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Hepatic Cholesterol (hepatic + cholesterol)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Novel pathways for glycaemic control in type 2 diabetes: focus on bile acid modulation

DIABETES OBESITY & METABOLISM, Issue 11 2008
Eliot A. Brinton
Type 2 diabetes is a common disorder with high risk of macrovascular and microvascular complications. These complications are largely driven by hyperglycaemia, dyslipidaemia and hypertension, for which aggressive treatment is thus warranted. Achieving and maintaining control of all three risk factors is especially difficult, however, and new therapeutic approaches could be useful. Bile acids have a well-established and important role in cholesterol homeostasis. Normally, their levels are maintained primarily by ileal reabsorption and enterohepatic recycling. Bile acid sequestrants bind bile acids in the intestine, reduce this recycling and deplete the bile acid pool, thereby stimulating use of hepatic cholesterol for bile acid synthesis, which leads to accelerated removal of LDL from the plasma and a decrease in LDL-cholesterol levels. Interestingly, recent evidence suggests that bile acid sequestrants can lower glucose levels to a clinically meaningful degree. This review presents this evidence and the possible mechanisms by which these glucose-lowering effects occur and discusses the apparently unique ability of bile acid sequestrants among lipid-lowering agents to significantly improve two cardiovascular risk factors, hyperglycaemia and dyslipidaemia. There is renewed interest in the use of bile acid sequestrants in individuals with type 2 diabetes, most of whom would benefit from additional reductions in both LDL-cholesterol and glycaemia. [source]

Bezafibrate induces multidrug-resistance P-Glycoprotein 3 expression in cultured human hepatocytes and humanized livers of chimeric mice

HEPATOLOGY RESEARCH, Issue 7 2007
Junichi Shoda
Aim and Methods: , A decreased function of multidrug-resistance 3 P-glycoprotein (MDR3), limiting the rate of biliary phospholipid secretion, predisposes individuals to cholestasis and/or cholangitis. Fibrates induce the expression of mdr2 (homolog of human MDR3) in rodents. To investigate the effects of bezafibrate (BF) on the expression levels of MDR3 in cultured human hepatocytes and human livers, the amount of protein and subcellular localization of MDR3 was assessed in HepG2 cells treated with BF and humanized livers of BF-treated chimeric mice. Results:, In HepG2 cells, while treatment with BF did not increase the protein levels of MDR3, the treatment caused a redistribution of MDR3 in the bile canaliculi. In humanized livers of chimeric mice, oral administration of BF induced a large increase in the protein amount of MDR3 and its redistribution in the bile canaliculi. Moreover, the modulatory effects of BF on key factors involved in hepatic cholesterol and bile acid metabolism in human subjects were traced in the humanized livers of BF-treated chimeric mice. Conclusion:, BF causes an induction of MDR3 expression in human livers. This provides a rationale for the beneficial role of BF in improving cholestasis and/or cholangitis associated with defective MDR3 expression and function in various types of cholestatic hepatobiliary diseases. [source]

Lipid-lowering efficacy of 3,4-di(OH)-phenylpropionic L -leucine in high-cholesterol fed rats

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2005
Soon-Ja Kim
Abstract A preliminary study revealed that 3,4-di(OH)-hydrocinnamate (HC), a polyphenolic compound, lowered the plasma lipids in high-cholesterol fed rats. Accordingly, this study was designed to test the lipid-lowering efficacy of a synthetic derivative, 3,4-di(OH)-phenylpropionic (L -leucine) amide (PPLA), in rats fed a high-cholesterol (1%, wt/wt) diet. As such, HC or PPLA was given as supplement to a high-cholesterol diet for 6 weeks at a dose of 0.137 mmol/100 g diet. The supplementation of HC and PPLA significantly lowered the plasma and hepatic cholesterol and triglyceride levels compared to the control group. The activities of hepatic HMG-CoA reductase (164 ± 9.12 and 124.74 ± 17.09 pmol/min/mg protein vs. 245.41 ± 13.01 pmol/min/mg protein, p < 0.05) and ACAT (411.49 ± 11.48 and 334.35 ± 17.68 pmol/min/mg protein vs. 490.41 ± 16.69 pmol/min/mg protein, p < 0.05) were significantly lower in the HC- and PPLA-supplemented groups than in the control group. However, PPLA was more effective in inhibiting the enzyme activities than HC. The excretion of neutral sterol was significantly higher in HC- and PPLA-supplemented groups than in the control group. Therefore, these results indicate that PPLA, a leucine-attached version of HC, exhibited a similar significant hypocholesterolemic effect to HC in rats fed a high-cholesterol diet. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:25,31, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20054 [source]

Comparative study on hypocholesterolemic effect of Rhodopseudomonas palustris and Rhodobacter capsulatus on rats fed a high cholesterol diet

ANIMAL SCIENCE JOURNAL, Issue 5 2007
Hirotada TSUJII
ABSTRACT This comparative study was to investigate the hypocholesterolemic effects of dietary Rhodopseudomonas palustris and Rhodobacter capsulatus on rats fed a high cholesterol diet. Thirty male Wister,Imamichi rats were assigned to three groups and fed on either a high cholesterol diet, or a high cholesterol diet supplemented with 2.0% R. palustris or R. capsulatus for 4 weeks. Compared to the control diet, both of the R. palustris and R. capsulatus supplemented diets significantly reduced the serum cholesterol, triglycerides, low-density lipoprotein, very low density lipoprotein cholesterol and hepatic triglycerides, but increased hepatic cholesterol in rats. In addition, both of the R. palustris and R. capsulatus supplemented diets may reduce the risk of atherosclerosis, as the ratio of high density lipoprotein cholesterol to the total cholesterol was significantly higher than in the control group (P < 0.05). Both the R. palustris and R. capsulatus supplemented diets led to an increase in the serum palmitic acid, compared with the oleic acid and linoleic acid. No significant differences were postulated between the rats fed R. palustris and R. capsulatus supplemented diets during the 4 weeks of the experimental period. Thus, the results may suggest that both R. palustris and R. capsulatus can contribute significant health benefits and seems to be feasible to investigate in future research. [source]