Hepatic Glycogen Content Research Articles

Hesperetin-copper (II) complex improves liver glucose metabolism by regulating the IRS-1/PI3K/AKT signaling pathway in T2DM mice

The metal complexes of flavonoids have attracted widespread attention because of their distinct structural and functional characteristics. Hesperetin-Cu(II) complex [Hsp-Cu(II)] showed good hypoglycemic potential, but its hypoglycemic effect and mechanism in vivo are still vague. This study aimed to investigate the hypoglycemic effects of Hsp-Cu(II) on type 2 diabetic (T2DM) mice and its underlying mechanism. The results showed that Hsp-Cu(II) (50 mg/kg) effectively improved hyperglycemia and dyslipidemia, increased the fast insulin level and HOMA-IR to alleviate the insulin resistance in the T2DM mice. Compared with the Diseased group, treatment of Hsp-Cu(II) at 50 mg/kg reduced the activities of α-amylase, phosphoenolpyruvate carboxy kinase (PEPCK) and glucose 6-phosphatase (G6Pase) by 31.7%, 45.5% and 35.1%, respectively; elevated the level of glutathione and activities of superoxide dismutase and catalase by 27.2%, 71.7% and 36.7%, respectively, and decreased the malondialdehyde content by 23.6% to improve the liver antioxidant abilities; reduced the activities of alanine aminotransferase and aspartate aminotransferase by 15.6% and 28.1%, as well as the levels of inflammatory factors to relieve liver damage. In addition, Hsp-Cu(II) activated the insulin receptor substrate-1/phosphoinositide-3-kinase/protein kinase B (IRS-1/PI3K/AKT) signaling pathway to up-regulate the protein expression levels of phospho-glycogen synthase kinase-3β (p-GSK-3β) and phospho-fork head box transcription factor O1 (p-FoxO1) and down-regulate the mRNA expression of PEPCK and G6Pase. Therefore, Hsp-Cu(II) may regulate hepatic glucose metabolism through IRS-1/PI3K/AKT‒GSK3β pathways to increase the hepatic glycogen content and IRS-1/PI3K/AKT‒FoxO1‒PEPCK/G6Pase pathways to inhibit gluconeogenesis, maintain hepatic glucose homeostasis, thus exerting the hypoglycemia effect in T2DM. These discoveries may provide a scientific basis for developing Hsp-Cu(II) as a food function factor to alleviate T2DM.

VEGFB ameliorates insulin resistance in NAFLD via the PI3K/AKT signal pathway

BackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most universal liver diseases with complicated pathogenesis throughout the world. Insulin resistance is a leading risk factor that contributes to the development of NAFLD. Vascular endothelial growth factor B (VEGFB) was described by researchers as contributing to regulating lipid metabolic disorders. Here, we investigated VEGFB as a main target to regulate insulin resistance and metabolic syndrome.MethodsIn this study, bioinformatics, transcriptomics, morphological experiments, and molecular biology were used to explore the role of VEGFB in regulating insulin resistance in NAFLD and its molecular mechanism based on human samples, animal models, and cell models. RNA-seq was performed to analyze the signal pathways associated with VEGFB and NAFLD; Palmitic acid and High-fat diet were used to induce insulin-resistant HepG2 cells model and NAFLD animal model. Intracellular glucolipid contents, glucose uptake, hepatic and serum glucose and lipid levels were examined by Microassay and Elisa. Hematoxylin-eosin staining, Oil Red O staining, and Periodic acid-schiff staining were used to analyze the hepatic steatosis, lipid droplet, and glycogen content in the liver. Western blot and quantitative real-time fluorescent PCR were used to verify the expression levels of the VEGFB and insulin resistance-related signals PI3K/AKT pathway.ResultsWe observed that VEGFB is genetically associated with NAFLD and the PI3K/AKT signal pathway. After VEGFB knockout, glucolipids levels were increased, and glucose uptake ability was decreased in insulin-resistant HepG2 cells. Meanwhile, body weight, blood glucose, blood lipids, and hepatic glucose of NAFLD mice were increased, and hepatic glycogen, glucose tolerance, and insulin sensitivity were decreased. Moreover, VEGFB overexpression reduced glucolipids and insulin resistance levels in HepG2 cells. Specifically, VEGFB/VEGFR1 activates the PI3K/AKT signals by activating p-IRS1Ser307 expression, inhibiting p-FOXO1pS256 and p-GSK3Ser9 expressions to reduce gluconeogenesis and glycogen synthesis in the liver. Moreover, VEGFB could also enhance the expression level of GLUT2 to accelerate glucose transport and reduce blood glucose levels, maintaining glucose homeostasis.ConclusionsOur studies suggest that VEGFB could present a novel strategy for treating NAFLD as a positive factor.Graphical

Antidiabetic Effect of Bifidobacterium animalis TISTR 2591 in a Rat Model of Type 2 Diabetes.

This study investigated the beneficial effects of probiotic Bifidobacterium animalis TISTR 2591 on the regulation of blood glucose and its possible mechanisms in a rat model of type 2 diabetes. The type 2 diabetic-Sprague Dawley rats were established by the combination of a high-fat diet and a low dose of streptozotocin. After 4weeks of treatment with 2 × 108CFU/ml of B. animalis TISTR 2591, fasting blood glucose (FBG), oral glucose tolerance, serum insulin, and pancreatic and hepatic histopathology were determined. Liver lipid accumulation, glycogen content, and gluconeogenic protein expression were evaluated. Oxidative stress and inflammatory status were determined. B. animalis TISTR 2591 significantly reduced FBG levels and improved glucose tolerance and serum insulin in the diabetic rats. Structural damage of the pancreas and liver was ameliorated in the B. animalis TISTR 2591-treated diabetic rats. In addition, significant decreases in hepatic fat accumulation, glycogen content, and phosphoenolpyruvate carboxykinase-1 protein expression were found in the diabetic rats treated with B. animalis TISTR 2591. The diabetic rats showed a significant reduction of inflammation following B. animalis TISTR 2591 supplementation, as demonstrated by decreasing hepatic NF-κB protein expression and serum and liver TNF-α levels. The B. animalis TISTR 2591 significantly decreased MDA levels and increased antioxidant SOD and GPx activities in the diabetic rats. In conclusion, B. animalis TISTR 2591 was shown to be effective in controlling glucose homeostasis and improving glucose tolerance in the diabetic rats. These beneficial activities were attributed to reducing oxidative and inflammatory status and modulating hepatic glucose metabolism.

Fibroblast growth factor 1 (FGF1) improves glucose homeostasis, modulates gut microbial composition, and reduces inflammatory responses in rainbow trout (Oncorhynchus mykiss) fed a high-fat diet

High-fat diets (HFDs) are widely used in aquaculture due to their lipid and protein-conserving effects, thereby reducing feed costs. However, prolonged feeding of HFD often leads to metabolic disorders in fish, such as disruption of hepatic lipid homeostasis, liver injury, and disruption of glucose homeostasis. Fibroblast growth factor 1 (FGF1) plays an essential role in controlling glucose levels in the body and dampening immune reactions. However, its impact on teleosts remains poorly researched. The therapeutic potential of recombinant FGF1 (rFGF1) was examined in a 6-week culture experiment involving rainbow trout (Oncorhynchus mykiss) that were fed an HFD. The results revealed that rFGF1 significantly reduced serum glucose levels and hepatic PEPCK and G6PC activities, but improved hepatic glycogen (P < 0.05), compared to the HFD + PBS group. Further experiments indicated that the inhibitory effect of rFGF1 on hepatic gluconeogenesis was mediated by the cAMP signaling pathway and was dependent on the high expression of PDE4D. In addition, rFGF1 increased hepatic glycogen content, which involves the AKT-GSK3β axis. Despite this increase, rFGF1 did not lead to glycogen storage disease, as shown by reduced hepatic inflammation as a result of decreased GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), and elevated SOD (superoxide dismutase) in the rFGF1-treated group, accompanied by decreased il-1β, il-6, and xbp-1, and elevated nrf2 and number of hepatocyte autophagosomes. Alterations in gut microbes and short-chain fatty acids (SCFAs) were noted, indicating that rFGF1 caused a notable rise in intestinal Lactobacillus, acetic acid, and butyric acid levels. This study investigated the molecular mechanisms of rFGF1 on glucose metabolism and inflammatory responses in an HFD-fed rainbow trout model, providing new insights to improve the regulation of glucose metabolism in carnivorous fish.

Ameliorative Effect of Curcuma longa Ethanolic Extract on the Histology, Hepatic Glycogen Content and Some Biochemical Parameters of the Liver in Streptozotocin-Induced Hyperglycemic Wistar Rats

Introduction: Diabetes mellitus is a life threatening disease that requires immediate medical treatment. Numerous medicinal plants have been known for their anti-diabetic effects and Curcuma longa (turmeric) is one of them. This attribute is possible due to the pharmacological properties of its bio-constituents. In this study, the ameliorative potential of ethanolic extract of Curcuma longa was investigated on the liver of hyperglycemic adult Wistar rats. The objectives were to determine its effects on liver histology, hepatic glycogen content and some liver biochemical parameters. Methods: Forty (40) rats weighing between 120-180g were used for the research. Sixteen (16) rats were used for its acute toxicity study, while twenty-four (24) rats were grouped into four. The groups were labelled A to D and contained six rats each. Group A (normal control) rats were given food pellets and distilled water only. Group B (diabetic control) rats were given 65mg/kg BW of streptozotocin IP. Group C served as the standard group and was given 65mg/kg of streptozotocin IP + 250mg/kg of metformin IP, while Group D (test group) rats were given 65mg/kg BW of streptozotocin IP + 500mg/kg of Curcuma longa extract. Curcuma longa extract was administered through the oral route with the aid of an oral gavage. The administration lasted for twenty-eight (28) days, after which the rats were made to fast overnight with access to only water. The rats were then anaesthetized and whole blood obtained through cardiac puncture for biochemical analysis. Liver tissue was obtained for histological and glycogen content analyses. Results: The results showed severe destruction of hepatocytes with widely spread cytoplasmic vacuolation, loss of hepatic lobules and hepatic inflammation in the diabetic group, whereas it showed prominent nuclei, hepatocytes and distinct sinusoidal spaces in the normal control group. The metformin group showed an intact architecture of the liver tissue with indicating regeneration in the liver, while the Curcuma longa extract group showed a preserved liver cytoarchitecture. There was a significant decrease (p&lt;0.05) in the fasting blood glucose level and liver enzyme activities in the standard and test groups compared to the diabetic group (p&lt;0.05). There was also improvement in glycogen content of the standard and test groups in comparison with the diabetic group (p&lt;0.05). Conclusion: Curcuma longa possesses hepato-protective properties and a strong anti-diabetic potential, therefore it can be considered as an alternative drug in the management of diabetes mellitus and its complications.

Physicochemical properties, structural characterization, and antidiabetic activity of selenylated low molecular weight apple pectin in HFD/STZ-induced type 2 diabetic mice

A novel selenylated low molecular weight apple pectin (Se-LMWAP) was prepared through enzymatic modification combined with selenylation. The physicochemical properties, the structural characterization of Se-LMWAP were evaluated by FT-IR, NMR and SEM. Moreover, the antidiabetic activity and potential mechanism of Se-LMWAP were investigated using high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetic mice. The results revealed that the physicochemical properties of Se-LMWAP were distinctly improved after modifications, and the primary structure was not altered significantly compared to apple pectin and low molecular weight apple pectin. Se-LMWAP had a relative molecular weight of 8.91 × 103 Da (accounted for 61.3 %) and total selenium content of 148.3 ± 2.0 μgselenium/gsample. It consisted of Rha, Ara, Gal, Glc, Xyl and GalA at a molar ratio of 0.093:0.014:0.132:0.020:0.118:0.622, with the selenium substitution occurred at the C-6 position. Se-LMWAP was able to significantly reduce weight loss, hyperglycemia, oxidative stress and liver, kidney and pancreas damage. Additionally, improved glucose tolerance, relieved lipid metabolism disorders, elevated hepatic glycogen content and ameliorated insulin resistance were observed in the Se-LMWAP group. Overall, Se-LMWAP can be used as a promising dietary selenium supplement to exert -antidiabetic effect through modulating hepatic glucose metabolism and liver insulin-signaling transduction and oxidative stress.

Taurine can play a positive role in growth, liver health and resistance to Aeromonas hydrophila of yellow catfish Pelteobagrus fulvidraco exposed to ammonia stress for a long time

Ammonia is an important environmental pollutant that is toxic to most aquatic animals, and nutrient manipulation is an effective regulatory pathway. To assess the influence of taurine supplementation on growth, liver detoxification and anti-bacterial infection of yellow catfish subjected to ammonia exposure for a long time, three experiment diets with different taurine levels (0.50, 1.00, and 2.00 %) were formulated and fed to fish (7.28 ± 0.05) g under three ammonia levels (0.00, 25.00 and 50.00 mg/L total ammonia nitrogen) for 56 days. The results showed that hepatic glycogen and whole-body protein contents were reduced, suggesting that energy deficiency caused by ammonia poisoning plays an important role in growth inhibition; elevated serum alanine aminotransferase and aspartate aminotransferase levels suggest liver injury, which may be caused by oxidative stress (decreased activities of superoxide dismutase and catalase, and expressions of SOD and CAT) and inflammation (increased contents of tumor necrosis factor α, interleukin 1 and interleukin 8, and expressions of TNF α, IL 1 and IL8), analysis of tissue sections further confirmed this finding. Furthermore, after injection with Aeromonas hydrophila, cumulative mortality increased proportionally with the rise in ammonia levels, the observed decrease in serum complements C3, C4, immunoglobulin M, and antibody titer contents emerged as a crucial factor contributing to the decreased disease resistance. The exogenous taurine was found to alleviate the negative impact of the above-mentioned ammonia poisoning. This study provides valuable insights into the mechanism of ammonia-induced aquatic toxicology in fish.

Effects of nano-Rhodiola rosea combined with treadmill exercise on anti-exercise fatigue in rats.

To explore the potential strategies and mechanisms for enhancing the bioavailability of Rhodiola rosea. 36 Sprague-Dawley rats (8-weeks-old) were randomly assigned to six groups (n = 6 per group). Groups I and II received nano-dose forms of R. rosea, groups III and IV received normal dose form of R. rosea, and groups V and VI served as distilled water control groups. Groups II, IV, and VI were combined with moderate -intensity treadmill exercise. Each group received a daily gavage with 0.5 mL of nano -R. rosea solution (0.01 mg/mL), normal R. rosea solution, and distilled water. All rats were subjected to exhaustive swimming after 4 weeks. Outcome measures include GSH-px activity, T-AOC activity, MDA content, hepatic glycogen content, and T-SOD activity. For plasma MDA content, group I was lower than group III (p < 0.01) and group V (p < 0.01), group II was lower than group III (p < 0.01), group VI was higher than group II (p < 0.05) and group IV (p < 0.05). For plasma T-AOC activity, group II was higher than group VI (p < 0.01). For plasma GSH-px activity, group I was lower than group IV (p < 0.05), groups II, III, and IV were higher than group V (p < 0.05), and group V was lower than that of group VI (p < 0.05). For T-SOD activity of quadriceps muscle, groups I and III were higher than that in group V (p < 0.05). R. rosea has a positive effect on anti-exercise fatigue in rats, with the nano-dosage form of R. rosea showing more significant efficacy than the normal form especially combined with aerobic exercise.

Valine biased glycogen consumption to promote energy metabolism of Portunus trituberculatus and increased protein and essential amino acid deposition in muscle

The present research assessed the impact of dietary valine on nutritional and energy metabolism, as well as muscle development in swimming crabs (Portunus trituberculatus) over a period of six weeks. Swimming crabs, initially weighing around 23.34 ± 0.03 g, were given six diets identical in nitrogen and lipid levels (45 % and 8 % respectively). These diets contained valine contents of 0.99 %, 1.24 %, 1.56 %, 1.69 %, 1.90 %, and 2.20 % respectively. One hundred and eighty crabs were randomized into six treatments, each treatment including three replicates. The results suggested that significant increases were discovered in FW, PWG, as well as SGR of crabs when dietary valine increasing from 0.99 % to 1.69 %, but these measurements decreased when dietary valine increased to 2.20 %. Compare to the control treatment, crabs that were given diets with 1.90 % and 2.20 % valine showed increased level of muscle protein. Crabs that were given the diets containing 1.56 % and 1.69 % valine showed significantly increased concentration of GLU in hemolymph compared to the control group. Additionally, crabs that were given the diets containing 1.69 % valine and 1.90 % valine respectively showed significantly increased concentrations of T-CHO and TG in hepatopancreas. Hepatic glycogen concentration significantly decreased as the level of valine in diets increased from 0.99 % to 1.56 %, but significantly increased as valine level further increased to 2.20 %. Compared with the control group, crabs that were given diets with 1.90 % valine showed increased expression levels of genes associated to amino acid metabolism (pi3k, akt, alt, ast, 4ebp1 and eif4e3) and energy metabolism (pk, cs1, idh, nd1, cytb and cox2). Crabs given diets containing 2.20 % valine showed significantly increased expression level of pepck in hepatopancreas, while crabs given diets containing 1.24 %, 1.56 %, and 1.69 % valine exhibited significantly increased expression level of cpt1 in hepatopancreas. Crabs given the diet with 1.69 % valine had the highest expression levels of tor and pax7 in muscle. Increased dietary valine significantly reduced myofiber density but promoted higher frequency of myofibers in larger diameters. In conclusion, the optimal valine requirement for P. trituberculatus was 1.56 % of diet based on PWG by a quadratic modeling. 1.69–1.90 % valine promoted amino acid metabolism and muscle growth, moreover, enhanced energy metabolism by driving the consumption of glycogen rather than lipids.

Liver Biopsy Technique for Analysis of Hepatic Content during Pregnancy and Early Lactation in Dairy Goats.

Biopsy techniques in dairy goats are currently limited. This study aimed to describe a liver biopsy technique in dairy goats and to evaluate liver triglyceride levels and glycogen content. Sixty-nine dairy goats in the final stage of pregnancy and early lactation period were selected. Fifty goats were selected randomly for hepatic biopsy (HB) according to gestational period and were characterized according to fetus number (single: n = 16, multiple: n = 34), supplementation with propylene glycol (diet: n = 23, diet+PG: n = 27), and milk production levels (high: 3.0 ± 0.4 L/day, n = 15; low: 1.4 ± 0.4 L/day, n = 26). Liver tissue samples were obtained through biopsy on days -30, -20, -15, -10, -5, and 15 days after calving. Hepatic triglyceride and glycogen were quantified. The results were analyzed using the F-test at a 5% significance level and a comparison of means using the Tukey test. The liver biopsies did not influence dry matter intake, body weight, or milk yield. Hepatic glycogen concentration was lower 15 days after calving than it was prior to calving, except on day -20. Goats that generated high levels of milk production had lower triglyceride levels than goats that generated low levels of milk production. The biopsy technique is a safe method for obtaining tissue and evaluating liver content in dairy goats. The milk production level and days relative to parturition influence the hepatic triglyceride and glycogen content in dairy goats.

The Effects of Water Flow Speed on Swimming Capacity and Energy Metabolism in Adult Amur Grayling (Thymallus grubii)

The present study aimed to explore whether water flow velocity could affect the swimming ability and overall energy metabolism of wild Amur grayling (Thymallus grubii). Swimming performance was assessed by measuring critical swimming speed (Ucrit), burst speed (Uburst), and oxygen consumption rate (MO2) based on the stepped velocity test method. Our results showed that the absolute values of Ucrit and Uburst tended to increase with body length. In contrast, the relative values of Ucrit and Uburst tended to decrease and increase, respectively. MO2 in Amur grayling was elevated with increasing velocity, suggesting relatively high swimming efficiency. We also measured the biochemical indices related to energy metabolism. Lactate dehydrogenase, hexokinase, and pyruvate kinase activities significantly increased (p &lt; 0.05). Hepatic glycogen, glucose, and muscle glycogen contents decreased with the increasing trend of velocity (p &lt; 0.05), the lactic acid contents of the blood and muscles increased significantly with the increase in velocities (p &lt; 0.05), and changes in creatine phosphate content showed no significant difference (p &gt; 0.05). The results not only denote the relationship between body size and swimming speed but also show the effects of water flow velocity on energy metabolism in Amur grayling. The results provide basic data for the construction of fish passage.

Apigenin-6-C-glucoside ameliorates MASLD in rodent models via selective agonism of adiponectin receptor 2

Adiponectin plays key roles in energy metabolism and ameliorates inflammation, oxidative stress, and mitochondrial dysfunction via its primary receptors, adiponectin receptors −1 and 2 (AdipoR1 and AdipoR2). Systemic depletion of adiponectin causes various metabolic disorders, including MASLD; however adiponectin supplementation is not yet achievable owing to its large size and oligomerization-associated complexities. Small-molecule AdipoR agonists, thus, may provide viable therapeutic options against metabolic disorders. Using a novel luciferase reporter-based assay here, we have identified Apigenin-6-C-glucoside (ACG), but not apigenin, as a specific agonist for the liver-rich AdipoR isoform, AdipoR2 (EC50: 384 pM) with >10000X preference over AdipoR1. Immunoblot analysis in HEK-293 overexpressing AdipoR2 or HepG2 and PLC/PRF/5 liver cell lines revealed rapid AMPK, p38 activation and induction of typical AdipoR targets PGC-1α and PPARα by ACG at a pharmacologically relevant concentration of 100 nM (reported cMax in mouse; 297 nM). ACG-mediated AdipoR2 activation culminated in a favorable modulation of key metabolic events, including decreased inflammation, oxidative stress, mitochondrial dysfunction, de novo lipogenesis, and increased fatty acid β-oxidation as determined by immunoblotting, QRT-PCR and extracellular flux analysis. AdipoR2 depletion or AMPK/p38 inhibition dampened these effects. The in vitro results were recapitulated in two different murine models of MASLD, where ACG at 10 mg/kg body weight robustly reduced hepatic steatosis, fibrosis, proinflammatory macrophage numbers, and increased hepatic glycogen content. Together, using in vitro experiments and rodent models, we demonstrate a proof-of-concept for AdipoR2 as a therapeutic target for MASLD and provide novel chemicobiological insights for the generation of translation-worthy pharmacological agents.

Effects of sodium dodecylbenzene sulfonate (SDBS), active principle of detergents, on the liver and kidney of zebrafish (Danio rerio)

ABSTRACT Sodium dodecylbenzene sulfonate (SDBS), a predominant component in detergents, requires an evaluation of its toxicological potential due to its hazardous environmental levels. Therefore, we evaluated the toxicological effects of SDBS on the liver and kidney of male D. rerio. Therefore, we evaluated the toxicological effects of SDBS on the liver and kidney of male D. rerio. The fish were divided into three groups: 0.0 (control), 0.25, and 0.5 mg/L of SDBS with exposure for up to 96 hours. After exposure, histopathological, histochemical (hepatic glycogen content), and biochemical analyses (SOD and CAT enzyme analysis) were performed on both organs. The results showed significant histopathological effects, such as circulatory disturbances and progressive and regressive alterations, leading to an altered histopathological alteration index. SOD and CAT enzymes exhibited prominent changes. Thus, it became clear that the surfactant SDBS can cause serious hepatic and renal problems in D. rerio fish, even with short-term exposure, necessitating more stringent control and regulation in the disposal of this surfactant.

Maternal protein restriction combined with postnatal sugar consumption alters liver proteomic profile and metabolic pathways in adult male offspring rats

This study investigated the impact of maternal protein restriction (MPR) and early postnatal sugar consumption (SUG) on the liver health of adult male descendant rats. Male offspring of mothers fed a normal protein diet (NPD) or a low protein diet (LPD) were divided into four groups: Control (CTR), Sugar Control (CTR + SUG), LPD during gestation and lactation (GLLP), and LPD with sugar (GLLP + SUG). Sugar consumption (10% glucose diluted in water) began after weaning on day 21 (PND 21), and at 90 days (PND 90), rats were sacrificed for analysis. Sugar intake reduced food intake and increased water consumption in CTR + SUG and GLLP + SUG compared to CTR and GLLP. GLLP and GLLP + SUG groups showed lower body weight and total and retroperitoneal fat compared to CTR and CTR + SUG. CTR + SUG and GLLP + SUG groups exhibited hepatocyte vacuolization associated with increased hepatic glycogen content compared to CTR and GLLP. Hepatic catalase activity increased in GLLP compared to CTR. Proteomic analysis identified 223 differentially expressed proteins (DEPs) among experimental groups. While in the GLLP group, the DEPs enriched molecular pathways related to cellular stress, glycogen metabolic pathways were enriched in the GLLP + SUG and CTR + SUG groups. The association of sugar consumption amplifies the effects of MPR, deregulating molecular mechanisms related to metabolism and the antioxidant system.

Phytosterol supplementation enhances the growth performance, feed utilization, antioxidant status and glucose metabolism of juvenile largemouth bass (Micropterus salmoides) fed a high-starch diet

IntroductionPrevious studies found that phytosterols could influence growth performance, feed utilization and lipid metabolism as well as improve the antioxidant capacity of animals.MethodsTo investigate the effects of dietary phytosterol supplementation on juvenile largemouth bass (Micropterus salmoides) fed a high-starch diet, a 56- day feedingtrial was conducted with four dietary feeds for juvenile largemouth bass: extruded floating feed isonitrogenous and isoenergetic diets were formulated to contain 10% and 15% α-starch; on the basis of a 15% α-starch diet, two other diets were formulated with supplementation of 0.1% and 0.5% phytosterol, respectively. After the feeding trials, the survival rate, weight gain and specific growth rate, feed conversion ratio, intraperitoneal fat ratio, feed intake, protein efficiency ratio and activities of three digestive enzymes, as well as the concentrations of nine plasma biochemical indices, hepatic enzyme activities and glycogen contents, were measured and calculated, and the data were statistically analyzed.ResultsThe results of the present study showed that the survival rate, weight gain and specificgrowthrates were significantly greater in plants fed high-starch diets supplemented with phytosterols. As the supplemental phytosterol concentration increased, the feed conversion ratio and intraperitoneal fat ratio significantly decreased; the protease and lipase levels in the pyloric zone markedly increased; the plasma cholesterol, triglyceride, glucose, malondialdehyde, aspartate transaminase and alanin transaminase levels significantly decreased; the glucokinase and pyruvate kinase levelsmarkedly increased; and the hepatic glycogen content significantly decreased.DiscussionIn summary, dietary phytosterol supplementation promoted the growth performance, feed utilization and antioxidant status of juvenile largemouth bass fed a highstarch diet; enhanced glucose utilization and metabolism; and alleviated the negative stimulation of glycemia stress in M. salmoide fed a high-starch diet.

AM Insulinization of the Liver Is an Important Driver of PM Hepatic Glucose Uptake

Glucose tolerance is significantly improved in response to consuming a second, identical meal later in the day. It is known that physiologic (portal vein) exposure to insulin in the morning primes the liver for increased hepatic glucose uptake and glycogen storage in the afternoon. Although this phenomenon has been observed in both healthy and diabetic individuals, it has not yet been established whether or not morning peripheral insulin delivery could bring about the same response. Thus, the aim of this study was to determine how the route of morning insulin delivery impacts the liver’s ability to extract and store glucose later in the day. To explore this aim, we delivered insulin into the portal vein (Po Ins) or a leg vein (Pe Ins) in the morning (AM) and subsequently challenged conscious dogs to a hyperinsulinemic-hyperglycemic (HIHG) clamp in the afternoon (PM). We then assessed the impact that each route of AM insulin delivery had on hepatic glucose uptake (HGU), non-HGU, and glycogen storage in the PM. The insulin infusion rates used in the Po Ins group were selected to mimic the rise in endogenous insulin secretion previously observed during a 4hr AM duodenal glucose infusion (2.1 mU/kg/min [0-30 min], 2.4 mU/kg/min [30-60 min], and 1.5 mU/kg/min [60-240 min]). In efforts to expose both groups to the same amount of insulin in the periphery while creating a difference at the liver, these rates were halved in the Pe Ins group. In the PM clamp, all groups received 4x basal insulin, 2x basal glycemia, and portal glucose infusion to simulate a second meal. During the 2.5hr PM clamp, the mean HGU was 1.8-fold higher in the Po Ins group vs. the Pe Ins group (HGU of 6.28±0.62 vs. 3.49±0.31 mg/kg/min; net AUC of 827±82 vs. 474±40 mg/kg/2.5hr, p&lt;0.002), respectively, with no significant difference in non-HGU (net AUC of 819±118 mg/kg/2.5hr in Po Ins vs. 684±83 mg/kg/2.5hr in Pe Ins). Additionally, mean PM hepatic glycogen content was 47% larger in Po Ins vs. Pe Ins (23.6±1.1 vs. 12.5±1.5 mg/g liver, p&lt;0.001), respectively. When compared to a group from an earlier study that received morning saline and a HIHG clamp in the afternoon (Sal Ctrl), there was no significant difference between Pe Ins and Sal Ctrl for any parameter measured. Therefore, physiologic hepatic insulin exposure in the morning is critical for increased hepatic glucose disposition and glycogen storage later in the day. 5T32DK007563 5R01DK131082-02. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exploring the relationship between dietary rapeseed meal, condensed tannin and growth, nutrive metabolism in largemouth bass (Micropterus salmoides)

This study evaluated the effects of rapeseed meal (RM) and condensed tannin (CT) on the growth and nutritional metabolism of largemouth bass (Micropterus salmoides), and speculated whether there was interaction between anti-nutritional factors in RM. Eight diets were formulated for 55-day feeding trial, six of which were practical diet groups, including control group (CG), five RM inclusive groups with graded RM levels of 5% (RM5), 10% (RM10), 15% (RM15), 20% (RM20) and 25% (RM25) partially replacing fishmeal, and the other two were semi-purified diets with 0.062% CT (CT5) ≈ the CT content in the RM5 and 0.31% CT (CT25) ≈ the CT content in the RM25. The results of the experiments on replacing fishmeal with RM demonstrated that with the increase of RM substitution level, the weight gain rate (WGR), survival rate (SR) and specific growth rate (SGR) of largemouth bass showed a downward trend. High levels of RM led to the inhibition of digestive enzyme activity in largemouth bass, as well as the manifestation of abnormal markers related to protein, fat, and carbohydrate metabolism in both plasma and liver. RM reduced muscle protein and fat content, although the effect was not statistically significant at 5% RM level. The results of CT concentration experiments showed that the addition of 0.31% CT significantly reduced WGR, SGR, SR, protein efficiency ratio (PER) and gastrointestinal digestive enzyme activity, and significantly increased the feed coefficient ratio (FCR), plasma ammonia (PA), plasma glucose (PG), and hepatic glycogen (HG) and liver triglyceride (TG). The addition of 0.062% CT significantly reduced PG and HG. Supplementation of CT significantly reduced muscle fat. Among the groups of CT supplementation and RM, CT5 exhibited superior WGR, PER and FCR compared to RM5, along with enhanced intestinal trypsin, amylase activity, liver glutamic pyruvic transaminase (GPT) activity and decreased content of HG and liver TG; CT25 exhibited decreased activities of gastric lipase (LPS), enteric trypsin and pepsin, and increased content of total cholesterol (T-CHO) and glucose in plasma in compariosn to RM25, accompanied with no significant change in growth performance. Therefore, largemouth bass exhibited tolerance to a 5% inclusion of RM in the feed without compromising their growth, digestion and metabolic functions. The incorporation of 5% RM, equivalent to a supplemental 0.062% CT, had regulatory effects on the digestion and metabolism of largemouth bass while improving feed utilization. There was an interaction among anti-nutritional factors in RM, with synergistic effect being evident at low RM levels, whereas antagonism more promient at high levels of RM.

Hypoglycemic Effects of Gynura divaricata (L.) DC Polysaccharide and Action Mechanisms via Modulation of Gut Microbiota in Diabetic Mice.

Aiming to provide a basis for the application of Gynura divaricata (L.) DC polysaccharide (GDP) in functional foods, the hypoglycemic effects of GDP, and action mechanisms, were investigated. Results showed that GDP effectively inhibited α-glucosidase and remarkably increased the glucose absorption, glycogen content, and pyruvate kinase and hexokinase activities of insulin-resistant HepG2 cells, indicating its potent in vitro hypoglycemic effect. In streptozotocin-induced type 2 diabetes mice, GDP significantly improved various glycolipid metabolism-related indices in serum and liver, e.g., fasting blood glucose, oral glucose tolerance, glycosylated serum protein content, serum insulin level, antioxidant enzyme activities, TG, TC, LDL-C, and HDL-C levels, and hepatic glycogen content, and recovered the structure of gut microbiota to the normal level. It was also found that GDP significantly affected the expression of related genes in the PI3K/Akt, AMPK, and GS/GSK-3β signaling pathways. Therefore, GDP regulates blood glucose possibly by directly inhibiting α-glucosidase, exerting antioxidant activity, and regulating intestinal microbiota.

The beneficial effects of metformin inclusion on growth performance, glucose utilization, antioxidant capacity and apoptosis of largemouth bass (Micropterus salmoides) fed with high dietary carbohydrates

The diabetic feature limits the utilization of dietary carbohydrates in carnivorous fish, and excessive dietary carbohydrate usually cause negative effects on health and growth of these fish. In this study, a 9-weeks' feeding experiment was conducted to figure out the influence of dietary metformin (MET), an effective agent for diabetes in mammals, supplementation on largemouth bass, a typical carnivorous fish, feeding high dietary carbohydrates. Compared with the low dietary carbohydrates (LC) group, high dietary carbohydrates (HC) impaired growth performance, which was improved by the inclusion of MET in HC diets. Meanwhile, compared with the HC group, dietary MET supplementation significantly reduced hepatic glycogen and serum glucose contents. Additionally, on the transcriptional level, HC repressed the insulin pathway and induced imbalanced regulation of glycolysis and glycogenesis compared with LC group. However, the MET supplementation significantly enhanced the genes' expression involved in insulin pathway (ira, irb, irs1, pi3kr1, akt1) followed by the activated expression of glycolysis (adpgk, pfkl, and pk) and inhibited expression of glycogenesis (g6pc and pepck). HC significantly reduced antioxidant capacity compared with the LC group, which was reversed with MET supplementation at both transcriptional and enzymatic levels. Additionally, high dietary carbohydrates inhibited apoptosis, which was activated with the inclusion of MET with the inhibition of bcl2/bax ratio and the activation of apoptosis-promoting genes (nfac1-l, arel1, and aif2). In summary, dietary MET inclusion in high carbohydrate diet improved glucose utilization via activating the insulin pathway, and further enhance the growth performance and antioxidant capacity.

The Role of Acyl-CoA Synthetase 1 in Bioactive Lipid Accumulation and the Development of Hepatic Insulin Resistance.

The liver plays a crucial role in glucose metabolism. Obesity and a diet rich in fats (HFD) contribute to the accumulation of intracellular lipids. The aim of the study was to explore the involvement of acyl-CoA synthetase 1 (ACSL1) in bioactive lipid accumulation and the induction of liver insulin resistance (InsR) in animals fed an HFD. The experiments were performed on male C57BL/6 mice divided into the following experimental groups: 1. Animals fed a control diet; 2. animals fed HFD; and 3. HFD-fed animals with the hepatic ACSL1 gene silenced through a hydrodynamic gene delivery technique. Long-chain acyl-CoAs, sphingolipids, and diacylglycerols were measured by LC/MS/MS. Glycogen was measured by means of a commercially available kit. The protein expression and phosphorylation state of the insulin pathway was estimated by Western blot. HFD-fed mice developed InsR, manifested as an increase in fasting blood glucose levels (202.5 mg/dL vs. 130.5 mg/dL in the control group) and inhibition of the insulin pathway, which resulted in an increase in the rate of gluconeogenesis (0.420 vs. 0.208 in the control group) and a decrease in the hepatic glycogen content (1.17 μg/mg vs. 2.32 μg/mg in the control group). Hepatic ACSL1 silencing resulted in decreased lipid content and improved insulin sensitivity, accounting for the decreased rate of gluconeogenesis (0.348 vs. 0.420 in HFD(+/+)) and the increased glycogen content (4.3 μg/mg vs. 1.17 μg/mg in HFD(+/+)). The elevation of gluconeogenesis and the decrease in glycogenesis in the hepatic tissue of HFD-fed mice resulted from cellular lipid accumulation. Inhibition of lipid synthesis through silencing ACSL1 alleviated HFD-induced hepatic InsR.