The metabolic response to dietary fat intake and its association with prediabetes are unclear. We aimed to identify the plasma metabolite profiles related to dietary fats and test if they are associated with prediabetes risk. Within the Precision Nutrition and Food Safety for Dietary Prevention of Chronic Disease cohort, we analyzed plasma metabolites from 207 participants (comprising 102 prediabetes cases and 105 controls) via untargeted metabolomics. Dietary fat intakes were assessed using a validated food frequency questionnaire. Metabolic signatures related to dietary fats were identified using elastic net regression and 10-fold cross-validation. The associations of metabolic signatures with prediabetes were evaluated using Poisson regression. We identified multi-metabolite profiles comprising 26 metabolites for intake of saturated fatty acids (SFAs), 32 metabolites for monounsaturated fatty acids (MUFAs), 27 metabolites for polyunsaturated fatty acids (PUFAs), 24 metabolites for n-3 PUFAs, and 25 metabolites for n-6 PUFAs. These metabolic signatures were robustly correlated with corresponding dietary fats intakes (Pearson r = 0.42–0.61; P < 0.001). After adjusting for potential risk factors, metabolic signatures of PUFAs (OR_{Q4 vs. Q1} = 0.57, 95% CI: 0.35–0.93) and n-3 PUFAs (OR_{Q4 vs. Q1} = 0.56, 95% CI: 0.34–0.92) were inversely associated with prediabetes prevalence but no significant associations were found for metabolic signatures of dietary SFAs, MUFAs, and n-6 PUFAs. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that dietary PUFAs and n-3 PUFAs promoted the pentose phosphate pathway and glycerolipid metabolism. Moreover, key metabolites related to PUFA/n-3 PUFA consumption were correlated with prediabetes. Our findings reveal the plasma metabolic signatures characterizing typical dietary fat intake and support the beneficial role of PUFAs, especially n-3 PUFAs, in prediabetes prevention by modulating the pentose phosphate pathway and glycerolipid metabolism.

Acrylamide is classified as a Class 2A carcinogen and mainly metabolized to produce hepatotoxicity. Phosphatidylcholine is thought to protect the liver from damage, but the protective role of phosphatidylcholine on acrylamide-exposed metabolic disorders remains unclear. We investigated protective effect of phosphatidylcholine on the hepatic metabolism in rats exposed to acrylamide using metabolomics and molecular biology approaches. Overall, 32 endogenous effect biomarkers and 4 exposure biomarkers were identified as differential signature metabolites responsible for acrylamide exposure and phosphatidylcholine protection. Acrylamide exposure interferes with glutathione metabolism by consuming antioxidant glutathione, cysteine and L-ascorbic acid, and disrupts lipid and carbohydrate metabolism through reducing carnitine content and increasing lipid peroxidation. The phosphatidylcholine treatment reduces the expression of cytochrome P450 2E1, alleviates the oxidative stress and inflammation of the liver, and stabilizes the content of glutathione, and thus alleviates the disorder of glutathione. Meanwhile, phosphatidylcholine shifted acrylamide-induced phosphatidylcholine into lysophosphatidylcholine to storage from lysophosphatidylcholine to diacylglycerol, thereby maintaining metabolic homeostasis of glycerophospholipid. The results suggested that phosphatidylcholine supplementation alleviate the disorder of glutathione and lipid metabolism caused by acrylamide exposure, but not significantly change the levels of mercapturic acid adducts of acrylamide, providing the evidence for phosphatidylcholine protection against acrylamide-induced liver injury.