PPARs have been known to regulate various metabolic processes by activating related transcription factors upon binding to their ligands. Among three different subtypes of PPAR, PPARδ has been implicated in energy metabolism and lipid oxidation process. However, roles of PPARδ in the development of pathologic conditions resulting from the abnormal lipid metabolism such as atherosclerosis and steatosis still remains unclear and controversial. Thus, we investigated the effect of PPARδ agonist on LDLR -/- mice fed western diet focusing on the formation of atherosclerotic lesion and steatosis in the liver.
For this study, LDLR -/- mice were received L-165041 (5 mg/kg/day, ip) or vehicle (0.1 N NaOH) with western diet for 16 weeks. L-165041 treatment had no significant effect on bodyweight and atherosclerotic lesion formation. For serum lipid profile, total cholesterol, LDL, and TG level was decreased with L-165041 treatment, although it was not statistically significant. Regarding the effect on the development of fatty liver (steatosis), microscopic examination of liver specimens shows that L-165041 treatment significantly inhibited lipid accumulation compared to the vehicle group. Furthermore, in line with this result, total hepatic TG and cholesterol contents were also lower in L-165041 treated group. RT-PCR results using liver homogenates and HL(hepatic lipase), LPL(lipoprotein lipase), and DGAT(diacylglycerol acyltransferase) specific primers shows that L-165041 treatment increased HL and LPL expression while it decreased DGAT expression.
Although no significant anti-atherogenic effect of L-165041 was observed in this study, our data indicate that L-165041 might be effective in controlling fatty liver.
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