Osthole Modulates Fatty Acid Metablism And Its Mechanisms In Adipose Tissue Of Fatty Liver Rats And Cultured Adipocytes

Aim: To observe that osthole modulated the fatty acid metabolism in adipose tissueof high-fat-induced fatty liver rats and cultured adipocytes, and to investigate itspotential mechanisms.Methods: Male SD rats were used and randomly divided into the control, model,osthole5,10and20mg/kg groups, positive drugs lipanthyl30mg/kg and rosiglitazone4mg/kg groups. The rat model was established by orally feeding high-fat emulsion bygavage for9weeks. These medications were taken orally for4weeks after oral high-fatemulsion for6weeks. Finally, all of the rats were sacrificed. The triglycerides (TG) andfree fatty acids (FFA) in serum were measured. The mRNA expressions of peroxisomeproliferator-activated receptor (PPAR)α, PPARγ, sterol regulatory element bindingprotein (SREBP)-1c, SREBP-2, fatty acid synthase (FAS), diacylglycerolacyltransferase (DGAT) and lipoprotein lipase (LPL) in the adipose tissue weredetermined by reverse transcription-polymerase chain reaction (RT-PCR) method. Thecultured3T3-L1adipocytes were divided into control, DMSO, osthole7.5,15and30μg/mL, fenofibrate200μg/mL, rosiglitazone10μg/mL groups, respectively. Afterincubation with drugs for24hours, the gene expressions of PPARα, PPARγ, SREBP-1c,SREBP-2, FAS, DGAT and LPL were measured with RT-PCR. In order to determinewhether the mechanisms of osthole regulatory effect were associated with the pathwayof PPARα/γ, the cultured adipocytes were pretreated with MK886(a PPARα inhibitor)and/or GW9662(a PPARγ inhibitor) for2hours, then incubation with30μg/mL ostholefor24hours, changes of these gene expressions including SREBP-1c, SREBP-2, FAS,DGAT and LPL were examined.Results: In vivo, after treatment with osthole for4weeks, the serum levels of TGand FFA were significantly lowered（P<0.05or P<0.01）. In vitro, the intracellular TG andFFA levels and cultured supernatant FFA level were significantly decreased after treatment with osthole for24h (P<0.05or P<0.01). Osthole could significantly increase the geneexpressions of PPARα and PPARγ（P<0.05or P<0.01）, decrease the gene expressionsof SREBP-1c, SREBP-2, FAS, DGAT and LPL in adipose tissue and3T3-L1adipocytes（P<0.05or P<0.01）.And after the pretreatment with MK886and/or GW9662for2h,the regulation of30μg/mL osthole on mRNA expressions of SREBP-1c, SREBP-2,FAS, DGAT and LPL was decreased or cancelled.Conclusion: Osthole not only decreased the TG and FFA levels in serum inhigh-fat-induced fatty liver rats, but also decreased the intracellular TG and FFA levelsin cultured adipocytes and the FFA level in cultured supernatant, and its mechanisms mightbe associated with activation of PPARα/γ and subsequent reduction of SREBP-1c/2,FAS, DGAT and LPL gene expressions.