Liver Glycogen Levels Research Articles

Ren-Shen-Bu-Qi decoction alleviates exercise fatigue through activating PI3K/AKT/Nrf2 pathway in mice.

Fatigue is a prevalent issue that can lead individuals to a sub-health condition, impacting their work efficiency and quality of life. There are limited effective treatment options available for fatigue. Ren-Shen-Bu-Qi decoction (RSBQD) is a proprietary herbal remedy that is designed to address fatigue. However, the specific pharmacological mechanisms and basis of RSBQD are not yet fully understood. This study aimed to investigate the pharmacological effects and mechanisms of RSBQD in a mouse model of exercise fatigue. UPLC-Q-Orbitrap HRMS was used to analyze the chemical composition of RSBQD. The pharmacological basis and molecular mechanism of RSBQD on exercise fatigue were predicted using network pharmacology analysis. Subsequently, an exercise fatigue mouse model was established and used to analysis the effects of RSBQD. The potential mechanisms were verified by hematoxylin-eosin (HE) staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking. The results showed that 88 main components of RSBQD were identified, which have mainly belonged to flavonoids and carboxylic acid compounds. The network pharmacology analysis indicated that RSBQD ameliorate fatigue through PI3K/AKT signaling pathway. Notably, RSBQD prolonged the swimming time and diminished body weight loss of exercise fatigue mice (P < 0.05). Meanwhile, RSBQD significantly alleviated the injury of liver and kidney induced by exhaustive exercise, and decreasing the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and BUN levels (P < 0.05). In addition, RSBQD was found could relieve exercise fatigue by decreasing the content of creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid (LA), but increasing the blood glucose (GLU) and liver glycogen (HG) levels (P < 0.05). RSBQD also significantly increased the hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) but decreased hepatic malondialdehyde (MDA) levels. Moreover, RSBQD was able to upregulate protein level of activated Nrf2 and PI3K/AKT signaling pathways. RSBQD mitigates exercise fatigue by reversing metabolic changes and reducing oxidative damage through the PI3K/AKT/Nrf2 signaling pathway. This study offers pharmacological support for the utilization of RSBQD in exercise fatigue treatment.

Establishing a Female Animal Model of Prediabetes Using a High-Carbohydrate, High-Fat Diet

Prediabetes is a condition that often precedes the onset of type 2 diabetes and is characterized by moderate levels of insulin resistance. This condition is well established in male animal models for diabetes; however, few female models exist. There is accumulating evidence that sex variations affect the pathogenesis, treatment, and consequences of numerous diseases, such as type 2 diabetes. Therefore, we sought to develop a diet-induced prediabetic female animal model to better understand prediabetes development and its effects in females. Female Sprague Dawley rats were randomly allocated to one of two groups: the standard diet (SD) group fed a standard diet with normal drinking water, and the high-carbohydrate, high-fat (HCHF) group fed a high-carbohydrate and high-fat diet with drinking water supplemented with fructose. During induction, we measured food intake, body weight, body mass index (BMI), and oral glucose tolerance response (OGT). After the induction period, biochemical analyses were conducted to assess the levels of plasma leptin, ghrelin, insulin, and glycated hemoglobin (HbA1c). Glycogen concentrations were quantified in the liver and skeletal muscles. The HCHF diet-fed group presented higher body weight gain, food intake, and BMI levels, which were accompanied by elevated plasma insulin, ghrelin, and liver and skeletal muscle glycogen levels compared to the SD-fed group. In the HCHF diet-fed group, the HOMA-IR was above 1.9, suggesting the presence of moderate levels of insulin resistance. The OGT response was significantly higher in the HCHF-fed group versus the SD-fed group, suggesting impaired glucose tolerance, thus displaying the signs and symptoms of prediabetes. The HCHF diet with fructose led to the induction of prediabetes in female Sprague Dawley rats. This model could be used to investigate and outline the pathophysiological complications associated with prediabetes in females as a result of the prolonged ingestion of a high carbohydrate, high-fat diet with fructose. The development of this model could also serve as an effort to further bridge the gap regarding the inclusion of females in biomedical research, thus providing advancements in deriving better, specified treatment strategies for women.

Preparation, Characterization, and In Vivo Anti‐Fatigue Evaluation of Octacosanol Nanoemulsions

ABSTRACTOctacosanol (OCT) is a natural aliphatic alcohol with multiple activities, but the poor solubility limited its wide applications. In this study, OCT nanoemulsions were prepared by a low‐energy emulsification method. The particle size, polydispersity index, and Zeta potential of OCT nanoemulsions were 12.59 nm, 0.131, and −10.54 mV, respectively. OCT nanoemulsions could keep stable up to 180 days at 4°C with particle size ranging from 12.61 to 16.57 nm. In addition, OCT nanoemulsions could remain stable upon exposure to autoclaving, acid–base (pH 2–8), freeze–thaw, ultraviolet (UV) irradiation, and low concentrations of ions. The grid test time and exhaustive swimming time of the OCT nanoemulsions group increased by 70% and 40% compared with the exercise control group, indicating that OCT nanoemulsions could enhance the muscle strength and endurance performance of mice. Compared with the exercise control group, the muscle glycogen, liver glycogen, superoxide dismutase (SOD), and glutathione peroxidase (GSH‐Px) levels of the OCT nanoemulsions group increased by 97%, 45%, 62%, and 20%, while the blood lactic acid and lactate dehydrogenase levels of the OCT nanoemulsions group decreased by 33% and 22%, respectively, suggesting that OCT nanoemulsions had the anti‐fatigue effect. Hematoxylin and eosin staining showed that OCT nanoemulsions could repair muscle damages induced by excessive exercise. These findings could pave the way for the development of OCT nanoemulsions with high stability and anti‐fatigue potential.

Therapeutic Effects of Proanthocyanidins on Diabetic Erectile Dysfunction in Rats.

The rising occurrence of erectile dysfunction related to diabetes mellitus (DMED) has led to the creation of new medications. Proanthocyanidins (PROs) is a potential agent for DMED. In this study, the DMED rat model was established using streptozotocin (STZ) and erectile function was assessed using apomorphine (APO) in rats. Following this, the rats were subjected to oral treatment with PRO. Then, we evaluated the influence of PROs on DMED rats. The findings suggest that PROs significantly enhance erectile function in DMED rats. PROs modulated glucose and lipid metabolism in DMED rats by decreasing blood glucose and lipid levels while increasing liver glycogen and serum insulin levels. Furthermore, PROs enhanced vascular endothelial function in DMED rats by augmenting nitric oxide (NO) levels and reducing the levels of endothelin-1 (ET-1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Additionally, PROs have been shown to elevate testosterone (T) levels, mitigate pathological testicular damage, and enhance sperm concentration and survival rates. Finally, the core targets were screened using network pharmacology, followed by validation through molecular docking, enzyme-linked immunoassay (ELISA), and real-time PCR methodologies. Our findings imply that PROs may treat DMED by elevating AKT1 levels while concurrently diminishing CASP3 levels, thereby effectively regulating the PI3K-Akt signaling pathway. Overall, these results support using PROs as a potential candidate for the treatment of DMED.

The Antioxidant and Anti-Fatigue Effects of Rare Ginsenosides and γ-Aminobutyric Acid in Fermented Ginseng and Germinated Brown Rice Puree.

γ-aminobutyric acid (GABA) and rare ginsenosides are good antioxidant and anti-fatigue active components that can be enriched via probiotic fermentation. In this study, ginseng and germinated brown rice were used as raw materials to produce six fermented purees using fermentation and non-fermentation technology. We tested the chemical composition of the purees and found that the content of GABA and rare ginsenoside (Rh4, Rg3, and CK) in the puree made of ginseng and germinated brown rice (FGB) increased significantly after fermentation. The antioxidant activity of the six purees was determined using cell-free experiments, and it was found that FGB had better ferric-ion-reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging rates, exhibiting better antioxidant effects. We then evaluated the antioxidant effect of FGB in HepG2 cells induced by H2O2 and found that FGB can reduce the generation of reactive oxygen species (ROS) in HepG2 cells and increase the membrane potential level, thereby improving oxidative damage in these cells. In vivo experiments also showed that FGB has good antioxidant and anti-fatigue activities, which can prolong the exhaustive swimming time of mice and reduce the accumulation of metabolites, and is accompanied by a corresponding increase in liver glycogen and muscle glycogen levels as well as superoxide dismutase and lactate dehydrogenase activities. Finally, we believe that the substances with good antioxidant and anti-fatigue activity found in FGB are derived from co-fermented enriched GABA and rare ginsenosides.

Non-human primate model of long-COVID identifies immune associates of hyperglycemia

Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are manifestations of the post-acute sequelae of SARS-CoV-2. Our understanding of metabolic decline after acute COVID-19 remains unclear due to the lack of animal models. Here, we report a non-human primate model of metabolic post-acute sequelae of SARS-CoV-2 using SARS-CoV-2 infected African green monkeys. Using this model, we identify a dysregulated blood chemokine signature during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. Hyperglycemia also correlates with liver glycogen levels, but there is no evidence of substantial long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the African green monkey model exhibits important similarities to humans and can be utilized to assess therapeutic candidates to combat COVID-related metabolic defects.

Hypoglycemic effect of orally administered resistant dextrins prepared with different acids on type 2 diabetes mice induced by high-fat diet and streptozotocin

A comparative study was performed to investigate the physicochemical properties and protective effects of hydrochloric acid-resistant dextrin (H-RD), citric acid-resistant dextrin (C-RD) and tartaric acid-resistant dextrin (T-RD) on the metabolic disorders and intestinal microbiota for type 2 diabetes mellitus (T2DM) mice. T-RD had the minimum molecular weight, with the highest short chain (DP 6–12) proportion and resistant starch content. After 4-week intervention with the three resistant dextrins, the body weight and fasting blood glucose of T2DM mice were improved significantly, accompanied by the reduction of serum indexes (TG, TC, LDL-C, ALT, AST, CRE, BUN, FINS, and GSP), but the serum HDL-C and liver glycogen levels increased. Among the three RDs intervention groups, T-RD showed the most significant improvement, followed by C-RD and finally H-RD. The 16 s rDNA results indicated that oral administration of resistant dextrins favored the proliferation of specific gut microbiota, including Faecalibaculum, Parabacteroides and Dubosiella, and reduced the ratio of Firmicutes/Bacteroidota, which is beneficial for reducing insulin resistance. Herein, the findings supported that the resistant dextrins exhibited a remission effect on T2DM, providing a basis for the development of functional food adjuvants for T2DM treatment.

Hesperetin-loaded chitosan nanoparticles ameliorate hyperglycemia by regulating key enzymes of carbohydrate metabolism in a diabetic rat model.

The study aimed to investigate the potential of hesperetin-loaded chitosan nanoparticles (HSPCNPs) in alleviating hyperglycemia by modulating key enzymes in diabetic rats. Chitosan nanoparticles loaded with hesperetin were prepared using the ionic gelation method and characterized with Electron microscope (SEM), zeta potential, particle size analysis, Fourier-transform infrared (FT-IR), Energy dispersive spectroscopy (EDS) and Encapsulation efficiency and Loading efficiency. To induce diabetes, rats were fed a high-fat beef tallow diet for 28 days, then given a single dose of streptozotocin (STZ) at 35 mg/kg b.w in 0.1 M citrate buffer (pH 4.0). Rats were treated with HSPCNPs at doses of 10, 20, and 40 mg/kg b.w. The analyzed parameters included body weight, food and water intake, plasma glucose and insulin, liver and skeletal muscle glycogen levels, and carbohydrate metabolism. SEM imaging revealed dimensions between 124.2and 251.6 nm and a mean particle size of 145.0 nm. FT-IR analysis confirmed the presence of functional groups in the chitosan nanoparticles, and the zeta potential was 35.5 mV. HSPCNP 40 mg/kg b.w significantly (p < 0.05) reduced blood glucose levels and glycosylated hemoglobin, improving body weight, food intake, and reducing water intake. In diabetic rats, enzymes for carbohydrate metabolism like fructose 1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose 6-phosphatase are evaluated in the liver, while glucose 6 phosphate dehydrogenase and hexokinase activity were significantly lower. Additionally, plasma insulin levels increased, indicating enhanced insulin sensitivity. The results show that HSPCNPs at 40 mg/kg b.w. ameliorate hyperglycemiato provide robust protection against diabetic complications and significantly improve metabolic health.

The Effects of Long-Term High Fat and/or High Sugar Feeding on Sources of Postprandial Hepatic Glycogen and Triglyceride Synthesis in Mice.

In MASLD (formerly called NAFLD) mouse models, oversupply of dietary fat and sugar is more lipogenic than either nutrient alone. Fatty acids suppress de novo lipogenesis (DNL) from sugars, while DNL inhibits fatty acid oxidation. How such factors interact to impact hepatic triglyceride levels are incompletely understood. Using deuterated water, we measured DNL in mice fed 18-weeks with standard chow (SC), SC supplemented with 55/45-fructose/glucose in the drinking water at 30% (w/v) (HS), high-fat chow (HF), and HF with HS supplementation (HFHS). Liver glycogen levels and its sources were also measured. For HS and HFHS mice, pentose phosphate (PP) fluxes and fructose contributions to DNL and glycogen were measured using [U-13C]fructose. The lipogenic diets caused significantly higher liver triglyceride levels compared to SC. DNL rates were suppressed in HF compared to SC and were partially restored in HFHS but supplied a minority of the additional triglyceride in HFHS compared to HF. Fructose contributed a significantly greater fraction of newly synthesized saturated fatty acids compared to oleic acid in both HS and HFHS. Glycogen levels were not different between diets, but significant differences in Direct and Indirect pathway contributions to glycogen synthesis were found. PP fluxes were similar in HS and HFHS mice and were insufficient to account for DNL reducing equivalents. Despite amplifying the lipogenic effects of fat, the fact that sugar-activated DNL per se barely contributes suggests that its role is likely more relevant in the inhibition of fatty acid oxidation. Fructose promotes lipogenesis of saturated over unsaturated fatty acids and contributes to maintenance of glycogen levels. PP fluxes associated with sugar conversion to fat account for a minor fraction of DNL reducing equivalents.

Polysaccharides from Artemisia argyi leaves: Environmentally friendly ultrasound-assisted extraction and antifatigue activities

Artemisia argyi leaf polysaccharide (AALPs) were prepared through ultrasound-assisted extraction (UAE), and their antifatigue activities were evaluated. Extraction was optimized using response surface methodology (RSM), which yielded the following optimal UAE conditions: ultrasonication power of 300 W, extraction temperature of 51 °C, liquid:solid ratio of 20 mL/g, and ultrasonication time of 47 mins. The above optimal conditions resulted in the maximum extraction rate of 10.49 %. Compared with hot water extraction (HWE), UAE supported higher yields and total sugar, uronic acid, and sulfate contents of AALPs. Meanwhile, AALP prepared through UAE (AALP-U) exhibited higher stability due to its smaller particle size and higher absolute value of zeta potential than AALP prepared through HWE (AALP-H). In addition, AALP-U demonstrated stronger antioxidant activity than AALP-H. In forced swimming tests on mice, AALP-U could significantly prolong swimming time with a dose-dependent effect, increase liver and muscle glycogen levels, and improve other biochemical indices, thus showing great potential for application in functional food.

Use of Bacillus subtilis multiplicate in the water used for biofloc formation: Growth, hemato-biochemistry, intestinal bacteria colonies, and bacterial resistance evaluations of Nile tilapia

Probiotics in the biofloc technology (BFT) system improve fish growth and immune response and promote a favorable intestinal microbiota balance. This study aimed to investigate the growth, hemato-biochemical parameters, bacterial resistance, and the number of intestinal bacteria colonies of Nile tilapia (6.23 g) reared in the BFT system with graded levels of Bacillus subtilis multiplicate (BSM) in the water. The multiplication of these microorganisms was performed in a biofactory. Fish were distributed into four different groups with graded BSM concentrations in the water of 0.00, 0.25, 0.50, and 0.75% (or 0; 750; 1500; and 2250 mL; called BSM0 (control), BSM25, BSM50, and BSM75, respectively). The experimental procedure had 45 days for growth performance evaluations and seven additional days of bacterial challenge with Aeromonas hydrophila. The experimental design was randomized into four treatments in triplicate (n = 20 fish per tank; initial stocking density of 0.50 kg m−3). Survival was 100% before and after the bacterial challenge. Increasing BSM in the BFT system had a positive linear effect on nitrite, nitrate, settled solids, hemoglobin, and hematimetric indices. BSM50 showed the highest specific growth rate, weight gain, intestinal total bacteria, and B. subtilis counts and the lowest feed conversion rate. In BSM50 and BSM75, liver glycogen levels and aspartate aminotransferase (AST) activity were higher and lower, respectively, than in the other treatments. Plasma total cholesterol, total proteins, albumin, and skin mucus total proteins and albumin were highest in BSM25. After the bacterial challenge, the number of lesions was lower in BSM75 than in the control group. In conclusion, we recommended BSM50 because it increased the growth performance and bacterial colonization in the intestine. It also decreased liver AST activity in Nile tilapia reared in the BFT system without compromising water quality and hematological and plasmatic parameters.

Hovenia dulcis Fruit Peduncle Polysaccharides Reduce Intestinal Dysbiosis and Hepatic Fatty Acid Metabolism Disorders in Alcohol-Exposed Mice.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) have the potential to alleviate alcoholic liver injury and play essential roles in treating alcohol-exposed liver disease; however, the hepatoprotective effects and mechanisms remain elusive. In this study, we investigated the hepatoprotective effects of HDPs and their potential mechanisms in alcohol-exposed mice through liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels, and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. When applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria, significant increases in Firmicutes at the phylum level, increased Lactobacillus abundance, and decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid and glycerophospholipid metabolism, and identified two important metabolites-C00157 (phosphatidylcholine, a glycerophospholipid plays a central role in energy production) and C04230 (1-Acyl-sn-glycero-3-phosphocholine, a lysophospholipid involved in the breakdown of phospholipids)-involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs have a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Chronic unpredictable mild stress increases serum aldosterone without affecting corticosterone levels and induces hepatic steatosis and renal injury in young adult male rats.

Stress is often associated with anxiety and depressive symptoms in adolescents. Stress is associated with components of metabolic syndrome and inflammation. The present study hypothesizes that aldosterone, more than corticosterone, promotes chronic stress-hepatic steatosis and fibrosis, as well as renal inflammation and fibrosis in young adult rats. Thirty-two young adult male Wistar rats of 51 days old were divided into four groups (n = 8 per group): Control (C), chronic unpredictable mild stress (CUMS), control plus vehicle (C plus veh), CUMS plus eplerenone, a selective aldosterone blocker (CUMS plus EP). On postnatal day 51, eplerenone was administered orally through a gastric tube two hours before the start of the stress test. The CUMS paradigm was administered once daily at different times, with no repetition of the stressor sequence for four weeks. Renal inflammation and fibrosis were measured, as well as liver glycogen, triacylglycerol, and fibrosis levels. The serum concentrations of corticosterone, aldosterone, sodium, and creatinine were measured in urine and serum. The CUMS group showed a high level of serum aldosterone without affecting the level of corticosterone, increased urinary sodium, tubular atrophy, glomerular sclerosis, the presence of inflammation, and fibrosis, without affecting creatinine, increased glycogen content, triacylglycerol, and moderate fibrosis in the liver, and treatment with eplerenone prevented the inflammation, fibrosis, glycogen, and triacylglycerol. Our results show that chronic stress-induced aldosterone promotes hepatic steatosis and renal injury more than corticosterone. The prevention by eplerenone supports our hypothesis.

Comparative effects of pravastatin and rosuvastatin on carbohydrate metabolism in an experimental diabetic rat model.

Statin treatment may increase the risk of diabetes; there is insufficient data on how statins affect glucose regulation and glycemic control and the effects of statins on liver enzymes related to carbohydrate metabolism have not been fully studied. Therefore, we aimed to compare the effects of the statin derivatives, pravastatin, and rosuvastatin, on carbohydrate metabolism in an experimental diabetic rat model. Female Wistar albino rats were used and diabetes was induced by intraperitoneal injection of streptozotocin. Thereafter, 10 and 20 mg kg-1 day-1 doses of both pravastatin and rosuvastatin were administered by oral gavage to the diabetic rats for 8 weeks. At the end of the experiment, body masses, the levels of fasting blood glucose, serum insulin, insulin resistance (HOMA-IR), liver glycogen, and liver enzymes related to carbohydrate metabolism were measured. Both doses of pravastatin significantly in creased the body mass in diabetic rats, however, rosuvastatin, especially at the dose of 20 mg kg-1 day-1 reduced the body mass signi ficantly. Pravastatin, especially at a dose of 20 mg kg-1 day-1, caused significant increases in liver glycogen synthase and glucose 6-phosphate dehydrogenase levels but significant decreases in the levels of glycogen phosphorylase, lactate dehydrogenase, and glucose-6-phosphatase. Hence, pravastatin partially ameliorated the adverse changes in liver enzymes caused by diabetes and, especially at the dose of 20 mg kg-1 day-1, reduced the fasting blood glucose level and increased the liver glycogen content. However, rosuvastatin, especially at the dose of 20 mg kg-1 day-1, significantly reduced the liver glycogen synthase and pyruvate kinase levels, but increased the glycogen phosphorylase level in diabetic rats. Rosuvastatin, 20 mg kg-1 day-1 dose, caused significant decreases in the body mass and the liver glycogen content of diabetic rats. It can be concluded that pravastatin, especially at the dose of 20 mg kg-1 day-1 is more effective in ameliorating the negative effects of diabetes by modulating carbohydrate metabolism.

Sonchus maritimus Extract-Loaded Niosomes Bioconjugated by Linoleic Acid in Hepatic Encephalopathy Induced by High-Fructose Diet in Albino Wistar Rats.

One of the major roles of nanotechnology in the pharmaceutical field is to provide a facility to improve drug delivery systems and design smart nanocarriers with the potential to deliver specific biomolecules to the target site for treatment. This study evaluated Sonchus maritimus-loaded niosomes (SmE-N) in hepatic encephalopathy induced by a high-fructose diet (HFD) in rats. High-performance liquid chromatography (HPLC) analysis of Sonchus maritimus extracts (SmE), the synthesis of niosomes, and their characterization were performed. For the in vivo study, 24 male rats were haphazardly divided into 4 groups (n=6) control, HFD (35%), HFD+SmE-N (50 mg/kg/day), and HFD+metformin (50 mg/kg/day). Clinical behaviors and biological markers were assessed for all groups. The in vitro results of the chromatographic analysis revealed that Sonchus maritimus contains important phenolic acids, including gallic acid, vanillic acid, chlorogenic acid, and caffeic acid, as well as diverse flavonoids, including quercetin, rutin, and naringin bioactive compounds. The niosome formulation, characterized by the encapsulation efficiency of SmE, reached up to 61.40%. The in vivo results of the HFD showed a significant change in behavior parameters, liver glycogen, transaminase enzymes, brain protein, and acetylcholine esterase levels. In addition, there was a significant increase in malondialdehyde levels and a decrease in glutathione, superoxide dismutase, and glutathione peroxidase activities in the HFD group compared to the control group. Furthermore, the histopathological observation recorded a profound modification in the liver and brain tissues of the HFD group. In contrast, the treatment with SmE-N and metformin assured a partial amelioration in the noticed parameters compared to the HFD group, but SmE-N led to a better improvement than metformin compared to the control group. In conclusion, the use of SmE-N bioconjugated by linoleic acid seems powerful in treating the complications of fructose-induced metabolic disorders due to its hepato-neuroprotective abilities.

Novel peptides from sea cucumber intestines hydrolyzed by neutral protease alleviate exercise-induced fatigue via upregulating the glutaminemediated Ca2+ /Calcineurin signaling pathway in mice.

Sea cucumber intestines are considered a valuable resource in the sea cucumber processing industry due to their balanced amino acid composition. Studies have reported that peptides rich in glutamate and branched-chain amino acids have anti-fatigue properties. However, the function of the sea cucumber intestine in reducing exercise-induced fatigue remains unclear. In this study, we enzymatically hydrolyzed low molecular weight peptides from sea cucumber intestines (SCIP) and administered SCIP orally to mice to examine its effects on exercise-induced fatigue using swimming and pole-climbing exhaustion experiments. The results revealed that supplementation with SCIP significantly prolonged the exhaustion time of swimming in mice, decreased blood lactate and urea nitrogen levels, and increased liver and muscle glycogen levels following a weight-loaded swimming test. Immunofluorescence analysis indicated a notable increase the proportion of slow-twitch muscle fiber and a significant decrease the proportion of fast-twitch muscle fiber following SCIP supplementation. Furthermore, SCIP upregulated mRNA expression levels of Ca2+ /Calcineurin upstream and downstream regulators, thereby contributing to the promotion of skeletal muscle fiber type conversion. This study presents the initial evidence establishing SCIP as a potential enhancer of skeletal muscle fatigue resistance, consequently providing a theoretical foundation for the valuable utilization of sea cucumber intestines.

Effects of Tannic Acid Supplementation of a High-Carbohydrate Diet on the Growth, Serum Biochemical Parameters, Antioxidant Capacity, Digestive Enzyme Activity, and Liver and Intestinal Health of Largemouth Bass, Micropterus salmoides.

We investigated the effects of dietary tannic acid (TA) supplementation of a high-carbohydrate diet on growth, feed utilization, whole-body proximate composition, serum biochemical indicators, antioxidant capacity, digestive enzyme activity, and liver and intestinal health of juvenile largemouth bass, Micropterus salmoides (initial mean weight: 8.08 ± 0.08 g). Five diets were prepared, including a positive control (dietary carbohydrate level, 16%, LC0), a negative control (dietary carbohydrate level, 21%, HC0), and three TA-supplementation diets based on the negative control diet with TA addition at 200, 400, and 800 mg/kg, respectively. After 8 weeks of feeding, the results showed that compared with the LC0 diet, 400-800 mg/kg dietary TA significantly improved the survival rate of largemouth bass (P < 0.05) while significantly reducing its weight-gain rate and specific growth rate (P < 0.05). Compared with the HC0 diet, 400 mg/kg dietary TA significantly increased serum catalase activity (P < 0.05), and significantly decreased serum malondialdehyde, liver glycogen, lightness (L ∗), and yellowness (b ∗) (P < 0.05). Moreover, compared with the HC0 diet, 200-400 mg/kg dietary TA effectively improved the vacuolation of hepatocytes caused by the high-carbohydrate diet and reduced the occurrence of intestinal epithelial cell vacuolation and necrosis. In turn, 800 mg/kg dietary TA significantly inhibited protease activity in the pyloric caecum and intestine (P < 0.05). In conclusion, dietary supplementation with TA inhibited protease activity, which resulted in decreased growth performance in largemouth bass. However, it was also found that 200-400 mg/kg TA enhanced the antioxidant capacity of largemouth bass in the case of the high-carbohydrate diet, reduced liver glycogen levels, and improved liver and intestinal health. Finally, it should be noted that, when the dietary TA level exceeded 800 mg/kg, TA appeared to play a pro-oxidation role in the liver, which may cause oxidative stress in the liver.

The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice.

Roux-en-Y gastric bypass (RYGB) leads to the improvement of many obesity-associated conditions. The degree to which post-operative macronutrient composition contributes to metabolic improvement after RYGB is understudied. A mouse model of RYGB was used to examine the effects of diet on the post-operative outcomes of RYGB. Obese mice underwent either Sham or RYGB surgery and were administered either chow or HFD and then monitored for an additional 8weeks. After RYGB, reductions to body weight, fat mass, and lean mass were similar regardless of diet. RYGB and HFD were independently detrimental to bone mineral density and plasma vitamin D levels. Independent of surgery, HFD accelerated hematopoietic stem and progenitor cell proliferation and differentiation and exhibited greater myeloid lineage commitment. Independent of diet, systemic iron deficiency was present after RYGB. In both Sham and RYGB groups, HFD increased energy expenditure. RYGB increased fecal energy loss, and HFD after RYGB increased fecal lipid content. RYGB lowered fasting glucose and liver glycogen levels but HFD had an opposing effect. Indices of insulin sensitivity improved independent of diet. HFD impaired improvements to dyslipidemia, NAFLD, and fibrosis. Post-operative diet plays a significant role in determining the degree to which RYGB reverses obesity-induced metabolic abnormalities such as hyperglycemia, dyslipidemia, and NAFLD. Diet composition may be targeted in order to assist in the treatment of post-RYGB bone mineral density loss and vitamin D deficiency as well as to reverse myeloid lineage commitment. HFD after RYGB continues to pose a significant multidimensional health risk.

Carotid body denervation improves hyperglycemia in obese mice.

The carotid bodies (CBs) have been implicated in glucose abnormalities in obesity via elevation of activity of the sympathetic nervous system. Obesity-induced hypertension is mediated by insulin receptor (INSR) signaling and by leptin, which binds to the leptin receptor (LEPRb) in CB and activates transient receptor potential channel subfamily M member 7 (TRPM7). We hypothesize that in mice with diet-induced obesity, hyperglycemia, glucose intolerance, and insulin resistance will be attenuated by the CB denervation (carotid sinus nerve dissection, CSND) and by knockdown of Leprb, Trpm7, and Insr gene expression in CB. In series of experiments in 75 male diet-induced obese (DIO) mice, we performed either CSND (vs. sham) surgeries or shRNA-induced suppression of Leprb, Trpm7, or Insr gene expression in CB, followed by blood pressure telemetry, intraperitoneal glucose tolerance and insulin tolerance tests, and measurements of fasting plasma insulin, leptin, corticosterone, glucagon and free fatty acids (FFAs) levels, hepatic expression of gluconeogenesis enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G-6-Pase) mRNA and liver glycogen levels. CSND decreased blood pressure, fasting blood glucose levels and improved glucose tolerance without any effect on insulin resistance. CSND did not affect any hormone levels and gluconeogenesis enzymes, but increased liver glycogen level. Genetic knockdown of CB Leprb, Trpm7, and Insr had no effect on glucose metabolism. We conclude that CB contributes to hyperglycemia of obesity, probably by modulation of the glycogen-glucose equilibrium. Diabetogenic effects of obesity on CB in mice do not occur via activation of CB Leprb, Trpm7, and Insr.NEW & NOTEWORTHY This paper provides first evidence that carotid body denervation abolishes hypertension and improves fasting blood glucose levels and glucose tolerance in mice with diet-induced obesity. Furthermore, we have shown that this phenomenon is associated with increased liver glycogen content, whereas insulin sensitivity and enzymes of gluconeogenesis were not affected.

1-Deoxynojirimycin Mitigates Glycogen and Carbohydrate Metabolic Enzyme Alterations in High Glucose-Induced Diabetic Tilapia: Implications for Therapeutic Intervention

This study investigated the effects of 1- deoxynojirimycin (DNJ) on blood glucose levels, body weight changes, glycogen levels, and carbohydrate marker enzyme activity in a high glucose-induced experimental diabetic tilapia model. We utilized spectrophotometry assay methods to achieve this objective. DNJ treatment significantly reduced blood glucose and mitigated body weight loss compared to the diabetic control group. Furthermore, DNJ treatment increased glycogen levels in liver and muscle tissues, suggesting its potential to enhance glycogen synthesis or reduce glycogen breakdown. DNJ treatment also modulated the activity of carbohydrate marker enzymes, indicating its possible inhibitory effect on enzymes involved in carbohydrate absorption and breakdown, which in turn may improve glucose homeostasis and control. The results of this study highlight DNJ's potential as a therapeutic agent for diseases associated with glycogen metabolism and glucose homeostasis, as well as its ability to influence body weight changes in diabetic conditions. Our findings contribute to the growing body of research on DNJ as a potential therapeutic agent for illnesses linked to glycogen and underscore its therapeutic potential for future treatments targeting glucose metabolism, glycemic control, and weight management.