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A Novel Selective PPARα Modulator (SPPARMα), K-877 (Pemafibrate), Attenuates Postprandial Hypertriglyceridemia in Mice
- Source :
- Journal of Atherosclerosis and Thrombosis
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Male
K-877 (Pemafibrate)
Apolipoprotein B
030204 cardiovascular system & hematology
Corrections
chemistry.chemical_compound
Mice
0302 clinical medicine
Fenofibrate
Chylomicrons
Chylomicron remnants
Hypolipidemic Agents
Hypertriglyceridemia
Benzoxazoles
Lipoprotein lipase
biology
Chemistry
digestive, oral, and skin physiology
Postprandial Period
Butyrates
Postprandial
Original Article
lipids (amino acids, peptides, and proteins)
Cardiology and Cardiovascular Medicine
medicine.drug
medicine.medical_specialty
Postprandial hypertriglyceridemia
Hyperlipidemias
030209 endocrinology & metabolism
Diet, High-Fat
03 medical and health sciences
Chylomicron remnant
Internal medicine
Internal Medicine
medicine
Animals
PPAR alpha
SPPARMα
Triglyceride
Biochemistry (medical)
medicine.disease
Mice, Inbred C57BL
PPAR gamma
030104 developmental biology
Endocrinology
biology.protein
Chylomicron
Subjects
Details
- ISSN :
- 18803873
- Volume :
- 25
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of atherosclerosis and thrombosis
- Accession number :
- edsair.doi.dedup.....62644f78df4e004e1e8a4ab61b51484b