Metabolic Organ Research Articles

Regulation of pancreatic β cells by exosomes from different sources.

Regulation of pancreatic β cells by exosomes from different sources.

NOTCH Signaling Networks in Perivascular Adipose Tissue.

Over a hundred years ago, mutants were detected in Drosophila melanogaster that led to a NOTCH in the wing tip. This original phenotype was reflected in the nomenclature of the gene family that was later cloned and characterized in the 1980s and found to be conserved across metazoans. NOTCH signaling relies on transmembrane ligands and receptors that require cellular contact for receptor activation, reflecting its role in multicellular organisms as an intercellular signaling strategy. In humans, mutations in genes encoding NOTCH and their ligands have been shown to promote human disease; these aspects have been extensively reviewed. Notch signaling plays important roles in vascular development (vasculogenesis and angiogenesis) and homeostasis. NOTCH signaling is also active in adipose tissue and contributes to adipocyte differentiation. In addition, NOTCH activity regulates functions of other metabolic organs. This review focuses on NOTCH activity in perivascular adipose tissue within the vascular microenvironment as defined by mouse studies and summarizes expression and potential signaling of the NOTCH signaling network in human perivascular adipose tissue. Due to the strong activity of NOTCH in regulation of metabolic function, activation of the NOTCH network in specific cell types in perivascular adipose tissue has implications for signaling to the underlying blood vessel and control of vascular health and disease.

Agrobacterium mediated manipulation of the expression of an polysaccharide biosynthetic phosphoglucose isomerase gene to improve polysaccharide production in Sanghuangporus vaninii.

Agrobacterium mediated manipulation of the expression of an polysaccharide biosynthetic phosphoglucose isomerase gene to improve polysaccharide production in Sanghuangporus vaninii.

Metabolic crosstalk and therapeutic interplay between diabetes and hyperuricemia.

Hyperuricemia and diabetes mellitus (DM) are prevalent metabolic disorders with high comorbidity, imposing a substantial global public health burden. Their coexistence is not merely additive but synergistic, exacerbating metabolic dysregulation through mechanisms such as insulin resistance and β-cell apoptosis, ultimately establishing a vicious cycle. Both disorders induce acute and chronic damage to vital organs, particularly the cardiovascular, renal systems. Hyperuricemia aggravates diabetic complications, notably diabetic cardiomyopathy, nephropathy and retinopathy via oxidative stress, inflammation, and metabolic dysregulation.Current urate-lowering therapies (ULTs), such as xanthine oxidase inhibitors and urate transporter 1 (URAT1, also known as SLC22A12) antagonists, demonstrate potential benefits in ameliorating diabetic complications but face challenges including safety concerns and dose adjustments. Similarly, several glucose-lowering drugs also exhibit the benefits of improving hyperuricemia. This review summarizes the metabolic crosstalk and therapeutic interplay between hyperuricemia and DM, examines the pathogenic role of uric acid in diabetic complications, and discusses the benefits and challenges of existing ULTs and glucose-lowering drugs in disrupting this cycle of metabolic dysregulation and concurrent organ damage. We hope our findings deepen the comprehension of the intricate metabolic crosstalk between glucose and urate homeostasis, providing novel therapeutic insights for patients with comorbid DM and hyperuricemia.

Impact of alcohol consumption on nature of nutrition, metabolism and human target organs. Part 3. The role and significance of micronutrients

It is known that excessive alcohol consumption is an important negative risk factor for human health, one of the leading causes of morbidity and mortality worldwide, as well as contributing to the development of more than 200 chronic diseases. This fact makes actual the problems related to the prevention and dietary therapy of alcohol-consuming subjects with the use of food macro- and micronutrients. Objective. To analyze the role and significance of micronutrients in dietary interventions in people who excessively consume alcohol. Materials and methods. We searched and summarized scientific literature from the PubMed, eLibrary, Scopus databases published between 2014 and 2025 to achieve the goal. Data search was performed on January 9, 2025 using the following keywords: alcohol, diet, micronutrients, biologically active substances, vitamins, minerals, polyphenols, synbiotics, intestinal microbiota. A number of publications equal 57 were selected as a result of the analysis. The review also presents 10 primary sources, dating back to 2014, as they contained valuable information on fundamental research on using diet therapy in alcohol consumption. Results. The review summarizes data on the role and significance of micronutrients in dietary intervention in subjects consuming alcohol. Pathogenetically substantiated approaches to the administration of vitamins, minerals and other minor components of nutrition were considered. Conclusion. Dietary intervention requires optimization of the diet with nutritional body’s support according to the stage of development of alcoholization process, metabolic disorders and the state of the consumer’s organs and systems. Alimentary micronutrient intervention can be a non-pharmacological both preventive and therapeutic measure in cases of alcohol-related diseases.

GMAMDA: Predicting Metabolite-Disease Associations Based on Adaptive Hardness Negative Sampling and Adaptive Graph Multiple Convolution.

Metabolites are small molecules produced during organism metabolism, with their abnormal concentrations closely linked to the onset and progression of various diseases. Accurate prediction of metabolite-disease associations is crucial for early diagnosis, mechanistic exploration, and treatment optimization. However, existing algorithms often overlook the integration of node features and neglect the impact of different hop domains on nodes in the processing of heterogeneous graphs. Furthermore, current methods solely rely on random sampling for selecting negative samples without considering their reliability, thereby compromising model stability. A novel metabolite-disease association prediction model, GMAMDA, is proposed to address these challenges. GMAMDA integrates adaptive hardness negative sampling, adaptive graph multiple convolution techniques, and a multiheterogeneous graph fusion strategy to forecast potential metabolite-disease associations. Initially, by computing multisource similarity information for metabolites and diseases, multiple heterogeneous graph networks are established for metabolite-disease association networks. Subsequently, the adaptive graph's multiconvolution mechanism is employed to generate feature-rich node representations across various heterogeneous graphs by dynamically leveraging information from different hop neighborhoods. The model then utilizes an adaptive hardness negative sampling approach based on principal component analysis to select negative samples with the highest information content for training, enabling the prediction of potential associations between new metabolites and diseases. Experimental findings demonstrate that GMAMDA outperforms state-of-the-art methods across various evaluation metrics, including AUC (0.9962 ± 0.0014), AUPR (0.9967 ± 0.0009), and accuracy (0.9733 ± 0.0042). Case studies focusing on Alzheimer's disease and kidney disease further validate GMAMDA's clinical potential in predicting metabolite markers.

BRCA1 influences whole body metabolism in humanized mice.

The role of BRCA1 in cellular metabolism is not fully characterized and what we do understand has been primarily demonstrated in vitro. Our studies aimed to characterize the role of BRCA1 in metabolic pathways in a whole body system. In vivo studies using C57BL/6 wild-type and transgenic humanized BRCA1 mice demonstrate the effect of human BRCA1 on the whole body metabolic phenotype and start to elucidate the mechanism by which this occurs. Promethion metabolic chambers and glucose tolerance tests measured a number of metabolic outputs of male and female mice that were either wild-type (normal mouse Brca1 gene) or humanized BRCA1 mice (knockout Brca1/knock-in human BRCA1 gene). Humanized BRCA1 mice are more lean, hyperactive, display higher energy expenditure, and demonstrate a sexual dimorphism in lean mass and glucose tolerance when compared with wild-type mice on the same genetic background. To begin to elucidate the mechanisms behind the observed metabolic phenotype, we performed mass spectrometry, SuperArray, and Western blot analysis using skeletal muscle, a metabolic organ that significantly impacts energy metabolism. Proteomic and genomic analysis revealed changes in a number of metabolic pathways that may be implicated in the observed whole body metabolic phenotype. We concluded that substituting BRCA1 for Brca1 in an in vivo model altered the overall metabolic profile of humanized BRCA1 mice. Thus, the Brca1/BRCA1 gene appears to have a significant impact on metabolic pathways, and these effects differ from mouse to human.NEW & NOTEWORTHY This is the first in vivo evidence demonstrating the complex effects of BRCA1 expression in whole body metabolism.

Transcriptome and metabolome analysis reveals different photosynthetic characteristics of mulberry trees with different ploidy levels

There are abundant mulberry germplasm resources in China. Generally, in order to better utilize these resources, a comprehensive evaluation is conducted, among which the evaluation of photosynthetic capacity is an important aspect. To evaluate the photosynthetic characteristics of mulberry trees with different ploidy levels, which determine the number of chromosome sets in a cell or organism, we compared the microstructural features and transcriptomes of triploid and diploid mulberry trees. Haploid (n) means having one set of chromosomes, diploid (2n) has two sets, triploid (3n) has three sets, and so on. We compared the microstructural features and transcriptomes of triploid and diploid mulberry trees. In this study, the photosynthetic rates (Pn) of ‘guisang6hao’ (hereinafter referred to as GS6, 2n = 3x = 42) were 1.2 times that of ‘guisangyou12’(hereinafter referred to as GSY12, 2n = 2x = 28). Here, GS6 and GSY12 are abbreviations for the two mulberry varieties. The leaf thickness, main vein thickness, epidermal thickness, palisade tissue thickness, spongy tissue thickness and lower epidermal stomatal density of GS6 were greater than those of GSY12. Additionally, the transcriptome characteristics of GS6 and GSY12 were characterised by Illumina Novaseq 6000 and the differentially expressed genes (DEGs) were significantly enriched in photosynthesis. Four differentially expressed metabolites (DEMs) related to photosynthesis were identified, playing key roles in chlorophyll metabolism and carbon fixation in photosynthetic organisms. The above results indicated that an increase in the ploidy level enhanced the photosynthetic capacity and utilisation of light energy, as well as the accumulation of chlorophyll content, of triploid mulberry trees. This study provides a technical and theoretical basis for germplasm innovation and the genetic improvement of mulberry.

Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity

ABSTRACT Insulin resistance (IR) is an early marker of cardiometabolic deterioration which may develop heterogeneously in key metabolic organs, including the liver (LIR) and skeletal muscle (MIR). This tissue-specific IR is characterized by distinct metabolic signatures, but the role of the gut microbiota in its etiology remains unclear. Here, we profiled the gut microbiota, its metabolites and the plasma metabolome in individuals with either a LIR or MIR phenotype (n = 233). We observed distinct microbial community structures LIR and MIR, and higher short-chain fatty acid (SCFA) producing bacteria, fecal SCFAs and branched-chain fatty acids and a higher postprandial plasma glucagon-like-peptide-1 response in LIR. In addition, we found variations in metabolome profiles and phenotype-specific associations between microbial taxa and functional metabolite groups. Overall, our study highlights association between gut microbiota and its metabolites composition with IR heterogeneity that can be targeted in precision-based strategies to improve cardiometabolic health. Clinicaltrials.gov registration: NCT03708419.

Genome-wide association study (GWAS) provides insights into the genomic basis of reproduction-related traits in Chouardia litardierei (Asparagaceae)

BackgroundChouardia litardierei, commonly known as amethyst meadow squill, is a plant species characterized by profound ecological plasti vcity. As a wild, non-model species, it represents a suitable system for gaining insights into the genomic background of the local adaptation process. By implementing a genome-environment and genome-wide association studies, we sought to investigate the genomic regions related to the local adaptation and the development of several reproduction-related traits in C. litardierei: for sexual reproduction, Average Height of Inflorescences (AHI) and Total Flower Count (TFC) per genotype, and for asexual reproduction, Bulb Count (BC) per genotype.ResultsA genome-environment association (GEA) study of selected C. litardierei populations revealed the precipitation of the coldest quarter as the bioclimatic variable with the most substantial influence on detected variability, with numerous candidate genes detected and functionally characterized. To evaluate the genetic basis of selected reproduction-related traits we combined phenotypic data of 214 individuals raised as a part of a common garden experiment with ddRADseq genotyping results. After implementing various single- and multi-locus GWAS models for all traits, multiple candidate loci affecting their development were recognized. In addition, high, narrow-sense heritability estimates indicated that genetic factors accounted for over 55% of the phenotypic variance in each trait. Notably, the highest heritability estimate was observed for the Average Height of Inflorescences (71.95%), suggesting its crucial role in reproductive success. Functional annotation of the associated genomic regions identified key protein families involved in reproduction-related biological pathways, including nitrogen metabolism, phytohormone regulation, and floral organs development.ConclusionBy implementing GEA and GWAS, we revealed a list of candidate loci significantly associated with adaptation to specific environmental variables and morphological traits related to sexual and asexual reproduction in C. litardierei. These findings provide a foundation for a deeper understanding of the molecular mechanisms driving the local adaptation processes occurring among C. litardierei populations from different habitat types. At the same time, the high heritability estimates of morphological traits further underscore the significance of genetic factors in the local adaptation process.

Construction and Validation of an Early Warning Model for Predicting the 28-Day Mortality in Sepsis Patients with Chronic Obstructive Pulmonary Disease.

In the intensive care unit (ICU), approximately 45.6% of patients diagnosed with chronic obstructive pulmonary disease (COPD) also presented with sepsis, and this cohort exhibited a significantly higher 28-day mortality rate compared to sepsis patients without COPD (23.6% versus 16.4%). A novel nomogram is necessary to predict the risk of mortality within 28 days for sepsis patients with COPD. Clinical data from 501 sepsis patients with COPD were sourced from the MIMIC-IV database. These data were randomly allocated into a training cohort and a validation cohort in a 3:1 ratio. Independent predictors of 28-day mortality were identified through both univariate and multivariate logistic regression analyses. Subsequently, a nomogram model was developed, and its performance was assessed using receiver operating characteristic (ROC) curve analysis, calibration plots, and decision curve analysis. The 28-day mortality rates in the training and validation cohorts were 32.7% and 27.2%, respectively. Multivariate regression analysis identified age, heart rate (HR), respiratory rate (RR), blood urea nitrogen (BUN), creatinine (Cr), lactate levels, pH, and urine output as independent risk factors for 28-day mortality in sepsis patients with COPD. Furthermore, the nomogram demonstrated superior predictive performance, with an area under the curve (AUC) of 0.784 for the training group and 0.689 for the validation group. This nomogram integrates laboratory indicators pertinent to the patient's metabolic status, hypoxia status, and organ function, thereby enhancing the accuracy of early prediction of 28-day mortality in sepsis patients with COPD. Additionally, the model's comparative advantage over existing scoring systems (eg, SOFA) would enhance its impact. Our findings hold substantial implications for early prognostic assessment and clinical decision-making in this patient population. Therefore, earlier diagnosis within 24hours of admission and proper identification of high-risk patients may reduce disease-related mortality by promoting timely treatment.

Drosophila as a Genetic Model System to Study Organismal Energy Metabolism.

Metabolism is the essential process by which an organism converts nutrients into energy to fuel growth, development, and repair. Metabolism at the level of a multicellular, multi-organ animal is inherently more complex than metabolism at the single-cell level. Indeed, each organ also must maintain its own homeostasis to function. At all three scales, homeostasis is a defining feature: as energy sources and energetic demands wax and wane, the system must be robust. While disruption of organismal energy homeostasis can be manifested in different ways in humans, obesity (defined as excess body fat) is an increasingly common outcome of metabolic imbalance. Here we will discuss the genetic basis of metabolic dysfunction that underlies obesity. We focus on what we are learning from Drosophila melanogaster as a model organism to explore and dissect genetic causes of metabolic dysfunction in the context of a whole organism.

Comparative effect of high intensity interval training and moderate intensity continuous training on metabolic improvements and regulation of Cidea and Cidec in obese C57BL/6 mice.

Obesity is a chronic disease associated with increased risk of cardiovascular disease, diabetes, metabolic dysfunction associated steatotic liver disease and certain cancers. High intensity interval training (HIIT) and moderate intensity continuous training (MICT) are effective in preventing and managing obesity. However, the comparative effects of these modalities on metabolic disorders need to be better mechanistically explored. This study aimed to comprehensively assess the effects of MICT and HIIT on key metabolic organs and underlying mechanisms. C57BL/6 mice were randomized to receive either a chow diet or high fat diet for 12 weeks, followed by random assignment of high-fat-fed mice to no exercise, MICT or HIIT groups for additional 5 weeks. At the end, both HIIT and MICT significantly alleviated high-fat-induced weight gain and lipids disorder and impaired liver function. HIIT was more effective in enhancing insulin sensitivity, ameliorating hepatic steatosis, reducing adipocyte hypertrophy. Additionally, HIIT restored the high-fat-induced downregulation of Cidea, Cidec and Atgl in inguinal white adipose tissue and liver. Furthermore, HIIT resulted in upregulation of interleukin 6 (Il-6) in skeletal muscle. The exogenous addition of Il-6 to primary white adipocytes significantly downregulated Cidec, and up-regulated Atgl expression. In conclusion, HIIT is superior to MICT in improving metabolic dysfunction, likely mediated through Il-6-induced downregulation of Cidea and Cidec, thereby promoting lipolysis.

Mechanism of GBE Combined with TP on the Effect of AMPK/SREBP-1C/ACC Pathway on Lipid Metabolism in Heat-Stressed Broiler Liver.

The liver accounts for almost 95% of lipid metabolism in broilers and serves as a crucial metabolic organ. Stress, which occurs when broilers are exposed to a heated environment, inhibits liver metabolism, significantly impacting their growth. This experiment investigated the combination of GBE with TP to improve hepatic lipid metabolism in heat-stressed broiler chickens by inhibiting the AMPK/SREBP-1C/ACC pathway. Three hundred broilers were reared usually until 21 days and randomly divided into six groups, namely CON group, HS group, TP group (300 mg/kg), GBE100 group (GBE100 mg/kg + TP300 mg/kg), GBE300 group (GBE 300 mg/kg + TP 300 mg/kg), GBE600 (600 mg/kg + TP 300 mg/kg) groups, where the CON group was kept at 23 °C, and the HS group and the TP, GBE100, GBE300, and GBE600 groups of each medication group were kept at 35 ± 2 °C for 10 h per day. Liver and serum samples were extracted at 28 and 42 days of age, respectively. The results showed that, at 42 days of age, the GBE600 group exhibited significantly superior performance to the HS group in ADG, ADFI, and F/G (p < 0.01). Serum TG, TC, and LDL-C levels were significantly lower (p < 0.01), while HDL-C levels were significantly higher (p < 0.05). Additionally, the mRNA expression levels of LKB1, AMPK, SREBP-1C, and ACC were markedly reduced (p < 0.01). In contrast, the mRNA expression of HSL and CPT1A was significantly elevated (p < 0.01), indicating that the GBE600 was more effective in mitigating heat stress in broiler chickens at 42 days of age. It showed that the GBE600 was more effective in ameliorating heat stress in broilers at 42 days of age, thus providing an ethical basis for ameliorating the flocculation of hepatic lipid metabolism in heat-stressed broilers.

A Cyanobacteria-derived RNA aptamer resensitizes prostate cancer to hormone therapy.

Prostate adenocarcinoma (PCa) resistance to androgen receptor (AR) signaling inhibitor therapy is associated with elevated glutamine (L-Gln). Glutamine sensors, present in conserved riboswitches (glnA), control nitrogen metabolism in many organisms, like cyanobacteria. Iterative in silico modifications of glnA found in Synechococcus elongatus and thermodynamic analysis of a 56mer aptamer resulted in high L-Gln specificity and affinity. The optimized aptamer depleted L-Gln from PCa cells by both L-Gln sequestration and extracellular glutaminase activation, serving as an allosteric activator. Glutamine depletion reduced FOXM1 transcriptional occupancy on the promoter of fibroblast growth factor 8 (FGF8), a known mediator of PCa castration resistance. A point mutation in the binding pocket of the 56mer rendered the aptamer ineffective in L-Gln binding and FGF8 regulation. Accordingly, the L-Gln-depleting aptamer, with demonstrated serum stability, limited the proliferation and promoted cell death of castration-resistant PCa alone and in combination therapy with AR antagonists, enzalutamide and apalutamide, in subcutaneous and orthotopic mouse models. Further selective tumor targeting was achieved by functionalizing gold nanoparticles with either the optimized L-Gln aptamer or the point-mutant aptamer. Castration sensitivity was restored by the L-Gln-depleting aptamer but not by the point-mutant. The functionalized nanoparticle demonstrated superior anti-tumor efficacy in an orthotopic PCa model over the untargeted aptamer. The anti-tumor activity of the aptamer helped support L-Gln as an oncometabolite in PCa that can be targeted to sensitize tumors to hormone therapy.

Human Gut Microbiome: A Connecting Organ Between Nutrition, Metabolism, and Health.

The gut microbiome plays a vital role in human health, functioning as a metabolic organ that influences nutrient absorption and overall well-being. With growing evidence that dietary interventions can modulate the microbiome and improve health, this review examines whether healthcare systems should prioritize personalized microbiome-targeted therapies, such as probiotics, prebiotics, and microbiota transplants, over traditional pharmaceutical treatments for chronic diseases like obesity, diabetes, cardiovascular risk, and inflammatory conditions. A systematic review using Web of Science and Scopus databases was conducted, followed by a scientometric analysis. Key metabolic pathways, such as dietary fiber fermentation and short-chain fatty acid production, were explored, focusing on their impact on lipid and glucose metabolism. The interactions between microbial metabolites and the immune system were also investigated. Dietary interventions, including increased fiber and probiotic intake, show potential for addressing dysbiosis linked to conditions, such as type 2 diabetes, obesity, and autoimmune diseases. The review emphasizes the need to incorporate microbiome modulation strategies into clinical practice and research, calling for a multidisciplinary approach that integrates nutrition, microbiology, and biochemistry to better understand the gut microbiome's complex role in health.

Microbes display broad diversity in cobamide preferences.

Cobamides, the vitamin B12 (cobalamin) family of cofactors, are used by most organisms but produced by only a fraction of prokaryotes, and are thus considered key shared nutrients among microbes. Cobamides are structurally diverse, with multiple different cobamides found in most microbial communities. The ability to use different cobamides has been tested for several bacteria and microalgae, and nearly all show preferences for certain cobamides. This approach is limited by the commercial unavailability of cobamides other than cobalamin. Here, we have extracted and purified seven commercially unavailable cobamides to characterize bacterial cobamide preferences based on growth in specific cobamide-dependent conditions. The tested bacteria include engineered strains of Escherichia coli, Sinorhizobium meliloti, and Bacillus subtilis expressing native or heterologous cobamide-dependent enzymes, cultured under conditions that functionally isolate specific cobamide-dependent processes such as methionine synthesis. Comparison of these results to those of previous studies of diverse bacteria and microalgae revealed that a broad diversity of cobamide preferences exists not only across different organisms but also between different cobamide-dependent metabolic pathways within the same organism. The microbes differed in the cobamides that support growth most efficiently, cobamides that do not support growth, and the minimum cobamide concentrations required for growth. The latter differ by up to four orders of magnitude across organisms from different environments and by up to 20-fold between cobamide-dependent enzymes within the same organism. Given that cobamides are shared, required for use of specific growth substrates, and essential for central metabolism in certain organisms, cobamide preferences likely impact community structure and function.IMPORTANCENearly all bacteria are found in microbial communities with tens to thousands of other species. Molecular interactions such as metabolic cooperation and competition are key factors underlying community assembly and structure. Cobamides, the vitamin B12 family of enzyme cofactors, are one such class of nutrients, produced by only a minority of prokaryotes but required by most microbes. A unique aspect of cobamides is their broad diversity, with nearly 20 structural forms identified in nature. Importantly, this structural diversity impacts growth as most bacteria that have been tested show preferences for specific cobamide forms. We measured cobamide-dependent growth in several model bacteria and compared the results to those of previous analyses of cobamide preference. We found that cobamide preferences vary widely across bacteria, showing the importance of characterizing these aspects of cobamide biology to understand the impact of cobamides on microbial communities.

Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.

Lysosomes are degradation centers and signaling hubs that in cells and play important roles in cellular homeostasis, development, and aging. Growing evidence has also implicated the role of lysosome-related mechanisms in the aging process. Meanwhile, the potential impact of lysosomal dysfunction on the production of inflammatory molecules, cellular metabolic status, and mitochondrial function is becoming increasingly significant. In this review, we provide a comprehensive overview of the physiological roles of lysosomes and their association with aging. At the cellular level, lysosomal dysfunction and cellular senescence show strong correlations. Herein, we elucidated the precise mechanisms by which lysosomal dysfunction contributes to various cellular physiological processes, as well as its potential implications in age-related hallmarks. More importantly, we discuss how lysosomal homeostasis is disrupted in several age-related diseases, including atherosclerosis, heart diseases, cancer, neurodegenerative diseases, metabolic disorders, and motor system diseases. Thus, a deeper understanding of lysosomal function may provide fundamental insights into human physiology and age-related diseases. Furthermore, these discoveries emphasize the role of the lysosome in the development of novel therapeutic strategies.

Liraglutide enhances myotube differentiation and muscle contractile activity upon electric pulse stimulation in mouse skeletal muscle cells

Abstract Glucagon-like peptide-1 (GLP-1) is a potent incretin hormone produced by L-cells in the ileum and colon. Skeletal muscle, the most important organ for glucose metabolism, is also affected by GLP-1. Short-term administration of liraglutide, a GLP-1 analog, ameliorated glucose uptake in palmitate-treated type II diabetes models; however, the influence of long-term liraglutide administration on normal muscle cells has not been evaluated. We analyzed the effects of chronic (3 consecutive days) administration of liraglutide at various concentrations on healthy C2C12 skeletal muscle cells by investigating morphological changes, muscle contractile properties, and glucose uptake. Liraglutide administration at an appropriate dose (0.5 μm) had positive effects, including the promotion of muscle hypertrophy, in C2C12 cells; however, excessive administration (10 μm) had atrophic effects. Therefore, proper liraglutide dosing is very important.

Progress in Understanding the Regulation of Glucose and Fructose Metabolism.

Hexoses, including glucose, fructose, and galactose, are six-carbon monosaccharides that play fundamental roles in mammalian metabolism, with glucose serving as the primary energy source and fructose and galactose metabolized through pathways converging with glucose metabolism. While glucose metabolism has been extensively studied over the past hundred years, the mechanisms of fructose metabolism and uptake, the transporters involved, and its roles in physiology and disease are far less explored. Recent data also suggest that excessive fructose intake can have detrimental effects on metabolic organs, including the liver. Emerging studies have uncovered novel regulatory mechanisms in glucose and fructose metabolism, including the role of posttranslational modifications of transporters and enzymes, and the discovery of regulators of transporters. Here, we highlight new findings on the regulation of glucose and fructose transporters and integrate recent molecular and clinical insights into how glucose and fructose contribute to metabolic diseases.