Hepatic Glycogen Levels Research Articles

Impact of different processing mulberry leaf on growth, metabolism and liver immune function of largemouth bass (Micropterus salmoides)

Mulberry leaf is abundant in bioactive ingredients, and their release could be affected by different treatment technologies. In this study, the mulberry leaf was treated with methods of superfine grinding (MG), wall-broken (MB), and water extraction-methanol precipitation (ME). Three processing mulberry leaves were equally added to the feed of largemouth bass (Micropterus salmoides), respectively, and the growth, liver health and intestinal microorganisms were analyzed. According to statistical analysis, the growth of the three experimental groups was remarkedly better than that of the control group fed with a basic diet. The MB group had a higher specific growth rate (SGR) and weight gain rate (WGR) than the MG and ME groups. Mulberry leaf supplementation could significantly reduced blood glucose and serum total cholesterol (TC), very low-density lipoprotein (VLDL) and triglyceride (TG) levels, improved hepatic glycogen, lipid and TG levels, and these parameter values of the MB group were superior to the other treatments. Additionally, MB treatment could up-regulate the expressions of gpx and cat in the liver compared with the control and boost the activities of antioxidant enzymes (GSH-Px and CAT). Meanwhile, MB supplementation suppressed the expressions of pro-inflammatory cytokines (TNFα and IL-8) and up-regulated anti-inflammatory cytokines (IL-10 and TGF-β) in liver compared to the control group. Accordingly, the hepatic histostructure showed an improvement in the treatment group, and mulberry leaf could also dramatically lower the apoptosis of hepatic cells, particularly in the MB group. Furthermore, MB treatment reduced gut dysbiosis by limiting the development of gram-negative and possibly dangerous bacteria. In sum, this study firstly disclosed that the biological effectiveness of mulberry leaf might be impacted by various processing techniques. Especially MB-treatment effectively ameliorates glucose, lipid metabolism and liver immunology in largemouth bass.

Antinutritional effect of lectin from faveira (Parkia platycephala) seeds in tambatinga (Colossoma macropomum x Piaractus brachypomus)

This study investigated the possible antinutritional effects of Parkia platycephala lectin (0, 20, 40, or 60 mg kg-1 of diet) on tambatinga feeding for 60 days as well as methods of inactivating this protein. Weight gain, specific growth rate, and relative weight gain decreased, and the feed conversion rate increased with the increase in dietary lectin. The hepatic glycogen levels of fish fed 60 mg kg-1 were higher than those of fish fed 20 and 40 mg kg-1. Diets containing 40 and 60 mg kg-1 increased muscle glucose levels compared to the control group. Fish-fed diets containing lectin showed reduced muscle glycogen compared to those receiving the control diet. Fish fed 60 mg kg-1 presented lower muscle protein levels than those fed 20 mg kg-1. In vitro tests showed that the hemagglutination activity of lectin was inhibited by d-mannose, d-glucose, and α-methyl-d-mannopyranoside. Thermal treatment at 50–60°C was sufficient to reduce the action of lectin, as well as a pH below and above the 6–7 range. Therefore, the use of P. platycephala meals as a dietary ingredient for tambatinga with no lectin inactivation is not recommended as it can negatively affect the fish’s biochemical parameters and growth. Acid or alkaline solutions can be an alternative for inactivating the protein and improving its use by fish and other animals.

Spexin Modulates the Glucose Homeostasis in Streptozotocin (STZ)-Induced Diabetes in Rat

Background; Despite the various pharmacological agents and insulin treatment, still, there is lack of an effective and therapeutic treatment for diabetes. The present study investigated the possible therapeutic role of SPX in glucose homeostasis both functionally and structurally in streptozotocin (STZ)-induced diabetic rats. Methods; Male Wistar albino rats(n=28) were randomly divided into the control(n=4), diabetes mellitus(DM+saline;1mL/kg), DM+S10(SPX;10 µg/kg/Ml), DM+S30(SPX; 30 µg/kg/mL) and DM+S100 (SPX; 100 µg/kg/mL). Diabetes was induced by administering a single dose of STZ (35mg/kg, i.p. Blood and pancreatic tissue samples were taken for insulin level measurements by ELISA. Liver and muscle tissue samples were taken for glycogen measurement. Histopathological changes in liver, muscle and pancreas tissues were examined. Data were analyzed by ANOVA, and the Mann-Whitney-U test was used for multiple comparisons. Results; STZ-induced diabetes increased blood and urine glucose levels in the DM group as compared to the control group and significantly decreased with 10 mg/kg dose of SPX treatment. Glucose loss rate (K value) in insulin sensitivity measurements was lowered by STZ-induced diabetes (8.030) vs the control group (9.973) witha weak negative correlation (R=-0.1786). Glycogen content in liver and muscle tissues has declined, and SPX limited the decrease in hepatic glycogen levels in the DM+S10 group. SPX treatment reduced the degeneration levels and tissue damage in all tissues. Conclusions; Our findings indicated that SPX has a regulatory role in glucose homeostasis via insulin secretion, glycogen metabolism, and blood glucose regulation in a dose-dependent manner.

Synergic effect of exogenous lactate and caffeine on fat oxidation and hepatic glycogen concentration in resting rats.

Although several physiological roles of lactate have been revealed in the last decades, its effects on energy metabolism and substrate oxidation remain unknown. Therefore, we investigated the effects of lactate on the energy metabolism of resting rats. Male rats were divided into control (Con; distilled water), caffeine (Caf; 10 mg/kg), L-lactate (Lac; 2 g/kg), and lactate-plus-caffeine (Lac+Caf; 2 g/ kg + 10 mg) groups. Following oral administration of supplements, resting energy expenditure (study 1), biochemical blood parameters, and mRNA expression involved in energy metabolism in the soleus muscle were measured at different time points within 120 minutes of administration (study 2). Moreover, glycogen level and Pyruvate dehydrogenase (PDH) activity were measured. Groups did not differ in total energy expenditure throughout the 6 hour post-treatment evaluation. Within the first 4 hours, the Lac and Lac+Caf groups showed higher fat oxidation rates than the Con group (p<0.05). Lactate treatment decreased blood free fatty acid levels (p<0.05) and increased the mRNA expression of fatty acid translocase (FAT/CD36) (p<0.05) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) (p<0.05) in the skeletal muscle. Hepatic glycogen level in the Lac+Caf group was significantly increased (p<0.05). Moreover, after 30 and 120 minutes, PDH activity was significantly higher in lactate-supplemented groups compared to Con group (p<0.05). Our findings showed that Lac+Caf enhanced fat metabolism in the whole body and skeletal muscle while increasing hepatic glycogen concentration and PDH activity. This indicates Lac+Caf can be used as a potential post-workout supplement.

Dandelion (Taraxacum mongolicum Hand.-Mazz.) suppresses the decrease in physical strength and exercise capacity caused by insufficient liver function

In this study, D-galactose was used to establish a model of liver dysfunction caused by oxidative stress in mice, and the effect of dandelion on improving the exercise capacity of mice with liver dysfunction was observed and its mechanism was expounded. This study examined the role and mechanism of dandelion in improving running ability, swimming endurance, blood biochemical indices, histopathological changes, and tissue mRNA expression changes. The animal results showed that dandelion extended the running and swimming time to exhaustion in liver dysfunctional mice, reduced the serum levels of blood urea nitrogen (BUN), blood lactic acid (BLA) and malondialdehyde (MDA) in the liver, and increased hepatic glycogen (HG) and muscle glycogen (MG) levels as well as uperoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Histopathological observations suggested that dandelion alleviated lesions in the liver. The quantitative polymerase chain reaction (qPCR) analysis results showed that dandelion downregulated inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) mRNA expression and neuronal nitric oxide synthase (nNOS), copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and catalase (CAT) expression in the liver and skeletal muscle of the liver-dysfunctional mice. In contrast, dandelion downregulated syncytin-1 mRNA expression in skeletal muscle of mice with a dysregulated liver. The positional analysis showed that the main components of dandelion were gallic acid, protocatechuic acid, chlorogenic acid, caffeic acid, p-coumaric acid, rutin, myricitrin, isoquercitrin, isochlorogenic acid A, and luteolin.

Polysaccharides from apple pomace exhibit anti-fatigue activity through increasing glycogen content.

The polysaccharides were isolated from apple pomace by hot-water extraction, and their anti-fatigue activity was evaluated in C2C12 muscle myoblasts and male Kunming mice. The purified polysaccharides from apple pomace (PAP) have a molecular weight of 1.74 × 105Da and were composed of mannose, rhamnose, glucose, galactose and arabinose. In C2C12 myoblasts, PAP showed no cytotoxicity in the concentrations of 0-300μg/ml. PAP treatment increased the glycogen content, while the ATP content was not affected in C2C12 myoblasts. Further investigation found that the activity and gene expression of glycogen synthase, rather than glycogen phosphorylase, were upregulated by PAP treatment. The studies in vivo showed that PAP treatment did not affect the food intake and weight again in mice. Importantly, PAP prolonged the exhaustive swimming time, increased hepatic and skeletal muscle glycogen levels, and effectively inhibited the accumulation of blood lactic and blood urea nitrogen in mice. Taken together, the results suggested that PAP exhibit anti-fatigue activity in vitro and in vivo through increasing glycogen content.

Exposure to 17α-Ethinylestradiol Results in Differential Susceptibility of Largemouth Bass (Micropterus salmoides) to Bacterial Infection.

Disease outbreaks, skin lesions, mortality events, and reproductive abnormalities have been observed in wild populations of centrarchids. The presence of estrogenic endocrine disrupting compounds (EEDCs) has been implicated as a potential causal factor for these effects. The effects of prior EEDC exposure on immune response were examined in juvenile largemouth bass (Micropterus salmoides) exposed to a potent synthetic estrogen (17α-ethinylestradiol, EE2) at a low (EE2Low, 0.87 ng/L) or high (EE2High, 9.08 ng/L) dose for 4 weeks, followed by transfer to clean water and injection with an LD40 dose of the Gram-negative bacteria Edwardsiella piscicida. Unexpectedly, this prior exposure to EE2High significantly increased survivorship at 10 d post-infection compared to solvent control or EE2Low-exposed, infected fish. Both prior exposure and infection with E. piscicida led to significantly reduced hepatic glycogen levels, indicating a stress response resulting in depletion of energy stores. Additionally, pathway analysis for liver and spleen indicated differentially expressed genes associated with immunometabolic processes in the mock-injected EE2High treatment that could underlie the observed protective effect and metabolic shift in EE2High-infected fish. Our results demonstrate that exposure to a model EEDC alters metabolism and immune function in a fish species that is ecologically and economically important in North America.

Anti-fatigue potential of Pinus koraiensis leaf extract in an acute exercise-treated mouse model

Pinus koraiensis leaf (PKL) extract exerts antihyperlipidemic, antidiabetic, and anticancer effects; however, its anti-fatigue properties have not been elucidated to date. In this study, the anti-fatigue properties of PKL were evaluated by assessing the endurance of mice by a weight-loaded forced swimming (WLFS) and rotarod (RR) tests. Subsequently, various behavioral, biochemical, and physiological parameters were measured. Treatment with PKL decreased hepatic and muscular glycogen levels in mice subjected to WLFS and RR test compared to those in acute exercise-treated (AET) mice. Additionally, plasma levels of stress-related biochemical factors (lactate, lactate dehydrogenase, aminotransferase, aspartate aminotransferase, and blood urea nitrogen) decreased significantly (P < 0.05), whereas the levels of superoxide dismutase and glutathione peroxidase increased. Furthermore, PKL potentially improved mental fatigue by decreasing corticosterone and increasing serotonin levels. PKL increased the expression of phosphorylated cyclic adenosine-3′,5′-monophosphate response element-binding protein and brain-derived neurotrophic factor in the hippocampus. Collectively, the anti-fatigue effects of PKL could be explained by its antioxidant activity, mediating effects on glycogen synthesis, and control over stress. In conclusion, the findings of the present study suggest that PKL is a potential nutraceutical for improving exercise performance and alleviating fatigue.

The Lack of Bmal1, a Core Clock Gene, in the Intestine Decreases Glucose Absorption in Mice.

The circadian clock network is an evolutionarily conserved system that regulates systemic metabolism, such as glucose homeostasis. Intestinal tissue is a pivotal organ for the regulation of glucose metabolism, mainly via glucose absorption into the circulation; however, the significance of the intestinal circadian clock network for glucose metabolism remains largely unclear. We herein utilized a mouse model in which Bmal1, a core clock gene, was deleted in an intestine-specific manner (Bmal1Int-/- mice) and demonstrated a rhythmic expression of Sglt1 with its peak at zeitgeber time (ZT) 10.7 ± 2.8 in control mice, whereas this was lost in Bmal1Int-/- mice. Mechanistically, chromatin immunoprecipitation analysis revealed rhythmic binding of CLOCK to the E-box elements in the Sglt1 gene in control mice; however, this was absent in Bmal1Int-/- mice. Accordingly, SGLT1 protein levels were decreased during the dark phase in Bmal1Int-/- mice and this was associated with impaired glucose absorption, leading to a decline in hepatic glycogen levels at ZT4, which was restored by ingestion of high-sucrose water. Additionally, when mice were starved from ZT0, greater expression of the lipolysis-related gene Pnpla2 was observed in adipose tissue of Bmal1Int-/- mice, and this was not noted when glycogen storage was restored by high-sucrose water prior to fasting, suggesting that higher Pnpla2 expression in Bmal1Int-/- mice was likely caused by lower glycogen storage. These results indicate that disruption of the intestinal circadian clock system impairs glucose absorption in the intestine and affects systemic glucose homeostasis.

Three weeks of time-restricted eating improves glucose homeostasis in adults with type 2 diabetes but does not improve insulin sensitivity: a randomised crossover trial

Aims/hypothesisTime-restricted eating (TRE) is suggested to improve metabolic health by limiting food intake to a defined time window, thereby prolonging the overnight fast. This prolonged fast is expected to lead to a more pronounced depletion of hepatic glycogen stores overnight and might improve insulin sensitivity due to an increased need to replenish nutrient storage. Previous studies showed beneficial metabolic effects of 6–8 h TRE regimens in healthy, overweight adults under controlled conditions. However, the effects of TRE on glucose homeostasis in individuals with type 2 diabetes are unclear. Here, we extensively investigated the effects of TRE on hepatic glycogen levels and insulin sensitivity in individuals with type 2 diabetes.MethodsFourteen adults with type 2 diabetes (BMI 30.5±4.2 kg/m2, HbA1c 46.1±7.2 mmol/mol [6.4±0.7%]) participated in a 3 week TRE (daily food intake within 10 h) vs control (spreading food intake over ≥14 h) regimen in a randomised, crossover trial design. The study was performed at Maastricht University, the Netherlands. Eligibility criteria included diagnosis of type 2 diabetes, intermediate chronotype and absence of medical conditions that could interfere with the study execution and/or outcome. Randomisation was performed by a study-independent investigator, ensuring that an equal amount of participants started with TRE and CON. Due to the nature of the study, neither volunteers nor investigators were blinded to the study interventions. The quality of the data was checked without knowledge on intervention allocation. Hepatic glycogen levels were assessed with 13C-MRS and insulin sensitivity was assessed using a hyperinsulinaemic–euglycaemic two-step clamp. Furthermore, glucose homeostasis was assessed with 24 h continuous glucose monitoring devices. Secondary outcomes included 24 h energy expenditure and substrate oxidation, hepatic lipid content and skeletal muscle mitochondrial capacity.ResultsResults are depicted as mean ± SEM. Hepatic glycogen content was similar between TRE and control condition (0.15±0.01 vs 0.15±0.01 AU, p=0.88). M value was not significantly affected by TRE (19.6±1.8 vs 17.7±1.8 μmol kg−1 min−1 in TRE vs control, respectively, p=0.10). Hepatic and peripheral insulin sensitivity also remained unaffected by TRE (p=0.67 and p=0.25, respectively). Yet, insulin-induced non-oxidative glucose disposal was increased with TRE (non-oxidative glucose disposal 4.3±1.1 vs 1.5±1.7 μmol kg−1 min−1, p=0.04). TRE increased the time spent in the normoglycaemic range (15.1±0.8 vs 12.2±1.1 h per day, p=0.01), and decreased fasting glucose (7.6±0.4 vs 8.6±0.4 mmol/l, p=0.03) and 24 h glucose levels (6.8±0.2 vs 7.6±0.3 mmol/l, p<0.01). Energy expenditure over 24 h was unaffected; nevertheless, TRE decreased 24 h glucose oxidation (260.2±7.6 vs 277.8±10.7 g/day, p=0.04). No adverse events were reported that were related to the interventions.Conclusions/interpretationWe show that a 10 h TRE regimen is a feasible, safe and effective means to improve 24 h glucose homeostasis in free-living adults with type 2 diabetes. However, these changes were not accompanied by changes in insulin sensitivity or hepatic glycogen.Trial registrationClinicalTrials.gov NCT03992248FundingZonMW, 459001013Graphical abstract

Caffeic acid regulates glucose homeostasis and inhibits purinergic and cholinergic activities while abating oxidative stress and dyslipidaemia in fructose-streptozotocin-induced diabetic rats.

The antidiabetic potential of caffeic acid in fructose/streptozotocin-induced type 2 diabetic rats was examined in this study. Male Sprague-Dawley rats were supplied with 10% fructose solution for 14 days followed by an intraperitoneal injection of 40 mg/kg bw streptozotocin to induce type 2 diabetes (T2D). Rats were treated with both low (150 mg/kg bw) and high (300 mg/kg bw) doses of caffeic acid for 5 weeks, while the positive control group was treated with metformin (200 mg/kg bw). Treatment with caffeic acid significantly decreased blood glucose levels and elevated serum insulin levels while improving glucose tolerance, pancreatic β-cell function and morphology. It also led to a significant reduction of serum cholesterol, triglyceride, LDL-cholesterol, ALT, AST, creatinine, urea and uric acid levels, while increasing HDL cholesterol levels. Caffeic acid significantly (P < 0.05) elevated hepatic glycogen level, serum and pancreatic glutathione level, superoxide dismutase and catalase activities with a concomitant decrease in malondialdehyde level, α-amylase, lipase, adenosine triphosphatase (ATPase), ectonucleoside triphosphate diphosphohydrolase (ENTPDase), 5'-nucleotidase (5'-NTD) and acetylcholinesterase activities. The results suggest caffeic acid as a potent natural product with therapeutic effects against T2D. Further molecular and clinical studies are, however, required to ascertain these findings.

Highly Efficient Biotransformation of Notoginsenoside R1 into Ginsenoside Rg1 by Dictyoglomus thermophilum β-xylosidase Xln-DT.

Notoginsenoside R1 and ginsenoside Rg1 are the main active ingredients of Panax notoginseng, exhibiting anti-fatigue, anti-tumor, anti-inflammatory, and other activities. In a previous study, a GH39 β-xylosidase Xln-DT was responsible for the bioconversion of saponin, a natural active substance with a xylose group, with high selectivity for cleaving the outer xylose moiety of notoginsenoside R1 at the C-6 position, producing ginsenoside Rg1 with potent anti-fatigue activity. The optimal bioconversion temperature, pH, and enzyme dosage were obtained by optimizing the transformation conditions. Under optimal conditions (pH 6.0, 75°C, enzyme dosage 1.0 U/ml), 1.0 g/l of notoginsenoside R1 was converted into 0.86 g/l of ginsenoside Rg1 within 30 min, with a molar conversion rate of approximately 100%. Furthermore, the in vivo anti-fatigue activity of notoginsenoside R1 and ginsenoside Rg1 were compared using a suitable rat model. Compared with the control group, the forced swimming time to exhaustion was prolonged in mice by 17.3% in the Rg1 high group (20 mg/kg·d). Additionally, the levels of hepatic glycogen (69.9-83.3% increase) and muscle glycogen (36.9-93.6% increase) were increased. In the Rg1 group, hemoglobin levels were also distinctly increased by treatment concentrations. Our findings indicate that treatment with ginsenoside Rg1 enhances the anti-fatigue effects. In this study, we reveal a GH39 β-xylosidase displaying excellent hydrolytic activity to produce ginsenoside Rg1 in the pharmaceutical and food industries.

On the Utilization of Dietary Glycerol in Carnivorous Fish - Part I: Insights Into Hepatic Carbohydrate Metabolism of Juvenile Rainbow Trout (Oncorhynchus mykiss) and European Seabass (Dicentrarchus labrax)

Glycerol is a 3-carbon sugar alcohol successfully employed as an alternative feed ingredient for land-farmed animals and more recently for farmed fish. While most studies address zootechnical performance, few have delved into the metabolic utilization of dietary glycerol. A growth trial was performed using diets with increasing levels of glycerol (0, 2.5 and 5%) on two relevant species for aquaculture: rainbow trout (8-week trial; 3 tank per diet/25 fish per tank, on a 15 ± 1°C flow-through freshwater system); and European seabass (6-week trial; 5 tank per diet/6-8 fish per tank on a 21°C indoor saltwater RAS system). After this period, fish were subjected to a metabolic trial consisting of a 6-day residence in deuterated water (2H2O). Measurements of blood glucose and hepatic glycogen 2H-enrichments through Nuclear Magnetic Resonance, complemented by mRNA levels of key-enzymes for intermediary metabolism were used to evaluate the catabolic pathways of dietary glycerol. Dietary glycerol had no impact on plasma glucose, but hepatic glycogen levels increased significantly with increasing dietary glycerol levels in both species. While trout was able to regulate circulating glycerol plasma, seabass presented elevated levels on the glycerol-supplemented diets. Despite revealing some significant differences between sampling time (6 and 24 h), none of the enzymes’ mRNA levels responded to the dietary treatment. In trout, the main source of blood glucose was not labeled with 2H (~60%, likely from diet) while other contributors did not differ with glycerol supplementation. In seabass, the unlabeled contribution was approximately half of that observed in trout (~30%), accompanied by a significant increase of gluconeogenic contributions at the triose-phosphate level to the blood glucose with increasing dietary glycerol. In trout, labeling from 2H2O into hepatic glycogen revealed significant differences, with the contribution from the indirect pathway at the triose-phosphate level increasing with increased dietary glycerol. No such differences were found in seabass’ glycogen pool. These findings suggest that fish species are able to retain, catabolize glycerol and incorporate it into carbohydrates. The gluconeogenic utilization of exogenous glycerol differed between species and affected the synthesis of hepatic glycogen in trout and the appearance of blood glucose in seabass.

A Novel Formula Comprising Wolfberry, Figs, White Lentils, Raspberries, and Maca (WFWRM) Induced Antifatigue Effects in a Forced Exercise Mouse Model.

Long-term body fatigue poses a threat to human health. To explore novel sources of antifatigue medicine and food, we developed a novel formula composed of wolfberry, figs, white lentils, raspberries, and maca (WFWRM) according to the theory of traditional Chinese medicine. In this study, we explored whether the administration of the WFWRM relieves fatigue. Thirty male Kunming mice were divided into three groups, which received either intragastric administration of saline, vitamin C (100 mg/kg), or WFWRM (1.00 g/kg) every day. After 30 days of treatment, all mice exhaustively performed weight-bearing swimming. Another ten mice that did not perform swimming were treated with saline for 30 days and used as sedentary control. The antifatigue effect and biochemical oxidation phenomena were assessed in the exercise-exhausted model and sedentary controls. The histopathological changes in the liver and kidney tissues of mice were observed by performing hematoxylin-eosin (HE) staining. After 30 days of oral administration, the liver and kidney tissues of mice were healthy and show no pathological changes. Compared to the fatigue model group, WFWRM significantly increased the rota-rod time of the mice. Also, the concentrations of lactic acid (LA), blood urea nitrogen (BUN), creatine kinase (CK), and lactate dehydrogenase (LDH) in the WFWRM group significantly reduced. On the contrary, the levels of hepatic glycogen (LG), muscle glycogen (MG), and serum glucose (GLU) increased in the WFWRM group. Besides, WFWRM markedly reduced the levels of malondialdehyde (MDA) but increased the levels of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD). Pearson correlation analysis indicated that the concentrations of the sources of energy (LG, MG, and GLU) significantly correlated with those of metabolites (BLA, BUN, CK, and LDH) and antioxidant levels (SOD, GSH-PX, and MDA). Overall, our results suggested that the supplementation of WFWRM could improve exercise capacity and relieve fatigue probably by normalizing energy metabolism and attenuating oxidation.

Anti-Fatigue and Exercise Performance Improvement Effect of Glossogyne tenuifolia Extract in Mice.

Glossogyne tenuifolia (GT) is a native perennial plant growing across the coastline areas in Taiwan. The current study aimed to examine the efficacy of GT extract in ameliorating physical fatigue during exercise and increasing exercise performance. Fifty male Institute of Cancer Research (ICR) mice were randomly segregated into five groups (n = 10) to GT extract orally for 4 weeks, at different concentrations (50, 100, 250, and 500 mg/kg BW/day): LGT 1X, MGT 2X, HGT 5X, and HGT 10X groups. Forelimb grip strength, endurance swimming time, serum biochemical marker levels, blood lipid profile and histological analysis of various organs were performed to assess the anti-fatigue effect and exercise performance of GT extract. The forelimb-grips strength and endurance-swimming time of GT-administered mice were increased significantly in a dose-dependent manner when compared to the control. Serum glucose, creatine kinase, and lactate levels were increased significantly in the HGT 10X group. Liver marker serum glutamic-oxaloacetic transaminase (GOT) was increased in the HGT 5X and HGT 10X groups, whereas Serum Glutamic Pyruvic Transaminase (GPT) was not altered. Renal markers, creatinine and uric acid levels, were not altered. Muscle and hepatic glycogen levels, which are essential for energy sources during exercise, were also significantly increased in a dose-dependent manner in all GT extract groups. No visible histological aberrations were observed in the vital organs after GT extract administration. The supplementation with GT extract could have beneficial effects on exercise performance and anti-fatigue function without toxicity at a higher dose.

Clozapine Induced Disturbances in Hepatic Glucose Metabolism: The Potential Role of PGRMC1 Signaling.

Newly emerging evidence has implicated that progesterone receptor component 1 (PGRMC1) plays a novel role not only in the lipid disturbance induced by atypical antipsychotic drugs (AAPD) but also in the deterioration of glucose homoeostasis induced by clozapine (CLZ) treatment. The present study aimed to investigate the role of PGRMC1 signaling on hepatic gluconeogenesis and glycogenesis in male rats following CLZ treatment (20 mg/kg daily for 4 weeks). Recombinant adeno-associated viruses (AAV) were constructed for the knockdown or overexpression of hepatic PGRMC1. Meanwhile, AG205, the specific inhibitor of PGRMC1 was also used for functional validation of PGRMC1. Hepatic protein expressions were measured by western blotting. Meanwhile, plasma glucose, insulin and glucagon, HbA1c and hepatic glycogen were also determined by assay kits. Additionally, concentrations of progesterone (PROG) in plasma, liver and adrenal gland were measured by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Our study demonstrated that CLZ promoted the process of gluconeogenesis and repressed glycogenesis, respectively mediated by PI3K-Akt-FOXO1 and GSK3β signaling via inhibition of PGRMC1-EGFR/GLP1R in rat liver, along with an increase in fasting blood glucose, HbA1c levels and a decrease in insulin and hepatic glycogen levels. Furthermore, through PGRMC1-EGFR/GLP1R-PI3K-Akt pathway, knockdown or inhibition (by AG205) of PGRMC1 mimics, whereas its overexpression moderately alleviates CLZ-induced glucose disturbances. Potentially, the PGRMC1 target may be regarded as a novel therapeutic strategy for AAPD-induced hepatic glucose metabolism disorder.

Effects of blood loss on organ attenuation on postmortem CT and organ weight at autopsy

BackgroundCases of external hemorrhage are difficult to recognize on postmortem computed tomography (PMCT).PurposeTo investigate the effects of blood loss on CT attenuation of the spleen, liver, kidneys, and lungs on PMCT and to assess the relationship between blood loss and organ weight.MethodsA total of 125 cases with blood loss were sex- and age-matched to 125 control cases without blood loss. Individual organ attenuation was measured on transverse CT images. Organ weights of the liver, spleen, kidneys, and lung were extracted from the autopsy protocols.ResultsOrgan weight was significantly lower in cases with blood loss (lung 30%, spleen 28%, kidneys 14%, liver 18%) than in controls. CT attenuation of the lungs was significantly lower (30%) in cases with blood loss than in controls. CT attenuation of the spleen and kidneys did not significantly differ between cases and controls. CT attenuation of the liver was significantly higher (25%) in cases with blood loss than in controls.ConclusionBlood loss decreases organ weight and CT attenuation of the lungs but appears to have no significant effect on CT attenuation of the spleen and kidneys. The increased liver attenuation in cases with blood loss compared to controls was an unexpected finding and remains challenging to explain. One probable interpretation refers to different levels of hepatic glycogen; however, further work is warranted to substantiate this hypothesis.

Role of Epigallocatechin Gallate in Glucose, Lipid, and Protein Metabolism and L-Theanine in the Metabolism-Regulatory Effects of Epigallocatechin Gallate.

Epigallocatechin gallate (EGCG) and L-theanine (LTA) are important bioactive components in tea that have shown promising effects on nutrient metabolism. However, whether EGCG alone or combined with LTA can regulate the glucose, lipid, and protein metabolism of healthy rats remains unclear. Therefore, we treated healthy rats with EGCG or the combination of EGCG and LTA (EGCG+LTA) to investigate the effects of EGCG on nutrient metabolism and the role of LTA in the metabolism-regulatory effects of EGCG. The results showed that compared with the control group, EGCG activated insulin and AMP-activated protein kinase (AMPK) signals, thus regulating glucose, lipid, and protein metabolism. Compared with EGCG, EGCG+LTA enhanced hepatic and muscle glycogen levels and suppressed phosphorylation of AMPK, glycogen synthase 2, mammalian target of rapamycin, and ribosomal protein S6 kinase. In addition, EGCG+LTA inhibited the expression of liver kinase B1, insulin receptor and insulin receptor substrate, and promoted the phosphorylation level of acetyl-CoA carboxylase. Furthermore, both EGCG and EGCG+LTA were harmless for young rats. In conclusion, EGCG activated AMPK and insulin pathways, thereby promoting glycolysis, glycogen, and protein synthesis and inhibiting fatty acid (FA) and cholesterol synthesis. However, LTA cooperated with EGCG to promote glycogen metabolism and suppressed the effect EGCG on FA and protein synthesis via AMPK signals.

Vanillin improves glucose homeostasis and modulates metabolic activities linked to type 2 diabetes in fructose–streptozotocin induced diabetic rats

Objective This study investigated the antidiabetic effect of vanillin using in vitro, in silico, and in vivo experimental models. Methodology Type 2 diabetes (T2D) was induced in male Sprague-Dawley (SD) rats using fructose–streptozotocin (STZ), then orally administered low (150 mg/kg bodyweight) or high (300 mg/kg bodyweight) dose of vanillin for 5 weeks intervention period. Results Vanillin suppressed the levels of blood glucose, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-c), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, uric acid, when elevated serum insulin, HDL-cholesterol, and concomitantly improved pancreatic β-cell function, glucose tolerance, and pancreatic morphology. It also elevated both serum and pancreatic tissue GSH level, SOD and catalase activities, and hepatic glycogen level, while depleting malondialdehyde level, α-amylase, lipase, acetylcholinesterase, ATPase, ENTPDase and 5′-nucleotidase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glycogen phosphorylase activities. Conclusions The results indicate the potent antidiabetic effect of vanillin against T2D and its associated complications.

Evaluation of toxicity, nephroprotective and hepatoprotective activities of Argan oil on CCl4-induced nephrotoxicity and hepatotoxicity in Wistar rats

In traditional therapy, Argania spinosa L. seeds oil used as a nephroprotective and hepatoprotective agent. The present work aims to investigate the acute toxicity of unroasted Argan oil, and studied the nephroprotective and the hepatoprotective activity of both oils Roasted (Roil) and unroasted Argan oil (UnRoil) on CCl 4 -induced liver and kidney damages in Wistar rats. Animals were divided into five equal groups; Control and CCl 4 groups are received only distilled water (10 mL/Kg/day). Control positive group received 50 mg/Kg/day of Silymarin. Roil and UnRoil groups treated with 2 mL/Kg/day of Roil and UnRoil. One week after each pretreatment, the rats are injected intraperitoneally with 1 mL/kg/week of CCl 4 . The treatment has lasted for 15 days. The body weight, urinary volume, water, and food intake were measured at the end of the treatment. Then, the animals are sacrificed; the blood and the liver samples were collected for determining the liver weight ratio and biochemical parameters. UnRoil did not show any sign of toxicity up to 5 mL/Kg. In Roil and UnRoil groups the water intake, ALT, AST, total and direct bilirubin, triglycerides, LDL, plasmatic creatinine, urea, uric acid, and MDA levels are reduced significantly as compared with the CCl 4 group. However, body weight,liver weight ratio, food intake, urine urea, urinary creatinine, hepatic glycogen, and GSH levels showed a significant increase compared to the CCl 4 group. Roil and UnRoil showed important nephroprotective and hepatoprotective effects against CCl 4 . Although, the roasting process does not influence the ability of Argan seed oils towards these activities. Keywords: