Matcha Green Tea Alleviates Non-Alcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice by Regulating Lipid Metabolism and Inflammatory Responses

Lately, matcha green tea has gained popularity as a beverage and food additive. It has proved to be effective in preventing obesity and related metabolic syndromes. However, the underlying mechanisms of its control effects against non-alcoholic fatty liver disease (NAFLD) are complicated and remain elusive. In the present study, we performed an in vivo experiment using male C57BL/6 mice fed with a high-fat diet and simultaneously treated with matcha for six weeks. Serum biochemical parameters, histological changes, lipid accumulation, inflammatory cytokines, and relevant indicators were examined. Dietary supplementation of matcha effectively prevented excessive accumulation of visceral and hepatic lipid, elevated blood glucose, dyslipidemia, abnormal liver function, and steatosis hepatitis. RNA sequencing analyses of differentially expressed genes in liver samples indicated that matcha treatment decreased the activity of lipid droplet-associated proteins and increased the activity of cytochrome P450 enzymes, suggesting improved metabolic capacity and liver function. The current study provided evidence for new dietary strategies based on matcha supplementation to ameliorate lipotoxicity-induced obesity and NALFD.     

孕期二苯基甲烷二异氰酸酯暴露对子代雄性小鼠性成熟后睾丸组织能量代谢功能的影响

目的探讨孕期二苯基甲烷二异氰酸酯(MDI)暴露对子代雄性小鼠性成熟后睾丸组织能量代谢功能的影响。方法将清洁级健康昆明种孕小鼠16只按体重随机分为高剂量(1/8LD50)、中剂量(1/16LD50)、低剂量(1/32LD50)MDI染毒组和溶剂对照组(玉米油),每组4只。于妊娠第14天开始,每日灌胃染毒,灌胃剂量为5ml/kg,持续至母鼠自然分娩。记录孕鼠染毒期间体重增量和分娩时间。待仔鼠8周龄(性成熟)时,分离双侧睾丸,称重,并计算睾丸的脏器系数。并检测睾丸组织中琥珀酸脱氢酶(SDH)、Na-K-ATP酶、Ca-Mg-ATP酶和总ATP酶的活力以及蛋白的含量。结果各组孕鼠分娩时间和体重增量间比较,差异均无统计学意义(P>0.05)。与高剂量MDI染毒组比较,中、低剂量MDI染毒组和溶剂对照组睾丸系数较高,差异均有统计学意义(P<0.01或P<0.05)。与溶剂对照组比较,高、中、低剂量MDI染毒组SDH、Na-K-ATPase、Ca-Mg-ATPase以及总ATPase酶活力均下降,差异均有统计学意义(P<0.01或P<0.05);且随着染毒剂量的增高,SDH、Na-K-ATPase、Ca-Mg-ATPase...     

氯氰菊酯暴露对青春期雄性小鼠精子发生的影响

[目的]探讨氯氰菊酯暴露对青春期雄性小鼠精子发生的影响及其可能机制。[方法]选择30只5周龄雄性ICR小鼠,随机分为暴露组和对照组,于出生后35天（PND35）至PND70,每天给予暴露组小鼠氯氰菊酯（25mg/kg）灌胃染毒,对照组以等容积的玉米油灌胃。末次染毒16h后,处死小鼠,取附睾尾评价精子数量;取睾丸称重并进行组织病理学检查;免疫组织化学法检测睾丸间质细胞;放射免疫分析法检测血清和睾丸组织睾酮水平;蛋白质免疫印迹法测定睾丸组织类固醇激素合成急性调节蛋白（StAR）和睾酮合成关键酶蛋白表达水平。[结果]暴露组小鼠睾丸生精小管管腔内出现大空泡。与对照组相比,暴露组第Ⅶ-Ⅷ期生精小管所占百分比明显下降,附睾尾精子数量明显减少,血清和睾丸组织睾酮含量明显降低,睾丸组织生成StAR的表达明显下调,而氯氰菊酯对小鼠睾丸间质细胞数量无影响。[结论]青春期氯氰菊酯暴露后对小鼠精子发生有损害作用,这可能与睾丸睾酮合成的降低有关。     

Psoralea corylifolia L. Seed Extract Attenuates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice

Nonalcoholic fatty liver disease (NAFLD), along with obesity, is increasing world-wide and is one of the major causes of chronic hepatic disease. The present study evaluated the ameliorative effect of extract of Psoralea corylifolia L. seed (PCS) on high fat diet-induced NAFLD in C57BL/6 mice after daily administration at 300 or 500 mg/kg for 12 weeks. Treatment with PCS extract significantly reduced body weight and blood glucose levels and improved glucose tolerance and insulin sensitivity. In addition, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels. Furthermore, the expression of lipogenic genes and inflammatory genes were reduced, and the expression of fat oxidation-related genes was increased in the liver of PCS extract-treated mice compared with control mice. Our study suggests the therapeutic potential of PCS extract for NAFLD by inhibiting lipid accumulation and inflammation in liver.     

A Lard and Soybean Oil Mixture Alleviates Low-Fat–High-Carbohydrate Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

Dietary habit is highly related to nonalcoholic fatty liver disease (NAFLD). Low-fat–high-carbohydrate (LFHC) diets could induce lean NAFLD in Asians. Previously, we found that a lard and soybean oil mixture reduced fat accumulation with a medium-fat diet; therefore, in this study, we evaluated the effect of a lard and soybean oil mixture (LFHC diet) on NAFLD and its underlying mechanisms. Mice in groups were fed with lard, soybean oil, or a lard and soybean oil mixture—an LFHC diet—separately. Our results showed that mixed oil significantly inhibited serum triglyceride, liver triglyceride, serum free fatty acids (FFAs), and liver FFAs compared with soybean oil or lard, and we found fewer inflammatory cells in mice fed with mixed oil. RNA-seq results indicate that mixed oil reduced FFAs transportation into the liver via decreasing liver fatty acid-binding protein 2 expression, inhibited oxidative phosphorylation via tumor necrosis factor receptor superfamily member 6 downregulation, and alleviated inflammation via downregulating inflammatory cytokine. The liquid chromatography–mass spectrometry results showed that the mixed oil promoted bile acid conjugated with taurine and glycine, thus activating G-protein-coupled bile acid receptor 1 for improved lipids metabolism. In conclusion, the lard and soybean oil mixture alleviated NAFLD.     

Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood

Nicotinamide riboside, an NAD⁺ precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders related to NAD⁺ decline in tissues. The metabolic programming activity of NR supplementation in early-life stages is much less known. Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. Suckling male mice received a daily oral dose of NR or vehicle (water) from day 2 to 20 of age, were weaned at day 21 onto a chow diet, and at day 90 were distributed to either a high-fat diet (HFD) or a normal-fat diet for 10 weeks. Compared to controls, NR-treated mice were protected against HFD-induced triacylglycerol accumulation in skeletal muscle and displayed lower triacylglycerol levels and steatosis degree in the liver and distinct capacities for fat oxidation and decreased lipogenesis in both tissues, paralleling signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling. These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.     

氯化三丁基锡对雄性小鼠睾酮和雌二醇水平的影响

目的探讨不同剂量氯化三丁基锡(TBTCl)对小鼠雌二醇(E2)、睾酮(T)水平的影响。方法将40只24日龄健康雄性SPF级昆明小鼠按体重随机分为4组,分别为1、0.1、0.01 mg/kg TBTCl染毒组和对照(玉米油)组,每组10只。采用腹腔注射方式染毒,每3天染毒1次,连续染毒25 d,染毒容量为10 ml/kg。观察包皮分离时间和体重变化,检测其血清、睾丸内T、E2水平,并对肝脏内脂肪滴进行病理学观察。结果与0.01 mg/kg TBTCl染毒组比较,对照组和1 mg/kg TBTCl染毒组小鼠体重均较低,差异有统计学意义(P0.05)。TBTCl染毒组与对照组小鼠包皮分离时间比较,差异无统计学意义。与对照组比较,1 mg/kg TBTCl染毒组小鼠血清和睾丸内T水平中位数均较低,0.01 mg/kg TBTCl染毒组小鼠睾丸内E2水平较低,差异有统计学意义(P0.05或P0.01)。而小鼠血清E2水平全部低于所用试剂盒的检测限(11 pg/ml)。TBTCl染毒未能导致小鼠肝脏内脂肪滴明显增加。结论 TBTCl暴露可导致小鼠睾酮和雌二醇水平降低,而不同剂量的TBTCl对小鼠的靶作用位点可能不同,导致对暴露小鼠体重的影响呈非单调性剂量-反应关系。     

Dietary Avian Proteins Are Comparable to Soybean Proteins on the Atherosclerosis Development and Fatty Liver Disease in Apoe-Deficient Mice

Background and aim: The type and amount of dietary protein has become a topic of renewed interest in light of their involvement in metabolic diseases, atherosclerosis and thrombosis. However, little attention has been devoted to the effect of avian proteins despite their wide human consumption. The aim was to investigate the influence of chicken and turkey as sources of protein compared with that of soybean on atherosclerosis and fatty liver disease. Methods and results: To this purpose, male and female Apoe-deficient were fed purified Western diets differing in their protein sources for 12 weeks. After this period, blood, liver, aortic tree and heart base samples were taken for analyses of plasma lipids and atherosclerosis. Plasma triglycerides, non-esterified fatty acids, esterified cholesterol levels and radical oxygen species in lipoproteins changed depending on the diet and sex. Females consuming the turkey protein-containing diet showed decreased atherosclerotic foci, as evidenced by the en face atherosclerosis analyses. The presence of macrophages and smooth muscle cells in plaques were not modified, and no changes were observed in hepatic lipid droplets in the studied groups either. Paraoxonase activity was higher in the group consuming turkey protein without sex differences, but only in females, it was significantly associated with aortic lesion areas. Conclusions: Compared to soybean protein, the consumption of avian proteins depending on sex resulted in similar or lower atherosclerosis development and comparable hepatic steatosis.     

亚慢性吸入环境烟草烟雾对雄性小鼠神经行为活动的影响

目的研究亚慢性吸入环境烟草烟雾(ETS)对雄性小鼠神经行为活动的影响并探讨其可能的机制。方法将60只SPF级昆明小鼠随机分为空白对照组、ETS暴露组、嗅上皮毁损组、嗅上皮毁损+ETS暴露组,每组15只。采取单支香烟暗火燃烧进行ETS暴露染毒,40min/次,2次/d,间隔6h,染毒8周。各组进行自主活动实验、洞板实验、Morris实验。结果小鼠自主活动、洞板实验结果显示,与空白对照组比较,ETS暴露组小鼠自主活动次数明显增加(P0.05),探洞次数明显减少(P0.05)。Morris水迷宫实验中,ETS暴露组、嗅上皮毁损+ETS暴露组游泳平均速度均低于空白对照组(P0.05),第一次穿越安全目标的潜伏期时间均明显长于空白对照组(P0.05),ETS暴露组穿越安全目标次数低于空白对照组(P0.05)。结论小鼠长期暴露于环境烟草烟雾中会导致空间学习记忆能力及探索认知能力下降,并伴有体质下降,其机制可能与嗅觉传导通路有关。     

Metabolic Syndrome in Childhood from Impaired Carbohydrate Metabolism to Nonalcoholic Fatty Liver Disease

Compelling evidence supports the concept that nonalcoholic fatty liver disease (NAFLD) represents the hepatic component of metabolic syndrome (MetS). Intrahepatic fat seems to predict more strongly than does visceral adiposity an individual's cardiovascular risk and the likelihood that metabolic abnormalities are present in youth.

Key teaching points:

? Overweight and obese youth should be screened for fatty liver disease once after puberty by liver function tests and ultrasonography.

? Screening for fatty liver should be accurately performed in young patients with features of metabolic syndrome.

? Obese patients with fatty liver are at increased risk for altered glucose metabolism, thus they should undergo an oral glucose tolerance test.

? A nutritional and behavioral intervention aimed at achieving a permanent change of the lifestyle in patients and their parents is recommended.

     

Ethanol Extract of Liriope platyphylla Root Attenuates Non-Alcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice via Regulation of Lipogenesis and Lipid Uptake

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder that causes excess lipid accumulation in the liver and is the leading cause of end-stage liver disease. Liriope platyphylla is a medicinal herb that has long been used to treat cough, obesity, and diabetes. However, the effect of Liriope platyphylla on NAFLD has not been studied. The aim of this study was to investigate the effect of Liriope platyphylla root ethanolic extract (LPE) on hepatic lipid accumulation in high-fat diet (HFD)-induced obese mice. Six-week-old C57BL/6 male mice were fed a HFD for 8 weeks and then treated with LPE (100 or 250 mg/kg/day) by oral gavage for another 8 weeks. Body weight gain and liver weight were significantly lower in the 250 mg/kg LPE-treated HFD group than in the vehicle-treated HFD group. Histological analysis of liver sections demonstrated that LPE treatment reduced lipid accumulation compared to the vehicle treatment. The serum total cholesterol, AST, and ALT levels significantly decreased in the LPE-treated HFD group compared to those in the vehicle-treated HFD group. The LPE significantly decreases the protein expression levels of SREBP1, ACC, p-ACC, FAS, and SCD1, which are involved in lipogenesis, and PPARγ, CD36/FAT, and FATP5, which are involved in fatty acid uptake, both in vivo and in vitro. Thus, LPE may attenuate HFD-induced NAFLD by decreasing lipid accumulation by inhibiting lipogenesis and fatty acid uptake.     

Early-Life Exposure to Famine and Risk of Metabolic Associated Fatty Liver Disease in Chinese Adults

Background: Early-life exposure to the Chinese famine has been related to the risk of obesity, type 2 diabetes, and nonalcoholic fatty liver disease later in life. Nevertheless, the long-term impact of famine exposure on metabolic associated fatty liver disease (MAFLD), a recently proposed term to describe liver disease associated with known metabolic dysfunction, remains unknown. The aim of our study was to explore the relationship between early famine exposure and MAFLD in adulthood. Methods: A total of 26,821 participants (10,994 men, 15,827 women) were recruited from a cohort study of Chinese adults in Shanghai. We categorized participants into four famine exposure subgroups based on the birth year as nonexposed (1963–1967), fetal-exposed (1959–1962), childhood-exposed (1949–1958), and adolescence-exposed (1941–1948). MAFLD was defined as liver steatosis detected by ultrasound plus one of the following three criteria: overweight/obesity, type 2 diabetes, or evidence of metabolic dysregulation. Multivariable logistic regression models were performed to examine the association between famine exposure and MAFLD. Results: The mean ± standard deviation age of the participants was 60.8 ± 6.8 years. The age-adjusted prevalence of MAFLD was 38.3, 40.8, 40.1, and 36.5% for the nonexposed, fetal-exposed, childhood-exposed, and adolescence-exposed subgroups, respectively. Compared with nonexposed participants, fetal-exposed participants showed an increased risk of adulthood MAFLD (OR = 1.10, 95% CI 1.00–1.21). The significant association between fetal famine exposure and MAFLD was observed in women (OR = 1.22, 95% CI 1.08–1.37), but not in men (OR = 0.88, 95% CI 0.75–1.03). In age-balanced analyses combining pre-famine and post-famine births as the reference, women exposed to famine in the fetal stage still had an increased risk of MAFLD (OR = 1.15, 95% CI 1.05–1.26). Conclusions: Prenatal exposure to famine showed a sex-specific association with the risk of MAFLD in adulthood.     

非酒精性脂肪肝与糖脂代谢异常的关系

目的探讨非酒精性脂肪肝（NAFLD）与糖脂代谢异常的关系。方法以3647名NAFLD患者与同时参加体检的6338名非脂肪肝健康体检者（对照组）的糖脂代谢相关指标进行统计分析。结果9985名企业退休人员体检检出NAFLD3647名，患病率为36．5％。NAFLD组的体重、体重指数（BMI）、收缩压（SBP）、舒张压（DBP）、胆固醇（TC）、甘油三酯（TG）、谷丙转氩酶（ALT）、空腹血糖（FBS）均高于对照组，差异有统计学意义。NAFLD组中高甘油三酯血症、高胆固醇血症、混合性高脂血症、超重、肥胖、空腹血糖受损、糖尿病的患病率均高于对照组。将NAFLD的可能危险因素进行logistic回归分析，相关性由高到低依次为：BMI（OR=1．785，P=0．000）、TG（OR=1．712，P=0．000）、FBS（OR=1．157，P=0．000）、TC（OR=1．138，P=0．005）、身高（OR=1．105，P=0．005）、ALT（OR：1.013，P=0．000）、DBP（OR=1．008，P=0．031）与NAFLD相关，而促甲状腺索（TSH）未能进人模型（P=0．631）。结论企业退休人员NAFLD的患病率高，NAFLD与糖脂代谢的多项指标相关，而TSH与NAFLD无显著相关。     

围产期低剂量氯化三丁基锡暴露对子代青春期雄性小鼠发育及性激素水平的影响

目的 探讨围产期低剂量氯化三丁基锡( TBTCl)暴露对子代雄性小鼠发育及血清、睾丸组织中雌激素(E2)和雄激素(T)水平的影响.方法 将20只妊娠6d的SPF级昆明小鼠采用经口灌胃方式进行染毒,剂量为0(对照,玉米油)、1、10、100 μg/kg TBTCl溶液,每组5只,染毒至哺乳期结束.仔鼠断乳后每周称量一次体重.出生49天(PN D49)时,每组随机抽取10只雄性仔鼠,测定睾丸、附睾、脑、肝、肾、胸腺重量,并计算脏器系数.测定血清和睾丸组织中E2和T水平.结果 与对照组相比,除100 μg/kg剂量组在PND21、28、35、42、49时体重显著降低(P＜0.05,P＜0.01)外,其他各组体重均无显著差异;除100μg/kg TBTCl染毒组睾丸系数升高(P＜0.01)外,肝脏、脾脏、肾脏、胸腺、附睾的脏器系数均无显著差异;除10及100 μg/kg TBTCl染毒组睾丸组织中E2水平降低(P＜0.05,P＜0.01)外,其他各组血清和睾丸组织中E2和T水平均无显著差异.结论 围产期低剂量TBTCl暴露不仅影响雄性小鼠的生长发育,而且降低了睾丸组织中E2水平,并可扰乱小鼠血清、睾丸组织内的雌、雄激素水平的平衡.     

终末期肝病患者肝移植前后的能量代谢特点

目的探讨乙肝病毒感染终末期肝病患者肝移植前后能量代谢及碳水化合物、蛋白质、脂肪氧化供能的特点。方法采用间接测热法应用CCM/D营养代谢测试系统测定10例终末期肝病患者肝移植术前1周及术后4～6月内的静息能量消耗(REE)、晨起空腹呼吸商(RQ)及三大营养物质的氧化率,并比较肝移植前后的差别。结果10例终末期肝病患者术前REE为(5983.5±2238.4)kJ/24h,夜间禁食晨起空腹时RQ为0.84±0.05,碳水化合物、蛋白质、脂肪氧化率依次为(38.20±20.05)%、(24.40±22.53)%、(37.30±24.94)%。肝移植术后,REE为(5084.3±1266.6)kJ/24h,与术前比较差异无显著性(P=0.105),晨起空腹RQ(0.93±0.11)、碳水化合物氧化率[(66.60±35.48)%]和蛋白质氧化率[(66.60±35.48)%]均较术前升高,但差异无显著性(P>0.05);脂肪氧化率显著降低至(2.20±47.70)%(P=0.049)。结论终末期肝病患者处于低代谢状态,对糖类利用存在障碍,只能通过加强脂肪动员供能。随着新肝植入及肝功能恢复,患者体内对糖类利用增加,脂肪...     

Effects of Combined Exposure to Lead and High-Fat Diet on Bone Quality in Juvenile Male Mice

Background

Lead (Pb) exposure and obesity are co-occurring risk factors for decreased bone mass in the young, particularly in low socioeconomic communities.

Objectives

The goal of this study was to determine whether the comorbidities of Pb exposure and high-fat diet–induced obesity amplify skeletal deficits independently associated with each of these risk factors, and to explore associated mechanisms of the observed deficiencies.

Methods

Five-week-old male C57BL/6J mice were placed on low-fat (10% kcal, LFD) or high-fat (60% kcal, HFD) diets for 12 weeks. Mice were exposed to lifetime Pb (50 ppm) through drinking water.

Results

HFD was associated with increased body mass and glucose intolerance. Both HFD and Pb increased fasting glucose and serum leptin levels. Pb and HFD each reduced trabecular bone quality and together had a further detrimental effect on these bone parameters. Mechanical bone properties of strength were depressed in Pb-exposed bones, but HFD had no significant effect. Both Pb and HFD altered progenitor cell differentiation, promoting osteoclastogenesis and increasing adipogenesis while suppressing osteoblastogenesis. In support of this lineage shift being mediated through altered Wnt signaling, Pb and non-esterified fatty acids in MC3T3 cells increased in vitro PPAR-γ activity and inhibited β-catenin activity. Combining Pb and non-esterified fatty acids enhanced these effects.

Conclusions

Pb and HFD produced selective deficits in bone accrual that were associated with alterations in progenitor cell activity that may involve reduced Wnt signaling. This study emphasizes the need to assess toxicants together with other risk factors relevant to human health and disease.

Citation

Beier EE, Inzana JA, Sheu TJ, Shu L, Puzas JE, Mooney RA. 2015. Effects of combined exposure to lead and high-fat diet on bone quality in juvenile male mice. Environ Health Perspect 123:935–943; http://dx.doi.org/10.1289/ehp.1408581     

非酒精性脂肪性肝病糖代谢异常与血清脂连素关系研究

目的探讨非酒精性脂肪性肝病(NAFLD)患者糖代谢与血清脂联素关系。方法选择2010年10月至2011年11月我院140例门诊确诊的非酒精性脂肪肝病患者,根据糖耐量结果,分为糖耐量正常组及糖代谢异常组,并选择50例健康体检者为对照组,测定所有体检者的IBM、血清谷丙转氨酶(ALT)水平,应用酶联免疫吸附法(ELISA)测定血清中脂联素含量。结果①NAFLD患者糖代谢异常的发生率高达55.7%。②NAFLD患者血清脂连素水平均低于健康对照组,其中合并糖代谢异常者下降更明显,肝功能损伤也更严重。结论血清脂联素水平、糖代谢异常与NAFLD发生、发展密切相关。OGTT及血清脂联素检测,有望作为临床评估NAFLD程度及判断预后的一项指标。     

牛膝对小鼠非酒精性脂肪肝改善作用研究

正非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)以脂肪在肝内沉积超过肝脏质量的5%～10%,弥漫性肝细胞大泡性脂肪变性为主要特征,包括从肝单纯脂肪变性到非酒精性脂肪肝炎(non-alcoholic steatohepatitis,NASH)最后发展为纤维化、癌变的一种临床病理综合征[1]。高脂饮食,营养失衡导致的肥胖和胰岛