Metabolic homeostasis and tissue renewal are dependent on beta1,6GlcNAc-branched N-glycans

Glycobiology. 2007 Aug;17(8):828-37. doi: 10.1093/glycob/cwm048. Epub 2007 May 4.


Golgi beta1,6-N-acetylglucosaminyltransferase V (Mgat5) produces beta1,6GlcNAc-branched N-glycans on glycoproteins, which increases their affinity for galectins and opposes loss from the cell surface to constitutive endocytosis. Oncogenic transformation increases Mgat5 expression, increases beta1,6GlcNAc-branched N-glycans on epidermal growth factor and transforming growth factor-beta receptors, and enhances sensitivities to ligands, cell motility, and tumor metastasis. Here, we demonstrate that Mgat5(-/-) mouse embryonic fibroblasts (MEFs) display reduced sensitivity to anabolic cytokines and reduced glucose uptake and proliferation. Mgat5(-/-) mice are also hypoglycemic, resistant to weight gain on a calorie-enriched diet, hypersensitive to fasting, and display increased oxidative respiration and reduced fecundity. Serum-dependent activation of the extracellular response kinase (growth) and Smad2/3 (arrest) pathways in Mgat5(-/-) MEFs and bone marrow cells reveals an imbalance favoring arrest. Mgat5(-/-) mice have fewer muscle satellite cells, less osteogenic activity in bone marrow, and accelerated loss of muscle and bone mass with aging. Our results suggest that beta1,6GlcNAc-branched N-glycans promote sensitivity to anabolic cytokines, and increase fat stores, tissue renewal, and longevity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Cells, Cultured
  • Glucose / metabolism
  • Glycoproteins / metabolism
  • Glycosylation
  • Homeostasis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • N-Acetylglucosaminyltransferases / chemistry
  • N-Acetylglucosaminyltransferases / metabolism*
  • Polysaccharides / metabolism*
  • Time Factors


  • Glycoproteins
  • Polysaccharides
  • N-Acetylglucosaminyltransferases
  • alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
  • Glucose