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

Frontiers in Medicine

article

Vanda Marques¹  Rita Luís²  Adília Costa²  Mariana V. Machado³  Cristina Alonso⁵  Enara Arretxe⁵  José M. Alustiza⁶  Marcin Krawczyk⁸  Frank Lammert⁸  Dina G. Tiniakos^1,10  Bertram Flehmig^1,12  Marta B. Afonso¹  Helena Cortez-Pinto³  Jesus M. Banales⁶  Rui E. Castro¹  Andrea Normann^1,12  Cecília M. P. Rodrigues¹  Nina Bierig^1,12  Filipa Duarte-Ramos¹  Álvaro Santos-Laso⁶  Raul Jimenez-Agüero⁶  Emma Eizaguirre⁶  Luis Bujanda⁶  Maria J. Pareja^1,16 

[1] Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa;Department of Pathological Anatomy, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte;Clinica Universitária de Gastrenterologia, Universidade de Lisboa;Department of Gastroenterology, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte;OWL Metabolomics, Bizkaia Technology Park;Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU);Radiology Service;Department of Medicine II, Saarland University Medical Center;Laboratory of Metabolic Liver Diseases, Department of General, Centre for Preclinical Research, Medical University of Warsaw;Faculty of Medical Sciences, Translational and Clinical Research Institute, Newcastle University, United Kingdom;Department of Pathology, Aretaieio Hospital, National and Kapodistrian University of Athens;Mediagnost;National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Instituto de Salud Carlos III);IKERBASQUE, Basque Foundation for Science;EPIUnit–Instituto de Saúde Pública, Universidade do Porto;Hospital de Valme

关键词: adiponectin;    circulating biomarkers;    fibrosis;    IGF-1;    leptin;    lipid metabolism;    NAFLD;   

DOI  :  10.3389/fmed.2021.683250

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY