Dataset Information

Dihydroceramides in Triglyceride-Enriched VLDL Are Associated with Nonalcoholic Fatty Liver Disease Severity in Type 2 Diabetes.

ABSTRACT: Plasma dihydroceramides are predictors of type 2 diabetes and related to metabolic dysfunctions, but the underlying mechanisms are not characterized. We compare the relationships between plasma dihydroceramides and biochemical and hepatic parameters in two cohorts of diabetic patients. Hepatic steatosis, steatohepatitis, and fibrosis are assessed by their plasma biomarkers. Plasma lipoprotein sphingolipids are studied in a sub-group of diabetic patients. Liver biopsies from subjects with suspected non-alcoholic fatty liver disease are analyzed for sphingolipid synthesis enzyme expression. Dihydroceramides, contained in triglyceride-rich very-low-density lipoprotein (VLDL), are associated with steatosis and steatohepatitis. Expression of sphingolipid synthesis enzymes is correlated with histological steatosis and inflammation grades. In conclusion, association of plasma dihydroceramides with nonalcoholic fatty liver might explain their predictive character for type 2 diabetes. Our results suggest a relationship between hepatic sphingolipid metabolism and steatohepatitis and an involvement of dihydroceramides in the synthesis/secretion of triglyceride-rich VLDL, a hallmark of NAFLD and type 2 diabetes dyslipidemia.

SUBMITTER: Carlier A

PROVIDER: S-EPMC7762772 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Dihydroceramides in Triglyceride-Enriched VLDL Are Associated with Nonalcoholic Fatty Liver Disease Severity in Type 2 Diabetes.

Carlier Aurélie A Phan Franck F Szpigel Anaïs A Hajduch Eric E Salem Joe-Elie JE Gautheron Jérémie J Le Goff Wilfried W Guérin Maryse M Lachkar Floriane F Ratziu Vlad V Hartemann Agnès A Ferré Pascal P Foufelle Fabienne F Bourron Olivier O

Cell reports. Medicine 20201222 9

Plasma dihydroceramides are predictors of type 2 diabetes and related to metabolic dysfunctions, but the underlying mechanisms are not characterized. We compare the relationships between plasma dihydroceramides and biochemical and hepatic parameters in two cohorts of diabetic patients. Hepatic steatosis, steatohepatitis, and fibrosis are assessed by their plasma biomarkers. Plasma lipoprotein sphingolipids are studied in a sub-group of diabetic patients. Liver biopsies from subjects with suspect ...[more]

PMID: 33377125

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Project description:Background & aimsAlterations in the gut microbiome have been associated with the severity of nonalcoholic fatty liver disease (NAFLD). Previous studies focused exclusively on the bacteria in the microbiome; we investigated changes in the viral microbiome (virome) in patients with NAFLD.MethodsIn a prospective, cross-sectional, observational study, we extracted RNA and DNA virus-like particles from fecal samples from 73 patients with NAFLD: 29 patients had an NAFLD Activity Score (NAS) of 0-4, 44 patients had an NAS of 5-8 or liver cirrhosis (LCI), 37 patients had F0-F1 fibrosis, and 36 patients had F2-F4 fibrosis. As controls, 9 individuals without liver disease and 13 patients with mild primary biliary cholangitis were included in the analysis. We performed shotgun metagenomic sequencing of virus-like particles.ResultsPatients with NAFLD and NAS 5-8/LCI had a significant decrease in intestinal viral diversity compared with patients with NAFLD and NAS 0-4 or control individuals. The presence of more advanced NAFLD was associated with a significant reduction in the proportion of bacteriophages compared with other intestinal viruses. Using multivariate logistic regression analysis with leave-1-out cross validation, we developed a model, including a viral diversity index and simple clinical variables, that identified patients with NAS 5-8/LCI with an area under the curve of 0.95 (95% confidence interval, 0.91-0.99) and F2-F4 fibrosis with an area under the curve of 0.88 (95% confidence interval, 0.80-0.95). Addition of data on viral diversity significantly improved multivariate models, including those based on only clinical parameters or bacterial diversity.ConclusionsIn a study of fecal viromes from patients with NAFLD and control individuals, we associated histologic markers of NAFLD severity with significant decreases in viral diversity and proportion of bacteriophages. We developed a model based on fecal viral diversity and clinical data that identifies patients with severe NAFLD and fibrosis more accurately than models based only on clinical or bacterial data.

Dataset Information

Dihydroceramides in Triglyceride-Enriched VLDL Are Associated with Nonalcoholic Fatty Liver Disease Severity in Type 2 Diabetes.

Publications

Dihydroceramides in Triglyceride-Enriched VLDL Are Associated with Nonalcoholic Fatty Liver Disease Severity in Type 2 Diabetes.

Similar Datasets

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