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.%目的：研究PPARα激活后对PPARγ诱导小鼠脂肪肝的影响。方法以4～5周龄C57BL／6J小鼠为模型，实验分为4组：正常饮食组；0.125％ Wy-14，643处理组；PPARγ腺病毒（ Ad／PPARγ）注射组；先给予0.125％Wy-14，643饮食再注射Ad／PPARγ组。实验结束时，收集肝脏组织称重、照相， H＆E、油红O 染色观察PPARα激活后对PPARγ诱导肝脏脂肪变性的影响。结果野生型小鼠给予PPARα激动剂Wy-14，643处理8 d，与对照组相比，处理组小鼠肝脏明显增大，呈现过氧化物酶体增殖反应；野生型小鼠给予Ad／PPARγ5 d，小鼠肝脏显著增大，出现脂肪肝；给予PPARα激动剂Wy-14，6433 d，再给予Ad／PPARγ5 d，小鼠肝脏增大更加显著，H＆E染色、油红O染色结果显示小鼠肝脏脂肪变性明显减轻。结论激活PPARα能够缓解PPARγ诱导的小鼠肝脏脂肪变，为脂肪肝的预防和治疗提供了新的研究思路和靶点。
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