Abstract 17813: A DPP-4 Inhibitor, Anagliptin, Attenuates Both Fasting and Postprandial Hypertriglyceridemia
Introduction: The postprandial accumulation of intestine-derived chylomicrons (CMs) and chylomicron remnants (CM-Rs) is often observed in patients with diabetes mellitus. Since CM-Rs directly invade the arterial wall and stimulate the foam cell formation of macrophages, the accumulation of CM-Rs may enhance atherogeniciy. In our preliminary analysis, we found that a DPP-4 inhibitor, anagliptin, decreased both fasting and postprandial accumulations of TG and CM-Rs in mice fed a western diet, however food intake and weight gain of these mice were also decreased.
Hypothesis: We assessed the effect of anagliptin on lipids and lipoprotein metabolism in mice fed a normal chow (NC) diet to evaluate the effects and molecular mechanisms for improving postprandial accumulation of CM-Rs.
Methods: Male C57BL/6J mice (8-week old) were fed a NC diet, or NC diet containing 0.3% anagliptin for 4 weeks (n=10/group). Oral fat loading (OFL) test was performed using olive oil (17μl/g body weight) after an overnight fast. TG, TC, FFA and apoB-48 levels were measured at fasting and 2, 4, 6 hours after OFL, and lipoprotein profiles of plasma and intestinal lymph 3 hours after OFL were analyzed by HPLC. Furthermore, the expression of mRNAs in small intestines and the liver related to lipid and lipoprotein metabolism was evaluated by quantitative RT-PCR.
Results: There was no significant difference in dietary intake and weight gain among the 2 groups. Anagliptin significantly decreased both fasting and postprandial levels of TG and apoB-48 mass. HPLC analysis showed that anagliptin decreased peaks of lipoproteins in the size of CM and VLDL in both plasma and intestinal lymph, suggesting that anagliptin decreased the synthesis and secretion of CMs. Anagliptin also suppressed the expression of NPC1L1 which uptakes cholesterol from the bile and that of DGAT1 which resynthesizes TG from DG, and that of MTP which binds apoB-48 on lipoprotein and produces CM.
Conclusions: Anagliptin attenuates postprandial hypertriglyceridemia and may suppress the atherogenicity in mice fed a NC independent of food intake or weight loss.
Author Disclosures: M. Sairyo: Research Grant; Significant; Sanwa Kagaku Kenkyusho Co. Ltd. Other Research Support; Significant; Sanwa Kagaku Kenkyusho Co. Ltd. D. Masuda: Research Grant; Significant; Sanwa Kagaku Kenkyusho Co. Ltd. Other Research Support; Significant; Sanwa Kagaku Kenkyusho Co. Ltd. T. Kobayashi: None. K. Kanno: None. H. Matsuda: None. T. Okada: None. T. Ohama: None. M. Koseki: None. M. Nishida: None. Y. Sakata: None. S. Yamashita: Research Grant; Significant; Sanwa Kagaku Kenkyusho Co. Ltd. Other Research Support; Significant; Sanwa Kagaku Kenkyusho Co. Ltd.
- © 2016 by American Heart Association, Inc.