AIMS: Fasting and postprandial hypertriglyceridemia (PHTG) are caused by the accumulation of triglyceride (TG)-rich lipoproteins and their remnants, which have atherogenic effects. Fibrates can improve fasting and PHTG; however, reduction of remnants is clinically needed to improve health outcomes. In the current study, we investigated the effects of a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), K-877 (Pemafibrate), on PHTG and remnant metabolism. METHODS: Male C57BL/6J mice were fed a high-fat diet (HFD) only, or an HFD containing 0.0005% K-877 or 0.05% fenofibrate, from 8 to 12 weeks of age. After 4 weeks of feeding, we measured plasma levels of TG, free fatty acids (FFA), total cholesterol (TC), HDL-C, and apolipoprotein (apo) B-48/B-100 during fasting and after oral fat loading (OFL). Plasma lipoprotein profiles after OFL, which were assessed by high performance liquid chromatography (HPLC), and fasting lipoprotein lipase (LPL) activity were compared among the groups. RESULTS: Both K-877 and fenofibrate suppressed body weight gain and fasting and postprandial TG levels and enhanced LPL activity in mice fed an HFD. As determined by HPLC, K-877 and fenofibrate significantly decreased the abundance of TG-rich lipoproteins, including remnants, in postprandial plasma. Both K-877 and fenofibrate decreased intestinal mRNA expression of ApoB and Npc1l1; however, hepatic expression of Srebp1c and Mttp was increased by fenofibrate but not by K-877.Hepatic mRNA expression of apoC-3 was decreased by K-877 but not by fenofibrate. CONCLUSION: K-877 may attenuate PHTG by suppressing the postprandial increase of chylomicrons and the accumulation of chylomicron remnants more effectively than fenofibrate.
AIMS: Fasting and postprandial hypertriglyceridemia (PHTG) are caused by the accumulation of triglyceride (TG)-rich lipoproteins and their remnants, which have atherogenic effects. Fibrates can improve fasting and PHTG; however, reduction of remnants is clinically needed to improve health outcomes. In the current study, we investigated the effects of a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), K-877 (Pemafibrate), on PHTG and remnant metabolism. METHODS: Male C57BL/6J mice were fed a high-fat diet (HFD) only, or an HFD containing 0.0005% K-877 or 0.05% fenofibrate, from 8 to 12 weeks of age. After 4 weeks of feeding, we measured plasma levels of TG, free fatty acids (FFA), total cholesterol (TC), HDL-C, and apolipoprotein (apo) B-48/B-100 during fasting and after oral fat loading (OFL). Plasma lipoprotein profiles after OFL, which were assessed by high performance liquid chromatography (HPLC), and fasting lipoprotein lipase (LPL) activity were compared among the groups. RESULTS: Both K-877 and fenofibrate suppressed body weight gain and fasting and postprandial TG levels and enhanced LPL activity in mice fed an HFD. As determined by HPLC, K-877 and fenofibrate significantly decreased the abundance of TG-rich lipoproteins, including remnants, in postprandial plasma. Both K-877 and fenofibrate decreased intestinal mRNA expression of ApoB and Npc1l1; however, hepatic expression of Srebp1c and Mttp was increased by fenofibrate but not by K-877.Hepatic mRNA expression of apoC-3 was decreased by K-877 but not by fenofibrate. CONCLUSION:K-877 may attenuate PHTG by suppressing the postprandial increase of chylomicrons and the accumulation of chylomicron remnants more effectively than fenofibrate.
Authors: H Iso; Y Naito; S Sato; A Kitamura; T Okamura; T Sankai; T Shimamoto; M Iida; Y Komachi Journal: Am J Epidemiol Date: 2001-03-01 Impact factor: 4.897
Authors: Min Jun; Celine Foote; Jicheng Lv; Bruce Neal; Anushka Patel; Stephen J Nicholls; Diederick E Grobbee; Alan Cass; John Chalmers; Vlado Perkovic Journal: Lancet Date: 2010-05-10 Impact factor: 79.321
Authors: E Meyer; H T Westerveld; F C de Ruyter-Meijstek; M M van Greevenbroek; R Rienks; H J van Rijn; D W Erkelens; T W de Bruin Journal: Atherosclerosis Date: 1996-08-02 Impact factor: 5.162
Authors: Jean-Charles Fruchart; Raul D Santos; Carlos Aguilar-Salinas; Masanori Aikawa; Khalid Al Rasadi; Pierre Amarenco; Philip J Barter; Richard Ceska; Alberto Corsini; Jean-Pierre Després; Patrick Duriez; Robert H Eckel; Marat V Ezhov; Michel Farnier; Henry N Ginsberg; Michel P Hermans; Shun Ishibashi; Fredrik Karpe; Tatsuhiko Kodama; Wolfgang Koenig; Michel Krempf; Soo Lim; Alberto J Lorenzatti; Ruth McPherson; Jesus Millan Nuñez-Cortes; Børge G Nordestgaard; Hisao Ogawa; Chris J Packard; Jorge Plutzky; Carlos I Ponte-Negretti; Aruna Pradhan; Kausik K Ray; Željko Reiner; Paul M Ridker; Massimiliano Ruscica; Shaukat Sadikot; Hitoshi Shimano; Piyamitr Sritara; Jane K Stock; Ta-Chen Su; Andrey V Susekov; André Tartar; Marja-Riitta Taskinen; Alexander Tenenbaum; Lale S Tokgözoğlu; Brian Tomlinson; Anne Tybjærg-Hansen; Paul Valensi; Michal Vrablík; Walter Wahli; Gerald F Watts; Shizuya Yamashita; Koutaro Yokote; Alberto Zambon; Peter Libby Journal: Cardiovasc Diabetol Date: 2019-06-04 Impact factor: 9.951