Increased Liver Glycogen Research Articles

Effect of Garcinia indica Powder on Metabolic Parameters and Body Composition in Genetically Mutant WNIN/GR-Ob Rats.

Obesity is associated with metabolic diseases, including insulin resistance, type 2 diabetes and dyslipidemia. Antiobesity drugs are available but have side effects. Hydroxy citric acid (HCA) with ATP-citrate lyase enzyme-inhibiting activity has been identified as a safe potential supplement for weight management and as an antiobesity agent. In the present study, we aim to test the antiobesity potential of the fruit rind powder of G. indica (a plant rich in HCA) in genetically obese rats. Forty-five-day-old Male WNIN/GR-Ob rats were divided equally into four groups with each group having six rats. Group 1 was fed with a standard powder diet (SPD), whereas Groups 2, 3, and 4 were fed with SPD containing 1%, 3%, and 5%, respectively, of G. indica powder for 12 weeks. Food intake, body composition, oral glucose tolerance test, plasma insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipid profile, hepatic glycogen, ATP-citrate lyase, and Glucose-6-Phosphate dehydrogenase (G6PDH) were measured. Histological analysis of vital organs and Immunohistochemistry (IHC) analysis was carried out in liver sections for citrate lyase score. G. indica significantly decreased food intake, body weight, body fat %, hepatic and circulating triglycerides, cholesterol, and liver steatosis. In addition, G6PDH and ATP-citrate lyase enzyme activities were decreased along with an increase in liver glycogen. The IHC scores of citrate lyase were lower in treated groups. The results indicate that G. indica exerts favorable effects on obesity with a possible mechanism of anorectic effects, suppressed citrate lyase enzyme activity, and improved insulin sensitivity due to the modulation of carbohydrate metabolism by the phytochemicals and secondary metabolites.

Natural Compounds from Hatikana Extract Potentiate Antidiabetic Actions as Displayed by In Vivo Assays and Verified by Network Pharmacological Tools.

Background Hatikana is a traditional medicinal plant used to treat inflammation, urolithiasis, goiter, cancer, wounds and sores, gastrointestinal, tumor, tetanus, arthritis, hepatic damage, neurodegeneration, and other ailments. The goal of this study is to investigate the antidiabetic properties of Hatikana extract (HKEx) and to construct the effects of its natural constituents on the genes and biochemical indices that are connected with them. Methods HKEx was evaluated using GC-MS and undertaken for a three-week intervention in fructose-fed STZ-induced Wistar albino rats at the doses of HKEx50, HKEx100, and HKEx200 mg/kg bw. Following intervention, blood serum was examined for biochemical markers, and liver tissue was investigated for the mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD1) by RTPCR analysis. Most abundant compounds (oleanolic acid, 7α, 28-olean diol, and stigmasterol) from GC-MS were chosen for the network pharmacological assay to verify function-specific gene-compound interactions using STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba. Results In vivo results showed a significant (P < 0.05) decrease of blood sugar, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase of liver glycogen, glucose load, and serum insulin. Out of three antioxidative genes, catalase (CAT) and superoxide dismutase (SOD1) were found to be few fold increased. Oleanolic acid and stigmasterol were noticed to strongly interact with 27 target proteins. Oleanolic acid interacted with the proteins AKR1B10, CASP3, CASP8, CYP1A2, CYP1A2, HMGB1, NAMPT, NFE2L2, NQO1, PPARA, PTGIR, TOP1, TOP2A, UGT2B10, and UGT2B11 and stigmasterol with ABCA1, ABCG5, ABCG8, CTSE, HMGCR, IL10, CXCL8, NR1H2, NR1H3, SLCO1B1, SREBF2, and TNF. Protein-protein interaction (PPI) analysis revealed the involvement of 25 target proteins out of twenty seven. Cytoscape plugin cytoHubba identified TNF, CXCL8, CASP3, PPARA, SREBF2, and IL10 as top hub genes. Pathway analysis identified 31 KEGG metabolic, signaling, and immunogenic pathways associated with diabetes. Notable degree of PPI enrichment showed that SOD1 and CAT are responsible for controlling signaling networks and enriched pathways. Conclusion The findings show that antioxidative genes have regulatory potential, allowing the HKEx to be employed as a possible antidiabetic source pending further validation.

Milled flaxseed-added diets ameliorated hepatic inflammation by reducing gene expression of TLR4/NF-κB pathway and altered gut microbiota in STZ-induced type 1 diabetic mice

Flaxseed has displayed the potential beneficial as functional foods. However, most studies focused on effects of flaxseed extracts or ingredients in flaxseed. Besides, few studies showed that flaxseed extracts contributed to anti-type 1 diabetes (T1D), yet the underlying mechanism is still unknown. In the present study, 16.7% of milled flaxseed (MF)-added diet was given to diabetic mice induced by streptozocin for 6 weeks. The results showed that MF feeding 1) slightly decreased blood glucose levels and improved the ability of glucose tolerance by oral glucose tolerance test, 2) decreased liver tumor necrosis factor-α levels and increased liver glycogen levels with significance via down-regulating TLR4/NF-κB pathways, 3) and significantly altered some beneficial bacteria in gut microbiota. In conclusion, the present study showed that milled flaxseed showed the potential on anti-T1D through anti-inflammation via TLR4/NF-κB and altering the gut microbiota in STZ-induced diabetic mice.

Dynamic interplay between AfadinS1795 phosphorylation and diet regulates glucose homeostasis in obese mice.

Afadin is a ubiquitously expressed scaffold protein with a recently discovered role in insulin signalling and glucose metabolism. Insulin-stimulated phosphorylation of Afadin at S1795 occurs in insulin-responsive tissues such as adipose tissue, muscle, liver, pancreas and heart. Afadin abundance and AfadinS1795 phosphorylation are dynamically regulated in metabolic tissues during diet-induced obesity progression. Genetic silencing of AfadinS1795 phosphorylation improves glucose homeostasis in the early stages of diet-induced metabolic dysregulation. AfadinS1795 phosphorylation contributes to the early development of obesity-related complications in mice. Obesity is associated with systemic insulin resistance and numerous metabolic disorders. Yet, the mechanisms underlying impaired insulin action during obesity remain to be fully elucidated. Afadin is a multifunctional scaffold protein with the ability to modulate insulin action through its phosphorylation at S1795 in adipocytes. In the present study, we report that insulin-stimulated AfadinS1795 phosphorylation is not restricted to adipose tissues, but is a common signalling event in insulin-responsive tissues including muscle, liver, pancreas and heart. Furthermore, a dynamic regulation of Afadin abundance occurred during diet-induced obesity progression, while its phosphorylation was progressively attenuated. To investigate the role of AfadinS1795 phosphorylation in the regulation of whole-body metabolic homeostasis, we generated a phospho-defective mouse model (Afadin SA) in which the Afadin phosphorylation site was silenced (S1795A) at the whole-body level using CRISPR-Cas9-mediated gene editing. Metabolic characterization of these mice under basal physiological conditions or during a high-fat diet (HFD) challenge revealed that preventing AfadinS1795 phosphorylation improved insulin sensitivity and glucose tolerance and increased liver glycogen storage in the early stage of diet-induced metabolic dysregulation, without affecting body weight. Together, our findings reveal that AfadinS1795 phosphorylation in metabolic tissues is critical during obesity progression and contributes to promote systemic insulin resistance and glucose intolerance in the early phase of diet-induced obesity.

Hypoglycemic effects of space-induced Lactobacillus plantarum SS18-5 on type 2 diabetes in a rat model.

Probiotics can improve dyslipidemia and promote metabolic control as a therapeutic approach for type 2 diabetes mellitus (T2DM). The hypoglycemic effects of space-induced Lactobacillus plantarum SS18-5 on T2DM were explored in 4-week-old male Sprague Dawley rats. The normal (N) group was fed a basal diet, while the other groups received a high glucose fat diet. T2DM was established by streptozotocin injection and the T2DM rats were randomly divided into three groups, a diabetic (D) group (T2DM rats treated with saline only), GS18 group (T2DM rats treated with 109 CFU/ml of L. plantarum GS18), and SS18-5 group (T2DM rats treated with 109 CFU/ml of L. plantarum SS18-5). After continuous gavage for 6weeks, blood biochemical indices were measured and livers were collected for histopathological examination. The colon contents were collected for counting of Escherichia coli, Clostridium perfringens, and Lactobacillus sp. The results showed that L. plantarum SS18-5 effectively controlled the weight of rats, reduced levels of fasting blood glucose, glycosylated hemoglobin, and insulin, increased liver glycogen levels, improved abnormal metabolism of blood lipids, enhanced the effect of anti-lipid peroxidation, alleviated chronic inflammation and fatty liver disease, and regulated the intestinal microbiota by reducing the numbers of E. coli and C. perfringens, and increasing the numbers of Lactobacillus sp. From these results, we conclude that space-induced L. plantarum SS18-5 has the potential to improve T2DM by alleviating hypoglycemia and regulating the intestinal microbiota. PRACTICAL APPLICATIONS: With the exploration of the universe, a large number of studies have observed the changes of microorganisms in space flight, which provided a new method for high-quality microbial pharmaceuticals in the space environment. In this study, the space environment mutated. Lactobacillus plantarum SS18-5 can effectively improve the blood glucose of rats with type 2 diabetes, relieve oxidative stress, reduce blood lipid content, enhance immune capacity, and regulate intestinal microflora, which has potential use in the treatment of type 2 diabetes.

Increased liver glycogen levels enhance exercise capacity in mice

Muscle glycogen depletion has been proposed as one of the main causes of fatigue during exercise. However, few studies have addressed the contribution of liver glycogen to exercise performance. Using a low-intensity running protocol, here, we analyzed exercise capacity in mice overexpressing protein targeting to glycogen (PTG) specifically in the liver (PTGOE mice), which show a high concentration of glycogen in this organ. PTGOE mice showed improved exercise capacity, as determined by the distance covered and time ran in an extenuating endurance exercise, compared with control mice. Moreover, fasting decreased exercise capacity in control mice but not in PTGOE mice. After exercise, liver glycogen stores were totally depleted in control mice, but PTGOE mice maintained significant glycogen levels even in fasting conditions. In addition, PTGOE mice displayed an increased hepatic energy state after exercise compared with control mice. Exercise caused a reduction in the blood glucose concentration in control mice that was less pronounced in PTGOE mice. No changes were found in the levels of blood lactate, plasma free fatty acids, or β-hydroxybutyrate. Plasma glucagon was elevated after exercise in control mice, but not in PTGOE mice. Exercise-induced changes in skeletal muscle were similar in both genotypes. These results identify hepatic glycogen as a key regulator of endurance capacity in mice, an effect that may be exerted through the maintenance of blood glucose levels.

Glucose clearance and uptake is increased in the SOD1G93A mouse model of amyotrophic lateral sclerosis through an insulin-independent mechanism.

Metabolic disturbances are associated with the progression of the neurodegenerative disorder, amyotrophic lateral sclerosis (ALS). However, the molecular events that drive energy imbalances in ALS are not completely understood. In this study, we aimed to elucidate deficits in energy homeostasis in the SOD1G93A mouse model of ALS. SOD1G93A mice and their wild-type littermates underwent indirect calorimetry and intraperitoneal glucose/insulin tolerance tests at both the onset and mid-symptomatic stages of the disease. Glucose uptake and the plasma glucoregulatory hormone profiles were analyzed. Pancreatic islet cell mass and function were assessed by measuring hormone concentrations and secretion in isolated islets, and pancreatic α- and β-cell immunoreactive areas. Finally, we profiled liver glycogen metabolism by measuring glucagon concentrations and liver metabolic gene expressions. We identified that mid-symptomatic SOD1G93A mice have increased oxygen consumption and faster exogenous glucose uptake, despite presenting with normal insulin tolerance. The capacity for pancreatic islets to secrete insulin appears intact, however, islet cell insulin concentrations and β-cell mass were reduced. Fasting glucose homeostasis was also disturbed, along with increased liver glycogen stores, despite elevated circulating glucagon, suggesting that glucagon signaling is impaired. Metabolic gene expression profiling of livers indicated that glucose cannot be utilized efficiently in SOD1G93A mice. Overall, we demonstrate that glucose homeostasis and uptake are altered in SOD1G93A mice, which is linked to an increase in insulin-independent glucose uptake, and a loss of β-cells, insulin production, and glucagon sensitivity. This suggests that the hormonal regulation of glucose concentrations may contribute to the progression of disease in this ALS mouse model.

The Effect of Lactobacillus plantarum CQPC02 on Fatigue and Biochemical Oxidation Levels in a Mouse Model of Physical Exhaustion.

Chinese Sichuan pickle is a fermented food rich in microorganisms. Microorganisms have the potential to become an important new form of potent future therapeutic capable of treating human disease. Selecting vitamin C as a positive control, a lactic acid bacteria (Lactobacillus plantarum CQPC02, LP-CQPC02) isolated from Sichuan pickle was given to mice over 4 weeks to investigate the effect of CQPC02 on fatigue levels and biochemical oxidation phenomena in exercise-exhausted Institute of Cancer Research (ICR) mice. The fatigue model was established by forced swimming of mice, the levels of hepatic glycogen, skeletal muscle glycogen, lactic acid, blood urea nitrogen and free fatty acid were measured by physicochemical methods, serum serum creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels were measured by kits, the histopathological changes in the livers of mice were observed by H&E slicing, and the mRNA changes in the livers and skeletal muscles were observed by quantitative polymerase chain reaction (qPCR). Both vitamin C and LP-CQPC02 increased swimming exhaustion time. The concentration of LP-CQPC02 and exhaustion time were positively correlated. LP-CQPC02 also increased liver glycogen, skeletal muscle glycogen and free fatty acid content in mice and reduced lactic acid and blood urea nitrogen content in a dose-dependent manner. As walnut albumin antioxidant peptide concentration increased, levels of mouse CK, AST, and AST gradually decreased. LP-CQPC02 increased SOD and CAT levels and decreased MDA levels in a dose-dependent fashion. LP-CQPC02 up-regulated expression of mRNA encoding copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT in swimming exhaustion mouse liver tissue. LP-CQPC02 also up-regulated alanine/serine/cysteine/threonine transporter 1 (ASCT1) expression while down-regulating syncytin-1, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) expression in swimming exhaustion mouse skeletal muscle. Overall, LP-CQPC02 had a clear anti-fatigue and anti-oxidation effect. This suggests that LP-CQPC02 can be developed as a microbiological therapeutic agent.

Liver glycogen-induced enhancements in hypoglycemic counterregulation require neuroglucopenia.

Iatrogenic hypoglycemia is a prominent barrier to achieving optimal glycemic control in patients with diabetes, in part due to dampened counterregulatory hormone responses. It has been demonstrated that elevated liver glycogen content can enhance these hormonal responses through signaling to the brain via afferent nerves, but the role that hypoglycemia in the brain plays in this liver glycogen effect remains unclear. During the first 4 h of each study, the liver glycogen content of dogs was increased by using an intraportal infusion of fructose to stimulate hepatic glucose uptake (HG; n = 13), or glycogen was maintained near fasting levels with a saline infusion (NG; n = 6). After a 2-h control period, during which the fructose/saline infusion was discontinued, insulin was infused intravenously for an additional 2 h to bring about systemic hypoglycemia in all animals, whereas brain euglycemia was maintained in a subset of the HG group by infusing glucose bilaterally into the carotid and vertebral arteries (HG-HeadEu; n = 7). Liver glycogen content was markedly elevated in the two HG groups (43 ± 4, 73 ± 3, and 75 ± 7 mg/g in NG, HG, and HG-HeadEu, respectively). During the hypoglycemic period, arterial plasma glucose levels were indistinguishable between groups (53 ± 2, 52 ± 1, and 51 ± 1 mg/dL, respectively), but jugular vein glucose levels were kept euglycemic (88 ± 5 mg/dL) only in the HG-HeadEu group. Glucagon and epinephrine responses to hypoglycemia were higher in HG compared with NG, whereas despite the increase in liver glycogen, neither increased above basal in HG-HeadEu. These data demonstrate that the enhanced counterregulatory hormone secretion that accompanies increased liver glycogen content requires hypoglycemia in the brain.NEW & NOTEWORTHY It is well known that iatrogenic hypoglycemia is a barrier to optimal glycemic regulation in patients with diabetes. Our data confirm that increasing liver glycogen content 75% above fasting levels enhances hormonal responses to insulin-induced hypoglycemia and demonstrate that this enhanced hormonal response does not occur in the absence of hypoglycemia in the brain. These data demonstrate that information from the liver regarding glycogen availability is integrated in the brain to optimize the counterregulatory response.

Effect of Inonotus obliquus (Fr.) Pilat extract on the regulation of glycolipid metabolism via PI3K/Akt and AMPK/ACC pathways in mice

Ethnopharmacological relevanceInonotus obliquus (Fr.) Pilat is a mushroom belonging to the family Hymenochaetaceae. It is popularly called the Chaga mushroom in Russian folk medicine and has been used as a traditional medicine to treat diabetes mellitus in Eastern European and Asian countries. However, its effects on glycolipid metabolism disorders and underlying molecular mechanism of action remain unclear. Aim of the studyI. obliquus contains abundant functional components, which provide potential medicinal value. The purpose of this study was to investigate compositions of I. obliquus extract with a high-pressure water extraction method, and investigate the anti-type 2 diabetic effects of I. obliquus extract and the possible underlying mechanisms involved. Materials and methodsThe I. obliquus was extracted by a high-pressure water extraction method, and tested its main components by special assay kit and instrumental analysis. Type 2 diabetic C57BL/6 mice were induced by high-fat diet with low-dose STZ injection, and were daily gavaged with different doses of I. obliquus extract for 8 weeks. Glycemic, blood lipid profile, and histopathology of liver and pancreas were assessed. Underlying mechanisms related to glycemic control in liver were further performed. ResultsThe I. obliquus extract main compounds were β-Glucans, triterpenoids and polyphenol by determination. Oral administration of 250 mg/kg and 500 mg/kg I. obliquus extract significantly alleviated blood glucose and insulin resistance. Moreover, 250 mg/kg and 500 mg/kg of I. obliquus extract increased liver glycogen content and high-density lipoprotein cholesterol (HDL-C) levels while decreased total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels. Furthermore, the protein expression levels of phosphatidylinositol-3 kinase (PI3K), p-protein kinase B (Akt), p-adenosine monophosphate activated protein kinase (AMPK), and p-acetyl-CoA carboxylase (ACC) were upregulated, whereas sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) were downregulated after supplement with 250 mg/kg and 500 mg/kg of I. obliquus extract. Interestingly, I. obliquus extract was a dose-effect relationship within a certain range. 250 mg/kg had obvious anti-diabetes effect, and the effect of 500 mg/kg dose was the same as that of metformin. ConclusionI. obliquus extract ameliorated insulin resistance and lipid metabolism disorders in diabetic mice. The hypoglycemic and hypolipidemic properties of I. obliquus extract were supposedly exerted via the regulation of the PI3K/Akt and AMPK/ACC signaling pathways.

Discovery of 5-(3-bromo-2-(2,3-dibromo-4,5-dimethoxybenzyl)-4,5-dimethoxybenzylidene)thiazolidine-2,4-dione as a novel potent protein tyrosine phosphatase 1B inhibitor with antidiabetic properties

Protein tyrosine phosphatase 1B (PTP1B) is a well-validated target in therapeutic interventions for type 2 diabetes mellitus (T2DM), however, PTP1B inhibitors containing negatively charged nonhydrolyzable pTyr mimetics are difficult to convert to the corresponding in vivo efficacy owing to poor cell permeability and oral bioavailability. In this work, molecules bearing less acidic heterocycle 2,4-thiazolidinedione and hydantoin were designed, synthesized and evaluated for PTP1B inhibitory potency, selectivity and in vivo antidiabetic efficacy. Among them, compound 5a was identified as a potent PTP1B inhibitor (IC50 = 0.86 μM) with 5-fold selectivity over the highly homologous TCPTP. Long-term oral administration of 5a at a dose of 50 mg/kg not only significantly reduced blood glucose levels, triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels but also ameliorated insulin sensitivity in diabetic BKS db mice. Moreover, 5a enhanced the insulin-stimulated phosphorylation of IRβ, IRS-1 and Akt in C2C12 myotubes. A histopathological evaluation of liver and pancreas demonstrated that 5a increased liver glycogen storage and improved islet architecture with more β-cells and fewer α-cells in diabetic mice. Thus, our work demonstrated that compound 5a could serve as a lead compound for the discovery of new antidiabetic drugs.

Increasing hepatic glycogen moderates the diabetic phenotype in insulin-deficient Akita mice

Hepatic glycogen metabolism is impaired in diabetes. We previously demonstrated that strategies to increase liver glycogen content in a high-fat-diet mouse model of obesity and insulin resistance led to a reduction in food intake and ameliorated obesity and glucose tolerance. These effects were accompanied by a decrease in insulin levels, but whether this decrease contributed to the phenotype observed in this animal was unclear. Here we sought to evaluate this aspect directly, by examining the long-term effects of increasing liver glycogen in an animal model of insulin-deficient and monogenic diabetes, namely the Akita mouse, which is characterized by reduced insulin production. We crossed Akita mice with animals overexpressing protein targeting to glycogen (PTG) in the liver to generate Akita mice with increased liver glycogen content (Akita-PTGOE). Akita-PTGOE animals showed lower glycemia, lower food intake, and decreased water consumption and urine output compared with Akita mice. Furthermore, Akita-PTGOE mice showed a restoration of the hepatic energy state and a normalization of gluconeogenesis and glycolysis back to nondiabetic levels. Moreover, hepatic lipogenesis, which is reduced in Akita mice, was reverted in Akita-PTGOE animals. These results demonstrate that strategies to increase liver glycogen content lead to the long-term reduction of the diabetic phenotype, independently of circulating insulin.

Effects of alfalfa (meal and extract) on digestive enzymes and liver composition in juveniles of common carp (Cyprinus carpio)

270 fish (with an average initial weight: 20.04±0.19 g) were randomly distributed in 27 polyethylene tanks and fed by the carp commercial diet. The experimental treatments of 9 groups (4 groups with 3, 6, 9, and 12% of alfalfa powder, 4 groups with 1, 2, 3, and 4% of alcoholic extract and one control group) with three replications were considered for 8 weeks. At the end of the experimental period, the activity of digestive enzymes was measured in terms of U/mg Protein and liver composition. Based on the results, the highest levels of activity of digestive enzymes, amylase (674.74±61.57), lipase (6/21±/096), alkaline phosphatase (452.84±28.18), trypsin (282.05±19.98) and chymotrypsin (0.10±0.001) in the extracts of 3%, 3%, 3%, 4% and 4% extracts, respectively, and the lowest amount of these enzymes were observed respectively with values of 388.17±38.27 (control), 2.51±0.55 (control), 187.7±19.36 (12% powder), 0.030±0.004 (12% powder) and 132.47±11.47 (9% powder) (P <0.05). The highest amount of hepatic glycogen (338.35±192.13 µg/g tissue) was measured in the 3% extract treatment and the lowest amount of hepatic glycogen (607.01±101.23 µg/g tissue was in the control treatment (P <0.05). The highest level of liver lipids (146.51±6.05 mg/g tissue) was observed in the treatment of 6% powder and the lowest level of liver lipids (72.99±4.46 mg/g tissue) was observed in the treatment of 12% powder (P <0.05). According to the present study, adding powder and especially alfalfa extract to the diet can increase the activity of digestive enzymes and increase liver lipid and glycogen at certain levels.

Effects of high-intensity infrasound on liver lipid content of rats

Previous experimental studies show that exposure to noise with high and audible frequencies causes multiple metabolic alterations, such as increased liver glycogen and triglycerides. However, the effect of exposure to sound with lower frequencies, such as high-intensity infrasound (frequency <20 Hz and sound pressure level >90 dB), on the liver lipid content is still unclear. As such, we aimed to study the effect of exposure to high-intensity infrasound of both normal and glucose intolerant rats on the liver lipid content. For this study, 79 wild-type male Wistar rats were randomly divided into two groups: G1, no treatment, and G2, induced glucose intolerance. Each of these two groups was randomly divided in two subgroups: s (animals kept in silence) and i (animals continuously exposed to high-intensity infrasound noise). At three noise-exposure time-points (1, 6 and 12 weeks) the rats were sacrificed, the liver was excised and hepatic lipids extracted. Data analysis was performed using a two-way ANOVA (p = 0.05). No significant effects due to interactions between the several factors exist on the liver lipid content (p=0.077). Moreover, no significant effects due to infrasound exposure (p=0.407) or glucose tolerance status (p=0.938) were observed. Our study shows that continuous exposure to high-intensity infrasound has no influence on the lipid content of the liver of both normal and glucose intolerant animals. This finding reinforces the need for further experimental studies on the physiological effects of infrasound due to its possible hazardous effects on human health.

MiR-34a Regulates the Activity of HIF-1a and P53 Signaling Pathways by Promoting GLUT1 in Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus) Under Hypoxia Stress.

In fish under hypoxia stress, homeostasis can become imbalanced, leading to tissue and organ damage and decreased survival. Therefore, it is useful to explore the molecular and physiological regulation mechanisms that function in fish under hypoxia stress. The microRNA miR-34a is involved in fat and glycogen metabolism, and in apoptosis. In this study, we first verified that GLUT1, the gene encoding glucose transporter 1, is a potential target gene of miR-34a in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) by dual luciferase reporter assays. Then, we clarified the regulatory relationship between miR-34a and GLUT1 by qRT-PCR analyses. We analyzed the regulatory effects of knockdown or promotion of GLUT1 expression in vitro and in vivo in GIFT under hypoxia stress. The results confirm that GLUT1 is a target gene of miR-34a in GIFT. Down-regulation of miR-34a significantly promoted GLUT1 expression. Knockdown of GLUT1 reduced the glycogen content in GIFT liver cells, inhibited HIF-1a gene expression, up-regulated the expression of genes involved in P53 signaling pathways (P53 and CASPASE-3 genes), and accelerated hepatocyte apoptosis under hypoxia stress. Compared with the control group, the group injected in the tail vein with miR-34a antagomir showed up-regulated expression of GLUT1 in the liver, increased liver glycogen content at 96 h of hypoxia stress, down-regulated expression of P53 and CASPASE-3, and decreased serum aspartate aminotransferase and alanine aminotransferase enzyme activities. Our results provide information about the molecular regulation mechanism of miRNAs and their target genes in fish during the response to hypoxia stress.

A four-week white bread diet does not alter plasma glucose concentrations, metabolic or vascular physiology in mourning doves, Zenaida macroura

Birds are an enigma: their plasma glucose concentration is 1.5–2 times higher than similar-sized mammals, yet they do not normally exhibit symptoms of diabetes. We hypothesized that feeding adult mourning doves a refined carbohydrate diet (white bread: WB) for four weeks would raise plasma glucose concentrations and alter metabolic pathways and endothelial function when compared to birds receiving a nutritionally-balanced diet (bird seeds: SD). Following the four-week long diets, birds were euthanized, and cardiac blood, liver, and pectoralis muscles were collected for metabolomics analyses and biochemical assays. Cranial tibial arteries were dissected to measure acetylcholine-mediated vasodilation. Contrary to the hypothesis, WB-fed birds did not have increased plasma glucose concentrations. Principle component analysis score plots suggest minimal differences between groups. However, we identified 15 changes in individual metabolite concentrations between diet groups that, although not statistically significant, are highly predictive (area under receive operating curve, AUROC>0.90; number of highly predictive metabolites: 5 of 123 in plasma, 4 of 92 in liver, and 6 of 92 in pectoralis muscle). Moreover, pathway analyses revealed no significantly altered metabolic pathways between groups. Biochemical assays revealed no significant group differences in plasma uric acid and insulin, or pectoralis muscle glycogen concentrations. However, hepatic glycogen concentration was 2.12-fold higher in the WB group than in control doves (p = .015). Diet type did not influence vasodilation. In conclusion, a four-week long white bread diet increased liver glycogen but did not alter plasma glucose concentrations, metabolic or vascular physiology in mourning doves.

Anti-fatigue effects of Elaeagnus multiflora fruit extracts in mice

The fruit, leaves, and roots of Elaeagnus multiflora Thunb. have been used in traditional Chinese medicine to treat cough, diarrhea, and itching. However, the anti-fatigue effects of E. multiflora fruit (EMF) extract have not been studied in detail. The aim of this study was to examine the effect of EMF on fatigue and exercise performance in BALB/c mice. EMF was orally administered to mice at four doses (10, 50, 100, and 200 mg/kg/ day) for 2 weeks. The anti-fatigue activity was evaluated by determining the exhaustive swimming time. Blood lactate and glucose levels and serum lactate levels after a 10 min swimming time, as well as ammonia, creatine kinase (CK), blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and glycogen contents after exhaustive swimming time were measured. The exhaustive swimming time of the EMF 200 group was significantly increased (p <0.01). The EMF groups showed significantly low levels of CK, BUN, LDH, and lactate compared with the control group (p <0.05). Increased liver glycogen was observed in the EMF 200 group (p <0.05). These results suggest that EMF can be utilized as an efficacious natural resource for its anti-fatigue effects.

Maintenance of liver glycogen during long-term fasting preserves energy state in mice.

Glycogen shortage during fasting coincides with dramatic changes in hepatic adenine nucleotide levels. The aim of this work was to study the relevance of liver glycogen in the regulation of the hepatic energy state during food deprivation. To this end, we examined the response of mice with sustained increased liver glycogen content to prolonged fasting. In order to increase hepatic glycogen content, we generated mice that overexpress protein targeting to glycogen (PTG) in the liver (PTGOE mice). Control and PTGOE mice were fed adlibitum or fasted for 36h.Upon fasting, PTGOE mice retained significant hepatic glycogen stores and maintained hepatic energy status.Furthermore, we show that liver glycogen controls insulin sensitivity, gluconeogenesis, lipid metabolism, and ketogenesis upon nutrient deprivation.

Dominant gut Prevotella copri in gastrectomised non-obese diabetic Goto\u2013Kakizaki rats improves glucose homeostasis through enhanced FXR signalling

Aims/hypothesisDrug and surgical-based therapies in type 2 diabetes are associated with altered gut microbiota architecture. Here we investigated the role of the gut microbiome in improved glucose homeostasis following bariatric surgery.MethodsWe carried out gut microbiome analyses in gastrectomised (by vertical sleeve gastrectomy [VSG]) rats of the Goto–Kakizaki (GK) non-obese model of spontaneously occurring type 2 diabetes, followed by physiological studies in the GK rat.ResultsVSG in the GK rat led to permanent improvement of glucose tolerance associated with minor changes in the gut microbiome, mostly characterised by significant enrichment of caecal Prevotella copri. Gut microbiota enrichment with P. copri in GK rats through permissive antibiotic treatment, inoculation of gut microbiota isolated from gastrectomised GK rats, and direct inoculation of P. copri, resulted in significant improvement of glucose tolerance, independent of changes in body weight. Plasma bile acids were increased in GK rats following inoculation with P. copri and P. copri-enriched microbiota from VSG-treated rats; the inoculated GK rats then showed increased liver glycogen and upregulated expression of Fxr (also known as Nr1h4), Srebf1c, Chrebp (also known as Mlxipl) and Il10 and downregulated expression of Cyp7a1.ConclusionsOur data underline the impact of intestinal P. copri on improved glucose homeostasis through enhanced bile acid metabolism and farnesoid X receptor (FXR) signalling, which may represent a promising opportunity for novel type 2 diabetes therapeutics.

Bredemolic Acid Ameliorates Selected Liver Function Biomarkers in a Diet-Induced Prediabetic Rat Model.

Background Prediabetes is an intermediary hyperglycaemic state that precedes type 2 diabetes mellitus (T2DM) in which abnormal metabolism of glucose and lipids occurs in organs such as the liver. Evidence has shown that, about 70% of T2DM patients develop hepatic dysfunction which is found to begin during the prediabetic stage. Bredemolic acid, a pentacyclic triterpene, has been found to improve insulin sensitivity in diet-induced prediabetic rats. The effects of this compound on liver function, however, are unknown. This study was therefore designed to investigate the effects of BA on liver function in high fat-high carbohydrate (HFHC) diet-induced prediabetic rats. Methods Thirty-six (36) male rats that weigh 150 g–180 g were divided into two groups, the non-prediabetic (n = 6) and the prediabetic groups (n = 6) and the prediabetic groups (n = 6) and the prediabetic groups (Results The induction of prediabetes resulted in increased release of liver enzymes (AST and ALT), increased liver glycogen and triglyceride, lipid peroxidation, and decreased sterol regulatory element-binding protein (SREBP1c) and antioxidant enzymes. However, the administration of BA decreased liver enzyme concentrations, decreased hepatic oxidative stress, and improved antioxidant enzymes such as SOD and GPx. Conclusion BA administration improved liver function in diet-induced prediabetic rats in the presence or absence of dietary intervention.