Ji Lijuan, Gupta Mihir, Feldman Brian J
Department of Pediatrics, Division of Pediatric Endocrinology, Stanford University School of Medicine, Stanford, California 94305-5457.
Endocrinology. 2016 Jan;157(1):91-7. doi: 10.1210/en.2015-1674. Epub 2015 Oct 21.
Fatty acids (FAs) are a major energy source in the body. White adipose tissue (WAT) is a primary site where FAs are stored as triacylglycerols. Brown adipose tissue also stores and recruits FAs as a carbon source for uncoupled β-oxidation during thermogenesis. The deletion of the vitamin D nuclear hormone receptor (VDR) gene in mice (VDRKO) results in a lean WAT phenotype with increased levels of expression of the brown adipose tissue marker Ucp1 in the WAT. However, the impact of vitamin D/VDR on FA composition in WAT has not been explored in detail. To address this question, we examined the FA composition of sc and visceral white adipose depots of VDRKO mice. We found that the levels of a subset of saturated and monounsaturated FAs of C18-C24 are specifically increased in the sc adipose depot in VDRKO mice. We revealed that a specific elongase enzyme (Elovl3), which has an important role in brown fat biology, is directly regulated by VDR and likely contributes to the altered FA composition in VDRKO mice. We also demonstrate that Elovl3 is regulated by vitamin D in vivo and tissue specifically in the sc WAT depot. We discovered that regulation of Elovl3 expression is mediated by ligand-dependent VDR occupancy of a negative-response element in the promoter proximal region of the Elovl3 gene. These data suggest that vitamin D/VDR tissue specifically modulates FA composition in sc WAT through direct regulation of Elovl3 expression.
脂肪酸（FAs）是机体的主要能量来源。白色脂肪组织（WAT）是脂肪酸以三酰甘油形式储存的主要部位。棕色脂肪组织也储存并募集脂肪酸，作为产热过程中解偶联β氧化的碳源。小鼠维生素D核激素受体（VDR）基因缺失（VDRKO）导致白色脂肪组织呈现瘦型表型，且白色脂肪组织中棕色脂肪组织标志物Ucp1的表达水平升高。然而，维生素D/VDR对白色脂肪组织中脂肪酸组成的影响尚未得到详细研究。为解决这个问题，我们检测了VDRKO小鼠皮下和内脏白色脂肪储存部位的脂肪酸组成。我们发现，VDRKO小鼠皮下脂肪储存部位中C18 - C24饱和脂肪酸和单不饱和脂肪酸子集的水平特异性升高。我们发现一种在棕色脂肪生物学中起重要作用的特定延长酶（Elovl3）受VDR直接调控，可能导致VDRKO小鼠脂肪酸组成改变。我们还证明Elovl3在体内受维生素D调控，且在皮下白色脂肪组织储存部位具有组织特异性。我们发现Elovl3表达的调控是由Elovl3基因启动子近端区域负反应元件的配体依赖性VDR占据介导的。这些数据表明，维生素D/VDR通过直接调控Elovl3表达在组织特异性上调节皮下白色脂肪组织中的脂肪酸组成。
