mir-33 inhibition attenuates the effect of liver x receptor agonist t0901317 on expression of liver x receptor alpha in mice liver

Background:micrornas play pivotal roles in metabolism and other aspects of cell biology. microrna-33 and liver x receptor (lxr) affect lipid metabolism and cholesterol trafficking. in this study, we evaluated effects of co-administration of mir-33 inhibitor and lxr activator on lxr-α and adenosine triphosphate-binding cassette transporter a1 (abca1) expression in mice liver.methods:twenty-four mice were randomly allocated into four groups (n = 6). group 1 mice received standard chow diet without any treatment, group 2 received 30 mg/kg/48 hour lxr agonist (t0901317), group 3 received 1 mg/kg/48 hour in vivo locked nucleic acids (lna)anti-mir-33 and group 4 received both t0901317 and in vivo lna anti-mir-33. all treatments were administrated through intraperitoneal injection(ip). after 7 days and at the end of the study, mice were sacrificed, liver tissues were excised and blood samples were collected. lxr-α and abca1 genes and protein expression were quantified by real-time polymerase chain reaction (pcr) and western blotting, respectively.results:lxr activation caused lxr-α and abca1 mrna (p < 0.050) and protein elevation as compared to control (p < 0.001). mir-33 inhibition attenuates t0901317 effect on lxr-α expression in group iv. co-administration of t0901317 and anti-mir-33 remarkably elevated high-density lipoprotein cholesterol (hdl-c) levels, compared to control group (p = 0.001). separate administration of t0901317 and anti-mir-33 also elevated hdl-c levels (p < 0.010).conclusion:co-administration of t0901317 and anti-mir-33 can be considered as a good therapeutic alternative for atherosclerosis because mir-33 inhibition reduced lipogenic effects of lxr-α activator and also helps lxr-α agonist to increase reverse cholesterol transport (rct) and also hdl-c as antiatherogenic effects.