glycogen and Sepsis

Topics: Animals; Animals, Newborn; Blood Glucose; Disease Models, Animal; Glucagon; Gluconeogenesis; Glycogen; Homeostasis; Humans; Infant, Newborn; Insulin; Liver; Sepsis

Topics: Animals; Blood Chemical Analysis; Disease Models, Animal; Glycogen; Humans; Hypothalamo-Hypophyseal System; Lipolysis; Liver Glycogen; Muscles; Pituitary-Adrenal System; Proteins; Sepsis; Wounds and Injuries

Metabolic reprogramming is the response of cells to environmental changes, such as cell activation, proliferation and differentiation, which involves changes in metabolism-related enzymes, metabolites and metabolic pathways. Sepsis-associated immune cells undergo metabolic reprogramming in response to inflammatory signals, which not only provides biological energy and biosynthesis requirements, but also determines cell fate and function in a highly specific way. In this paper, the changes in glycolysis, tricarboxylic acid cycle, oxidative phosphorylation and other glucose metabolism pathways of macrophages, T lymphocytes, dendritic cells, neutrophils and other sepsis related immune cells are described, so as to provide feasibility for future research and metabolic therapy.

Topics: Dendritic Cells; Glycogen; Glycolysis; Humans; Oxidative Phosphorylation; Sepsis

BACKGROUND Whey acidic protein/four-disulfide core domain 21 (Wfdc21), also known as Lnc-DC, it has been reported to be correlated with immune response. However, the role of Wfdc21 in the pathogenesis of sepsis is still unknown. In the present study, we aimed to investigate the role of Wfdc21 in the pathogenesis of sepsis. MATERIAL AND METHODS The cecal ligation and puncture (CLP)-induced sepsis model was established in Balb/c mice. Animals were euthanized 4, 8, 16, or 24 h after CLP. The glycogen distribution in the kidney and liver was checked by Periodic acid-Schiff (PAS) staining. Changes in the serum interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) concentrations were monitored with ELISA, and Wdfc21 expression was determined by qPCR. Mouse macrophage-like RAW264.7 cells were treated with different doses of lipopolysaccharide (LPS) from Escherichia coli to mimic sepsis in vitro. Western blot analysis was performed to confirm whether LPS-induced in vitro sepsis was correlated with the involvement of the Stat3/TLR4 signaling pathway. In addition, RAW 264.7 cells were infected with lentiviruses containing Wfdc21 shRNA to further confirm the role of Wfdc21 in the pathogenesis of sepsis. RESULTS We found that Wfdc21 level was elevated in the CLP-induced animal model and LPS-treated RAW264.7 cells. Furthermore, the downregulation of Wfdc21 modulated the concentration of pro-inflammatory factors in LPS-treated macrophages, such as IL-1β and TNF-α, in LPS-treated macrophages. This regulatory effect was mediated through the Stat3/TLR4 signaling pathway, since Wfdc21 can regulate p-Stat3 and TLR4 levels in LPS-treated macrophages. CONCLUSIONS Wfdc21 plays a critical role in the pathogenesis of sepsis and may provide a therapeutic target for sepsis treatment.

Topics: Animals; Disease Models, Animal; Down-Regulation; Female; Glycogen; Interleukin-1beta; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred BALB C; RAW 264.7 Cells; RNA, Long Noncoding; Sepsis; Signal Transduction; STAT3 Transcription Factor; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Myocardial contractile dysfunction in sepsis has been attributed mainly to increased inflammatory cytokines, insulin resistance, and impaired oxidative phosphorylation of fatty acids (FAs). However, precise molecular mechanisms underlying the cardiac dysfunction in sepsis remain to be determined. We previously reported major shift in myocardial energy substrates from FAs to glucose, and increased hepatic ketogenesis in mice lacking fatty acid-binding protein 4 (FABP4) and FABP5 (DKO).. We sought to determine whether a shift of energy substrates from FAs to glucose and increased availability of ketone bodies are beneficial or detrimental to cardiac function under the septic condition.. Lipopolysaccharide (LPS, 10mg/kg) was intraperitoneally injected into wild-type (WT) and DKO mice. Twelve hours after injection, cardiac function was assessed by echocardiography and serum and hearts were collected for further analyses.. Cardiac contractile function was more deteriorated by LPS injection in DKO mice than WT mice despite comparable changes in pro-inflammatory cytokine production. LPS injection reduced myocardial uptake of FA tracer by 30% in both types of mice, while uptake of the glucose tracer did not significantly change in either group of mice in sepsis. Storage of glycogen and triacylglycerol in hearts was remarkably increased by LPS injection in both mice. Metabolome analysis revealed that LPS-induced suppression of pool size in the TCA cycle was more enhanced in DKO hearts. A tracing study with. Our study demonstrated that LPS-induced cardiac contractile dysfunction is associated with the robust suppression of catabolism of energy substrates including FAs, glucose and ketone bodies and accumulation of glycogen and triacylglycerol in the heart. Thus, a fuel shift from FAs to glucose and/or ketone bodies may be detrimental rather than protective under septic conditions.

Topics: Animals; Energy Metabolism; Fatty Acid-Binding Proteins; Fatty Acids; Glucose; Glycogen; Heart; Ketone Bodies; Lipopolysaccharides; Mice; Mice, Knockout; Myocardium; Neoplasm Proteins; Sepsis; Triglycerides

The metabolic profile is very affected in sepsis, which is the most important cause of extrapulmonary acute lung injury (ALI-EX). The aim of the present study was to investigate whether sepsis-induced ALI-EX in mice affects the glycogen content in different tissues. This measurement could indicate performance limitations of tissues and constitute a novel biochemical aspect of ALI. ALI was induced by cecal ligation and puncture (CLP), which is a model that reproduces clinical and pathological alterations stemming from sepsis. Control group mice were sham-operated. Glycogen content (mg/g tissue) from different tissues was measured using the anthrone reagent. Glycogen content in the diaphragm (0.3 +/- 0.1) and gastrocnemius muscle (0.4 +/- 0.1) was lower in the sepsis group than the control group (0.9 +/- 0.1 and 1.1 +/- 0.2, respectively). However, there were no significant differences in glycogen content in the heart and kidney. Sepsis caused a greater thickening of the alveolar walls, more areas of atelectasis, and a greater abundance of inflammatory cells in comparison to the control group. These results demonstrate that glycogen content in sepsis-induced ALI-EX is altered in different tissues.

Topics: Acute Lung Injury; Animals; Diaphragm; Disease Models, Animal; Glycogen; Kidney; Lung; Male; Mice; Mice, Inbred BALB C; Muscle, Skeletal; Myocardium; Sepsis

MAPKs are crucial for TNF-alpha and IL-6 production by innate immune cells in response to TLR ligands. MAPK phosphatase 1 (Mkp-1) deactivates p38 and JNK, abrogating the inflammatory response. We have previously demonstrated that Mkp-1(-/-) mice exhibit exacerbated inflammatory cytokine production and increased mortality in response to challenge with LPS and heat-killed Staphylococcus aureus. However, the function of Mkp-1 in host defense during live Gram-negative bacterial infection remains unclear. We challenged Mkp-1(+/+) and Mkp-1(-/-) mice with live Escherichia coli i.v. to examine the effects of Mkp-1 deficiency on animal survival, bacterial clearance, metabolic activity, and cytokine production. We found that Mkp-1 deficiency predisposed animals to accelerated mortality and was associated with more robust production of TNF-alpha, IL-6 and IL-10, greater bacterial burden, altered cyclooxygenase-2 and iNOS expression, and substantial changes in the mobilization of energy stores. Likewise, knockout of Mkp-1 also sensitized mice to sepsis caused by cecal ligation and puncture. IL-10 inhibition by neutralizing Ab or genetic deletion alleviated increased bacterial burden. Treatment with the bactericidal antibiotic gentamicin, given 3 h after Escherichia coli infection, protected Mkp-1(+/+) mice from septic shock but had no effect on Mkp-1(-/-) mice. Thus, during Gram-negative bacterial sepsis Mkp-1 not only plays a critical role in the regulation of cytokine production but also orchestrates the bactericidal activities of the innate immune system and controls the metabolic response to stress.

Topics: Animals; Cyclooxygenase 2; Dual Specificity Phosphatase 1; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Escherichia coli Infections; Glucose; Glycogen; Gram-Negative Bacterial Infections; Hyperlipidemias; Inflammation; Interleukin-10; Interleukin-6; Lipid Metabolism; Mice; Mice, Knockout; Nitric Oxide Synthase Type II; Sepsis; Tumor Necrosis Factor-alpha

We report a false negative histochemical reaction for myophosphorylase in the case of an 11 year old with fulminant Staphylococcus aureus. Due to increased creatine kinase levels and marked myoglobinuria a muscle biopsy was performed prior to death. The biopsy revealed rhabdomyolysis, glycogen depletion and absent myophosphorylase reactivity. Subsequent myophosphorylase quantification was normal. This unique case of a false negative myophosphorylase histochemical reaction is apparently related to sepsis.

Topics: Autopsy; Biomarkers; Child; Creatine Kinase; Diagnosis, Differential; False Negative Reactions; Fatal Outcome; Glycogen; Glycogen Phosphorylase, Muscle Form; Histocytochemistry; Humans; Male; Methicillin Resistance; Muscle, Skeletal; Myocardium; Rhabdomyolysis; Sepsis; Staphylococcal Infections; Staphylococcus aureus

Carbohydrate dyshomeostasis is a characteristic feature of sepsis. Sepsis elevates glucose uptake and cellular lactate levels in muscle. The mechanisms responsible for these alterations are unknown. We examined the effects of a chronic, intra-abdominal septic abscess upon glucose uptake, the expression of the insulin receptor, glucose transporter proteins (Glut-1 and Glut-4) and mRNA, and the content of glycolytic intermediates in muscle from the hindlimb. Sepsis caused a 67% increase in glucose uptake compared with control. A differential expression of the Glut-1 and Glut-4 transporter proteins in skeletal muscle of septic rats was observed. Sepsis increased the expression of Glut-1 protein 1.7-fold. The increased Glut-1 protein correlated with a similar increase in the relative abundance of Glut-1 mRNA. In contrast, sepsis did not alter the amount of Glut-4 protein and mRNA or insulin receptor protein. The tissue content of glucose-6-phosphate was increased approximately twofold compared with control. The increase in the glucose-6-phosphate content was not associated with increased glycogen deposition in skeletal muscle of septic animals. Analysis of the glycolytic intermediates showed that only the lactate content of muscles from septic rats was significantly elevated in sepsis. The results are consistent with the hypothesis that sepsis enhances glucose uptake secondary to increased Glut-1 expression. Furthermore, once transported, glucose may be preferentially metabolized to lactate.

Topics: Animals; Glucose; Glucose Transporter Type 1; Glucose Transporter Type 4; Glycogen; Male; Monosaccharide Transport Proteins; Muscle Proteins; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Receptor, Insulin; RNA, Messenger; Sepsis

1. The effects of non-lethal bacteraemia or endotoxaemia on insulin-stimulated glucose metabolism were studied in isolated, incubated soleus muscle of rats after 24 and 48 h. 2. The insulin-stimulated rates of lactate formation and glycogen synthesis were similar in muscles isolated from control and bacteraemic rats. 3. Endotoxaemia increased the rates of lactate formation, at all levels of insulin, both at 24 h (approximately 32%) and 48 h (approximately 26%). Endotoxaemia did not alter the sensitivity of glycolysis to insulin. 4. Endotoxaemia decreased the rates of glycogen synthesis at all concentrations of insulin both at 24 h (approximately 39%) and 48 h (approximately 23%). 5. The increase in the rate of glycolysis was related in a dose-dependent manner to the amount of endotoxin given to the animals. 6. Endotoxaemia decreased plasma tri-iodothyronine levels (41%). However, the effects of endotoxaemia (48 h) on glucose metabolism in muscle are similar to those caused by hyperthyroidism. In hypothyroid rats, endotoxin administration increased the rates of glycolysis in muscle in vitro. 7. It is concluded that there are enhanced basal and insulin-stimulated rates of glycolysis in soleus muscle from endotoxaemic rats. This may be due to both increased glucose transport and decreased glycogen synthesis.

Topics: Animals; Endotoxins; Glucose; Glycogen; Insulin; Lactates; Male; Muscles; Rats; Rats, Inbred Strains; Sepsis

Cecal ligation and puncture (CLP) has been extensively used as a model of sepsis in adult rats. It is not known if the response to sepsis is similar in young and adult rats. This investigation was done to compare hemodynamic and metabolic alterations in young (four to six weeks of age, 60 to 90 grams) and adult (12 to 14 weeks of age, 270 to 340 grams) rats after CLP. In one series of experiments, survival rate was determined for 96 hours, and in other experiments, mean arterial blood pressure (MAP), heart rate (HR), white blood cell count, hematocrit, platelets, plasma glucose, lactate, amino acids, blood urea nitrogen (BUN), blood and peritoneal cultures and resting energy expenditure (REE) were determined eight and 16 hours after CLP. Levels of glycogen in liver and muscle were determined 16 hours after CLP. Mortality rate was similar in young and adult rats. MAP was stable throughout the course of sepsis, with no significant differences between the two groups of rats. HR was higher in young rats at all times studied. The adult rats became hyperglycemic after CLP while the young were hypoglycemic eight hours after CLP but normalized at 16 hours. Plasma lactate and BUN were similar in the two groups of rats, and no alterations were seen during sepsis. Both young and adult rats became hypoaminoacidemic after CLP. The phenylalanine to tyrosine ratio increased in a similar manner during sepsis in both experimental groups. REE was higher in young than in adult rats, but no significant changes were observed during the course of sepsis in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Age Factors; Amino Acids; Animals; Cecum; Disease Models, Animal; Energy Metabolism; Glycogen; Hemodynamics; Ligation; Male; Peritoneal Cavity; Punctures; Rats; Rats, Inbred Strains; Sepsis; Time Factors

The host defense against respiratory tract infection with Klebsiella pneumoniae was much weaker in 60-week-old mice than in 4-week-old mice, but the resistance against systemic infection by intravenous and intraperitoneal challenge with K. pneumoniae in 60-week-old mice did not differ from that in 4-week-old mice. The number of alveolar macrophages at the resting stage in 60-week-old mice was the same as in 4-week-old mice, but the number of macrophages and polymorphonuclear leukocytes in the pulmonary cavity 4 h after challenge with formalinized K. pneumoniae in aerosol doubled in parallel with body weight. Phagocytosis and killing activities and superoxide anion production as measured by the Nitro Blue Tetrazolium reduction test of alveolar macrophages in 60-week-old mice were significantly weaker than in 4-week-old mice. The surfaces of the alveolar macrophages of the 60-week-old mice shrunk and a few adhered weekly to the glass plate, but the alveolar macrophages of the 4-week-old mice stretched to their full length and adhered firmly to the glass plate. These functions of alveolar macrophages clearly differed from those of peritoneal macrophages in 60-week-old mice, but those of the peritoneal phagocytes did not differ between 60-week-old and 4-week-old mice. The results suggest that the susceptibility to respiratory tract infection in 60-week-old mice is affected by a decline in the functions of alveolar macrophages rather than by the number of alveolar macrophages and exudated polymorphonuclear leukocytes in the lungs.

Topics: Aging; Animals; Chemotaxis, Leukocyte; Exudates and Transudates; Glycogen; Klebsiella pneumoniae; Lung; Macrophages; Mice; Mice, Inbred ICR; Neutrophils; Phagocytes; Pulmonary Alveoli; Respiratory Tract Infections; Sepsis; Superoxides

Topics: Animals; Escherichia coli Infections; Glycogen; Microscopy, Electron; Mitochondria; Muscles; Myocardium; Myofibrils; Rats; Rats, Inbred Strains; Sepsis

Topics: Acetates; Adenosine Diphosphate; Adenosine Triphosphate; Amino Acids; Animals; Carbohydrate Metabolism; Carbon Isotopes; Disease Models, Animal; Glucose; Glycogen; Lactates; Lipid Metabolism; Liver; Liver Glycogen; Lung; Muscles; Myocardium; Penicillin G; Pneumococcal Infections; Proteins; Pyruvates; Rabbits; Sepsis; Streptococcus pneumoniae

Topics: Animals; Glycogen; Hematopoiesis; Leukocytes; Oxidoreductases; Peroxidases; Rabbits; Radiation Injuries; Radiation Injuries, Experimental; Radiometry; Research; RNA; Sepsis

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: Bacterial Infections; Carbohydrate Metabolism; Carbohydrates; Female; Glycogen; Humans; Physical Therapy Modalities; Pre-Eclampsia; Pregnancy; Sepsis