Zheng_2017_Metabolism_73_125

OBJECTIVE: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is attributed to a "multi-hits hypothesis" involving insulin resistance, oxidative stress and inflammation. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing the"multi-hits". Hence, we investigated the association between plasma DPP4 activity and NAFLD in nondiabetic Chinese population. DESIGN AND METHODS: We performed a cross-sectional study using data from 1105 subjects (36-79years) in Guilin between 2015 and 2016. Plasma DPP4 activity, homeostatic model assessment of insulin resistance (HOMA-IR), oxidative stress parameters, and inflammatory markers were measured in all participants. NAFLD and its severity were diagnosed by ultrasound after the exclusion of alcohol abuse and other liver diseases. RESULTS: Participants in the highest quartile of DPP4 activity had higher HOMA-IR, nitrotyrosine, 8-iso-PGF2a, interleukin-6, CRP, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase compared with those in the lowest quartile (all P<0.05). Plasma DPP4 activity gradually increased across the groups according to the ultrasonographic severity of steatosis (P<0.001 for the trend). In the highest DPP4 quartile, NAFLD risk was higher (odds ratio 1.88; 95% CI 1.04-3.37) than in the lowest quartile after adjustment for confounders. The risk for NAFLD increased more with higher levels of DPP4 activity, HOMA-IR, nitrotyrosine, 8-iso-PGF2a, interleukin-6 and CRP. CONCLUSIONS: Plasma DPP4 activity is significantly associated with NAFLD. The underlying mechanisms may be partly attributed to the interactions between insulin resistance, oxidative stress, inflammation, and DPP4.