Activation of PPARαimproves PPARγ-induced fatty liver in the mouse / 中国实验动物学报

ABSTRACT

Object To investigate the effect of PPARαactivation on PPARγ-induced fatty liver in the mouse. Methods Wild type mice ( C57BL/6) aged 4 to 5 weeks were used as animal models.All mice were divided into four groups.The mice in the first group were fed with chow diet.The mice in the second group were fed with a diet containing 0.125%Wy-14,643, an agonist of PPARa, for 8 days.The mice in the third group were injected with Ad/PPARγvia tail vein for 5 day.The mice in the fourth group were firstly fed with Wy-14,643 diet for 3 days and then injected with Ad/PPARγvia tail vein for another 5 day.Mouse livers were collected and photographed.The effect of PPARαactivation on PPARγ-induced fatty liver was observed by H&E and Oil red O staining.Results Compared with the controls, wild-type mice treated with Wy-14,643 for 8 days exhibited marked hypertrophy of hepatocytes with increased cytoplasmic eosinophil-ia and proliferation of peroxisomes.The liver size was significantly increased in the wild-type mice treated with Ad/PPARγfor 5 days, and over-expression of PPARγstrongly induced hepatic steatosis.Importantly, the wild-type mice pretreated with Wy-14,643 for 3 days and then given Ad/PPARγinjection exhibited dramatically the increase of liver size, which might be due to the dual function of PPARa and PPARγ.Compared with the Ad/PPARγgroup, the Wy-14,643 pretreat-ment group showed a reduced hepatic steatosis.Conclusions Activation of PPARαby Wy-14,643 effectively improves PPARγ-stimulated hepatic steatosis, which provides a novel target for prevention and therapy of fatty liver.