Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, 80131 Naples, Italy.
Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
Nutrients. 2019 Jun 10;11(6):1310. doi: 10.3390/nu11061310.
Vitamin D deficiency and obesity are two public health problems extensively exacerbated over the last years. Among the several mechanisms proposed to account for the complex interplay between vitamin D and obesity, one that has gained particular attention is related to the emerging role of obesity-related changes in gut microbiota and gut-derived metabolites, such as Trimethylamine-N-oxide (TMAO). Vitamin D deficiency and high circulating TMAO levels are associated with body weight and the severity of non-alcoholic fatty liver disease (NAFLD). Considering the link of obesity with vitamin D on the one hand and obesity with TMAO on the other hand, and the central role of the liver in both the vitamin D and TMAO metabolism, the aim of this cross-sectional observational study was first, to confirm the possible inverse association between vitamin D and TMAO across different body mass index (BMI) classes and second, to investigate if this association could be influenced by the presence of NAFLD. One hundred and four adult subjects (50 males and 54 females; 35.38 ± 7.49 years) were enrolled. The fatty liver index (FLI) was used as a proxy for the diagnosis of NAFLD. Vitamin D deficiency was found in 65 participants (62.5%), while 33 subjects (31.7%) had insufficient levels, and the remaining subjects had sufficient levels of vitamin D. Subjects with both vitamin D deficiency and FLI-NAFLD had the highest TMAO levels ( < 0.001). By stratifying the sample population according to the BMI classes, vitamin D levels decreased significantly along with the increase of plasma TMAO concentrations, with the lowest vitamin D levels and highest TMAO, respectively, in class III obesity. Vitamin D levels showed significant opposite associations with circulating levels of TMAO ( = -0.588, < 0.001), but this association was no longer significant after the adjustment for FLI values. The highest values of TMAO were significantly associated with the severity of obesity (OR 7.92; < 0.001), deficiency of vitamin D (OR 1.62; < 0.001), and FLI-NAFLD (OR 3.79; < 0.001). The most sensitive and specific cut-off for vitamin D to predict the circulating levels of TMAO was ≤19.83 ng/mL ( < 0.001). In conclusion, our study suggests that high TMAO levels are associated with vitamin D deficiency and NAFLD. Further studies are required to investigate if there is a causality link or whether all of them are simply the consequence of obesity.
维生素 D 缺乏症和肥胖症是近年来广泛加剧的两个公共卫生问题。在解释维生素 D 和肥胖症之间复杂相互作用的几种机制中，有一种机制引起了特别关注，即与肥胖相关的肠道微生物群和肠道衍生代谢物（如三甲胺 N-氧化物（TMAO））的变化有关。维生素 D 缺乏症和高循环 TMAO 水平与体重和非酒精性脂肪性肝病（NAFLD）的严重程度有关。考虑到肥胖症与维生素 D 之间的联系、肥胖症与 TMAO 之间的联系，以及肝脏在维生素 D 和 TMAO 代谢中的核心作用，本横断面观察性研究的目的首先是确认不同体重指数（BMI）类别中维生素 D 和 TMAO 之间可能存在的反比关系，其次是调查这种关联是否会受到 NAFLD 的影响。研究共纳入 104 名成年受试者（50 名男性和 54 名女性；35.38±7.49 岁）。脂肪肝指数（FLI）被用作诊断 NAFLD 的替代指标。65 名参与者（62.5%）存在维生素 D 缺乏症，33 名参与者（31.7%）存在维生素 D 不足，其余参与者的维生素 D 水平充足。同时患有维生素 D 缺乏症和 FLI-NAFLD 的受试者的 TMAO 水平最高（<0.001）。通过根据 BMI 类别对样本人群进行分层，维生素 D 水平随着血浆 TMAO 浓度的升高而显著降低，在 III 类肥胖中，维生素 D 水平最低，TMAO 水平最高。维生素 D 水平与循环 TMAO 水平呈显著负相关（= -0.588，<0.001），但在校正 FLI 值后，这种相关性不再显著。TMAO 的最高值与肥胖症的严重程度显著相关（OR 7.92；<0.001）、维生素 D 缺乏症（OR 1.62；<0.001）和 FLI-NAFLD（OR 3.79；<0.001）。维生素 D 预测 TMAO 循环水平的最敏感和最特异的截断值为≤19.83ng/ml（<0.001）。总之，我们的研究表明，高 TMAO 水平与维生素 D 缺乏症和 NAFLD 有关。需要进一步研究以确定是否存在因果关系，或者它们是否仅仅是肥胖的结果。
