title: Differential effects of 1α,25-dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes.
abstract: OBJECTIVE
  Obesity is characterized by a low-grade inflammation in white adipose tissue (WAT), which promotes insulin resistance. Low serum levels of 1α,25-dihydroxycholecalciferol (DHCC) associate with insulin resistance and higher body mass index although it is unclear whether vitamin D supplementation improves insulin sensitivity. We investigated the effects of DHCC on adipokine gene expression and secretion in adipocytes focusing on two key factors with pro-inflammatory [monocyte chemoattractant protein-1 (MCP-1/CCL2)] and anti-inflammatory [adiponectin (ADIPOQ)] effects.
  
  
  METHODS
  Pre-adipocytes were isolated from human subcutaneous WAT and cultured until full differentiation. Differentiated adipocytes were either pre-treated with DHCC (10(-7) M) and subsequently incubated with tumor necrosis factor-α (TNFα, 100 ng/mL) or concomitantly incubated with TNFα/DHCC. MCP1 and adiponectin mRNA expression was measured by RT-PCR and protein release by ELISA.
  
  
  RESULTS
  DHCC was not toxic and did not affect adipocyte morphology or the mRNA levels of adipocyte-specific genes. TNFα induced a significant increase in CCL2 mRNA and protein secretion, while DHCC alone reduced CCL2 mRNA expression (~25%, p < 0.05). DHCC attenuated TNFα-induced CCL2 mRNA expression in both pre-incubation (~15%, p < 0.05) and concomitant (~60%, p < 0.01) treatments. TNFα reduced ADIPOQ mRNA (~80%) and secretion (~35%). DHCC alone decreased adiponectin secretion to a similar degree (~35%, p < 0.05). Concomitant treatment with DHCC/TNFα for 48 h had an additive effect, resulting in a pronounced reduction in adiponectin secretion (~70%).
  
  
  CONCLUSIONS
  DHCC attenuates MCP-1 and adiponectin production in human adipocytes, thereby reducing the expression of both pro- and anti-inflammatory factors. These effects may explain the difficulties so far in determining the role of DHCC in insulin sensitivity and obesity in humans.
authors.affiliation: Department of Medicine Huddinge, Lipid Laboratory, Karolinska Institutet, NVS, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden. Silvia.Lorente-Cebrian@ki.se
authors.forename: Silvia
authors.initials: S
authors.lastname: Lorente-Cebrián
authors.forename: Anna
authors.initials: A
authors.lastname: Eriksson
authors.forename: Thomas
authors.initials: T
authors.lastname: Dunlop
authors.forename: Niklas
authors.initials: N
authors.lastname: Mejhert
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.forename: Gaby
authors.initials: G
authors.lastname: Aström
authors.forename: Eva
authors.initials: E
authors.lastname: Sjölin
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wåhlén
authors.forename: Carsten
authors.initials: C
authors.lastname: Carlberg
authors.forename: Jurga
authors.initials: J
authors.lastname: Laurencikiene
authors.forename: Per
authors.initials: P
authors.lastname: Hedén
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052438:Adipocytes, White / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001823:Body Composition / Q000187:drug effects; D015992:Body Mass Index; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007333:Insulin Resistance; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D014409:Tumor Necrosis Factor-alpha; D002117:Calcitriol