title: Hexosamine biosynthesis is a possible mechanism underlying hypoxia's effects on lipid metabolism in human adipocytes.
abstract: BACKGROUND
  Hypoxia regulates adipocyte metabolism. Hexosamine biosynthesis is implicated in murine 3T3L1 adipocyte differentiation and is a possible underlying mechanism for hypoxia's effects on adipocyte metabolism.
  
  
  METHODS
  Lipid metabolism was studied in human visceral and subcutaneous adipocytes in in vitro hypoxic culture with adipophilic staining, glycerol release, and palmitate oxidation assays. Gene expression and hexosamine biosynthesis activation was studied with QRTPCR, immunofluorescence microscopy, and Western blotting.
  
  
  RESULTS
  Hypoxia inhibits lipogenesis and induces basal lipolysis in visceral and subcutaneous human adipocytes. Hypoxia induces fatty acid oxidation in visceral adipocytes but had no effect on fatty acid oxidation in subcutaneous adipocytes. Hypoxia inhibits hexosamine biosynthesis in adipocytes. Inhibition of hexosamine biosynthesis with azaserine attenuates lipogenesis and induces lipolysis in adipocytes in normoxic conditions, while promotion of hexosamine biosynthesis with glucosamine in hypoxic conditions slightly increases lipogenesis.
  
  
  CONCLUSIONS
  Hypoxia's net effect on human adipocyte lipid metabolism would be expected to impair adipocyte buffering capacity and contribute to systemic lipotoxicity. Our data suggest that hypoxia may mediate its effects on lipogenesis and lipolysis through inhibition of hexosamine biosynthesis. Hexosamine biosynthesis represents a target for manipulation of adipocyte metabolism.
authors: Department of Surgery, Oregon Health and Science University, Portland, Oregon, United States of America. orourkro@ohsu.edu
authors: Robert W
authors: RW
authors: O'Rourke
authors: Kevin A
authors: KA
authors: Meyer
authors: Garen
authors: G
authors: Gaston
authors: Ashley E
authors: AE
authors: White
authors: Carey N
authors: CN
authors: Lumeng
authors: Daniel L
authors: DL
authors: Marks
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation; D015687:Cell Hypoxia; D005260:Female; D006595:Hexosamines / Q000096:biosynthesis*; D006801:Humans; D050155:Lipogenesis; D008066:Lipolysis; D008297:Male; D008875:Middle Aged
chemical_list: D006595:Hexosamines
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