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Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles

I. Martínez-Arranz, C. Bruzzone, M. Noureddin, R. Gil-Redondo, I. Mincholé, M. Bizkarguenaga, E. Arretxe, M. Iruarrizaga-Lejarreta, D. Fernández-Ramos, F. Lopitz-Otsoa, R. Mayo, N. Embade, E. Newberry, B. Mittendorf, L. Izquierdo-Sánchez, V....

. 2022 ; 76 (4) : 1121-1134. [pub] 20220317

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22024276

Grantová podpora
R01 DK123763 NIDDK NIH HHS - United States
P30DK52574 NIH HHS - United States
P30DK56341 NIH HHS - United States
R01DK119437 NIH HHS - United States
UL1TR002345 NIH HHS - United States

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.

1st Faculty of Medicine Charles University Prague Czech Republic

Alcalá University School of Medicine and Health Sciences University Hospital Prıncipe de Asturias Madrid Spain

Center for Human Nutrition Washington University School of Medicine St Louis Missouri USA

Centro de Envejecimiento y Regeneración Santiago Chile

CIC bioGUNE BRTA CIBERehd Derio Bizkaia Spain

Departamento de Gastroenterologia Escuela de Medicina Pontificia Universidad Católica de Chile Santiago de Chile Chile

Department of Digestive Disease Clinic University Hospital University Hospital of Valladolid Valladolid Spain

Department of Digestive System Osakidetza Basque Health Service Donostia University Hospital San Sebastian Spain

Department of Liver and Gastrointestinal Diseases Biodonostia Research Institute Donostia University Hospital Donostia Spain

Department of Medicine 2 Saarland University Medical Center Homburg Germany

Department of Medicine Washington University School of Medicine St Louis Missouri USA

Department of Metabolic Health Research Netherlands Organization for Applied Scientific Research Leiden The Netherlands

Division of Endocrinology Diabetes and Metabolism University of Florida and Malcom Randall VAMC Gainesville Florida USA

Galmed Pharmaceuticals Tel Aviv Israel

Gastroenterology Department University of Turin Turin Italy

Karsh Division of Gastroenterology and Hepatology Cedars Sinai Medical Center Los Angeles California USA

Laboratory of Metabolic Liver Diseases Center for Preclinical Research Department of General Transplant and Liver Surgery Medical University of Warsaw Warsaw Poland

Marqués de Valdecilla University Hospital Cantabria University Santander Spain

Newcastle NIHR Biomedical Research Center Newcastle Upon Tyne Hospitals NHS Trust Newcastle Upon Tyne UK

OWL Metabolomics Derio Bizkaia Spain

Translational and Clinical Research Institute Faculty of Medical Sciences Newcastle University Newcastle Upon Tyne UK

University of the Basque Country CIBERehd IKERBASQUE Donostia Spain

Valme University Hospital CiBERehd Sevilla Spain

Citace poskytuje Crossref.org

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