynthetic and Golgi N-Glycan Branching Pathways".SCIENTIFIC REPORTS 6(2016).