First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
Anticancer Res. 2019 Dec;39(12):6653-6660. doi: 10.21873/anticanres.13880.
The aim of this study was to investigate the effects of medium-chain triglycerides (MCTs) on chemically-induced hepatic carcinogenesis (HCC) in mice.
In a first set of experiments, mice were treated with diethylnitrosoamine intraperitoneally at two weeks of age. They were fed chow containing MCT or a normal chow diet and sacrificed after 28 weeks. Incidence of hepatic tumor was compared between the two groups. Expression of oxidative stress, and inflammatory cytokines and chemokines in liver tissues were examined. In a second set of experiments, the histopathological findings of the intraperitoneal adipose tissue were assessed, and expression of adipocytokines in the fat tissue was measured. In a third set of experiments, plasma β-hydroxybutyrate (HB) concentration was measured in both animals fed chow containing MCT and a normal chow diet. Mouse HCC cells were co-cultured with β-HB, and the numbers of tumor cells were counted at days 3 and 7.
In the first set of experiments, the tumor count observed in the control group was significantly blunted in the MCT group. Maximum tumor diameter also decreased in the MCT group compared to the control group. The expression of inflammatory cytokines and chemokines was significantly decreased by MCT. Furthermore, expression of 4-hydroxynonenal was lower in the MCT group compared to the control group. In the second set of experiments, hypertrophy of the adipocytes was suppressed, and the concentration of adiponectin and leptin in the adipose tissue decreased by MCT. In the third set of experiments, plasma β-HB concentration increased in the MCT group as expected. β-HB significantly inhibited the proliferation of HCC cells.
MCT administration markedly suppresses the incidence of chemically-induced HCC by inhibition of inflammation and increase of ketone bodies.
本研究旨在探讨中链甘油三酯(MCT)对小鼠化学诱导肝癌(HCC)的影响。
在一组实验中,将二乙基亚硝胺腹腔内注射于小鼠 2 周龄时。它们分别喂食含 MCT 的饲料或正常饲料,28 周后处死。比较两组肝脏肿瘤的发生率。检测肝组织氧化应激、炎症细胞因子和趋化因子的表达。在第二组实验中,评估腹腔内脂肪组织的组织病理学发现,并测量脂肪组织中脂肪细胞因子的表达。在第三组实验中,测量喂食含 MCT 和正常饲料的两组动物的血浆β-羟丁酸(HB)浓度。将 HCC 细胞与β-HB 共培养,并在第 3 天和第 7 天计数肿瘤细胞数。
在第一组实验中,对照组的肿瘤数量明显减少,MCT 组的肿瘤数量明显减少。与对照组相比,MCT 组的最大肿瘤直径也减小。MCT 显著降低了炎症细胞因子和趋化因子的表达。此外,与对照组相比,MCT 组 4-羟壬烯醛的表达降低。在第二组实验中,MCT 抑制了脂肪细胞肥大,降低了脂肪组织中脂联素和瘦素的浓度。在第三组实验中,如预期的那样,MCT 组血浆β-HB 浓度增加。β-HB 显著抑制 HCC 细胞的增殖。
MCT 给药通过抑制炎症和增加酮体显著抑制化学诱导的 HCC 的发生率。