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Background: To explore the efficacy of powder of ginsengporia and atractylodis macrocephalae combined with aerobic exercise in the treatment of obese T2DM and its influence on glucose and lipid metabolism indices. Results: Both groups of patients were given metformin drug treatment. The control group was given aerobic exercise intervention, and the observation group was given ginsengporia and atractylodis macrocephalae on the basis of the control group. The total effective rate of the observation group (95.74%) was higher than that of the control group (82.98%) (P 0.05). Conclusions: Powder of ginsengporia and atractylodis macrocephalae combined with aerobic exercise is effective in treating obese T2DM, which can alleviate clinical symptoms and the disorder of glucose and lipid metabolism, and improve the islet function and gastrointestinal function.How to cite: Liu G, Kanti Das S. Efficacy of powder of ginsengporia and atractylodis macrocephalae combined with aerobic exercise in the treatment of obese T2DM: A randomized controlled clinical trial. Electron J Biotechnol 2024;71. https://doi.org/10.1016/j.ejbt.2024.04.006.

Objectives: Reprogramming of energy metabolism is a well-established hallmark of cancer, with aerobic glycolysis classically considered a prominent feature. We investigate the heterogeneity in glucose metabolism pathways within resectable primary lung adenocarcinoma and its clinical significance. Methods: Using The Cancer Genome Atlas data, RNA expressions were extracted from 489 primary lung adenocarcinoma samples. Prognostic influence of glycolytic, aerobic, and mitochondrial markers (monocarboxylate transporter [MCT]4, MCT1, and translocase of outer mitochondrial membrane 20, respectively) was assessed using Kaplan-Meier analysis. Clustering of 35 genes involved in glucose metabolism was performed using the k-means method. The clusters were then analyzed for associations with demographic, clinical, and pathologic variables. Overall survival was assessed using the Kaplan-Meier estimator. Multivariate analysis was performed to assess the independent prognostic value of cluster membership. Results: Classical statistical approach showed that higher expression of MCT4 was associated with a significantly worse prognosis. Increased expression of translocase of outer mitochondrial membrane 20 was associated with a nonsignificant trend toward better prognosis, and increased expression of MCT1 was associated with a better outcome. Clustering identified 3 major metabolic phenotypes, dominantly hypometabolic, dominantly oxidative, and dominantly mixed oxidative/glycolytic with significantly different pathologic stage distribution and prognosis; mixed oxidative/glycolytic was associated with worse survival. Cluster membership was independently associated with survival. Conclusions: This study demonstrates the existence of distinct glucose metabolism clusters in resectable lung adenocarcinoma, providing valuable prognostic information. The findings highlight the potential relevance of considering metabolic profiles when designing strategies for reprogramming energy metabolism. Further studies are warranted to validate these findings in different cancer types and populations.

Background: Liver plays a central role in systemic glucose and lipid metabolism. High-fat diet (HFD) and obesity are related to hepatic lipid accumulation and insulin resistance (InsR). Diacylglycerols (DAG) play a key role in the induction of InsR, however their involvement in hepatic InsR remains debated. This study aimed to clarify and confirm the role of glycero-3-phosphate acyltransferase 1 (GPAT1), a rate-limiting enzyme in DAG synthesis, in the progression of hepatic InsR in the context of HFD-induced lipid accumulation and insulin resistance in the liver. Methods: Liver-targeted GPAT1 silencing was performed using shRNA-mediated hydrodynamic gene delivery. Lipid species including LCA-CoA, sphingolipids, DAG and acyl-carnitines were quantified using UHPLC/MS/MS while insulin signalling was assessed at protein level by Western Blot. Hepatic glucose metabolism, including glucose-6-pasphate content and gluconeogenesis rate was evaluated using GC/MS. Results: HFD-fed animals developed InsR, evidenced by increased HOMA-IR, enhanced gluconeogenesis and reduced glycogen content compared to controls. Hepatic GPAT1 silencing in HFD-fed animals resulted in a significant reduction of DAG and TAG levels, increased acyl-carnitines content and upregulated mitochondrial β-oxidation protein expression. These changes were accompanied by improved insulin signalling, enhanced glycogen storage, and reduced gluconeogenesis. Conclusions: Silencing GPAT1, and thereby reducing glycerolipid synthesis, promotes β-oxidation and ameliorates HFD-induced hepatic insulin resistance, confirming the enzyme's pivotal role in liver metabolic dysfunction associated with increased lipid supply.

Glucose metabolism disturbances may result in diabetes-associated cognitive decline (DACI). Methionine restriction (MR) diet has emerged as a potential dietary strategy for managing glucose homeostasis. However, the effects and underlying mechanisms of MR on DACI have not been fully elucidated. Here, we found that a 13-week MR (0.17 % methionine, w/w) intervention starting at 8 weeks of age improved peripheral insulin sensitivity in male db/db mice, a model for type 2 diabetes. Notably, MR significantly improved working as well as long-term memory in db/db mice, accompanied by increased PSD-95 level and reduced neuroinflammatory factors, malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG). We speculate that this effect may be mediated by MR activating hepatic fibroblast growth factor 21 (FGF21) and the brain FGFR1/AMPK/GLUT4 signaling pathway to enhance brain glucose metabolism. To further delineate the mechanism, we used intracerebroventricular injection of adeno-associated virus to specifically knock down FGFR1 in the brain to verify the role of FGFR1 in MR-mediated DACI. It was found that the positive effects of MR on DACI were offset, reflected in decreased cognitive function, impaired synaptic plasticity, upregulated neuroinflammation, and balanced enzymes regulating reactive oxygen species (Sod1, Sod2, Nox4). Of note, the FGFR1/AMPK/GLUT4 signaling pathway and brain glucose metabolism were inhibited. In summary, our study demonstrated that MR increased peripheral insulin sensitivity, activated brain FGFR1/AMPK/GLUT4 signaling through FGF21, maintained normal glucose metabolism and redox balance in the brain, and thereby alleviated DACI. These results provide new insights into the effects of MR diet on cognitive dysfunction caused by impaired brain energy metabolism.

Generally, energy expenditure and compensation according to food deprivation and refeeding often occur along the life cycle of farmed-raised fish. Fasting and refeeding are also hypothesised to modulate carbohydrate metabolism particularly for herbivorous and/or omnivorous. This study aims to investigate the effects of short-term fasting and subsequent refeeding with high or low−carbohydrate diets on the intermediary carbohydrate metabolism of juvenile and adult Nile tilapia (Oreochromis niloticus) which is known to be a good user of carbohydrate as an energy source. Fish were fasted for 4 days and subsequently refed with either a low carbohydrate and high protein (LC/HP) or high carbohydrate and low protein (HC/LP) diet for 4 days. Our results showed that 4 days of refeeding with either one of the diets could compensate for weight loss due to fasting. Thus, we investigated the effects of a 4-day-refeeding strategy and different carbohydrate−refeeding diets on plasma metabolites, nutrient composition, and glucose and its related metabolism in the liver and muscle of adult fish. Refeeding had similar effects in adults and juveniles and induced modulations to the intermediary metabolism: (1) refeeding with the HC/LP diet elevated plasma glucose levels; (2) refeeding with both diets increased triglyceride levels in the plasma, liver, and muscle, but the effect of the HC/LP diet was superior; (3) refeeding elevated plasma cholesterol levels in adults, irrespective of diet; (4) refeeding with both diets increased hepatic lipid levels in juveniles, with stronger effects observed in those fed the HC/LP diet, and refeeding with the HC/LP diet elevated hepatic lipid levels in adults; (5) refeeding with both diets increased the plasma protein content, but the effect of the LC/HP diet was superior; (6) refeeding with the LC/HP diet increased hepatic protein content in adults; and (7) refeeding with both diets increased hepatic glycogen levels, but the effect of the HC/LP diet was superior. Additionally, in juveniles and adults, refeeding with the HC/LP diet upregulated the expression of glycolytic genes in the liver and muscle, lipogenic genes in the liver, and glucose transport genes. Moreover, refeeding with the HC/LP diet downregulated the expression of gluconeogenic and amino acid catabolism genes in the liver and amino acid catabolism genes in the muscle. Collectively, the effect of short-term refeeding with a high carbohydrate diet on intermediary metabolism resembled that of long-term feeding, supporting the hypothesis that Nile tilapia, an omnivorous fish, is highly responsive to dietary carbohydrates.

The pathogenesis of osteoporosis is driven by several mechanisms including the imbalance between osteoblastic bone formation and osteoclastic bone resorption. Currently, the role of Niacin (NA), also known as vitamin B3, in the regulation of osteoblastic differentiation is not fully understood. Data from the NHANES database were employed to investigate the association of NA intake with the prevalence of osteoporosis. Alterations in mRNA and protein levels of genes and proteins involved in osteogenic differentiation were evaluated via techniques including qRT-PCR, protein immunoblotting, Alkaline Phosphatase (ALP) activity analysis, ALP staining, and Alizarin Red staining. Changes in the mouse skeletal system were investigated by organizational analysis and Micro-CT. The results indicated that NA promoted osteogenic differentiation. Co-immunoprecipitation and chromatin immunoprecipitation were performed to explore the underlying mechanisms. It was observed that NA promoted AREG expression by deacetylating C/EBPβ via SIRT2, thereby activating the PI3K-AKT signaling pathway. It also enhanced the activity of the pivotal glycolytic enzyme, PFKFB3. This cascade amplified osteoblast glycolysis, facilitating osteoblast differentiation. These findings demonstrate that NA modulates glucose metabolism and influences osteogenic differentiation via the SIRT2-C/EBPβ-AREG pathway, suggesting that NA may be a potential therapeutic agent for the management of osteoporosis, and AREG could be a plausible target.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutant huntingtin protein with an abnormal CAG/polyQ expansion in the N-terminus of HTT exon 1. HD is characterized by progressive neurodegeneration and metabolic abnormalities, particularly in the brain, which accounts for approximately 20 % of the body's resting metabolic rate. Dysregulation of energy homeostasis in HD includes impaired glucose transporters, abnormal functions of glycolytic enzymes, changes in tricarboxylic acid (TCA) cycle activity and enzyme expression in the basal ganglia and cortical regions of both HD mouse models and HD patients. However, current understanding of brain cell behavior during energy dysregulation and its impact on neuron–glia crosstalk in HD remains limited. This review provides a comprehensive summary of the current understanding of the differences in glucose metabolism between neurons and glial cells in HD and how these differences contribute to disease development compared with normal conditions. We also discuss the potential impact of metabolic shifts on neuron–glia communication in HD. A deeper understanding of these metabolic alterations may reveal potential therapeutic targets for future drug development.

Cancer growth requires high amount of nicotinamide adenine dinucleotide phosphate (NADPH) to feed the anabolic reactions and preserve the redox balance. NADPH level is largely preserved by the oxidative arm of the pentose phosphate pathway (PPP). Here, we show that prolonged glucose deprivation of triple negative breast cancer MDA-MB-231 cells decreases proliferation rate, promotes hexose funneling to glycolysis hampering the PPP. The impairment in PPP activity and the consequent NADPH depletion are partially counterbalanced by enhancing the malic enzyme-1 catalyzed conversion of glutamine-derived malate to pyruvate. However, the use of these glucose-independent carbons implies the integrity of the two PPPs represented in all eukaryotic cells, i.e., the well-recognized cytosolic PPP, triggered by glucose-6-phosphate dehydrogenase (G6PD) and its reticular counterpart, triggered by hexose-6P-dehydrogenase (H6PD). This evidence configures the reticular PPP as a mandatory player in the regeneration of NADPH reductive power by cancer cells.

Background: Parkinson's disease (PD) is a common central neurodegenerative disease in middle-aged and elderly people. The progressive degeneration and death of dopaminergic neurons leads to insufficient dopamine (DA) neurotransmitters. Acupuncture and moxibustion can alleviate the aging of neurons. Therefore, studying the neuroprotective effects of electroacupuncture (EA) in PD mice is particularly important. Methods: Intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was used to establish a PD mouse model, and lipopolysaccharide (LPS) was used to induce microglia polarization. Western blotting, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), Nissl staining and immunohistochemistry were used to detect neuronal apoptosis and injury, α-syn expression and microglial accumulation in PD mice. In addition, the levels of inflammatory factors were determined using enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the Ca2+ content. The fluorescein isothiocyanate (FITC) labeling method was used to assess glucose uptake. A reagent kit was used to detect glucose and lactate levels. Results: MPTP induced the selective loss of DA neurons in the SN of mice, altered Ca2+ homeostasis, and induced an inflammatory response. In addition, maintaining Ca2+ homeostasis depends on the activity of transient receptor potential channel 1 (TRPC1). EA therapy promotes TRPC1 expression, which has a negative regulatory effect on sodium–glucose cotransporter 1 (SGLT1). Under the action of EA, TRPC1 protein expression increased, Ca2+ concentrations increased, and the effect of SGLT1 was inhibited, thereby facilitating glucose metabolism, blocking the activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, restraining M1 polarization of microglia, and alleviating the PD process. Conclusion: EA promotes TRPC1/Ca2+ pathway activation, inhibits SGLT1-mediated regulation of glucose metabolism and PI3K/AKT pathway activation, inhibits microglial M1 polarization, and alleviates PD.

Background: Chronic stress can induce the cognitive impairment, and even promote the occurrence and development of Alzheimer's disease (AD). Evidence has suggested that chronic stress impacts on glucose metabolism, and both of these have been implicated in AD. Here we focused on the effect of insulin resistance in glucose metabolism, and further evaluated the changes in cognition and pathology. Methods: Male 9-month-old wild-type and APP/PS1 mice were randomly divided into 4 groups. Mice in the chronic unpredictable mild stress (CUMS) groups were exposed for 4 weeks. Homeostatic Model Assessment (HOMA) was utilized to evaluate insulin sensitivity. A total of eighty-four genes related to the insulin signaling pathway were examined for rapid screening. Additionally, the phosphorylated protein expressions of insulin receptors (IR), IR substrate 1 (IRS1), c-Jun N-terminal kinase (JNK), and amyloid were detected in the hippocampus. Cognitive function was assessed through ethological methods. Cognitive function was assessed using both the Morris water maze (MWM) and the Passive avoidance test (PAT). Results: Four weeks of CUMS exposure significantly increased the HOMA value, indicating reduced insulin sensitivity. The gene expressions of Insr and Lipe were downregulated. Additionally, the analysis revealed a significant interaction between the genotype (wild-type vs. APP/PS1) and CUMS treatment on the phosphorylated protein expressions of insulin receptor substrate 1 (IRS1). Specifically, CUMS exposure increased the inhibitory phosphorylation site (IRS1-pSer636) and decreased the excitatory phosphorylation site (IRS1-pTyr465) in the post-insulin receptor signaling pathway within the hippocampus of both wild-type and APP/PS1 mice. Moreover, CUMS exposure induced and exacerbated cognitive impairments in both wild-type and APP/PS1 mice, as assessed by the Morris water maze (MWM) and Passive avoidance test (PAT). However, there was no significant effect of CUMS on senile plaque deposition or levels of Aβ42 and Aβ40 in wild-type mice. Conclusions: Chronic stress significantly affects hippocampal cognitive function through insulin resistance and exacerbates AD pathology. This study reveals the complex relationship between chronic stress, insulin resistance, and AD, providing new insights for developing interventions targeting chronic stress and insulin resistance.

Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.

Objective: Excessive consumption of added sugars has been linked to the rise in obesity and associated metabolic abnormalities. Non-nutritive sweeteners (NNSs) offer a potential solution to reduce sugar intake, yet their metabolic safety remains debated. This study aimed to systematically assess the long-term metabolic effects of commonly used NNSs under both normal and obesogenic conditions. Methods: To ensure consistent sweetness level and controlling for the acceptable daily intake (ADI), eight weeks old C57BL/6 male mice were administered with acesulfame K (ace K, 535.25 mg/L), aspartame (411.75 mg/L), sucralose (179.5 mg/L), saccharin (80 mg/L), or steviol glycoside (Reb M, 536.25 mg/L) in the drinking water, on the background of either regular or high-fat diets (in high fat diet 60% of calories from fat). Water or fructose-sweetened water (82.3.gr/L), were used as controls. Anthropometric and metabolic parameters, as well as microbiome composition, were analyzed following 20-weeks of exposure. Results: Under a regular chow diet, chronic NNS consumption did not significantly affect body weight, fat mass, or glucose metabolism as compared to water consumption, with aspartame demonstrating decreased glucose tolerance. In diet-induced obesity, NNS exposure did not increase body weight or alter food intake. Exposure to sucralose and Reb M led to improved insulin sensitivity and decreased weight gain. Reb M specifically was associated with increased prevalence of colonic Lachnospiracea bacteria. Conclusions: Long-term consumption of commonly used NNSs does not induce adverse metabolic effects, with Reb M demonstrating a mild improvement in metabolic abnormalities. These findings provide valuable insights into the metabolic impact of different NNSs, aiding in the development of strategies to combat obesity and related metabolic disorders.

Immune metabolism is a result of many specific metabolic reactions, such as glycolysis, the tricarboxylic acid (TCA) pathway, the pentose phosphate pathway (PPP), mitochondrial oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), fatty acid biosynthesis (FAs) and amino acid pathways, which promote cell proliferation and maintenance with structural and pathological energy to regulate cellular signaling. The metabolism of macrophages produces many metabolic intermediates that play important regulatory roles in tissue repair and regeneration. The metabolic activity of proinflammatory macrophages (M1) mainly depends on glycolysis and the TCA cycle system, but anti-inflammatory macrophages (M2) have intact functions of the TCA cycle, which enhances FAO and is dependent on OXPHOS. However, the metabolic mechanisms of macrophages in tissue repair and regeneration have not been well investigated. Thus, we review how three main metabolic mechanisms of macrophages, glucose metabolism, lipid metabolism, and amino acid metabolism, regulate tissue repair and regeneration.

Cadmium (Cd) is an environmental endocrine disruptor. Despite increasing research about the metabolic effects of Cd on HepG2 cells, information about the metabolic effects of Cd on insulin resistance HepG2 (IR-HepG2) cells is limited. Currently, most individuals with diabetes are exposed to Cd due to pollution. Previously, we reported that Cd exposure resulted in decreased blood glucose levels in diabetic mice, the underlying mechanism deserves further study. Therefore, we used palmitic acid (0.25 mM) to treat HepG2 cells to establish IR-HepG2 model. IR-HepG2 cells were exposed to CdCl2 (1 μM and 2 μM). Commercial kits were used to measure glucose production, glucose consumption, ROS and mitochondrial membrane potential. Western blot and qRT-PCR were used to measure the proteins and genes of glucose metabolism. In the current study setting, we found no significant changes in glucose metabolism in Cd-exposed HepG2 cells, but Cd enhanced glucose uptake, inhibited gluconeogenesis and activated the insulin signaling pathway in IR-HepG2 cells. Meanwhile, we observed that Cd caused oxidative stress and increased the intracellular calcium concentration and inhibited mitochondrial membrane potential in IR-HepG2 cells. Cd compensatingly increased glycolysis in IR-HepG2 cells. Collectively, we found Cd ameliorated glucose metabolism disorders in IR-HepG2 cells. Furthermore, Cd exacerbated mitochondrial damage and compensatory increased glycolysis in IR-HepG2 cells. These findings will provide novel insights for Cd exposure in insulin resistant individuals.

Mice models of Alzheimer's disease (APP/PS1) typically experience cognitive decline with age. G6PD overexpressing mice (G6PD-Tg) exhibit better protection from age-associated functional decline including improvements in metabolic and muscle functions as well as reduced frailty compared to their wild-type counterparts. Importantly G6PD-Tg mice show diminished accumulation of DNA oxidation in the brain at different ages in both males and females. To further explore the potential benefits of modulating the G6PD activity in neurodegenerative diseases, triple transgenic mice (3xTg G6PD) were generated, overexpressing APP, PSEN1, and G6PD genes. The cognitive decline characteristic of APP/PS1 mice was prevented in 3xTg G6PD mice, despite similar amyloid-β (Aβ) levels in the hippocampus. This challenges the dominant hypothesis in Alzheimer's disease (AD) etiology and the majority of therapeutic efforts in the field, based on the notion that Aβ is pivotal in cognitive preservation.Notably, the antioxidant properties of G6PD led to a decrease in oxidative stress parameters, such as improved GSH/GSSG and GSH/CysSSG ratios, without major changes in oxidative damage markers. Additionally, metabolic changes in 3xTg G6PD mice increased brain energy status, countering the hypometabolism observed in Alzheimer's models. Remarkably, a higher respiratory exchange ratio suggested increased carbohydrate utilization. The relative failures of Aβ-targeted clinical trials have raised significant skepticism on the amyloid cascade hypothesis and whether the development of Alzheimer's drugs has followed the correct path. Our findings highlight the significance of targeting glucose-metabolizing enzymes rather than solely focusing on Aβ in Alzheimer's research, advocating for a deeper exploration of glucose metabolism's role in cognitive preservation.

Metformin, or 1,1-dimethylbiguanide, is a hypoglycemic drug that lowers blood glucose by reducing glycogen synthesis and increasing glucose uptake in peripheral tissues. Six diets with iso-nitrogenous and iso-lipid compositions were prepared, including a positive control (20 % carbohydrate, PC) and a negative control (30 % carbohydrate, T0). The experimental diets contained 0.2 % (T2), 0.4 % (T4), 0.6 % (T6), and 0.8 % (T8) metformin based on the negative control diet. A total of 540 hybrid groupers, with consistent size and health conditions, were randomly assigned to six groups. Each group contained 30 fish, with three replicates per group, and they were fed for eight weeks. The high-carbohydrate diet reduced weight gain, digestive enzyme activities and specific growth rates (P>0.05), while significantly increasing hepatosomatic indices (P

Epigallocatechin gallate (EGCG) and L-theanine (LTA) are two key bioactive components of tea that modulate nutrient metabolism. However, whether the combination of EGCG and LTA will result in synergistic benefits for glucose and lipid metabolism disorders is still unclear. Here, we treated leptin receptor-knockout (Lepr-KO) rats with EGCG and EGCG combined with LTA to examine how combined EGCG and LTA affect glucose and lipid metabolism disorders. Our data suggested that EGCG or EGCG plus LTA all significantly reduced serum triglycerides, total cholesterol, random blood glucose, and increased glucose tolerance, as well as alleviated fatty liver formation in Lepr-KO rats. Moreover, compared with EGCG alone, EGCG plus LTA significantly reduced random blood glucose and plasma triacylglycerols (TG) levels, and alleviated hepatic steatosis. Mechanistic analysis revealed that EGCG plus LTA improved glucose metabolism disorders by activating hepatic glucokinase (GCK) and glycogen synthase 2 (GYS2) expression, and inhibited fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1) for lowering hepatic TG accumulation. This study demonstrated that LTA enhances the improvements of EGCG on glucose and lipid metabolism disorders in Lepr-KO rats, especially in glycometabolism.

Largemouth bass (Micropterus salmoides) is poor at utilizing starch, and it is not clear whether commensal microorganisms can alleviate the adverse influences of high wheat starch in M. salmoides. Here, twelve autochthonous microorganisms with amylase producing abilities were isolated from the M. salmoides fed with diets containing 6 %, 12 %, or 18 % starch. Among them, Citrobacter freundii F1, Bacillus altitudinis F7, Enterococcus casseliflavus D12, Plesiomonas shigelloides D15, Bacillus cabrialesii D16, Citrobacter portucalensis K25 and Serratia oryzae K28 showed no hemolytic activity and were safety for M. salmoides. A 42-d feeding experiment was performed to study the functions of the seven microorganisms. A total of 810 fish (5.9 ± 0.01 g) were equally distributed into 9 groups. The control groups C6 and C18 were respectively fed with 6 % and 18 % wheat starch diets, the groups F1, F7, D12, D15, D16, K25 and K28 were fed with 18 % wheat starch diets respectively supplemented with 1.0×108 CFU/g C. freundii F1, B. altitudinis F7, E. casseliflavus D12, P. shigelloides D15, B. cabrialesii D16, C. portucalensis K25 and S. oryzae K28. The results indicated that compared with 6 % starch, 18 % level inhibited the growth performance, increased the hepatic glycogen and fat contents, improved the activities of glycolysis-related enzymes (hexokinase (HK), glucokinase (GK), phosphofructokinase (PFK), pyruvate kinase (PK)), decreased the activities of gluconeogenesis-related enzymes, pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK), promoted the activity of lipid synthases-related enzyme carnitine palmitoyl transferaseⅠ (CPT1) and reduced the activity of lipolytic enzymes-related lipoprotein lipase (LPL). C. freundii F1, P. shigelloides D15, C. portucalensis K25 and S. oryzae K28 had relatively poor alleviating effects, while B. altitudinis F7, E. casseliflavus D12 and B. cabrialesii D16 significantly promoted the final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER), decreased feed conversion rate (FCR), significantly reduced the hepatic glycogen and fat contents, decreased the activities of glycolysis-related enzymes (HK, GK, PK), improved the activities of gluconeogenesis-related enzymes (PC, PEPCK), reduced the activity of lipid synthases-related enzyme CPT1 (P < 0.05), which proved that these three strains could effectively alleviate the negative effects of high starch in M. salmoides. In conclusion, among the seven autochthonous microorganisms, B. altitudinis F7, E. casseliflavus D12 and B. cabrialesii D16 presented better potential advantages in improving glucose and lipid metabolisms, thus promoting the growth performance of M. salmoides fed with high wheat starch diet.

Sudachitin, a member of the flavonoid family, reportedly improves glucose metabolism after long-term administration, but details of the underlying mechanisms are unknown. We found that Sudachitin approximately doubles insulin secretion under high glucose concentrations in mouse pancreatic islets and MIN6 cells. When Sudachitin was orally administered to mice, early-phase insulin secretion was increased and a 30 % reduction in blood glucose levels was demonstrated 30 min after glucose loading. Insulin tolerance tests also showed Sudachitin to increase systemic insulin sensitivity. Additionally, we observed that Sudachitin raised intracellular cAMP levels in pancreatic islets. Phosphodiesterase (PDE) activity assays revealed Sudachitin to inhibit PDE activity and computer simulations predicted a high binding affinity between PDEs and Sudachitin. These findings suggest that Sudachitin enhances both insulin secretion and insulin sensitivity via an increase in intracellular cAMP resulting from PDE inhibition. These insights may facilitate understanding the mechanisms underlying the regulation of glucose metabolism by Sudachitin and other isoflavones.

Folic acid (FA) is an essential vitamin for the growth and health of aquatic organisms in the aquaculture industry. The purpose of this study was to investigate the effects and potential mechanisms of action of dietary FA on the growth and immune response of red swamp crayfish (Procambius clarkii). Crayfish (n = 360; 3 tanks of 20 crayfish for each dietary treatment) were fed diets containing different levels of FA (0 [control], 0.5, 1, 2, 4, and 8 mg/kg dry feed weight) for 60 d. Broken-line analysis based on the final weight and specific growth rate revealed that the optimal dietary FA level for promoting growth was 2 mg/kg. Villus length, lipase activity, and antioxidant superoxide dismutase activity significantly increased under the 2 mg/kg treatment. Transcriptome analysis identified 177 upregulated and 298 downregulated differentially expressed genes (DEGs) between the 0 (control) and 2 mg/kg groups. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the most significantly enriched pathways were related to glucose metabolism. Among the DEGs involved in glucose metabolism, Tpi1 (triosephosphate isomerase 1) and Pck1 (phosphoenolpyruvate carboxykinase 1) were upregulated and downregulated under FA treatment, respectively. Our findings suggest that the optimal dietary FA requirement for crayfish is 2 mg/kg and that dietary FA may enhance nutrient bioavailability and regulate glucose metabolism to improve crayfish growth performance.

The aim of this study was to investigate effects of dietary metformin supplementation on growth performance, liver function, and glucose metabolism of rice field eel (Monopterus albus) fed high carbohydrate diets (HCDs). Four isonitrogenous and isolipid diets were formulated, different in 15% α-starch (LC), 35% α-starch (HC), and 35% α-starch supplemented with 0.25% (HCM0.25) and 0.5% metformin (HCM0.5), respectively. After 8 weeks, the results showed that HCDs did not affect growth performance, but reduced the activities of amylase and trypsin, and damaged liver function together with the increase of hepatic glycogen content. HCM0.25 did not affect whereas HCM0.5 damaged the growth performance. Activities of amylase in HCM0.25 group and trypsin in both HCM0.25 and HCM0.50 groups were increased. While HCM0.25 lowered serum AST and ALT activities, HCM0.5 showed an increase. HCM0.25 caused a reduction in vacuoles size and a increase in nuclei number, whereas HCM0.5 failed to induce similar effects. The liver glycogen content was reduced by both HCM0.25 and HCM0.5 whereas the muscle glycogen content remained stable. Both HCM0.25 and HCM0.5 enhanced glycolysis–related enzymatic activities (PFK, PK) in liver, while reducing gluconeogenesis (FBPase). Similarly, both treatments upregulated gene expression of pk in liver, while downregulated g6pase, fbpase and pepck. Moreover, HCM0.25 and HCM0.5 increased PFK, G6Pase, FBPase and PEPCK activity in muscle, with HCM0.25 further upregulating gene expressions of hk, pfk, g6pase and pepck. Both treatments downregulated the gene expression of g6pd in muscle, whereas only HCM0.25 upregulated ampkα1, tbc1d1 and glut4. In summary, dietary 0.25% metformin improved liver function, reduced liver glycogen content, and regulated glucose metabolism and AMPKα-TBC1D1-GLUT4 pathway. However, 0.50% metformin did not demonstrate positive effects and even had adverse effects on growth performance.

Muscle is the main edible part of bony fish. The purpose of this study was to investigate the influences of phenylalanine (Phe) on muscle quality, amino acid composition, fatty acid composition, glucose metabolism, and protein deposition in adult grass carp. The diets at 2.30, 4.63, 7.51, 10.97, 13.53, and 17.07 g/kg Phe levels were fed for 9 weeks. The results manifested that Phe (10.97–13.53 g/kg) increased the pH of the fillets and decreased muscle cooking loss and lactic acid content; Phe (7.51–17.07 g/kg) improved the composition of the fillets in terms of flavor (free) amino acids, bound amino acids (especially EAA), and fatty acids (especially EPA and DHA); Phe (7.51–13.53 g/kg) increased muscle glycogen content (possibly related to the AMPK signaling pathway) and muscle protein deposition (possibly related to IGF-1/4EBP1/TOR and AKT/FOXOs signaling pathways). In conclusion, a diet with appropriate Phe levels could improve fillet quality.

Objectives: During fasting, liver pivotally regulates blood glucose levels through glycogenolysis and gluconeogenesis. Kidney also produces glucose through gluconeogenesis. Gluconeogenic genes are transactivated by fasting, but their expression patterns are chronologically different between the two organs. We find that renal gluconeogenic gene expressions are positively correlated with the blood β-hydroxybutyrate concentration. Thus, we herein aim to investigate the regulatory mechanism and its physiological implications. Methods: Gluconeogenic gene expressions in liver and kidney were examined in hyperketogenic mice such as high-fat diet (HFD)-fed and ketogenic diet-fed mice, and in hypoketogenic PPARα knockout (PPARα−/−) mice. Renal gluconeogenesis was evaluated by rise in glycemia after glutamine loading in vivo. Functional roles of β-hydroxybutyrate in the regulation of renal gluconeogenesis were investigated by metabolome analysis and RNA-seq analysis of proximal tubule cells. Results: Renal gluconeogenic genes were transactivated concurrently with blood β-hydroxybutyrate uprise under ketogenic states, but the increase was blunted in hypoketogenic PPARα−/− mice. Administration of 1,3-butandiol, a ketone diester, transactivated renal gluconeogenic gene expression in fasted PPARα−/− mice. In addition, HFD-fed mice showed fasting hyperglycemia along with upregulated renal gluconeogenic gene expression, which was blunted in HFD-fed PPARα−/− mice. In vitro experiments and metabolome analysis in renal tubular cells showed that β-hydroxybutyrate directly promotes glucose and NH3 production through transactivating gluconeogenic genes. In addition, RNA-seq analysis revealed that β-hydroxybutyrate-induced transactivation of Pck1 was mediated by C/EBPβ. Conclusions: Our findings demonstrate that β-hydroxybutyrate mediates hepato–renal interaction to maintain homeostatic regulation of blood glucose and systemic acid-base balance through renal gluconeogenesis regulation.

Diabetes mellitus (DM) plays a causative role in memory impairment. Neuroprotective effects of tea polyphenol (TP), a unique and vital functional component of tea, have been widely investigated in neurodegenerative diseases, but the exact mechanisms have still not been entirely clarified yet. Here, we conducted the experiment to assess whether TP could protect the aged T2DM rats from memory impairment and its potential mechanisms. Our study revealed that memory impairment in aged T2DM rats was alleviated after TP treatment. Both in vivo and in vitro experiments showed that TP raised expression of GLUT4, activities of key enzymes of glucose metabolism and production of ATP in the model group, along with elevated O-GlcNAc glycosylation and reduced phosphorylation of Tau. Collectively, TP ameliorates memory impairment in aged T2DM rats via modulating hippocampal glucose uptake/metabolism and O-GlcNAc glycosylation/phosphorylation of Tau, which provides new insights into the beneficial effect of TP on DM-related memory impairment.

Accumulated alterations in metabolic control provide energy and anabolic demands for enhanced cancer cell proliferation. Exemplified by the Warburg effect, changes in glucose metabolism during cancer progression are widely recognized as a characteristic of metabolic disorders. Since telomerases are a vital factor in maintaining DNA integrity and stability, any damage threatening telomerases could have a severe impact on DNA and, subsequently, whole-cell homeostasis. However, it remains unclear whether the regulation of glucose metabolism in cancer is connected to the regulation of telomerase. In this review, we present the latest insights into the crosstalk between telomerase function and glucose metabolism in cancer cells. However, at this moment this subject is not well investigated that the association is mostly indirectly regulations and few explicit regulating pathways were identified between telomerase and glucose metabolism. Therefore, the information presented in this review can provide a scientific basis for further research on the detail mechanism and the clinical application of cancer therapy, which could be valuable in improving the effectiveness of chemotherapy.

ABSTRACT: This study aimed to test possible metabolic differences between ewes and goats in response to an intravenous glucose infusion. Thirty-six animals, 18 mature Sarda dairy ewes and 18 mature Saanen goats (from 15 to 150 ± 11 d in milk [DIM], mean ± SD; body weight: 49.8 ± 6.8 kg for ewes, 60.6 ± 7.3 kg for goats) were compared simultaneously. In early lactation, both species received the same high-starch diet (HS: 20.4% starch, 35.4% neutral detergent fiber [NDF], on dry matter [DM] basis), whereas from 92 ± 11 DIM both species were randomly allocated to 2 dietary treatments: HS (20.0% starch, 36.7% NDF, on DM basis) and low-starch (LS: 7.8% starch, 48.8% NDF, on DM basis) diets. At 50 and 150 ± 11 DIM, ewes and goats were challenged with an intravenous glucose tolerance test and peripheral concentrations of glucose and insulin were determined 15 min before and 5, 10, 15, 30, 45, 90, and 180 min after glucose infusion. In early lactation, baseline plasma glucose and insulin concentrations tended to be higher in ewes than in goats (glucose: 55.8 vs. 42.9 ± 7.3 mg/dL; insulin: 0.13 vs. 0.05 ± 0.04 µg/L). After glucose infusion, glucose and insulin concentrations were higher in ewes than in goats (278.6 vs. 247.6 ± 13.1 mg/dL; 0.82 vs. 0.46 ± 0.12 µg/L). In mid-lactation, the dietary treatment (HS vs. LS) did not affect glucose and insulin metabolism. Baseline plasma glucose was numerically highest in ewes, while baseline insulin was higher in ewes than in goats (0.39 vs. 0.12 ± 0.099 µg/L). After glucose infusion, glucose concentration did not differ between ewes and goats, while insulin concentration was highest in ewes. Compared with goats, ewes showed in both periods a higher peak insulin, insulin increment, linear insulin area under the curve, insulin resistance index, and lower insulin sensitivity indices. In conclusion, despite the limitations associated with the use of intravenous glucose tolerance test to assess glucose regulation mechanisms, this study indicated large species differences in both early and mid-lactation and a more evident anabolic status in the ewes compared with the goats.

The present study investigated the effects of dietary Cr on growth performance, antioxidant capacity, immunity response, insulin signaling pathway, and glucose-lipid metabolism in juvenile oriental river prawns (Macrobrachium nipponense). Moreover, the study also evaluated the optimal dietary Cr required for supplementation in juvenile oriental river prawns. Five semi-purified experimental diets were prepared by adding 0, 0.3, 0.6, 1.2 and 2.4 mg Cr kg−1 diet to a basal diet resulting into 0.74, 1.07, 1.35, 1.87 and 2.51 mg Cr kg−1 diets, respectively. The results showed that the prawns fed on 1.35 mg Cr kg−1 had significantly higher growth performance and triglyceride content, acid phosphatase, alkaline phosphatase, and antioxidant capacity activities (P

Osteoarthritis (OA) is a degenerative disease characterised by articular cartilage destruction, and its complex aetiology contributes to suboptimal clinical treatment outcomes. A close association exists between glucose metabolism dysregulation and OA pathogenesis. Owing to the unique environment of low oxygen and glucose concentrations, chondrocytes rely heavily on their glycolytic capacity, exhibiting distinct spatiotemporal differences. However, under pathological stimulation, chondrocytes undergo excessive glycolytic activity while mitochondrial respiration and other branches of glucose metabolism are compromised. This metabolic change induces cartilage degeneration by reprogramming the inflammatory responses. Sirtuins, a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, regulate glucose metabolism in response to energy fluctuations in different cellular compartments，alleviating metabolic stress. SIRT1, the most extensively studied sirtuin, participates in maintaining glucose homeostasis in almost all key metabolic tissues. While actively contributing to the OA progression and displaying diverse biological effects in cartilage protection, SIRT1’s role in regulating glucose metabolism in chondrocytes has not received sufficient attention. This review focuses on discussing the beneficial role of SIRT1 in OA progression from a metabolic regulation perspective based on elucidating the primary characteristics of chondrocyte glucose metabolism. We also summarise the potential mechanisms and therapeutic strategies targeting SIRT1 in chondrocytes to guide clinical practice and explore novel therapeutic directions.

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder experienced by women of reproductive age and is marked by insulin resistance (IR) and menstrual cycle abnormalities. In this study, we set out to assess how the level of menstrual abnormalities relates to the degree of IR in women with PCOS. Methods: The participants in this study were 93 women diagnosed with PCOS and 100 controls with regular vaginal bleeding. Data was collected through blood samples, physical examinations, and medical histories. The primary outcome measures were body mass index (BMI), fasting glucose, fasting insulin, homeostatic model assessment for IR (HOMA-IR), and hormonal parameters. Results: Values for BMI and HOMA-IR were higher in PCOS cases than in controls [(28.6 ± 1.9 vs. 23.7 ± 2.3) and (2.29 ± 2.87 vs. 1.48 ± 1.02), respectively]. Oligomenorrhea was documented in 79.4% of women with PCOS, with the others experienced vaginal bleeding intervals under 45 days. The greater the menstrual irregularity, the higher the levels of luteinizing hormone/follicle-stimulating hormone and testosterone. Among the PCOS group, those with vaginal bleeding intervals of above 90 days had a higher HOMA-IR values (2.46 ± 2.77), after adjustments for age and BMI, than the participants who went

Holarrhena pubescens is widely used in Indian and Chinese medicine in the treatment of diabetes. The current work determined the oral hypoglycemic and antidiabetic effects of seed extract in rats. The probable mechanism of action was evaluated in-vitro by α - glucosidase inhibition, glucose metabolism in insulinoma (INS-1) cells to reflect secretion of insulin, and protein glycation inhibition. Its potential for herb-drug interaction was evaluated in the cytochrome P450 3A4 (CYP3A4) inhibition assay. The seed extract increased serum insulin levels and reduced serum blood glucose levels in the oral glucose tolerance test. It also reduced the serum glucose levels in streptozocin-induced diabetes. The extract also inhibited α –glucosidase enzyme activity and demonstrated that it can increase the secretion of insulin from INS to 1-rat insulinoma cell line cells in-vitro in a concentration-dependent manner. However, it had a very weak inhibitory effect on protein glycation and it did not affect the activity of CYP3A4. The results of the study showed that H. pubescens seed extract increases insulin secretion and inhibits glucose absorption both in-vivo and in-vitro with a weak protein glycation inhibitory effect. The herb is devoid of CYP3A4 inhibitory effect indicating that it may not have pharmacokinetic interaction with the drug metabolized by this enzyme.

This study intends to explore the antihyperglycemic effect and the possible hypoglycemic mechanism of garlic (Allium sativum L.) polysaccharide (GP) using an animal model. Kunming mice were fed with GP (1.25, 2.5, 5.0 g/kg‧bw) for five weeks after insulin resistance (IR) engendering by a high-oil-high-sugar diet and streptozotocin (STZ). Intragastric administration of GP effectively improved the disease of polyphagia and polydipsia in diabetic mice. The fasting blood glucose (FBG) in the high-dose GP (DGH) group was meaningfully 42% lower than that in the diabetic model (DC) group showing its hypoglycemic effect. GP might manipulate hepatic glycogen metabolism by regulating the content of glucokinase (GK), glycogen synthase (GS), and phosphoenolpyruvate carboxykinase (PEPCK). Results showed that GP with a low relative molecular weight (MW) of 2.0 kDa consisted predominately of a 2,1-β-D-Fruf backbone with 20.7% side chains owning the structure-effect on hypoglycemia indicating it could be a potential supplement for the intervention and management of hyperglycemia.

Objective: Ferritin, the principal iron storage protein, is essential to iron homeostasis. How iron homeostasis affects the adipose tissue is not well understood. We investigated the role of ferritin heavy chain in adipocytes in energy metabolism. Methods: We generated adipocyte-specific ferritin heavy chain (Fth, also known as Fth1) knockout mice, herein referred to as FthAKO. These mice were analyzed for iron homeostasis, oxidative stress, mitochondrial biogenesis and activity, adaptive thermogenesis, insulin sensitivity, and metabolic measurements. Mouse embryonic fibroblasts and primary mouse adipocytes were used for in vitro experiments. Results: In FthAKO mice, the adipose iron homeostasis was disrupted, accompanied by elevated expression of adipokines, dramatically induced heme oxygenase 1(Hmox1) expression, and a notable decrease in the mitochondrial ROS level. Cytosolic ROS elevation in the adipose tissue of FthAKO mice was very mild, and we only observed this in the brown adipose tissue (BAT) but not in the white adipose tissue (WAT). FthAKO mice presented an altered metabolic profile and showed increased insulin sensitivity, glucose tolerance, and improved adaptive thermogenesis. Interestingly, loss of ferritin resulted in enhanced mitochondrial respiration capacity and a preference for lipid metabolism. Conclusions: These findings indicate that ferritin in adipocytes is indispensable to intracellular iron homeostasis and regulates systemic lipid and glucose metabolism.

Metabolic reprogramming is an adaptive response of tumour cells under hypoxia and low nutrition conditions. There is increasing evidence that glucose metabolism reprogramming can regulate the growth and metastasis of osteosarcoma (OS). Reprogramming in the progress of OS can bring opportunities for early diagnosis and treatment of OS. Previous research mainly focused on the glycolytic pathway of glucose metabolism, often neglecting the tricarboxylic acid cycle and pentose phosphate pathway. However, the tricarboxylic acid cycle and pentose phosphate pathway of glucose metabolism are also involved in the progression of OS and are closely related to this disease. The research on glucose metabolism in OS has not yet been summarized. In this review, we discuss the abnormal expression of key molecules related to glucose metabolism in OS and summarize the glucose metabolism related signaling pathways involved in the occurrence and development of OS. In addition, we discuss some of the targeted drugs that regulate glucose metabolism pathways, which can lead to effective strategies for targeted treatment of OS.

Sleep discrepancy (negative discrepancy reflects worse self-reported sleep than objective measures, such as actigraphy, and positive discrepancy the opposite) has been linked to adverse health outcomes. This study is first to investigate the relationship between sleep discrepancy and brain glucose metabolism (assessed globally and regionally via positron emission tomography), and to evaluate the contribution of insomnia severity and depressive symptoms to any associations. Using data from cognitively unimpaired community-dwelling older adults (N = 68), cluster analysis was used to characterise sleep discrepancy (for total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE)), and logistic regression was used to explore sleep discrepancy’s associations with brain glucose metabolism, while controlling for insomnia severity and depressive symptoms. Lower glucose metabolism across multiple brain regions was associated with negative discrepancy for WASO and SE, and positive discrepancy for WASO only (large effect sizes; β ≥ 0.5). Higher glucose metabolism in the superior parietal and posterior cingulate regions was associated with negative discrepancy for TST (large effect sizes; β ≥ 0.5). These associations remained when controlling for insomnia severity and depressive symptoms, suggesting a unique role of sleep discrepancy as a potential early behavioural marker of brain health.

Our meta-analysis aimed to assess the effectiveness of probiotics in weight loss and glucose and lipid metabolism in overweight or obese women. PubMed, EMBASE, Cochrane Library, and Web of Science were used from inception until March 2024 to identify randomized controlled trials (RCT's) literature. Finally, 11 RCTs were included. Following critical appraisal, a meta-analysis was conducted using the fixed effects model and the random effects model found that probiotic consumption significantly decreased waist circumference (WC) (SMD = −0.39 cm, 95% CI: −0.60, −0.18 cm, P

The main function of the renin-angiotensin-aldosterone system (RAAS) is the regulation of blood pressure; therefore, researchers have focused on its study to treat cardiovascular and renal diseases. One of the most widely used treatments derived from the study of RAAS, is the use of angiotensin-converting enzyme inhibitors (ACEi). Since it was discovered, the main target of ACEi has been the cardiovascular and renal systems. However, being the RAAS expressed locally in several specialized tissues and cells such as pneumocytes, hepatocytes, spleenocytes, enterocytes, adipocytes, and neurons the effect of inhibitors has expanded, because it is expected that RAAS has a role in the specific function of those cells. Many chronic degenerative diseases compromise the correct function of those organs, and in most of them, the RAAS is overactivated. Therefore, the use of ACEi must exert a benefit on an impaired system. Accordingly, the objective of this review is to present a brief overview of the cardiovascular and renal actions of ACEi and its effects in organs that are not the classic targets of ACEi that carry on glucose and lipid metabolism.

PDHα1 gene encodes catalytic subunit PDHE1α of pyruvate dehydrogenase (PDH) complex. Based on previous studies, it is hypothesized that inhibition of PDH activity prevents the entry of glycolytic pyruvate into TCA cycle, while promotes fatty acid oxidation and reduces liver triglyceride (TG) level, thereby alleviating nonalcoholic fatty liver disease (NAFLD). In this study, an in vitro model for NAFLD was established with medical fat emulsion; the most effective siRNA for PDHα1 gene was screened out by qPCR technology; the alterations in metabolism of glucose and lipid, and structure & function of mitochondria in the NAFLD cells were primarily evaluated after transfecting PDHα1 siRNA. As the results showed, after inhibiting the expression of PDHα1 gene, glucose level in culture medium was time-dependently increased, and LDH activity in the cells was moderately elevated after 24 h of transfection and then returned to the normal level after 48 h; intracellular TG level was decreased while LPS activity was increased in a time-dependent manner; no significant change in mitochondrial structure was observed with or without siRNA transfection, and ATP content was obviously reduced after 24 h of transfection, followed by restoration after 48 h. It can be concluded that inhibiting PDHα1 gene in fatty liver cells enhances lipid degradation, and represses the utilization of glucose to an extent, thus reducing TG level without impacting energy generation required for cell survival.

Glucose and lipid metabolism are involved in maintaining metabolic homeostasis, and their dysregulation contributes directly to the development of metabolic disorders. The role of diet and functional foods is pivotal in the quest for non-pharmacological strategies to prevent and ameliorate physiological and biochemical dysfunctions in metabolic disorders and comorbidities. In this view, the diverse marine ecosystem harbors and offers bioactive compounds with healthy potential. Astaxanthin, a xanthophyll carotenoid found in various marine organisms, holds great promise as a natural compound for promoting glucose and lipid homeostasis. This review summarizes the current knowledge on the molecular mechanisms underlying the positive effects of astaxanthin on glucose and lipid metabolism, including its impact on insulin signaling, glucose uptake and homeostasis, and lipid synthesis and turnover. Additionally, we discuss the potential applications of astaxanthin in developing targeted non-pharmacological prevention and interventions for metabolic disorders and comorbidities.

Consuming whole grains contributes to the preservation of glucose homeostasis and supports intestinal health, primarily attributed to the presence of functional components like polyphenols and dietary fiber. However, it is not well understood how the combined influence of cereal polyphenols and dietary fiber could benefit the glucose metabolism and alter the gut microbiota. Our results showed that compared to ferulic acid alone, ferulic acid combined with arabinoxylan or β-glucan could significantly improve glucose tolerance and maintain intestinal homeostasis in high-fat diet-fed mice. Ferulic acid combined with β-glucan significantly increased serum GLP-1 level and tight junction proteins expression in colon. Ferulic acid combined arabinoxylan increased the abundance of Bifidobacterium and Faecalibaculum. Ferulic acid combined with β-glucan increased the abundance of Akkermansia and norank_f_Muribaculaceae, which were negatively correlated with impaired glucose tolerance. Therefore, ferulic acid combined with arabinoxylan or β-glucan ameliorates glucose metabolism and protects intestinal barrier integrity by regulating gut microbiota.

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aβ25–35-induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aβ25–35-injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aβ25–35-induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aβ25–35-induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aβ25–35-induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling.

Summary: Background: Characterizing prediabetes phenotypes may be useful in guiding diabetes prevention efforts; however, heterogeneous criteria to define prediabetes have led to inconsistent prevalence estimates, particularly in low- and middle-income countries. Here, we estimated trends in prediabetes prevalence in Mexico across different prediabetes definitions and their association with prevalent cardiometabolic conditions. Methods: We conducted a serial cross-sectional analysis of National Health and Nutrition Surveys in Mexico (2016–2022), totalling 22 081 Mexican adults. After excluding individuals with diagnosed or undiagnosed diabetes, we defined prediabetes using ADA (impaired fasting glucose [IFG] 100–125 mg/dL and/or HbA1c 5.7–6.4%), WHO (IFG 110–125 mg/dL), and IEC criteria (HbA1c 6.0–6.4%). Prevalence trends of prediabetes over time were evaluated using weighted Poisson regression and its association with prevalent cardiometabolic conditions with weighted logistic regression. Findings: The prevalence of prediabetes (either IFG or high HbA1c [ADA]) in Mexico was 20.9% in 2022. Despite an overall downward trend in prediabetes (RR 0.973, 95% CI 0.957–0.988), this was primarily driven by decreases in prediabetes by ADA-IFG (RR 0.898, 95% CI 0.880–0.917) and WHO-IFG criteria (RR 0.919, 95% CI 0.886–0.953), while prediabetes by ADA-HbA1c (RR 1.055, 95% CI 1.033–1.077) and IEC-HbA1C criteria (RR 1.085, 95% CI 1.045–1.126) increased over time. Prediabetes prevalence increased over time in adults >40 years, with central obesity, self-identified as indigenous or living in urban areas. For all definitions, prediabetes was associated with an increased risk of cardiometabolic conditions. Interpretation: Prediabetes rates in Mexico from 2016 to 2022 varied based on defining criteria but consistently increased for HbA1c-based definitions and high-risk subgroups. Funding: This research was supported by Instituto Nacional de Geriatría in Mexico. JAS was supported by NIH/NIDDK Grant# K23DK135798.

Objective: Glucose-dependent insulinotropic polypeptide (GIP) has a role in controlling postprandial metabolic tone. In humans, a GIP receptor (GIPR) variant (Q354, rs1800437) is associated with a lower body mass index (BMI) and increased risk for Type 2 Diabetes. To better understand the impacts of GIPR-Q354 on metabolism, it is necessary to study it in an isogeneic background to the predominant GIPR isoform, E354. To accomplish this objective, we used CRISPR-CAS9 editing to generate mouse models of GIPR-Q354 and GIPR-E354. Here we characterize the metabolic effects of GIPR-Q354 variant in a mouse model (GIPR-Q350). Methods: We generated the GIPR-Q350 mice for in vivo studies of metabolic impact of the variant. We isolated pancreatic islets from GIPR-Q350 mice to study insulin secretion ex vivo. We used a β−cell cell line to understand the impact of the GIPR-Q354 variant on the receptor traffic. Results: We found that female GIPR-Q350 mice are leaner than littermate controls, and male GIPR-Q350 mice are resistant to diet-induced obesity, in line with the association of the variant with reduced BMI in humans. GIPR-Q350 mice of both sexes are more glucose tolerant and exhibit an increased sensitivity to GIP. Postprandial GIP levels are reduced in GIPR-Q350 mice, revealing feedback regulation that balances the increased sensitivity of GIP target tissues to secretion of GIP from intestinal endocrine cells. The increased GIP sensitivity is recapitulated ex vivo during glucose stimulated insulin secretion assays in islets. Generation of cAMP in islets downstream of GIPR activation is not affected by the Q354 substitution. However, post-activation traffic of GIPR-Q354 variant in β-cells is altered, characterized by enhanced intracellular dwell time and increased localization to the Trans-Golgi Network (TGN). Conclusions: Our data link altered intracellular traffic of the GIPR-Q354 variant with GIP control of metabolism. We propose that this change in spatiotemporal signaling underlies the physiologic effects of GIPR-Q350/4 and GIPR-E350/4 in mice and humans. These findings contribute to a more complete understanding of the impact of GIPR-Q354 variant on glucose homeostasis that could perhaps be leveraged to enhance pharmacologic targeting of GIPR for the treatment of metabolic disease.

Objectives: To explore the optimal exercise parameters of Tai Chi for improving glucose and lipid metabolism in type 2 diabetes mellitus (T2DM) patients. Methods: This meta-analysis was conducted in accordance with the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Six databases were retrieved, with retrieval dates ranging from the establishment of the databases to December 2022. Data extraction and study quality assessment were independently performed by two researchers according to the Physical Therapy Evidence Database (PEDro) scale. The effects of different Tai Chi exercise parameters on glucose and lipid metabolism in T2DM patients were analyzed by subgroup analyses and meta-regressions. Results: A total of sixteen randomized controlled trials were included in the meta-analysis. The results indicated that Tai Chi had a significant and moderate impact on fasting blood glucose in T2DM patients, as well as a significant and large impact on glycosylated hemoglobin. Tai Chi had a significant and moderate impact on triglyceride, and a small, non-significant improvement on total cholesterol. The intervention frequency and duration of a single session were identified as predictors of the impact of Tai Chi on triglyceride. The optimal exercise parameters identified were the 24-style simplified Tai Chi, with a recommended exercise duration of 45–60 min per session, performed 5–7 times per week, and continued for at least 4–7 weeks. Conclusions: Tai Chi can significantly improve the glucose and lipid metabolism in T2DM patients, and the 24-style simplified Tai Chi with high exercise frequency and short duration may be the optimal exercise parameter for enhancing glucose and lipid metabolism. Prospero: Registration number: CRD42023395282

Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

Purpose: The aim of the present study was to determine the association between adherence to the 24-h movement guidelines during middle adolescence and glucose outcomes (glycated hemoglobin and fasting glucose) and type 2 diabetes mellitus (T2DM) in adulthood, 14 and 22 years later. Methods: We analyzed data from apparently healthy adolescents aged 12–18 years who participated in Waves I and II (1994–1996, n = 14,738), Wave IV (2008–2009, n = 8913), and Wave V (2016–2018, n = 3457) of the National Longitudinal Study of Adolescent to Adult Health (Add Health) in the United States. Physical activity, screen time, and sleep duration were measured using questionnaires, and the 24-h guidelines were defined as: 5 or more times moderate-to-vigorous physical activity per week, ≤2 h per day of screen time, and 9–11 h of sleep for 12–13 years and 8–10 h for 14–17 years. Capillary and venous whole blood was collected and analyzed to determine glycated hemoglobin and fasting glucose for Waves IV and V, respectively. Results: Only 2.1% of the adolescents met all the 3 guidelines, and 37.8% met none of them. In both waves IV and V, adolescents who met physical activity and screen time guidelines had lower odds of T2DM in adulthood than those who did not meet any of these guidelines (Wave IV; prevalence ratio (PR) = 0.57, 95% confidence interval (95%CI): 0.21–0.89; Wave V: PR = 0.43, 95%CI: 0.32–0.74). Only for Wave V did adolescents who met all 3 guidelines have lower odds of T2DM at follow-up compared with those who did not meet any of these guidelines (PR = 0.47, 95%CI: 0.24–0.91). Also, for each increase in meeting one of the 24-h recommendations, the odds of T2DM decreased by 18% (PR = 0.82, 95%CI: 0.61–0.99) and 15% (PR = 0.85, 95%CI: 0.65–0.98) in adulthood for Waves IV and V, respectively. Conclusion: Promoting all 24-h movement guidelines in adolescence, especially physical activity and screen time, is important for lowering the potential risk of T2DM in adulthood.

Diabetes has emerged as one the leading detrimental factors for human life expectancy worldwide. The disease is mainly considered as outcome of dysregulation in glucose metabolism, resulting in consistent high glucose concentration in blood. At initial stages, the diabetes particularly type 2 diabetes, is manageable by lifestyle interventions such as regular physical activity and diet with less carbohydrates. However, in advance stage, regular intake of external insulin dose and medicines like metformin are recommended. The long-term consumption of metformin is associated with several side effects such as nausea, vomiting, diarrhoea, lectic acidosis etc., In this scenario, several plant-based medicines have shown promising potential for the prevention and treatment of diabetes. Berberine is the bioactive compound present in the different plant parts of berberis family. Biochemical studies have shown that berberine improve insulin sensitivity and insulin secretion. Additionally, berberine induces glucose metabolism by activating AMPK signaling and inhibition of inflammation. A series of studies have demonstrated the antidiabetic potential of berberine at in vitro, pre-clinical and clinical trials. This review provides comprehensive details of preventive and therapeutic potential of berberine against diabetes.

Background: Abnormal cardiac metabolism is a key factor in the development of cardiovascular diseases. Consequently, there has been considerable emphasis on researching and developing drugs that regulate metabolism. This study employed bibliometric methods to comprehensively and objectively analyze the relevant literature, offering insights into the knowledge dynamics in this field. Methods: The data source for this study was the Web of Science Core Collection (WoSCC), from which the collected data were imported into bibliometric software for analysis. Results: The United States was the leading contributor, accounting for 38.33 % of publications. The University of Washington and Damian J. Tyler were the most active institution and author, respectively. The American Journal of Physiology-Heart and Circulatory Physiology, Journal of Molecular and Cellular Cardiology, Cardiovascular Research, Circulation Research, and American Journal of Physiology-Endocrinology and Metabolism were highly influential journals that published numerous high-quality articles on cardiac metabolism. Common keywords in this research area included heart failure, insulin resistance, skeletal muscle, mitochondria, as well as topic words such as cardiac metabolism, fatty acid oxidation, glucose metabolism, and myocardial metabolism. Co-citation analysis has shown that research on heart failure and in vitro modeling of cardiovascular disease has gained prominence in recent years and making it a research hotspot. Conclusion: Research on cardiac metabolism is steadily growing, with a specific focus on heart failure and the interplay between mitochondrial dysfunction, insulin resistance, and cardiac metabolism. An emerging trend in this field involves the enhancement of maturation in human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) through the manipulation of cardiac metabolism.

Summary: Background: Paediatric Huntington disease with highly expanded mutations (HE-PHD; >80 CAG repeats) presents atypically, compared to adult-onset Huntington disease (AOHD), with neurodevelopmental delay, epilepsy, abnormal brain glucose metabolism, early striatal damage, and reduced lifespan. Since genetic GLUT-1 deficiency syndrome shows a symptom spectrum similar to HE-PHD, we investigated the potential role of the two main glucose transporters, GLUT-1 and GLUT-3, in HE-PHD. Methods: We compared GLUT-1 and GLUT-3 protein expression in HE-PHD, juvenile-onset (JOHD), and AOHD brains (n = 2; n = 3; n = 6) and periphery (n = 3; n = 2; n = 2) versus healthy adult controls (n = 6; n = 6). We also investigated mitochondrial complexes and hexokinase-II protein expression. Findings: GLUT-1 and GLUT-3 expression were significantly lower in HE-PHD frontal cortex (p = 0.009, 95% [CI 13.4, 14.7]; p = 0.017, 95% [CI 14.2, 14.5]) versus controls. In fibroblasts, GLUT-1 and GLUT-3 expression were lower compared to controls (p

Activation of brown adipose tissue (BAT) contributes to energy dissipation and metabolic health. Although mineralocorticoid receptor (MR) antagonists have been demonstrated to improve metabolism under obesity, the underlying mechanisms remain incompletely understood. We aimed to evaluate the role of BAT MR in metabolic regulation. After 8 weeks of high-fat diet (HFD) feeding, BAT MR KO (BMRKO) mice manifested significantly increased bodyweight, fat mass, serum fasting glucose, and impaired glucose homeostasis compared with littermate control (LC) mice, although insulin resistance and fasting serum insulin were not significantly changed. Metabolic cage experiments showed no change in O2 consumption, CO2 production, or energy expenditure in obese BMRKO mice. RNA sequencing analysis revealed downregulation of genes related to fatty acid metabolism in BAT of BMRKO-HFD mice compared with LC-HFD mice. Moreover, H&E and immunohistochemical staining demonstrated that BMRKO exacerbated HFD-induced macrophage infiltration and proinflammatory genes in epididymal white adipose tissue (eWAT). BMRKO-HFD mice also manifested significantly increased liver weights and hepatic lipid accumulation, an increasing trend of genes related to lipogenesis and lipid uptake, and significantly decreased genes related to lipolytic and fatty acid oxidation in the liver. Finally, the level of insulin-induced AKT phosphorylation was substantially blunted in eWAT but not liver or skeletal muscle of BMRKO-HFD mice compared with LC-HFD mice. These data suggest that BAT MR is required to maintain metabolic homeostasis, likely through its regulation of fatty acid metabolism in BAT and impacts on eWAT and liver.

Maternal diets during pregnancy and lactation are key determinants that regulate the development of metabolic syndrome (MetS) in offspring. l-malic acid (MA) was previously reported to improve antioxidant capacity and aerobic metabolism. However, the effects of maternal MA consumption on the metabolic features of offspring remain largely unexplored. Herein, through pig models consuming MA-enriched diets during late pregnancy and lactation, we found that maternal MA consumption potentiated the anti-inflammatory and antioxidant capacity of sows, thereby improving their reproductive performance and the growth performance of piglets. Maternal MA consumption also induced a transition of slow-twitch to fast-twitch fibers in the early life of offspring. Along with muscle growth and fiber-type transition, insulin sensitivity and glucose metabolism, including aerobic metabolism and glycolysis, were improved in the skeletal muscle of offspring. An untargeted metabolomic analysis further revealed the contribution of modified amino acid metabolism to the improved aerobic metabolism. Mechanistically, maternal MA consumption remodeled colonic microbiota of their offspring. Briefly, the abundance of Colidextribacter, Romboutsia, and Family_XIII_AD3011_group increased, which were positively associated with the antioxidant capacity and glucose metabolism of skeletal muscles. A decreased abundance of Prevotella, Blautia, Prevotellaceae_NK3B31_group, and Collinsella was also detected, which were involved in less insulin sensitivity. Notably, milk metabolites, such as ascorbic acid (AA) and granisetron (GS), were found as key effectors regulating the gut microbiota composition of piglets. The properties of AA and GS in alleviating insulin resistance, inflammation, and oxidative stress were further verified through mice treated with high-fat diets. Overall, this study revealed that maternal MA consumption could modulate the inflammatory response, antioxidant capacity, and glucose metabolism by regulating the gut microbiota of offspring through the vertical transmission of milk metabolites. These findings suggest the potential of MA in the prevention and treatment of MetS in early life.