脱氢表雄酮对高脂饮食诱导肥胖大鼠肝脏脂肪酸代谢的影响

Effect of dehydroepiandrosterone on fatty acid metabolism in the liver of high-fat diet-induced obese rats

目的 探讨脱氢表雄酮（DHEA）对高脂饮食诱导肥胖大鼠肝脏脂肪酸代谢的影响。方法 27只SD大鼠分为对照组、高脂组和高脂联合DHEA组（DHEA组），每组9只。取大鼠血清，测定血糖和胰岛素；用液相色谱质谱联用（LC-MS）测定肝脏游离脂肪酸（FFA）水平，用实时定量PCR检测激素敏感性脂肪酶（HSL）、脂蛋白酯酶（LPL）、乙酰辅酶A羧化酶（ACC）、脂肪酸合成酶（FAS）、肉碱酯酰辅酶A转移酶（CPT）、硬脂酰辅酶A去饱和酶1（SCD1）mRNA的表达，以油红O染色观察肝脏脂质沉积的改变。结果 （1）高脂组肝脏FFA含量显著高于对照组（P〈0．05），而DHEA组与高脂组相比，FFA显著下降（P〈0．05）：（2）DHEA组HSL、LPL、ACC、FAS的mRNA表达显著低于高脂组，而CPT和SCD1的mRNA表达则显著高于高脂组，差异具有统计学意义（P〈0．05）。（3）油红O染色显示高脂喂养后大鼠肝脏脂质含量均显著增加（P〈0．05），高脂组和DHEA组之间差异无统计学意义，但与DHEA组相比，高脂组结构破坏更明显。结论 DHEA可能通过抑制FFA的生成，促进FFA的β氧化，降低高脂诱导肥胖大鼠肝脏FFA的含量。

Objective To explore the role of dehydroepiandrosterone （DHEA） in fatty acid metabolism in the liver of obese rats induced by high fat diet. Methods Twenty-seven SD rats were divided into control group, highfat diet group （ HF group） , and high-fat diet combined with DHEA treatment group （ DHEA group）. The serum glucose and insulin levels were determined, while the free fatty acids （FFA） level was measured by liquid chromatography-tandem mass spectrometry （LC-MS）. The mRNA expressions of hormone-sensitive lipase （HSL） , lipoprotein lipase （LPL）, acetyl-CoA carboxylase （ACC）, fatty acid synthase （FAS）, carnitine acyl-CoA transferase （CPT）, and stearoyl-CoA desaturase 1 （SCD1） were measured by real-time PCR. Finally, oil red O staining was also used to observe the changes in hepatic lipid deposition. Results （ 1 ） The content of hepatic FFA in HF group was significantly higher than that in control group （P〈0.05） , but decreased in DHEA group compared with that in HF group （P〈0.05）. （2） Compared with HF group, the mRNA expressions of HSL, LPL, ACC, FAS in DHEA group were significantly lower while the mRNA expressions of CPT1, CPT2, and SCD1 were significantly higher （ all P 〈 0.05）. （3） Oil-red O staining showed that the liver lipid content in high fat diet-fed rats were significantly increased compared with that in the chow diet group（ P〈0.05 ）, but there was no difference between HF and DHEA groups. However, the structural damage of HF group was more evident compared with DHEA group. Conclusion DHEA may reduce the content of hepatic FFA in high-fat diet-induced obese rats via inhibiting the production of FFA and promoting the β-oxidation of FFA.