PMID- 28187222 OWN - NLM STAT- MEDLINE DCOM- 20171004 LR - 20180515 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 102 IP - 7 DP - 2017 Jul 1 TI - Impaired Release of Vitamin D in Dysfunctional Adipose Tissue: New Cues on Vitamin D Supplementation in Obesity. PG - 2564-2574 LID - 10.1210/jc.2016-3591 [doi] AB - CONTEXT: Vitamin D accumulates in adipose tissue (AT), and vitamin D deficiency is frequent in obesity. OBJECTIVE: We hypothesize that trafficking of vitamin D is altered in dysfunctional AT. DESIGN, PATIENTS, SETTINGS: Fifty-four normal-weight and 67 obese males were recruited in a prospective study and randomly assigned to supplementation with 50 microg/wk 25-hydroxyvitamin-D3 or 150 microg/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. METHODS: 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), 1alpha-hydroxylase (Cyp27b1), and vitamin D receptor (Vdr) was analyzed by real-time polymerase chain reaction. RESULTS: 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 beta2-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. CONCLUSION: 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. CI - Copyright (c) 2017 by the Endocrine Society FAU - Di Nisio, Andrea AU - Di Nisio A AD - Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, 35128 Padova, Italy. FAU - De Toni, Luca AU - De Toni L AD - Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, 35128 Padova, Italy. FAU - Sabovic, Iva AU - Sabovic I AD - Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, 35128 Padova, Italy. AD - Familial Tumor Unit, Veneto Institute of Oncology Istituto Oncologico Veneto-Istituto di Ricovero e Cura a Carattere Scientifico, 35128 Padova, Italy. FAU - Rocca, Maria Santa AU - Rocca MS AD - Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, 35128 Padova, Italy. FAU - De Filippis, Vincenzo AU - De Filippis V AD - Laboratory of Protein Chemistry, Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35128 Padova, Italy. FAU - Opocher, Giuseppe AU - Opocher G AD - Familial Tumor Unit, Veneto Institute of Oncology Istituto Oncologico Veneto-Istituto di Ricovero e Cura a Carattere Scientifico, 35128 Padova, Italy. FAU - Azzena, Bruno AU - Azzena B AD - Burn Unit and Plastic Surgery, University Hospital of Padova, 35128 Padova, Italy. FAU - Vettor, Roberto AU - Vettor R AD - Department of Medicine, Internal Medicine, University of Padova, 35128 Padova, Italy. FAU - Plebani, Mario AU - Plebani M AD - Department of Medicine, Laboratory Medicine, University of Padova, 35128 Padova, Italy. FAU - Foresta, Carlo AU - Foresta C AD - Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, 35128 Padova, Italy. LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 1406-16-2 (Vitamin D) RN - P6YZ13C99Q (Calcifediol) SB - IM MH - Adipose Tissue/*metabolism/physiopathology MH - Administration, Oral MH - Adult MH - Blotting, Western MH - Body Mass Index MH - Body Weight MH - Calcifediol/*administration & dosage/pharmacokinetics MH - Case-Control Studies MH - *Dietary Supplements MH - Humans MH - Italy MH - Male MH - Middle Aged MH - Obesity/*drug therapy/metabolism MH - Prospective Studies MH - Reference Values MH - Treatment Outcome MH - Vitamin D/*administration & dosage/pharmacokinetics EDAT- 2017/02/12 06:00 MHDA- 2017/10/05 06:00 CRDT- 2017/02/11 06:00 PHST- 2016/11/02 00:00 [received] PHST- 2017/02/07 00:00 [accepted] PHST- 2017/02/12 06:00 [pubmed] PHST- 2017/10/05 06:00 [medline] PHST- 2017/02/11 06:00 [entrez] AID - 2982841 [pii] AID - 10.1210/jc.2016-3591 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2017 Jul 1;102(7):2564-2574. doi: 10.1210/jc.2016-3591.