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

J Endocrinol Invest. 2021 May;44(5):979-988. doi: 10.1007/s40618-020-01392-5. Epub 2020 Aug 27.

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.

MeSH terms

  • Bariatric Surgery / methods
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Biopsy / methods
  • Cardiometabolic Risk Factors
  • Cost-Benefit Analysis
  • Dipeptidyl Peptidase 4* / blood
  • Dipeptidyl Peptidase 4* / metabolism
  • Disease Progression
  • Female
  • Humans
  • Italy / epidemiology
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Non-alcoholic Fatty Liver Disease* / diagnosis
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Non-alcoholic Fatty Liver Disease* / pathology
  • Obesity* / diagnosis
  • Obesity* / epidemiology
  • Obesity* / metabolism
  • Obesity* / surgery
  • Patient Acuity
  • Risk Assessment / methods

Substances

  • Biomarkers
  • Dipeptidyl Peptidase 4