Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
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, Krawczyk Marcin, Marigorta Urko M, Morrison Martine C, Kleemann Robert, Martín-Duce Antonio, Hayardeny Liat, Vitek Libor, Bruha Radan, Aller de la Fuente Rocío, Crespo Javier, Romero-Gomez Manuel, Banales Jesus M, Arrese Marco, Cusi Kenneth, Bugianesi Elisabetta, Klein Samuel, Lu Shelly C, Anstee Quentin M, Millet Oscar, Davidson Nicholas O, Alonso Cristina, Mato José M
Аннотация
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.