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Background <p>Non-alcoholic fatty liver disease (NAFLD) has been associated with metabolic syndrome (MetS). One of the underlying mechanisms of NAFLD is an aberration in amino acid metabolism and signalling. The tocotrienol-rich fraction (TRF) has been shown to improve NAFLD and is thus recommended as a supplement in NAFLD. However, TRF often exhibits low bioavailability. Recently, our group reported that TRF with medium-chain triglyceride (MCT) carriers could potentially improve steatosis, bile acid metabolism, lipid, and fatty acid metabolism.</p> Objective <p>This study investigated the effects of TRF-MCT on amino acid metabolism in an NAFLD mice model.</p> Methods <p>Male B6.Cg-LepOb/J mice were used as an NAFLD mouse model and randomly divided into three groups: high-fat diet only (HFD), TRF-MCT, and palm kernel oil (PKO) (vehicle MCT). After 6 weeks of supplementation, serum was collected for untargeted metabolomic analysis using ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS), significant metabolic features were annotated to determine the fold change (FC), and analysis was performed (SIMCA and MetaboAnalyst).</p> Results <p>In the TRF-MCT group, 11 amino acids were annotated. Urocanic acid group (<i>FC</i> = 1.0146), ascorbic acid 2-sulphate (<i>FC</i> = 0.81939), 3-isoproprylmalic acid (<i>FC</i> = 0.66469), and 6-methylnicotamide (<i>FC</i> = 0.6507) were the most upregulated (<i>p</i> &lt; 0.05). Lysine (<i>FC</i> = − 0.88836), leucine (<i>FC</i> = − 0.7949), pyridoxamine (<i>FC</i> = − 0.76347), 3-indoxyl sulphate (<i>FC</i> = − 0.73989), threonine (<i>FC</i> = − 0.66945), and indolelactic acid (<i>FC</i> = − 0.61605) were the most downregulated (<i>p</i> &lt; 0.05). Glutamic acid (<i>FC</i> = 0.79069) levels were upregulated in the PKO-treated group compared to the HFD group (<i>p</i> &lt; 0.05).</p> Conclusion <p>TRF-MCT-supplemented NAFLD mouse model shown an altered amino acid which involves in valine, leucine, and isoleucine biosynthesis, aminoacyl-transfer RNA (aminoacyl-tRNA) biosynthesis, and vitamin B6 metabolism. Thus, suggesting TRF-MCT has a protective effect and repairing activities in the liver of the NAFLD mouse model.</p>

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Tocotrienol-rich fraction in medium-chain triglyceride carrier upregulates purine metabolism in non-alcoholic fatty liver disease (NAFLD) animal model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月8日

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  • Mohd Danial Mohd Efendy Goon,
  • Sharaniza Ab-Rahim,
  • Siti Hamimah Sheikh Abdul Kadir,
  • Effendi Ibrahim,
  • Musalmah Mazlan,
  • Normala Abd Latip

摘要

Background

Non-alcoholic fatty liver disease (NAFLD) has been associated with metabolic syndrome (MetS). One of the underlying mechanisms of NAFLD is an aberration in amino acid metabolism and signalling. The tocotrienol-rich fraction (TRF) has been shown to improve NAFLD and is thus recommended as a supplement in NAFLD. However, TRF often exhibits low bioavailability. Recently, our group reported that TRF with medium-chain triglyceride (MCT) carriers could potentially improve steatosis, bile acid metabolism, lipid, and fatty acid metabolism.

Objective

This study investigated the effects of TRF-MCT on amino acid metabolism in an NAFLD mice model.

Methods

Male B6.Cg-LepOb/J mice were used as an NAFLD mouse model and randomly divided into three groups: high-fat diet only (HFD), TRF-MCT, and palm kernel oil (PKO) (vehicle MCT). After 6 weeks of supplementation, serum was collected for untargeted metabolomic analysis using ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS), significant metabolic features were annotated to determine the fold change (FC), and analysis was performed (SIMCA and MetaboAnalyst).

Results

In the TRF-MCT group, 11 amino acids were annotated. Urocanic acid group (FC = 1.0146), ascorbic acid 2-sulphate (FC = 0.81939), 3-isoproprylmalic acid (FC = 0.66469), and 6-methylnicotamide (FC = 0.6507) were the most upregulated (p < 0.05). Lysine (FC = − 0.88836), leucine (FC = − 0.7949), pyridoxamine (FC = − 0.76347), 3-indoxyl sulphate (FC = − 0.73989), threonine (FC = − 0.66945), and indolelactic acid (FC = − 0.61605) were the most downregulated (p < 0.05). Glutamic acid (FC = 0.79069) levels were upregulated in the PKO-treated group compared to the HFD group (p < 0.05).

Conclusion

TRF-MCT-supplemented NAFLD mouse model shown an altered amino acid which involves in valine, leucine, and isoleucine biosynthesis, aminoacyl-transfer RNA (aminoacyl-tRNA) biosynthesis, and vitamin B6 metabolism. Thus, suggesting TRF-MCT has a protective effect and repairing activities in the liver of the NAFLD mouse model.