血清25-羟维生素D与脂肪组织维生素D受体基因表达：与肥胖症和2型糖尿病的关系

Serum 25-hydroxyvitamin D and adipose tissue vitamin D receptor gene expression: relationship with obesity and type 2 diabetes.

作者信息

Clemente-Postigo Mercedes, Muñoz-Garach Araceli, Serrano Marta, Garrido-Sánchez Lourdes, Bernal-López M Rosa, Fernández-García Diego, Moreno-Santos Inmaculada, Garriga Nuria, Castellano-Castillo Daniel, Camargo Antonio, Fernández-Real Jose M, Cardona Fernando, Tinahones Francisco J, Macías-González Manuel

机构信息

Unidad de Gestión Clínica Endocrinología y Nutrición (M.C.-P., A.M.-G., L.G.-S., D.F.-G., D.C.-C., F.C., F.J.T., M.M.-G.), Instituto de Investigación Biomédica de Málaga (IBIMA), Complejo Hospitalario de Málaga (Virgen de la Victoria)/Universidad de Málaga, 29010 Málaga, Spain; Centro de Investigación Biomédica En Red, Pathophysiology of Obesity and Nutrition (CB06/03) (M.C.-P., L.G.-S., D.F.-G., A.C., J.M.F.-R., F.C., F.J.T., M.M.-G.), 28029, Madrid, Spain; Service of Diabetes, Endocrinology, and Nutrition (M.S., N.G., J.M.F.-R.), Institut d'Investigació Biomédica de Girona, 17007 Girona, Spain; Biomedical Research Laboratory (M.R.B.-L.), Internal Medicine Department, IBIMA, Regional University Hospital of Malaga (Carlos Haya Hospital), Universidad de Málaga, 29010 Málaga, Spain; Área del Corazón del Complejo Hospitalario de Málaga (Virgen de la Victoria) (I.M.-S.), IBIMA/Universidad de Malaga, Red de Investigación Cardiovascular, 29010 Málaga, Spain; and Lipid and Atherosclerosis Research Unit (IMIBIC) (A.C.), Reina Sofia University Hospital, University of Cordoba, 14004 Cordoba, Spain.

出版信息

J Clin Endocrinol Metab. 2015 Apr;100(4):E591-5. doi: 10.1210/jc.2014-3016. Epub 2015 Feb 23.

DOI:10.1210/jc.2014-3016

PMID:25706239

Abstract

CONTEXT

The relationship between 25-hydroxyvitamin D [25(OH)D] and obesity and type 2 diabetes is not completely understood. Vitamin D receptor (VDR) expression in adipose tissue (AT) is related to obesity and might be regulated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3].

OBJECTIVE

To analyze serum 25(OH)D and VDR gene expression in AT according to body mass index (BMI) and glycemic status and the effect of 1,25(OH)2D3 on AT according to BMI.

DESIGN AND PATIENTS

Two cohorts were studied: 1) 118 subjects classified according to their BMI (lean, overweight, obese, or morbidly obese [MO]) and their glycemic status (normoglycemic [NG] and prediabetic and diabetic [P&D]); and 2) 30 obese subjects (BMI > 30 kg/m(2)) classified as NG and P&D. VDR gene expression was analyzed during preadipocyte differentiation and in vitro stimulation with 1,25(OH)2D3 of AT explants from donors with different BMI values.

SETTING

University Hospital.

MAIN OUTCOME MEASURES

Serum 25(OH)D, parathyroid hormone (PTH), and AT VDR gene expression.

RESULTS

25(OH)D levels were lower in P&D than NG subjects, significantly so in the lean and MO groups (P < .05). 25(OH)D levels correlated negatively with homeostasis model of assessment for insulin resistance (HOMA-IR) (r = -0.200; P = .032) and glucose (r = -0.295; P = .001), but not with BMI. VDR gene expression was higher in MO than in the other BMI groups (P < .05). 1,25(OH)2D3 increased VDR gene expression in AT from obese patients (P < .05) but not from lean subjects.

CONCLUSIONS

25(OH)D levels are diminished in P&D compared to NG subjects, independently of BMI, and are closely related to glucose metabolism variables, suggesting that vitamin D deficiency is associated more with carbohydrate metabolism than with obesity. Moreover, AT has a different response to 1,25(OH)2D3 depending on the degree of obesity.

摘要

背景

25-羟基维生素D[25(OH)D]与肥胖症及2型糖尿病之间的关系尚未完全明确。脂肪组织（AT）中的维生素D受体（VDR）表达与肥胖症相关，且可能受1,25-二羟基维生素D3[1,25(OH)2D3]调控。

目的

根据体重指数（BMI）和血糖状态分析血清25(OH)D及AT中VDR基因表达情况，以及根据BMI分析1,25(OH)2D3对AT的影响。

设计与患者

研究了两个队列：1）118名受试者，根据其BMI（消瘦、超重、肥胖或病态肥胖[MO]）及血糖状态（血糖正常[NG]、糖尿病前期及糖尿病[P&D]）进行分类；2）30名肥胖受试者（BMI>30kg/m²），分为NG和P&D组。在脂肪前体细胞分化过程中以及用1,25(OH)2D3对来自不同BMI值供体的AT外植体进行体外刺激时，分析VDR基因表达。

地点

大学医院。

主要观察指标

血清25(OH)D、甲状旁腺激素（PTH）及AT中VDR基因表达。

结果

P&D组的25(OH)D水平低于NG组，在消瘦和MO组中差异显著（P<.05）。25(OH)D水平与胰岛素抵抗稳态模型评估（HOMA-IR）呈负相关（r=-0.200；P=.032），与血糖呈负相关（r=-0.295；P=.001），但与BMI无关。MO组的VDR基因表达高于其他BMI组（P<.05）。1,25(OH)2D3可增加肥胖患者AT中的VDR基因表达（P<.05），但对消瘦受试者无效。