Effects of DPP-4 Inhibition on Liver Function

(HealthDay News) — Dipeptidyl peptidase-4 (DPP-4) inhibition may attenuate hepatic steatosis and insulin resistance induced by the Western diet through hepatic lipid remodeling and modulation of hepatic mitochondrial function, according to research published in Diabetes.

Annayya R. Aroor, MD, of the University of Missouri in Columbia, and colleagues assessed hepatic function in 4-week-old C57Bl/6 mice who were fed a high-fat, high-fructose Western diet vs. those who were fed the Western diet containing the DPP-4 inhibitor MK0626 for 16 weeks.

The researchers found that insulin suppression of hepatic glucose output was enhanced in mice receiving the DPP-4 inhibitor and the Western diet. Accumulation of hepatic triacylglycerol (TAG) and diacylglycerol (DAG) content also was reduced. 

Mitochondrial incomplete palmitate oxidation was reduced, and indices of pyruvate dehydrogenase activity, tricarboxylic acid cycle flux and hepatic TAG secretion were increased. Following DDP-4 treatment, plasma uric acid levels decreased in Western diet-fed mice.

“These studies suggest that DPP-4 inhibition ameliorates hepatic steatosis and insulin resistance by suppressing hepatic TAG and DAG accumulation through enhanced mitochondrial carbohydrate utilization and hepatic TAG secretion/export with concomitant reduction of uric acid production,” the researchers wrote.

Two authors disclosed financial ties to Merck, which partially funded the study and manufactures MK0626.


  1. Aroor AR et al. Diabetes. 2015;doi:10.2337/db14-0804.