The effect of diet on the response of low-density lipoprotein receptor knockout mice to the liver X receptor agonist T1317.

Journal of Cardiovascular Pharmacology
Lu PengDacheng Peng

Abstract

It has been previously observed that low-density lipoprotein receptor knockout (LDLR--/--) mice fed a Western-type diet without cholate and given the liver X receptor agonist T1317 develop a persistent and enhanced hypertriglyceridemia. In contrast, LDLR--/-- mice fed a Paigen diet with cholate exhibit only a transient increase in plasma triglycerides when given T1317. Cholate as an activator of farnesoid X receptor may attenuate T1317-induced triglyceridemia. To determine if cholate was responsible for this transient nature of the hypertriglyceridemia, we orally administered T1317 to LDLR--/-- mice fed a modified Paigen diet without cholate. T1317 transiently elevated plasma triglycerides by increasing plasma very-low-density lipoprotein. Cholesterol and triglyceride levels in plasma very-low-density lipoprotein in T1317-treated mice decreased from peak levels to levels found in vehicle-treated mice after 8 weeks of treatment. A gradual decline of hepatic cholesterol and a transient increase in hepatic triglycerides were also observed in T1317-treated mice. T1317 only transiently activated the expression of genes related to liver de novo lipogenesis, whereas genes related to lipid metabolism were induced in T1317-treated mice,...Continue Reading

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Citations

Mar 16, 2012·Current Opinion in Lipidology

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