关键词: esculeogenin A high-fat diet inflammation nonalcoholic fatty liver disease obesity oxidative stress steatosis

Mesh : Rats Male Animals Non-alcoholic Fatty Liver Disease / drug therapy genetics Antioxidants / pharmacology Solanum lycopersicum PPAR alpha / genetics NF-E2-Related Factor 2 NF-kappa B Liver Diet, High-Fat / adverse effects Triglycerides / pharmacology Anti-Inflammatory Agents / pharmacology Cholesterol / pharmacology RNA, Messenger

来  源:   DOI:10.3390/nu15224755   PDF(Pubmed)

Abstract:
This study examined the preventative effects of esculeogenin A (ESGA), a newly discovered glycan from tomato, on liver damage and hepatic steatosis in high-fat-diet (HFD)-fed male rats. The animals were divided into six groups (each of eight rats): a control group fed a normal diet, control + ESGA (200 mg/kg), HFD, and HFD + ESAG in 3 doses (50, 100, and 200 mg/kg). Feeding and treatments were conducted for 12 weeks. Treatment with ESGA did not affect gains in the body or fat weight nor increases in fasting glucose, insulin, and HOMA-IR or serum levels of free fatty acids (FFAs), tumor-necrosis factor-α, and interleukin-6 (IL-6). On the contrary, it significantly reduced the serum levels of gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-c) in the HFD-fed rats. In addition, it improved the liver structure, attenuating the increase in fat vacuoles; reduced levels of TGs and CHOL, and the mRNA levels of SREBP1 and acetyl CoA carboxylase (ACC); and upregulated the mRNA levels of proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase I (CPT I) in HFD-fed rats. These effects were concomitant with increases in the mRNA, cytoplasmic, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO); a reduction in the nuclear activity of nuclear factor-kappa beta (NF-κB); and inhibition of the activity of nuclear factor kappa B kinase subunit beta (IKKβ). All of these effects were dose-dependent effects in which a normal liver structure and normal levels of all measured parameters were seen in HFD + ESGA (200 mg/kg)-treated rats. In conclusion, ESGA prevents NAFLD in HFD-fed rats by attenuating hyperlipidemia, hepatic steatosis, oxidative stress, and inflammation by acting locally on Nrf2, NF-κB, SREBP1, and PPARα transcription factors.
摘要:
这项研究检查了esculeogeninA(ESGA)的预防作用,一种新发现的来自番茄的聚糖,高脂饮食(HFD)喂养的雄性大鼠的肝损伤和肝脂肪变性。将动物分为六组(每组八只大鼠):对照组饲喂正常饮食,对照+ESGA(200mg/kg),HFD,和HFD+ESAG,3个剂量(50、100和200mg/kg)。喂养和治疗进行12周。用ESGA治疗不会影响身体或脂肪重量的增加,也不会增加空腹血糖,胰岛素,和HOMA-IR或游离脂肪酸(FFA)的血清水平,肿瘤坏死因子-α,和白细胞介素-6(IL-6)。相反,它显著降低血清γ-谷氨酰转肽酶(GGT)的水平,天冬氨酸转氨酶(AST),丙氨酸氨基转移酶(ALT),总甘油三酯(TG),胆固醇(CHOL),HFD喂养大鼠的低密度脂蛋白胆固醇(LDL-c)。此外,它改善了肝脏结构,减轻脂肪空泡的增加;TGs和CHOL水平降低,和SREBP1和乙酰辅酶A羧化酶(ACC)的mRNA水平;并上调HFD喂养的大鼠中增殖物激活受体α(PPARα)和肉碱棕榈酰转移酶I(CPTI)的mRNA水平。这些作用伴随着mRNA的增加,细胞质,和核因子红系2相关因子2(Nrf2)的核水平,谷胱甘肽(GSH),超氧化物歧化酶(SOD),过氧化氢酶(CAT),和血红素加氧酶-1(HO);核因子-κB(NF-κB)的核活性降低;并抑制核因子κB激酶亚基β(IKKβ)的活性。所有这些作用是剂量依赖性作用,其中在HFD+ESGA(200mg/kg)处理的大鼠中观察到正常肝脏结构和所有测量参数的正常水平。总之,ESGA通过减轻高脂血症来预防HFD喂养大鼠的NAFLD,肝脂肪变性,氧化应激,和炎症通过局部作用于Nrf2,NF-κB,SREBP1和PPARα转录因子。
公众号