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.

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.

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 Aβ 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 Aβ 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 Aβ positivity (odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.13-4.98), whereas obesity decreased Aβ positivity risk (OR = 0.63, 95% CI 0.50-0.80). Especially, obesity decreased the risk of Aβ 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 Aβ positivity mediate the relationship between obesity and higher HV and MMSE scores, particularly in the MH group. Obesity demonstrated a slower decline in MMSE (β = 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.

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.

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.
OBJECTIVE: 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.

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.

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.

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.
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).
CONCLUSIONS: TRE improved beta-cell function and insulin resistance in overweight patients with early diabetes, accompanied by beneficial effects on adiposity.

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.

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.