Glycogen Content Research Articles

Postprandial Regulation of Glucose Metabolism and Insulin Signaling Pathways in Macrobrachium rosenbergii

To better understand postprandial glucose metabolic mechanisms in crustaceans, the pathways involved in glucose transport, breakdown, synthesis, and regulation were investigated in the giant freshwater prawn Macrobrachium rosenbergii after feeding. Prawns were fasted for 48hours and then refed to satiation. Glucose and glycogen contents, along with the transcriptional levels of glucose metabolism-related genes, were measured at 0, 1, 3, 6, and 10hours after feeding (HAF). Plasma glucose levels peaked at 3 HAF and returned to basal levels by 6-10 HAF. Hepatopancreas glucose followed a similar trend, except for a notable increase at 10 HAF, suggesting gluconeogenesis at this time point. Expression analysis of glucose transporter genes in hepatopancreas revealed a significant upregulation of GLUT1 at 3, 6, and 10 HAF, while GLUT2 showed significant decreases only at 6 HAF. Glycolysis-related genes (GK and PK) exhibited transient increases post-feeding, whereas the gluconeogenesis-related gene FBP was initially suppressed, with expression recovering from 6 HAF onward. The glycogenesis-related gene GS was significantly upregulated at 3, 6, and 10 HAF, correlating with increased glycogen levels in the hepatopancreas. Conversely, the expression of the glycogenolysis-related gene GDE was inhibited after feeding, along with a decrease in the glycogenesis inhibitory gene GSK3. Genes in the insulin signaling pathway (ILP, PI3KCa, and AKT) were upregulated post-feeding, peaking at 3 HAF and subsequently declining. These results suggest that feeding stimulates the insulin signaling pathway and GLUT1 to transport excess glucose, inducing glycolysis and hepatopancreatic glycogenesis, while inhibiting gluconeogenesis and glycogenolysis.

Evaluation of black soldier fly (Hermetia illucens) larvae oil as a potential lipid source for largemouth bass (Micropterus salmoides): Growth performance, myofiber development and glucolipid metabolism

Black soldier fly larvae oil (BSFLO) is considered as a by-product of the production process of defatted black soldier fly larvae meal at present, and may show the potential to be used as a lipid source for aquafeeds. In this study, a total of 300 largemouth bass (initial body weight 7.95g) were fed diets containing different levels of BSFLO for 56 d to evaluate its effects on the growth performance, fatty acid composition, antioxidant capacity and glucolipid metabolism. Five isonitrogenous and isolipidic diets were designed with fish oil supplemented feed (FO) as the control diet and then feeds with BSFLO replacing 12.5%, 25%, 50% and 100% of the fish oil (BSFLO12.5, BSFLO25, BSFLO50, BSFLO100) as the treatment diets. No significant changes in weight gain and specific growth rate were observed between groups, but BSFLO100 showed a significant change in feed conversion ratio, higher than the control group (P < 0.05). The muscle and liver C12:0 and ∑n-6 PUFA content increased with the addition of BSFLO, while C20:5n-3, C22:6n-3 and ∑n-3 PUFA content gradually decreased, and significant differences were observed between FO and BSFLO100 (P < 0.05). Expression of hepatic Δ6fad and FABP genes was lower in the FO group and the highest in BSFLO50 and BSFLO100 (P < 0.05). In terms of myofiber development, Dietary BSFLO led to e a progressive increase in myofiber diameter and area, while the expression of smad-2 gene in muscle was significantly reduced in BSFLO25 and BSFLO50 (P < 0.05). Besides, the serum glucose levels were significantly lower in BSFO12.5, BSFLO50 and BSFLO100, and dietary 8% BSFLO (BSFLO100) resulted in a decrease in hepatic glycogen content from 94mgg-1 to 71.78mgg-1, along with the expression of glycolysis-related genes (GK, PK and PFK) and enzyme (PK and PFK) activities (P < 0.05), while the expression of gluconeogenesis-related genes (G6Pase) was significantly increased (P < 0.05). Dietary 4% BSFLO (BSFLO50) increased muscle and liver T-SOD activity and simultaneously reduced muscle MDA content (P < 0.05), which has the best antioxidant properties. One-variable linear regression analysis revealed that various parameters of feed utilization, glucose metabolism, and muscle development in fish were significantly and linearly affected by dietary BSFLO levels (P < 0.05). In summary, if only optimal glucose lowering is considered, 8% BSFLO is recommended. However, if feed utilization efficiency is taken into account, it is recommended that dietary BSFLO be added at no more than 4%.

Long-chain perfluoroalkylether carboxylic acids PFO5DoA and PFO4DA alter glucose, bile acid, and thyroid hormone homeostasis in fetal rats from 5-day maternal oral exposure

Chemical monitoring studies in North Carolina, USA and Shandong, China have reported detections of perfluoroalkylether carboxylic acids of increasing chain length with ether bonds between each fluorinated carbon. Despite detection there is limited hazard data available to inform risk assessment. Here, we exposed pregnant Sprague-Dawley rats to two of these compounds, perfluoro-3,5,7,9-butaoxadecanoic acid (PFO4DA) and perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA), from gestation days 18-22 across a series of doses (0.3-62.5mg/kg/d) via oral gavage. PFO5DoA was acutely toxic to rat dams and fetuses at the top two doses (30 and 62.5mg/kg), while PFO4DA did not cause acute toxicity at any doses tested. PFO5DoA significantly increased maternal liver weight (≥3mg/kg; 28% increase at 10mg/kg) while PFO4DA did not affect maternal liver weight up to 62.5mg/kg. PFO4DA and PFO5DoA both significantly reduced serum total thyroxine in maternal (≥10mg/kg for both) and fetal (≥1mg/kg) rats. Both compounds significantly reduced fetal liver glycogen concentrations, increased fetal serum total bile acids, and altered expression levels of multiple genes associated with glucose metabolism in the fetal liver. Serum concentrations of PFO5DoA were higher than PFO4DA in both rat dams and fetuses at equivalent maternal oral doses indicating greater accumulation. Dose response modelling of several fetal endpoints as a function of serum molar concentration indicates PFO5DoA was ∼3-4-fold more potent than PFO4DA. PFO5DoA and PFO4DA produced maternal and fetal toxicity from short-term oral maternal exposure indicating need for additional toxicity data to evaluate potential human health risks.

Toxic effects of chlorpyrifos on biochemical composition, enzyme activity and gill surface ultrastructure of three species of small fishes from India.

The effects of chlorpyrifos, a frequently detected organophosphate in aquatic ecosystems, on biochemical (protein and glycogen) contents and oxidative enzyme activities (catalase and lipid peroxidation) in liver, muscle and gill tissues of three freshwater fish Trichogaster fasciata, Mystus vittatus and Heteropneustes fossilis were evaluated after 21-day exposure to 1 and 10% of 96h LC50 of this pesticide, which were 1.63 and 16.3µg L-1; 5.87 and 58.7µg L-1 and 2.12 and 21.2µg L-1, respectively. On comparing with control, significant reductions in protein concentration were found in liver, muscle and gill of the three fishes treated with both higher as well as lower concentrations of the pesticide except in gill of M. vittatus and liver of H. fossilis treated with the lower concentrations. Glycogen content reductions were significant in the liver and muscle of the fishes, as well as gill tissue of T. fasciata treated with the two pesticide concentrations. Significant elevations of catalase activity were found in liver of the three fishes treated with the higher concentrations, in muscle tissues of both T. fasciata and M. vittatus treated with both the concentrations and in gills of the three fishes except H. fossilis treated with the lower concentration of the pesticide. Significant elevations of lipid peroxidation level were also found in liver of all the three fish species treated with the higher concentrations, in the muscle tissue of M. vittatus as well as in the gill of T. fasciata and H. fossilis treated with both the concentrations of the pesticide. Chlorpyrifos exposed gill ultrastructure of T. fasciata, M. vittatus and H. fossilis revealed concentration-dependent effects of the pesticide on gill surface ultrastructure which include distortion of primary and secondary lamellae, deterioration of pavement cell and microridge structures, extrusion of red blood cells (RBCs), secretion of mucous layer on filament, sloughing of primary lamellae and clumping of secondary lamellae. The present study parameters could serve as useful biomarkers for evaluating the risk of pesticide toxicity to fish. These findings also point out the possible health risks to the consumers of these fish captured from contaminated water bodies.

Genetic reduction of skeletal muscle glycogen synthase 1 abundance reveals that the refeeding-induced reversal of elevated insulin-stimulated glucose uptake after exercise is not attributable to achieving a high muscle glycogen concentration.

One exercise session can increase subsequent insulin-stimulated glucose uptake (ISGU) by skeletal muscle. Postexercise refeeding induces reversal of postexercise (PEX)-enhanced ISGU concomitant with attaining high muscle glycogen in rats. To test the relationship between high glycogen and reversal of PEX-ISGU, we injected one epitrochlearis muscle from each rat with adeno-associated virus (AAV) small hairpin RNA (shRNA) that targets glycogen synthase 1 (GS1) and injected contralateral muscles with AAV-shRNA-Scrambled (Scr). Muscles from PEX and sedentary rats were collected at 3-hour PEX (3hPEX) or 6-hour PEX (6hPEX). Rats were either not refed or refed rat-chow during the recovery period. Isolated muscles were incubated with [3H]-3-O-methylglucose, with or without insulin. The results revealed: (1) GS1 abundance was substantially lower for AAV-shRNA-GS1-treated versus AAV-shRNA-Scr-treated muscles; (2) reduced GS1 abundance in refed-rats induced much lower glycogen in AAV-shRNA-GS1-treated versus AAV-shRNA-Scr-treated muscles at 3hPEX or 6hPEX; (3) PEX-ISGU was elevated in not refed-rats at either 3hPEX or 6hPEX versus sedentary controls, regardless of GS1 abundance; (4) PEX-ISGU was not reversed by 3 h of refeeding, regardless of GS1 abundance; (5) despite substantially lower glycogen in AAV-shRNA-GS1-treated versus AAV-shRNA-Scr-treated muscles, elevated PEX-ISGU was eliminated at 6hPEX in both of the paired muscles of refed-rats; and (6) 3hPEX versus sedentary non-refed rats had greater AMP-activated protein kinase-γ3 activity in both paired muscles, but this exercise effect was eliminated in both paired muscles by 3 h of refeeding. In conclusion, the results provided compelling evidence that the reversal of exercise-enhanced ISGU by refeeding was not attributable to the accumulation of high muscle glycogen concentration.

Avenanthramides Ameliorate Insulin Resistance by Modulating Gluconeogenesis and Glycogen Synthesis in HepG2 Cells.

Diabetes mellitus (DM) is a multifaceted metabolic condition, mainly defined by elevated blood glucose levels. A feature of type 2 DM includes insulin resistance (IR), which involves impairments within the insulin signaling pathways. Avenanthramides (AVNs) are phenolic alkaloids found in Avena sativa L. The major AVNs are AVN A, AVN B, and AVN C. They have been reported to offer benefits in preventing inflammation, cancer, and cardiovascular diseases. However, the effects of AVNs on the liver glucose metabolism pathways remain unknown. This study examined the effects and underlying mechanisms through which AVNs alleviate IR induced by free fatty acid (FFA) in HepG2 cells. The results indicated that FFA treatment significantly decreased glucose consumption by 34.54% compared to the control. However, treatments with AVN A, B, and C at 100 μM increased glucose uptake by 57.93%, 58.28%, and 53.10%, respectively, compared to FFA treatment alone. This effect occurs through the increased expression of glucose transporter 4. Furthermore, AVNs significantly enhanced the glycogen content. AVNs induced increased phosphorylation of insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (Akt). AVNs treatment decreased the levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in HepG2 cells. This effect was attributed to AMP-activated protein kinase activation and inhibition of forkhead box protein O1. Collectively, these results suggest that AVNs regulate glucose metabolism by activating the IRS-1/PI3K/Akt pathway, which is related to glycogen synthesis, and by inhibiting key molecules that promote gluconeogenesis.

Maternal under-nutrition during pregnancy alters the molecular response to over-nutrition in multiple organs and tissues in nonhuman primate juvenile offspring.

Previous studies in rodents suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We hypothesized that in nonhuman primates (NHP), fetal programming of maternal undernutrition (MUN) persists postnatally with a dietary mismatch altering metabolic molecular systems that precede standard clinical measures. We used unbiased molecular approaches to examine response to a high fat, high-carbohydrate diet plus sugar drink (HFCS) challenge in NHP juvenile offspring of MUN pregnancies compared with controls (CON). Pregnant baboons were fed ad libitum (CON) or 30% calorie reduction from 0.16 gestation through lactation; weaned offspring were fed chow ad libitum. MUN offspring were growth restricted at birth. Liver, omental fat, and skeletal muscle gene expression, and liver glycogen, muscle mitochondria, and fat cell size were quantified. Before challenge, MUN offspring had lower body mass index (BMI) and liver glycogen, and consumed more sugar drink than CON. After HFCS challenge, MUN and CON BMIs were similar. Molecular analyses showed HFCS response differences between CON and MUN for muscle and liver, including hepatic splicing and unfolded protein response. Altered liver signaling pathways and glycogen content between MUN and CON at baseline indicate in utero programming persists in MUN juveniles. MUN catchup growth during consumption of HFCS suggests increased risk of obesity, diabetes, and cardiovascular disease. Greater sugar drink consumption in MUN demonstrates altered appetitive drive due to programming. Differences in blood leptin, liver glycogen, and tissue-specific molecular response to HFCS suggest MUN significantly impacts juvenile offspring ability to manage an energy rich diet.

Anti-fatigue effect of pigeon meat hydrolysate on exercise mice and its underlying mechanism: Related to oxidative stress and energy metabolism

With the acceleration of the pace in modern society, fatigue caused by high-intensity physical work, long-term heavy mental work and lack of sleep has become a widespread and noticeable health problem. In this study, pigeon meat hydrolysate (PMH) with good antioxidant activity was prepared and the anti-fatigue effects of fractions in PMH with different molecular weights (MW) on exercise mice and the underlying mechanism were investigated. Results showed that mice gavaged with PMH and its fractions exhibited improved exhaustive swimming time when compared to the Control, with fraction at MW 1–5 kDa (PP2) showed the highest improvement. Meanwhile, PP2 decreased the levels of blood lactate acid (BLA) and blood urea nitrogen (BUN), and increased the contents of muscle and liver glycogen. And the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in myocyte of mice were significantly enhanced, with the outflow of creatine kinase (CK) reduced. PP2 also exhibited significant antioxidant activity by increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and reducing the production of malondialdehyde (MDA), especially at relative higher dosages (M-PP2 and H-PP2). Metabolomics study indicated that the differential metabolites between PP2 and the Control group in liver tissues of mice were mainly related to the energy metabolism and central nervous system regulation pathways. All these results demonstrated that PP2 fraction in PMH at a dosage higher than 0.5 mg/g of mice body weight could significantly enhance the exercise endurance of mice and exert excellent anti-fatigue ability via alleviating oxidative stress and modulating energy metabolism in mice.

Cold Tolerance and Physiological Response of Natural Overwintering Pomacea canaliculata in South China.

Pomacea canaliculata (Lamarck 1822), a freshwater gastropod indigenous to lower Del Plata Basin of Argentina, has become the most destructive and invasive rice pests in south China since its introduction in the 1980s. In Guangdong, the main production areas for double rice, most of P. canaliculata overwinter in paddy field ditches after late-rice harvesting in mid-November and diapause to temporarily to avoid the damaging effects of extreme low temperatures. This pest aroused from diapause and migrated to the paddy field after early-rice reviving in next late March. Overwintering and cold tolerance of natural P. canaliculata have a non-negligible impact on population dynamics and distribution in the following year. We tested the supercooling capability, levels of cryoprotectant synthesis, activity of antioxidant defense system (antioxidant enzymes and reduced glutathione), and degree of oxidative damage (concentration of malondialdehyde as an index of lipid peroxidation) monthly, using natural P. canaliculata samples with a size-gender structure (i.e., juveniles, female, and male adults) from experimental ponds during the period of mid-November to the following April. P. canaliculata survived the winter with a monthly death rate of 7%-16.5% in coldest January. The supercooling point (SCP) of overwintering P. canaliculata decreased initially before increasing subsequently with monthly changes in water temperature. P. canaliculata accumulated a high glycogen content before December, which depleted towards the end of January, while lipid content reached peak in January and depleted since February. Activity of antioxidant defense system of P. canaliculata exhibited significant monthly differences and showed relatively higher size heterogeneity than monthly variations. The results contribute to the knowledge of adaptability in overwintering P. canaliculata and help to understand the mechanism of the invasive success of this species.

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 effect 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.

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.

Exercise-induced interactions between skeletal muscle and bone via myokines and osteokine in mice: Role of FNDC5/irisin, IGF-1, and osteocalcin

Skeletal muscle and bone interact to maintain their structure and function. Physical exercise is the most effective and easily applicable strategy to maintain their functions; however, exercise-induced interactions by soluble factors remained elusive. Our study aimed to identify exercise-induced interactions between muscle and bone by examining (1) the effects of myokine on bone and (2) the effects of osteocalcin (OCN) on skeletal muscle. To understand the effects of exercise-induced myokines on bone, we examined the effects of FNDC5 for aerobic exercise and IGF-1 for resistance exercise using a muscle-specific myokine overexpression model. To examine OCN effects on muscle, mice were intraperitoneally administered OCN-neutralizing antibody during long-term exercise. Our result showed that aerobic exercise tended to increase serum HA-tag protein attached to FNDC5 in muscle-specific overexpression groups. In addition, osteoblastic activation was increased only after aerobic exercise with HA/FNDC5 overexpression. Resistance exercise did not alter circulating HA-tag (muscle-derived IGF-1) and bone metabolism after IGF-1/HA overexpression. In the OCN study, aerobic exercise enhanced endurance capacity by restoring muscle glycogen content; however, OCN neutralization returned these to baseline. After resistance exercise, OCN suppression inhibited muscle hypertrophy and strength gains by preventing protein synthesis. Our results suggest that aerobic exercise following FNDC5 muscle overexpression promotes osteoblast activity, which may be partially caused by muscle-derived FNDC5 secretion. In addition, OCN was necessary for muscle adaptation in both aerobic and resistance exercises.

New Insights on the potential therapeutic effects of glibenclamide and Obeticholic acid against Alloxan-Induced diabetes mellitus in rat model

Diabetes mellitus (DM) represents a highly prevalent metabolic disorder across the globe. This study aimed to determine the ameliorative efficacy of glibenclamide (Gli) and obeticholic acid (OCA) against biochemical and pathological changes related to alloxan-induced diabetes. Twenty male Wistar rats were allocated into four groups; Control group, Diabetic group: received intraperitoneal injection of alloxan (120 mg/kg) for induction of diabetes, Diabetic + Gli group: Diabetic rats treated daily with oral Gli (5 mg/kg) and Diabetic + OCA group: Diabetic rats treated daily with oral OCA (10 mg/kg). All rats were subjected to 30 days treatments. Our results indicated that Gli successfully ameliorated hyperglycemia and dyslipidemia with a significant decline in serum pancreatic lipase activity and increased insulin level, while OCA had the same effect but without any enhancement in serum insulin levels. Additionally, the disturbances in liver function-related parameters and the evoked oxidative stress, interleukin(IL)-6 and IL-10 in the liver and pancreas were abrogated upon treatment with Gli and OCA. Furthermore, Gli and OCA increased AMP-activated protein kinase (P-AMPK), insulin receptor substrate 1 (IRS1), farnesoid X receptor (FXR), and glucagon-like peptide-1 receptor (GLP-1R) expressions and downregulated sterol regulatory element binding protein-1c mRNA expression. Besides, Gli and OCA have alleviated diabetes-induced histopathological distortions in hepatic and pancreatic tissues and enhanced the immunoexpression of insulin, and proliferating cell nuclear antigen with decreased immune reactivity of glucagon within pancreatic tissues. Gli and OCA decreased the immune reactivity of nuclear factor kappa B and increased the glycogen content of hepatic tissues. In conclusion, OCA is efficacious in the management of dyslipidemia and hyperglycemia of DM and its related oxidative stress.

Evaluating the impact of gadolinium contamination on the marine bivalve Donax trunculus: Implications for environmental health

Gadolinium (Gd), commonly used in contrast agents for medical imaging, has been detected in hospital wastewater and aquatic environments, raising environmental concerns. This study examined the accumulation and cellular impacts of Gd in the clam species Donax trunculus, commonly used as bioindicator of contamination. Gadolinium accumulation in clams increased with exposure and over time. Biological responses varied with Gd levels: low concentrations (10 and 50 µg/L) led to low metabolic activity and glycogen content, but high antioxidant activities and lipid peroxidation levels (LPO); high concentrations (250 and 500 µg/L) resulted in increased metabolic activity, while antioxidant enzyme activity was inhibited and LPO levels were the lowest. Metabolic activity decreased after two weeks, suggesting limited long-term metabolic resilience. The study underscores D. trunculus as an effective early warning species for Gd pollution and highlights the ecological risks of rising Gd levels, emphasizing the need for environmental monitoring and regulation.

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

Cardiac corin and atrial natriuretic peptide regulate liver glycogen metabolism and glucose homeostasis

BackgroundCardiovascular function and metabolic homeostasis are closely linked, but the underlying mechanisms are not fully understood. Corin is a protease that activates atrial natriuretic peptide (ANP), an essential hormone for normal blood pressure and cardiac function. The goal of this study is to investigate a potential corin and ANP function in regulating liver glycogen metabolism and glucose homeostasis.MethodsLiver glycogen and blood glucose levels were analyzed in Corin or Nppa (encoding ANP) knockout (KO) mice. ANP signaling was examined in livers from Corin and Nppa KO mice and in cultured human and mouse hepatocytes by western blotting.ResultsWe found that Corin and Nppa KO mice had reduced liver glycogen contents and increased blood glucose levels. By analyzing conditional KO mice lacking either cardiac or renal Corin, we showed that cardiac corin and ANP act in an endocrine manner to enhance cGMP-protein kinase G (PKG)-AKT-GSK3 signaling in hepatocytes. In cultured hepatocytes, ANP treatment stimulated PKG signaling, glucose uptake, and glycogen production, which could be blocked by small molecule PKG and AKT inhibitors.ConclusionsOur results indicate that corin and ANP are important regulators in liver glycogen metabolism and glucose homeostasis, suggesting that defects in the corin and ANP pathway may contribute to both cardiovascular and metabolic diseases.

The relation between dietary polysaccharide intake and urinary excretion of tetraglucoside.

The urinary metabolite tetraglucoside (Glc4) is a potential biomarker for hepatic glycogen storage diseases (GSDs). Glc4 is believed to reflect body glycogen content and/or turnover. However, dietary polysaccharide intake may influence Glc4 excretion, potentially limiting the utility of Glc4 as a monitoring biomarker in hepatic GSDs. We aimed to investigate the association of dietary polysaccharide intake with Glc4 excretion. Urinary Glc4 excretion (mmol/mmol creatinine and mmol/24 h) was analyzed using a validated LC-MS/MS method. Data was analyzed from 65 kidney transplant recipients and 58 healthy kidney donors in the TransplantLines cohort study. Spearman's correlation and multivariable linear regression analyses were performed. In the multivariable analysis, dry lean body mass (DLBM), dietary polysaccharide intake, transplantation status, age, sex, and glycated hemoglobin (HbA1c) served as independent variables. Daily variation was examined in 21 healthy individuals of urinary Glc4 excretion in 2-h collections over a 24-h period. Mixed generalized additive models were built to study the association of prior polysaccharide intake with Glc4 excretion. No (univariate) associations were found between polysaccharide intake and Glc4 excretion. However, a significant interaction between DLBM and polysaccharide on 24 h Glc4 excretion was observed in the multivariate analysis. Glc4 excretion throughout the day exhibited no relationship to prior polysaccharide intake. Our findings suggest an indirect effect of polysaccharide intake on Glc4 excretion, potentially due to changes in muscle glycogen content and/or turnover. We have found no evidence that dietary polysaccharides under normal intakes increase urinary Glc4 directly.

Propylthiouracil thyroid manipulation positively affects the metabolic adaptability of primiparous dairy cows to early lactation requirements

The study examined effects of thyroid manipulation with propylthiouracil (PTU) on the metabolic adaptability of transitional dairy cows to early lactation. The study included 30 primiparous Holstein-Friesian cows, which were divided into two groups: PTU+ (n = 15; received orally 4 mg/kg PTU during 20 days before expected calving) and PTU− (n = 15; did not receive orally PTU). Blood was sampled from each cow consecutively from − 20, − 17, − 13, − 5, − 4, − 3, − 2, and − 1 days before the expected term of calving, calving day (0), and + 1, + 2, + 3, + 4, + 5, + 10, + 15, + 30 and + 60 days after the calving to measure thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), insulin, glucose, beta-hydroxybutyrate (BHB), bilirubin, total protein and albumin concentrations. Liver samples were biopsied at −7 ± 2 and +7 day relative to calving from both groups of cows to determine deiodinase (DIO) expressions and fat and glycogen content. Additionally, milk yield was monitored during the first 60 days of lactation. PTU successfully induced thyroid suppression by significantly reducing T3 and T4 concentrations and hepatic DIO1 expressions and caused PTU+ cows to have significantly higher insulin and glucose concentration in the precalving period. After calving, PTU+ cows had higher insulin and glucose concentration, liver glycogen content and overall milk production, lower BHB concentration, BCS loss, and liver fat deposits. Accordingly, cows treated with PTU have a more favourable energy balance and metabolic adaptation to early lactation.

Spatheliachromen mitigates methylglyoxal-induced myotube atrophy by activating Nrf2, inhibiting ubiquitin-mediated protein degradation, and restoring mitochondrial function

BackgroundMethylglyoxal (MGO) is a potent precursor of glycative stress that leads to oxidative stress and muscle atrophy in diabetes. Spatheliachromen (FPATM-20), derived from Ficus pumila var. awkeotsang, exhibited potential antioxidant activity. PurposeThis study aimed to evaluate the potential impact and underlying mechanisms of FPATM-20 on MGO-induced myotube atrophy and mitochondrial dysfunction in mouse skeletal C2C12 myotubes. MethodsAtrophic and antioxidant factors were evaluated using immunofluorescence, enzyme-linked immunosorbent assay, and western blotting. Mitochondrial function was assessed using the ATP assay and Seahorse Cell Mito Stress Test. The glycogen content was determined using periodic acid-Schiff staining. Molecular docking was performed to determine the interaction between FPATM-20 and Keap1. ResultsIn myotubes treated with MGO, FPATM-20 activated the Nrf2 pathway, reduced ROS levels, enhanced antioxidant defense, and increased glycogen content. FPATM-20 improved myotube viability and size, upregulated myosin heavy chain (MyHC) expression, modulated ubiquitin-proteasome molecules (nuclear FoxO3a, atrogin-1, MuRF-1, and p62/SQSTM1), and inhibited apoptosis (Bax/Bcl-2 ratio and cleaved caspase 3). Moreover, FPATM-20 restored mitochondrial function, including mitochondrial membrane potential, mitochondrial oxygen consumption rate, and mitochondrial biogenesis pathway (nuclear PGC-1α/TFAM/FNDC5). The inhibition of Nrf2 with ML385 reversed the effects of FPATM-20 on MGO. Furthermore, molecular docking confirmed the binding of FPATM-20 to Keap1, a suppressor of Nrf2, showing the crucial role of Nrf2 in protective effects. ConclusionsFPATM-20 protects myotubes from MGO toxicity by activating the Nrf2 antioxidant defense, reducing protein degradation and apoptosis, and enhancing mitochondrial function. Thus, FPATM-20 may be a novel agent for preventing skeletal muscle atrophy.

Subacute Effects of Moderate-Intensity Aerobic Exercise in the Fasted State on Cell Metabolism and Signaling in Sedentary Rats.

Background: Physical inactivity induces insulin resistance (IR) and metabolic imbalances before any significant changes in adiposity. Recent studies suggest that the beneficial effects of exercise can be potentiated if performed while fasting. This work aimed to compare the subacute effects of fed- and fasted-state single-bout exercise on biochemical parameters and cellular signaling in the metabolism. Methods: The animals were allocated into fed rest (FER), fasting rest (FAR), fed exercise (FEE), and fasting exercise (FAE) groups. The exercise protocol was a 30 min treadmill session at 60% of V˙O2max. The fasting groups fasted for 8 h before exercise and were killed after 12 h post-exercise. Results: Soleus glycogen concentration increased only in the fasting groups, whereas the triglyceride (TGL) content increased in brown adipose tissue (BAT) and liver in the FAE. The FAE showed decreased plasma total cholesterol concentration compared withthe FAR group. Immunocontent of HSP70, SIRT1, UCP-1, and PGC1-α did not change in any tissue investigated. Conclusions: Our results indicate that physical exercise while fasting can have beneficial metabolic effects on sedentary animals. Remarkably, in the FAE group, there was a reduction in total plasma cholesterol and an increase in the capacity of BAT to metabolize and store nutrients in the form of TGLs.