Circulating dipeptidyl peptidase-4 is independently associated with the presence and severity of NAFLD/NASH in individuals with and without obesity and metabolic disease

• Published in: Journal of endocrinological investigation 2021-05, Vol.44 (5), p.979-988
• Main Authors: Barchetta, Ilaria, Ceccarelli, Valentina, Cimini, Flavia A., Barone, Eugenio, Sentinelli, Federica, Coluzzi, Mariagrazia, Chiappetta, Caterina, Bertoccini, Laura, Tramutola, Antonella, Labbadia, Giancarlo, Di Cristofano, Claudio, Silecchia, Gianfranco, Leonetti, Frida, Cavallo, Maria G.
• Format: Article
• Language: English
• Subjects: Biopsy; Cardiovascular diseases; Coexistence; Dipeptidyl-peptidase IV; Disease; Endocrinology; Gastrointestinal surgery; Inflammation; Internal Medicine; Liver diseases; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic disorders; mRNA; Obesity; Original; Original Article; Peptidase; Steatosis; Surgery
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-020-01392-5

Introduction Dipeptidyl peptidase 4 (DPP4) levels are associated to metabolic and cardiovascular diseases in humans; initial evidence reported a relationship between DPP4 and chronic liver diseases. Aim of this study was to investigate hepatic and systemic DPP4 levels/activity in relation to NAFLD/NASH in individuals with and without metabolic disease. Methods We recruited fifty-two obese individuals undergoing bariatric surgery and intra-operative liver biopsy at Sapienza University, Rome, Italy. The association between DPP4 levels/activity and NAFLD was also evaluated in 126 non-obese individuals recruited in the same setting. Results NAFLD patients had significantly higher circulating DPP4 activity than no-NAFLD in both the obese and non-obese cohorts; plasma DPP4 activity and levels linearly correlated with steatosis grade and inflammation at the liver biopsy. Hepatic DPP4 mRNA was not associated to either its circulating levels/activity or NAFLD. In the multivariate logistic regression analysis on all the study participants ( n  = 178), higher circulating DPP4 activity was associated with NAFLD independently of potential confounders with OR (95% CI): 3.5 (1.2–10.21), p  = 0.022. Conclusions This study demonstrates the coexistence of increased plasma DPP4 levels and activity in NAFLD. Circulating DPP4 measurement may represent a novel cost-effective strategy for NAFLD/NASH risk stratification and a potential tool for monitoring disease’s progression in established NAFLD.