Reversal of Lipid Metabolism Dysregulation by Selenium and Folic Acid Co-Supplementation to Mitigate Pathology in Alzheimer’s Disease

Zhang, Zhong-Hao; Cao, Xian-Chun; Peng, Jia-Ying; Huang, Shaoling; Chen, Chen; Jia, Shi-Zheng; Ni, Jiazuan; Song, Guo-Li

doi:10.3390/antiox11050829

Cited by 10 publications

(8 citation statements)

References 65 publications

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“…Secondly, the anti-inflammatory effect of folate [ 47 ] may also be a mechanism for decreasing the risk of functional disability [ 48 , 49 ]. In addition, folate as a coenzyme of one-carbon metabolism involved homocysteine methylation and promotes homocysteine to methionine conversion [ 50 , 51 , 52 ]. Several studies have suggested that elevated homocysteine levels may be a risk factor for functional disability [ 17 ] or physical function decline [ 18 , 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Associations between Serum Folate Concentrations and Functional Disability in Older Adults

Zhang

et al. 2023

Antioxidants

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Folate may have beneficial effects on physical function through its antioxidant effect. Thus, we investigated the associations between serum folate and functional disability in older adults. Data from the National Health and Nutrition Examination Survey 2011–2018 were used. Serum folate included 5-methyltetrahydrofolate and total folate. Five domains of functional disability, including lower extremity mobility (LEM), instrumental activities of daily living (IADL), activities of daily living (ADL), leisure and social activities (LSA), and general physical activities (GPA), were self-reported. Multivariable-adjusted logistic regression models and restricted cubic splines were employed. 5-Methyltetrahydrofolate was inversely associated with IADL and GPA disability, and the multivariate-adjusted ORs (95% CIs) in the highest versus lowest quartiles were 0.65 (0.46–0.91) and 0.70 (0.50–0.96), respectively. The total folate was also inversely associated with IADL (OR quartile 4vs1 = 0.65, 95% CI: 0.46–0.90) and GPA (OR quartile 3vs1 = 0.66, 95% CI: 0.44–0.99) disability. The dose–response relationships showed a gradual decrease in the risk of IADL and GPA disability as serum folate increased. In the sex, age, BMI, and alcohol consumption subgroup analyses, we saw that the associations were primarily found in females, under 80 years old, normal weight, and non-drinkers. Sensitivity analyses further confirmed the robustness of our results. Our results indicated that serum folate concentrations were negatively associated with IADL and GPA disability, especially in females. In other subgroup analyses, we discovered that these negative associations were primarily prevalent in participants under 80 years old, normal weight, and non-drinkers.

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Section: Discussionmentioning

confidence: 99%

Associations between Serum Folate Concentrations and Functional Disability in Older Adults

Zhang

et al. 2023

Antioxidants

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“…The 3× Tg-AD mice (B6; 129-Psen1tm1MpmTg (APPSwe, tauP301L) 1 Lfa/J), as described previously [ 19 ], were purchased from The Jackson Laboratory (Bar Harbor, ME). They were housed in cages with free access to food and water at 22 ± 2 °C under a 12 h alternating light/dark cycle.…”

Section: Methodsmentioning

confidence: 99%

Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease

et al. 2023

Self Cite

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Owing to the strong antioxidant capacity of selenium (Se) in vivo, a variety of Se compounds have been shown to have great potential for improving the main pathologies and cognitive impairment in Alzheimer’s disease (AD) models. However, the differences in the anti-AD effects and mechanisms of different Se compounds are still unclear. Theoretically, the absorption and metabolism of different forms of Se in the body vary, which directly determines the diversification of downstream regulatory pathways. In this study, low doses of Se-methylselenocysteine (SMC), selenomethionine (SeM), or sodium selenate (SeNa) were administered to triple transgenic AD (3× Tg-AD) mice for short time periods. AD pathology, activities of selenoenzymes, and metabolic profiles in the brain were studied to explore the similarities and differences in the anti-AD effects and mechanisms of the three Se compounds. We found that all of these Se compounds significantly increased Se levels and antioxidant capacity, regulated amino acid metabolism, and ameliorated synaptic deficits, thus improving the cognitive capacity of AD mice. Importantly, SMC preferentially increased the expression and activity of thioredoxin reductase and reduced tau phosphorylation by inhibiting glycogen synthase kinase-3 beta (GSK-3β) activity. Glutathione peroxidase 1 (GPx1), the selenoenzyme most affected by SeM, decreased amyloid beta production and improved mitochondrial function. SeNa improved methionine sulfoxide reductase B1 (MsrB1) expression, reflected in AD pathology as promoting the expression of synaptic proteins and restoring synaptic deficits. Herein, we reveal the differences and mechanisms by which different Se compounds improve multiple pathologies of AD and provide novel insights into the targeted administration of Se-containing drugs in the treatment of AD.

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“…Untargeted metabolomic analysis after Se supplementation have been performed using mice models [47,73,[85][86][87][88][89][90][91][92][93][94][95][96][97][98], pigs [99][100][101][102], broilers [103], cells [104], rats [105][106][107], gazelle [108], zebra fish [109], humans [110], donkeys [111], salmon [112], and catfish [113]. These studies reported a wide range of altered metabolites after Se supplementation focused on liver [73, 91, 94-96, 100-102, 105, 112] and plasma/serum metabolism [73,92,96,101,105,108,110], but also in muscle [99,103], kidneys [73,93], testes [73], lungs [73,90], spleen [96], blood…”

Section: Metabolomic Studies Related To the Impact Of Dietary Seleniu...mentioning

confidence: 99%

“…A summary of the metabolomics studies reported after Se supplementation using different analytical platforms is shown in Table 2. As can be seen, metabolomics is usually combined with transcriptomics [47,90,94,99,101,103,109,111], histopathology [98,103,106,109], metallomics [73,90,91,98,99,105,107], proteomics [96,101], enzymatic activities [91,97,98], or targeted metabolomics [100,109]. Several studies focused on metataxonomics and gut metabolomics [95,96,101,106,113].…”

Section: Metabolomic Studies Related To the Impact Of Dietary Seleniu...mentioning

confidence: 99%

“…Untargeted metabolomic analysis after Se supplementation have been performed using mice models [47, 73, 85–98], pigs [99–102], broilers [103], cells [104], rats [105–107], gazelle [108], zebra fish [109], humans [110], donkeys [111], salmon [112], and catfish [113]. These studies reported a wide range of altered metabolites after Se supplementation focused on liver [73, 91, 94–96, 100–102, 105, 112] and plasma/serum metabolism [73, 92, 96, 101, 105, 108, 110], but also in muscle [99, 103], kidneys [73, 93], testes [73], lungs [73, 90], spleen [96], blood [97, 102, 106, 113], urine [107], feces or fecal/gut content [47, 96, 106], semen [106], follicular fluid [111], brain [47, 73, 93, 97, 109], and brain sections [98]. A summary of the metabolomics studies reported after Se supplementation using different analytical platforms is shown in Table 2.…”

Section: Metabolomic Approaches To Delve Into the Responses To Dietar...mentioning

confidence: 99%

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Omics insights into the responses to dietary selenium

Arias‐Borrego,

Callejón‐Leblic,

Collado

et al. 2023

Proteomics

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Selenium is a well‐known health‐relevant element related with cancer chemoprevention, neuroprotective roles, beneficial in diabetes, and in several infectious diseases, among others. It is naturally present in some foods, but deficiency in people led to the production of nutraceuticals, supplements, and functional food enriched in this element. There is a U‐shaped link between selenium levels and health and a narrow range between toxic and essential levels, and thus, supplementation should be performed carefully. Omics methodologies have become valuable approaches to delve into the responses of dietary selenium in mammals that allowed a deeper knowledge about the metabolism of this element as well as its biological role. In this review, we discuss omics approaches from the workflows to their applications that has been previously used to deep insight into the metabolism of dietary selenium. There is a special focus on selenoproteins, metabolomics responses in blood and tissues (e.g., brain, reproductive organs, etc.) as well as the impact on gut microbiota and its metabolites profile. Thus, we mainly reviewed heteroatom‐tagged proteomics, metallomics, metabolomics, and metataxonomics, usually combined with transcriptomics, genomics, and other molecular methods.

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Reversal of Lipid Metabolism Dysregulation by Selenium and Folic Acid Co-Supplementation to Mitigate Pathology in Alzheimer’s Disease

Cited by 10 publications

References 65 publications

Associations between Serum Folate Concentrations and Functional Disability in Older Adults

Associations between Serum Folate Concentrations and Functional Disability in Older Adults

Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease

Omics insights into the responses to dietary selenium

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