Effects of probiotic yogurt consumption on metabolic factors in individuals with nonalcoholic fatty liver disease

The aim of this study was to investigate the effects of probiotic yogurt consumption on some metabolic factors in nonalcoholic fatty liver disease (NAFLD) patients. This double-blind, randomized, controlled clinical trial was conducted on 72 patients with NAFLD (33 males and 39 females) aged 23 to 63 yr. Subjects in the intervention group (n = 36) consumed 300 g/d of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 and those in the control group (n = 36) consumed 300 g/d of conventional yogurt for 8 wk. Fasting blood samples, anthropometric measurements, and dietary records (24 h/d for 3 d) were collected at baseline and at the end of the trial. Probiotic yogurt consumption resulted in reductions of 4.67, 5.42, 4.1, and 6.92% in serum levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, and low-density lipoprotein cholesterol, respectively, compared with control group. No significant changes were observed in levels of serum glucose, triglycerides, or high-density lipoprotein cholesterol in either group. Probiotic yogurt consumption improved hepatic enzymes, serum total cholesterol, and low-density lipoprotein cholesterol levels in studied subjects and might be useful in management of NAFLD risk factors.     

辣木多糖提取物对大鼠非酒精性脂肪性肝病保护效果

目的 通过建立非酒精性脂肪性肝病(NAFLD)评价模型,研究辣木多糖提取物预防NAFLD的功效及其作用机制。方法 50只雄性大鼠随机分为阴性对照组、模型对照组以及低、中、高剂量组。各剂量组予以辣木多糖提取物水溶液灌胃(10 ml/kg BW),阴性对照组和模型对照组以同等体积纯水灌胃,每日一次,直至第90天。试验结束后,检测血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)、丙二醛(MDA)、白细胞介素6(IL-6)、白细胞介素1(IL-1)、坏死因子-α(TNF-α)。对所有的肝组织进行组织病理学检查。结果 各剂量组与模型对照组体质量比较,差异均有统计学意义(P＜0.05)。不同剂量组大鼠血清中抗氧化、抗炎指标含量与模型对照组比较,差异均有统计学意义(P＜0.05),且随着剂量的增加,其各指标含量趋向于阴性对照组的含量,血脂指标高剂量组大鼠LDL含量与模型对照组比较差异有统计学意义(P＜0.05)。病理镜下发现,各剂量组肝细胞虽有一定程度损伤,但病变种类较模型对照组少,且程度轻,有不同程度的改善。肝细胞脂肪变性程度随着剂量的升高而减轻。结论 本研究结果表明,辣木多糖提取物可改善NAFLD的脂质代谢紊乱、降低大鼠血脂水平、对抗氧自由基的攻击、改善炎症反应,保护肝脏。这种保护作用可能是通过抗氧化、抗炎途径而实现的。     

膳食油脂与非酒精性脂肪肝病形成相关研究进展

市场中的膳食油脂产品琳琅满目,消费者在选择食用油的过程中通常会考虑其对健康的影响,尤其是广泛流行的营养代谢性疾病非酒精性脂肪肝病（NAFLD）。我国NAFLD的患病率持续增长,给个人和社会造成巨大的压力。大量的研究表明,膳食油脂与NAFLD的形成关系密切,合理的膳食用油能有效预防NAFLD。通过对油脂脂肪酸链长、饱和度及双键位置、奇偶性与NAFLD形成的相关研究进行梳理,结合饮食模式综述了膳食油脂与NAFLD形成相关研究进展,以期为学术探索和日常膳食油脂提供依据。     

马尾松花粉提取物对小鼠非酒精性脂肪肝的预防作用

目的研究马尾松花粉提取物对小鼠非酒精性脂肪肝的预防作用,并探讨潜在的作用机制。方法将60只小鼠随机分为空白对照组、高脂模型组、低剂量(20 mg/kg·d)、中剂量(40 mg/kg·d)和高剂量(80 mg/kg·d)马尾松花粉提取物组及葵花护肝片组(0.7 g/kg·d),马尾松花粉提取物组灌胃相应剂量的马尾松花粉提取物,连续2周给予高脂鼠粮,同时灌胃相应受试物,空白对照组和模型组给予同体积生理盐水。实验结束后检测小鼠血清中丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、超氧化物歧化酶(superoxide dismutase,SOD)活性和低密度脂蛋白(low-density lipoprotein,LDL-C)、高密度脂蛋白(high density lipoprotein,HDL-C)、甘油三酯(triglycerides,TG)及总胆固醇(total cholesterol,TC)水平;并检测肝组织中还原性谷胱甘肽(glutathione,GSH)和丙二醛(malondialdehyde,MDA)含量及SOD活性。结果松花粉提取物明显降低高脂饮食所致小鼠血清ALT、AST活性以及TG、TC、LDL-C水平(P0.05),提高SOD活性及HDL-C含量;同时小鼠肝组织MDA含量显著下降,GSH含量提高,SOD活性升高(P0.05)。病理学结果显示,MPPE能显著减轻肝脏病理学损伤程度,表现为肝细胞脂肪变性及炎症的减轻。结论松花粉提取物对小鼠非酒精性脂肪肝具有明显的保护作用,其机制可能与抗氧化有关,并且具有剂量依赖性。     

Beneficial effects of Lactobacillus rhamnosus hsryfm 1301 fermented milk on rats with nonalcoholic fatty liver disease

A growing stream of research suggests that probiotic fermented milk has a good effect on nonalcoholic fatty liver disease. This work aimed to study the beneficial effects of Lactobacillus rhamnosus hsryfm 1301 fermented milk (fermented milk) on rats with nonalcoholic fatty liver disease induced by a high-fat diet. The results showed that the body weight and the serum levels of total cholesterol, total glyceride, low-density lipoprotein, alanine transaminase, aspartate aminotransferase, free fatty acid, and reactive oxygen species were significantly increased in rats fed a high-fat diet (M) for 8 wk, whereas high-density lipoprotein cholesterol and superoxide dismutase were significantly decreased. However, the body weight and the serum levels of total cholesterol, total glyceride, alanine transaminase, aspartate aminotransferase, free fatty acid, reactive oxygen species, interleukin-8, tumor necrosis factor-α, and interleukin-6 were significantly decreased with fermented milk (T) for 8 wk, and the number of fat vacuoles in hepatocytes was lower than that in the M group. There were significant differences in 19 metabolites in serum between the M group and the C group (administration of nonfermented milk) and in 17 metabolites between the T group and the M group. The contents of 7 different metabolites, glycine, glycerophosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, thioetheramide-PC, d-aspartic acid, oleic acid, and l-glutamate, were significantly increased in the M group rat serum, and l-palmitoyl carnitine, N6-methyl-l-lysine, thymine, and 2-oxadipic acid were significantly decreased. In the T group rat serum, the contents of 8 different metabolites—1-O-(cis-9-octadecenyl)-2-O-acetyl-sn-glycero-3-phosphocholine, acetylcarnitine, glycine, glycerophosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, d-aspartic acid, oleic acid, and l-glutamate were significantly decreased, whereas creatinine and thymine were significantly increased. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that 50 metabolic pathways were enriched in the M/C group and T/M group rat serum, of which 12 metabolic pathways were significantly different, mainly distributed in lipid metabolism, amino acid, and endocrine system metabolic pathways. Fermented milk ameliorated inflammation, oxygenation, and hepatocyte injury by regulating lipid metabolism, amino acid metabolic pathways, and related metabolites in the serum of rats with nonalcoholic fatty liver disease.     

Effects and molecular mechanisms of Ninghong black tea extract in nonalcoholic fatty liver disease of rats

The aim of this study is to observe the effects of Ninghong black tea extract on fat deposition and high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) and to explore the potential mechanisms of these effect. Under 2% Ninghong black tea extract diet feeding in rat model, the results showed that Ninghong black tea extract decreased the body fat ratio and the number of lipid droplets in the liver and significantly alleviated NAFLD in the rat model. The real-time fluorescence quantitative polymerase chain reaction results showed that Ninghong black tea extract significantly upregulated the expression of peroxisome proliferator-activated receptor α (PPARα), which is important in fatty acid β-oxidation, and microsomal triglyceride transfer protein (MTP), which plays an important role in the synthesis of very low density lipoprotein (VLDL). By promoting the expression of PPARα and MTP in liver tissue and thereby promoting fatty acid β-oxidation and VLDL synthesis, Ninghong black tea extract relieves high-fat diet-induced NAFLD.     

Chemoprevention of nonalcoholic fatty liver disease by dietary natural compounds

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease that is not from excess alcohol consumption, but is often associated with obesity, type 2 diabetes, and metabolic syndrome. NAFLD pathogenesis is complicated and involves oxidative stress, lipotoxicity, mitochondrial damage, insulin resistance, inflammation, and excessive dietary fat intake, which increase hepatic lipid influx and de novo lipogenesis and impair insulin signaling, thus promoting hepatic triglyceride accumulation and ultimately NAFLD. Overproduction of proinflammatory adipokines from adipose tissue also affects hepatic metabolic function. Current NAFLD therapies are limited; thus, much attention has been focused on identification of potential dietary substances from fruits, vegetables, and edible plants to provide a new strategy for NAFLD treatment. Dietary natural compounds, such as carotenoids, omega‐3‐PUFAs, flavonoids, isothiocyanates, terpenoids, curcumin, and resveratrol, act through a variety of mechanisms to prevent and improve NAFLD. Here, we summarize and briefly discuss the currently known targets and signaling pathways as well as the role of dietary natural compounds that interfere with NAFLD pathogenesis.     

Cornus officinalis vinegar reduces body weight and attenuates hepatic steatosis in mouse model of nonalcoholic fatty liver disease

This study aimed to determine the main bioactive components of Cornus officinalis vinegar (COV) and assess the effects of COV on the body weight (BW) and hepatic steatosis in a nonalcoholic fatty liver disease (NAFLD) mouse model. Seven-week-old KM female mice were divided into five treatment groups: (1) Normal control (NC) group, (2) high fat diet (HFD) group, (3) low concentration treatment group (3.5% COV), (4) medium concentration treatment group (5.0% COV), and (5) high concentration treatment group (6.5% COV). Mice in the NC group were fed with a normal chow diet, and those in the other four groups were fed with a HFD known for causing obesity for 10 weeks. Then, mice in the three COV treatment groups were orally administered with COV once a day for 6 weeks. Results showed that the contents of loganin and morroniside in COV reached 16.82 and 51.17 µg/ml, respectively, and COV also contained multiple organic acids. COV significantly reduced BW, abdominal fat weight, liver weight, and the levels of glucose, triglyceride, and low-density lipoprotein cholesterol of serum and increased the levels of high-density lipoprotein cholesterol of serum (p < 0.05). COV also improved the liver function and anti-oxidant activity of liver (p < 0.05). COV treatments increased the interleukin-10 expression and reduced the tumor necrosis factor-α expression in the liver tissue of NAFLD mice (p < 0.05). Histopathological observation revealed that COV suppressed hepatic lipid accumulation and steatosis. The results suggest that COV may contribute to the alleviation of NAFLD and obesity.     

n-3多不饱和脂肪酸、内质网应激与非酒精性脂肪肝病的研究进展

非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)已逐渐成为一个全球性健康问题, 但其发病的具体机制不甚明朗。内质网是细胞内蛋白质加工、脂质合成和钙储存的主要场所, 内质网结构和功能的失常所致的内质网应激(endoplasmic reticulum stress, ERS)对脂代谢和细胞功能具有重要调控作用, 可能是NAFLD的发生和发展的重要机制。近来大量研究显示, 脂类中特定的脂质负荷(饱和脂肪酸、胆固醇)可能是诱导ERS导致NAFLD重要原因, 而另一方面, n-3多不饱和脂肪酸(n-3 polyunsaturated fatty acids, n-3 PUFA)的摄入量却与NAFLD患病率呈负相关。本文就脂肪酸与内质网应激及其与NAFLD的联系作一综述, 进一步探讨n-3多不饱和脂肪酸防治NAFLD的机制。     

Positive effect of Limosilactobacillus plantarum grx16 on nonalcoholic fatty liver disease in rats

We aimed to investigate the potential and mechanism of probiotics as digestive enzyme inhibitors to alleviate nonalcoholic fatty liver disease (NAFLD). We compared the level of NAFLD in rats before and after Limosilactobacillus plantarum grx16 intervention, as well as changes in gut digestive enzymes and inflammatory factors. L. plantarum grx16 inhibited the absorption of starch and triglycerides by inhibiting the activity of gut amylase and lipase to alleviate insulin resistance and reduce lipid accumulation in the body, thereby alleviating the inflammatory response, and thus alleviating NAFLD in rats.     

Effects of probiotic and prebiotic supplementation on metabolic parameters,liver aminotransferases,and systemic inflammation in nonalcoholic fatty liver disease: A randomized clinical trial

This study aimed to evaluate the clinical efficacy of probiotic and prebiotic supplementation on the metabolic parameters, liver enzymes, and inflammation in patients with nonalcoholic fatty liver disease (NAFLD). In this study, patients with NAFLD were assigned to receive either probiotic capsule + placebo of prebiotic (probiotic group), oligofructose + placebo of probiotic (prebiotic group), or placebo of probiotic + placebo of prebiotic (control group) for 12 weeks. All participants followed a weight loss diet and physical activity recommendation during intervention. Anthropometric measurements decreased in all three groups, but there was no significant difference among groups. Probiotic supplementation was able to decrease triglyceride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and alkaline phosphatase compared to control group. The serum levels of triglyceride, total and low-density lipoprotein cholesterol, ALT, AST, and GGT differed significantly in prebiotic group in comparison to the placebo. High-sensitive C-reactive protein significantly decreased within all groups; however, there was no significant difference among groups after intervention. Probiotic and prebiotic may be beneficial in improving liver enzymes and lipid profile in patients with NAFLD.     

肠道微生态与非酒精性脂肪性肝病研究进展

目的：运用网络药理学的方法,研究荔枝核提取物（Lychee kernel extract,LKE）干预非酒精性脂肪性肝病（Nonalcoholic fatty liver disease,NAFLD）的作用及分析潜在机制。方法：通过中药系统药理学数据库和分析平台（TCMSP）获取荔枝核的成分和作用靶点,通过疾病靶点数据Genecard获取NAFLD的疾病靶点,然后取交集,通过Cytoscape获取通路-靶点互作网络图,利用微生信网站进行 GO生物过程分析和 KEGG 通路富集分析。建立饮食诱导的肥胖（diet-induced obsisity,DIO）小鼠NAFLD动物模型并用LKE灌胃给药。HE染色观察肝脏脂质变化;试剂盒检测TG、TC、ALT、AST含量。结果：获得荔枝核潜在活性成分18个,与NAFLD疾病交集靶点52个,关键靶点为INS、TNF、HSP90AA1,通过KEGG通路富集筛选得到信号通路20条,主要为癌症通路（pathways in cancer）、动脉粥样硬化通路（Fluid shear stress and atherosclerosis）、糖尿病并发症的信号通路（AGE-RAGE signaling pathway in diabetic complications）;模型组小鼠肝脏病变严重,给药组小鼠肝脏病变相对于模型组明显减轻,给药组小鼠血清转氨酶也明显降低,接近正常组,给药组血脂代谢也趋于正常组,且差异均具有显著性（P<0.05）。结论：荔枝核可能通过作用于INS、TNF、HSP90AA1等靶点,调节脂质和动脉粥样硬化通路等起到治疗NAFLD的作用。     

超重肥胖儿童非酒精性脂肪肝与内脏脂肪指数的相关性研究

目的 对鹤壁市超重肥胖儿童非酒精性脂肪肝（NAFLD）与内脏脂肪指数（VAI）情况及相关性进行分析,以期为早期预防肥胖超重儿童发生NAFLD提供理论参考。方法 择2020年5月至2021年5月于鹤壁市疾病预防控制中心体检的1013例一年级儿童,筛选出肥胖超重儿童243例,依据其NAFLD患病情况分为非NAFLD组和NAFLD组,对比两组患儿基础临床资料、VAI、血脂相关指标及胰岛素抵抗指数（HOMD-IR）,以二元Logistic回归分析单因素显著差异的因子与NAFLD间的相关性。结果 本研究从243例肥胖超重儿童中筛查出46例NAFLD患儿,占比18.93%。NAFLD组患儿女童数、VAI、腰围、BMI、HOMA-IR及TG均显著高于非NAFLD组,男童数、HDL-C显著低于非NAFLD组（P<0.05）。两组TC、年龄及LDL-C无显著差异（P>0.05）。Spearman秩相关分析知,肥胖超重儿童HDL-C与NAFLD间呈显著负相关（P<0.01）,TG(P<0.01)、HOMA-IR(P<0.01)和VAI(P<0.05)与NAFLD间呈显著...     

Relationship between structure and efficacy of sea cucumber saponins echinoside A and its derivatives on hemolytic activity and prevention of nonalcoholic fatty liver disease

The hemolytic property discourages the development of sea cucumber saponins on alleviating lipids metabolism disturbance. The hemolytic activity of saponins has been reported to be highly correlative to their chemical structures. The aim of this study was to reduce the hemolytic activity of sea cucumber-derived saponins echinoside A (EA) and simultaneously remain its effect on alleviating non-alcoholic fatty liver disease (NAFLD) by structural modifications. Administration with EA and its derivatives for 8 weeks remarkably mitigated orotic acid-induced NAFLD via inhibiting the activities and mRNA expressions of enzymes involved in lipogenesis, enhancing the activities and expressions of enzymes related to hepatic lipolysis in a rat model. Importantly, aglycone exhibited a distinct advantage in stimulating hepatic lipolysis compared with EA and dsEA, meanwhile possessed lowest hemolytic activity. This study may provide the theoretical basis to strengthen the application of sea cucumber saponins as food supplements and/or functional ingredients.     

The potential of flavonoids in the treatment of non-alcoholic fatty liver disease

The contemporary pathophysiological model of non-alcoholic fatty liver disease (NAFLD) comprises multiple parallel pathways with a dynamic cross talk that cumulate in steatosis and inflammation, and ultimately fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. So far, no pharmacological treatment has been approved. A major impediment of drugs, in general, is that they are intended to act on one single target in the pathology of a disease. However, the multitude of pathways involved in the pathogenesis of NAFLD underpins the need for treatments that address these various pathways. Interestingly, flavonoids have been found to have positive effects on lipid metabolism, insulin resistance, inflammation, and oxidative stress, the most important pathophysiological pathways in NAFLD. This puts flavonoids in the spotlight for the treatment of NAFLD and prompted us to review the existing evidence for the use of these food-derived compounds in the treatment of NAFLD.     

Invited review: pathology, etiology, prevention, and treatment of fatty liver in dairy cows

Fatty liver (i.e., hepatic lipidosis) is a major metabolic disorder of many dairy cows in early lactation and is associated with decreased health status and reproductive performance. In severe cases, milk production and feed intake are decreased. Therefore, a practical preventative or an efficacious treatment of fatty liver could save millions of dollars yearly in treatment, replacement, and production losses for dairy farmers. Fatty liver develops when the hepatic uptake of lipids exceeds the oxidation and secretion of lipids by the liver, which usually is preceded by high concentrations of plasma NEFA mobilized from adipose tissue. Excess lipids are stored as triacylglycerol in the liver and are associated with decreased metabolic functions of the liver. Liver can be categorized into normal liver or mild, moderate, or severe fatty liver; the latter can be subdivided further into nonencephalopathic severe fatty liver and hepatic encephalopathy. Insufficient or unbalanced dietary intake, obesity, and elevated estrogen concentrations are involved in the etiology of fatty liver, which is associated with greater incidence of dystocia, diseases, infections, and inflammations. Because even mild fatty liver is associated with decreased health status and reproductive performance of dairy cows, prevention of fatty liver by supplying cows with sufficient nutrients and a clean and health-promoting environment in the peripartal period would reduce production losses of cows more than would any treatment of fatty liver. This, however, might not be enough for cows that are obese or do not eat well, had calving difficulties or twins, have metabolic or infectious diseases, or are in severe negative energy balance because of high milk production immediately after calving. Potential and commonly used preventatives, as well as treatments, are discussed in the review. Currently, detection of fatty liver is possible only by minor surgery. Ultrasonic techniques offer a potential tool to noninvasively detect fatty liver. Future gene-array and proteomic studies may provide means to detect early molecular events in the etiology of fatty liver plus their connection with immune function and reproductive performance so that more effective treatments and preventatives of fatty liver can be developed. Such advances hopefully will make fatty liver a problem of the past.