Abstract
IntroductionDipeptidyl 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.MethodsWe 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.ResultsNAFLD 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.ConclusionsThis 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.
Highlights
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
Plasma DPP4 activity was significantly higher in Non-alcoholic fatty liver disease (NAFLD) than in no-NAFLD patients (209,481.8 ± 62,658.3 nmol/ min/ml vs. 167,287 ± 61,513.2 nmol/min/ml, p = 0.02) and directly correlated with the severity of hepatic impairment, as expressed by greater steatosis grade (r = 0.33, p = 0.04) and lobular inflammation (r = 0.31, p = 0.03) at the biopsy and higher AST (r = 0.41, p = 0.027), ALT (r = 0.30 p = 0.03), GGT (r = 0.41, p = 0.017), Low-density lipoprotein (LDL) cholesterol (r = 0.31, p = 0.048) and FIB-4 (r = 0.52, p = 0.004)
The main finding of this study is that individuals with NAFLD have increased plasma DPP4 activity than noNAFLD subjects, regardless of the presence of obesity and metabolic disease
Summary
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. The association between DPP4 levels/activity and NAFLD was evaluated in 126 non-obese individuals recruited in the same setting. DPP4 is highly expressed in liver [7, 8]; increased hepatic and circulating DPP4 levels have been associated with chronic hepatic diseases in both humans [12,13,14] and murine models [8, 15]. Transgenic mice with hepatocyte-specific DPP4 overexpression fed with high-fat diet (HFD) displayed greater hepatic fat content and signs of liver damage than wild type [8]; DPP4 knocking out was shown to protect mice from experimentally-induced liver injury [15]
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