title: Hypoxia increases adipogenesis and affects adipocytokine production in orbital fibroblasts-a possible explanation of the link between smoking and Graves' ophthalmopathy.
abstract: OBJECTIVE
  To assess the effects of hypoxia on human orbital fibroblasts (OF) on adipogenesis and adipocytokine production.
  
  
  METHODS
  Human OF were derived from tissues obtained from patients with Graves' ophthalmopathy (GO) and from patients without known thyroid diseases undergoing blepharoplasty. The OF were cultured separately under normoxic and hypoxic conditions. Comparisons of adipocytokine concentrations using multiplex ELISA and lipid accumulation in the cells using Oil Red O staining were subsequently performed.
  
  
  RESULTS
  There was increased adipogenesis in OF from GO subject when exposed to hypoxic culture conditions. This was not observed in OF from normal controls. Hypoxia led to an increase in leptin and a decrease in MCP-1 secretion in OF cultures.
  
  
  CONCLUSIONS
  Hypoxia induces adipogenesis in OF and may represent a mechanism by which smoking contributes to deterioration of GO. We also found novel changes to leptin and MCP-1 production in OF cultures exposed to hypoxia suggesting important roles of these cytokines in the disease process.
authors: Department of Endocrinology, Singapore General Hospital, Level 3, the Academia, 20 College Road 169856, Singapore.
authors: Chiaw Ling
authors: CL
authors: Chng
authors: Department of Clinical Research, Academia Discovery Tower Level 9 Research Office 2, 20 College Road 169856, Singapore.
authors: Oi Fah
authors: OF
authors: Lai
authors: Department of Clinical Research, Academia Discovery Tower Level 9 Research Office 2, 20 College Road 169856, Singapore.
authors: Charmaine Sze-Min
authors: CS
authors: Chew
authors: Department of Clinical Research, Academia Discovery Tower Level 9 Research Office 2, 20 College Road 169856, Singapore.
authors: Yu Pei
authors: YP
authors: Peh
authors: Department of Clinical Research, Academia Discovery Tower Level 9 Research Office 2, 20 College Road 169856, Singapore.
authors: Stephanie Man-Chung
authors: SM
authors: Fook-Chong
authors: Oculoplastic/Aesthetic Eyeplastic Service, Singapore National Eye Centre, 11 Third Hospital Avenue 168751, Singapore.
authors: Lay Leng
authors: LL
authors: Seah
authors: Department of Endocrinology, Singapore General Hospital, Level 3, the Academia, 20 College Road 169856, Singapore.
authors: Daphne Hsu-Chin
authors: DH
authors: Khoo
keywords: Graves' ophthalmopathy; hypoxia; smoking