Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
Hepatology. 2013 Sep;58(3):976-82. doi: 10.1002/hep.26342. Epub 2013 Jul 29.
Dysregulation of the cholesterol synthesis pathway and accumulation of cholesterol in the liver are linked to the pathogenesis of nonalcoholic steatohepatitis (NASH). Therefore, we investigated the association of serum and liver levels of cholesterol precursors with NASH. Liver histology was assessed in 110 obese patients (Kuopio Obesity Surgery Study [KOBS] study, age 43.7 ± 8.1 years [mean ± standard deviation, SD], body mass index [BMI] 45.0 ± 6.1 kg/m(2) ). Serum and liver levels of cholesterol precursors were measured with gas-liquid chromatography. The association between cholesterol precursors and serum alanine aminotransferase (ALT), as a marker of liver disease, was also investigated in a population cohort of 717 men (Metabolic Syndrome in Men Study [METSIM] study, age 57.6 ± 5.8 years, BMI 27.1 ± 4.0 kg/m(2) ). Serum desmosterol levels and the desmosterol-to-cholesterol ratio were higher in individuals with NASH, but not in individuals with simple steatosis, compared to obese subjects with normal liver histology (P = 0.002 and P = 0.003, respectively). Levels of serum and liver desmosterol correlated strongly (r = 0.667, P = 1 × 10(-9) ), suggesting a shared regulation. Both serum and liver desmosterol levels correlated positively with steatosis and inflammation in the liver (P < 0.05). Serum desmosterol had a higher correlation with the accumulation of cholesterol in the liver than serum cholesterol. Serum desmosterol levels (P = 2 × 10(-6) ) and the serum desmosterol-to-cholesterol ratio (P = 5 × 10(-5) ) were associated with serum ALT in the population study.
Levels of desmosterol in serum and the liver were associated with NASH. These results suggest that serum desmosterol is a marker of disturbed cholesterol metabolism in the liver. Whether desmosterol has a more specific role in the pathophysiology of NASH compared to other cholesterol precursors needs to be investigated.
胆固醇合成途径失调和肝脏胆固醇积累与非酒精性脂肪性肝炎（NASH）的发病机制有关。因此，我们研究了胆固醇前体在血清和肝脏水平与 NASH 的相关性。对 110 名肥胖患者（库奥皮奥肥胖手术研究 [KOBS] 研究，年龄 43.7±8.1 岁[均值±标准差]，体重指数 [BMI] 45.0±6.1kg/m(2)）进行肝组织学评估。用气相色谱法测定胆固醇前体在血清和肝脏中的水平。还在一个 717 名男性的人群队列（代谢综合征男性研究 [METSIM] 研究，年龄 57.6±5.8 岁，BMI 27.1±4.0kg/m(2)）中研究了胆固醇前体与血清丙氨酸氨基转移酶（ALT，作为肝脏疾病的标志物）之间的关系。结果：与肝脏组织学正常的肥胖者相比，NASH 患者的血清去甲固醇水平和去甲固醇/胆固醇比值升高，但单纯脂肪变性患者的这两项指标并未升高（分别为 P=0.002 和 P=0.003）。血清和肝脏去甲固醇水平高度相关（r=0.667，P=1×10(-9)），提示两者的调节方式相似。血清和肝脏去甲固醇水平与肝脏脂肪变性和炎症呈正相关（P<0.05）。与血清胆固醇相比，血清去甲固醇与肝脏胆固醇积累的相关性更高。在人群研究中，血清去甲固醇水平（P=2×10(-6)）和血清去甲固醇/胆固醇比值（P=5×10(-5)）与血清 ALT 相关。结论：血清和肝脏去甲固醇水平与 NASH 相关。这些结果表明，血清去甲固醇是肝脏胆固醇代谢紊乱的一个标志物。去甲固醇与其他胆固醇前体相比，在 NASH 的病理生理学中是否具有更特异的作用，尚需进一步研究。
