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Background: Alzheimer's disease (AD) is the most common form of dementia. Although drugs focusing on reducing amyloid β slow progression, they fail to improve cognitive function. Deficits in glucose metabolism are reflected in FDG-PET and parallel the neurodegeneration and synaptic marker loss closely preceding cognitive decline, but the role of metabolic deficits as a cause or consequence of neurodegeneration is unclear. Pyruvate dehydrogenase (PDH) is lost in AD and an important enzyme connecting glycolysis and the tricarboxylic acid (TCA) cycle by converting pyruvate into acetyl-CoA. It is negatively regulated by pyruvate dehydrogenase kinase (PDHK) through phosphorylation. Methods: In the present study, we assessed the in vitro/ in vivo pharmacological profile of the novel PDHK inhibitor that we discovered, Compound A. We also assessed the effects of Compound A on AD-related phenotypes including neuron loss and cognitive impairment using 5xFAD model mice. Results: Compound A inhibited human PDHK1, 2 and 3 but had no inhibitory activity on PDHK4. In primary neurons, Compound A enhanced pyruvate and lactate utilization, but did not change glucose levels. In contrast, in primary astrocytes, Compound A enhanced pyruvate and glucose utilization and enhanced lactate production. In an efficacy study using 5xFAD mice, Compound A ameliorated the cognitive dysfunction in the novel object recognition test and Morris water maze. Moreover, Compound A prevented neuron loss in the hippocampus and cerebral cortex of 5xFAD without affecting amyloid β deposits. Conclusions: These results suggest ameliorating metabolic deficits by activating PDH by Compound A can limit neurodegeneration and is a promising therapeutic strategy for treating AD. [ABSTRACT FROM AUTHOR]

Excessive fat deposition leads to obesity and cardiovascular diseases with abnormal metabolism. Pantothenic acid (PA) is a major B vitamin required for energy metabolism. However, the effect of PA on lipid metabolism and obesity has not been explored. We investigated the effects and molecular mechanism of PA on fat accumulation as well as the influence of adipogenic marker genes in both adult male mice and primary adipocytes. First, we demonstrated that PA attenuates weight gain in mice fed high-fat diet (HFD). Besides, PA supplementation substantially improved glucose tolerance and lipid metabolic disorder in obese mice. Furthermore, PA significantly inhibited white adipose tissue (WAT) deposition as well as fat droplets visualized by magnification in both chow and HFD group. More importantly, PA obviously suppressed the mRNA levels of CD36, IL-6, and TNF-α to alleviate inflammation and reduced the levels of PPARγ, aP2, and C/EBPα genes that are related to lipid metabolism in inguinal white adipose tissue (ing-WAT) and epididymal white adipose tissue (ei-WAT). In vitro, PA supplementation showed a lower lipid droplet aggregation as well as reduced expression levels of adipogentic genes. Finally, we identified that PA inhibits the phosphorylation levels of p38 and JNK in murine primary adipocytes. Collectively, our data demonstrated for the first time that PA attenuates lipid metabolic disorder as well as fat deposition by JNK/p38 MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

This document, titled "New Insights into Adipose Tissue Metabolic Function and Dysfunction, 2nd Edition," provides an overview of the different types of adipose tissue and their roles in energy storage, thermogenesis, and endocrine signaling. It discusses the unique characteristics of white, brown, and beige adipocytes, as well as their potential to transdifferentiate into other cell types. The document also explores the impact of adipose tissue dysfunction on metabolic disorders such as insulin resistance, obesity, and type 2 diabetes. Additionally, it highlights the effects of factors such as age-related adipose tissue senescence, intermittent cold exposure, exposure to particulate matter, COVID-19 infection, and the consumption of purine nucleotide Inosine 5′-monophosphate (IMP) on adipose tissue and metabolic health. The document concludes by discussing new therapeutic approaches, including gene therapy, cell-based treatments, and the use of carotenoid-rich nanoparticles, for treating obesity and its associated conditions. [Extracted from the article]

The interplay between asthma and glucose metabolism disorders, such as hyperglycemia, has gained increasing attention due to the potential exacerbation of asthma symptoms and severity. This review explores the complex relationship between hyperglycemia and asthma, emphasizing the pathophysiological links, the impact of glucose metabolism disorders on asthma, and the effects of asthma medications on glucose levels. Hyperglycemia, often induced by asthma treatments like corticosteroids, has been associated with an increased risk of asthma exacerbations. This review delves into the pathophysiology underlying this association, highlighting the role of insulin resistance, metabolic syndrome, and obesity in both the development and management of asthma. Metabolic syndrome, characterized by abdominal obesity and hyperglycemia, independently increases the risk of worsening respiratory symptoms and asthma. Furthermore, this review examines the influence of various antidiabetic medications on asthma outcomes. Biguanides, like metformin, have shown promise in improving asthma outcomes in patients with type 2 diabetes mellitus and asthma. However, other medications have mixed results regarding their impact on asthma control and lung function. Considering these findings, this review advocates for further research into the role of metabolic pathways in asthma management. It calls for comparative studies and the inclusion of asthma-related outcomes in clinical trials of antidiabetic drugs to better understand their potential benefits for individuals with obesity and concurrent asthma. [ABSTRACT FROM AUTHOR]

Objective: Disorders of glucose metabolism in children with obesity are less common than in adults. There is also evidence that they may be transient. The aims of this study were to determine the prevalences of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (DM2) and its reversibility in pediatric patients with obesity and to define the factors determining the reversibility of prediabetes or progression to diabetes. Methods: Retrospective analysis included of young patients with obesity. Patients presented and were treated between 2000-2022 at a single center. Results: The study included 573 (316 girls; 55.15%) Caucasian patients with median body mass index (BMI) Z-score of 3.95 (range 2.0-9.9) and median age 13.9 (2.9-17.1) years old. OGTT results were normal in 90.8% (n=520) and signs of prediabetes occurred in 9.2% (n=53); IFG 17%, IGT 88.7%, DM 0%. Among those who underwent OGTT twice (n=53), impaired glucose regulation was present in 9.3% (n=5) (IFG 40%, IGT 80%, DM 0%) at baseline and in 14.8% subject (n=8) (IFG 25%, IGT 50%, DM 25%) at follow-up after lifestyle modification only. After 12-36 months of follow up, in those with a history of IGT, 60% reverted to normal glucose tolerance, while IFG and IGT persisted in 20% and 20%, respectively, and none progressed to DM. The risk factors for progression of glucose metabolism disorders were increase of BMI Z-score, higher insulin levels and elevated homeostatic model assessment-insulin resistance. Conclusion: IFG and IGT are common in pediatric patients with obesity, while the progression to DM2 is rare. Disorders of glucose metabolism have reversible character. [ABSTRACT FROM AUTHOR]

Background: Association between liver cirrhosis (LC) and glucose intolerance has been known since long. Many studies in the past have attempted to explore the correlation of glucose metabolism disorders (GMD) with the severity of LC with mixed results (some favouring i.e. higher prevalence of GMD in more severe LC; others negating). This study was conducted to shed further light on the significance of this association. Objective: This study has been carried out with the aim of studying the correlation between GMD and the severity of LC, as determined by the Child-Turcotte-Pughe (CTP) score. Methods: 100 patients with LC admitted in medical wards were studied and tested with fasting plasma glucose (FPG), 2 h post-75 g oral glucose load plasma glucose (PPG), glycosylated haemoglobin (HbA1c) and fasting plasma insulin. They were categorized based on the severity of LC into CTP A, B or C class and then patients belonging to different classes were compared for the presence of GMD and insulin resistance (IR). Conclusion: Out of 100 patients, 6, 21 and 73 were respectively found as falling under CTP class A, B and C of LC. The frequency of diabetes mellitus (DM) was found to progressively increase with worsening grade of cirrhosis (17%-A, 24%-B and 27%-C), however this was not significant (p value 0.82). The p values for IR, GMD (pre-diabetes or DM), pre-diabetes (pre-DM) were 0.629, 0.382 and 0.189 respectively. To conclude, development of GMD and IR may be independent of the severity of LC. However more studies may be required to further study this association. [ABSTRACT FROM AUTHOR]

The adzuki bean is a mature seed of the red bean leguminous plant, and people like to eat it because of its nutritious properties and moderate proportion of amino acids. Adzuki bean germination and the enrichment of GABA greatly improve the health effects of the adzuki bean. The effects of the GABA-rich adzuki bean on the expression of insulin-pathway-related genes and proteins in the liver of T2DM mice were studied via Western blotting and qPCR. The results showed that a GABA-rich adzuki bean diet could promote glycogen synthesis in the liver of T2DM mice, inhibit the activities of PEPCK and G-6-Pase, and significantly down-regulate the gene expression levels of PEPCK, G6PC and FOXO1 (p < 0.05) and the phosphorylation levels of FOXO1 and GSK3β. In addition, it can also up-regulate the expression of the AMPKα gene and down-regulate the expression of the SREBP1c gene to inhibit the synthesis of triglycerides and cholesterol in T2DM mice. Lipid accumulation in mice can alleviate glucose and lipid metabolism disorders and play an effective role in regulating blood glucose at liver tissue targets. This study suggested that the GABA-rich adzuki bean can improve hyperglycemia in type 2 diabetic mice by activating the IRS/PI3K/AKT signaling pathway in the liver. [ABSTRACT FROM AUTHOR]

The role of Auricularia auricula polysaccharide (AP) in the regulation of glycolipid metabolism was investigated using a high-fat-diet-induced hyperlipidemic mouse model. In a further step, its potential mechanism of action was investigated using microbiome analysis and widely targeted lipidomics. Compared to high-fat mice, dietary AP supplementation reduced body weight by 13.44%, liver index by 21.30%, epididymal fat index by 50.68%, fasting blood glucose (FBG) by 14.27%, serum total cholesterol (TC) by 20.30%, serum total triglycerides (TGs) by 23.81%, liver non-esterified fatty acid (NEFA) by 20.83%, liver TGs by 20.00%, and liver malondialdehyde (MDA) by 21.05%, and increased liver glutathione oxidase (GSH-PX) activity by 52.24%, total fecal bile acid (TBA) by 46.21%, and fecal TG by 27.16%, which significantly regulated glucose and lipid metabolism. Microbiome analysis showed that AP significantly downregulated the abundance of the Desulfobacterota phylum, as well as the genii Desulfovibrio, Bilophila, and Oscillbacter in the cecum of hyperlipidemic mice, which are positively correlated with high lipid indexes, while it upregulated the abundance of the families Eubacterium_coprostanoligenes_group and Ruminococcaceae, as well as the genii Eubacterum_xylanophilum_group, Lachnospiraceae_NK4A136_group, Eubacterium_siraeum_group, and Parasutterella, which were negatively correlated with high lipid indexes. In addition, AP promoted the formation of SCFAs by 119.38%. Widely targeted lipidomics analysis showed that AP intervention regulated 44 biomarkers in metabolic pathways such as sphingolipid metabolism and the AGE-RAGE signaling pathway in the hyperlipidemic mice (of which 15 metabolites such as unsaturated fatty acids, phosphatidylserine, and phosphatidylethanolamine were upregulated, and 29 metabolites such as phosphatidylcholine, ceramide, carnitine, and phosphatidylinositol were downregulated), thereby correcting glucose and lipid metabolism disorders. [ABSTRACT FROM AUTHOR]

Simple Summary: The aims of this study are to analyze prevalence rates, influence, and genetic parameters (heritability, genetic, and phenotypic correlations) of mastitis (MAS), endometritis (MET), and ketosis (KET) in Chinese Holstein Cattle. Data from 37,836 dairy cows in Central China were analyzed using the logistic regression method, a mixed linear model, and an animal model (BLUP). The prevalence rates of MAS, MET, and KET were 20.04%, 10.68%, and 7.33%, respectively. MAS and MET had a negative effect on production traits. High-milk yield cows had high KET prevalence rates. MAS, MET, and KET all had negative influences on reproduction traits. The heritabilities of predispositions to MAS, MET, and KET were 0.09, 0.01, and 0.02, respectively. Mastitis (MAS), endometritis (MET), and ketosis (KET) are prevalent diseases in dairy cows that result in substantial economic losses for the dairy farming industry. This study gathered 26,014 records of the health and sickness of dairy cows and 99,102 data of reproduction from 13 Holstein dairy farms in Central China; the milk protein and milk fat content from 56,640 milk samples, as well as the pedigree data of 37,836 dairy cows were obtained. The logistic regression method was used to analyze the variations in the prevalence rates of MAS, MET, and KET among various parities; the mixed linear model was used to examine the effects of the three diseases on milk production, milk quality, and reproductive traits. DMU software (version 5.2) utilized the DMUAI module in conjunction with the single-trait and two-trait animal model, as well as best linear unbiased prediction (BLUP), to estimate the genetic parameters for the three diseases, milk production, milk quality, and reproductive traits in dairy cows. The primary findings of the investigation comprised the following: (1) The prevalence rates of MAS, MET, and KET in dairy farms were 20.04%, 10.68%, and 7.33%, respectively. (2) MAS and MET had a substantial impact (p < 0.01) on milk production, resulting in significant decreases of 112 kg and 372 kg in 305-d Milk Yield (305-d MY), 4 kg and 12 kg in 305-d Protein Yield (305-d PY), and 6 kg and 16 kg in 305-d Fat Yield (305-d FY). As a result of their excessive 305-d MY, some cows were diagnosed with KET due to glucose metabolism disorder. The 305-d MY of cows with KET was significantly higher than that of healthy cows (205 kg, p < 0.01). (3) All three diseases resulted in an increase in the Interval from Calving to First Service (CTFS, 0.60–1.50 d), Interval from First Service to Conception (FSTC, 0.20–16.20 d), Calving Interval (CI, 4.00–7.00 d), and Number of Services (NUMS, 0.07–0.35). (4) The heritabilities of cows with MAS, MET, and KET were found to be low, with values of 0.09, 0.01, and 0.02, respectively. The genetic correlation between these traits ranged from 0.14 to 0.44. This study offers valuable insights on the prevention and control of the three diseases, as well as feeding management and genetic breeding. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown. Methods: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis (B. uniformis) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD). Results: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product—vaccarin (VAC)—that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice. Conclusions: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver. [ABSTRACT FROM AUTHOR]

Objective: To identify whether Banxia Xiexin Decoction (BXD) alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice. Methods: Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table (n=15 per group), including a model group (MG), a liraglutide group (LG) and a BXD group (BG). Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group (CG). Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg•d) for 3 months, while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection (25 nmol/kg) for 3 months. Firstly, liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD. Then, the cognitive deficits, Aβ pathological change and synaptic plasticity markers, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), were measured in APP/PS1 mice. Brain glucose uptake was detected by micropositron emission tomography. Intestinal microbial constituents were detected by 16S rRNA sequencing. The levels of intestinal glucagon-like peptide 1 (GLP-1) and cerebral GLP-1 receptor (GLP-1R), as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3β (PI3K/Akt/GSK3β) insulin signaling pathway were determined by immunohistochemical (IHC) staining and Western blot analysis, respectively. Results: BXD ameliorated cognitive deficits and Aβ pathological features (P<0.01). The expressions of SYP and PSD95 in the BG were higher than those in the MG (P<0.01). Brain glucose uptake in the BG was higher than that in the MG (P<0.01). The intestinal microbial composition in the BG was partially reversed. The levels of intestinal GLP-1 in the BG were higher than those in the MG (P<0.01). Compared with the MG, the expression levels of hippocampal GLP-1R, Akt, PI3K and p-PI3K in the BG were significantly increased (P<0.01), while the levels of GSK3β were reduced (P<0.01). Conclusion: BXD exhibited protective effects against Alzheimer's disease by regulating the gut microbiota/GLP-1/GLP-1R, enhancing PI3K/Akt/GSK3β insulin signaling pathway, and improving brain glucose metabolism. [ABSTRACT FROM AUTHOR]

Aronia melanocarpa, a plant rich in anthocyanins, has been studied for its potential to regulate blood sugar and blood lipids, although the specific mechanism is not yet understood. This research aims to identify the differential bacterial flora and elucidate the mechanism by which it improves glucose and lipid metabolism disorders through 16S rDNA gene sequencing. The study reveals the protective effect of Aronia melanocarpa extract (AME) on liver damage in type 2 diabetic rats. Experimental results demonstrate that AME can effectively modulate the abundance of intestinal flora, reduce colon tissue damage, enhance the weight of diabetic rats, and lower levels of fasting blood sugar, low‐density lipoprotein (LDL), and triglycerides (TG). Additionally, liver morphology analysis shows that AME can effectively mitigate liver tissue structural damage in type 2 diabetic rats. In conclusion, AME regulates glucose and lipid metabolism by influencing intestinal flora, ultimately regulating glucose and lipid metabolism in type 2 diabetic rats. [ABSTRACT FROM AUTHOR]

This document is a compilation of scientific articles that discuss the role of gut microbiota in human metabolic health and disease. The articles explore topics such as the impact of gut microbiota on glucose control, energy metabolism, inflammation, and insulin resistance in conditions like type 2 diabetes and prediabetes. They also examine the influence of dietary fiber, short-chain fatty acids, and specific bacteria on gut homeostasis and immune responses. The articles provide insights into the complex interactions between the gut microbiome and host metabolism, suggesting the potential for microbiota-based interventions in the prevention and treatment of metabolic diseases. [Extracted from the article]

Objective: It is well known that glucose and lipid metabolism disorders and insulin resistance are common in sepsis, which affect the occurrence and prognosis of multiple organ dysfunction in septic patients. Previous study reported the predictive value of triglyceride-glucose index (TyG), a clinical indicator for insulin resistance, in postoperative delirium patients. However, it remains unclear whether the TyG index is a novel predictive biomarker for sepsis-associated delirium. The aim of this study is to explore the relationship between TyG index and the risk of delirium in patients with sepsis. Methods: Adult septic patients were identified from the MIMIC-IV database and divided into four groups based on the mean value of TyG. The primary outcome was the incidence of delirium. The association between TyG and the risk of developing delirium was evaluated by restricted cubic spline (RCS), multivariate logistic regression and subgroup analysis. Propensity Score Matching (PSM) method was used to balance the baseline data. Results: A total of 3,331 septic patients were included in the analysis, and further divided into four groups: Q1 (TyG ≤ 8.67), Q2 (8.67 < TyG ≤ 9.08), Q3 (9.08 < TyG ≤ 9.61), and Q4 (TyG > 9.61). The RCS curves demonstrated a non-linear positive relationship between TyG index and the risk of developing delirium, and an optimal cut-of value 9.09 was recommended. After balancing the baseline information by PSM, patients in the TyG > 9.09 group had a significant higher incidence of delirium compared with those in the TyG ≤ 9.09 group. In logistic regression analysis, TyG > 9.09 was significantly associated with lower risk of developing delirium in both original cohort (OR 1.54–1.78, all P < 0.001) and the PSM cohort (OR 1.41–1.48, all P < 0.001). No association was found between the TyG index and mortality (all P > 0.05). In subgroup analysis, our findings were consistent (all OR > 1 in all subgroups). Conclusion: Our study demonstrated an independent association between TyG index and increased risk of delirium in septic patients, indicating that TyG index can serve as a biomarker for delirium in sepsis. [ABSTRACT FROM AUTHOR]

The incidence of lung cancer brain metastasis combined with hemorrhagic cerebral venous sinus thrombosis (CVST) is very rare, and the understanding and treatment experience of this case is insufficient. We reported a case of lung cancer brain metastasis accompanied by venous sinus thrombosis, and describe the diagnosis and treatment plan for colleagues to learn from experience and lessons. Key points: 1. The incidence of lung cancer brain metastasis combined with hemorrhagic CVST is very rare, and the understanding and treatment experience of this case is insufficient. 2. The clinical manifestations of metastatic tumors and CVST in patients are not specific, and the evolution of the medical history should be inquired in detail, with careful physical examination and imaging review. 3. CVST should be considered in patients with risk factors. The incidence of hemorrhagic CVST is relatively rare, and due to atypical symptoms and imaging manifestations, it is easy to miss and misdiagnose. 4. The responsible lesion should be determined based on the evolution of the medical history, the treatment of the responsible lesion should be prioritized, symptoms should be relieved in a timely manner and the optimal treatment time should be strived for. [ABSTRACT FROM AUTHOR]

Background: β-blockers have been widely used in patients with extensive cardiovascular disease (CVD) and have provided benefits. However, they are more likely to cause symptomatic bradycardia, hypotension, or glucose metabolism disorders, which may lead to an increased risk of atrial fibrillation (AF), but evidence is lacking. Aims: This study was to analyze the association between the use of β-blockers and the risk of developing AF. Methods: This nationwide, prospective cohort study utilized data from the 2013--2020 National Health and Nutrition Examination Survey (NHANES). The patients were stratified into a β-blocker treatment group (n = 2585) and a non-β-blocker treatment group (n = 8525). Univariate and multivariate logistic regression analyses were performed to identify the relationship between β-blockades and the risk of AF. Propensity matching analysis was used to balance patient baseline characteristics and to control for confounders. Results: A total of 11,110 subjects were included in this study (mean [SD] age, 59.89 [15.07] years; 5657 [49.7%] males). A total of 111/2585 subjects developed AF in the β-blocker treatment group, and 75/8525 developed AF in the non-β-blocker treatment group (incidence rate, 4.2% vs. 0.8%). Compared with the non-β-blocker group, the β-blocker group had an increased risk of incident AF (aOR, 2.339; 95% CI, 1.614--3.410). Some sensitivity analyses also revealed consistent findings of increased AF risk associated with β-blocker treatment. Conclusion: The findings from this study suggest that β-blocker treatment is associated with an increased risk of incident AF and may help physicians select a modest medication for patients while also assessing the risk of AF. [ABSTRACT FROM AUTHOR]

Metabolic disorders are currently threatening public health worldwide. Discovering new targets and developing promising drugs will reduce the global metabolic-related disease burden. Metabolic disorders primarily consist of lipid and glucose metabolic disorders. Specifically, metabolic dysfunction-associated steatosis liver disease (MASLD) and alcohol-associated liver disease (ALD) are two representative lipid metabolism disorders, while diabetes mellitus is a typical glucose metabolism disorder. In this review, we aimed to summarize the new drug candidates with promising efficacy identified in clinical trials for these diseases. These drug candidates may provide alternatives for patients with metabolic disorders and advance the progress of drug discovery for the large disease burden. [ABSTRACT FROM AUTHOR]

Background: Daylength and the rates of changes in daylength have been associated with seasonal fluctuations in psychiatric symptoms and in cognition and mood in healthy adults. However, variations in human brain glucose metabolism in concordance with seasonal changes remain under explored. Methods: In this cross-sectional study, we examined seasonal effects on brain glucose metabolism, which we measured using 18F-fluorodeoxyglucose-PET in 97 healthy participants. To maximize the sensitivity of regional effects, we computed relative metabolic measures by normalizing the regional measures to white matter metabolism. Additionally, we explored the role of rest–activity rhythms/sleep–wake activity measured with actigraphy in the seasonal variations of regional brain metabolic activity. Results: We found that seasonal variations of cerebral glucose metabolism differed across brain regions. Glucose metabolism in prefrontal regions increased with longer daylength and with greater day-to-day increases in daylength. The cuneus and olfactory bulb had the maximum and minimum metabolic values around the summer and winter solstice respectively (positively associated with daylength), whereas the temporal lobe, brainstem, and postcentral cortex showed maximum and minimum metabolic values around the spring and autumn equinoxes, respectively (positively associated with faster daylength gain). Longer daylength was associated with greater amplitude and robustness of diurnal activity rhythms suggesting circadian involvement. Conclusions: The current findings advance our knowledge of seasonal patterns in a key indicator of brain function relevant for mood and cognition. These data could inform treatment interventions for psychiatric symptoms that peak at specific times of the year. [ABSTRACT FROM AUTHOR]

Glypican-4 belongs to a group of poorly understood adipokines, with potential importance in people with metabolic syndrome, especially in groups of patients with glucose metabolism disorder. This study aimed to assess the effect of physical activity on serum glypican-4 and irisin levels and total antioxidant status (TAS) in plasma and saliva in women with metabolic syndrome (MetS). Seventy-two Caucasian women aged 25–60 were included in the study (36 women with MetS and 36 women without MetS (control group, CONTR)). The glypican-4 and irisin concentrations, total antioxidant status, glycemia, lipid profile, anthropometric parameters, and blood pressure were analyzed before and after 28 days of controlled physical activity. Serum glypican-4 and plasma TAS levels were higher (p = 0.006 and p = 0.043, respectively) on the 28th day than on the first day of the study only in the CONTR group. In the MetS group, 28 days of physical activity caused a reduction in body fat mass (p = 0.049) without changes in glypican-4, irisin, or TAS levels. In both groups, glypican-4 levels correlated positively with irisin levels and negatively with Waist-Hip Ratio (WHR), while irisin levels correlated positively with High-Density Lipoprotein Cholesterol (HDL-C) levels and negatively with waist circumference (WC) and WHR values on the 28th day of the study. To summarize, a 28-day moderate training, accompanied by a reduction in body fat mass, stabilized glypican-4 levels and TAS in female patients with MetS. [ABSTRACT FROM AUTHOR]

Obesity is an ongoing global health problem, and Cichorium glandulosum (CG, chicory) is traditionally used as a hepatoprotective and lipid-lowering drug. However, there is still a lack of research on the role of CG in the treatment of obesity. In the present study, we found that CG significantly delayed weight gain and positively affected glucolipid metabolism disorders, serum metabolism levels, and the degree of liver and kidney oxidative stress in high-fat diet (HFD) mice. Further examination of the effects of CG on intestinal microenvironmental dysregulation and its metabolites in HFD mice revealed that the CG ethanol extract high-dose group (CGH) did not have a significant regulatory effect on short-chain fatty acids. Still, CGH significantly decreased the levels of 12α-OH/non-12α-OH bile acids and also found significant upregulation of proteobacteria and downregulation of cyanobacteria at the phylum level. CG may have ameliorated obesity and metabolic abnormalities in mice by repairing gut microbiota dysbiosis and modulating bile acid biosynthesis. [ABSTRACT FROM AUTHOR]

Background: While previous population studies have shown that higher triglyceride-glucose (TyG) index values are associated with an increased risk of congestive heart failure (CHF), the relationship between TyG and CHF in patients with abnormal glucose metabolism remains understudied. This study aimed to evaluate the association between TyG and CHF in individuals with diabetes and prediabetes. Methods: The study population was derived from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. The exposure variable, TyG, was calculated based on triglyceride and fasting blood glucose levels, while the outcome of interest was CHF. A multivariate logistic regression analysis was employed to assess the association between TyG and CHF. Results: A total of 13,644 patients with diabetes and prediabetes were included in this study. The results from the fitting curve analysis demonstrated a non-linear U-shaped correlation between TyG and CHF. Additionally, linear logistic regression analysis showed that each additional unit of TyG was associated with a non-significant odds ratio (OR) of 1.03 (95%CI: 0.88–1.22, P = 0.697) for the prevalence of CHF. A two-piecewise logistic regression model was used to calculate the threshold effect of the TyG. The log likelihood ratio test (p < 0.05) indicated that the two-piecewise logistic regression model was superior to the single-line logistic regression model. The TyG tangent point was observed at 8.60, and on the left side of this point, there existed a negative correlation between TyG and CHF (OR: 0.54, 95%CI: 0.36–0.81). Conversely, on the right side of the inflection point, a significant 28% increase in the prevalence of CHF was observed per unit increment in TyG (OR: 1.28, 95%CI: 1.04–1.56). Conclusions: The findings from this study suggest a U-shaped correlation between TyG and CHF, indicating that both elevated and reduced levels of TyG are associated with an increased prevalence of CHF. [ABSTRACT FROM AUTHOR]

Patients with cystic fibrosis (CF) are at risk to develop CF related diabetes (CFRD) and subsequently even diabetic neuro- and/or vasculopathy. We sought to determine if there are typical signs of diabetes-related retinal alterations present in CF patients with preserved and impaired glycemic control. During routine annual examination CF patients were offered an additional 7-day period of real time continuous glucose monitoring (rtCGM) and an ophthalmological examination including retinal optical coherence tomography (OCT). Patients were categorized according to the glycemic control, i.e. the results of an oral glucose tolerance test (OGTT) and rtCGM were taken into consideration. OCT data was analyzed by our previously published visual analysis software generating dedicated and spatially resolved deviation maps for visualization and quantification of differences in total retinal thickness and thickness of retinal nerve fiber layer (RNFL) as well as ganglion cell layer (GCL) in comparison to age-matched healthy controls and patients with either type 1 or type 2 diabetes mellitus. Results of the rtCGM and/or OGTT enabled discrimination between patients with normal glycemic control (CFNG; n = 6), with abnormal glycemic control (CFAG; n = 6) and overt CFRD (n = 4). OCT data indicates gradually increasing retinal thinning in all 3 groups, depending on the degree of glucose metabolism disorder compared to healthy controls. At the foveal region total retinal thickness and GCL thickness were significantly thinner in CFRD patients compared to CFNG patients (total retinal thickness: 260.4 µm (239.3–270.8) vs. 275.4 µm (254.3–289.5); GCL: 11.82 µm (11.16–15.25) vs. 17.30 µm (13.95–19.82); each p < 0.05). Although we investigated a rather small number of patients, we obtained evidence that intraretinal neurodegenerative changes occur in each of our subgroups (CFNG, CFAG, CFRD). Beyond this, our results favor the detrimental role of additional diabetes, as the deviations from healthy controls were most pronounced in the CFRD group and are similar to those seen in patients suffering from type 1 or type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is a complex group of chronic metabolic conditions. The incidence of frailty, sarcopenia, geriatric syndrome, and multiple chronic conditions is high in older patients with diabetes, who often require multiple medications for optimal glucose control and treatment of associated chronic complications. Unfortunately, polypharmacy is associated with a high risk of adverse outcomes, such as hypoglycemia, drug-drug interactions, and an increased socioeconomic burden in older adults with diabetes. Current Concepts: Elderly patients with diabetes are at a high risk for polypharmacy and consequently, a high risk of adverse drug reactions. Polypharmacy is defined as the cumulative use of five or more medications. Comprehensive management and deprescribing are the most important approaches to reduce polypharmacy. Deprescription refers to reduction in or cessation of inappropriate medications. Discussion and Conclusion: Polypharmacy continues to increase the risk of morbidity and mortality among older adults with diabetes. A comprehensive polypharmacy management and deprescription plan is warranted for significant risk reduction in elderly patients with diabetes. [ABSTRACT FROM AUTHOR]

Background Polycystic ovary syndrome with insulin resistance (PCOS-IR) is recognized as one of the most challenging subtypes of PCOS to treat due to its intricate pathogenesis and significant individual variability. Although Metformin, as a first-line medication, can ameliorate blood glucose levels and enhance insulin sensitivity, its efficacy in regulating hormonal imbalances and improving ovarian function is limited. Additionally, its gastrointestinal side effects often hinder patient adherence. Objective To evaluate the efficacy and safety of Yishen Quzhuo Formula compared to metformin in the treatment of PCOS-IR. Methods A prospective study enrolled 102 PCOS-IR patients from June 2022 to October 2023 at the Department of Gynecology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. Patients were randomly assigned in a 2∶1 ratio to the experimental group (n=68) treated with Yishen Quzhuo Formula or the control group (n=34) treated with metformin. The comparison was made between the two groups in terms of ovulation rate, pregnancy rate, sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, testosterone (T), anti-Müllerian hormone (AMH) ], glucose and lipid metabolism indicators, BMI, waist-hip ratio (WHR), and incidence of adverse reactions. Results After treatment, the basal body temperature (BBT) ovulation rate in the experimental group increased compared to before treatment (P0.05). After treatment, both groups showed a decrease in LH/FSH compared to before treatment (P0.05). After treatment, the waist circumference of the control group was lower than that of the experimental group (P0.05). During treatment, adverse reactions such as hypoglycemia, fatigue, epigastric discomfort, and diarrhea occurred in patients, with a lower incidence of adverse reactions in the experimental group (5/68, 7.35%) than in the control group (15/31, 48.39%) (χ2=20.404, P

Background Porphyromonas gingivalis (Pg.) is the main pathogen of periodontitis. Studies have found that Pg. can affect systemic diseases including type 2 diabetes mellitus (T2DM) through oral-intestinal pathway, but its specific mechanism remains unclear. Objective To explore whether Pg. has an effect on T2DM by changing intestinal mechanical and immune barriers. Methods A total of 24 among 40 SPF mice were randomly selected to construct T2DM models, among the successful models, 16 mice were selected to be divided into the model group (DM group, n=8) and model+Pg. group (PD group, n=8), and the other 16 mice were divided into the control group (N group, n=8) and Pg. group (n=8). After modeling, body mass and fasting plasma glucose (FPG) of mice were observed, and oral glucose tolerance test (OGTT) was performed at the 5th week, OGTT curve was plotted and the area under the curve (AUC) was calculated. Pg. group and PD group were gavaged with Pg. bacterial solution from the 7th week for 5 consecutive weeks. Lipopolysaccharide (LPS) was determined by enzyme-related immunosorbent assay (ELISA), colonic tight-junction protein and inflammatory factors were detected by real-time fluorescence quantitative PCR, and colonic tissue lesions were observed by hematoxylin-eosin (HE) staining. Pearson correlation or Spearman correlation analysis was used to investigate the relationship of FPG with colonic tight junction protein mRNA expression and serum LPS levels in mice. Results Body weight of DM group was higher than that of N group and Pg. group at 2nd to 6th weeks before irrigation (P

Background: Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous. Methods: A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 < AIP ≤ 0.329), Q3 (0.329 < AIP ≤ 0.562), and Q4 (AIP > 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan–Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states. Results: During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan–Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values < 0.05). After adjusting for potential confounders, the risk of stroke was significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group in all participants. The respective hazard ratios (95% confidence interval) for stroke in the Q2, Q3, and Q4 groups were 1.34 (1.05–1.71), 1.52 (1.19–1.93), and 1.84 (1.45–2.34). Furthermore, high levels of AIP were found to be linked to an increased risk of stroke in both pre-diabetic and diabetic participants across all three Cox models. However, this association was not observed in participants with normal glucose regulation (NGR) (p > 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders. Conclusions: An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual's glucose metabolism status. [ABSTRACT FROM AUTHOR]

The literature on green tea consumption and glucose metabolism has reported conflicting findings. This cross-sectional study examined the association of green tea consumption with abnormal glucose metabolism among 3000 rural residents aged 40–60 years in Khánh Hòa province in Vietnam. Multinomial logistic regression analysis was conducted to examine the association of green tea consumption (0, < 200, 200–< 400, 400–< 600 or ≥ 600 ml/d) with prediabetes and diabetes (based on the American Diabetes Association criteria). Linear regression analysis was performed to examine the association between green tea consumption and the log-transformed homeostatic model assessment of insulin resistance (HOMA-IR) (a marker of insulin resistance) and the log-transformed homeostatic model assessment of β -cell function (HOMA- β) (a marker of insulin secretion). The OR for prediabetes and diabetes among participants who consumed ≥ 600 ml/d v. those who did not consume green tea were 1·61 (95 % CI = 1·07, 2·42) and 2·04 (95 % CI = 1·07, 3·89), respectively. Higher green tea consumption was associated with a higher level of log-transformed HOMA-IR (P for trend = 0·04) but not with a lower level of log-transformed HOMA- β (P for trend = 0·75). Higher green tea consumption was positively associated with the prevalence of prediabetes, diabetes and insulin resistance in rural Vietnam. The findings of this study indicated prompting the need for further research considering context in understanding the link between green tea consumption and glucose metabolism, especially in rural settings in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the consensus regarding the association between exercise training and adaptive alterations, the potential biological effects on the liver have yet to be elucidated. In particular, the modulation of the mechanistic target of rapamycin (mTOR) is known to be involved in controlling the processes of glucose and lipid homeostasis, as well as hepatic morphological changes. This narrative review aimed to describe how exercise training interventions affect signaling pathways related to mTOR, its modulation, and other effects on the liver tissue in experimental models. The literature offers a consensus on the association between exercise training (ET) protocols based on the adequate parameters of intensity and frequency, and several adaptive alterations in the liver. Indeed, regular ET can reverse glucose and lipid metabolism disorders, especially from aerobic modalities, which can decrease intrahepatic fat formation. In terms of molecular mechanisms, the regulation of hepatic fat formation would be directly related to the modulation of the mechanistic target of rapamycin (mTOR), which would be stimulated by insulin signaling and Akt activation, from the following three different primary signaling pathways: (I) growth factor, (II) energy/ATP-sensitive, and (III) amino acid-sensitive signaling pathways, respectively. Hyperactivation of the Akt/mTORC1 pathway induces lipogenesis by regulating the action of sterol regulatory element binding protein-1 (SREBP-1). Exercise training interventions have been associated with multiple metabolic and tissue benefits. However, it is worth highlighting that the mTOR signaling in the liver in response to exercise interventions remains unclear. Hepatic adaptive alterations seem to be most outstanding when sustained by chronic interventions or high-intensity exercise protocols. [ABSTRACT FROM AUTHOR]

Previous studies have shown that feeding mice with food containing mantle tissue from Japanese scallops results in aggravated liver and kidney damage, ultimately resulting in mortality within weeks. The aim of this study is to evaluate the toxicity of scallop mantle in China's coastal areas and explore the impact of scallop mantle toxins (SMT) on intestinal barrier integrity and gut microbiota in mice. The Illumina MiSeq sequencing of V3-V4 hypervariable regions of 16S ribosomal RNA was employed to study the alterations in gut microbiota in the feces of SMT mice. The results showed that intestinal flora abundance and diversity in the SMT group were decreased. Compared with the control group, significant increases were observed in serum indexes related to liver, intestine, inflammation, and kidney functions among SMT-exposed mice. Accompanied by varying degrees of tissue damage observed within these organs, the beneficial bacteria of Muribaculaceae and Marinifilaceae significantly reduced, while the harmful bacteria of Enterobacteriaceae and Helicobacter were significantly increased. Taken together, this article elucidates the inflammation and glucose metabolism disorder caused by scallop mantle toxin in mice from the angle of gut microbiota and metabolism. SMT can destroy the equilibrium of intestinal flora and damage the intestinal mucosal barrier, which leads to glucose metabolism disorder and intestinal dysfunction and may ultimately bring about systemic toxicity. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, which begins with liver lipid accumulation and is associated with metabolic syndrome. Also, the name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). We performed focused drug screening and found that Cilostazol effectively ameliorated hepatic steatosis and might offer potential for NAFLD treatment. Our aim was to investigate the therapeutic effects of Cilostazol on the glycolipid metabolism and intestinal flora in NAFLD mice and explore the specific mechanism. In this study, 7-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, and then treated with intragastric administration for 12 weeks. The results showed that Cilostazol inhibited liver lipid de novo synthesis by regulating the AMPK-ACC1/SCD1 pathway and inhibited liver gluconeogenesis by the AMPK-PGC1α-G6P/PEPCK pathway. Cilostazol improved the intestinal flora diversity and intestinal microbial composition in the NAFLD mice, and specifically regulated Desulfovibrio and Akkermansia. In addition, Cilostazol increased the level of short-chain fatty acids in the NAFLD mice to a level similar to that in the blank Control group. Cilostazol reduces liver lipid accumulation in NAFLD mice by improving glucose and lipid metabolism disorders and intestinal dysfunction, thereby achieving the purpose of treating NAFLD. [ABSTRACT FROM AUTHOR]

In diabetes mellitus, disordered glucose and lipid metabolisms precipitate diverse complications, including nonalcoholic fatty liver disease, contributing to a rising global mortality rate. Theaflavins (TFs) can improve disorders of glycolipid metabolism in diabetic patients and reduce various types of damage, including glucotoxicity, lipotoxicity, and other associated secondary adverse effects. TFs exert effects to lower blood glucose and lipids levels, partly by regulating digestive enzyme activities, activation of OATP-MCT pathway and increasing secretion of incretins such as GIP. By the Ca2+-CaMKK ꞵ-AMPK and PI3K-AKT pathway, TFs promote glucose utilization and inhibit endogenous glucose production. Along with the regulation of energy metabolism by AMPK-SIRT1 pathway, TFs enhance fatty acids oxidation and reduce de novo lipogenesis. As such, the administration of TFs holds significant promise for both the prevention and amelioration of diabetes mellitus. [ABSTRACT FROM AUTHOR]

The flowers of Edgeworthia gardneri are used as herbal tea and medicine to treat various metabolic diseases including hyperglycemia, hypertension, and hyperlipidemia. This paper investigate the chemical constituents and biological activities of ethanolic extract and its different fractions from E. gardneri flowers. Firstly, the E. gardneri flowers was extracted by ethanol-aqueous solution to obtain crude extract (CE), which was subsequently fractionated by different polar organic solution to yield precipitated crystal (PC), dichloromethane (DCF), ethyl acetate (EAF), n-butanol (n-BuF), and residue water (RWF) fractions. UHPLC-ESI-HRMS/MS analysis resulted in the identification of 25 compounds, and the main compounds were flavonoids and coumarins. The precipitated crystal fraction showed the highest phenolic and flavonoid contents with 344.4 ± 3.38 mg GAE/g extract and 305.86 ± 0.87 mg RE/g extract. The EAF had the strongest antioxidant capacity and inhibitory effect on α-glucosidase and pancreatic lipase with IC50 values of 126.459 ± 7.82 and 23.16 ± 0.79 µg/mL. Besides, both PC and EAF significantly regulated the glucose and lipid metabolism disorders by increasing glucose consumption and reducing TG levels in HepG2 cells. Molecular docking results suggested that kaempferol-3-O-glucoside and tiliroside had good binding ability with enzymes, indicating that they may be potential α-glucosidase and pancreatic lipase inhibitors. Therefore, the E. gardneri flowers could be served as a bioactive agent for the regulation of metabolic disorders. [ABSTRACT FROM AUTHOR]

Disorders of glucose and lipid metabolism are important causes of type 2 diabetes mellitus (T2DM). Defining the molecular mechanisms of metabolic disorders and exploring drug targets are key to the treatment of T2DM. The study discovered the effects of catalpol on insulin resistance (IR) and lipid metabolism disorder (LMD) in type 2 diabetes mellitus (T2DM). A T2DM mouse model was established by a high-fat diet and a single intraperitoneal injection of streptozotocin. and injected with catalpol at 10 mg/kg for 12 weeks, and the lentiviral vector of miR-101-3p or Fosrelated antigen 2 (FOSL2) expression was interfered with intravenously mouse insulin resistance (IR) and lipid metabolism disorder (LMD)-related indices were then measured. Pancreatic histopathology was observed by hematoxylin and eosin (HE) staining and TUNEL staining. The miR-101-3p and FOSL2 were detected by RT-qPCR or Western blot. In results: catalpol improved IR and LMD (both P<0.05) in diabetic mice, and alleviated the histopathological changes in the pancreas. miR-101-3p was upregulated (P<0.05), and FOSL2 was downregulated (P<0.05) in T2DM mice, while catalpol rescued their expression pattern (both P<0.05). The miR-101-3p targeted FOSL2. Down-regulating miR-101-3p or up-regulating FOSL2 improved IR and LMD (all P<0.05) in diabetic mice, and alleviated pancreatic histopathological changes. Overexpressing miR-101-3p or suppressing FOSL2 weakened the ameliorative effects of catalpol in T2DM mice (all P<0.05). We conclude that catalpol improves IR and LMD in diabetic mice by inhibiting miR-101-3p to up-regulate FOSL2. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART)‐associated metabolic abnormalities, including impairment of glucose metabolism, are prevalent in adults living with HIV. However, the prevalence and pathogenesis of impaired glucose metabolism in children and adolescents living with HIV, particularly in sub‐Saharan Africa, are not well characterized. We investigated the prevalence of impaired glucose metabolism among children and adolescents living with perinatally infected HIV in Ghana. Methods: In this multicentre, cross‐sectional study, we recruited participants from 10 paediatric antiretroviral treatment clinics from January to June 2022 in 10 facilities in Greater Accra and Eastern regions of Ghana. We determined impaired glucose metabolism in the study sample by assessing fasting blood sugar (FBS), insulin resistance as defined by the homeostatic model assessment for insulin resistance (HOMA‐IR) index and glycated haemoglobin (HbA1c) levels. The prevalence of impaired glucose metabolism using each criterion was stratified by age and sex. The phenotypic correlates of glucose metabolism markers were also assessed among age, sex, body mass index (BMI) and waist‐to‐hip ratio (WHR). Results: We analysed data from 393 children and adolescents living with HIV aged 6–18 years. A little over half (205/393 or 52.25%) of the children were female. The mean age of the participants was 11.60 years (SD = 3.50), with 122/393 (31.00%) aged 6–9 years, 207/393 (52.67%) aged 10–15 years, and 62/393 (15.78%) aged 16–18 years. The prevalence rates of glucose impairment in the study population were 15.52% [95% confidence interval (CI): 12.26–19.45], 22.39% (95% CI: 18.54–26.78), and 26.21% (95% CI: 22.10–30.78) using HbA1c, HOMA‐IR, and FBS criteria, respectively. Impaired glucose metabolism detected by FBS and HOMA‐IR was higher in the older age group, whereas the prevalence of abnormal HbA1c levels was highest among the youngest age group. Age and BMI were positively associated with FBS and HOMA‐IR (p < 0.001). However, there was negative correlation of WHR with HOMA‐IR (p < 0.01) and HbA1c (p = 0.01). Conclusion: The high prevalence of impaired glucose metabolism observed among the children and adolescents living with HIV in sub‐Saharan Africa is of concern as this could contribute to the development of metabolic syndrome in adulthood. [ABSTRACT FROM AUTHOR]

This study was to investigate the effect and possible mechanism of circadian rhythm change on the development of nonalcoholic fatty liver disease (NAFLD) in mice. A total of 80 male SPF-grade 4-week C57BL/6J mice were randomly divided into normal diet normal light/dark cycle (ND-LD) and high-fat diet all dark (HFD-DD) groups. Weight measurements were taken weekly, and after 24 weeks of intervention, 24 mice from both groups were randomly selected and analyzed. Additionally, the remaining mice in the HFD-DD group were divided into two groups: one group continued the high-fat all-dark treatment (HFD-DD-DD), and the other group was restored to normal light/dark cycle treatment (HFD-DD-LD). Mice were euthanized after a total of 48 weeks of intervention. Measurements were taken for each mouse including liver function serum indicators, liver tissue pathological sections, rhythm-related proteins, and determination of the gut microbiota community. The HFD induced NAFLD in mice, exhibiting symptoms such as obesity, lipid and glucose metabolism disorders, elevated liver enzymes, and decreased gut microbiota diversity. The composition of the gut microbiota was significantly different from that of the normal diet group, with a significant increase in the ratio of Firmicutes to Bacteroides. Restoration of normal light/dark cycles exacerbated the disorder of lipid metabolism, liver steatosis, and the expression of BMAL1 in mice and significantly reduced the diversity of gut microbiota. Circadian rhythm changes aggravate the development of NAFLD induced by a high-fat diet by affecting glucose metabolism, liver steatosis, and gut microbiota diversity. Restoration of normal circadian rhythm did not improve NAFLD. Our findings open up new avenues for the prevention, diagnosis, and treatment of NAFLD. • High-fat diet and circadian changes reduce gut microbiome richness and diversity. • HFD-DD (24th week) BMAL1 is higher than HFD-LD, indicating circadian influence. • HFD groups show elevated body weights, liver ratios, and abnormal liver structure. • HFD-DD-LD shows reduced gut microbiome richness compared to HFD-DD-DD. • Rhythm restoration didn't improve metabolism or steatosis in HFD-fed mice. [ABSTRACT FROM AUTHOR]

The circadian timing system controls glucose metabolism in a time‐of‐day dependent manner. In mammals, the circadian timing system consists of the main central clock in the bilateral suprachiasmatic nucleus (SCN) of the anterior hypothalamus and subordinate clocks in peripheral tissues. The oscillations produced by these different clocks with a period of approximately 24‐h are generated by the transcriptional‐translational feedback loops of a set of core clock genes. Glucose homeostasis is one of the daily rhythms controlled by this circadian timing system. The central pacemaker in the SCN controls glucose homeostasis through its neural projections to hypothalamic hubs that are in control of feeding behavior and energy metabolism. Using hormones such as adrenal glucocorticoids and melatonin and the autonomic nervous system, the SCN modulates critical processes such as glucose production and insulin sensitivity. Peripheral clocks in tissues, such as the liver, muscle, and adipose tissue serve to enhance and sustain these SCN signals. In the optimal situation all these clocks are synchronized and aligned with behavior and the environmental light/dark cycle. A negative impact on glucose metabolism becomes apparent when the internal timing system becomes disturbed, also known as circadian desynchrony or circadian misalignment. Circadian desynchrony may occur at several levels, as the mistiming of light exposure or sleep will especially affect the central clock, whereas mistiming of food intake or physical activity will especially involve the peripheral clocks. In this review, we will summarize the literature investigating the impact of circadian desynchrony on glucose metabolism and how it may result in the development of insulin resistance. In addition, we will discuss potential strategies aimed at reinstating circadian synchrony to improve insulin sensitivity and contribute to the prevention of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Sepsis-induced myocardial injury, as one of the important complications of sepsis, can significantly increase the mortality of septic patients. Our previous study found that nucleolin affected mitochondrial function in energy synthesis and had a protective effect on septic cardiomyopathy in mice. During sepsis, glucose metabolism disorders aggravated myocardial injury and had a negative effect on septic patients. Objectives: We investigated whether nucleolin could regulate glucose metabolism during endotoxemia-induced myocardial injury. Methods: The study tested whether the nucleolin cardiac-specific knockout in the mice could affect glucose metabolism through untargeted metabolomics, and the results of metabolomics were verified experimentally in H9C2 cells. The ATP content, lactate production, and oxygen consumption rate (OCR) were evaluated. Results: The metabolomics results suggested that glycolytic products were increased in endotoxemia-induced myocardial injury, and that nucleolin myocardial-specific knockout altered oxidative phosphorylation-related pathways. The experiment data showed that TNF-α combined with LPS stimulation could increase the lactate content and the OCR values by about 25%, and decrease the ATP content by about 25%. However, interference with nucleolin expression could further decrease ATP content and OCR values by about 10–20% and partially increase the lactate level in the presence of TNF-α and LPS. However, nucleolin overexpression had the opposite protective effect, which partially reversed the decrease in ATP content and the increase in lactate level. Conclusion: Down-regulation of nucleolin can exacerbate glucose metabolism disorders in endotoxemia-induced myocardial injury. Improving glucose metabolism by regulating nucleolin was expected to provide new therapeutic ideas for patients with septic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Prediabetes is a metabolic condition characterized by blood glucose levels higher than normal but below the threshold for diabetes mellitus. It represents a critical stage in the progression towards type 2 diabetes mellitus (T2DM) and is associated with an increased risk of cardiovascular disease and other complications. The two major pathophysiologic defects responsible for losing glucose tolerance are insulin resistance and β-cell glucose insensitivity, both appearing in subjects of Intermediate Hyperglycaemia. In classical literature, Unani physicians have described the initial symptoms and factors leading to the pathology, the risk factors are described in terms of ‘Su-e-mizaj’ as per the concept of Tibb. So, it is considered in the context of Ziabetus which is described as a disease that develops due to Sue-mizaj haar (abnormal hot temperament). The symptoms mentioned in Unani medicine are increased frequency of micturition (ants and flies are attracted to urine), increased thirst, nocturia, dryness of mouth and whole body, fatigue, loss of weight, malaise, and cramps in lower extremities. The modern drug-based approach for the management of Intermediate Hyperglycaemia is associated with inherent drawbacks, including toxicity, tolerability, cost, and efficacy.Objective: The purpose of this review is to provide an in-depth understanding of prediabetes concerning the classical literature of Greek medicine based on the analysis of certain parameters like etiopathophysiology, current diagnostic criteria, risk factors, and evidence-based management strategies. By synthesizing findings from epidemiological studies, and clinical trials, this paper aims to enhance understanding of prediabetes and facilitate effective preventive measures and interventions [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common systemic disorder related to endocrine disorders, affecting the fertility of women of childbearing age. It is associated with glucose and lipid metabolism disorders, altered gut microbiota, and insulin resistance. Modern treatments like pioglitazone, metformin, and spironolactone target specific symptoms of PCOS, while in Chinese medicine, moxibustion is a common treatment. This study explores moxibustion’s impact on PCOS by establishing a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Thirty-six specific pathogen-free female Sprague-Dawley rats were divided into four groups: a normal control group (CTRL), a PCOS model group (PCOS), a moxibustion treatment group (MBT), and a metformin treatment group (MET). The MBT rats received moxibustion, and the MET rats underwent metformin gavage for two weeks. We evaluated ovarian tissue changes, serum testosterone, fasting blood glucose (FBG), and fasting insulin levels. Additionally, we calculated the insulin sensitivity index (ISI) and the homeostasis model assessment of insulin resistance index (HOMA-IR). We used 16S rDNA sequencing for assessing the gut microbiota, 1 H NMR spectroscopy for evaluating metabolic changes, and Spearman correlation analysis for investigating the associations between metabolites and gut microbiota composition. The results indicate that moxibustion therapy significantly ameliorated ovarian dysfunction and insulin resistance in DHEA-induced PCOS rats. We observed marked differences in the composition of gut microbiota and the spectrum of fecal metabolic products between CTRL and PCOS rats. Intriguingly, following moxibustion intervention, these differences were largely diminished, demonstrating the regulatory effect of moxibustion on gut microbiota. Specifically, moxibustion altered the gut microbiota by increasing the abundance of UCG-005 and Turicibacter, as well as decreasing the abundance of Desulfovibrio. Concurrently, we also noted that moxibustion promoted an increase in levels of short-chain fatty acids (including acetate, propionate, and butyrate) associated with the gut microbiota of PCOS rats, further emphasizing its positive impact on gut microbes. Additionally, moxibustion also exhibited effects in lowering FBG, testosterone, and fasting insulin levels, which are key biochemical indicators associated with PCOS and insulin resistance. Therefore, these findings suggest that moxibustion could alleviate DHEA-induced PCOS by regulating metabolic levels, restoring balance in gut microbiota, and modulating interactions between gut microbiota and host metabolites. [ABSTRACT FROM AUTHOR]

Hyperglycemia is correlated with worse in-hospital outcomes in acute infectious diseases such as coronavirus disease 2019 (COVID-19) and severe fever with thrombocytopenia syndrome (SFTS). This study assessed the relationship between fasting plasma glucose (FPG) levels and in-hospital mortality, disease type, and secondary infections among individuals with SFTS without preexisting diabetes. The clinical data and laboratory results upon admission of 560 patients with SFTS without preexisting diabetes meeting the inclusion criteria at Wuhan Union Hospital were collected. FPG levels in surviving patients with SFTS subjects were significantly lower than those in patients with SFTS who had died (P<0.0001). In multivariate Cox regression, high FPG level (≥11.1 mmol/L) was a risk factor independently associated with the in-hospital death of patients with SFTS without preexisting diabetes. Similarly, the FPG levels in general patients with SFTS were significantly lower than those in patients with severe SFTS (P<0.0001). Multivariate logistic regression identified high FPG level (7.0–11.1 mmol/L) as a risk factor independently associated with SFTS severity. While FPG levels were comparable between patients with SFTS with and without secondary infection (P = 0.5521), logistic regression analysis revealed that high FPG levels were not a risk factor for secondary infection in patients with SFTS without preexisting diabetes. High FPG level on admission was an independent predictor of in-hospital death and severe disease in individuals with SFTS without preexisting diabetes. FPG screening upon admission and glycemic control are effective methods for improving the prognosis of patients with SFTS. Author summary: Diabetes is a risk factor for a less favorable prognosis in patients with cancer or autoimmune diseases, but few studies have explored the association between fasting plasma glucose (FPG) levels and in-hospital mortality, disease type, and secondary infections among individuals with severe fever and thrombocytopenia syndrome (SFTS). Our study reveal that high FPG level on admission was an independent predictor of in-hospital death and severe disease in individuals with SFTS without preexisting diabetes. FPG screening upon admission and glycemic control are effective methods to assess the prognosis and disease type of patients with SFTS regardless of diabetes status, as most individuals with SFTS are prone to glucose metabolism disorders. [ABSTRACT FROM AUTHOR]

Metabolism-associated fatty liver disease (MAFLD) is the hepatic manifestation of metabolic syndrome, with a global incidence up to 25% in adults, and has replaced viral hepatitis as the first chronic liver disease in China. Adenosine monophosphate-activated protein kinase (AMPK) is an important key enzyme in the regulation of glycolipid metabolism in vivo. The activation of AMPK is thought to have the ability to improve glucose and lipid metabolism disorder, alleviate oxidative stress, possess anti-inflammatory, regulate autophagy affects, and protect the mitochondria to play a therapeutic role in the treatment of MAFLD. As an important treasure trove of medicinal resources in traditional Chinese medicine, natural products of Li medicine have been widely found to activate AMPK and exhibit excellent effects in improving MAFLD. Therefore, this review is planned to summarize the association mechanisms between MAFLD improvement and AMPK activation of Li medicine and its natural products, to provide theoretical references for the exploration and development of Li medicine and its natural products. There by promoting modernization industry development of Li medicine. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosteroneinduced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS. [ABSTRACT FROM AUTHOR]

Patients with inflammatory liver diseases, particularly alcohol-associated liver disease and metabolic dysfunction-associated fatty liver disease (MAFLD), have higher incidence of infections and mortality rate due to sepsis. The current focus in the development of drugs for MAFLD is the resolution of non-alcoholic steatohepatitis and prevention of progression to cirrhosis. In patients with cirrhosis or alcoholic hepatitis, sepsis is a major cause of death. As the metabolic center and a key immune tissue, liver is the guardian, modifier, and target of sepsis. Septic patients with liver dysfunction have the highest mortality rate compared with other organ dysfunctions. In addition to maintaining metabolic homeostasis, the liver produces and secretes hepatokines and acute phase proteins (APPs) essential in tissue protection, immunomodulation, and coagulation. Inflammatory liver diseases cause profound metabolic disorder and impairment of energy metabolism, liver regeneration, and production/secretion of APPs and hepatokines. Herein, the author reviews the roles of (1) disorders in the metabolism of glucose, fatty acids, ketone bodies, and amino acids as well as the clearance of ammonia and lactate in the pathogenesis of inflammatory liver diseases and sepsis; (2) cytokines/chemokines in inflammatory liver diseases and sepsis; (3) APPs and hepatokines in the protection against tissue injury and infections; and (4) major nuclear receptors/signaling pathways underlying the metabolic disorders and tissue injuries as well as the major drug targets for inflammatory liver diseases and sepsis. Approaches that focus on the liver dysfunction and regeneration will not only treat inflammatory liver diseases but also prevent the development of severe infections and sepsis. [ABSTRACT FROM AUTHOR]

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown neuroprotective effects in obese mice. However, whether SGLT2i can ameliorate high-fat diet (HFD)-related ovulation disorders remains unknown. The aim of this research was to investigate whether dapagliflozin improves HFD-induced ovulatory dysfunction by attenuating microglia-mediated hypothalamic inflammation. Methods: C57BL/6J female mice fed HFD were treated with dapagliflozin (1 mg/kg) for 22 weeks. Plasma insulin, leptin, luteinizing hormone (LH), estradiol (E2), and IL-1β levels were also tested. Microglial morphology, cell numbers, and SGLT2 expression were evaluated using immunofluorescence. The expression of IL-1β, NLRP3, kisspeptin, gonadotropin-releasing hormone (GnRH), SGLT2, insulin, and leptin receptors in the hypothalamus was determined using immunohistochemical staining. We also examined the effects of dapagliflozin on glucose metabolism and the release of inflammatory factor in palmitic acid (PA)-treated HMC3 cells. Results: As expected, dapagliflozin improved HFD-induced metabolic disturbances, peripheral versus central insulin and leptin resistance and also restored the regular estrous cycle. Furthermore, dapagliflozin blunted microglia activation, NLRP3 inflammasome priming, hypothalamic inflammation, and increased the expression of GnRH and kisspeptin at proestrus in the hypothalamus. Additionally, dapagliflozin markedly reduced IL-6 and NO release and fat accumulation, decreased lactic acid production and glucose consumption, and inhibited mammalian target of rapamycin (mTOR) and hexokinase 2 (HK2) expression in PA-treated HMC3 cells. These effects suggest that dapagliflozin reduced the mTOR/HK2-mediated aerobic glycolysis. Conclusions: Dapagliflozin improved HFD-related ovulation disorders by regulating glucose metabolism through mTOR/HK2 signaling and attenuating microglia-mediated hypothalamic inflammation. These results validate the novel role for the neuroprotection of SGLT2i in HFD-induced obesity and ovulation disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lead (Pb) is an ancient toxic metal and is still a major public health issue. Our previous study found that Pb exposure promotes metabolic disorders in obese mice, but the molecular mechanisms remain unclear. The present study explored the effects of Pb exposure on glucose homeostasis in mice fed a normal diet (ND) and high-fat diet (HFD) from the perspective of gut microbiota. RESULTS: Pb exposure had little effect on glucose metabolism in ND mice, but exacerbated hyperglycemia and insulin resistance, and impaired glucose tolerance in HFD mice. Pb exposure impaired intestinal tight junctions and mucin expression in HFD mice, increasing intestinal permeability and inflammation. Moreover, Pb exposure altered the composition and structure of the gut microbiota and decreased short-chain fatty acids (SCFAs) levels in HFD mice. Correlation analysis revealed that the gut microbiota and SCFAs were significantly correlated with the gut barrier and glucose homeostasis. Furthermore, the fecal microbiota transplantation from Pb-exposed HFD mice resulted in glucose homeostasis imbalance, intestinal mucosal structural damage and inflammation in recipient mice. However, Pb did not exacerbate the metabolic toxicity in HFD mice under depleted gut microbiota. CONCLUSION: The findings of the present study suggest that Pb induces impairment of glucose metabolism in HFD mice by perturbing the gut microbiota. Our study offers new perspectives on the mechanisms of metabolic toxicity of heavy metals and demonstrates that the gut microbiota may be a target of action for heavy metal exposure. [ABSTRACT FROM AUTHOR]

Aronia melanocarpa fruit contains a variety of active ingredients, such as phenolic acids, anthocyanins, proanthocyanidins, etc. Relevant in vivo and in vitro studies have concluded that it has beneficial effects in terms of treating dyslipidemia, hypertension, glucose metabolism disorders, etc. This article discusses the nutritional value and food processing of Aronia melanocarpa and reviews the chemical components of Aronia melanocarpa and the pharmacological activities of related substances in order to summarize the chemical characteristics of the fruit and its development prospects. The process optimization of juice production, the impact of antioxidant capacity, and the comprehensive utilization of pomace in feed are discussed. This article provides a reference for future comprehensive application research and product development of Aronia melanocarpa. [ABSTRACT FROM AUTHOR]

Maintaining blood glucose at an appropriate physiological level requires precise coordination of multiple organs and tissues. The vagus nerve bidirectionally connects the central nervous system with peripheral organs crucial to glucose mobilization, nutrient storage, and food absorption, thereby presenting a key pathway for the central control of blood glucose levels. However, the precise mechanisms by which vagal populations that target discrete tissues participate in glucoregulation are much less clear. Here we review recent advances unraveling the cellular identity, neuroanatomical organization, and functional contributions of both vagal efferents and vagal afferents in the control of systemic glucose metabolism. We focus on their involvement in relaying glucoregulatory cues from the brain to peripheral tissues, particularly the pancreatic islet, and by sensing and transmitting incoming signals from ingested food to the brain. These recent findings - largely driven by advances in viral approaches, RNA sequencing, and cell-type selective manipulations and tracings - have begun to clarify the precise vagal neuron populations involved in the central coordination of glucose levels, and raise interesting new possibilities for the treatment of glucose metabolism disorders such as diabetes. [ABSTRACT FROM AUTHOR]

Background: Alisol A can ameliorate glucose metabolism disorders, however, there is no data regarding its role in diabetic nephropathy (DN). The present work evaluates the role of Alisol A in DN and the underlying mechanism. Methods: RNA expression of circ_0001831, miR‐346, and lin‐28 homolog B (LIN28B) was detected by qRT‐PCR. Cell viability and proliferation were investigated by MTT assay and EdU assay, respectively. The inflammatory cytokines were examined by ELISAs. Oxidative stress was evaluated by the commercial kits. Protein expression was detected by western blotting. The interactions among circ_0001831, miR‐346, and LIN28B were identified by dual‐luciferase reporter assay and RIP assay. DN mouse model assay was used to analyse the effect of Alisol A on renal injury of diabetic mice. Results: HG treatment promoted HRMC proliferation, fibrosis, inflammation, and oxidative stress; however, these effects were reversed after Alisol A treatment. Alisol A treatment ameliorated STZ‐induced renal injury of diabetic mice. Additionally, circ_0001831 or LIN28B overexpression or miR‐346 downregulation relieved Alisol A‐induced effects under HG conditions. Mechanistically, circ_0001831 acted as a miR‐346 sponge, and LIN28B was identified as a target gene of miR‐346. Further, the regulation of circ_0001831 in HG‐induced HRMC dysfunction involved LIN28B. Conclusion: Alisol A ameliorated HG‐induced HRMC fibrosis, inflammation, and oxidative stress and STZ‐induced renal injury of diabetic mice by regulating the circ_0001831/miR‐346/LIN28B pathway. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a metabolic inflammatory disease with a high incidence worldwide. Patients with DM are at a high risk for all types of infections. Type 1 DM is characterised with immune destruction of pancreatic β cells, while type 2 diabetes is characterised with insulin resistance and β cell dysfunction, both of which result in disorders of glucose and lipid metabolism. This metabolic disorder causes functional defects of immune cells, aberrant production of inflammatory cytokines, dysregulated immune responses, advanced pathophysiological injury of the body, and increased mortality in populations with DM upon infections. Starting with the change of natural immune system in patients with DM, this paper focused on the enhanced severity of infections in DM and the underlying innate immune alterations in preclinical and clinical studies, aiming to better understand the influence of DM on the susceptibility, pathophysiology, and clinical outcomes in infections. [ABSTRACT FROM AUTHOR]

Introduction: Treatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long‐acting GLP‐1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice. Methods: Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety‐ and depression‐like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography–tandem mass spectrometry‐based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment. Results: Three weeks of dulaglutide treatment significantly reversed depressive‐like but not anxiety‐like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy. Conclusion: The antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant‐like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression. [ABSTRACT FROM AUTHOR]