Department of Gastroenterology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Sci Rep. 2019 Jul 23;9(1):10663. doi: 10.1038/s41598-019-47216-2.
Metabolic disturbance of lipids is a hallmark of nonalcoholic fatty liver disease (NAFLD). In this study, we measured the serum levels of 15 acylcarnitine species of various carbon chain lengths from 2 to 18 in 241 patients with biopsy-proven NAFLD, including 23 patients with hepatocellular carcinoma (HCC), and analyzed the relationship between serum acylcarnitine profile and NAFLD status. Long-chain acylcarnitines AC14:1 and AC18:1 increased gradually with the progression of fibrosis and further increased in patients with HCC, whereas the middle-chain acylcarnitine AC5:0 exhibited the opposite trend. In particular, AC18:1, which we previously showed to possess a tumor promoting effect, was significantly elevated in patients with HCC compared to those without HCC. In addition, long-chain acylcarntines including AC18:1 were positively correlated with serum levels of inflammatory cytokines. Although none of the acylcarnitine species were independently associated with the presence of HCC, (AC16:0 + AC18:1)/AC2:0, an index for the diagnosis of carnitine palmitoyltransferase 2 (CPT2) deficiency, was independently associated with the presence of HCC after adjusting for age and liver fibrosis stage, likely reflecting the downregulation of CPT2 in HCC tissues. Thus, serum acylcarnitine profiles changed significantly according to the status of NAFLD, which may be implicated in the pathogenesis of NAFLD.
脂质代谢紊乱是非酒精性脂肪性肝病（NAFLD）的一个标志。在这项研究中，我们测量了 241 例经活检证实的 NAFLD 患者（包括 23 例肝细胞癌 [HCC] 患者）血清中各种碳链长度为 2 至 18 的 15 种酰基辅酶 A 物质的水平，并分析了血清酰基辅酶 A 谱与 NAFLD 状态之间的关系。长链酰基辅酶 A AC14:1 和 AC18:1 随着纤维化的进展逐渐增加，在 HCC 患者中进一步增加，而中链酰基辅酶 A AC5:0 则呈现相反的趋势。特别是我们之前发现具有促进肿瘤作用的 AC18:1，在 HCC 患者中明显高于无 HCC 患者。此外，长链酰基辅酶 A 包括 AC18:1 与血清炎症细胞因子水平呈正相关。虽然没有一种酰基辅酶 A 物质与 HCC 的存在独立相关，但（AC16:0 + AC18:1）/AC2:0，一种诊断肉碱棕榈酰转移酶 2（CPT2）缺乏症的指标，在调整年龄和肝纤维化阶段后与 HCC 的存在独立相关，可能反映了 HCC 组织中 CPT2 的下调。因此，血清酰基辅酶 A 谱根据 NAFLD 的状态发生显著变化，这可能与 NAFLD 的发病机制有关。
