Non-alcoholic fatty liver disease (NAFLD) is a metabolic-related disorder induced by multiple factors and mainly characterized by excessive fat buildup in hepatocytes. With the consumption of a Western-style diet and obesity prevalence in recent years, the incidence of NAFLD has gradually increased, becoming an increasingly serious public health problem. Bilirubin is a heme metabolite and a potent antioxidant. Studies have demonstrated that bilirubin levels have an inverse correlation with the incidence rate of NAFLD; however, which form of bilirubin plays the main protective role is still controversial. It is considered that the main protective mechanisms for NAFLD are bilirubin antioxidant properties, insulin resistance reduction, and mitochondrial function. This article summarizes the correlation, protective mechanism, and possible clinical application of NAFLD and bilirubin.
Humans ; Non-alcoholic Fatty Liver Disease/metabolism* ; Bilirubin ; Antioxidants ; Obesity/complications* ; Hepatocytes/metabolism* ; Liver/metabolism*

Nonalcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury that is closely associated with insulin resistance and genetic susceptibility. The continuum of liver injury in NAFLD can range from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and even lead to cirrhosis and liver cancer. The pathogenesis of NAFLD is complicated. Pro-inflammatory cytokines, lipotoxicity, and gut bacterial metabolites play a key role in activating liver-resident macrophages (Kupffer cells, KCs) and recruiting circulating monocyte-derived macrophages (MoDMacs) to deposit fat in the liver. With the application of single-cell RNA-sequencing, significant heterogeneity in hepatic macrophages has been revealed, suggesting that KCs and MoDMacs located in the liver exert distinct functions in regulating liver inflammation and NASH progression. This study focuses on the role of macrophage heterogeneity in the development and occurrence of NAFLD and NASH, in view of the fact that innate immunity plays a key role in the development of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/pathology* ; Liver/pathology* ; Macrophages/metabolism* ; Liver Cirrhosis/complications* ; Disease Progression

Aged ; Fatty Liver ; complications ; metabolism ; Female ; Humans ; Insulin Resistance ; Lipids ; Liver ; metabolism ; Male ; Metabolic Diseases ; metabolism ; Middle Aged ; Non-alcoholic Fatty Liver Disease

OBJECTIVETo observe the expression of SIRT1 and mitochondrial uncoupling protein 2 (UCP2) in the liver of rats with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver (NAFLD) and explore the possible pathogenesis of T2DM and NAFLD.

METHODSTwenty-four male SD rat were randomized equally into control group and T2DM and NAFLD group (MC group), fed with standard diet and high-fat and high-sugar diet, respectively. At 12 weeks, the rats in MC group received a single dose of STZ (30 mg/kg) injected into the abdominal cavity for pancreatic islet destruction, and those in the control group received an equivalent volume of citric acid buffer. At 14 weeks, the body weight, FBG, hepatic function, blood lipid levels, FFAs, FINs and HOMA-IR of the rats were measured, and the liver pathology was examined with HE staining. The expression of SIRT1 and UCP2 in the rat liver was detected by immunohistochemistry and real-time quantitative PCR.

RESULTSAt 14 weeks, FBG, ALT, AST, TC, TG, LDL-C, VLDL, FFAs, FINs and HOMA-IR were significantly higher and HDL-C was significantly lower in MC group than in the control group (P<0.05). Pathological examination showed good structural integrity of the liver in the control group, and the liver cells were closely arranged with rich cytoplasm and round cell nuclei; in MC group, moderate to severe fatty liver was detected, and the liver cells showed severe ballooning degeneration and contained lipid vacuoles in the cytoplasm. The expression of SIRT1 was significantly lower and UCP2 significantly higher in MC group than in the control group (P<0.05).

CONCLUSIONThe expression of SIRT1 is significantly lowered and UCP2 increased in the liver of rats with T2DM and NAFLD.

Animals ; Diabetes Mellitus, Type 2 ; complications ; metabolism ; Fatty Liver ; complications ; metabolism ; Ion Channels ; metabolism ; Liver ; metabolism ; Male ; Mitochondrial Proteins ; metabolism ; Non-alcoholic Fatty Liver Disease ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1 ; metabolism ; Uncoupling Protein 2

BACKGROUND/AIMS: Nonalcoholic steatohepatitis can develop from nonalcoholic fatty liver and progress to severe liver disease such as cirrhosis. The mechanism determining the progression from fatty liver to steatohepatitis is unknown. Iron is suspected to enhance hepatic damage associated with nonalcoholic fatty liver disease (NAFLD). The aims of this study were to evaluate the relationship of serum iron indices and hepatic iron deposition with hepatic fibrosis or inflammation, and to assess whether the increased hepatic iron deposition is an independent predictor of progression to liver injury. METHODS: The biochemical and histopathological data of thirty-nine patients with NAFLD were analyzed. Liver biopsy findings were graded according to the method described by Brunt, et al. Hepatic iron concentration was available in 29 of 39 patients. RESULTS: The mean hepatic iron concentration and hepatic iron indices were 1,349+/-1,188 microgram/g dry weight and 0.9+/-0.7 microgram/g/age. Serum ferritin and body mass indices were associated with hepatic inflammation (p=0.001, p=0.006) and fibrosis (p=0.005, p=0.013). Hepatic iron concentration and hepatic iron index were not associated with hepatic inflammation and fibrosis. Multivariate analysis did not identify serum ferritin or body mass index as an independent predictor of liver injury. CONCLUSIONS: Hepatic iron deposition shows no association with the degree of hepatic inflammation or fibrosis. Hepatic iron is not an independent predictor of hepatic injury in patients with NAFLD.
Adolescent ; Adult ; Fatty Liver/complications/*metabolism ; Female ; Ferritins/blood ; Humans ; Inflammation ; Iron/blood/*metabolism ; Liver/*metabolism/pathology ; Liver Cirrhosis/*etiology/metabolism/pathology ; Male ; Middle Aged

OBJECTIVETo observe the therapeutic effect of resolving method of Chinese medicine (CM) on the lipid metabolism in polycystic ovary syndrome (PCOS) patients accompanied with non-alcoholic fatty liver disease (NAFLD), to analyze the correlation between PCOS and NAFLD, and to study its mechanisms.

METHODSTotally 70 female PCOS patients in the reproductive age (20 -40 years old) were recruited. Among them, 35 PCOS patients accompanied with NAFLD were recruited as Group A, and 35 PCOS patients without complicated NAFLD were recruited as Group B. At the same time, 20 healthy female volunteers were recruited as the control group. All subjects had their personal medical records after relevant questionnaire. Their clinical data including body height (BH), body weight (BW), body mass index (BMI), waist circumference (WC), hip circumference (HC), testosterone (T), prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), leptin, fasting blood glucose (FBG), fasting insulin (FINS), 2 h postprandial blood glucose (2 h PBG), homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), etc. were detected. Patients in Group A were treated by the resolving method for 3 months. The follow-up was continued for 6 months after ending treatment.

RESULTSThe levels of BW, BMI, WHR, T, LH, LH/FSH, leptin, FINS, 2 h PBG, HOMA-IR, and LDL-C were significantly higher in Group B than in the control group (P < 0.05). The level of FSH was significantly lower in Group B than in the control group (P < 0.05). The levels of BW, BMI, WC, HC, waist-hip-ratio (WHR), leptin, FINS, 2 h PBG, HOMA-IR, TG, LDL-C, ALT, and AST were significantly higher in Group A than in Group B (P < 0.05). The HDL-C level was significantly lower in Group A than in Group B (P < 0.05). In Group A after treatment by resolving method of CM, the menstrual cycle was recovered in 83.87% patients (26/31 cases), reduced fatty liver degree or disappearance of fatty liver degree occurred in 32.26% patients (10/31 cases), with the total effective rate being 85.71% (24/28 cases).48.28% (14/29) patients were pregnant. The levels of BW, BMI, FBG, leptin, TG, ALT, and AST significantly decreased when compared with those before treatment (P < 0.05). The level of SHBG significantly increased (P < 0.05). There was no significant difference in the levels of HOMA-IR, FINS, T, FSH, LH, or LH/FSH between before and after treatment (P > 0. 05).

CONCLUSIONSThe metabolic disorder of glycolipid exists in PCOS patients, and more serious in PCOS patients accompanied with NAFLD. Resolving method can effectively restore the metabolic disturbance in PCOS patients accompanied with NAFLD, recover their fatty liver degrees, recover normal menstrual cycles, and elevate their pregnancy rates. Further studies are necessary on whether its mechanisms lie on lowering leptin levels and correcting lipid metabolisms to relieve patient's clinical symptoms.

Adult ; Case-Control Studies ; Fatty Liver ; complications ; metabolism ; therapy ; Female ; Humans ; Lipid Metabolism ; Medicine, Chinese Traditional ; methods ; Non-alcoholic Fatty Liver Disease ; Polycystic Ovary Syndrome ; complications ; metabolism ; therapy ; Pregnancy ; Pregnancy Rate ; Young Adult

OBJECTIVEThe incidences of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are very high in obese children, and insulin resistance may be the key point linking them together. Debates still remain as to whether NAFLD could be a component of MS. Some researchers reported that NAFLD was a composition of MS, while the others stated that NAFLD was an independent predicting factor of MS. Here we analyzed the prevalence of NAFLD and MS in 308 obese children who came to our endocrinology department from June 2003 to September 2006, and we also evaluated the relationship between NAFLD and MS in this group of obese children.

METHODTotally 308 obese children aged from 9 to 14 years with mean age of (10.7 +/- 2.6) years were enrolled. Two hundred and thirty one were males, and 77 were females. Body mass index (BMI), waist circumference (WC), biochemical indicators, liver B-mode ultrasound examination, oral glucose tolerance test (OGTT) and insulin releasing test were performed for all of the cases. The incidences of NAFLD including simple nonalcoholic fatty liver (SNAFL) and nonalcoholic steatohepatitis (NASH) as well as MS were calculated. Three subgroups were selected according to the diagnostic criteria: Group 1: OCWLD (obese children without liver disorder), Group 2: SNAFL and Group 3: NASH. The prevalence of MS, components of MS, free insulin, whole body insulin sensitivity index (WBISI), homeostasis model of insulin resistance (HOMA(IR)) were compared among these three subgroups.

RESULT(1) Among all the obese children, the prevalence of NAFLD, SNAFL, NASH and MS was 65.9% (203), 45.5% (140), 20.5% (63) and 24.7% (76) respectively. Among all the MS children, the prevalence of NAFLD was 84.2% (64/76). The prevalence of MS was 29.3% (41/140) in SNAFL group and 36.5% (23/63) in NASH group, which was significantly higher than that of OCWLD group 11.4% (12/105) (P < 0.05), but no significant difference was found between SNAFL group and NASH group (P > 0.05). Moreover, there were significantly higher incidences in NASH group concerning every component of MS (hypertension, hyperlipidemia, hyperglycemia) compared with that of OCWLD group. The incidence of hypertension in SNAFL was significantly higher than that of OCWLD group. And the incidence of hyperlipidemia was markedly increased in NASH group compared with SNAFL group. NAFLD group had higher free insulin and more severe IR compared with that of OCWLD group. When OCWLD developed to SNAFL and NASH, free insulin and IR deteriorated calculated by HOMA-IR and WBISI. However there was no significant difference between NAFLD and MS children concerning free insulin and IR.

CONCLUSIONThe prevalence of NAFLD and MS hits high in obese children. The prevalence of NAFLD was very high among children with MS and NAFLD and MS shared the common mechanism of IR. The higher prevalence of MS and higher frequencies of MS components were tightly associated with the development of NAFLD and severity of IR.

Adolescent ; Child ; Fatty Liver ; diagnosis ; epidemiology ; etiology ; metabolism ; Female ; Humans ; Male ; Metabolic Syndrome ; diagnosis ; epidemiology ; Obesity ; complications ; epidemiology ; Prevalence

Animals ; Endotoxemia ; complications ; Fatty Liver ; etiology ; Hepatitis ; etiology ; Male ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; metabolism

Animals ; Fatty Liver ; complications ; genetics ; metabolism ; virology ; Hepatitis B virus ; genetics ; isolation & purification ; physiology ; Hepatitis C, Chronic ; complications ; genetics ; metabolism ; virology ; Humans

Animals ; Fatty Liver ; complications ; metabolism ; Hepatitis ; etiology ; metabolism ; Male ; NF-kappa B ; metabolism ; PPAR alpha ; biosynthesis ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood