非靶向代谢组学揭示了通过磁共振成像评估的胰腺和肝脏异位脂肪的血浆代谢物预测因子：TOFI_Asia 研究。
Untargeted metabolomics reveals plasma metabolites predictive of ectopic fat in pancreas and liver as assessed by magnetic resonance imaging: the TOFI_Asia study.
机构信息
Food Nutrition & Health, Food and Bio-based Products, AgResearch Limited, Palmerston North, New Zealand.
School of Health Sciences, Massey University, Palmerston North, New Zealand.
出版信息
Int J Obes (Lond). 2021 Aug;45(8):1844-1854. doi: 10.1038/s41366-021-00854-x. Epub 2021 May 16.
BACKGROUND
Excess visceral obesity and ectopic organ fat is associated with increased risk of cardiometabolic disease. However, circulating markers for early detection of ectopic fat, particularly pancreas and liver, are lacking.
METHODS
Lipid storage in pancreas, liver, abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from 68 healthy or pre-diabetic Caucasian and Chinese women enroled in the TOFI_Asia study was assessed by magnetic resonance imaging/spectroscopy (MRI/S). Plasma metabolites were measured with untargeted liquid chromatography-mass spectroscopy (LC-MS). Multivariate partial least squares (PLS) regression identified metabolites predictive of VAT/SAT and ectopic fat; univariate linear regression adjusting for potential covariates identified individual metabolites associated with VAT/SAT and ectopic fat; linear regression adjusted for ethnicity identified clinical and anthropometric correlates for each fat depot.
RESULTS
PLS identified 56, 64 and 31 metabolites which jointly predicted pancreatic fat (R2Y = 0.81, Q2 = 0.69), liver fat (RY2 = 0.8, Q2 = 0.66) and VAT/SAT ((R2Y = 0.7, Q2 = 0.62)) respectively. Among the PLS-identified metabolites, none of them remained significantly associated with pancreatic fat after adjusting for all covariates. Dihydrosphingomyelin (dhSM(d36:0)), 3 phosphatidylethanolamines, 5 diacylglycerols (DG) and 40 triacylglycerols (TG) were associated with liver fat independent of covariates. Three DGs and 12 TGs were associated with VAT/SAT independent of covariates. Notably, comparison with clinical correlates showed better predictivity of ectopic fat by these PLS-identified plasma metabolite markers.
CONCLUSIONS
Untargeted metabolomics identified candidate markers of visceral and ectopic fat that improved fat level prediction over clinical markers. Several plasma metabolites were associated with level of liver fat and VAT/SAT ratio independent of age, total and visceral adiposity, whereas pancreatic fat deposition was only associated with increased sulfolithocholic acid independent of adiposity-related parameters, but not age.
背景
过多的内脏肥胖和异位器官脂肪与心血管代谢疾病风险增加有关。然而，目前缺乏用于早期检测异位脂肪的循环标志物，特别是胰腺和肝脏的标志物。
方法
通过磁共振成像/光谱（MRI/S）评估了来自 68 名健康或前驱糖尿病的白种人和中国人的胰腺、肝脏、腹部皮下脂肪组织（SAT）和内脏脂肪组织（VAT）的脂质储存。使用非靶向液相色谱-质谱（LC-MS）测量血浆代谢物。多元偏最小二乘（PLS）回归确定了预测 VAT/SAT 和异位脂肪的代谢物；通过单变量线性回归调整潜在协变量，确定了与 VAT/SAT 和异位脂肪相关的单个代谢物；通过线性回归调整种族，确定了每个脂肪库的临床和人体测量学相关性。
结果
PLS 鉴定出 56、64 和 31 种代谢物，它们共同预测胰腺脂肪（R2Y=0.81，Q2=0.69）、肝脏脂肪（RY2=0.8，Q2=0.66）和 VAT/SAT（R2Y=0.7，Q2=0.62）。在 PLS 鉴定的代谢物中，在调整所有协变量后，没有一种代谢物与胰腺脂肪仍显著相关。二氢神经酰胺（dhSM（d36：0））、3 种磷酯酰乙醇胺、5 种二酰甘油（DG）和 40 种三酰甘油（TG）与肝脏脂肪独立于协变量相关。3 种 DG 和 12 种 TG 与 VAT/SAT 独立于协变量相关。值得注意的是，与临床相关性的比较表明，这些通过非靶向代谢组学鉴定的血浆代谢物标志物对异位脂肪的预测性更好。
结论
非靶向代谢组学鉴定出了内脏和异位脂肪的候选标志物，这些标志物提高了脂肪水平预测的准确性，优于临床标志物。一些血浆代谢物与肝脏脂肪水平和 VAT/SAT 比值相关，独立于年龄、总脂肪量和内脏脂肪量，而胰腺脂肪沉积仅与 Sulfolithocholic 酸的增加相关，独立于与肥胖相关的参数，但与年龄无关。
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