title: Impaired Release of Vitamin D in Dysfunctional Adipose Tissue: New Cues on Vitamin D Supplementation in Obesity.
abstract: Vitamin D accumulates in adipose tissue (AT), and vitamin D deficiency is frequent in obesity.
  
  
  
  We hypothesize that trafficking of vitamin D is altered in dysfunctional AT.
  
  
  
  Fifty-four normal-weight and 67 obese males were recruited in a prospective study and randomly assigned to supplementation with 50 µg/wk 25-hydroxyvitamin-D3 or 150 µg/wk vitamin D3 for 1 year, raising dosage by 50% if vitamin D sufficiency [serum 25-hydroxyvitamin-D3 >50 nmol/L], was not achieved at 6 months; 97 subjects completed the study.
  
  
  
  Vitamin D3 and 25-hydroxyvitamin-D3 were quantified by HPLC-MS in control and insulin-resistant (IR) 3T3-L1 cells and subcutaneous AT (SAT) from lean and obese subjects, incubated with or without adrenaline; expression of 25-hydroxylase (Cyp27a1), 1α-hydroxylase (Cyp27b1), and vitamin D receptor (Vdr) was analyzed by real-time polymerase chain reaction.
  
  
  
  In IR adipocytes, uptake of D3 and 25-hydroxyvitamin-D3 was higher, but, after adrenaline stimulation, the decrement in D3 and 25-hydroxyvitamin-D3 was stronger in control cells, which also showed increased expression of Cyp27a1 and Cyp27b1 and higher levels of 25-hydroxyvitamin-D3. In SAT from obese subjects, adrenaline-induced release of D3 and 25-hydroxyvitamin-D3 was blunted; in both IR cells and obese SAT, protein expression of β2-adrenergic receptor was reduced. Supplementation with 25-hydroxyvitamin-D3 was more effective in achieving vitamin D sufficiency in obese, but not in normal weight subjects.
  
  
  
  Dysfunctional AT shows a reduced catecholamine-induced release of D3 and 25-hydroxyvitamin-D3 and altered activity of vitamin D-metabolizing enzymes; for these reasons supplementation with 25-hydroxyvitamin-D3 is more effective in obese individuals.
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, 35128 Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Nisio
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, 35128 Padova, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: De Toni
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, 35128 Padova, Italy.|Familial Tumor Unit, Veneto Institute of Oncology Istituto Oncologico Veneto-Istituto di Ricovero e Cura a Carattere Scientifico, 35128 Padova, Italy.
authors.forename: Iva
authors.initials: I
authors.lastname: Sabovic
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, 35128 Padova, Italy.
authors.forename: Maria Santa
authors.initials: MS
authors.lastname: Rocca
authors.affiliation: Laboratory of Protein Chemistry, Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35128 Padova, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Filippis
authors.affiliation: Familial Tumor Unit, Veneto Institute of Oncology Istituto Oncologico Veneto-Istituto di Ricovero e Cura a Carattere Scientifico, 35128 Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Opocher
authors.affiliation: Burn Unit and Plastic Surgery, University Hospital of Padova, 35128 Padova, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Azzena
authors.affiliation: Department of Medicine, Internal Medicine, University of Padova, 35128 Padova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.affiliation: Department of Medicine, Laboratory Medicine, University of Padova, 35128 Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.affiliation: Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, 35128 Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology; D000284:Administration, Oral; D000328:Adult; D015153:Blotting, Western; D015992:Body Mass Index; D001835:Body Weight; D002112:Calcifediol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016022:Case-Control Studies; D019587:Dietary Supplements; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D011446:Prospective Studies; D012016:Reference Values; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D014807:Vitamin D; D002112:Calcifediol