Dept. of Internal Medicine, University of Tübingen, German Center for Diabetes Research, Germany.
Am J Physiol Endocrinol Metab. 2011 Feb;300(2):E321-6. doi: 10.1152/ajpendo.00306.2010. Epub 2010 Nov 2.
Stearoyl-CoA desaturase-1 (SCD1) has gained much interest as a future drug target to treat fatty liver and its consequences. However, there are few and inconsistent human data about expression and activity of this important enzyme. We investigated activity and expression of SCD1 and their relationships with liver fat (LF) content in human liver samples. Fifty subjects undergoing liver surgery were studied. SCD1 activity was estimated from the ratio of oleate (C18:1) to stearate (C18:0) within lipid subfractions. Furthermore, SCD1 mRNA expression and LF content were measured. Similarly to previous studies, we observed a strong positive correlation between LF content and the C18:1/C18:0 ratio in the combined fatty acid (FA) fractions (r = 0.96, P < 0.0001), which could be interpreted as higher SCD1 activity with increasing LF. However, hepatic SCD1 mRNA expression did not correlate with LF (r = 0.16, P = 0.13). To solve these conflicting data, we analyzed the FA composition of hepatic lipid subfractions. With increasing LF content the amount of FAs from the triglyceride (TG) fraction increased (r = 0.96, P < 0.0001), whereas the FAs from the phospholipid (PL) fraction remained unchanged (r = -0.17, P = 0.19). Of these two major lipid fractions, the C18:1/C18:0 ratio in TG was 16-fold higher than in PL. Supporting the SCD1 mRNA expression data, the C18:1/C18:0 ratio of the TG or PL fraction did not correlate with LF (r = 0.26, P = 0.12 and r = 0.08, P = 0.29). We provide novel information that SCD1 activity and mRNA expression appear not to be elevated in subjects with high LF content. We suggest that the FA composition of lipid subclasses, rather than of mixed lipids, should be analyzed to estimate SCD1 activity.
硬脂酰辅酶 A 去饱和酶-1（SCD1）作为治疗脂肪肝及其后果的未来药物靶点备受关注。然而，关于这种重要酶的表达和活性的人体数据很少且不一致。我们研究了人类肝组织样本中 SCD1 的活性和表达及其与肝脂肪（LF）含量的关系。研究了 50 名接受肝手术的患者。通过脂质亚组分中油酸（C18:1）与硬脂酸（C18:0）的比值来估计 SCD1 活性。此外，还测量了 SCD1 mRNA 表达和 LF 含量。与之前的研究类似，我们观察到 LF 含量与组合脂肪酸（FA）亚组分中的 C18:1/C18:0 比值之间存在很强的正相关（r = 0.96，P <0.0001），这可以解释为随着 LF 的增加，SCD1 活性增加。然而，肝 SCD1 mRNA 表达与 LF 不相关（r = 0.16，P = 0.13）。为了解决这些相互矛盾的数据，我们分析了肝脂质亚组分的 FA 组成。随着 LF 含量的增加，甘油三酯（TG）亚组分中的 FA 量增加（r = 0.96，P <0.0001），而磷脂（PL）亚组分中的 FA 量保持不变（r = -0.17，P = 0.19）。在这两个主要的脂质亚组分中，TG 中的 C18:1/C18:0 比值比 PL 高 16 倍。支持 SCD1 mRNA 表达数据，TG 或 PL 亚组分的 C18:1/C18:0 比值与 LF 不相关（r = 0.26，P = 0.12 和 r = 0.08，P = 0.29）。我们提供了新的信息，表明 SCD1 活性和 mRNA 表达在 LF 含量高的受试者中似乎没有升高。我们建议，应分析脂质亚类的 FA 组成，而不是混合脂质的 FA 组成，以估计 SCD1 活性。
