Circulating dipeptidyl peptidase-4 is independently associated with the presence and severity of NAFLD/NASH in individua
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ORIGINAL ARTICLE
Circulating dipeptidyl peptidase‑4 is independently associated with the presence and severity of NAFLD/NASH in individuals with and without obesity and metabolic disease Ilaria Barchetta1 · Valentina Ceccarelli1 · Flavia A. Cimini1 · Eugenio Barone2 · Federica Sentinelli1 · Mariagrazia Coluzzi3 · Caterina Chiappetta3 · Laura Bertoccini1 · Antonella Tramutola2 · Giancarlo Labbadia4 · Claudio Di Cristofano3 · Gianfranco Silecchia3 · Frida Leonetti3 · Maria G. Cavallo1 Received: 8 July 2020 / Accepted: 7 August 2020 © The Author(s) 2020
Abstract 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. Keywords DPP4 · Fatty liver
Background
I. Barchetta, V. Ceccarelli contributed equally to this work. * Maria G. Cavallo [email protected] 1
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
2
Department of Biochemical Sciences “A. Rossi‑Fanelli”, Sapienza University of Rome, Rome, Italy
3
Department of Medical‑Surgical Sciences and Bio‑Technologies, Sapienza University of Rome, Rome, Italy
4
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
Non-alcoholic fatty liver disease (NAFLD) is a chronic pathological condition characterized by an excessive deposition of triglycerides in the hepatocytes and has become one of the most epidemic hepatic diseases worldwide [1]. NAFLD development is tightly connected to the presence of metabolic diseases, so that its incidence has considerably increased in the last decades, paralleling the growing prevalence of obesity and type 2 diabetes melli
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