Metabolomic tissue signature in human non‐alcoholic fatty liver disease identifies protective candidate metabolites

Schönfels, Witigo von; Patsenker, E.; Fahrner, René; Itzel, Timo; Hinrichsen, Holger; Brosch, Mario; Erhart, Wiebke; Gruodyte, Auste; Vollnberg, Bernd; Richter, K; Landrock, A.; Schreiber, Stefan; Brückner, Stephan; Beldi, Guido; Sipos, Bence; Becker, Thomas; Röcken, Christoph; Teufel, Andreas; Stickel, Felix; Schafmayer, Clemens; Hampe, Jochen

doi:10.1111/liv.12476

Cited by 28 publications

(16 citation statements)

References 38 publications

(37 reference statements)

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“…Finally, both N-methyl nicotinate and hydroquinone (HQ) urinary levels tended to be associated with a possible beneficial effect against liver steatosis, already signaled in adult NAFLD [51], in keeping with a cytoprotective role [52]. …”

Section: Discussionmentioning

confidence: 99%

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

et al. 2017

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To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass index <85th or >95th percentile, respectively) ± ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was increased in all obese children (p = 0.0022), IP preferentially in those with NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary metabolome correctly allocated children based on their obesity, NAFLD, visceral fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients; and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter especially in children without NAFLD. The metabolic pathways of BCAA and/or their metabolites correlated with excess of visceral fat centimeters (leucine/oxo-valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome analysis contributes to define a metabolic fingerprint of pediatric obesity and related NAFLD, by identifying metabolic pathways/metabolites reflecting typical obesity dietary habits and GLA perturbations.

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Section: Discussionmentioning

confidence: 99%

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

et al. 2017

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“…All biopsies were evaluated for fibrosis and inflammatory activity according to the standard METAVIR scoring system. Histologically normal liver biopsies from patients who underwent bariatric surgery (Department of Visceral Surgery, University of Schleswig-Holstein, Kiel, Germany) ( n = 6) [ 39 ] and cholecystectomy (Inselspital, Bern) ( n = 3) served as controls. The human study was approved by the ethical committees of the two participating centers.…”

Section: Methodsmentioning

confidence: 99%

Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation

Patsenker

Sachse

Chicca

et al. 2015

IJMS

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The endocannabinoid (EC) system is implicated in many chronic liver diseases, including hepatitis C viral (HCV) infection. Cannabis consumption is associated with fibrosis progression in patients with chronic hepatitis C (CHC), however, the role of ECs in the development of CHC has never been explored. To study this question, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were quantified in samples of HCV patients and healthy controls by gas and liquid chromatography mass spectrometry. Fatty acid amide hydrolase (FAAH) and monoaclyglycerol lipase (MAGL) activity was assessed by [3H]AEA and [3H]2-AG hydrolysis, respectively. Gene expression and cytokine release were assayed by TaqMan PCR and ELISpot, respectively. AEA and 2-AG levels were increased in plasma of HCV patients, but not in liver tissues. Hepatic FAAH and MAGL activity was not changed. In peripheral blood mononuclear cells (PBMC), ECs inhibited IFN-γ, TNF-α, and IL-2 secretion. Inhibition of IL-2 by endogenous AEA was stronger in PBMC from HCV patients. In hepatocytes, 2-AG induced the expression of IL-6, -17A, -32 and COX-2, and enhanced activation of hepatic stellate cells (HSC) co-cultivated with PBMC from subjects with CHC. In conclusion, ECs are increased in plasma of patients with CHC and might reveal immunosuppressive and profibrogenic effects.

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“…When HFD was supplemented with nicotinic acid or hydroquinone, nicotinic acid prevented fat accumulation in mouse liver and reduced serum ALT (Table 4). The authors discussed the use of nicotinic acid as a lipid lowering agent and the potential of future such studies in identifying novel therapeutic targets for NAFLD [204]. Another dual human and mouse liver investigation conducted a metabolomic and lipidomic analysis of Mat1a-KO and WT mouse liver and serum.…”

Section: Nafl and Nashmentioning

confidence: 99%

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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In recent years, there has been a plethora of attempts to discover biomarkers that are more reliable than α-fetoprotein for the early prediction and prognosis of hepatocellular carcinoma (HCC). Efforts have involved such fields as genomics, transcriptomics, epigenetics, microRNA, exosomes, proteomics, glycoproteomics, and metabolomics. HCC arises against a background of inflammation, steatosis, and cirrhosis, due mainly to hepatic insults caused by alcohol abuse, hepatitis B and C virus infection, adiposity, and diabetes. Metabolomics offers an opportunity, without recourse to liver biopsy, to discover biomarkers for premalignant liver disease, thereby alerting the potential of impending HCC. We have reviewed metabolomic studies in alcoholic liver disease (ALD), cholestasis, fibrosis, cirrhosis, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Specificity was our major criterion in proposing clinical evaluation of indole-3-lactic acid, phenyllactic acid, N-lauroylglycine, decatrienoate, N-acetyltaurine for ALD, urinary sulfated bile acids for cholestasis, cervonoyl ethanolamide for fibrosis, 16α-hydroxyestrone for cirrhosis, and the pattern of acyl carnitines for NAFL and NASH. These examples derive from a large body of published metabolomic observations in various liver diseases in adults, adolescents, and children, together with animal models. Many other options have been tabulated. Metabolomic biomarkers for premalignant liver disease may help reduce the incidence of HCC.

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Metabolomic tissue signature in human non‐alcoholic fatty liver disease identifies protective candidate metabolites

Abstract: This first small-molecular screen of human liver tissue identified two replicated protective metabolites. Either the use of NA or targeting its regulatory pathways might be explored to treat or prevent human NAFLD.

Cited by 28 publications

References 38 publications

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

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