Department of Community Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Int J Obes (Lond). 2018 Oct;42(10):1782-1796. doi: 10.1038/s41366-018-0107-0. Epub 2018 Jun 11.
Uncertainty remains about the effect of vitamin D therapy on biomarkers of health status in obesity. The molecular basis underlying this controversy is largely unknown.
To address the existing gap, our study sought to compare changes in metabolomic profiles of obesity phenotypes (metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO)) patients with sub-optimal levels of vitamin D following vitamin D supplementation.
We conducted two randomized double-blind clinical trials on participants with either of the two obesity phenotypes from Tehran province. These phenotypes were determined by the Adult Treatment Panel-III criteria. Patients in each of the MHO (n = 110) and MUHO (n = 105) groups were separately assigned to receive either vitamin D (4000 IU/d) or placebo for 4 months. Pre- and post-supplementation plasma metabolomic profiling were performed using Liquid chromatography coupled to a triple quadrupole mass spectrometry. Multivariable linear regression was used to explore the association of change in each metabolite with the trial assignment (vitamin D/placebo) across obesity phenotypes.
Metabolites (n = 104) were profiled in 82 MHO and 78 MUHO patients. After correction for multiple comparisons, acyl-lysophosphatidylcholines C16:0, C18:0, and C18:1, diacyl-phosphatidylcholines C32:0, C34:1, C38:3, and C38:4, and sphingomyelin C40:4 changed significantly in response to vitamin D supplementation only in MUHO phenotype. The interaction analysis revealed that vitamin D therapy was different between the two obesity phenotypes based on acyl-lysophosphatidylcholines C16:0 and C16:1 and citrulline which were altered significantly after supplementation. Changes in metabolites were associated with changes in cardiometabolic biomarkers after the intervention.
Vitamin D treatment influenced the obesity-related plasma metabolites only in adults with obesity and metabolically unhealthy phenotype. Therefore, not all patients with obesity may benefit from an identical strategy for vitamin D therapy. These findings provide mechanistic basis highlighting the potential of precision medicine to mitigate diseases in health-care settings.
维生素 D 治疗对肥胖患者健康状况生物标志物的影响仍存在不确定性。这种争议的根本原因在很大程度上尚不清楚。
为了解决这一现有差距，我们的研究旨在比较维生素 D 补充后，维生素 D 水平不理想的肥胖表型（代谢健康肥胖（MHO）和代谢不健康肥胖（MUHO））患者的代谢组学谱变化。
我们在德黑兰省进行了两项针对两种肥胖表型患者的随机双盲临床试验。这些表型是根据成人治疗小组-III 标准确定的。MHO 组（n=110）和 MUHO 组（n=105）中的每位患者分别被随机分配接受维生素 D（4000 IU/d）或安慰剂治疗 4 个月。使用液相色谱-三重四极杆质谱联用对预补充和补充后的血浆代谢组学进行分析。多变量线性回归用于探索每个代谢物的变化与试验分配（维生素 D/安慰剂）之间的关联，以及在肥胖表型中的变化。
在 82 名 MHO 和 78 名 MUHO 患者中分析了 104 种代谢物。经多次比较校正后，酰基辅酶 A-溶血磷脂酰胆碱 C16:0、C18:0 和 C18:1、二酰基磷脂酰胆碱 C32:0、C34:1、C38:3 和 C38:4、和鞘磷脂 C40:4 在 MUHO 表型中仅对维生素 D 补充有显著变化。交互分析显示，两种肥胖表型之间的维生素 D 治疗不同，基于酰基辅酶 A-溶血磷脂酰胆碱 C16:0 和 C16:1 和瓜氨酸，这些物质在补充后有明显变化。干预后，代谢物的变化与心脏代谢生物标志物的变化相关。
维生素 D 治疗仅在肥胖且代谢不健康的成年人中影响与肥胖相关的血浆代谢物。因此，并非所有肥胖患者都可能从相同的维生素 D 治疗策略中受益。这些发现提供了机制基础，强调了精准医学在医疗保健环境中减轻疾病的潜力。
