BACKGROUND: Physical activity (PA) that includes an accumulated exercise regimen that meets or exceeds a certain intensity reduces intrahepatic fat, leading to the improvement of nonalcoholic fatty liver disease (NAFLD) in afflicted patients. However, whether an increase in comprehensive PA, including activities of daily living, contributes to ameliorating the pathophysiology of NAFLD remains unclear. This study aimed to examine whether PA improves liver function in patients with NAFLD. METHODS: The study included 45 patients with NAFLD who underwent follow-up examinations at least 6 months-but no later than 1 year-after their baseline examinations. The patients were interviewed about their daily activities and exercise habits to determine whether they had engaged in at least 3 metabolic equivalents (METs) per day during the previous 6 months; the quantity of PA, expressed in Ekusasaizu (Ex) units, was calculated as METs multiplied by hours. Patients who had achieved at least a 1-Ex increase in PA per week compared to baseline at the time of their follow-up interview (the PA increase group) were compared to those whose PA was the same or lower at the time of follow-up (the PA non-increase group). RESULTS: There were no significant changes in all blood and biochemical parameters in the PA non-increase group at the time of follow-up when compared with baseline levels. In the PA increase group, aspartate aminotransferase, alanine aminotransferase, and γ-guanosine triphosphate levels were all significantly lower at follow-up than they were at baseline. Body weight did not change significantly from baseline to follow-up in both groups. CONCLUSIONS: In the present study, hepatic inflammation improvement was accompanied by increased PA but not decreased body weight. Increasing PA may be effective for the improvement of hepatic inflammation even without body weight loss. Our results indicate the effectiveness of PA monitoring for the management of NAFLD. TRIAL REGISTRATION UMIN-CTR, UMIN000038530.
Activities of Daily Living ; Adult ; Aged ; Aged, 80 and over ; Body Weight ; Exercise ; Female ; Hepatitis ; etiology ; physiopathology ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; complications ; Weight Loss ; Young Adult

Objective To understand the prevalence and metabolic abnormalities of fatty liver disease among adults in Mianyang City,Sichuan Province,and to analyze their influencing factors.Methods Totally 294 603 adults aged 18 years and older were enrolled by using a multi-stage stratified random sampling method in Mianyang City from November 1,2014 to September 30,2015.Fatty liver was diagnosed by abdominal ultrasound.The general demographic characteristics,smoking history,drinking history,and history of chronic disease were collected through questionnaires.Meanwhile,10 217 subjects were randomly selected for biochemical tests[fasting plasma gluose(FPG),triacylglycerol(TG),total cholesterol(TC),and alanine aminotransferase(ALT)].Results Of these 294 603 subjects,17 105(5.81%)had fatty liver.After having been age-adjusted based on the results of the sixth national census in 2010,the standardized prevalence was 5.32%.The prevalence was significantly higher in males(6.76%;standardized prevalence:7.24%)than in females(5.09%;standardized prevalence:4.08%)(=365.814,<0.001)。The prevalence of fatty liver disease was significantly higher in people with current smokers(8.52%)/ex-smokers(8.89%),occasional alcohol users(6.79%)/regular alcohol users(10.51%)/daily alcohol users(10.62%),and patients with hypertension(12.14%)/diabetes(15.19%)/coronary heart disease(10.22%)than those without corresponding characteristics(all <0.001).Abnormal increase in body mass index,diastolic blood pressure,FPG,TG,TC,and ALT were risk factors for fatty liver in Logistic regression model.Conclusions The prevalence of fatty liver in adults is relatively low in Mianyang City.Patients with fatty liver usually have varying degrees of abnormal increase in blood lipids,blood glucose,blood pressure,and ALT.Healthy lifestyles and comprehensively assessment of metabolic status are conducive to the prevention and treatment of fatty liver and extrahepatic complications.
Alcohol Drinking ; Body Mass Index ; China ; Fatty Liver ; metabolism ; physiopathology ; Female ; Humans ; Hypertension ; Male ; Prevalence ; Risk Factors ; Smoking

OBJECTIVE: To investigate the mechanism of inflflammatory-mediated toll-like receptor 4 (TLR4)-p38 mitogen-activated protein kinase (p38 MAPK) pathway in Kupffer cells (KCs) of non-alcoholic steatohepatitis (NASH) rats and the intervention effect of soothing Gan (Liver) and invigorating Pi (Spleen) recipes on this pathway. METHODS: After 1 week of acclimatization, 120 Sprague-Dawley male rats were randomly divided into 8 groups using a random number table (n=15 per group): normal group, model group, low-dose Chaihu Shugan Powder (, CHSG) group (3.2 g/kg), high-dose CHSG group (9.6 g/kg), low-dose Shenling Baizhu Powder (, SLBZ) group (10 g/kg), high-dose SLBZ (30 g/kg) group, and low- and highdose integrated recipe (L-IR, H-IR) groups. All rats in the model and treatment groups were fed with a high-fat diet (HFD). The treatments were administrated by gastrogavage once daily and lasted for 26 weeks. The liver tissues were detected with hematoxylin-eosin (HE) and oil red O staining. Levels of liver lipids, serum lipids and transaminases were measured. KCs were isolated from the livers of rats to evaluate the mRNA expressions of TLR4 and p38 MAPK by real-time flfluorescence quantitative polymerase chain reaction, and proteins expressions of TLR4, p-p38 MAPK and p38 MAPK by Western blot. Levels of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin (IL)-1 and IL-6 in KCs were measured by enzyme-linked immunosorbent assay. RESULTS: After 26 weeks of HFD feeding, HE and oil red O staining showed that the NASH model rats successfully reproduced typical pathogenesis and histopathological features. Compared with the normal group, the model group exhibited significant increases in body weight, liver weight, liver index, serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol, and aspartate aminotransferase as well as TC and TG levels in liver tissues, and significant decrease in serum level of high-density lipoprotein cholesterol (Plt;0.05 or Plt;0.01), while those indices were significantly ameliorated in the H-IR group (Plt;0.05 or Plt;0.01). Higher levels of TNF-α, IL-1 and IL-6 in KCs were observed in the model group compared with the normal group (Plt;0.01). Significant decreases in TNF-α, IL-1 and IL-6 were observed in the H-SLBZ, H-IR and L-IR groups compared with the model group (Plt;0.05 or Plt;0.01). The mRNA expressions of TLR4 and p38 MAPK and protein expressions of TLR4, p38 MAPK and p-p38 MAPK in KCs in the model group were significantly higher than the normal group (Plt;0.01), while those expression levels in the L-IR and H-IR groups were significantly lower than the model group (Plt;0.05 or Plt;0.01). CONCLUSION Inflflammation in KCs might play an important role in the pathogenesis of NASH in rats. The data demonstrated the importance of TLR4-p38MAPK signaling pathway in KCs for the anti-inflflammatory effect of soothing Gan and invigorating Pi recipes.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Kupffer Cells ; drug effects ; physiology ; MAP Kinase Signaling System ; drug effects ; Male ; Medicine, Chinese Traditional ; Non-alcoholic Fatty Liver Disease ; drug therapy ; physiopathology ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Toll-Like Receptor 4 ; physiology ; p38 Mitogen-Activated Protein Kinases ; physiology

Cardiovascular disease (CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A (IA) is one of the main bioactive compounds in 'Shan-lv-cha', an herbal tea commonly used in China. In the present study, we investigated the possible synergistic therapeutic effects of IA and simvastatin (SV) on NAFLD. IA or SV showed beneficial effects on the rats with NAFLD by lowering the liver weight, liver index and plasma levels of alanine aminotransferase and aspartate aminotransferase, regulating abnormal metabolism of lipids and ameliorating steatosis in liver. IA significantly enhanced the hypolipidemic and anti-inflammation effects of SV. Furthermore, a sensitive, accurate, convenient and reproducible LC-MS method was developed to investigate the effects of IA on the pharmacokinetics of SV. No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone. The mRNA levels and activity of CYP3A1 were not altered by IA. In conclusion, the results obtained from the present study should be helpful for further clinical application of SV and IA alone or in combination.
Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Cytochrome P-450 CYP3A ; genetics ; metabolism ; Diet, High-Fat ; Disease Models, Animal ; Drug Synergism ; Drug Therapy, Combination ; Lipids ; blood ; Liver ; metabolism ; pathology ; physiopathology ; Male ; Molecular Structure ; Non-alcoholic Fatty Liver Disease ; blood ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Simvastatin ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; Transcription, Genetic ; Triterpenes ; chemistry ; therapeutic use

Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg·d) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; Diabetes Mellitus, Type 2 ; blood ; chemically induced ; drug therapy ; metabolism ; Diet, High-Fat ; adverse effects ; Disease Models, Animal ; Down-Regulation ; drug effects ; Insulin ; blood ; Insulin Resistance ; physiology ; Lipid Metabolism ; drug effects ; genetics ; Liver ; drug effects ; physiopathology ; Male ; Morus ; Non-alcoholic Fatty Liver Disease ; blood ; chemically induced ; drug therapy ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Streptozocin

OBJECTIVES: To study the effects of ursolic acid on liver injury in diabetic mice induced by high-fat diet combined with streptozotocin(STZ), and to explore its possible mechanisms. METHODS: Diabetes mellitus was induced in twenty male ICR mice by a combination of high-fat diet for 6 weeks with low-dose streptozotocin (30 mg/kg, i. p.) for 5 consecutive days. After 9 days, fasting blood glucose levels were determined. Mice with fasting blood glucose levels exceeded 11. 1 mmol/L were diagnosed as diabetic mice and selected for further experiment. These mice were randomly divided into two groups(each group of 10):diabetic group, ursolic acid group (100 mg/kg, i. g.), and another 10 mice were set as control group. After continuous administration for 8 weeks, body weight (BW) were weighed, fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate transaminase (AST) in serum and superoxide dismutase (SOD), malondialdehyde (MDA) in liver were measured. HE staining was used to observe pathological changes of liver tissue. RESULTS: Compared with the control group, the level of FBG, TC, TG, ALT, AST, MDA were dramatically increased (<0. 05, <0. 01) and SOD was markedly decreased (<0.01) in the diabetic group; HE staining showed that parts of liver cells swelled and had a light fatty degeneration as well as lymphocyte infiltrated around the portal area in model group. Compared with the diabetic group, the level of FBG, TC, TG, ALT, AST, MDA were significantly declined (<0.05, <0.01) and SOD was considerably increased (<0.01) in the ursolic acid group; HE staining showed that the liver cells relatively arranged in order, edema was not obvious and inflammatory cells infiltrated lightly in the ursolic acid group. CONCLUSIONS Ursolic acid has a protective effect on liver injury in diabetic mice induced by high-fat diet combined with STZ by intraperitoneal ingector, and its mechanism may be associated with lowering blood glucose, regulating the lipid metabolism, reducing oxidative stress and enhancing the ability of anti-oxidation in liver.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Glucose ; Cholesterol ; blood ; Diabetes Mellitus, Experimental ; physiopathology ; Diet, High-Fat ; Fatty Liver ; drug therapy ; Liver ; metabolism ; physiopathology ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Random Allocation ; Superoxide Dismutase ; metabolism ; Triglycerides ; blood ; Triterpenes ; pharmacology

To explore the effect of leech on lipid metabolism and liver function in hyperlipidemia rats and the possible mechanism, biochemical analyzer was used to examine the regulation of leech on levels of serum triglycerides(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C). The levels of ALT and AST in serum were detected by ELISA. The proteins expression of ACAT-2, Fas and HMGCR in liver tissue was detected by Western blot. The weight of body and liver were weighed, and liver index was calculated. Oil red O staining was used to observe the lipid accumulation in liver tissue of rats by light Microscope. The results showed that leech could decrease the levels of TC, LDL-C obviously, and increase HDL-C, decrease the levels of ALT, AST and the liver index, down-regulate the proteins expression of ACAT-2, Fas and HMGCR. And oil red O staining indicated that the lipid accumulation was less in the liver tissue of the rats intervented by leech. These data indicated that leech may affect the expression of ACAT-2, Fas and HMGCR in liver tissue to reduce the synthesis of cholesterol and fatty acid, and promote the cholesterol transforming, then regulate lipid metabolism to decrease the levels of serum lipid, and reduce lipid accumulation in liver tissue and ease liver injury of rats, then slowing down the process of nonalcoholic fatty liver disease(NAFLD) in hyperlipidemia rats.
Animals ; Cholesterol ; blood ; Hydroxymethylglutaryl CoA Reductases ; metabolism ; Hyperlipidemias ; therapy ; Leeches ; Lipid Metabolism ; Liver ; physiopathology ; Non-alcoholic Fatty Liver Disease ; therapy ; Rats ; Sterol O-Acyltransferase ; metabolism ; Triglycerides ; blood ; fas Receptor ; metabolism

OBJECTIVETo investigate the roles of microRNA-21 (miR-21) in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) with high-fat diet-induced insulin resistance (IR) and diabetes mellitus (DM) mice model.

METHODSEight-week-old C57BL/6 mice were allocated into control group, IR group, and DM group. Body mass was recorded. Intraperitoneal glucose tolerance test was performed to determine any abnormal glucose metabolism. The liver pathological changes were detected by biopsy. Changes in free blood glucose, free serum insulin, blood fat and tumor necrosis factor Α level were measured. Differences in miR-21 expression and peroxidase proliferator-activated receptor subtypes (PPAR-Γ and PPAR-Α) and adipocyte fatty acid binding protein (aP2) in the liver were detected both at the mRNA and protein levels.

RESULTSAfter one 8-week high-fat diet, the body mass, free serum insulin, and homeostasis model IR index significantly increased in the IR group (P<0.01, P<0.05, compared with control group), while the free blood glucose increased and the free serum insulin decreased in DM group (P<0.05). Free serum insulin level were significantly increased in IR group (P<0.05). Serum tumor necrosis factor-Α levels exhibited an upward trend in control group, IR group, and DM group (P<0.05, P<0.01). With exacerbation in NAFLD, liver miR-21 expression level went further down in both IR and DM groups (P<0.05). The downregulated miR-21 expression level showed negative correlation with upregulated PPAR-Α, ΑP2, and PPAR-Γ genetic expression (r=-0.696, r=-0.664, and r=-0.766, respectively; P<0.05) in IR group and with upregulated PPAR-Α and PPAR-Γ genetic expression in DM group (r=-0.676 and r=-0.550, respectively; P<0.05). In terms of the changes in protein expression level,only on the protein expressions of aP2 and PPAR-Γ in IR group showed significant change (P<0.05, P<0.01, compared with control group).

CONCLUSIONSThe miR-21 expression is downregulated in both IR and DM-induced NAFLD mice. It may be involved in the pathogenesis of NAFLD by regulating the expressions of PPAR subtypes.

Animals ; Blood Glucose ; analysis ; Diabetes Mellitus, Experimental ; physiopathology ; Diet, High-Fat ; Disease Models, Animal ; Insulin ; blood ; Insulin Resistance ; Mice ; Mice, Inbred C57BL ; MicroRNAs ; metabolism ; Non-alcoholic Fatty Liver Disease ; physiopathology ; PPAR alpha ; metabolism ; PPAR gamma ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the effect of intermittent fasting on metabolize and gut microbiota in obese presenium rats fed with high-fat-sugar-diet.

METHODSWe fed the Wistar rats with high-fat and high-sugar diet to induce adiposity, and the rats for intermittent fasting were selected base on their body weight. The rats were subjected to fasting for 72 h every 2 weeks for 18 weeks. OGTT test was performed and fasting blood samples and fecal samples were collected for measurement of TC, TG, HDL-C and LDL-C and sequence analysis of fecal 16S rRNA V4 tags using Illumina. Gut microbial community structure was analyzed with QIIME and LEfSe.

RESULTSAfter the intervention, the body weight of the fasting rats was significantly lower than that in high-fat diet group (P<0.01). OGTT results suggested impairment of sugar tolerance in the fasting group, which showed a significantly larger AUC than compared with the high-fat diet group (P<0.05). Intermittent fasting significantly reduced blood HDL-C and LDL-C levels (P<0.05) and partially restored liver steatosis, and improved the gut microbiota by increasing the abundance of YS2, RF32 and Helicobacteraceae and reducing Lactobacillus, Roseburia, Erysipelotrichaceae and Ralstonia. Bradyrhizobiaceae was found to be positively correlated with CHOL and HDL-C, and RF39 was inversely correlated with the weight of the rats.

CONCLUSIONIntermittent fasting can decrease the body weight and blood lipid levels and restore normal gut microbiota but can cause impairment of glucose metabolism in obese presenium rats.

Animals ; Body Weight ; Diet, High-Fat ; Fasting ; Fatty Liver ; microbiology ; physiopathology ; Gastrointestinal Microbiome ; Lipids ; blood ; Obesity ; microbiology ; physiopathology ; RNA, Ribosomal, 16S ; Rats ; Rats, Wistar

According to the increasing need for accurate staging of hepatic fibrosis, the ultrasound (US) elastography techniques have evolved significantly over the past two decades. Currently, US elastography is increasingly used in clinical practice. Previously published studies have demonstrated the excellent diagnostic performance of US elastography for the detection and staging of liver fibrosis. Although US elastography may seem easy to perform and interpret, there are many technical and clinical factors which can affect the results of US elastography. Therefore, clinicians who are involved with US elastography should be aware of these factors. The purpose of this article is to present a brief overview of US techniques with the relevant technology, the clinical indications, diagnostic performance, and technical and biological factors which should be considered in order to avoid misinterpretation of US elastography results.
Disease Progression ; Elasticity Imaging Techniques/instrumentation/*methods ; Fatty Liver/complications/diagnostic imaging ; Humans ; Hypertension, Portal/complications ; Liver/*diagnostic imaging/physiopathology ; Liver Cirrhosis/diagnostic imaging/pathology