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Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles

Abstract: Background and aims: We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors. Approach and results: We analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6 , and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A. Conclusions: Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.

 Fuente: Hepatology . 2022 Oct;76(4):1121-1134

 Editorial: American Association for the Study of Liver Diseases

 Año de publicación: 2022

 Nº de páginas: 14

 Tipo de publicación: Artículo de Revista

 DOI: 10.1002/hep.32427

 ISSN: 0270-9139,1527-3350

 Proyecto español: SAF2017-88041- R

 Url de la publicación: https://www.doi.org/10.1002/hep.32427

Autoría

MARTÍNEZ-ARRANZ, IBON

BRUZZONE, CHIARA

NOUREDDIN, MAZEN

GIL-REDONDO, RUBEN

MINCHOLÉ, ITZIAR

BIZKARGUENAGA, MAIDER

ARRETXE, ENARA

IRUARRIZAGA-LEJARRETA, MARTA

FERNÁNDEZ-RAMOS, DAVID

LOPITZ-OTSOA, FERNANDO

MAYO, REBECA

EMBADE, NIEVES

NEWBERRY, ELIZABETH

MITTENDORF, BETTINA

IZQUIERDO-SÁNCHEZ, LAURA

SMID, VACLAV

ARNOLD, JORGE

IRUZUBIETA, PAULA

PÉREZ CASTAÑO, YLENIA