Gemfibrozil reduces non-high-density lipoprotein cholesterol in exogenously hypercholesterolemic (ExHC) rats fed a high-cholesterol diet

Nagao, Koji; Yoshida, Susumu; Nakagiri, Hideaki; Sakono, Masafumi; Sato, Masao; Imaizumi, Kazunori

doi:10.1016/s0305-0491(98)10049-4

Cited by 9 publications

(4 citation statements)

References 33 publications

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“…have been shown to improve lipid profiles in rats (Nagao et al 1998;Miao et al 2004;Guo et al 2006). In the current studies, a significant rise in HDL-C (40%, P < 0.01) was observed in rats treated with CM108, which was greater than the increases with gemfibrozil and GW3965 (31% and 21%, respectively).…”

Section: Discussionsupporting

confidence: 40%

Hypolipidaemic mechanisms of action of CM108 (a flavone derivative) in hyperlipidaemic rats

Guo

Lian

et al. 2008

Journal of Pharmacy and Pharmacology

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In the present study, the molecular mechanisms by which CM108, a flavone derivative, improves lipid profiles were investigated further. Hyperlipidaemia was induced by oral administration of high cholesterol and fat. After 4 weeks of treatment, the lipid levels in the serum, liver and faeces were measured and the liver genes involved in lipid metabolism were analysed to explore the molecular mechanisms of lowering lipids. CM108 modulated lipid profiles, including elevating the level of high-density lipoprotein cholesterol (HDL-C; 40%) and reducing serum levels of triglyceride (10%), total cholesterol (10%) and low-density lipoprotein cholesterol (26%). Levels of triglyceride and total cholesterol in the liver were reduced by 18% and 24%, respectively. Increased HDL-C level was attributed to the synergic effects of CM108 in increasing levels of ATP-binding cassette transporter (ABC)A1, apolipoprotein AI and apolipoprotein AII in the liver. Intriguingly, CM108 induced genes, including fatty acid transport protein, acyl-CoA synthetase and lipoprotein lipase that are important for more efficient fatty acid beta-oxidation, thereby reducing serum and liver triglyceride levels. In addition, induction of ABCG5, ABCG8 and cholesterol 7alpha-hydroxylase contributed to cholesterol metabolism, leading to decreases in serum and liver cholesterol levels. Thus, the genes involved in lipid metabolism were systemically modulated by CM108, which contributed to the improvement of lipid profiles in hyperlipidaemic rats.

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Section: Discussionsupporting

confidence: 40%

Hypolipidaemic mechanisms of action of CM108 (a flavone derivative) in hyperlipidaemic rats

Guo

Lian

et al. 2008

Journal of Pharmacy and Pharmacology

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“…Cholesterol metabolism has been analyzed in detail in ExHC rats [14,15,17,39]. Cholesterol intestinal absorption [14], hepatic synthesis [39], and excretion in feces [15] in ExHC rats are similar to those in SD rats.…”

Section: Discussionmentioning

confidence: 99%

“…Cholesterol intestinal absorption [14], hepatic synthesis [39], and excretion in feces [15] in ExHC rats are similar to those in SD rats. We have also reported that when ExHC rats are fed a cholesterol diet, the uptake of blood β-VLDL by the liver is lower in ExHC rats compared with that in SD rats fed a cholesterol diet because both the association and the degradation of β-VLDL by the liver cells is lower in ExHC rats [17].…”

Section: Discussionmentioning

confidence: 99%

Unavailability of liver triacylglycerol increases serum cholesterol concentration induced by dietary cholesterol in exogenously hypercholesterolemic (ExHC) rats

et al. 2014

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BackgroundExogenously hypercholesterolemic (ExHC) rats develop hypercholesterolemia and low hepatic triacylglycerol (TAG) levels when dietary cholesterol is loaded. The responsible gene Smek2 was identified via linkage analysis using the original strain Sprague–Dawley (SD) rats. In this study, we compared SD and ExHC rats to investigate a relationship between hypercholesterolemia and the low hepatic TAG levels observed in ExHC rats.MethodsMale 4-weeks-old ExHC and SD rats were fed a 1% cholesterol diet for 1 week. Serum and liver parameters were analyzed. Gene expression and enzyme activities related to TAG metabolism were also assessed.ResultsWe reproducibly observed higher serum cholesterol and lower hepatic TAG levels in ExHC rats than in SD rats. Golgi apparatus in the livers of ExHC rats secreted β-very-low-density lipoprotein (β-VLDL) that had higher cholesterol ester (CE) and lower TAG content than those in the β-VLDL secreted by SD rats. Gene expression related to fatty acid and TAG synthesis in ExHC rats was lower than that in SD rats. Enzymatic activities for fatty acid synthesis were also relatively lower in ExHC rats. Moreover, the fatty acid composition of hepatic and serum CE in ExHC rats showed that these CEs were not modified after secretion from the liver despite the similar activities of serum lecithin-cholesterol acyltransferase (LCAT) in ExHC rats to those in SD rats.ConclusionsLow production of liver TAG and secretion of CE-rich, TAG-poor β-VLDL without modification by LCAT in the circulation contributed to hypercholesterolemia induced by dietary cholesterol in ExHC rats.

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“…Exogenously hypercholesterolemic (ExHC) rats, initially isolated from the Sprague-Dawley (SD) strain by Imai and Matsumura (8), show a ready hypercholesterolemia upon cholesterol feeding in the absence of hypothyroidism and bile salt in diet (9)(10)(11)(12). It is considered that polygenes would be involved in stable hypercholesterolemia in this strain (8), but detailed mechanisms have not been clarified yet.…”

mentioning

confidence: 99%

Ethanol‐extracted soy protein isolate results in elevation of serum cholesterol in exogenously hypercholesterolemic rats

Yoshida

Tsuda

et al. 1999

Lipids

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Soy protein preparations were reported to have hypocholesterolemic actions in experimental animals and humans, while the active components and the mechanism by which this occurs are not clarified yet. The objective of this study is to address these issues by using exogenously hypercholesterolemic rats which are susceptible to dietary cholesterol. Two groups of five rats (male, 12-wk-old) were fed on AIN 93G-based diet with soy protein isolate (SPI) or ethanol-extracted SPI (EE-SPI) for 2 wk. EE-SPI was prepared by ethanol extraction to remove isoflavones and other components. Concentrations of serum and liver total cholesterol were lower in rats fed SPI than in those fed EE-SPI. The abundances of mRNA for 7alpha-hydroxylase and low density lipoprotein receptor in the liver were lower in EE-SPI group than those in SPI group. These results suggest that the ethanol extract from SPI has a factor(s) to alleviate hypercholesterolemia by increasing the removal of cholesterol from serum through the receptor pathway and then from liver through enhancement of bile acid synthesis.

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Gemfibrozil reduces non-high-density lipoprotein cholesterol in exogenously hypercholesterolemic (ExHC) rats fed a high-cholesterol diet

Cited by 9 publications

References 33 publications

Hypolipidaemic mechanisms of action of CM108 (a flavone derivative) in hyperlipidaemic rats

Hypolipidaemic mechanisms of action of CM108 (a flavone derivative) in hyperlipidaemic rats

Unavailability of liver triacylglycerol increases serum cholesterol concentration induced by dietary cholesterol in exogenously hypercholesterolemic (ExHC) rats

Ethanol‐extracted soy protein isolate results in elevation of serum cholesterol in exogenously hypercholesterolemic rats

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