glycogen and Hepatitis

Topics: Diabetes Mellitus; Fatty Liver; Glycogen; Hemochromatosis; Hepatitis; Hepatitis A; Humans; Insulin; Liver; Liver Cirrhosis

Topics: Alanine Transaminase; Aspartate Aminotransferases; Clinical Enzyme Tests; Diabetes Mellitus; Fatty Liver; Glycogen; Glycogen Storage Disease; Hepatitis; Hepatitis A; Humans; Jaundice; Liver Cirrhosis; Liver Diseases; Liver Glycogen; Splenomegaly

Pandemic vitamin D deficiency is associated with insulin resistance and type 2 diabetes. Vitamin D supplementation has been reported to have improved glucose homeostasis. However, its mechanism to improve insulin sensitivity remains unclear.. Male C57BL/6J mice are fed with/without vitamin D control (CD) or Western (WD) diets for 15 weeks. The vitamin-D-deficient lean (CDVDD) and obese (WDVDD) mice are further subdivided into two groups. One group is re-supplemented with vitamin D for 6 weeks and hepatic insulin signaling is examined. Both CD and WD mice with vitamin D deficiency developed insulin resistance. Vitamin D supplementation in CDVDD mice significantly improved insulin sensitivity, hepatic inflammation, and antioxidative capacity. The hepatic insulin signals like pAKT, pFOXO1, and pGSK3β are increased and the downstream Pepck, G6pase, and Pgc1α are reduced. Furthermore, the lipogenic genes Srebp1c, Acc, and Fasn are decreased, indicating that hepatic lipid accumulation is inhibited.. The results demonstrate that vitamin D deficiency induces insulin resistance. Its supplementation has significant beneficial effects on pathophysiological mechanisms in type 2 diabetes but only in lean and not in the obese phenotype. The increased subacute inflammation and insulin resistance in obesity cannot be significantly alleviated by vitamin D supplementation. This needs to be taken into consideration in the design of new clinical trials.

Topics: Animals; Body Weight; Diet, High-Fat; Forkhead Box Protein O1; Gluconeogenesis; Glucose; Glycogen; Hepatitis; Insulin Resistance; Liver; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Vitamin D; Vitamin D Deficiency

While thioridazine (Tio) inhibits the antioxidant defenses of Trypanosoma cruzi, the gold standard antitrypanosomal drug benznidazole (Bz) has potent anti-inflammatory and pro-oxidant properties. The combination of these drugs has never been tested to determine the effect on T. cruzi infection. Thus, we compared the impact of Tio and Bz, administered alone and in combination, on the development of skeletal myositis and liver inflammation in T. cruzi-infected mice. Swiss mice were randomized into six groups: uninfected untreated, infected untreated, treated with Tio (80 mg/kg) alone, Bz (50 or 100 mg/kg) alone, or a combination of Tio and Bz. Infected animals were inoculated with a virulent T. cruzi strain (Y) and treated by gavage for 20 days. Mice untreated or treated with Tio alone developed the most intense parasitemia, highest parasitic load, elevated IL-10, IL-17, IFN-γ, and TNF-α plasma levels, increased N-acetylglucosaminidase and myeloperoxidase activity in the liver and skeletal muscle, as well as severe myositis and liver inflammation (P < 0.05). All parameters were markedly attenuated in animals receiving Bz alone (P < 0.05). However, the co-administration of Tio impaired the response to Bz chemotherapy, causing a decrease in parasitological control (parasitemia and parasite load), skeletal muscle and liver inflammation, and increased microstructural damage, when compared to the group receiving Bz alone (P < 0.05). Altogether, our findings indicated that Tio aggravates systemic inflammation, skeletal myositis and hepatic inflammatory damage in T. cruzi-infected mice. By antagonizing the antiparasitic potential of Bz, Tio limits the anti-inflammatory, myoprotectant and hepatoprotective effects of the reference chemotherapy, aggravating the pathological remodeling of both organs. As the interaction of T. cruzi infection, Bz and Tio is potentially toxic to the liver, inducing inflammation and microvesicular steatosis; this drug combination represents a worrying pharmacological risk factor in Chagas disease.

Topics: Acetylglucosaminidase; Animals; Chagas Disease; Cytokines; Disease Models, Animal; Drug Combinations; Female; Glycogen; Hepatitis; Mice; Muscle, Skeletal; Myositis; NADH, NADPH Oxidoreductases; Nitroimidazoles; Parasite Load; Parasitemia; Peroxidase; Thioridazine; Transaminases; Trypanocidal Agents; Trypanosoma cruzi

Replacing part of glucose with galactose in the post-weaning diet beneficially affects later life metabolic health in female mice. The liver is the main site of galactose metabolism, but the direct effects of this dietary intervention on the liver in the post-weaning period are not known. The aim of this study was to elucidate this. Weanling female mice (C57BL/6JRccHsd) were fed a starch containing diet with glucose (32 en%) monosaccharide (GLU), or a diet with glucose and galactose (1:1 both 16 en%) (GLU+GAL). Body weight, body composition, and food intake were determined weekly. After 3 weeks, mice were sacrificed, and serum and liver tissues were collected. Global hepatic mRNA expression was analyzed and hepatic triglyceride (TG) and glycogen contents were determined by enzymatic assays. Body weight and body composition were similar in both groups, despite higher food intake in mice on GLU+GAL diet. Hepatic TG content was lower in GLU+GAL-fed than GLU-fed females, while glycogen levels were unaffected. Analysis of global expression patterns of hepatic mRNA showed that mainly inflammation-related pathways were affected by the diet, which were predominantly downregulated in GLU+GAL-fed females compared to GLU-fed females. This reduction in inflammation in GLU+GAL-fed females was also reflected by decreased serum concentrations of acute phase protein Serum amyloid A 3. In conclusion, replacing part of glucose with galactose in the post-weaning diet reduces hepatic TG content and hepatic inflammation.

Topics: Animals; Body Composition; Body Weight; Diet; Eating; Female; Galactose; Gene Expression; Glucose; Glycogen; Hepatitis; Liver; Mice; Mice, Inbred C57BL; RNA, Messenger; Triglycerides; Weaning

Glycogenic hepatopathy is a rare condition that causes significant hepatomegaly and elevated liver enzyme levels in uncontrolled type 1 diabetic patients. It develops due to excessive accumulation of glycogen in the hepatocytes. It is typically reversible with good glycemic control and rarely progresses to mild fibrosis, but not cirrhosis.

Topics: Child; Diabetes Mellitus, Type 1; Female; Glycogen; Hepatitis; Humans; Recurrence

End-stage liver diseases frequently require liver transplantation. Cell therapy could be an alternative. This study aimed to analyze whether undifferentiated mesenchymal stromal cells (U-MSCs) or MSC-derived hepatocyte-like cells (DHLCs) from adipose tissue (AT), umbilical cord blood (UCB) and bone marrow (BM) would better restore damaged liver.. AT was obtained from lipo-aspiration, UCB from an Umbilical Cord Blood Bank and BM from a BM Transplantation Unit. AT (collagenase digestion), UCB and BM (Ficoll gradient) were cultured (Dulbecco's modified Eagle's medium, low glucose, FBS) for 3 days. Detached adherent cells, at passage 4, were characterized as MSCs. Genetic stability was investigated by means of telomerase enzyme activity and karyotype. Hepatocyte differentiation protocol was performed with the use of Dulbecco's modified Eagle's medium, hepatocyte growth factor, basic fibroblast growth factor and nicotinamide (7 days); maturation medium (oncostatin, dexamethasone, insulin, transferrin and selenium) was added at 36 days. Hepatogenesis analyses were performed by use of morphology and albumin, AF, tyrosine-aminotransferase and glutamine synthetase gene expression and quantitative reverse transcription-polymerase chain reaction on days 9, 18, 25 and 36. Functionality was assessed through glycogen storage detection, indocyanine green absorption and transplantation procedure. U-MSCs and DHLCs were injected 48 h after induced fulminant hepatitis (intraperitoneal injection of carbon tetrachloride) in SCID/BALB-c mice. Histopathologic analyses were performed on days 7 and 15. Human origin included albumin and CK19 human markers.. All MSCs differentiated into functional hepatocyte-like cells, stored glycogen and absorbed indocyanine green. AT-MSC DHLC gene expression was more consistent with a normal hepatogenic-differentiation profile. UCB-MSCs expanded weakly, impairing their use for the transplantation procedure. AT and BM U-MSCs and DHLCs regenerated liver injury equally. Regenerated hepatocytes exhibited human origin.. AT might be the source and U-MSCS the stem cells useful for liver-regenerative therapy.

Topics: Adipose Tissue; Animals; Biomarkers; Bone Marrow Cells; Carbon Tetrachloride; Cell Differentiation; Cell- and Tissue-Based Therapy; Disease Models, Animal; Fetal Blood; Gene Expression; Glycogen; Hepatitis; Hepatocyte Growth Factor; Hepatocytes; Humans; Liver Failure, Acute; Liver Regeneration; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Mice, SCID

Mauriac syndrome is characterised by growth failure, cushingoid appearance and hepatomegaly which occurs in patients with insulin dependent diabetes and was first described shortly after the introduction of insulin as a treatment for the condition.. To describe the clinical features, histological findings and outcome of young people with glycogenic hepatopathy, the hepatic manifestation of Mauriac syndrome (MS).. Retrospective cohort study.. Young people with glycogenic hepatopathy.. Tertiary paediatric hepatology unit.. Thirty-one young people (16 M), median age of 15.1 years (IQR 14-16.2) presented within the study period. Median age of diagnosis of diabetes was 10 years (IQR 8-11). Median insulin requirement was 1.33 units/kg/day; median HbA1c was 96.7 mmol/mol (IQR 84.7-112.0). Growth was impaired: median height z-score was -1.01 (-1.73 to 0.4) and median body mass index (BMI) z-score was 0.28 (-0.12 to 0.67). Hepatomegaly was universal with splenomegaly in 16%. Transaminases were abnormal with a median aspartate aminotransferase (AST) of 76 IU/L and gamma glutamyltransferase of 71 IU/L. Liver biopsy was undertaken in 19 (61%). All showed enlarged hepatocytes with clear cytoplasm with glycogenated nuclei in 17. Steatosis was present in the majority. Inflammation was present in 8 (42%). Fibrosis was seen in 14 (73%) and was generally mild though 2 had bridging fibrosis. Megamitochondria were described in 7. Presence of megamitochondria correlated with AST elevation (p=0.026) and fibrosis on biopsy (p=0.007). At follow-up 17 children had normal or improved transaminases, in 13 there was no change. Transaminases followed the trend of the child's HbA1c.. Despite modern insulin regimens and monitoring in children with type 1 diabetes, MS still exists. Significant steatosis, inflammation and fibrosis were all seen in liver biopsies.

Topics: Adolescent; Biopsy; Diabetes Mellitus, Type 1; Fatty Liver; Female; Glycogen; Growth Disorders; Hepatitis; Hepatomegaly; Humans; Liver; Liver Cirrhosis; Male; Retrospective Studies; Syndrome

Viral hepatitis resulting in chronic liver disease is an important clinical challenge and insight into the cellular processes that drive pathogenesis will be critical in order to develop new diagnostic and therapeutic options. Nuclear inclusions in viral and non-viral hepatitis are well documented and have diagnostic significance in some disease contexts. However, the origins and functional consequences of these nuclear inclusions remain elusive. To date the clinical observation of nuclear inclusions in viral and non-viral hepatitis has not been explored at depth in murine models of liver disease. Herein, we report that in a transgenic model of hepatitis B surface antigen mediated hepatitis, murine hepatocytes exhibit nuclear inclusions. Cells bearing nuclear inclusions were more likely to express markers of cell proliferation. We also established a correlation between these inclusions and oxidative stress. N-acetyl cysteine treatment effectively reduced oxidative stress levels, relieved endoplasmic reticulum (ER) stress, and the number of nuclear inclusions we observed in the transgenic mice. Our results suggest that the presence of nuclear inclusions in hepatocytes correlates with oxidative stress and cellular proliferation in a model of antigen mediated hepatitis.

Topics: Aldehydes; Animals; Biomarkers; Cell Death; Cell Nucleus; Cell Nucleus Size; Cellular Senescence; Disease Models, Animal; Endoplasmic Reticulum; Glycogen; Hepatitis; Hepatitis B Surface Antigens; Hepatocytes; Intranuclear Inclusion Bodies; Mice, Inbred C57BL; Mice, Transgenic; Oxidative Stress; Proliferating Cell Nuclear Antigen; Vacuoles

Air pollution is a global challenge to public health. Epidemiological studies have linked exposure to ambient particulate matter with aerodynamic diameters<2.5 μm (PM(2.5)) to the development of metabolic diseases. In this study, we investigated the effect of PM(2.5) exposure on liver pathogenesis and the mechanism by which ambient PM(2.5) modulates hepatic pathways and glucose homeostasis.. Using "Ohio's Air Pollution Exposure System for the Interrogation of Systemic Effects (OASIS)-1", we performed whole-body exposure of mice to concentrated ambient PM(2.5) for 3 or 10 weeks. Histological analyses, metabolic studies, as well as gene expression and molecular signal transduction analyses were performed to determine the effects and mechanisms by which PM(2.5) exposure promotes liver pathogenesis.. Mice exposed to PM(2.5) for 10 weeks developed a non-alcoholic steatohepatitis (NASH)-like phenotype, characterized by hepatic steatosis, inflammation, and fibrosis. After PM(2.5) exposure, mice displayed impaired hepatic glycogen storage, glucose intolerance, and insulin resistance. Further investigation revealed that exposure to PM(2.5) led to activation of inflammatory response pathways mediated through c-Jun N-terminal kinase (JNK), nuclear factor kappa B (NF-κB), and Toll-like receptor 4 (TLR4), but suppression of the insulin receptor substrate 1 (IRS1)-mediated signaling. Moreover, PM(2.5) exposure repressed expression of the peroxisome proliferator-activated receptor (PPAR)γ and PPARα in the liver.. Our study suggests that PM(2.5) exposure represents a significant "hit" that triggers a NASH-like phenotype and impairs hepatic glucose metabolism. The information from this work has important implications in our understanding of air pollution-associated metabolic disorders.

Topics: Animals; Disease Models, Animal; Fatty Liver; Glucose; Glucose Intolerance; Glycogen; Hepatitis; Homeostasis; Inhalation Exposure; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Non-alcoholic Fatty Liver Disease; Particulate Matter; Phenotype; PPAR alpha; PPAR gamma; Signal Transduction; Toll-Like Receptor 4

Our group recently demonstrated that maternal high-fat diet (HFD) consumption is associated with non-alcoholic fatty liver disease, increased apoptosis, and changes in gluconeogenic gene expression and chromatin structure in fetal nonhuman primate (NHP) liver. However, little is known about the long-term effects that a HFD has on hepatic nervous system development in offspring, a system that plays an important role in regulating hepatic metabolism. Utilizing immunohistochemistry and Real-Time PCR, we quantified sympathetic nerve fiber density, apoptosis, inflammation, and other autonomic components in the livers of fetal and one-year old Japanese macaques chronically exposed to a HFD. We found that HFD exposure in-utero and throughout the postnatal period (HFD/HFD), when compared to animals receiving a CTR diet for the same developmental period (CTR/CTR), is associated with a 1.7 fold decrease in periportal sympathetic innervation, a 5 fold decrease in parenchymal sympathetic innervation, and a 2.5 fold increase in hepatic apoptosis in the livers of one-year old male animals. Additionally, we observed an increase in hepatic inflammation and a decrease in a key component of the cholinergic anti-inflammatory pathway in one-year old HFD/HFD offspring. Taken together, these findings reinforce the impact that continuous exposure to a HFD has in the development of long-term hepatic pathologies in offspring and highlights a potential neuroanatomical basis for hepatic metabolic dysfunction.

Topics: Animals; Apoptosis; Cytokines; Diet, High-Fat; Female; Gene Expression; Gene Expression Regulation, Developmental; Glucose Transporter Type 2; Glycogen; Hepatitis; Inflammation Mediators; Liver; Macaca; Male; Maternal-Fetal Exchange; Neuropeptide Y; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, Neuropeptide Y; Receptors, Nicotinic; Sympathetic Fibers, Postganglionic; Sympathetic Nervous System; Tyrosine 3-Monooxygenase

Foci of altered hepatocytes (FAH) represent preneoplastic lesions, as shown in various animal models of hepatocarcinogenesis, but their significance in the human liver has not been established. The cellular composition, size distribution and proliferation kinetics of FAH in 163 explanted and resected human livers with or without hepatocellular carcinoma (HCC) and their possible association with small-cell change of hepatocytes (SCC) were therefore studied. FAH, including glycogen-storing foci, were found in 84 of 111 cirrhotic livers, demonstrating higher incidences in cases with (29/32) than in those without HCC (55/79). FAH were observed more frequently in HCC-free cirrhosis associated with hepatitis B or C virus or chronic alcoholic abuse (high-risk group) (37/47) than in that due to other causes (low-risk group) (12/21). MCF, predominant in cirrhotic livers of the high-risk group, were more proliferative, larger and more often involved in formation of nodules of altered hepatocytes (39.3%) than were GSF (8.5%). The results suggest that the FAH are preneoplastic lesions, MCF being more advanced than GSF. Oncocytic and amphophilic cell foci were also observed, but their significance remains to be clarified. Two types of SCC, namely diffuse and intrafocal SCC, were identified, but only intrafocal SCC was found to be related to increased proliferative activity and more frequent nodular transformation of the FAH involved, suggesting a close association with progression from FAH to HCC.

Topics: Adolescent; Adult; Aged; Carcinoma, Hepatocellular; Cell Division; Child; Child, Preschool; Female; Glycogen; Hepatitis; Humans; Immunohistochemistry; Infant; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Precancerous Conditions; Proliferating Cell Nuclear Antigen

Topics: Acute Disease; Adult; Chronic Disease; Female; Glycogen; Hepatitis; Humans; Leukocytes; Liver Cirrhosis; Male; Middle Aged; Phagocytes; Phagocytosis

Topics: Carbon Isotopes; Glucose; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycoside Hydrolases; Hepatitis; Humans; Jaundice, Chronic Idiopathic; Liver Diseases; Liver Glycogen; Molecular Weight; Muscular Diseases; Phosphorylases; Ultracentrifugation

Topics: Adolescent; Carcinoma, Hepatocellular; Cortisone; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Hepatitis; Humans; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Microscopy, Electron; Norethandrolone

Topics: Adolescent; Adult; Age Factors; Aged; Alcoholism; Animals; Cell Nucleolus; Cell Nucleus; Child; Child, Preschool; Collagen; Cytoplasm; Cytoplasmic Granules; Diabetes Complications; Diabetes Mellitus; Diet, Diabetic; Female; Glycogen; Hepatitis; Hepatomegaly; Humans; Infant; Insulin; Liver Cirrhosis; Liver Function Tests; Lysosomes; Male; Microscopy, Electron; Middle Aged; Mitochondria, Liver; Reticulum; Sex Factors; Splenomegaly; Sulfonamides

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Biological Transport; Chronic Disease; Dihydrolipoamide Dehydrogenase; Electron Transport Complex IV; Glutamate Dehydrogenase; Glycerolphosphate Dehydrogenase; Glycogen; Hepatitis; Histocytochemistry; Humans; Liver; Liver Cirrhosis; Malate Dehydrogenase; Methods; Protein Biosynthesis; RNA; Succinate Dehydrogenase

Topics: Asthma; Cell Nucleus; Colitis, Ulcerative; Eosinophils; Eye Injuries; Glycogen; Hepatitis; Humans; Leukemia; Leukocytes; Lung Diseases; Schistosomiasis; Skin Window Technique

Topics: Adolescent; Biopsy; Cell Nucleus; Child; Child, Preschool; Diagnosis, Differential; Female; Glycogen; Hepatitis; Histocytochemistry; Humans; Infant; Infectious Mononucleosis; Jaundice; Liver; Male

Topics: Alkaline Phosphatase; Animals; Antitoxins; Chemical and Drug Induced Liver Injury; Corynebacterium; Corynebacterium pyogenes; Exotoxins; Female; Glycogen; Goats; Hepatitis; Histocytochemistry; Humans; Liver; Liver Glycogen; Mammary Glands, Animal; Mastitis; Research; Toxins, Biological

Topics: Alkaloids; Animals; Chemical and Drug Induced Liver Injury; Glycogen; Growth Hormone; Hepatitis; Lipid Metabolism; Liver; Liver Cirrhosis; Liver Cirrhosis, Experimental; Liver Glycogen; Pharmacology; Rats; Research

Topics: Biopsy; Blood Platelets; Electrons; Glycogen; Hepatitis; Hepatitis A; Humans; Kidney Glomerulus; Kidney Tubules; Leukocytes; Liver Glycogen; Macrophages; Microscopy; Microscopy, Electron; Muscles; Parathyroid Glands; Peritoneum; Skin

Topics: Alkaline Phosphatase; Animals; Bile; Carbohydrate Metabolism; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Dogs; Glycogen; Hepatitis; Hormones; Lipid Metabolism; Liver; Pharmacology; Pineal Gland; Rats

Topics: Alkaline Phosphatase; Blood Cells; Endocarditis; Endocarditis, Bacterial; Female; Glycogen; Hepatitis; Hepatitis A; Histocytochemistry; Humans; Infant, Newborn; Infectious Mononucleosis; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Polycythemia Vera; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Primary Myelofibrosis; Sepsis

Topics: Blood Glucose; Child; Glucagon; Glycogen; Glycogen Storage Disease; Glycoside Hydrolases; Hepatitis; Hepatitis A; Humans; Infant; Metabolic Diseases; Phosphoric Monoester Hydrolases

Topics: Biopsy; Glycogen; Hepatitis; Histocytochemistry; Humans; Liver; Liver Cirrhosis; Liver Diseases; Liver Glycogen; Liver Neoplasms; Phosphorylases; Phosphotransferases

Topics: Diabetes Mellitus; Glycogen; Hepatitis; Humans

Topics: Diabetes Mellitus; Epinephrine; Glycogen; Hepatitis; Humans