健脾益肝方对非酒精性脂肪性肝病患者脂肪分布及脂代谢的影响

目的:探讨健脾益肝方对非酒精性脂肪性肝病(NAFLD)患者脂肪分布及脂代谢的影响。方法:将80例NAFLD患者随机分为对照组和治疗组各40例。两组患者均在多学科联合管理下给予个体化的饮食、运动等生活方式指导,治疗组患者在此基础上加用健脾益肝方,疗程均为3个月。通过生物电阻抗技术测量患者治疗前后脂肪质量及分布,定期监测肝肾功能、血脂指标。比较两组患者肥胖、脂肪分布、血脂指标变化。结果:治疗组患者有效率为97.5%,明显高于对照组的82.5%,差异有统计学意义(P<0.05);治疗组患者BMI、BFP、WHR、TC、TG及LDL-C水平明显低于对照组,差异有统计学意义(均P<0.05);治疗组患者躯干及内脏脂肪沉积改善明显优于对照组,差异有统计学意义(均P<0.05)。结论:生活方式干预联合健脾益肝方治疗NAFLD患者能显著改善患者的肥胖及脂代谢紊乱,并且与躯干和内脏脂肪质量的下降密切相关。     

Melatonin safeguards against fatty liver by antagonizing TRAFs‐mediated ASK1 deubiquitination and stabilization in a β‐arrestin‐1 dependent manner

Melatonin has been previously shown to prevent nonalcoholic fatty liver disease (NAFLD), yet the underlying mechanisms are poorly understood. Here, we identified a previously unknown regulatory action of melatonin on apoptosis signal‐regulating kinase 1 (ASK1) signaling pathway in the pathogenesis and development of NAFLD. Although melatonin administration did not alter food intake, it significantly alleviated fatty liver phenotypes, including the body weight gain, insulin resistance, hepatic lipid accumulation, steatohepatitis, and fibrosis in a high‐fat diet (HFD)‐induced NAFLD mouse model (in vivo). The protection of melatonin against NAFLD was not affected by inactivation of Kupffer cell in this model. In NAFLD mice liver, ASK1 signal cascade was substantially activated, evidence by the enhancement of total ASK1, phospho‐ASK1, phospho‐MKK3/6, phospho‐p38, phospho‐MKK4/7, and phospho‐JNK. Melatonin treatment significantly suppressed the ASK1 upregulation and the phosphorylation of ASK1, MKK3/6, MKK4/7, p38, and JNK. Mechanistically, we found that lipid stress triggered the interaction between ASK1 and TNF receptor‐associated factors (TRAFs), including TRAF1, TRAF2, and TRAF6, which resulted in ASK1 deubiquitination and thereby increased ASK1 protein stability. Melatonin did not alter ASK1 mRNA level; however, it activated a scaffold protein β‐arrestin‐1 and enabled it to bind to ASK1, which antagonized the TRAFs‐mediated ASK1 deubiquitination, and thus reduced ASK1 protein stability. Consistent with these findings, knockout of β‐arrestin‐1 in mice partly abolished the protection of melatonin against NAFLD. Taken together, our results for the first time demonstrate that melatonin safeguards against NAFLD by eliminating ASK1 activation via inhibiting TRAFs‐mediated ASK1 deubiquitination and stabilization in a β‐arrestin‐1 dependent manner.     

小柴胡汤对非酒精性脂肪性肝炎模型小鼠的保护作用研究

目的通过构建蛋氨酸-胆碱缺乏(MCD)饮食诱导的小鼠非酒精性脂肪性肝炎(NASH)模型,研究小柴胡汤对NASH模型小鼠的保护作用。方法选择C57BL/6小鼠为研究对象,将其随机分为对照组、模型组、小柴胡汤(高、中、低剂量)组、易善复组和强肝胶囊组。通过饲喂MCD饲料建立NASH模型,造模同时按分组给予不同药物进行干预;实验过程中记录小鼠体质量、日摄食量、日饮水量变化,实验结束对肝组织进行HE染色观察病理变化,检测血清生化指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、白细胞介素6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平变化,检测肝组织中TC、TG的水平变化,利用q RT-PCR技术检测肝组织脂肪酸合成酶(FAS)和固醇调节元件结合蛋白1c(SREBP-1c)的表达水平。结果小鼠体质量、日摄食量、日饮水量及肝脏系数等数据显示MCD饮食诱导的模型组小鼠会出现体质量降低、摄入量减少及肝脏湿质量下降的特点,而小柴胡汤给药组小鼠体质量、摄入量及肝脏系数较模型组小鼠显著升高;HE染色结果显示小柴胡汤可明显减轻肝组织脂肪变性和炎症程度,改善肝细胞的形态和结构;生化指标检测结果显示小柴胡汤能显著降低NASH模型小鼠血清及肝组织TG、TC水平,升高血清中HDL-C水平,降低血清中AST、ALT、IL-6、TNF-α水平;q RT-PCR结果显示模型组小鼠肝组织FAS和SREBP-1c的基因表达水平明显升高,小柴胡汤可显著降低FAS和SREBP-1c的基因表达水平。结论小柴胡汤对MCD饮食诱导的NASH模型小鼠有明显保护作用,其机制可能通过调控抑制脂肪酸合成基因(FAS、SREBP-1c)的表达,减少脂肪堆积,实现调脂作用,并通过抑制炎症因子的表达改善肝组织的损伤。     

The effects of curcumin supplementation on body mass index,body weight,and waist circumference in patients with nonalcoholic fatty liver disease: A systematic review and dose–response meta‐analysis of randomized controlled trials

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver‐related morbidity; its prevalence is elevating due to the rising epidemic of obesity. Several clinical trials have examined the effects of curcumin supplementation on anthropometric variables in NAFLD patients with inconclusive results. This dose–response meta‐analysis aimed to evaluate the impact of curcumin supplementation on body mass index (BMI), body weight, and waist circumference (WC) in patients with NAFLD. A systematic review of the literature was conducted using PubMed/Medline, ISI Web of Science, Scopus, Cochrane Library, EMBASE, Google Scholar, Sid.ir, and Magiran.com to identify eligible studies up to March 2019. A meta‐analysis of eligible studies was performed using the random‐effects model to estimate the pooled effect size. Eight randomized controlled trials with 520 participants (curcumin group = 265 and placebo group = 255) were included. Supplementation dose and duration ranged from 70 to 3,000 mg/day and 8 to 12 weeks, respectively. Curcumin supplementation significantly reduced BMI (weighted mean difference [WMD] = ?0.34 kg/m², 95% CI [?0.64, ?0.04], p < .05) and WC (WMD = ?2.12 cm, 95% CI [?3.26, ?0.98], p < .001). However, no significant effects of curcumin supplementation on body weight were found. These results suggest that curcumin supplementation might have a positive effect on visceral fat and abdominal obesity that have been associated with NAFLD.     

Therapies for non-alcoholic fatty liver disease: A 2022 update

The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing and lifestyle interventions to treat this disease by addressing the underlying metabolic syndrome are often limited. Many pharmacological interventions are being studied to slow or even reverse NAFLD progression. This review for hepatologists aims to provide an updated understanding of the pathogenesis of NAFLD, current recommended therapies, and the most promising treatment options that are currently under development.     

Niche-Specific Reprogramming of Epigenetic Landscapes Drives Myeloid Cell Diversity in Nonalcoholic Steatohepatitis

1. Download : Download high-res image (250KB)
2. Download : Download full-size image