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Probiotics have shown potential in managing hypercholesterolemia and related metabolic conditions. This study evaluated the effects of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 on the gut microbiome and metabolic health in patients with hypercholesterolemia, and was registered in the Thai Clinical Trial Registry (TCTR 20220917002). In a randomized, double-blind, placebo-controlled trial, 22 hypercholesterolemic participants received either the probiotic or a placebo daily for 90 days. Fecal samples collected before and after the intervention revealed significant microbiome changes, including a decrease in Subdoligranulum, linked to rheumatoid arthritis, and an increase in Flavonifractor, known for its anti-inflammatory properties. Additionally, the probiotic group exhibited a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels. These findings suggest that L. paracasei TISTR 2593 can modulate the gut microbiome and improve metabolic health, warranting further investigation into its mechanisms and long-term benefits.

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Suboptimal nutrition is a leading cause of cardiometabolic disease and mortality. Biological sex is a variable that influences individual responses to dietary components and may modulate the impact of diet on metabolic health and disease risk. This review describes findings of studies reporting how biological sex may associate with or affect metabolic outcomes or disease risk in response to varying dietary macronutrient content, Mediterranean diet, Western diet, and medical very low-calorie diet. Although few dietary interventions have been specifically designed to identify sex-diet interactions, future studies improving understanding how sex influences dietary responses could inform precision nutrition interventions for disease prevention and management.

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Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, with dyslipidemia being a significant risk factor. This meta-analysis provides a comprehensive evaluation of the impact of bovine dairy-derived milk fat globule membrane (MFGM) supplementation on blood lipid profiles in adults. A systematic search was conducted across various databases up until March 2024, resulting in the inclusion of 6 trials with a total of 464 participants. The findings indicated that MFGM phospholipid supplementation may significantly reduce total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels. A combined analysis of the effects on TC, LDL, and triglycerides (TG) revealed a significant overall reduction in these markers. However, no significant increase or reduction was observed on high-density lipoprotein (HDL) and TG levels. Overall, MFGM phospholipid intake may significantly decrease the level of TC and LDL, while no significant changes in TG and HDL were observed. These results suggest that MFGM supplementation could be a promising dietary intervention for improving lipid profiles in adults. Nonetheless, further research is warranted to confirm these results and to better understand the potential variability in the impact of MFGM on blood lipid levels.

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AIMS/HYPOTHESIS: Metabolic abnormalities such as central obesity, insulin resistance, dyslipidaemia and hypertension, often referred to as 'the metabolic syndrome' (or 'combined metabolic abnormalities'), are increasingly being identified in people living with type 1 diabetes, accelerating the risk for CVD. As a result, in recent years, treatment in people living with type 1 diabetes has shifted to improving overall metabolic health rather than glucose control alone. In Belgium, diabetes care for people living with type 1 diabetes is centrally organised. The Initiative for Quality Improvement and Epidemiology in Diabetes, imposed by the Belgian health insurance system, has systematically collected data from patients on intensive insulin therapy treated in all 101 diabetes clinics in Belgium since 2001. The aim of this real-world study is to describe the evolution of treatment and metabolic health, including the prevalence of obesity and combined metabolic abnormalities, in people living with type 1 diabetes over the past 20 years, and to compare the treatment and prevalence of complications between those with and without combined metabolic abnormalities. METHODS: We analysed data on adults (≥16 years old) living with type 1 diabetes, who were diagnosed at age ≤45 years and who had a diabetes duration ≥1 year, collected between 2001 and 2022. The evolution of HbA1c, BMI, LDL-cholesterol, systolic BP, lipid-lowering therapy and antihypertensive therapy over time was analysed. The prevalence of individual and multiple metabolic abnormalities according to various definitions of the metabolic syndrome/combined metabolic abnormalities was analysed, and the association between combined metabolic abnormalities and metabolic health indicators, complications and treatment was investigated in the 2022 data. RESULTS: The final dataset consisted of 26,791 registrations of adults living with type 1 diabetes collected between 2001 and 2022. Although glycaemic and lipid control generally improved over time, the prevalence of obesity strongly increased (12.1% in 2001 vs 21.7% in 2022, p<0.0001), as did the presence of combined metabolic abnormalities (WHO criteria: 26.9% in 2001 vs 42.9% in 2022 in women, p<0.0001; 30.4% in 2001 vs 52.1% in 2022 in men, p<0.0001; WHO criteria without albuminuria: 22.3% in 2001 vs 40.6% in 2022 in women, p<0.0001; 25.1% in 2001 vs 49.2% in 2022 in men, p<0.0001; NCEP-ATPIII criteria: 39.9% in 2005 vs 57.2% in 2022 in women, p<0.0001; 40.8% in 2005 vs 60.9% in 2022 in men, p<0.0001; IDF criteria: 43.9% in 2005 vs 59.3% in 2022 in women, p<0.001; 33.7% in 2005 vs 50.0% in 2022 in men, p<0.0001). People with combined metabolic abnormalities had higher glucose levels compared to those without combined metabolic abnormalities (HbA1c >58 mmol in men: 48.9% vs 36.9%; HbA1c >58 mmol in women: 53.3% vs 41.1%, p<0.0001). People with combined metabolic abnormalities were more often treated with adjunct therapies such as metformin, sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists. In both men and women, the presence of combined metabolic abnormalities was strongly related to the presence of eye complications, peripheral neuropathy, chronic kidney disease and CVD, corrected for age, diabetes duration and HbA1c. CONCLUSIONS/INTERPRETATION: Overweight, obesity and combined metabolic abnormalities are increasingly being identified in people living with type 1 diabetes, further accelerating the risk of microvascular and macrovascular complications. Early identification of the presence of combined metabolic abnormalities should enable therapeutic interventions to be modified towards multifactorial approaches, with attention to education on avoidance of overweight (e.g. dietary counselling) in addition to strict glycaemic control and intensification of use of antihypertensive agents and statins. Use of adjunct therapies in this population as a tool should be explored more thoroughly to reduce risk of complications.

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BACKGROUND: Reducing the number of active compounds for lifelong HIV treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control, support the robustness and safety of 2DR (2-drug regimen) ART compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts and sustained immunological control. METHODS: The Rumba study is the first prospective randomized controlled trial evaluating the impact of switch from 3DR to 2DR on the viral reservoir. Participants on any stable 2nd generation INSTI-based 3DR regimen with HIV-1 RNA<50 copies/ml plasma for at least 3 months were randomized to switch to dolutegravir/lamivudine (DTG/3TC, N=89) or to switch or stay on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, N=45). After 48 weeks, virological, immunological and metabolic parameters were evaluated. RESULTS: We did not observe a significant difference in change over time in the mean number of intact HIV-1 DNA copies/million CD4+ T cells with DTG/3TC compared to B/F/TAF. There was no evidence in this study that switching to DTG/3TC increased the active reservoir by HIV-1 transcription. No significant changes in pro-inflammatory cytokines or major immune cell subsets were observed. Changes in exhaustion and activation of specific cellular subsets were small and bidirectional. Metabolic outcomes are similar between the treatment regimens. CONCLUSIONS: This study confirms the safety of DTG/3TC compared to B/F/TAF through viral control after in-depth investigations of the intact HIV-1 reservoir, HIV-1 transcription and inflammatory markers.

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The increasing global burden of metabolic disorders including obesity and diabetes necessitates a comprehensive understanding of their etiology, which not only encompasses genetic and environmental factors but also parental influence. Recent evidence has unveiled paternal obesity as a contributing factor to offspring's metabolic health via sperm epigenetic modifications. In this study, we investigated the impact of a Western diet-induced obesity in C57BL/6 male mice on sperm chromatin accessibility and the subsequent metabolic health of their progeny. Utilizing Assay for Transposase-Accessible Chromatin with sequencing, we discovered 450 regions with differential accessibility in sperm from obese fathers, implicating key developmental and metabolic pathways. Contrary to expectations, these epigenetic alterations in sperm were not predictive of long-term metabolic disorders in offspring, who exhibited only mild transient metabolic changes early in life. Both male and female F1 progeny showed no enduring predisposition to obesity or diabetes. These results underscore the biological resilience of offspring to paternal epigenetic inheritance, suggesting a complex interplay between inherited epigenetic modifications and the offspring's own developmental compensatory mechanisms. This study calls for further research into the biological processes that confer this resilience, which could inform interventional strategies to combat the heritability of metabolic diseases.

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OBJECTIVE: Time-restricted eating (TRE) which consists of restricting the eating window to typically 4-8h (while fasting for the remaining hours of the day) has been proposed as a non-pharmacological strategy with cardio-metabolic benefits but little is known about its metabolic impact in type 2 diabetes (T2DM). We evaluated whether TRE can improve pancreatic beta-cell function and metabolic status in overweight individuals with early T2DM. RESEARCH DESIGN AND METHODS: In a randomized cross-over trial, 39 participants [mean 2.9 years of diabetes duration, baseline glycated hemoglobin (HbA1c) 6.6% ± 0.7% and body mass index (BMI) 32.4 ± 5.7 kg/m2] were randomized to either an initial intervention consisting of 6-weeks of TRE (20h-fasting/4h-eating) or standard lifestyle. The primary outcome of beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2) derived from an oral glucose tolerance test. Trial registration: clinicaltrials.gov NCT05717127. RESULTS: As compared to standard lifestyle, TRE induced a 14% increase in ISSI-2 (+14.0 ± 39.2%, p = 0.03) accompanied by 14% reduction of hepatic insulin resistance as evaluated by HOMA-IR [-11.6% (-49.3-21.9), p = 0.03]. Fasting glucose did not differ between interventions, but TRE yielded a significant reduction in HbA1c (-0.32 ± 0.48%, p <0.001). These metabolic improvements were coupled by a reduction of body weight of 3.86% (-3.86 ± 3.1%, p <0.001) and waist circumference of 3.8 cm (-3.8 ± 7.5 cm, p = 0.003). CONCLUSION: TRE improved beta-cell function and insulin resistance in overweight patients with early diabetes, accompanied by beneficial effects on adiposity.

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Obesity significantly impacts gut microbial composition, exacerbating metabolic dysfunction and weight gain. Traditional treatment methods often fall short, underscoring the need for innovative approaches. Glucagon-like peptide-1 (GLP-1) agonists have emerged as promising agents in obesity management, demonstrating significant potential in modulating gut microbiota. These agents promote beneficial bacterial populations, such as Bacteroides, Lactobacillus, and Bifidobacterium, while reducing harmful species like Enterobacteriaceae. By influencing gut microbiota composition, GLP-1 agonists enhance gut barrier integrity, reducing permeability and systemic inflammation, which are hallmarks of metabolic dysfunction in obesity. Additionally, GLP-1 agonists improve metabolic functions by increasing the production of short-chain fatty acids like butyrate, propionate, and acetate, which serve as energy sources for colonocytes, modulate immune responses, and enhance the production of gut hormones that regulate appetite and glucose homeostasis. By increasing microbial diversity, GLP-1 agonists create a more resilient gut microbiome capable of resisting pathogenic invasions and maintaining metabolic balance. Thus, by shifting the gut microbiota toward a healthier profile, GLP-1 agonists help disrupt the vicious cycle of obesity-induced gut dysbiosis and inflammation. This review highlights the intricate relationship between obesity, gut microbiota, and GLP-1 agonists, providing valuable insights into their combined role in effective obesity treatment and metabolic health enhancement.

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BACKGROUND: Epicardial adipose tissue (EAT) is associated with the development of cardiovascular disease and long-term survival. This study aimed to assess the characteristics of EAT according to the metabolic health and obesity status using low-dose chest computed tomography (CT). METHODS: A total of 1074 asymptomatic adults who underwent a medical health check-up were enrolled. Subjects were categorized into the following four groups according to the metabolic health and obesity status: metabolically healthy non-obese (MHNO); metabolically unhealthy non-obese (MUNO); metabolically healthy obese (MHO); and metabolically unhealthy obese (MUO). EAT on low-dose chest CT was measured by using automatic, quantitative measurement software. RESULTS: MUO showed the highest EAT volume and lowest EAT radiodensity in comparison with MHNO (p < 0.001). The MUNO (n = 70), MHO (n = 259), and MUO (n = 231) groups had increased EAT volume (ß [95 % CI], 37.65 [23.11,52.18], 56.79 [47.56,66.02], 84.85 [74.59,95.11] respectively, all p < 0.001), decreased EAT radiodensity (ß [95 % CI], - 3.22 [- 4.59,- 1.85], - 4.48 [- 5.30,- 3.66], - 6.03 [- 6.90,- 5.16] respectively, all p < 0.001) in comparison with the MHNO (n = 514) group by using multivariable linear regression models. CONCLUSIONS: Both metabolic abnormalities and obesity were closely associated with EAT characteristics. Characteristics of EAT are similar in MHO and MUNO. This finding suggests that MHO is not a favorable condition in terms of cardiac health, as assessed by the characteristics of EAT. The combination of obesity and metabolically unhealthy status has a synergistic adverse effect on EAT. Measurement of EAT could be a useful imaging biomarker for evaluation of an individual's metabolic health/obesity status.

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Background: We applied the novel Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations to evaluate cardiovascular-kidney-metabolic (CKM) health and estimated CVD risk, including heart failure (HF), after bariatric surgery. Methods: Among 7804 patients (20-79 years) undergoing bariatric surgery at Vanderbilt University Medical Center during 1999-2022, CVD risk factors at pre-surgery, 1-year, and 2-year post-surgery were extracted from electronic health records. The 10- and 30-year risks of total CVD, atherosclerotic CVD (ASCVD), coronary heart disease (CHD), stroke, and HF were estimated for patients without a history of CVD or its subtypes at each time point, using the social deprivation index-enhanced PREVENT equations. Paired t-tests or McNemar tests were used to compare pre- with post-surgery CKM health and CVD risk. Two-sample t-tests were used to compare CVD risk reduction between patient subgroups defined by age, sex, race, operation type, weight loss, and history of diabetes, hypertension, and dyslipidemia. Results: CKM health was significantly improved after surgery with lower systolic blood pressure, non-high-density-lipoprotein cholesterol (non-HDL), and diabetes prevalence, but higher HDL and estimated glomerular filtration rate (eGFR). The 10-year total CVD risk decreased from 6.51% at pre-surgery to 4.81% and 5.08% at 1- and 2-year post-surgery (relative reduction: 25.9% and 16.8%), respectively. Significant risk reductions were seen for all CVD subtypes (i.e., ASCVD, CHD, stroke, and HF), with the largest reduction for HF (relative reduction: 55.7% and 44.8% at 1- and 2-year post-surgery, respectively). Younger age, White race, >30% weight loss, diabetes history, and no dyslipidemia history were associated with greater HF risk reductions. Similar results were found for the 30-year risk estimates. Conclusions: Bariatric surgery significantly improves CKM health and reduces estimated CVD risk, particularly HF, by 45-56% within 1-2 years post-surgery. HF risk reduction may vary by patient's demographics, weight loss, and disease history, which warrants further research.

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BACKGROUND: Poor cardiovascular-kidney-metabolic (CKM) health is associated with premature mortality and excess morbidity in the United States. Adverse social conditions have a prominent impact on cardiometabolic diseases during the life course. We aim to examine the association between social risk profile (SRP) and CKM multimorbidity among US adults. METHODS AND RESULTS: We used data from the National Health and Nutrition Examination Survey from 1999 to 2018. The definition of CKM syndrome is the coexistence of subclinical or clinical cardiovascular disease, chronic kidney disease, and metabolic disorders. We classified participants by 4 CKM stages according to the different clinical severity of different forms of CKM syndrome. We calculated the summed number of positive SRP measures, including employed, high-income level, food secure, high education attainment, private insurance, owning a house, and married, as SRP scores and classified them into 4 levels by quartiles: low (0-2), lower-middle (3-4), upper-middle (5-6), and high (7-8). A total of 18 373 US adults, aged 20 to 79 years, were included in our analyses. There were 2567 (9.4%) participants with low SRP score level. Most individual SRP measures and a combined SRP score were associated with CKM stages. Compared with high SRP score level, low SRP level was associated with higher odds of having CKM stage 1 (odds ratio [OR], 1.34 [95% CI, 1.06-1.70]), CKM stage 2 (OR, 2.03 [95% CI, 1.59-2.58]), CKM stage 3 (OR, 5.28 [95% CI, 3.29-8.47]), and CKM stage 4 (OR, 5.97 [95% CI, 4.20-8.49]). CONCLUSIONS: Cumulative social disadvantage, denoted by higher SRP burden, was associated with higher odds of CKM multimorbidity, independent of demographic and lifestyle factors.

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The objective of this study is to explore the associations between obesity, body composition, and the self-reported risk of obstructive sleep apnea (OSA) and to examine whether the risk of OSA is related to metabolic abnormalities in children and adolescents aged 6-17 years. Utilizing data from the 2022 to 2023 Beijing Children and Adolescents Health Cohort baseline survey, 5000 school-aged participants were analyzed. OSA risk was assessed via the Pediatric Sleep Questionnaire, with anthropometric and body composition measurements taken. Metabolic markers included blood pressure, lipid levels, blood glucose, and uric acid. Associations were analyzed using logistic regression and generalized linear models. Results showed that 88.6% were low-risk and 11.4% were high-risk for OSA. Overweight (aOR 1.53, 95% CI 1.22-1.92), obesity (aOR 1.94, 95% CI 1.57-2.40), and abdominal obesity (aOR 1.59, 95% CI 1.31-1.93) significantly increased OSA risk. High fat mass was a critical factor, while muscle mass was not, especially in those who were overweight and obese. Associations of OSA risk with metabolic abnormalities were non-significant after adjusting for BMI. Our research highlights the significant associations of obesity and body composition with OSA risk, with child BMI influencing the relationship between OSA and metabolic abnormalities. Future research should explore causative relationships and the enduring impacts of OSA on metabolic health in children.

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BACKGROUND: Metabolic syndrome increases the risk of heart disease and diabetes. Early identification and management are crucial, especially in economically challenged regions with limited healthcare access. AIMS: To develop nomograms for individualized risk estimation for metabolic syndrome in young people from low-income regions. METHODS: We assessed 496 college students from two Brazilian cities with Gini indices ≤0.56. Of these, 69.9% were female, 65.1% were younger than 20 years, 71.8% were non-white, and 64.3% were enrolled in health-related courses. For external validity, we assessed metabolic syndrome in a subset of 375 students. RESULTS: We found 10 variables associated with abdominal obesity by logistic regression: age, biological sex, physical education facilities, enrollment in sports competitions during elementary school, grade retention, physical education as the preferred subject, physical education classes per week, and enrollment in sports training in secondary school (score A); adherence to 24 h movement behaviors (B score); and body weight (score C). We designed three nomograms (for scores A, B, and C), all of which showed acceptable performance according to the area under the receiver operating characteristic curve (≥0.70) and calibration (Hosmer-Lemeshow test, p > 0.05). In the external validation, we observed higher predictive capability for the A and B scores, while the C score had lower but still acceptable predictive ability. CONCLUSIONS: User-friendly self-reported data accurately predict metabolic syndrome among youths from economically challenging areas.

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Diabetes is a metabolic disorder associated with chronic inflammation; pre-diabetes phase promotes to inflammatory mechanism then finally progress to diabetes and its associated complications. Therefore, it is of interest to investigate the changes in inflammatory biomarkers Evidence that inflammatory markers play a role in the development as well as severity of Type 2 diabetes mellitus (T2DM). This study has been designed to decipher the involvement of Tumor Necrosis Factor (TNFα), Interleukin-6 (IL-6), Nesfatin-1 and Blood sugar in the etiopathogenesis of T2DM. This retrospective observational study analyzed patient records from our hospital, focusing on those with diabetes or pre-diabetes. Glycosylated hemoglobin, inflammatory biomarkers, Fasting Blood Glucose, and Post-Prandial Blood Glucose were assessed. SPSS 28 facilitated statistical analysis; utilizing Bivariate Correlation assessed the relationship between inflammatory biomarkers and diabetes status (glycosylated hemoglobin). In the pre-diabetic vs. diabetic groups, significant differences exist in IL-6 (p=0.0344), TNF-α (p=0.041), Nesfatin-1 (p=0.0485), fasting blood glucose (p=0.036), and 2h post-prandial blood glucose (p=0.048). IL6 (AUC=0.729, p<0.001), TNF (AUC=0.761, p<0.001), and Nesfatin1 (AUC=0.892, p<0.001) show moderate discriminative power. PP (AUC=0.992, p<0.001) and hbA1c (AUC=0.993, p<0.001) exhibit excellent discriminatory ability. Correlations: IL6 with TNF (r=0.672, p<0.001) and Nesfatin1 (r=0.542, p<0.001); TNF with Nesfatin1 (r=0.591, p<0.001), hbA1c (r=0.683, p<0.001), and PP (r=0.367, p<0.001); Nesfatin1 with PP (r=0.594, p<0.001) and hbA1c (r=0.800, p<0.001). Age has a negative correlation with hbA1c (r=-0.119, p=0.086). Thus, data shows a significant association between inflammatory markers, blood glucose levels, and the progression from pre-diabetes to diabetes.

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BACKGROUND: Obesity has been suggested to be associated with the coronavirus disease 2019 (COVID-19); however, it is unclear whether obesity or metabolic abnormalities accompanied by obesity have a stronger association with COVID-19 risk. METHODS: This study used the Korea Disease Control and Prevention Agency database, which includes information about the COVID-19 diagnosis and mortality dates of the entire Korean population between October 2020 and December 2021 (for diagnosis) or March 2022 (for mortality). A total of 24,310,283 adults were included and classified into four metabolic obesity phenotypes: (1) metabolically healthy and normal weight (MHNW), (2) metabolically unhealthy and normal weight (MUNW), (3) metabolically healthy and obese (MHO), and (4) metabolically unhealthy and obese (MUO). COVID-19 mortality and severity were compared according to metabolic obesity phenotypes in the total population and in each age group (20-<50 years, 50-<70 years, and ≥ 70 years). Additionally, major adverse cardiovascular events (MACE) after COVID-19 infection were compared according to metabolic obesity phenotypes. RESULTS: A total of 3, 956, 807 participants (16.3%) were diagnosed with COVID-19 during the study period. Among them, metabolically unhealthy subjects had higher mortality rates than metabolically healthy subjects (0.81% for MUNW, 0.40% for MUO, 0.23% for MHNW, and 0.19% for MHO). The rates of severe hospitalized disease were also higher in metabolically unhealthy subjects than in healthy subjects (0.59% for MUNW, 0.55% for MUO, 0.19% for MHNW, and 0.31% for MHO). In the subgroup analyses by age, similar trends were observed in subjects aged 20-50 and 50-70 years, respectively. Additionally, the incidence of total MACE was increased in metabolically unhealthy individuals. CONCLUSIONS: The study shows that metabolic health is more strongly associated with COVID-19 mortality and severity than obesity, particularly in adults aged < 70 years.

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Akkermansia muciniphila (A. muciniphila) and its derivatives, including extracellular vesicles (EVs) and outer membrane proteins, are recognized for enhancing intestinal balance and metabolic health. However, the mechanisms of Akkermansia muciniphila's action and its effects on the microbiome are not well understood. In this study, we examined the influence of A. muciniphila and its derivatives on gastrointestinal (GI) and metabolic disorders through a meta-analysis of studies conducted on mouse models. A total of 39 eligible studies were identified through targeted searches on PubMed, Web of Science, Science Direct, and Embase until May 2024. A. muciniphila (alive or heat-killed) and its derivatives positively affected systemic and gut inflammation, liver enzyme level, glycemic response, and lipid profiles. The intervention increased the expression of tight-junction proteins in the gut, improving gut permeability in mouse models of GI and metabolic disorders. Regarding body weight, A. muciniphila and its derivatives prevented weight loss in animals with GI disorders while reducing body weight in mice with metabolic disorders. Sub-group analysis indicated that live bacteria had a more substantial effect on most analyzed biomarkers. Gut microbiome analysis using live A. muciniphila identified a co-occurrence cluster, including Desulfovibrio, Family XIII AD3011 group, and Candidatus Saccharimonas. Thus, enhancing the intestinal abundance of A. muciniphila and its gut microbial clusters may provide more robust health benefits for cardiometabolic, and age-related diseases compared with A. muciniphila alone. The mechanistic insight elucidated here will pave the way for further exploration and potential translational applications in human health.

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As environmental and health concerns of beef production and consumption mount, there is growing interest in agroecological production methods, including finishing beef cattle on pastures with phytochemically diverse grasses, forbs, and/or shrubs. The goal of this metabolomics, lipidomics, and fatty acid methyl ester profiling study was to compare meat (pectoralis profundus) of Black Angus cattle from two commercial US beef finishing systems (pasture-finished on Western U.S. rangeland; n = 18 and grain-finished in a Midwest U.S. feedlot; n = 18). A total of 907 out of 1575 compounds differed in abundance between pasture-finished and grain-finished beef samples (all, false discovery rate adjusted P < 0.05). Pasture-finished beef contained higher levels of phenolic antioxidants (2.6-fold), alpha-tocopherol (3.1-fold), nicotinate/vitamin B3 (9.4-fold), choline (1.2-fold), myo-inositol (1.8-fold), and omega-3 fatty acids (4.1-fold). Grain-finished beef contained higher levels of gamma-tocopherol (14.6-fold), nicotinamide/vitamin B3 (1.5-fold), pantothenate/vitamin B5 (1.3-fold), and pyridoxine/vitamin B6 (1.3-fold); indicating that feeding some grain (by-products) could be beneficial to increase levels of certain B-vitamins. Pasture-finished beef samples also displayed lower levels of oxidative stress (homocysteine, 0.6-fold; and 4-hydroxy-nonenal-glutathione, 0.4-fold) and improved mitochondrial function (1.3-fold) compared to grain-finished animals. Two potential metabolites of fluoroquinolone antibiotics, 2,8-quinolinediol and 2,8-quinolinediol sulfate, were only observed in grain-finished beef, though the source remains unknown. While pasture-finished cattle displayed improved markers of metabolic health and concentrated additional, potentially health-promoting compounds in their meat, our findings should not be interpreted as that grain-finished beef is unhealthy to consume. Randomized controlled trials in humans are required to further assess whether observed differences between pasture-finished and feedlot-finished beef have an appreciable effect on human health.

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Menopause is a critical stage in a woman's life in which cardiometabolic alterations appear, such as insulin resistance or a predisposition to visceral fat deposits, leading to an increased risk of cardiometabolic diseases (R-CMBs). New strategies to reduce the R-CMBs in postmenopausal women using natural compounds without adverse effects are desirable. In this sense, plant-based diets rich in fruits and vegetables could play a fundamental role due to the high content of bioactive compounds found in these diets, such as (poly)phenols, known for their antioxidant, anti-inflammatory and vasodilator properties. The aim of this research was to carry out a dietary trial to evaluate the effect of the daily intake of different (poly)phenol-rich foods (PP-rich foods) for 2 months on the modulation of the main cardiometabolic risk biomarkers of postmenopausal women. The results showed a slight improvement in blood pressure (BP), lipid profile and oxidative stress, endothelial function and inflammatory biomarkers. These findings suggest that daily consumption of PP-rich foods alleviated the R-CMBs of postmenopausal women by reducing the oxidative stress and, thus, the risk of cardiovascular events; however, the magnitude of the cardioprotective effect of (poly)phenols depends on inter-individual variability.

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Workplaces cause employees to adopt sedentary behaviors for most of their daytime, negatively impacting psychophysical health. A new office concept (UP150) was designed to reduce sedentary behaviors at work through architectural changes, proactive technologies, and wellness coaches (education to active lifestyles). The present study examined the effects of the UP150 concept, previously investigated in dedicated workspaces, with a 12-month longitudinal trial in a real worksite environment. Forty-eight desk workers comprised the experimental (EG) and control (CG) groups. All participants worked in the same working environment, having the UP150 features inserted in a usual working environment, but the CG was not allowed to interact with the UP150 specifics. During the experimental year, physical (physical activity, motor efficiency, and anthropometric features), clinical (metabolic parameters and cognitive-capacity-related parameters), and psychological (well-being and discomfort, job social and psychological perceptions, and perceived workload) features were assessed. The prolonged application of the UP150 procedure in a mixed working context for involvement in corporate policies positively affected EG workers' physical (physical activity and motor efficiency increased, and body fat unchanged), clinical (blood glucose, insulin, and total cholesterol decreased; HDL increased), and psychological (well-being and social support raised; job demand and perceived workload lowered) parameters, confirming the previous studies.

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BACKGROUND: Increasing evidence supports the association between body mass index (BMI), Alzheimer's disease, and vascular markers. Recently, metabolically unhealthy conditions have been reported to affect the expression of these markers. We aimed to investigate the effects of BMI status on Alzheimer's and vascular markers in relation to metabolic health status. METHODS: We recruited 1,736 Asians without dementia (71.6 ± 8.0 years). Participants were categorized into underweight, normal weight, or obese groups based on their BMI. Each group was further divided into metabolically healthy (MH) and unhealthy (MU) groups based on the International Diabetes Foundation definition of metabolic syndrome. The main outcome was Aß positivity, defined as a Centiloid value of 20.0 or above and the presence of vascular markers, defined as severe white matter hyperintensities (WMH). Logistic regression analyses were performed for Aß positivity and severe WMH with BMI status or interaction terms between BMI and metabolic health status as predictors. Mediation analyses were performed with hippocampal volume (HV) and baseline Mini-Mental State Examination (MMSE) scores as the outcomes, and linear mixed models were performed for longitudinal change in MMSE scores. RESULTS: Being underweight increased the risk of Aß positivity (odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.13-4.98), whereas obesity decreased Aß positivity risk (OR = 0.63, 95% CI 0.50-0.80). Especially, obesity decreased the risk of Aß positivity (OR = 0.38, 95% CI 0.26-0.56) in the MH group, but not in the MU group. Obesity increased the risk of severe WMH (OR = 1.69, 1.16-2.47). Decreased Aß positivity mediate the relationship between obesity and higher HV and MMSE scores, particularly in the MH group. Obesity demonstrated a slower decline in MMSE (ß = 1.423, p = 0.037) compared to being normal weight, especially in the MH group. CONCLUSIONS: Our findings provide new evidence that metabolic health has a significant effect on the relationship between obesity and Alzheimer's markers, which, in turn, lead to better clinical outcomes.

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