Journal Article

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

Jimenez-Agüero, Raul, Rodrigues, Cecília M. P., Marques, Vanda, Flehmig, Bertram, Cortez-Pinto, Helena, Arretxe, Enara, Tiniakos, Dina G., Afonso, Marta B., Banales, Jesus M., Luís, Rita, Machado, Mariana V., Alustiza, José M., Normann, Andrea, Bierig, Nina, Krawczyk, Marcin, Costa, Adília, Lammert, Frank, Eizaguirre, Emma, Pareja, Maria J., Alonso, Cristina, Castro, Rui E., Santos-Laso, Álvaro, Bujanda, Luis, Duarte-Ramos, Filipa

2021

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: adiponectin / Biomarkers / Biopsy / Body mass index / Chromatography / circulating biomarkers / Data analysis / Diabetes / Fatty liver / fibrosis / Gastrointestinal surgery / Hormones / Hypertension / IGF-1 / Inflammation / Insulin-like growth factors / leptin / lipid metabolism / Lipids / Liver cirrhosis / Liver diseases / Magnetic resonance imaging / Mass spectrometry / Medicine / Metabolic syndrome / Metabolites / Morbidity / Obesity / Pathogenesis / Patients / Regression analysis / Scientific imaging