Improvement Of Metabolism Research Articles

Association of bodyweight loss with changes in lipids, blood pressure, and fasting serum glucose following tirzepatide treatment in Japanese participants with type 2 diabetes: Apost hoc analysis of the SURPASS J-mono trial.

In the SURPASS J-mono trial, tirzepatide demonstrated significant improvements in bodyweight and several metabolic parameters in Japanese participants with type 2 diabetes. This post hoc analysis evaluated the potential relationships between weight loss and metabolic improvements in SURPASS J-mono. Metabolic parameter data from tirzepatide-treated participants were analyzed by weight loss subgroups and compared to dulaglutide 0.75 mg. Correlations between changes from baseline to week 52 in weight loss and each metabolic parameter were assessed; Pearson correlation coefficients were derived. Mediation analyses were conducted to evaluate weight loss-associated and -unassociated effects of tirzepatide vs dulaglutide 0.75 mg. This analysis included 548 participants (tirzepatide: n = 411, dulaglutide: n = 137). Weight loss subgroups showed greater improvement in metabolic parameters with greater bodyweight loss. Significant (P < 0.05) but weak correlations between changes in bodyweight and triglycerides (r = 0.18-0.25), high-density lipoprotein cholesterol (r = -0.37 to -0.29), and systolic blood pressure (r = 0.19-0.41) were observed across treatment groups; in diastolic blood pressure in the tirzepatide 5-mg (r = 0.28), pooled tirzepatide (r = 0.20), and dulaglutide 0.75-mg (r = 0.23) groups; and in fasting serum glucose in the dulaglutide 0.75-mg (r = 0.18) and pooled tirzepatide (r = 0.13) groups. Weight loss was associated with treatment differences between tirzepatide and dulaglutide 0.75 mg to varying degrees across metabolic parameters, with improvements in fasting serum glucose having the lowest association with weight loss (36.6%-43.5%). In this post hoc analysis, non-glycemic and glycemic parameter improvements appeared differentially associated with weight loss, suggesting both weight loss-associated and -unassociated effects of tirzepatide.

Maternal exercise prevents metabolic disorders in offspring mice through SERPINA3C.

Maternal exercise can improve the metabolic health of the offspring. However, the molecular mechanisms underlying the beneficial effects of maternal exercise on the offspring remain unclear. Here, we show that maternal exercise during pregnancy alleviates high-fat diet (HFD)-induced adipose inflammation and glucose intolerance in offspring mice, accompanied by upregulation of the adipokine serine protease inhibitor A3C (SERPINA3C) both in maternal adipose tissues and the fetal circulation. Adipose SERPINA3C knockdown impairs, but its overexpression in dams mimics, maternal exercise-mediated metabolic benefits in HFD-fed offspring. Maternal SERPINA3C is transported into the fetal circulation and promotes Krüppel-like factor 4 (Klf4) gene promoter demethylation in fetal preadipocytes to increase KLF4 expression, which inhibits adipose inflammation in HFD-fed offspring mice. The SERPINA3C-cathepsin G-integrin β1 axis activates phosphatidylinositol 3-kinase signalling in preadipocytes. This promotes nuclear translocation of the p110β subunit to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the nucleus. O-linked β-N-acetylglucosamine (O-GlcNAc) transferase then binds to PIP3 to promote ten-eleven translocation methylcytosine dioxygenase 1 (TET1) O-GlcNAcylation, thereby enhancing TET1 activity to facilitate Klf4 gene promoter demethylation. These results provide mechanistic insights into maternal exercise-mediated improvement of offspring metabolism.

Impacts of Behavioral Compliance on Weight-Loss and Metabolic Profile in a Smartphone App-Based Lifestyle Intervention or Plus Dietitian Supporting: A Randomized and Controlled Trial Among Chinese

Abstract Mobile health technologies provided innovative solutions for lifestyle interventions and offered reliable methods to evaluate behavioral phenotypes during such interventions. To systematically quantify the impacts of behavioral compliance on weight-loss and metabolic profiles during lifestyle intervention, a total of 395 Chinese adults with overweight/obesity (BMI ≥ 24 kg/m2) or central obesity (waistline ≥ 90 cm for men or ≥ 80 cm for women) were randomly assigned to a smartphone app-based arm (SAA, n = 197) or smartphone app plus dietitian arm (SADA, n = 198) for 6 months. Compliance scores (0–5) were determined based on fulfilling five behavioral tasks: completing online courses, wearing a smart band, and recording weight, food intake, and blood pressure. SADA had greater weight-loss (− 4.94% vs. − 2.28%, p &lt; 0.001) and lower triglyceride, but higher HDL-C levels (both p &lt; 0.05) than SAA after six months. Between-group weight-loss differences were attenuated at compliance scores ≥ 3 (SADA: − 6.30% vs. SAA: − 4.79%, p = 0.07). Mediation analysis suggested that compliance scores explained approximately 30% of the additional weight loss in the SADA (p &lt; 0.001), and self-weighing was the primary mediator (p &lt; 0.05). Higher educational levels, greater initial weight loss, self-perceived simplicity, and satisfaction with the program were potential determinants of intervention compliance. Overall, the superior weight loss and metabolic improvements in the SADA group could be mediated by behavioral compliance, which was possibly influenced by some demographic and intervention response features. Our findings highlighted the roles of behavioral phenotypes and adherence in app-based lifestyle interventions, and added evidence for the future development of more precise strategies in long-term weight management.

Chrysanthemum extract mitigates high-fat diet-induced inflammation, intestinal barrier damage and gut microbiota disorder.

An effective intervention for obesity without side effects is needed. Chrysanthemum may be the preferred choice due to its influence in the improvement of glycolipid metabolism. This study assessed the efficacy of chrysanthemum and its flavonoids in mitigating high-fat diet (HFD) induced obesity, focusing on the integrity of the intestinal barrier, inflammation, and gut microbiota. Fifty male C57BL/6J mice were divided into 5 groups randomly: normal control (NC), HFD, HFD with chrysanthemum aqueous extract (CM), HFD with a low-dose flavonoid extract of chrysanthemum (FLL), and HFD with a high-dose flavonoid extract of chrysanthemum (FLH). The results showed that after 9 weeks of intervention with CM, FLL and FLH, the body weight and blood lipid levels of mice were reduced. The chrysanthemum treatment regimens down-regulated the gene expression and protein levels of TLR4, MyD88, TRAF6 and NF-κB, upregulated the gene expression levels of ZO-1 and occludin, and decreased the levels of LPS and diamine oxidase (DAO) in the serum. With CM, FLL and FLH, the levels of the inflammatory factors IL-1β, TNF-α, and IL-6 were decreased, and the abundance of pernicious bacteria Lachnoclostridium, Streptococcus and Enterococcus was decreased. Notably, the purified chrysanthemum flavonoid extract showed greater effects as compared to the CM. The study demonstrated that chrysanthemum extracts could achieve anti-obesity effects by strengthening the intestinal barrier function, relieving inflammation and modulating the gut microbial composition.

Advances in inflammatory senescence in liver disease.

Inflammatory senescence is a process of cellular dysfunction associated with chronic inflammation, which plays a significant role in the onset and progression of liver diseases,and the research on its mechanisms becomes a hotspot currently. In viral hepatitis, the mechanisms of inflammatory senescence primarily involve oxidative stress, cell apoptosis and necrosis, as well as gut microbiota dysbiosis. In non-alcoholic fatty liver disease, the mechanisms of inflammatory senescence are more complex, involving insulin resistance, fat deposition, lipid metabolism disorders, gut microbiota dysbiosis, and NAD+ metabolism abnormalities. In liver tumors, inflammatory senescence is characterized by the weakening of tumor suppressive mechanisms, remodeling of the liver microenvironment, metabolic reprogramming, and enhanced immune evasion. Therapeutic strategies targeting inflammatory senescence have been developing recently, and antioxidant therapy, metabolic disorder improvement, and immunotherapy emerging are important interventions for liver diseases. This review focuses on the mechanisms of inflammatory secescence in liver diseases, aiming to provide novel insights for the prevention and treatment of liver diseases.

Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery Stenosis.

Carotid endarterectomy (CEA) is widely used to treat carotid artery stenosis (CAS). However, the effects of CEA on unilateral CAS-induced cognitive impairment and the underlying mechanism remain poorly understood. Thirteen patients diagnosed with unilateral severe CAS underwent pre- and post-CEA assessments, including 18fluoro-2-deoxy-d-glucose positron emission tomography/magnetic resonance imaging, cognitive assessments, and routine blood tests before and after CEA. Unilateral carotid common artery occlusion and ligation release (reperfusion) surgeries were performed in mice to mimic CAS and CEA. Cognitive function, cerebral blood flow, and white matter damage were evaluated in mice using the Morris water maze test, Doppler flowmetry, laser-speckle imaging, diffusion tensor imaging, Luxol fast blue staining, transmission electron microscopy, and western blot assays post unilateral carotid common artery occlusion and reperfusion. Genomic sequencing of the white matter was performed to explore the potential underlying mechanism. CEA significantly enhanced the Montreal Cognitive Assessment scores in patients with CAS and preoperative cognitive impairment. Moreover, CEA led to notable improvements in cerebral blood flow, energy metabolism, and white matter integrity, while concurrently reducing blood inflammation. In the mouse model, reperfusion surgery alleviated cognitive deficits, increased cerebral blood flow, and alleviated white matter damage following unilateral carotid common artery occlusion. Furthermore, transcriptional surveys have revealed substantial alterations in the upregulation of Nrf2 signaling and metabolic pathways, coupled with the inhibition of neuroinflammation, cellular communication, and immune cell population signaling following reperfusion. CEA ameliorated CAS-induced cognitive dysfunction by improving the cerebral functional structure. These beneficial effects may be attributed to their antioxidant and anti-inflammatory properties.

Dapagliflozin combined with metformin improves blood glucose, bone metabolism and bone mineral density in elderly patients with type 2 diabetes mellitus complicated with osteoporosis.

The incidence of type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP) (T2DM-OP) is growing. Dapagliflozin and metformin are commonly prescribed to manage glycemic levels in T2DM patients. We investigated the clinical efficacy of combining dapagliflozin with metformin in elderly patients with T2DM-OP. Totally 144 T2DM-OP patients were prospectively enrolled and allocated into two groups: the Metformin and Dapagliflozin + Metformin groups. Each group received treatment for 12 months. Fasting peripheral blood samples were collected before and after 12 months of treatment. Glycemic parameters and bone metabolic parameters were measured using oral glucose tolerance test, automatic biochemical analyzers, or liquid chromatography. Bone mineral density (BMD) changes at lumbar vertebrae (L1-4), femoral neck (FN) and total hip (TH) were assessed using dual-energy X-ray bone mineral densitometry. Pain severity was evaluated using the visual analog scale (VAS). The total effective rate, fracture incidence, and adverse reaction rate were also evaluated. After 12 months, both groups showed improvements in glycemic parameters, bone metabolic parameters, and BMD at L1-4, FN, and TH, and reductions in VAS scores. The Dapagliflozin + Metformin group exhibited more significant improvements. The overall effective rate was higher and fracture incidence, was lower in Dapagliflozin + Metformin group, with comparable rates of adverse reactions and safety profiles between the two groups. Taken together, treatment with a combination of dapagliflozin and metformin led to improvements in blood glucose levels, bone metabolism, and BMD in elderly patients with T2DM-OP, demonstrating superior efficacy and safety compared to metformin monotherapy.

Born of frustration: the emergence of Camelina sativa as a platform for lipid biotechnology.

The emerging crop Camelina sativa (L.) Crantz (camelina) is a Brassicaceae oilseed with a rapidly growing reputation for the deployment of advanced lipid biotechnology and metabolic engineering. Camelina is recognised by agronomists for its traits including yield, oil/protein content, drought tolerance, limited input requirements, plasticity and resilience. Its utility as a platform for metabolic engineering was then quickly recognised, and biotechnologists have benefited from its short life cycle and facile genetic transformation, producing numerous transgenic interventions to modify seed lipid content and generate novel products. The desire to work with a plant that is both a model and crop has driven the expansion of research resources for camelina, including increased availability of genome and other "-omics" data sets. Collectively the expansion of these resources has established camelina as an ideal plant to study the regulation of lipid metabolism and genetic improvement. Furthermore, the unique characteristics of camelina enables the design-build-test-learn cycle to be transitioned from the controlled environment to the field. Complex metabolic engineering to synthesize and accumulate high levels of novel fatty acids and modified oils in seeds, can be deployed, tested and undergo rounds of iteration in agronomically relevant environments. Engineered camelina oils are now increasingly being developed and used to sustainably supply, improved nutrition, feed, biofuels and fossil fuel replacements for high-value chemical products. In this review, we provide a summary of seed fatty acid synthesis and oil assembly in camelina, highlighting how discovery research in camelina supports the advance of metabolic engineering towards the predictive manipulation of metabolism to produce desirable bio-based products. Further examples of innovation in camelina seed lipid engineering and crop improvement are then provided, describing how technologies (e.g., genetic modification (GM), gene editing (GE), RNAi, alongside GM and GE stacking) can be applied to produce new products and denude undesirable traits. Focusing on the production of long chain polyunsaturated omega-3 fatty acids in camelina, we describe how lipid biotechnology can transition from discovery to a commercial prototype. The prospects to produce structured triacylglycerol with fatty acids in specified stereospecific positions are also discussed, alongside the future outlook for the agronomic uptake of camelina lipid biotechnology.

Skeletal muscle-specific Bambi deletion induces hypertrophy and oxidative switching coupling with adipocyte thermogenesis against metabolic disorders.

Skeletal muscle plays a significant role in both local and systemic energy metabolism. The current investigation aims to explore the role of the Bambi gene in skeletal muscle, focusing on its implications for muscle hypertrophy and systemic metabolism. We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy, improves metabolic performance, and activates thermogenic adipocytes via the reprogramming of progenitor of iWAT, offering potential therapeutic strategies for metabolic syndromes. Leveraging the Chromatin immunoprecipitation (ChIP)-seq and bioinformatics analysis, Bambi gene is shown to be a direct target of HIF2α, which is further confirmed by ChIP-qPCR and promoter luciferase assay. Skeletal muscle-specific Bambi deletion led to significant muscle hypertrophy and improved metabolic parameters, even under high-fat diet conditions. This deletion induced metabolic reprogramming of stromal vascular fractions (SVFs) into thermogenic adipocytes, contributing to systemic metabolic improvements, potentially through the secretory factor. Notably, mice with skeletal muscle-specific Bambi deletion demonstrate resistance to high-fat diet-induced metabolic disorders, highlighting a potential therapeutic pathway for metabolic syndrome management. Thus, skeletal muscle-specific deletion of Bambi triggers muscle growth, enhances metabolic performance, and activates thermogenic adipocytes. These findings suggest Bambi as a novel therapeutic target for metabolic syndromes, providing new insights into the interaction between muscle hypertrophy and systemic metabolic improvement. The study underscores the potential of manipulating muscle physiology to regulate whole-body metabolism, offering a novel perspective on treating metabolic disorders.

Environmental enrichment normalizes metabolic function in the murine model of Prader-Willi syndrome Magel2-null mice.

Prader-Willi syndrome (PWS) is a rare genetic disease that causes developmental delays, intellectual impairment, constant hunger, obesity, endocrine dysfunction, and various behavioral and neuropsychiatric abnormalities. Standard care of PWS is limited to strict supervision of food intake and growth hormone therapy, highlighting the unmet need for new therapeutic strategies. Environmental enrichment (EE), a housing environment providing physical, social, and cognitive stimulations, exerts broad benefits on mental and physical health. Here, we assessed the metabolic and behavioral effects of EE in the Magel2-null mouse model of PWS. EE initiated after the occurrence of metabolic abnormality was sufficient to normalize body weight and body composition, reverse hyperleptinemia, and improve glucose metabolism in the male Magel2-null mice. These metabolic improvements induced by EE were comparable to those achieved by a hypothalamic brain-derived neurotrophic factor (BDNF) gene therapy although the underlying mechanisms remain to be determined. These data suggest biobehavioral interventions such as EE could be effective in the treatment of PWS-related metabolic abnormalities.

Immunometabolic Changes Following Gastric Bypass and Sleeve Gastrectomy: A Comparative Study.

Immunometabolism is the interaction between immune system and nutrient metabolism. Severe obesity is considered a state of meta-inflammation associated with obesity that influences the development of chronic-degenerative diseases. We aimed to establish the immunometabolic differences in bariatric patients and to determine whether cellular immunity is associated with metabolic changes. We conducted an observational study in patients who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB). We explored the differences in the immunometabolic profile before and after surgery in the study group, by surgical technique, and we evaluated the changes in immunological variables as a function of metabolic variables with correlation analysis. The follow-up rate was 88.7%. After the intervention, there were changes in cellular immunity, with a decrease in effector T lymphocytes (CD8+CD28-) and an increase in B lymphocytes, memory helper T cells, and cytotoxic T lymphocytes. LSG resulted in a greater decrease in (CD4+CD62-) T lymphocytes compared with LRYGB. Patients who underwent surgery with LRYGB presented greater clinical and metabolic improvements, as well as improvement of obesity-associated medical problems. Women who underwent LRYGB showed a greater reduction in fat-free mass compared with women who underwent LSG. Bariatric surgery, mainly LRYGB, leads to immunometabolic changes and improves associated medical problems.

Impact of a very low-calorie ketogenic diet on metabolic and microbiota outcomes in post-bariatric patients and bariatric-Naïve individuals: A comparative pilot study.

To date, bariatric surgery (BS) is the most effective long-term treatment for obesity, but weight regain (WR) is common. The very low-calorie ketogenic diet (VLCKD) is effective for weight loss and may influence gut microbiota (GM) composition, but it has been scarcely evaluated in post-bariatric patients. This study compared the efficacy and safety of a VLCKD in patients with WR post-bariatric surgery (BS+) and in bariatric surgery-naïve patients (BS-). In this prospective, case-control study, 33 patients (15 BS+, 18 BS-) underwent an 8-week-long VLCKD. Outcomes included weight loss, metabolic profile, safety and GM composition. Both groups achieved significant weight loss (BS+: -6.9%, BS-: -8.3%), but the BS+ group showed slightly less metabolic improvement, particularly in insulin resistance and triglycerides. GM composition differed at baseline, reflecting the lasting effects of BS, and VLCKD led to significant changes in both groups. Microbial diversity and specific taxonomic shifts were more pronounced in BS- patients. Mild renal function changes were noted in BS+ patients, though these remained within clinically acceptable ranges. VLCKD is effective in both BS+ and BS- patients, though metabolic and microbial responses may be less robust post-surgery, possibly due to anatomical and physiological changes. Tailored approaches may be therefore needed to optimize outcomes in post-bariatric patients.

Comparative study on blood pressure and metabolic improvements in hypertensive patients using copper bianstone scraping.

To evaluate the effectiveness and feasibility of the copper bianstone scraping combined with Chinese modified termination hypertension dietary therapy program by comparing and analyzing the improvement of blood pressure, blood lipids and blood glucose in hypertensive patients who received copper bianstone scraping combined with Chinese modified termination hypertension dietary therapy intervention. We selected 160 cases of hypertensive patients from July 2022 to March 2024 for the study. They were divided into 80 cases in the comparison group and 80 cases in the observation group according to whether or not they underwent copper bianstone scraping combined with Chinese modified dietary therapy for termination of hypertension. In the comparison group, conventional Chinese dietary therapy with improved termination of hypertension was used, and in the observation group, copper bianstone scraping combined with Chinese dietary therapy with improved termination of hypertension (DASH) was used on the basis of the comparison group. Differences in vitamin D, Homocysteine and serum calcium levels, blood pressure, blood glucose and lipid levels were compared between the 2 groups. The decreases of glycosylated hemoglobin, fasting blood glucose and 2-hour postprandial blood glucose in the observation group were greater than those in the comparison group; the decreases of blood pressure and BMI in the observation group were greater than those in the comparison group. The difference in comparison was statistically significant (P-value < 0.05). After the intervention, the improvement of homocysteine, vitamin D, serum calcium, albumin, hemoglobin and transferrin in the observation group was greater than that in the comparison group, and the difference was statistically significant (P-value < 0.05). Copper bianstone scraping combined with Chinese modified termination of hypertension dietary therapy in hypertensive patients has a better effect, can effectively improve the patient's blood glucose and lipid levels, improve the nutritional status of the patient, can be promoted in the rehabilitation management of hypertension.

Exploring the Therapeutic Role of Flavonoids Through AMPK Activation in Metabolic Syndrome: A Narrative Review.

Metabolic syndrome (MetS) is a cluster of interrelated metabolic abnormalities that significantly elevate the risk of cardiovascular disease, obesity, and diabetes. Flavonoids, a diverse class of bioactive polyphenolic compounds found in plant-derived foods and beverages, have garnered increasing attention as potential therapeutic agents for improving metabolic health. This review provides a comprehensive analysis of the therapeutic effects of flavonoids in the context of the MetS, with a particular focus on their modulation of the AMP-activated protein kinase (AMPK) pathway. AMPK serves as a central regulator of cellular energy balance, glucose metabolism, and lipid homeostasis, making it a critical target for metabolic intervention. Through a systematic review of the literature up to April 2024, preclinical studies across various flavonoid subclasses, including flavonols, and flavan-3-ols, were analysed to elucidate their mechanistic roles in metabolic regulation. Many studies suggests that flavonoids enhance glycolipid metabolism by facilitating glucose transporter 4 (GLUT4) translocation and activating the AMPK pathway, thereby improving glycemic control in diabetes models. In obesity-related studies, flavonoids demonstrated significant inhibitory effects on lipid synthesis, reduced adipogenesis, and attenuated proinflammatory cytokine secretion via AMPK activation. These findings show the broad therapeutic potential of flavonoids in addressing the MetS and its associated disorders. While these preclinical insights highlight flavonoids as promising natural agents for metabolic health improvement, it is important to note that their excessive concentrations may disrupt these pathways, potentially leading to metabolic imbalance and cytotoxicity. Further studies and clinical trials are essential to determine optimal dosing regimens, formulations, and the long-term safety and efficacy of flavonoids. This review highlights the importance of flavonoids for natural interventions targeting MetS and its comorbidities, offering a foundation for future translational research.

Effect of Total and Partial Meal Replacements on Factors Related to Glucose Metabolism: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Although some evidence shows the beneficial effects of meal replacements (MRs) on glucose metabolism as one of the main factors of diabetes, there are still no comprehensive findings in this field. We investigated the effects of total and partial MRs on fasting blood sugar (FBS), insulin, glycated hemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR) in this comprehensive study and meta-analysis. To find pertinent randomized controlled trials (RCTs) up to March 2024, databases including PubMed/Medline, Web of Science, Scopus, and Embase were searched. This study included all RCTs investigating the effects of MRs on factors related to glucose metabolism. The pooled weighted mean difference (WMD) and 95% CIs were computed using the random-effects model. The findings from 52 studies indicated significant reductions in FBS (WMD: -3.10 mg/dL; 95% CI: -4.99, -1.20; P < .001), insulin (WMD: -1.79 μU/mL; 95% CI: -3.51, -0.08; P = .40), HOMA-IR (WMD: -0.86; 95% CI: -1.68, -0.04; P = .040), and HbA1c (WMD: -0.24%; 95% CI: -0.35%, -0.13%; P < .001) levels following MR consumption compared with the control group. The findings obtained from the subgroup analysis showed that MRs cause a greater decrease in FBS, insulin, and HOMA-IR in the >50-years age group compared with those aged ≤50 years and also during interventions ≤24 weeks compared with >24 weeks. In conclusion, it appears that MRs, along with other lifestyle factors, can lead to significant improvements in glucose metabolism.

Low-dose IL-2 restores metabolic dysfunction and immune dysregulation in mice with type 2 diabetes induced by a high-fat, high-sugar diet and streptozotocin.

Interleukin-2 (IL-2) is pivotal in immune regulation, particularly in the promotion of regulatory T (Treg) cells and the maintenance of immune tolerance. While its efficacy in autoimmune diseases is well established, its role in type 2 diabetes (T2D) remains largely unexplored. This study investigates the effects of low-dose IL-2 in a KM mouse model of T2D induced by streptozotocin (STZ) and a high-fat, high-sugar (HFHS) diet. We found that low-dose IL-2 administration significantly improved fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) levels, and glucose tolerance, indicating better glycemic control. Additionally, IL-2 treatment improved insulin sensitivity, enhanced insulin secretion, and ameliorated lipid metabolism, as evidenced by reduced cholesterol and triglyceride levels. These metabolic improvements were associated with a modulation of inflammation, including a reduction in pro-inflammatory cytokines (TNF-α, IL-1β) and an increase in anti-inflammatory cytokines (IL-10). Importantly, IL-2 also altered the gut microbiome, reducing intestinal inflammation and endotoxin levels, which suggests a broader impact on metabolic health beyond immune regulation. These findings support the potential of low-dose IL-2 as an immunotherapeutic approach for improving metabolic dysfunction and inflammation in T2D.

Multicenter Study of the Impact of COVID-19 in Type 2 Diabetes Quality Management.

Epidemics and pandemics have been shown to have widespread effects on health systems. Diabetes is a condition of particular risk during national emergencies such as the COVID-19 pandemic. The aim of this study is to determine the influence of COVID-19 in the patient's diabetes quality management. We conducted a retrospective multicenter cohort study. Data from type 2 diabetes patients living in Sevilla were included into the study. The study was divided into two observation periods, before and during COVID-19. Metabolic status was assessed using the levels of hemoglobin A1c (A1C) measured during the pre- and CO-VID-19 period. The time interval between sequential A1C tests were also measured. We as well identified the loca-tions where the burden of diabetes quality management is clustered and their relation with demographic and economic factors. We included a total of 106,336 patients from four different hospitals. A significant number patients have worsened their quality management during COVID-19. During the first year of the pandemic, 72,235 patients did not have any hemoglobin A1c (A1C) control. By the time of data extraction, the time between A1C controls was significantly increased by 309 days (from 211 to 520). In addition, 34,001 patients who had A1C control during the COVID-19 period did not reveal a deterioration of their metabolic status. They showed a small but significant metabolic improvement indicated by reduced A1C levels from 52 mmol/mol to 51 mmol/mol. Just like the other group, these patients showed a significant increase of 29 days (from 195 to 224) between A1C controls. COVID-19 increased the substantial clustering for diabetes quality management in specific locations, mostly along the rural southeastern area of Sevilla and these variations were associated with economic and socio-demographic variants. Our study highlighted the great impact of the COVID-19 in diabetes quality management exacerbating the previous inequities and disparities. Our results highlight the need for urgent patient intervention in the areas with high burdens of poorer quality management.

Gut mycobiome alterations in obesity in geographically different regions

ABSTRACT The gut fungi play important roles in human health and are involved in energy metabolism. This study aimed to examine gut mycobiome composition in obese subjects in two geographically different regions in China and to identify specific gut fungi associated with obesity. A total of 217 subjects from two regions with different urbanization levels [Hong Kong (HK): obese, n = 59; lean, n = 59; Kunming (KM): obese, n = 50; lean, n = 49. Mean body mass index (BMI) for obesity = 33.7] were recruited. We performed deep shotgun metagenomic sequencing on fecal samples to compare gut mycobiome composition and trophic functions in lean and obese subjects across these two regions. The gut mycobiome of obese subjects in both HK and KM were altered compared to those of lean subjects, characterized by a decrease in the relative abundance of Nakaseomyces, Schizosaccharomyces pombe, Candida dubliniensis and an increase in the abundance of Lanchanceathermotolerans, Saccharomyces paradox, Parastagonospora nodorum and Myceliophthorathermophila. Reduced fungal – bacterial and fungal – fungal correlations as well as increased negative fungal-bacterial correlations were observed in the gut of obese subjects. Furthermore, the anti-obesity effect of fungus S. pombe was further validated using a mouse model. Supplementing high-fat diet-induced obese mice with the fungus for 12 weeks led to a significant reduction in body weight gain (p < 0.001), and an improvement in lipid and glucose metabolism compared to mice without intervention. In conclusion, the gut mycobiome composition and functionalities of obese subjects were altered. These data shed light on the potential of utilizing fungus-based therapeutics for the treatment of obesity. S. pombe may serve as a potential fungal probiotic in the prevention of diet-induced obesity and future human trials are needed.

The Effects of CrossFit® Practice on Physical Fitness and Overall Quality of Life.

We have examined the impact of CrossFit® workout sessions on physical fitness, comparing the obtained outcomes with the recommendations of the American College of Sports Medicine. In addition, we provide suggestions to improve training monitoring, as well as practical applications for researchers, coaches and practitioners. CrossFit® imposes high cardiorespiratory and metabolic demands, promoting improvements in circulatory capacity, oxidative metabolism and muscular endurance. Sustained elevations in heart rate contribute to cardiovascular conditioning, while a post-exercise hypotensive effect may help to reduce cardiovascular risks. Structured CrossFit® programs have led to improvements in maximal strength and muscular endurance, with substantial increases in squat performance observed in both untrained and recreationally active individuals. In addition, CrossFit® improves mental health through its motivating community. However, the high metabolic demands, increased creatine kinase levels and reduced performance in the countermovement jump reveal that muscle damage and neuromuscular fatigue can persist for up to 48 h. Balancing these intense sessions with adequate recovery is crucial, as improper management may lead to overtraining and compromise fitness gains. Future research should explore long-term cardiovascular adaptations, differences in gains and recovery between males and females and the application of real-time biomarker and artificial intelligence technologies to improve the training efficiency and safety. Machine learning algorithms could further personalize feedback, adapting to each individual's biomechanics and physiological responses over time.

Fecal microbiota transplantation as a potential therapeutic approach to improve impaired glucose tolerance via gut microbiota modulation in rat model.

To investigate the impact of diet-induced gut microbiota alterations on type 2 diabetes and assess the therapeutic potential of Fecal Microbiota Transplantation (FMT) in restoring a balanced gut microenvironment. To induce type 2 diabetes, rats were fed a high-sugar high-fat diet (HSFD) for 90 days. After diabetes induction, animals were divided into an HSFD control group, a metformin group (100mg/kg), and an FMT group (100mg/kg), receiving treatment for an additional 90 days. Fasting blood glucose levels, glucose tolerance, serum markers (HbA1C, free fatty acids, lipopolysaccharides, pro-inflammatory and anti-inflammatory cytokines), and gut microbiota profiles via cecal metagenome sequencing were analyzed post-treatment. FMT effectively restored gut microbiota composition to a profile similar to healthy controls, rebalancing the Firmicutes/Bacteroidetes ratio and increasing beneficial taxa, including Prevotella ruminicola, Akkermansia muciniphila, Roseburia, and Faecalibacterium prausnitzii. These microbial shifts corresponded with significant metabolic improvements: FMT reduced inflammatory markers (LPS and FFA), lowered HbA1c, and improved glucose tolerance. Enhanced gut barrier integrity observed in FMT-treated animals likely contributed to reduced endotoxemia and systemic inflammation, distinguishing FMT's metabolic effects from those of metformin. Notably, FMT addressed the dysbiosis associated with HSFD, promoting microbial resilience and mitigating the metabolic disruptions linked to type 2 diabetes. These findings underscore the potential of FMT as a targeted therapeutic approach to modulate gut microbiota composition and mitigate metabolic dysregulation induced by high sugar high fat diet.