Choline and Fructooligosaccharide: Non-alcoholic Fatty Liver Disease, Cardiac Fat Deposition, and Oxidative Stress Markers

Haubert, Nádia Juliana Beraldo Goulart Borges; Marchini, Júlio Sérgio; Cunha, Selma Freire de Carvalho da; Suen, Vívian Marques Miguel; Padovan, Gilberto João; Jordão, Alceu Afonso; Alves, Claudia Maria Meirelles Marchini; Marchini, Júlio Flávio Meirelles; Vannucchi, Hélio

doi:10.4137/nmi.s24385

Cited by 15 publications

(4 citation statements)

References 47 publications

(64 reference statements)

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“…For example, CHO administration has been reported to increase the DHA to DPA ratio within phosphatidylcholine and phosphatidylethanolamine pools of plasma 43 , a defect of which is believed to represent a lipidomic signatures of the impaired FA elongation and desaturation metabolism of the fatty liver along with increased (relative to palmitate and absolute) concentrations of the monounsaturated species palmitoleate (16:1 n7) and oleate (18:1 n9) 44 . Furthermore, the presence of CHO in multivitamin supplements containing vitamin E may help to increase the hepatic availability of this vitamin 45 .…”

Section: Discussionmentioning

confidence: 99%

Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH

Torquato

Giusepponi

Alisi

et al. 2019

Sci Rep

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Two recent randomized controlled trials demonstrated improved radiographic, histological and hepatometabolic cues of non-alcoholic steatohepatitis (NASH) in pediatric patients treated with the ω-3 fatty acid docosahexaenoic acid (DHA) in combination with vitamin D (VD) or with choline (CHO) and vitamin E (VE), the DHA-VD and DHA-CHO-VE trials, respectively). In the present study we verified the nutritional compliance to these DHA-based multivitamin treatments; lipidomics biomarkers of the reported outcome on NASH indicators were also investigated. Samples were obtained from 30 biopsy-proven pediatric NASH patients of the DHA-CHO-VE trial randomized in multivitamin treatment group and placebo group (n = 15 each), and from 12 patients of the treatment group of the DHA-VD trial. All patients underwent 6-month therapy plus 6 months of follow-up. Plasma samples and clinical data were obtained at baseline and at the end of the study (12 months). Selected biomarkers included the free form of DHA and other ω-3 fatty acid arachidonic acid (AA), indices of the vitamin E status, and some hepatic metabolites of these lipids. Radiographic and histological improvements of treated patients were associated with increased concentrations of DHA, α-linolenic acid and α-tocopherol (i.e. VE), and with decreased AA that was also investigated in complex lipids by untargetd lipidomics. As a result a significantly lowered AA/DHA ratio was observed to represent the main indicator of the response to the DHA-based therapy. Furthermore, baseline levels of AA/DHA showed strong association with NAS and US improvement. A stable correction of DHA AA metabolism interaction is associated with the curative effect of this therapy and may represent a key nutritional endpoint in the clinical management of pediatric NASH.

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Section: Discussionmentioning

confidence: 99%

Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH

Torquato

Giusepponi

Alisi

et al. 2019

Sci Rep

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“…The intestinal microbiota was also improved. Moreover, it has been reported that FOS reduced liver fat content [ 98 ]. In the animal model of NAFLD, induced by 70% sucrose, treatment of FOS reduced hepatic and cardiac steatosis.…”

Section: Modulation Of Gut Microbiota and Its Metabolitesmentioning

confidence: 99%

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

Chen¹,

Vitetta

2020

IJMS

194

137

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Gut microbiota dysregulation plays a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through its metabolites. Therefore, the restoration of the gut microbiota and supplementation with commensal bacterial metabolites can be of therapeutic benefit against the disease. In this review, we summarize the roles of various bacterial metabolites in the pathogenesis of NAFLD and their therapeutic implications. The gut microbiota dysregulation is a feature of NAFLD, and the signatures of gut microbiota are associated with the severity of the disease through altered bacterial metabolites. Disturbance of bile acid metabolism leads to underactivation of bile acid receptors FXR and TGR5, causal for decreased energy expenditure, increased lipogenesis, increased bile acid synthesis and increased macrophage activity. Decreased production of butyrate results in increased intestinal inflammation, increased gut permeability, endotoxemia and systemic inflammation. Dysregulation of amino acids and choline also contributes to lipid accumulation and to a chronic inflammatory status. In some NAFLD patients, overproduction of ethanol produced by bacteria is responsible for hepatic inflammation. Many approaches including probiotics, prebiotics, synbiotics, faecal microbiome transplantation and a fasting-mimicking diet have been applied to restore the gut microbiota for the improvement of NAFLD.

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“…A lack of choline leads to the accumulation of lipids in the liver (Hensley et al, 2000). As a therapeutic drug it is widely used for treating nonalcoholic fatty liver disease, as well other liver disorders (Borges Haubert et al, 2015). Choline had a preventive effect on oxidative damage in mice (Li et al, 2016).…”

Section: Identification Of Biomarkers and Metabolic Pathways In Drug ...mentioning

confidence: 99%

The assessment of the potential hepatotoxicity of new drugs by in vitro metabolomics

2023

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Drug hepatotoxicity assessment is a relevant issue both in the course of drug development as well as in the post marketing phase. The use of human relevant in vitro models in combination with powerful analytical methods (metabolomic analysis) is a promising approach to anticipate, as well as to understand and investigate the effects and mechanisms of drug hepatotoxicity in man. The metabolic profile analysis of biological liver models treated with hepatotoxins, as compared to that of those treated with non-hepatotoxic compounds, provides useful information for identifying disturbed cellular metabolic reactions, pathways, and networks. This can later be used to anticipate, as well to assess, the potential hepatotoxicity of new compounds. However, the applicability of the metabolomic analysis to assess the hepatotoxicity of drugs is complex and requires careful and systematic work, precise controls, wise data preprocessing and appropriate biological interpretation to make meaningful interpretations and/or predictions of drug hepatotoxicity. This review provides an updated look at recent in vitro studies which used principally mass spectrometry-based metabolomics to evaluate the hepatotoxicity of drugs. It also analyzes the principal drawbacks that still limit its general applicability in safety assessment screenings. We discuss the analytical workflow, essential factors that need to be considered and suggestions to overcome these drawbacks, as well as recent advancements made in this rapidly growing field of research.

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Choline and Fructooligosaccharide: Non-alcoholic Fatty Liver Disease, Cardiac Fat Deposition, and Oxidative Stress Markers

Cited by 15 publications

References 47 publications

Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH

Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH

Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

The assessment of the potential hepatotoxicity of new drugs by in vitro metabolomics

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