Glucose Metabolism Research Articles

Comparative Environmental Impact Assessment of Resistant Starch-Rich Pastas Produced from High-Amylose Soft Wheat or Malted Bean Flour

Flours rich in resistant starch (RS) are crucial for producing low glycemic index foods, as per Commission Regulation (EU) No. 432/2012. This study assessed the environmental profiles of two high-RS fresh pasta variants: one from malted and decorticated Gradoli Purgatory beans, and another from amylose-rich soft wheat flour, using the Product Environmental Footprint standard method. Both pastas had similar carbon footprints, but the overall weighted score of malted bean pasta was 38% higher than that of the high-amylose wheat pasta, making the latter more economically and environmentally viable. Climate change and water use were major contributors to their environmental footprints, influenced by cultivation practices. Mitigation strategies, such as cultivating drought-resistant beans, are recommended. Although greenhouse gas emissions per gram of protein or RS were similar, overall scores varied, emphasizing the need for sustainable crop selection. Consumer preferences may favor high-amylose wheat for glucose metabolism, while gluten-free, protein-rich needs can be met with malted bean flour, despite its higher environmental impact.

Identification and Characterization of a Novel Insulin-like Receptor (LvRTK2) Involved in Regulating Growth and Glucose Metabolism of the Pacific White Shrimp Litopenaeus vannamei.

The insulin receptor (IR) plays a crucial role in the growth and metabolism of animals. However, there are still many questions regarding the IR in crustaceans, particularly their role in shrimp growth and glucose metabolism. In this study, we identified a novel insulin-like receptor gene in Litopenaeus vannamei and cloned its full length of 6439 bp. This gene exhibited a highly conserved sequence and structural characteristics. Phylogenetic analysis confirmed it as an unreported RTK2-type IR, namely, LvRTK2. Expression pattern analysis showed that LvRTK2 is primarily expressed in female reproductive and digestive organs. Through a series of in vivo and in vitro experiments, including glucose treatment, exogenous insulin treatment, and starvation treatment, LvRTK2 was confirmed to be involved in the endogenous glucose metabolic pathway of shrimp under different glucose variations. Moreover, long-term and short-term interference experiments with LvRTK2 revealed that the interference significantly reduced the shrimp growth rate and serum glucose clearance rate. Further studies indicated that LvRTK2 may regulate shrimp growth by modulating the downstream PI3K/AKT signaling pathway and a series of glucose metabolism events, such as glycolysis, gluconeogenesis, glycogen synthesis, and glycogenolysis. This report on the characteristics and functions of LvRTK2 confirms the important role of RTK2-type IRs in regulating shrimp growth and glucose metabolism.

NMDA Receptors in POMC Neurons Connect Exercise With Insulin Sensitivity.

Increased arcuate proopiomelanocortin (POMC) neuron activity improves glucose metabolism and reduces appetite, facilitating weight loss. We recently showed that arcuate POMC neurons are activated by exercise. However, the role of excitatory glutamatergic input in these neurons and the metabolic outcomes of exercise remains undefined. To investigate this, we developed a mouse model with NMDA receptors (NMDARs) selectively deleted from POMC neurons of adult mice. We performed metabolic assessments, including the monitoring of body weight, body composition analysis, and glucometabolic tolerance tests. We also examined the metabolic outcomes of these mice in response to exercise, including changes in arcuate POMC neuronal activity and insulin sensitivity. Loss of NMDARs in POMC neurons failed to alter body weight or body composition. Notably, however, we did observe a marked impairment in glucose tolerance and insulin sensitivity. Additionally, exercise resulted in activation of arcuate POMC neurons and a sustained improvement in insulin sensitivity, an effect that was abrogated in mice deficient for NMDARs in POMC neurons when compared with their respective sedentary controls. This underscores an important link among exercise, hypothalamic neuron function, and metabolic health. Moreover, this highlights an underappreciated role of hypothalamic POMC neurons in mediating beneficial effects of exercise on glucose metabolism.

Pyruvate dehydrogenase kinase 1 controls triacylglycerol hydrolysis in cardiomyocytes.

Pyruvate dehydrogenase kinase (PDK) 1 is one of four isozymes that inhibit the oxidative decarboxylation of pyruvate to acetyl-CoA via pyruvate dehydrogenase. PDK activity is elevated in fasting or starvation conditions to conserve carbohydrate reserves. PDK has also been shown to increase mitochondrial fatty acid utilization. In cardiomyocytes, metabolic flexibility is crucial for the fulfillment of high energy requirements. The PDK1 isoform is abundant in cardiomyocytes, but its specific contribution to cardiomyocyte metabolism is unclear. Here we show that PDK1 regulates cardiomyocyte fuel preference by mediating triacylglycerol turnover in differentiated H9c2 myoblasts using lentiviral shRNA to knockdown Pdk1 . Somewhat surprisingly, PDK1 loss did not affect overall PDH activity, basal glycolysis, or glucose oxidation revealed by oxygen consumption rate experiments and 13 C 6 glucose labelling. On the other hand, we observed decreased triacylglycerol turnover in H9c2 cells with PDK1 knockdown, which was accompanied by decreased mitochondrial fatty acid utilization following nutrient deprivation. 13 C 16 palmitate tracing of uniformly labelled acyl chains revealed minimal acyl chain shuffling within triacylglycerol, indicating that the triacylglycerol hydrolysis, and not re-esterification, was dysfunctional in PDK1 suppressed cells. Importantly, PDK1 loss did not significantly impact the cellular lipidome or triacylglycerol accumulation following palmitic acid treatment, suggesting that effects of PDK1 on lipid metabolism were specific to the nutrient-deprived state. We validated that PDK1 loss decreased triacylglycerol turnover in Pdk1 knockout mice. Together, these findings implicate a novel role for PDK1 in lipid metabolism in cardiomyocytes, independent of its canonical roles in glucose metabolism.

Association of serum Metrnl levels and high-density lipoprotein cholesterol in patients with type 2 diabetes mellitus: a cross-sectional study.

Meteorin-like (Metrnl) is a novel adipokine which is highly expressed in adipose tissue and has a beneficial effect on glucose and lipid metabolism. High density lipoprotein cholesterol (HDL-C) is well recognized to be inversely associated with cardiovascular events. However, the relationship between serum Metrnl levels and HDL-C in the type 2 diabetes mellitus (T2DM) remains unclear. Therefore, the present study aimed to evaluate the association of serum Metrnl with HDL-C levels in T2DM. Eighty participants with T2DM were included in this cross-sectional study. They were divided into two groups according to HDL-C levels: Group1 (lower HDL-C group): HDL-C < 1.04 mmol/L; Group2 (higher HDL-C group): HDL-C ≥ 1.04 mmol/L. Serum Metrnl levels were measured by enzyme-linked immunosorbent assay (ELISA). As compared with lower HDL-C levels groups, serum Metrnl levels were significantly higher in the group with higher HDL-C. Binary logistic regression analysis showed serum Metrnl levels were positively associated with HDL-C group after adjustment with sex, age, body mass index (BMI), mean arterial pressure (MAP), fasting blood glucose (FPG), triglyceride (TG). Furthermore, serum Metrnl levels were inversely correlated with insulin resistance index (HOMA-IR). HDL-C levels were lowest in the group with the lowest Metrnl levels group and remained positively associated with Metrnl after adjustment for sex, age, BMI, TG, and HOMA-IR by using multivariate logistic regression analysis. Serum Metrnl levels were positively associated with HDL-C levels in patients with T2DM.This suggests that increasing serum Metrnl levels maybe a candidate for improving lipid metabolism and preventing cardiovascular events in T2DM. The study was registered in the Chinese clinical trial registry (ChiCTR- 2100047148).

PET Imaging of Breast Cancer: Current Applications and Future Directions.

As molecular imaging use expands for patients with breast cancer, it is important for breast radiologists to have a basic understanding of molecular imaging, including PET. Although breast radiologists may not directly interpret such studies, basic knowledge of molecular imaging will enable the radiologist to better direct diagnostic workup of patients as well as discuss diagnostic imaging with the patient and other treating physicians. Several new tracers are now available to complement imaging glucose metabolism with FDG. Because it provides a noninvasive assessment of disease status across the whole body, PET offers specific advantages over tissue-based assays. Paired with targeted therapy, molecular imaging has the potential to guide personalized treatment of breast cancer, including guiding dosing during drug trials as well as predicting and assessing clinical response. This review discusses the current established applications of FDG, which remains the most widely used PET radiotracer for malignancy, including breast cancer, and highlights potential areas for expanded use based on recent research. It also summarizes research to date on the U.S. Food and Drug Administration (FDA)-approved PET tracer 16α-18F-fluoro-17β-estradiol (FES), which targets ER, including the current guidelines from the Society of Nuclear Medicine and Molecular Imaging on the appropriate use of FES-PET/CT for breast cancer as well as areas of active investigation for other potential applications. Finally, the review highlights several of the most promising novel PET tracers that are poised for clinical translation in the near future.

Arabinoxylan Alleviates Obesity by Regulating Gut Microbiota and Bile Acid Metabolism.

Overweight and obesity are major and increasingly global public health concern. High intake of dietary fiber is negatively correlated with obesity and obesity-related metabolic diseases. Here, we investigated the impact of arabinoxylan on obesity based on the modification of gut microecology. Arabionxylan reduced body weight and improved glucose metabolism, as well as intestinal barrier function and metabolic endotoxemia in obese mice. Supplementation with arabinoxylan increased the relative abundance of Prevotellaceae_UCG_001, Lachnospiraceae_NK4A136_group, Clostridia_UCG_014, Alistipes, Bacteroides, and Ruminococcus, which was associated with the upregulated 7α-dehydroxylation function and production of secondary bile acids (deoxycholic acid and lithocholic acid). The modification of gut microbiota by arabinoxylan also influenced the production of SCFAs, genistein, daidzein, indolelactic acid, and indoleacetic acid, contributing to the amelioration of obesity. Our study highlights the antiobesity effects of arabinoxylan through the modification of gut microbiota and the production of bioactive metabolites.

In vivo mapping of postprandial hepatic glucose metabolism using dynamic magnetic resonance spectroscopy combined with stable isotope flux analysis in Roux-en-Y gastric bypass adults and non-operated controls: A case-control study.

Roux-en-Y gastric bypass (RYGB) surgery alters postprandial glucose profiles, causing post-bariatric hypoglycaemia (PBH) in some individuals. Due to the liver's central role in glucose homeostasis, hepatic glucose handling might differ in RYGB-operated patients with PBH compared to non-operated healthy controls (HC). We enrolled RYGB-operated adults with PBH and HCs (n = 10 each). Participants ingested 60 g of [6,6'-2H2]-glucose (d-glucose) after an overnight fast. Deuterium metabolic imaging (DMI) with interleaved 13C magnetic resonance spectroscopy was performed before and until 150 min post-d-glucose intake, with frequent blood sampling to quantify glucose enrichment and gluco-regulatory hormones until 180 min. Glucose fluxes were assessed by mathematical modelling. Outcome trajectories were described using generalized additive models. In RYGB subjects, the hepatic d-glucose signal increased early, followed by a decrease, whereas HCs exhibited a gradual increase and consecutive stabilization. Postprandial hepatic glycogen accumulation and the suppression of endogenous glucose production were lower in RYGB patients than in HCs, despite higher insulin exposure, indicating lower hepatic insulin sensitivity. The systemic rate of ingested d-glucose was faster in RYGB, leading to a higher, earlier plasma glucose peak and increased insulin secretion. Postprandial glucose disposal increased in RYGB patients, without between-group differences in peripheral insulin sensitivity. Exploiting DMI with stable isotope flux analysis, we observed distinct postprandial hepatic glucose trajectories and parameters of glucose-insulin homeostasis in RYGB patients with PBH versus HCs. Despite altered postprandial glucose kinetics and higher insulin exposure, there was no evidence of impaired hepatic glucose uptake or output predisposing to PBH in RYGB patients.

Ruminant Trans Fatty Acid Intake Modulates Inflammation Pathways in the Adipose Tissue Transcriptome of C57BL/6 Mice.

The study aims to analyze transcriptomic profiles in adipose tissues postconsumption of elaidic acid (EA; trans-18:1n-9) and trans-palmitoleic acid (TPA; trans-16:1n-7), elucidating their different effects on inflammation and glucose metabolism. Twenty C57BL/6 mice are divided into four groups. Each group receives one of the following formulations in drinking water: lecithin nanovesicles, nanovesicles containing either lecithin with EA or TPA (86:14 w/w), or water (control) for 28 days with a regular fat diet (18% calories from fat). Total RNA is extracted, and paired-end sequencing is performed. TPA intake alters the expression of 351 genes compared to EA intake, including 11 downregulated and 340 upregulated genes (fold change [FC] >1.5, p < 0.05). TPA compares to EA upregulated: Slc5a8, Lcn2, Csf3, Scube1, Mapk13, Bdkrb2, Ctla2a, Slc2a1, Oas3, Cx3cl1, Oas2, Nlrp6, Pycard, Cyba, Ddr1, and Prkab1 and downregulated Fas gene. These genes are related to the NOD-like receptor, lipid and atherosclerosis, IL-17 signaling, TNF, nonalcoholic fatty liver disease, cytokine-cytokine receptor interaction, adipocytokine, glucagon, insulin resistance, and inflammatory mediator regulation of TRP channels signaling. TPA intake has a distinct impact on the regulation of inflammation and diabetes-related pathways in adipose tissue compared to EA.

Moderate-intensity continuous training and high-intensity interval training alleviate glycolipid metabolism through modulation of gut microbiota and their metabolite SCFAs in diabetic rats

Glucose and lipid metabolism disorders are typical of diabetic patients and are important factors leading to macrovascular and microvascular complications. The aim of this study was to understand the effects of different exercises on glycolipid metabolism in diabetic rats and the role of gut flora in metabolic maintenance. We measured glycolipid metabolic indices and short-chain fatty acids (SCFAs) content and sequenced and analyzed gut microbes after 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) programs in type 2 diabetic rats(T2DM). We found that Enterococcaceae, Enterococcus, Subdoligranulum, Kurthia, Bacillales, and Planococcaceae may be key bacterial taxa related to T2DM and that both programs of exercise regulated the intestinal flora of rats with T2DM, improved their glycolipid metabolism, increased the abundance of SCFA-producing intestinal bacteria, and it was found that the PWY-5676 and P163-PWY pathways which are closely related to production of SCFAs were significantly upregulated in the exercise groups. Notably, MICT appeared to be more effective than HIIT in increasing the homogeneity of rat intestinal flora, enriching species, and increasing acetic acid and butyric acid content. These results suggest that exercise improves glycolipid metabolism in diabetic rats, which may be attributed to alterations in the structure of their intestinal flora.

Therapeutic Effects of Proanthocyanidins on Diabetic Erectile Dysfunction in Rats.

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

Spatial multiomics atlas reveals smooth muscle phenotypic transformation and metabolic reprogramming in diabetic macroangiopathy

BackgroundDiabetic macroangiopathy has been the main cause of death and disability in diabetic patients. The mechanisms underlying smooth muscle cell transformation and metabolic reprogramming other than abnormal glucose and lipid metabolism remain to be further explored.MethodSingle-cell transcriptome, spatial transcriptome and spatial metabolome sequencing were performed on anterior tibial artery from 11 diabetic patients with amputation. Multi-omics integration, cell communication analysis, time series analysis, network analysis, enrichment analysis, and gene expression analysis were performed to elucidate the potential molecular features.ResultWe constructed a spatial multiomics map of diabetic blood vessels based on multiomics integration, indicating single-cell and spatial landscape of transcriptome and spatial landscape of metabolome. At the same time, the characteristics of cell composition and biological function of calcified regions were obtained by integrating spatial omics and single cell omics. On this basis, our study provides favorable evidence for the cellular fate of smooth muscle cells, which can be transformed into pro-inflammatory chemotactic smooth muscle cells, macrophage-like smooth muscle cells/foam-like smooth muscle cells, and fibroblast/chondroblast smooth muscle cells in the anterior tibial artery of diabetic patients. The smooth muscle cell phenotypic transformation is driven by transcription factors net including KDM5B, DDIT3, etc. In addition, in order to focus on metabolic reprogramming apart from abnormal glucose and lipid metabolism, we constructed a metabolic network of diabetic vascular activation, and found that HNMT and CYP27A1 participate in diabetic vascular metabolic reprogramming by combining public data.ConclusionThis study constructs the spatial gene-metabolism map of the whole anterior tibial artery for the first time and reveals the characteristics of vascular calcification, the phenotypic transformation trend of SMCs, and the transcriptional driving network of SMCs phenotypic transformation of diabetic macrovascular disease. In the perspective of combining the transcriptome and metabolome, the study demonstrates the activated metabolic pathways in diabetic blood vessels and the key genes involved in diabetic metabolic reprogramming.Graphical abstract

Food intake enhances hippocampal sharp wave-ripples.

Effective regulation of energy metabolism is critical for survival. Metabolic control involves various nuclei within the hypothalamus, which receive information about the body's energy state and coordinate appropriate responses to maintain homeostasis, such as thermogenesis, pancreatic insulin secretion, and food-seeking behaviors. It has recently been found that the hippocampus, a brain region traditionally associated with memory and spatial navigation, is also involved in metabolic regulation. Specifically, hippocampal sharp wave ripples (SWRs), which are high-frequency neural oscillations supporting memory consolidation and foraging decisions, have been shown to influence peripheral glucose metabolism. However, whether SWRs are enhanced by recent feeding-when the need for glucose metabolism increases, and if so, whether feeding-dependent modulation of SWRs is communicated to other brain regions involved in metabolic regulation, remains unknown. To address these gaps, we recorded SWRs from the dorsal CA1 region of the hippocampus of mice during sleep sessions before and after consumption of meals of varying caloric values. We found that SWRs occurring during sleep are significantly enhanced following food intake, with the magnitude of enhancement being dependent on the caloric content of the meal. This pattern occurred under both food-deprived and ad libitum feeding conditions. Moreover, we demonstrate that neuronal populations in the lateral hypothalamus, which regulates food intake, exhibit robust SWR-triggered increase in activity. These findings identify the satiety state as a factor modulating SWRs and suggest that hippocampal-lateral hypothalamic communication is a potential mechanism by which SWRs could modulate peripheral metabolism and food intake.

Bacterial and clinical metabolic signatures and their interactions in obese patients post-bariatric surgery

BackgroundObesity is a growing health concern in China, closely linked to metabolic disorders such as type 2 diabetes. Laparoscopic Sleeve Gastrectomy (LSG) is effective in promoting weight loss and improving metabolic outcomes. Emerging evidence highlights the role of gut microbiota in metabolic regulation, yet the specific alterations in gut microbiota and their association with metabolic changes post-surgery in Chinese patients remain unclear. Understanding these shifts could provide key insights into optimizing treatment strategies for metabolic improvement following bariatric surgery.MethodsStool samples and clinical data were collected from 30 obese patients before and 6 months after surgery. The composition of the gut microbiota was analyzed through 16S rRNA sequencing, and Spearman correlation analysis was used to determine the association between gut microbiota and clinical indicators.ResultsThe analysis of 30 patients showed a significant decrease in Body Mass Index (BMI) (36.75 ± 4.09 kg/m2 vs 26.37 ± 3.47 kg/m2, p < 0.0001). Glucose metabolism, including Hemoglobin A1C levels, improved significantly (6.05 ± 0.96 vs 5.05 ± 0.25, p < 0.0001), and liver function as well as serum lipid levels were also notably improved. LSG increased the richness and composition of gut microbiota in obese patients post-surgery. These changes in gut microbiota were closely associated with improved clinical metabolic parameters.ConclusionLSG not only significantly reduces body weight while also alleviating metabolic syndrome and comorbidities by altering gut microbiota.

The Versatile Role of Peroxisome Proliferator-Activated Receptors in Immune-Mediated Intestinal Diseases.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that sense lipophilic molecules and act as transcription factors to regulate target genes. PPARs have been implicated in the regulation of innate immunity, glucose and lipid metabolism, cell proliferation, wound healing, and fibrotic processes. Some synthetic PPAR ligands are promising molecules for the treatment of inflammatory and fibrotic processes in immune-mediated intestinal diseases. Some of these are currently undergoing or have previously undergone clinical trials. Dietary PPAR ligands and changes in microbiota composition could modulate PPARs' activation to reduce inflammatory responses in these immune-mediated diseases, based on animal models and clinical trials. This narrative review aims to summarize the role of PPARs in immune-mediated bowel diseases and their potential therapeutic use.

Light modulates glucose and lipid homeostasis via the sympathetic nervous system.

Light is an important environmental factor for vision, and for diverse physiological and psychological functions. Light can also modulate glucose metabolism. Here, we show that in mice, light is critical for glucose and lipid homeostasis by regulating the sympathetic nervous system, independent of circadian disruption. Light deprivation from birth elicits insulin hypersecretion, glucagon hyposecretion, lower gluconeogenesis, and reduced lipolysis by 6-8 weeks, in male, but not, female mice. These metabolic defects are consistent with blunted sympathetic activity, and indeed, sympathetic responses to a cold stimulus are significantly attenuated in dark-reared mice. Further, long-term dark rearing leads to body weight gain, insulin resistance, and glucose intolerance. Notably, metabolic dysfunction can be partially alleviated by 5 weeks exposure to a regular light-dark cycle. These studies provide insight into circadian-independent mechanisms by which light directly influences whole-body physiology and inform new approaches for understanding metabolic disorders linked to aberrant environmental light conditions.

Hexokinase Domain Containing 1 (HKDC1) Gene Variants and Their Association With Gestational Diabetes Mellitus: A Mini-Review

Abstract Gestational diabetes mellitus (GDM) is the most common metabolic disorder during the gestational period. Maternal glucose metabolism differs significantly from nonpregnant levels during pregnancy, with increased insulin resistance being the main physiological response. Maternal glucose levels during pregnancy, have a significant impact on the development of early and long-term metabolic health of the offspring. Therefore, a better understanding of the GDM pathophysiology is needed. Hexokinase domain containing 1 (HKDC1) gene was discovered as a gene related to glucose metabolism during pregnancy compared with nongravid state. HKDC1 plays a critical role in glucose homeostasis during pregnancy. Haplotypes of HKDC1 genetic variants associated with 2-h plasma glucose (2hPG) in pregnancy, disrupt regulatory element activity, thereby reducing HKDC1 expression in different tissues. The association of HKDC1 variants with gestational diabetes and 2hPG was investigated in several ethnic groups. These studies suggested that HKDC1 plays a more important role in glucose metabolism during pregnancy than outside of it and also demonstrated that while GDM and type 2 diabetes mellitus have many similarities, there are differences in at least one underlying pathway. This review focuses on the findings of the genetic studies on HKDC1 and GDM.

Lysozyme coupling protease pretreatment to relieve the humic acid inhibition on excess sludge anaerobic fermentation

The asynchronous dosed protease and lysozyme combination pretreatment was proved to be effective in enhancing the anaerobic fermentation of waste activated sludge (WAS). However, humic acid (HA) in the sludge could interact with hydrolase and restrain the hydrolysis efficiency, thus inhibiting short-chain fatty acids (SCFAs) production. This study investigated the effectiveness and mechanism of enzymatic pretreatment against HA. Results showed that the enzyme cocktail method increased the extracellular bioavailable contents by 34 %, which raised SCFAs production by 89.69 % (1269.65 mg COD /L). The balanced ratio of hydrolysis and fermentation communities suggested that the small molecular organics generated by the hydrolysis community could be sufficiently utilized by fermentation communities. The metabolism of amino acids and glucose was facilitated, and the activities of key enzymes were enhanced. These results clarified the effect of asynchronous enzyme cocktail pretreatment against HA inhibition and contributed to SCFAs production, which offered fresh perspectives on carbon recovery.

GR113808, a serotonin receptor 4 antagonist, prevents high-fat-diet-induced obesity, fatty liver formation, and insulin resistance in C57BL/6J mice

BackgroundThe burden of nonalcoholic fatty liver disease is increasing, and limited therapeutic drugs are available for its treatment. Serotonin binds to approximately 14 serotonin receptors (HTR) and plays diverse roles in obesity and metabolic complications. In this study, we focused on the function of HTR4 on nonalcoholic fatty liver disease using GR113808, a selective HTR4 antagonist.MethodsMale C57BL/6J mice were fed high-fat diet for 12 weeks with intraperitoneal GR113808 injection, and HTR expression, weight changes, glucose and lipid metabolism, hepatic fat accumulation, changes in adipose tissue, the changes in transcriptional factors of signaling pathways, and inflammations were assessed. Hep3B cells and 3T3-L1 cells were treated with siRNA targeting HTR4 to downregulate its expression and then cultured with palmitate to mimic a high-fat diet. The changes in transcriptional factors of signaling pathways, and inflammations were assessed in those cells.ResultsAfter feeding a high-fat diet to male C57BL/6J mice, HTR4 expression in the liver and adipose tissues decreased. GR113808 suppressed body weight gain and improved glucose intolerance. Furthermore, GR113808 not only decreased fatty liver formation but also reduced adipose tissue size. Additionally, GR113808 reduced inflammatory cytokine serum levels and inflammasome complex formation in both tissues. Palmitate treatment in HTR4-downregulated Hep3B cells, also reduced peroxisome proliferator-activated receptor γ and sterol regulatory element-binding protein-1 pathway induction as well as inflammasome complex formation, thus decreasing inflammatory cytokine levels. HTR4 downregulation in 3T3-L1 cells also reduced palmitate-induced inflammasome complex formation and inflammatory cytokine production. Palmitate-induced insulin resistance in Hep3B cells, but not in 3T3-L1 cells, was improved by HTR4 downregulation.ConclusionsIn summary, GR113808 protected against fatty liver formation and improved inflammation in the liver and adipose tissue. Downregulation of HTR4 ameliorated insulin resistance in the liver. These results suggest that HTR4 could serve as a promising therapeutic target for metabolic diseases.

Harnessing Prebiotics to Improve Type 2 Diabetes Outcomes.

The gut microbiota, a complex ecosystem of microorganisms in the human gastrointestinal tract (GI), plays a crucial role in maintaining metabolic health and influencing disease susceptibility. Dysbiosis, or an imbalance in gut microbiota, has been linked to the development of type 2 diabetes mellitus (T2DM) through mechanisms such as reduced glucose tolerance and increased insulin resistance. A balanced gut microbiota, or eubiosis, is associated with improved glucose metabolism and insulin sensitivity, potentially reducing the risk of diabetes-related complications. Various strategies, including the use of prebiotics like inulin, fructooligosaccharides, galactooligosaccharides, resistant starch, pectic oligosaccharides, polyphenols, β-glucan, and Dendrobium officinale have been shown to improve gut microbial composition and support glycemic control in T2DM patients. These prebiotics can directly impact blood sugar levels while promoting the growth of beneficial bacteria, thus enhancing glycemic control. Studies have shown that T2DM patients often exhibit a decrease in beneficial butyrate-producing bacteria, like Roseburia and Faecalibacterium, and an increase in harmful bacteria, such as Escherichia and Prevotella. This review aims to explore the effects of different prebiotics on T2DM, their impact on gut microbiota composition, and the potential for personalized dietary interventions to optimize diabetes management and improve overall health outcomes.