BACKGROUND: In animals, dietary sulfur amino acid restriction (SAAR) improves metabolic health, possibly mediated by altering sulfur amino acid metabolism and enhanced anti-obesogenic processes in adipose tissue. AIM: To assess the effects of SAAR over time on the plasma and urine SAA-related metabolites (sulfurome) in humans with overweight and obesity, and explore whether such changes were associated with body weight, body fat and adipose tissue gene expression. METHODS: Fifty-nine subjects were randomly allocated to SAAR (∼2 g SAA, n = 31) or a control diet (∼5.6 g SAA, n = 28) consisting of plant-based whole-foods and supplemented with capsules to titrate contents of SAA. Sulfurome metabolites in plasma and urine at baseline, 4 and 8 weeks were measured using HPLC and LC-MS/MS. mRNA-sequencing of subcutaneous white adipose tissue (scWAT) was performed to assess changes in gene expression. Data were analyzed with mixed model regression. Principal component analyses (PCA) were performed on the sulfurome data to identify potential signatures characterizing the response to SAAR. RESULTS: SAAR led to marked decrease of the main urinary excretion product sulfate (p < 0.001) and plasma and/or 24-h urine concentrations of cystathionine, sulfite, thiosulfate, H2S, hypotaurine and taurine. PCA revealed a distinct metabolic signature related to decreased transsulfuration and H2S catabolism that predicted greater weight loss and android fat mass loss in SAAR vs. controls (all pinteraction < 0.05). This signature correlated positively with scWAT expression of genes in the tricarboxylic acid cycle, electron transport and β-oxidation (FDR = 0.02). CONCLUSION: SAAR leads to distinct alterations of the plasma and urine sulfurome in humans, and predicted increased loss of weight and android fat mass, and adipose tissue lipolytic gene expression in scWAT. Our data suggest that SAA are linked to obesogenic processes and that SAAR may be useful for obesity and related disorders. TRIAL IDENTIFIER: https://clinicaltrials.gov/study/NCT04701346.

• MeSH
• aminokyseliny sírové * metabolismus   krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolom MeSH
• nadváha * metabolismus   genetika   MeSH
• obezita * metabolismus   genetika   MeSH
• regulace genové exprese MeSH
• tuková tkáň * metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

AIM: The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics. METHOD: Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention. RESULTS: MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds. CONCLUSION: We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.

• MeSH
• diabetes mellitus 2. typu * MeSH
• inulin * metabolismus   farmakologie   MeSH
• lidé MeSH
• multiomika MeSH
• nadváha metabolismus   MeSH
• obezita metabolismus   MeSH
• průřezové studie MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

BACKGROUND & AIMS: Reward circuitry in the brain plays a key role in weight regulation. We tested the effects of a plant-based meal on these brain regions. METHODS: A randomized crossover design was used to test the effects of two energy- and macronutrient-matched meals: a vegan (V-meal) and a conventional meat (M-meal) on brain activity, gastrointestinal hormones, and satiety in participants with type 2 diabetes (T2D; n = 20), overweight/obese participants (O; n = 20), and healthy controls (H; n = 20). Brain perfusion was measured, using arterial spin labeling functional brain imaging; satiety was assessed using a visual analogue scale; and plasma concentrations of gut hormones were determined at 0 and 180 min. Repeated-measures ANOVA was used for statistical analysis. Bonferroni correction for multiple comparisons was applied. The Hedge's g statistic was used to measure the effect size for means of paired difference between the times (180-0 min) and meal types (M-V meal) for each group. RESULTS: Thalamus perfusion was the highest in patients with T2D and the lowest in overweight/obese individuals (p = 0.001). Thalamus perfusion decreased significantly after ingestion of the M-meal in men with T2D (p = 0.04) and overweight/obese men (p = 0.004), and it decreased significantly after ingestion of the V-meal in healthy controls (p < 0.001; Group x Meal x Time: F = 3.4; p = 0.035). The effect size was -0.41 (95% CI, -1.14 to 0.31; p = 0.26) for men with diabetes; -0.72 (95% CI, -1.48 to 0.01; p = 0.05) for overweight/obese men; and 0.82 (95% CI, 0.09 to 1.59; p = 0.03) for healthy men. Postprandial secretion of active GLP-1 increased after the V-meal compared with the M-meal by 42% (95% CI 25-62%; p = 0.003) in men with T2D and by 41% (95% CI 24-61%; p = 0.002) in healthy controls. Changes in thalamus perfusion after ingestion of both test meals correlated with changes in satiety (r = +0.68; p < 0.01), fasting plasma insulin (r = +0.40; p < 0.01), C-peptide (r = +0.48; p < 0.01) and amylin (r = +0.55; p < 0.01), and insulin secretion at 5 mmol/l (r = +0.77; p < 0.05). CONCLUSIONS: The higher postprandial GLP-1 secretion after the V-meal in men with T2D, with concomitant greater satiety and changes in thalamus perfusion, suggest a potential use of plant-based meals in addressing the key pathophysiologic mechanisms of food intake regulation. Trial registration ClinicalTrials.gov number, NCT02474147.

• MeSH
• diabetes mellitus 2. typu metabolismus   MeSH
• dieta vegetariánská metody   MeSH
• dieta metody   MeSH
• dospělí MeSH
• energetický příjem * MeSH
• jídla MeSH
• klinické křížové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nadváha metabolismus   MeSH
• obezita metabolismus   MeSH
• senioři MeSH
• thalamus krevní zásobení   metabolismus   MeSH
• živiny metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Importance: Excess body weight and insulin resistance lead to type 2 diabetes and other major health problems. There is an urgent need for dietary interventions to address these conditions. Objective: To measure the effects of a low-fat vegan diet on body weight, insulin resistance, postprandial metabolism, and intramyocellular and hepatocellular lipid levels in overweight adults. Design, Setting, and Participants: This 16-week randomized clinical trial was conducted between January 2017 and February 2019 in Washington, DC. Of 3115 people who responded to flyers in medical offices and newspaper and radio advertisements, 244 met the participation criteria (age 25 to 75 years; body mass index of 28 to 40) after having been screened by telephone. Interventions: Participants were randomized in a 1:1 ratio. The intervention group (n = 122) was asked to follow a low-fat vegan diet and the control group (n = 122) to make no diet changes for 16 weeks. Main Outcomes and Measures: At weeks 0 and 16, body weight was assessed using a calibrated scale. Body composition and visceral fat were measured by dual x-ray absorptiometry. Insulin resistance was assessed with the homeostasis model assessment index and the predicted insulin sensitivity index (PREDIM). Thermic effect of food was measured by indirect calorimetry over 3 hours after a standard liquid breakfast (720 kcal). In a subset of participants (n = 44), hepatocellular and intramyocellular lipids were quantified by proton magnetic resonance spectroscopy. Repeated measure analysis of variance was used for statistical analysis. Results: Among the 244 participants in the study, 211 (87%) were female, 117 (48%) were White, and the mean (SD) age was 54.4 (11.6) years. Over the 16 weeks, body weight decreased in the intervention group by 5.9 kg (95% CI, 5.0-6.7 kg; P < .001). Thermic effect of food increased in the intervention group by 14.1% (95% CI, 6.5-20.4; P < .001). The homeostasis model assessment index decreased (-1.3; 95% CI, -2.2 to -0.3; P < .001) and PREDIM increased (0.9; 95% CI, 0.5-1.2; P < .001) in the intervention group. Hepatocellular lipid levels decreased in the intervention group by 34.4%, from a mean (SD) of 3.2% (2.9%) to 2.4% (2.2%) (P = .002), and intramyocellular lipid levels decreased by 10.4%, from a mean (SD) of 1.6 (1.1) to 1.5 (1.0) (P = .03). None of these variables changed significantly in the control group over the 16 weeks. The change in PREDIM correlated negatively with the change in body weight (r = -0.43; P < .001). Changes in hepatocellular and intramyocellular lipid levels correlated with changes in insulin resistance (both r = 0.51; P = .01). Conclusions and Relevance: A low-fat plant-based dietary intervention reduces body weight by reducing energy intake and increasing postprandial metabolism. The changes are associated with reductions in hepatocellular and intramyocellular fat and increased insulin sensitivity. Trial Registration: ClinicalTrials.gov Identifier: NCT02939638.

• MeSH
• absorpční fotometrie MeSH
• C-peptid metabolismus   MeSH
• cholesterol metabolismus   MeSH
• dieta s omezením tuků * MeSH
• dieta veganská * MeSH
• dospělí MeSH
• energetický metabolismus MeSH
• energetický příjem MeSH
• glykovaný hemoglobin metabolismus   MeSH
• HDL-cholesterol metabolismus   MeSH
• hepatocyty metabolismus   MeSH
• inzulin metabolismus   MeSH
• inzulinová rezistence MeSH
• játra diagnostické zobrazování   metabolismus   MeSH
• kosterní svalová vlákna metabolismus   MeSH
• kosterní svaly diagnostické zobrazování   metabolismus   MeSH
• krevní glukóza metabolismus   MeSH
• LDL-cholesterol metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolismus lipidů MeSH
• nadváha dietoterapie   metabolismus   MeSH
• nitrobřišní tuk diagnostické zobrazování   MeSH
• obezita dietoterapie   metabolismus   MeSH
• postprandiální období MeSH
• protonová magnetická rezonanční spektroskopie MeSH
• senioři MeSH
• složení těla MeSH
• tělesná hmotnost MeSH
• triglyceridy metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVE: While circulating nucleosome levels are high in obese mouse models, it is unknown where these nucleosomes originate from and whether they are a marker of cardio-metabolic health in humans. Here, we aimed to determine whether an association exists between circulating nucleosomes and the risk of developing obesity, metabolic syndrome (MetS) and/or a dysfunctional cardiovascular performance. METHODS: We randomly selected 120 participants of the Kardiovize Brno 2030 study across three BMI strata: BMI 18-25, 25-30, and > 30. We assessed the association between circulating nucleosome levels and the risk of obesity, MetS, and poor cardiovascular health. We then cultured human neutrophils, adipocytes, and hepatoma cells to study nucleosome origins in a fat-rich environment. RESULTS: Circulating nucleosome levels positively correlated with BMI (R = 0.602, p < 0.05), fatty liver index (R = 0.622, p < 0.05), left ventricular mass (R = 0.457, p < 0.05), and associated with MetS (p < 0.001) and poor cardiovascular health (p < 0.001). Incubating neutrophils with 1-10 μM free fatty acids triggered nucleosome production without concomitant cell death. Nucleosomes were not produced during pre-adipocyte differentiation or upon incubation of hepatic cells with palmitic acid. CONCLUSIONS: Neutrophils are a bona fide source of circulating nucleosomes in an obesogenic environment and in overweight/obese patients. High nucleosome levels are associated with MetS and cardiovascular performance, and might represent novel candidate biomarkers for cardio-metabolic health.

• MeSH
• buňky Hep G2 MeSH
• dospělí MeSH
• index tělesné hmotnosti MeSH
• kardiovaskulární nemoci etiologie   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolický syndrom krev   komplikace   MeSH
• nadváha krev   komplikace   metabolismus   MeSH
• neutrofily cytologie   metabolismus   MeSH
• nukleozomy metabolismus   MeSH
• obezita krev   komplikace   metabolismus   MeSH
• senioři MeSH
• tukové buňky cytologie   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• lidé MeSH
• metabolické nemoci patofyziologie   MeSH
• metabolický syndrom MeSH
• nadváha klasifikace   metabolismus   terapie   MeSH
• obezita * klasifikace   metabolismus   terapie   MeSH
• tuková tkáň fyziologie   MeSH
• Check Tag
• lidé MeSH

OBJECTIVE: The evidence for liquid meal replacements in diabetes has not been summarized. Our objective was to synthesize the evidence of the effect of liquid meal replacements on cardiometabolic risk factors in overweight/obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Data sources included MEDLINE, EMBASE, and the Cochrane Library through 10 December 2018. We included randomized trials of ≥2 weeks assessing the effect of liquid meal replacements in weight loss diets compared with traditional weight loss diets on cardiometabolic risk factors in overweight/obese subjects with type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. Data were pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: Nine trial comparisons (N = 961 [median follow-up 24 weeks]) met eligibility criteria. Mean differences were for body weight -2.37 kg (95% CI -3.30 to -1.44), BMI -0.87 kg/m2 (-1.31 to -0.42), body fat -1.66% (-2.17 to -1.15), waist circumference -2.24 cm (-3.72 to -0.77), HbA1c -0.43% (-0.66 to -0.19) (-4.7 mmol/mol [-7.2 to -2.1]), fasting glucose -0.63 mmol/L (-0.99 to -0.27), fasting insulin -11.83 pmol/L (-23.11 to -0.54), systolic blood pressure -4.97mmHg (-7.32 to -2.62), and diastolic blood pressure -1.98 mmHg (-3.05 to -0.91). There was no effect on blood lipids. The overall certainty of the evidence was low to moderate owing to imprecision and/or inconsistency. CONCLUSIONS: Liquid meal replacements in weight loss diets lead to modest reductions in body weight, BMI, and systolic blood pressure, and reductions of marginal clinical significance in body fat, waist circumference, HbA1c, fasting glucose, fasting insulin, and diastolic blood pressure. More high-quality trials are needed to improve the certainty in our estimates.

• MeSH
• diabetes mellitus 2. typu komplikace   dietoterapie   epidemiologie   metabolismus   MeSH
• diabetické angiopatie epidemiologie   etiologie   prevence a kontrola   MeSH
• dospělí MeSH
• inzulin krev   MeSH
• jídla * MeSH
• kardiovaskulární nemoci epidemiologie   etiologie   prevence a kontrola   MeSH
• lidé MeSH
• nadváha komplikace   dietoterapie   epidemiologie   metabolismus   MeSH
• obezita komplikace   dietoterapie   epidemiologie   metabolismus   MeSH
• omezení příjmu potravy fyziologie   MeSH
• randomizované kontrolované studie jako téma statistika a číselné údaje   MeSH
• redukční dieta * škodlivé účinky   statistika a číselné údaje   MeSH
• rizikové faktory MeSH
• tělesná hmotnost fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH

• MeSH
• alanintransaminasa metabolismus   MeSH
• aspartátaminotransferasy metabolismus   MeSH
• dítě MeSH
• dyslipidemie metabolismus   MeSH
• gama-glutamyltransferasa metabolismus   MeSH
• glukózový toleranční test MeSH
• HDL-cholesterol MeSH
• hmotnostní úbytek * MeSH
• jaterní testy MeSH
• krevní glukóza metabolismus   MeSH
• krevní tlak MeSH
• LDL-cholesterol MeSH
• lidé MeSH
• mladiství MeSH
• nadváha metabolismus   terapie   MeSH
• obezita dětí a dospívajících * metabolismus   terapie   MeSH
• triglyceridy metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• komentáře MeSH
• souhrny MeSH

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• nadváha etiologie   metabolismus   MeSH
• optimální tělesná hmotnost fyziologie   MeSH
• věkové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH

INTRODUCTION: Obesity and dyslipidemia may negatively affect brain health and are frequent medical comorbidities of schizophrenia and related disorders. Despite the high burden of metabolic disorders, little is known about their effects on brain structure in psychosis. We investigated, whether obesity or dyslipidemia contributed to brain alterations in first-episode psychosis (FEP). METHODS: 120 participants with FEP, who were undergoing their first psychiatric hospitalization, had <24 months of untreated psychosis and were 18-35 years old and 114 controls within the same age range participated in the study. We acquired 3T brain structural MRI, fasting lipids and body mass index. We used machine learning trained on an independent sample of 504 controls to estimate the individual brain age of study participants and calculated the BrainAGE score by subtracting the chronological from the estimated brain age. RESULTS: In a multiple regression model, the diagnosis of FEP (B = 1.15, SE B = 0.31, p < 0.001) and obesity/overweight (B = 0.92, SE B = 0.35, p = 0.008) were each additively associated with BrainAGE scores (R2 = 0.22, F(3, 230) = 21.92, p < 0.001). BrainAGE scores were highest in participants with FEP and obesity/overweight (3.83 years, 95%CI = 2.35-5.31) and lowest in normal weight controls (-0.27 years, 95%CI = -1.22-0.69). LDL-cholesterol, HDL-cholesterol or triglycerides were not associated with BrainAGE scores. CONCLUSIONS: Overweight/obesity may be an independent risk factor for diffuse brain alterations manifesting as advanced brain age already early in the course of psychosis. These findings raise the possibility that targeting metabolic health and intervening already at the level of overweight/obesity could slow brain ageing in FEP.

• MeSH
• dospělí MeSH
• dyslipidemie krev   epidemiologie   MeSH
• komorbidita MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• nadváha diagnostické zobrazování   epidemiologie   metabolismus   MeSH
• obezita diagnostické zobrazování   epidemiologie   metabolismus   MeSH
• psychotické poruchy diagnostické zobrazování   epidemiologie   patologie   MeSH
• rizikové faktory MeSH
• rozpoznávání automatizované MeSH
• schizofrenie diagnostické zobrazování   epidemiologie   patologie   MeSH
• strojové učení MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH