Ameliorating effects of D-47, a newly developed compound, on lipid metabolism in an animal model of familial hypercholesterolemia (WHHLMI rabbits)

Shohei Tamura, Yui Koike, Hiroaki Takeda, Tomonari Koike, Yoshihiro Izumi, Ryosuke Nagasaka, Tetsuto Tsunoda, Motoo Tori, Kazuo Ogawa, Takeshi Bamba, Masashi Shiomi

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Abstract

Improvements induced in lipid metabolism in the liver by D-47, a newly developed compound, were examined herein. WHHLMI rabbits, an animal model of hypercholesterolemia and coronary atherosclerosis, was fed D-47-supplemented chow for 5 weeks at a dose of 30 mg/kg. Lipid concentration were assayed using enzymatic methods. Plasma lipoproteins were fractionated with an ultracentrifuge. mRNA expression was analyzed with real-time PCR. Lipidome analyses of lipoproteins were performed using supercritical fluid chromatography mass spectrometry. In the D-47-treated group, serum lipid levels decreased by 23% for total cholesterol and by 40% for triglycerides. These reductions were mainly attributed to decreases in the VLDL fraction. Compared with the control, in the D-47 group, lipid contents in the liver were decreased by 22% in cholesterol and by 69% in triglycerides, and fat accumulation was decreased by 57% in pericardial fat and by 17% in mesenteric fat. In lipidome analyses of VLDL fraction, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylethanolamine plasmalogen, sphingomyelin, and ceramide were decreased by the D-47 treatment. mRNA expression in the liver was 51% lower for FAS and 24% lower for MTP, but 5.9- and 5.1-fold higher for CYP7A1 and CPT-1, respectively, in the D-47 group than in the control. mRNA expression was 72%, 64%, and 36% higher for LPL, CTP-1, and PPARγ, respectively, in mesenteric fat in the D-47 group. D-47 is a potent lipid-lowering compound that uses a different mechanism of action from that of statins. It has potential as a compound in the treatment of steatohepatitis and metabolic syndrome.

Original languageEnglish
Pages (from-to)147-153
Number of pages7
JournalEuropean Journal of Pharmacology
Volume822
DOIs
Publication statusPublished - Mar 5 2018

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Hyperlipoproteinemia Type II
Lipid Metabolism
Animal Models
Rabbits
Fats
Lipids
Messenger RNA
Lipoproteins
Liver
Triglycerides
Cholesterol
Supercritical Fluid Chromatography
Cytidine Triphosphate
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lysophosphatidylcholines
Peroxisome Proliferator-Activated Receptors
Sphingomyelins
dibenzthione
Ceramides
Fatty Liver

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Ameliorating effects of D-47, a newly developed compound, on lipid metabolism in an animal model of familial hypercholesterolemia (WHHLMI rabbits). / Tamura, Shohei; Koike, Yui; Takeda, Hiroaki; Koike, Tomonari; Izumi, Yoshihiro; Nagasaka, Ryosuke; Tsunoda, Tetsuto; Tori, Motoo; Ogawa, Kazuo; Bamba, Takeshi; Shiomi, Masashi.

In: European Journal of Pharmacology, Vol. 822, 05.03.2018, p. 147-153.

Research output: Contribution to journalArticle

Tamura, Shohei ; Koike, Yui ; Takeda, Hiroaki ; Koike, Tomonari ; Izumi, Yoshihiro ; Nagasaka, Ryosuke ; Tsunoda, Tetsuto ; Tori, Motoo ; Ogawa, Kazuo ; Bamba, Takeshi ; Shiomi, Masashi. / Ameliorating effects of D-47, a newly developed compound, on lipid metabolism in an animal model of familial hypercholesterolemia (WHHLMI rabbits). In: European Journal of Pharmacology. 2018 ; Vol. 822. pp. 147-153.
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AU - Izumi, Yoshihiro

AU - Nagasaka, Ryosuke

AU - Tsunoda, Tetsuto

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AU - Ogawa, Kazuo

AU - Bamba, Takeshi

AU - Shiomi, Masashi

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