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Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD

Lookup NU author(s): Dr Dina Tiniakos



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© Copyright © 2021 Marques, Afonso, Bierig, Duarte-Ramos, Santos-Laso, Jimenez-Agüero, Eizaguirre, Bujanda, Pareja, Luís, Costa, Machado, Alonso, Arretxe, Alustiza, Krawczyk, Lammert, Tiniakos, Flehmig, Cortez-Pinto, Banales, Castro, Normann and Rodrigues.Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome. Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics. Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p < 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p < 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p < 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p < 0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p < 0.01). Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis.

Publication metadata


Publication type: Article

Publication status: Published

Journal: Frontiers in Medicine

Year: 2021

Volume: 8

Print publication date: 01/06/2021

Online publication date: 23/06/2021

Acceptance date: 10/05/2021

Date deposited: 21/07/2021

ISSN (electronic): 2296-858X

Publisher: Frontiers Media S.A.


DOI: 10.3389/fmed.2021.683250


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