Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, Taiwan.
Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.
Lipids Health Dis. 2020 May 25;19(1):105. doi: 10.1186/s12944-020-01274-y.
Fat accumulation in the liver contributes to the development of non-alcoholic fatty liver disease (NAFLD). N-acetylcysteine (NAC) is an antioxidant, acting both directly and indirectly via upregulation of cellular antioxidants. We examined the mechanisms of liver steatosis after 12 months high fat (HF) diet and tested the ability of NAC to rescue liver steatosis.
Seven-week-old C57BL/6 (B6) male mice were administered HF diet for 12 months (HF group). Two other groups received HF diet for 12 months accompanied by NAC for 12 months (HFD + NAC(1-12)) or 6 months (HFD + NAC(1-6)). The control group was fed regular diet for 12 months (CD group).
Liver steatosis was more pronounced in the HF group than in the CD group after 12 month feeding. NAC intake for 6 or 12 months decreased liver steatosis in comparison with HF diet (p < 0.05). Furthermore, NAC treatment also reduced cellular apoptosis and caspase-3 expression. In the unfolded protein response (UPR) pathway, the expression of ECHS1, HSP60, and HSP70 was decreased in the HFD group (p < 0.05) and rescued by NAC therapy. With regards to the endoplasmic reticulum (ER) stress, Phospho-PERK (p-PERK) and ATF4 expression was decreased in the HF group, and only the HFD + NAC(1-12), but not HFD + NAC(1-6) group, showed significant improvement.
HF diet for 12 months induces significant liver steatosis via altered ER stress and UPR pathway activity, as well as liver apoptosis. NAC treatment rescues the liver steatosis and apoptosis induced by HF diet.
肝脏脂肪堆积会导致非酒精性脂肪性肝病（NAFLD）的发生。N-乙酰半胱氨酸（NAC）是一种抗氧化剂，可通过直接和间接途径上调细胞抗氧化剂来发挥作用。我们研究了高脂肪（HF）饮食 12 个月后肝脂肪变性的机制，并测试了 NAC 恢复肝脂肪变性的能力。
7 周龄 C57BL/6（B6）雄性小鼠给予 HF 饮食 12 个月（HF 组）。另外两组给予 HF 饮食 12 个月，同时给予 NAC 饮食 12 个月（HFD+NAC(1-12)）或 6 个月（HFD+NAC(1-6)）。对照组给予常规饮食 12 个月（CD 组）。
12 个月喂养后，HF 组肝脂肪变性比 CD 组更明显。与 HF 饮食相比，NAC 摄入 6 个月或 12 个月可减少肝脂肪变性（p<0.05）。此外，NAC 治疗还降低了细胞凋亡和 caspase-3 表达。在未折叠蛋白反应（UPR）通路中，HFD 组 ECHS1、HSP60 和 HSP70 的表达降低（p<0.05），NAC 治疗可恢复其表达。关于内质网（ER）应激，HF 组磷酸化 PERK（p-PERK）和 ATF4 的表达降低，只有 HFD+NAC(1-12)组，而不是 HFD+NAC(1-6)组，显示出显著改善。
12 个月 HF 饮食通过改变 ER 应激和 UPR 通路活性以及肝凋亡诱导显著的肝脂肪变性。NAC 治疗可挽救 HF 饮食引起的肝脂肪变性和凋亡。
