A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1.

Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.

Effects of Wheat Biscuits Enriched with Plant Proteins Incorporated into an Energy-Restricted Dietary Plan on Postprandial Metabolic Responses of Women with Overweight/Obesity.

This study investigates the effect of daily consumption of wheat biscuits enriched with plant proteins in postprandial metabolic responses of women with overweight/obesity who follow an energy-restricted diet. Thirty apparently healthy women participated in a 12-week randomized controlled trial and were assigned either to a control (CB) or an intervention (PB) group. Participants consumed daily either a conventional (CB) or an isocaloric wheat biscuit enriched with plant proteins (PB) containing high amounts of amino acids with appetite-regulating properties, i.e., BCAAs and L-arg. At baseline and the end of the intervention, a mixed meal tolerance test was performed. The responses of glucose, insulin, ghrelin, GLP-1, and glicentin were evaluated over 180 min. After 12 weeks, both groups experienced significant decreases in body weight, fat mass, and waist circumference. In the PB group, a trend towards higher weight loss was observed, accompanied by lower carbohydrate, fat, and energy intakes (p < 0.05 compared to baseline and CB group), while decreases in fasting insulin and the HOMA-IR index were also observed (p < 0.05 compared to baseline). In both groups, similar postprandial glucose, ghrelin, and GLP-1 responses were detected, while iAUC for insulin was lower (p < 0.05). Interestingly, the iAUC of glicentin was greater in the PB group (p < 0.05 compared to baseline). Subjective appetite ratings were beneficially affected in both groups (p < 0.05). Consumption of wheat biscuits enriched in plant proteins contributed to greater weight loss, lower energy intake, and insulin resistance and had a positive impact on postprandial glicentin response, a peptide that can potentially predict long-term weight loss and decreased food intake.

Hair cortisol levels are associated with overweight and obesity in the ELSA-Brasil cohort.

Introduction: Hair cortisol level has recently been identified as a promising marker for detecting long-term cortisol levels and a marker of hypothalamic-pituitary-adrenal cortex (HPA) axis activity. However, research on the association between obesity and an altered cortisol metabolism remains controversial. Objective: This study aimed to investigate the relationship between hair cortisol levels and overweight and obesity in participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: This was a cross-sectional study involving 2,499 participants from the second follow-up (visit 3, 2017-2019) attending research centers in Rio de Janeiro and Rio Grande do Sul states. Hair samples were collected, and cortisol levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Cortisol levels were classified as low (< 40 pg/mg), medium (40-128 pg/mg), or high (> 128 pg/mg). The participants were classified as eutrophic, overweight, or obese according to their weight (kg) and height (m2). Odds ratios (ORs) with 95% confidence intervals (95%CI) were estimated. Results: Of the 2499 individuals, 30% had eutrophic weight, 40% were overweight, and 30% were obese. Notably, cortisol levels gradually increased with increasing body weight. Among participants with high hair cortisol levels, 41.2% were classified as overweight and 34.2% as obese. Multinomial logistic regression analysis indicated that participants with high cortisol levels were 43% (OR =1.43; 95%CI: 1.02-2.03) more likely to be overweight and 72% (OR =1.72; 95%CI:1.20-2.47) more likely to be obese than participants with low hair cortisol levels. After adjustment for all covariates, high cortisol levels remained associated with obesity (OR = 1.54; 95%CI:1.02-2.31) and overweight (OR =1.33; 95%CI:0.91-1.94). Conclusion: In the ELSA-Brazil cohort, hair stress were positively associated with overweight and obesity. These results underscore the importance of considering stress and cortisol as potential factors in obesity prevention and intervention efforts, and highlight a novel aspect of the complex relationship between stress and obesity in the Brazilian population.

[Characteristics of resting energy expenditure and evaluation of prediction formulas in young men with different body mass indexes].

OBJECTIVE: To compare the resting energy expenditure (REE) characteristics among young men with different body mass indexes (BMI). METHODS: Thirty young men [average age was (26.93±4.16) years] were enrolled in this study. They underwent resting metabolism tests in the Department of Sports Medicine of Peking University Third Hospital from December 2017 to June 2021. The resting metabolic rate (RMR) was measured by indirect calorimetry, the body composition was measured by bioresistance antibody component analyzer. The REE characteristics were analyzed, and 11 predictive equations were used to estimate RMR and compared with the measured value. The differences were analyzed by paired t-test and intra-class correlation coefficient (ICC). RESULTS: The RMR of the overall 30 young men was (1 960.17±463.11) kcal/d (1 kcal=4.186 8 kJ). Including (1 744.33±249.62) kcal/d in those with normal BMI, which was significantly lower than that in those who were overweight or obese [(2 104.06± 520.32) kcal/d, P < 0.01], but the weight-corrected RMR in those with normal BMI was significantly higher than that in those who were overweight or obese [(24.02±2.61) kcal/(kg·d) vs. (19.98±4.38) kcal/(kg·d), P < 0.01]. The RMR was significantly and positively correlated with body weight, adiposity, lean body mass, body surface area, and extracellular fluid in the subjects with diffe-rent BMI (all P < 0.05). The predicted values of the 11 prediction equations were not in good agreement with the measured values (all ICC < 0.75), with relatively high agreement between the predicted and measured values of the World Health Organization (WHO) equation in overweight obese young men (ICC=0.547, P < 0.01). CONCLUSION: There were significant differences in RMR among young men with different BMI, and the RMR after weight correction should be considered for those who were overweight or obese. The consistency between the predicted values of different prediction equations and the actual measured values of RMR was relatively poor, and it is recommended to accurately measure RMR by indirect calorimetry. For overweight or obese young men, the WHO prediction equation can be considered to calculate RMR, but it is necessary to establish an RMR prediction equation applicable to different BMI populations.

Does Yogurt Enriched with Platelet-Activating Factor Inhibitors from Olive Oil By-Products Affect Gut Microbiota and Faecal Metabolites in Healthy Overweight Subjects? (A randomized, parallel, three arm trial.).

OBJECTIVE: The effect of the daily consumption of a low-fat yogurt (150 g) enriched with Platelet-Activating Factor receptor (PAF-R) antagonists, or the plain one, on gut microbiota and faecal metabolites was investigated in healthy overweight subjects. METHODS: A randomized, three-arm, double-blind, placebo-controlled, parallel-group study was performed that lasted 8 weeks. Blood and stools were collected and analyzed before and after the intervention. RESULTS: Our findings revealed that the intake of the enriched yogurt resulted in a significant increase in the levels of Bifidobacterium spp., Clostridium perfringens group and Firmicutes-to-Bacteroidetes (F/B) ratio. On the other hand, a significant increase in the levels of Lactobacillus and C. perfringens group was detected after the intake of the plain yogurt. The increase in the levels of C. perfringens group was inversely associated with the plasma catabolic enzyme of PAF, namely LpPLA2 (lipoprotein-associated phospholipase A2), a cardiovascular risk marker that has been linked with inflammation and atherosclerosis. Moreover, in the enriched with PAF-R antagonists yogurt group, the increased levels of C. perfringens group were also associated with lower PAF action assessed as ex vivo human platelet-rich plasma (PRP) aggregation. Additionally, a higher % increase in molar ratio of Branched Short Chain Fatty Acids (BSCFAs) was detected for both yogurt groups after the 8 week-intervention compared to control. The consumption of the enriched yogurt also resulted in a significant drop in faecal caproic levels and a trend for lower ratio of butyrate to total volatile fatty acids (VFAs) compared to baseline levels. CONCLUSION: Yogurt consumption seems to favorably affect gut microbiota while its enrichment with PAF-R antagonists from olive oil by-products, may provide further benefits in healthy overweight subjects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02259205).

Effect of overweight/obesity on relationship between fractional exhaled nitric oxide and airway hyperresponsiveness in Chinese elderly patients with asthma.

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.

Investigation of the interaction between genetic risk score (GRS) and fatty acid quality indices on metabolic syndrome among overweight and obese women.

BACKGROUND AND AIM: Metabolic syndrome is one of the major public-health challenges, affecting one-quarter of the world population. Fatty acid quality indices are novel determinants of this disease and their interactions with genetic factors may have an impact on metabolic syndrome risk. Therefore, we aimed to investigate the interaction between genetic risk score (GRS) and fatty acid quality indices with metabolic syndrome (MetS) among overweight and obese women. METHODS: In the present cross-sectional study, 279 overweight and obese women (18-48 years old) were included. Several anthropometric measurements such as weight, height, body mass index (BMI), waist circumference (WC), and body fat percent (BF%) were measured. Also, systolic and diastolic blood pressure (SBP and DBP) were measured. Biochemical determination was performed for fasting blood glucose (FBS), triglyceride (TG), and high-density lipoprotein (HDL). MetS was determined according to National Cholesterol Education Program (NCEP ATP III) criteria. Dietary intake was evaluated by a validated and reliable 147-item semi-quantitative food frequency questionnaire. Cholesterol-saturated fat index (CSI) and the ratio of omega-6/omega-3 (ω-6/ω-3) essential fatty acids were considered as fat quality indices. The salting-out method was used to extract the total DNA. The unweighted GRS was calculated using the risk alleles of the three single nucleotide polymorphisms. The total average GRS value was 2 and the sum of the risk alleles of the 3 polymorphisms was 6. RESULT: The results of our analysis showed that after controlling for age, energy intake, BMI, and physical activity, there was a positive interaction between T2 of GRS and T2 of N6/N3 ratio on WC (ß = 7.95, 95%CI = 0.83,15.08, P = 0.029), T3 of GRS and T2 of N6/N3 ratio on DBP (ß = 5.93, 95%CI= -0.76,12.63, P = 0.083), and FBS (ß = 6.47, 95%CI = 0.59,13.53, P = 0.073), T3 of GRS and T3 of N6/N3 ratio on TG (ß = 54.42, 95%CI = 1.76,107.08, P = 0.043), and T3 of GRS and T3 of CSI on BF% (ß = 3.55, 95%CI= -0.35,7.45, P = 0.075). Also T2 of GRS in the interaction with T3 of CSI leads to an decrease - 8.35 mg/dl in HDL level after adjustment in (ß= -8.35, 95%CI= -17.34,0.62, P = 0.068). CONCLUSION: It seems the interaction of GRS and fatty acid quality indices is positively associated with several components of metabolic syndrome such as WC, TG and BF%. Our findings are of importance to public health, considering the high consumption of foods that are high on fatty acids. Conflicting evidence of many previous studies regarding the effect of fat intake and obesity and cardiovascular diseases could be because of the gene-diet interactions and genetic heterogeneity across various ethnic groups. Hence, the synergism effect of genetic and dietay intakes should be considered in future studies.

Impaired muscle oxygenation despite normal pulmonary function in type 2 diabetes without complications.

Long-term hyperglycemia in individuals with type 2 diabetes (T2D) can detrimentally impact pulmonary function and muscle oxygenation. As a result, these factors can impede the body's adaptation to physical exertion. We aimed to evaluate the oxygen pathway during maximal exercise among overweight/obese individuals with type 2 diabetes free from complications, in comparison with a group of matched overweight/obese individuals without diabetes, specifically concentrating on the effects on pulmonary function and muscle oxygenation. Fifteen overweight/obese adults with type 2 diabetes [glycated hemoglobin (HbA1c) = 8.3 ± 1.2%] and 15 matched overweight/obese adults without diabetes underwent pre- and post exercise lung function assessment. A maximal incremental exercise test was conducted, monitoring muscle oxygenation using near-infrared spectroscopy and collecting arterial blood gas samples. Both groups exhibited normal lung volumes at rest and after exercise. Spirometric lung function did not significantly differ pre- and post exercise in either group. During maximal exercise, the type 2 diabetes group showed significantly lower augmentation in total hemoglobin and deoxygenated hemoglobin compared with the control group. Despite comparable usual physical activity levels and comparable heart rates at exhaustion, the type 2 diabetes group had a lower peak oxygen consumption than controls. No significant differences were found in arterial blood gas analyses ([Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]) between the groups. Individuals with type 2 diabetes free from complications displayed normal pulmonary function at rest and post exercise. However, impaired skeletal muscle oxygenation during exercise, resulting from reduced limb blood volume and altered muscle deoxygenation, may contribute to the lower V̇o2peak observed in this population.NEW & NOTEWORTHY Individuals with type 2 diabetes free from micro- and macrovascular complications have normal resting pulmonary function, but their V̇o2peak is impaired due to poor skeletal muscle oxygenation during exercise. Tailoring exercise regimes for this population should prioritize interventions aimed at enhancing muscle oxygenation and blood flow improvement.

Intestinal alterations and mild glucose homeostasis impairments in the offspring born to overweight rats.

The gut plays a crucial role in metabolism by regulating the passage of nutrients, water and microbial-derived substances to the portal circulation. Additionally, it produces incretins, such as glucose-insulinotropic releasing peptide (GIP) and glucagon-like derived peptide 1 (GLP1, encoded by gcg gene) in response to nutrient uptake. We aimed to investigate whether offspring from overweight rats develop anomalies in the barrier function and incretin transcription. We observed pro-inflammatory related changes along with a reduction in Claudin-3 levels resulting in increased gut-permeability in fetuses and offspring from overweight rats. Importantly, we found decreased gip mRNA levels in both fetuses and offspring from overweight rats. Differently, gcg mRNA levels were upregulated in fetuses, downregulated in female offspring and unchanged in male offspring from overweight rats. When cultured with high glucose, intestinal explants showed an increase in gip and gcg mRNA levels in control offspring. In contrast, offspring from overweight rats did not exhibit any response in gip mRNA levels. Additionally, while females showed no response, male offspring from overweight rats did exhibit an upregulation in gcg mRNA levels. Furthermore, female and male offspring from overweight rats showed sex-dependent anomalies when orally challenged with a glucose overload, returning to baseline glucose levels after 120 min. These results open new research questions about the role of the adverse maternal metabolic condition in the programming of impairments in glucose homeostasis, enteroendocrine function and gut barrier function in the offspring from overweight mothers and highlight the importance of a perinatal maternal healthy metabolism.

Relative Body Mass Index Improves the BMI Percentile Performance for Detection and Monitoring of Excess Adiposity in Adolescents.

Obesity is defined as excess adipose tissue; however, commonly used methods may under-detect adiposity in adolescents. This study compared the performance of body mass index percentile (BMI%) and relative body mass index (RBMI) in identifying excess body fat percentage (BF%) and estimated RBMI cut points to better stratify severity of adiposity. In 567 adolescents ages 11-19 year, BF% measured by DXA was used to compare BMI% and RBMI performance at different degrees of adiposity. RBMI cut points for adiposity detection were derived via ROC curve analysis. BF% was strongly correlated with BMI% (r = 0.889, p < 0.001) and RBMI (r = 0.901, p < 0.001). However, RBMI exhibited less dispersion and better discriminated the relationship with BF% independent of age, race, and gender. Both BMI% and RBMI performed similarly for detecting high BF% (≥25 BF% in males; ≥30 BF% in females). Nonetheless, the relationship of BMI% with BF% was diminished among leaner adolescents. RBMI detected overweight in 21.3% more females and 14.2% more males. RBMI improved the detection of excess adiposity in individuals otherwise classified as having normal weight or overweight by BMI%. RBMI is a valuable and accessible tool for earlier detection, intervention, and effective follow-up of excess adiposity in youth at higher risk for complications.

A comparative analysis of energy expenditure and substrate metabolism in male university students with overweight/obesity: Tabata vs HIIT and MICT.

Introduction: Exploring the energy expenditure and substrate metabolism data during exercise, 10-minute recovery, and 20-minute recovery phases in Tabata, HIIT(High-Intensity Interval Training), and MICT(Moderate-Intensity Continuous Training). This study explores the scientific aspects of weight reduction strategies, examining energy expenditure and substrate metabolism from various training perspectives. The aim is to establish a theoretical foundation for tailoring targeted exercise plans for individuals within the population with overweight/obesity. Methods: This study used an experimental design with fifteen male university students with overweight/obesity. Participants underwent random testing with Tabata, HIIT, and MICT. Tabata involved eight sets of 20 seconds exercise and 10 seconds rest, totaling 4 minutes. HIIT included four sets of power cycling: 3 minutes at 80% VO2max intensity followed by 2 minutes at 20% VO2max. MICT comprised 30 minutes of exercise at 50% VO2max intensity. Gas metabolism indices were continuously measured. Subsequently, fat and glucose oxidation rates, along with energy expenditure, were calculated for each exercise type. Results: During both the exercise and recovery phases, the Tabata group exhibited a significantly higher fat oxidation rate of (0.27 ± 0.03 g/min) compared to the HIIT group (0.20 ± 0.04 g/min, p<0.05) and the MICT group (0.20 ± 0.03g/min, p<0.001). No significant difference was observed between the HIIT and MICT groups (p=0.854). In terms of energy expenditure rate, the Tabata group maintained a substantially elevated level at 5.76 ± 0.74kcal/min compared to the HIIT group (4.81 ± 0.25kcal/min, p<0.01) and the MICT group (3.45 ± 0.25kcal/min, p<0.001). Additionally, the energy expenditure rate of the HIIT group surpassed that of the MICT group significantly (p<0.001). Conclusion: The study finds that male college students with overweight/obesity in both exercise and recovery, Tabata group has lower fat and glucose oxidation rates, and energy expenditure compared to HIIT and MICT groups. However, over the entire process, Tabata still exhibits significantly higher rates in these aspects than HIIT and MICT. Despite a shorter exercise duration, Tabata shows a noticeable "time-efficiency" advantage. Tabata can be used as an efficient short-term weight loss exercise program for male college students with overweight/obesity.

Association Between Pro-inflammatory Cytokine Levels (IL-1ß, IL-6, and TNF-α) in Human Colostrum and Maternal Body Composition Components.

Background: Obesity is characterized as a low-grade chronic inflammatory state, marked by elevated inflammatory biomarkers. Breast milk (BM) is rich in nutritional elements, vitamins, minerals, immunological factors, and bioactive components. These bioactive components, capable of influencing biological processes, may vary in concentration based on maternal body composition. Research Aim/Question(s): This study aimed to explore the association between pro-inflammatory cytokine levels (interleukin-1 beta [IL-1ß], interleukin-6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) in human colostrum and maternal body composition, as analyzed through bioelectrical impedance vector analysis (BIVA). Method: In this cross-sectional study, 117 healthy postpartum participants were included, with each group (normal weight, overweight, and obese) comprising 39 individuals, as classified by BIVA. Colostrum samples were collected within the first 24 hours postpartum. Results: IL-1ß levels did not significantly differ across the groups, with concentrations of 69.5 ± 103 pg/mL in normal-weight, 79.7 ± 97.9 pg/mL in overweight, and 68.7 ± 108 pg/mL in obese women. IL-6 levels were significantly higher in the overweight group (55 ± 72.4 pg/mL) than in the normal-weight (48.1 ± 74.1 pg/mL) and obese groups (28.9 ± 36.2 pg/mL) (p = 0.02). Similarly, TNF-α levels were higher in the overweight group, with concentrations of 58.7 ± 74.9 pg/mL, than in the normal-weight group, with concentrations of 38.6 ± 95.4 pg/mL, and 52.6 ± 115 pg/mL in obese women (p = 0.02). Conclusion: This study shows that IL-6 and TNF-α concentrations were statistically higher in the colostrum of overweight women, suggesting that maternal body composition may influence the inflammatory profile of BM.

Correlation between skeletal muscle acetylcarnitine and phosphocreatine metabolism during submaximal exercise and recovery: interleaved 1H/31P MRS 7 T study.

Acetylcarnitine is an essential metabolite for maintaining metabolic flexibility and glucose homeostasis. The in vivo behavior of muscle acetylcarnitine content during exercise has not been shown with magnetic resonance spectroscopy. Therefore, this study aimed to explore the behavior of skeletal muscle acetylcarnitine during rest, plantar flexion exercise, and recovery in the human gastrocnemius muscle under aerobic conditions. Ten lean volunteers and nine overweight volunteers participated in the study. A 7 T whole-body MR system with a double-tuned surface coil was used to acquire spectra from the gastrocnemius medialis. An MR-compatible ergometer was used for the plantar flexion exercise. Semi-LASER-localized 1H MR spectra and slab-localized 31P MR spectra were acquired simultaneously in one interleaved exercise/recovery session. The time-resolved interleaved 1H/31P MRS acquisition yielded excellent data quality. A between-group difference in acetylcarnitine metabolism over time was detected. Significantly slower τPCr recovery, τPCr on-kinetics, and lower Qmax in the overweight group, compared to the lean group was found. Linear relations between τPCr on-kinetics, τPCr recovery, VO2max and acetylcarnitine content were identified. In conclusion, we are the first to show in vivo changes of skeletal muscle acetylcarnitine during acute exercise and immediate exercise recovery with a submaximal aerobic workload using interleaved 1H/31P MRS at 7 T.

Urolithin A production drives the effects of pomegranate on the gut microbial metabolism of bile acids and cholesterol in mild dyslipidaemic overweight and obese individuals.

The metabolism of (poly)phenols and some host metabolites, including bile acids (BAs) and cholesterol, varies among individuals depending on their gut microbiota. The gut microbial metabolism of ellagitannins (ETs) and ellagic acid (EA) produces urolithins (Uros), yielding three metabotypes with quantitative and qualitative differences based on dissimilar Uro-producing profiles (UM-A, UM-B, and UM-0, i.e., non-producers). Previous animal studies demonstrated that polyphenols impact BAs and cholesterol microbial metabolism, but data on their effects in humans and data regarding the inter-individual variability of these metabolic conversions are scant. We evaluated whether UMs, as distinctive functional gut-microbiome signatures, could determine the potential effect of a pomegranate extract (PE) rich in ET-EA on the metabolism of BAs and cholesterol in mild dyslipidaemic overweight-obese individuals, with possible consequences on host-lipid homeostasis and gut health. At the baseline, UM-B presented the highest levels of faecal total and secondary BAs and coprostanol, suggesting that the lipid absorption capacity and gut cytotoxic risk could be augmented in UM-B. PE intake significantly reduced faecal coprostanol and BA production, especially secondary BAs, and modulated the gut microbiome, reducing the gut cytotoxic risk, especially in UM-B individuals. The lowering of faecal microbial coprostanol and BAs and some BA-metabolising bacteria was quantitatively correlated with Uro concentrations, mainly faecal Uro-A. This suggests that PE consumption could exert cardiovascular and gut protection through Uro-A production as a direct driver of the effects and indirectly by reducing the Coriobacteriaceae family and BA pool, known factors involved in the gut absorption of lipids.

Association Between Clonal Hematopoiesis Driver Mutations, Immune Cell Function, and the Vasculometabolic Complications of Obesity.

BACKGROUND: Obesity is accompanied by dysregulated inflammation, which can contribute to vasculometabolic complications including metabolic syndrome and atherosclerosis. Recently, clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a risk factor for cardiovascular diseases. We aimed to determine how CHIP is related to immune cell function, systemic inflammation, and vasculometabolic complications in obese individuals. METHODS AND RESULTS: Two hundred ninety-seven individuals with overweight and obesity, between the ages of 54 and 81 years, were recruited in a cross-sectional study. Clonal hematopoiesis driver mutations (CHDMs) were identified with an ultrasensitive targeted assay. Assessment of carotid artery atherosclerosis was performed with ultrasound. Detailed immunological parameters, including cytokine production capacity of peripheral blood mononuclear cells, and targeted plasma proteomics analysis, were studied. Adipose tissue inflammation was determined in subcutaneous fat biopsies. Individuals with CHIP had higher concentrations of circulating IL (interleukin)-6. Total number of leukocytes and neutrophils were higher in individuals with CHIP. In contrast, ex vivo cytokine production capacity of peripheral blood mononuclear cells was significantly lower in individuals with CHIP. Sex-stratified analysis showed that men with CHDMs had significantly higher leukocyte and neutrophil counts, and ex vivo cytokine production capacity was lower in women with CHDMs. Surprisingly, the presence of atherosclerotic plaques was significantly lower in individuals with CHDMs. There was no relation between CHIP and metabolic syndrome. CONCLUSIONS: In individuals with overweight or obesity, CHDMs are not associated with vasculometabolic complications, but rather with a lower presence of carotid plaques. CHDMs associate with increased circulating inflammatory markers and leukocyte numbers, but a lower peripheral blood mononuclear cell cytokine production capacity.

A ketogenic diet lowers myocardial fatty acid oxidation but does not affect oxygen consumption: a study in overweight humans.

OBJECTIVE: A ketogenic diet (KD) characterized by very low carbohydrate intake and high fat consumption may simultaneously induce weight loss and be cardioprotective. The "thrifty substrate hypothesis" posits that ketone bodies are more energy efficient compared with other cardiac oxidative substrates such as fatty acids. This work aimed to study whether a KD with presumed increased myocardial ketone body utilization reduces cardiac fatty acid uptake and oxidation, resulting in decreased myocardial oxygen consumption (MVO2 ). METHODS: This randomized controlled crossover trial examined 11 individuals with overweight or obesity on two occasions: (1) after a KD and (2) after a standard diet. Myocardial free fatty acid (FFA) oxidation, uptake, and esterification rate were measured using dynamic [11 C]palmitate positron emission tomography (PET)/computed tomography, whereas MVO2 and myocardial external efficiency (MEE) were measured using dynamic [11 C]acetate PET. RESULTS: The KD increased plasma ß-hydroxybutyrate, reduced myocardial FFA oxidation (p < 0.01) and uptake (p = 0.03), and increased FFA esterification (p = 0.03). No changes were observed in MVO2 (p = 0.2) or MEE (p = 0.87). CONCLUSIONS: A KD significantly reduced myocardial FFA uptake and oxidation, presumably by increasing ketone body oxidation. However, this change in cardiac substrate utilization did not improve MVO2 , speaking against the thrifty substrate hypothesis.

The interaction between MALAT1 and TUG1 with dietary fatty acid quality indices on visceral adiposity index and body adiposity index.

We aimed to investigate the interaction between the transcript levels of taurine-upregulated gene 1 (TUG1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the Cholesterol-Saturated Fat Index (CSI) in relation to the visceral adiposity index (VAI) and body adiposity index (BAI). This cross-sectional study involved 346 women classified as obese and overweight, aged between 18 and 48 years. Dietary intake and the quality of dietary fat were assessed using a validated and reliable 147-item semi-quantitative food frequency questionnaire, with the Cholesterol-Saturated Fat Index (CSI) used as an indicator. Transcription levels of MALAT1 and TUG1 were evaluated through real-time polymerase chain reaction following the criteria outlined in the Minimum Information for Publication of Quantitative standards. Serum profiles were measured using standard protocols. We observed a positive association between transcription level of MALAT1 and VAI in both crude (ß = 3.646, 95% CI 1.950-5.341, p < 0.001) and adjusted (ß = 8.338, 95% CI 6.110-10.566, p < 0.001) models. Furthermore, after adjusting for confounders, a significant positive interaction was noted between MALAT1 expression and CSI on BAI (ß: 0.130, 95% CI 0.019, 0.240, p = 0.022), with a marginal positive interaction observed on VAI (ß: 0.718, 95% CI - 0.028, 1.463, p = 0.059). It seems that there may be a positive interaction between MALAT1 transcription level and CSI on VAI and BAI among overweight and obese women. However, no associations were seen between TUG1 mRNA level and the above-mentioned outcomes. Further functional studies are still required to elucidate this concept.

Adults with metabolically healthy overweight or obesity present more brown adipose tissue and higher thermogenesis than their metabolically unhealthy counterparts.

BACKGROUND: There is a subset of individuals with overweight/obesity characterized by a lower risk of cardiometabolic complications, the so-called metabolically healthy overweight/obesity (MHOO) phenotype. Despite the relatively higher levels of subcutaneous adipose tissue and lower visceral adipose tissue observed in individuals with MHOO than individuals with metabolically unhealthy overweight/obesity (MUOO), little is known about the differences in brown adipose tissue (BAT). METHODS: This study included 53 young adults (28 women) with a body mass index (BMI) ≥25 kg/m2 which were classified as MHOO (n = 34) or MUOO (n = 19). BAT was assessed through a static 18F-FDG positron emission tomography/computed tomography scan after a 2-h personalized cooling protocol. Energy expenditure, skin temperature, and thermal perception were assessed during a standardized mixed meal test (3.5 h) and a 1-h personalized cold exposure. Body composition was assessed by dual-energy x-ray absorptiometry, energy intake was determined during an ad libitum meal test and dietary recalls, and physical activity levels were determined by a wrist-worn accelerometer. FINDINGS: Participants with MHOO presented higher BAT volume (+124%, P = 0.008), SUVmean (+63%, P = 0.001), and SUVpeak (+133%, P = 0.003) than MUOO, despite having similar BAT mean radiodensity (P = 0.354). In addition, individuals with MHOO exhibited marginally higher meal-induced thermogenesis (P = 0.096) and cold-induced thermogenesis (+158%, P = 0.050). Moreover, MHOO participants showed higher supraclavicular skin temperature than MUOO during the first hour of the postprandial period and during the cold exposure, while no statistically significant differences were observed in other skin temperature parameters. We observed no statistically significant differences between MHOO and MUOO in thermal perception, body composition, outdoor ambient temperature exposure, resting metabolic rate, energy intake, or physical activity levels. INTERPRETATION: Adults with MHOO present higher BAT volume and activity than MUOO. The higher meal- and cold-induced thermogenesis and cold-induced supraclavicular skin temperature are compatible with a higher BAT activity. Overall, these results suggest that BAT presence and activity might be linked to a healthier phenotype in young adults with overweight or obesity. FUNDING: See acknowledgments section.

Conversions between metabolically unhealthy and healthy obesity from midlife to late-life.

INTRODUCTION: Metabolically healthy obesity may be a transient phenotype, but studies with long follow-up, especially covering late-life, are lacking. We describe conversions between cross-categories of body mass index (BMI) and metabolic health in 786 Swedish twins with up to 27 years of follow-up, from midlife to late-life. METHODS: Metabolic health was defined as the absence of metabolic syndrome (MetS). We first visualized conversions between BMI-metabolic health phenotypes in 100 individuals with measurements available at ages 50-64, 65-79, and ≥80. Next, we modeled conversion in metabolic health status by BMI category in the full sample using Cox proportional hazards regression. RESULTS: The proportion of individuals with MetS and with overweight or obesity increased with age. However, one-fifth maintained a metabolically healthy overweight or obesity across all three age categories. Among those metabolically healthy at baseline, 59% converted to MetS during follow-up. Conversions occurred 56% more often among individuals with metabolically healthy obesity, but not overweight, compared to normal weight. Among those with MetS at baseline, 60% regained metabolic health during follow-up, with no difference between BMI categories. CONCLUSIONS: Conversions between metabolically healthy and unhealthy status occurred in both directions in all BMI categories. While conversions to MetS were more common among individuals with obesity, many individuals maintained or regained metabolic health during follow-up.

Gender-related differences in cardiometabolic risk factors and oxidative stress among prepubertal children with obesity.

OBJECTIVES: Gender-related differences in oxidative stress, nitric oxide bioavailability, and cardiometabolic risk factors were examined in a cross-sectional study involving 313 prepubertal children (8-9 years old) from the generation XXI birth-cohort. METHODS: Anthropometric measurements, cardiometabolic variables, and redox markers were assessed, including plasma and urinary isoprostanes (P-Isop, U-Isop), plasma total antioxidant status (P-TAS), serum myeloperoxidase (MPO), plasma and urinary nitrates and nitrites (P-NOX, U-NOX), and urinary hydrogen peroxide (U-H2O2). RESULTS: Girls showed higher levels of total/non-HDL cholesterol, triglycerides, and insulin resistance (HOMA-IR) compared to boys. Notably, U-H2O2 values were lower in girls. When stratifying by body mass index (BMI) and gender, both girls and boys exhibited higher MPO concentration and U-Isop values. Uric acid concentration was higher in overweight and obese girls than in normal weight girls, while no significant differences were observed among boys across BMI categories. Furthermore, U-NOX values differed only in boys, with higher levels observed in overweight and obese individuals compared to those with normal weight. Multivariate analysis, adjusted for age and BMI z-score, demonstrated inverse associations between U-H2O2 and pulse wave velocity values, as well as between U-NOX and total or non-HDL cholesterol, exclusively in boys. In girls, a positive association between U-Isop and HOMA-IR values was observed. CONCLUSIONS: In conclusion, gender differentially impacts oxidative stress, nitric oxide bioavailability, and cardiometabolic risk factors in prepubertal children. Prepubertal girls appear more susceptible to oxidative stress-induced metabolic dysfunction, while in boys, elevated levels of redox and nitric oxide bioavailability markers seem to provide protection against arterial stiffness and lipid homeostasis.