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Untargeted serum metabolites profiling in high-fat diet mice supplemented with enhanced palm tocotrienol-rich fraction using UHPLC-MS.

ABSTRACT: Excessive high fat dietary intake promotes risk of developing non-alcoholic fatty liver disease (NAFLD) and predisposed with oxidative stress. Palm based tocotrienol-rich fraction (TRF) has been reported able to ameliorate oxidative stress but exhibited poor bioavailability. Thus, we investigated whether an enhanced formulation of TRF in combination with palm kernel oil (medium-chain triglycerides) (ETRF) could ameliorate the effect of high-fat diet (HFD) on leptin-deficient male mice. All the animals were divided into HFD only (HFD group), HFD supplemented with ETRF (ETRF group) and HFD supplemented with TRF (TRF group) and HFD supplemented with PKO (PKO group). After 6 weeks, sera were collected for untargeted metabolite profiling using UHPLC-Orbitrap MS. Univariate analysis unveiled alternation in metabolites for bile acids, amino acids, fatty acids, sphingolipids, and alkaloids. Bile acids, lysine, arachidonic acid, and sphingolipids were downregulated while xanthine and hypoxanthine were upregulated in TRF and ETRF group. The regulation of these metabolites suggests that ETRF may promote better fatty acid oxidation, reduce oxidative stress and pro-inflammatory metabolites and acts as anti-inflammatory in fatty liver compared to TRF. Metabolites regulated by ETRF also provide insight of its role in fatty liver. However, further investigation is warranted to identify the mechanisms involved.

SUBMITTER: Goon DE

PROVIDER: S-EPMC8546078 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Untargeted serum metabolites profiling in high-fat diet mice supplemented with enhanced palm tocotrienol-rich fraction using UHPLC-MS.

Goon Danial Efendy DE Ab-Rahim Sharaniza S Mohd Sakri Amir Hakimi AH Mazlan Musalmah M Tan Jen Kit JK Abdul Aziz Mardiana M Mohd Noor Norizal N Ibrahim Effendi E Sheikh Abdul Kadir Siti Hamimah SH

Scientific reports 20211025 1

Excessive high fat dietary intake promotes risk of developing non-alcoholic fatty liver disease (NAFLD) and predisposed with oxidative stress. Palm based tocotrienol-rich fraction (TRF) has been reported able to ameliorate oxidative stress but exhibited poor bioavailability. Thus, we investigated whether an enhanced formulation of TRF in combination with palm kernel oil (medium-chain triglycerides) (ETRF) could ameliorate the effect of high-fat diet (HFD) on leptin-deficient male mice. All the a ...[more]

PMID: 34697380

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Project description:The greatest significant influence on human life span and health is inevitable ageing. One of the distinguishing characteristics of ageing is the gradual decrease of muscle mass and physical function. There has been growing evidence that tocotrienol can guard against age-associated chronic diseases and metabolic disorders. This study aimed to elucidate the effects of tocotrienol-rich fraction (TRF) on muscle metabolomes and metabolic pathways in ageing Sprague Dawley (SD) rats. Three months, 9 months, and 21 months old male SD rats were divided into control and treated groups with 10 rats per group. Rats in control and treated groups were given 60 mg/kg body weight/day of palm olein and 60 mg/kg body weight/day of TRF, respectively, via oral gavage for 3 months. Muscle performance was assessed at 0 and 3 months of treatment by measuring muscle strength and function. Our results showed that TRF treatment caused a significant increase in the swimming time of the young rats. Comparison in the control groups showed that metabolites involved in lipid metabolisms such as L-palmitoyl carnitine and decanoyl carnitine were increased in ageing. In contrast, several metabolites, such as 3-phosphoglyceric acid, aspartic acid and aspartyl phenylalanine were decreased. These findings indicated that muscle metabolomes involved in lipid metabolism were upregulated in aged rats. In contrast, the metabolites involved in energy and amino acid metabolism were significantly downregulated. Comparison in the TRF-supplemented groups showed an upregulation of metabolites involved in energy and amino acid metabolism. Metabolites such as N6-methyl adenosine, spermine, phenylalanine, tryptophan, aspartic acid, histidine, and N-acetyl neuraminic acid were up-regulated, indicating promotion of amino acid synthesis and muscle regeneration. Energy metabolism was also improved in adult and old rats with TRF supplementation as indicated by the upregulation of nicotinamide adenine dinucleotide and glycerol 3-phosphate compared to the control group. In conclusion, the mechanism underlying the changes in skeletal muscle mass and functions in ageing was related to carbohydrate, lipid and amino acid metabolism. Tocotrienol supplementation showed beneficial effects in alleviating energy and amino acid synthesis that may promote the regeneration and renewal of skeletal muscle in ageing rats.

Project description:BACKGROUND:Several natural products have been reported to elicit beneficial effects against neurodegenerative disorders due to their vitamin E contents. However, the neuroprotective efficacy of palm oil or its tocotrienol-rich fraction (TRF) from the pre-clinical cell and animal studies have not been systematically reviewed. METHODS:The protocol for this systematic review was registered in "PROSPERO" (CRD42019150408). This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Medical Subject Heading (MeSH) descriptors of PubMed with Boolean operators were used to construct keywords, including ("Palm Oil"[Mesh]) AND "Nervous System"[Mesh], ("Palm Oil"[Mesh]) AND "Neurodegenerative Diseases"[Mesh], ("Palm Oil"[Mesh]) AND "Brain"[Mesh], and ("Palm Oil"[Mesh]) AND "Cognition"[Mesh], to retrieve the pertinent records from PubMed, Scopus, Web of Science and ScienceDirect from 1990 to 2019, while bibliographies, ProQuest and Google Scholar were searched to ensure a comprehensive identification of relevant articles. Two independent investigators were involved at every stage of the systematic review, while discrepancies were resolved through discussion with a third investigator. RESULTS:All of the 18 included studies in this review (10 animal and eight cell studies) showed that palm oil and TRF enhanced the cognitive performance of healthy animals. In diabetes-induced rats, TRF and ?-tocotrienol enhanced cognitive function and exerted antioxidant, anti-apoptotic and anti-inflammatory activities, while in a transgenic Alzheimer's disease (AD) animal model, TRF enhanced the cognitive function and reduced the deposition of ?-amyloid by altering the expression of several genes related to AD and neuroprotection. In cell studies, simultaneous treatment with ?-tocotrienols and neurotoxins improved the redox status in neuronal cells better than ?- and ?-tocotrienols. Both pre-treatment and post-treatment with ?-tocotrienol relative to oxidative insults were able to enhance the survival of neuronal cells via increased antioxidant responses. CONCLUSIONS:Palm oil and its TRF enhanced the cognitive functions of healthy animals, while TRF and ?-tocotrienol enhanced the cognitive performance with attenuation of oxidative stress, neuroinflammation and apoptosis in diabetes-induced or transgenic AD animal models. In cell studies, TRF and ?-tocotrienol exerted prophylactic neuroprotective effects, while ?-tocotrienol exerted therapeutic neuroprotective effects that were superior to those of ?- and ?-tocotrienol isomers.

Dataset Information

Untargeted serum metabolites profiling in high-fat diet mice supplemented with enhanced palm tocotrienol-rich fraction using UHPLC-MS.

Publications

Untargeted serum metabolites profiling in high-fat diet mice supplemented with enhanced palm tocotrienol-rich fraction using UHPLC-MS.

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