Novel proteomic signatures may indicate MRI-assessed intrahepatic fat state and changes: The DIRECT PLUS clinical trial.

Here, we investigated the baseline proteomic profile associated with IHF% and the changes in proteomics associated with IHF% changes induced by lifestyle intervention.

在这里，我们研究了与IHF%相关的基线蛋白质组学特征，以及由生活方式干预引起的IHF%变化与蛋白质组学变化的关系。

approach_and_results

We calculated IHF% by proton magnetic resonance spectroscopy (normal IHF% <5% and abnormal IHF% ≥5%).

我们通过质子磁共振波谱法计算了IHF%（正常IHF% <5%，异常IHF% ≥5%）

We assayed baseline and 18-month samples for 95 proteomic biomarkers.Participants (age = 51.3 ± 10.8 y; 89% men; and body mass index = 31.3 ± 3.9 kg/m 2 ) had an 89.8% 18-month retention rate; 83% had eligible follow-up proteomics measurements, and 78% had follow-up proton magnetic resonance spectroscopy.

我们对基线和18个月的样本进行了95种蛋白质生物标志物的测定。参与者（年龄=51.3 ± 10.8岁；89%为男性；体质指数=31.3 ± 3.9 kg/m2）的18个月留存率为89.8%；83%有符合条件的随访蛋白质组学测量，78%有随访质子磁共振波谱。

At baseline, 39 candidate proteins were significantly associated with IHF% (false discovery rate <0.05), mostly related to immune function pathways (eg, hydroxyacid oxidase 1).

在基线时，39种候选蛋白与IHF%显著相关（假发现率<0.05），大多数与免疫功能通路相关（例如，羟酸氧化酶1）。

An IHF% prediction based on the DIRECT PLUS by combined model ( R2 = 0.47, root mean square error = 1.05) successfully predicted IHF% ( R2 = 0.53) during testing and was stronger than separately inputting proteins/traditional markers ( R2 = 0.43/0.44).

基于DIRECT PLUS的组合模型预测的IHF%（R2 = 0.47，均方根误差 = 1.05）在测试期间成功预测了IHF%（R2 = 0.53），并且比单独输入蛋白质/传统标志物（R2 = 0.43/0.44）更强。

The 18-month lifestyle intervention induced changes in 18 of the 39 candidate proteins, which were significantly associated with IHF% change, with proteins related to metabolism, extracellular matrix remodeling, and immune function pathways.

18个月的生活方式干预引起了39个候选蛋白中的18个发生变化，这些变化与内脏脂肪百分比（IHF%）的变化显著相关，涉及代谢、细胞外基质重塑和免疫功能通路的蛋白。

Thrombospondin-2 protein change was higher in the green-MED compared to the MED group, beyond weight and IHF% loss ( p = 0.01).

与MED组相比，绿色MED组的血小板反应蛋白-2（Thrombospondin-2）的变化更大，这超出了体重和内脏脂肪百分比（IHF%）的减少（p = 0.01）。

Protein principal component analysis revealed differences in the third principal component time distinct interactions across abnormal/normal IHF% trajectory combinations; p < 0.05 for all).

蛋白质主成分分析揭示了在第三主成分时间上，异常/正常IHF%轨迹组合之间存在显著差异（所有p < 0.05）。

Conclusions

Our findings suggest novel proteomic signatures that may indicate MRI-assessed IHF state and changes during lifestyle intervention.

我们的发现提示了可能指示MRI评估的IHF状态及其在生活方式干预期间变化的新蛋白质组学标志物。

Specifically, carbonic anhydrase 5A, hydroxyacid oxidase 1, and thrombospondin-2 protein changes are independently associated with IHF% change, and thrombospondin-2 protein change is greater in the green-MED/high polyphenols diet.

具体来说，碳酸酐酶5A、羟酸氧化酶1和血小板反应蛋白-2蛋白质的变化与IHF%变化独立相关，且血小板反应蛋白-2蛋白质在绿色-MED/高多酚饮食中的变化更为显著。