A Novel Selective PPARα Modulator (SPPARMα), K-877 (Pemafibrate), Attenuates Postprandial Hypertriglyceridemia in Mice

Fig. 1.. Body weight gain and food intake in mice fed after treatment with K-877 and fenofibrate. Mice (n = 10, male, C57B6/J) were fed a normal chow diet up to 8 weeks of age, and they were then fed with a HFD only, an HFD containing 0.0005% K-877, or an HFD containing 0.05% fenofibrate for 4 weeks (A). Body weight gain from the baseline level (g) (B) and food intake (g/day) (C) were observed in these groups from 8 to 12 weeks of age. *: p < 0.05, **: p < 0.01 compared to HFD only.

Fig. 2.. Oral fat loading test after treatment with K-877 and fenofibrate. At twelve weeks of age, the OFL test was performed using olive oil by gavage (17 µL/g body weight) after an overnight fast. Blood (50 µL) was drawn from an orbital vein, and plasma levels of TGs (A, B), FFA (C, D), TC (E,F) and HDL-cholesterol (HDL-C) (G) were measured, and these levels were compared on the basis of incremental AUC. Lipoprotein lipase (LPL) activities were compared among the three groups during the fasting state. *: p < 0.05, **: p < 0.01 compared with HFD only.

Fig. 3.. Lipoprotein profile and apolipoprotein B-48/B-100 relative mass of plasma after the oral fat load Lipoprotein profiles were analyzed and compared among the 3 groups by measurement of TG and cholesterol concentrations of every sub-fractionated sample 4 hours after OFL by using HPLC. Increases in apoB-48 and apoB-100 concentrations after OFL were compared by western blot using a rabbit polyclonal anti-apoB antibody. *: p < 0.05, **: p < 0.01 compared with HFD only.

Fig. 4.. Fasting and postprandial messenger RNA expressions of genes related to lipoprotein metabolism after treatment with K-877 and fenofibrate. Gene expression in the intestinal epithelial cells and hepatocytes was measured with qRT-PCR. Intestinal mRNA expressions of Apob(A), Npc1l1(B), Srebp1c(C) and Mttp(D) were compared among the 3 groups, and hepatic mRNA expressions of ApoB(E) and ApoC3(F) were compared in the same manner. The relative gene expression values were normalized to those of GAPDH gene expression. *: p < 0.05, **: p < 0.01 compared with HFD only, #: p < 0.05, ##: p < 0.01 compared with HFD containing fenofibrate.