Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults

Background: Succinate is produced by both host and microbiota, with a key role in the interplay of immunity and metabolism and an emerging role as a biomarker for infammatory and metabolic disorders in middle-aged adults. The relationship between plasma succinate levels and cardiovascular disease (CVD) risk in young adults is unknown. Methods: Cross-sectional study in 100 (65% women) individuals aged 18–25 years from the ACTIvating Brown Adipose Tissue through Exercise (ACTIBATE) study cohort. CVD risk factors, body composition, dietary intake, basal metabolic rate, and cardiorespiratory ftness were assessed by routine methods. Plasma succinate was measured with an enzyme-based assay. Brown adipose tissue (BAT) was evaluated by positron emission tomography, and circulating oxylipins were assessed by targeted metabolomics. Fecal microbiota composition was analyzed in a sub-sample. Results: Individuals with higher succinate levels had higher levels of visceral adipose tissue (VAT) mass (+42.5%), tri‑ glycerides (+63.9%), C-reactive protein (+124.2%), diastolic blood pressure (+5.5%), and pro-infammatory omega-6 oxylipins than individuals with lower succinate levels. Succinate levels were also higher in metabolically unhealthy individuals than in healthy overweight/obese peers. Succinate levels were not associated with BAT volume or activity or with fecal microbiota composition and diversity. Conclusions: Plasma succinate levels are linked to a specifc pro-infammatory omega-6 signature pattern and higher VAT levels, and seem to refect the cardiovascular status of young adults.Spanish Ministry of Economy and Competitiveness via Retos de la Sociedad (DEP2016-79512-R to JRR and RTI2018-093919-B to SFV)European Regional Development Funds (ERDF)Spanish Ministry of Education (FPU16/02828, FPU16/05159, FPU17/01523 and FPU19/01609)University of Granada Plan Propio de Investigación 2016-Excellence actions–Unit of Excellence on Exercise and Health (UCEES)Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF: ref. SOMM17/6107/UGR)The Spanish Ministry of Science and Innovation (PI20/00095 to VCM and PI20/00338 to JV) co-fnanced by the European Regional Development Fund (ERDF)Ramón y Cajal program (RYC2019026490-I) from the Spanish Ministry of Science and Innovation, co-fnanced by the ERDFy Fundación Bancaria Caixa d’Estalvis i Pensions de Barcelona (HR20-00051 to S.F.-V.)The Netherlands CardioVascular Research Initiative: ‘the Dutch Heart Foundation, Dutch Federation of University Medical Centers, The Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Sciences’ (CVON2017-20 GENIUS-2) to PCNRChinese Scholarship Council (CSC, No. 201707060012) to XDMiguel Servet tenure-track program (CP10/00438 and CPII16/00008) from the Fondo de Investigación Sanitaria, co-fnanced by the ERDFFundación Alfonso Martin Escuder

Omega-6 and omega-3 oxylipins as potential markers of cardiometabolic risk in young adults

Objective Omega-6 and omega-3 oxylipins are known to play a role in inflammation and cardiometabolic diseases in preclinical models. The associations between plasma levels of omega-6 and omega-3 polyunsaturated fatty acid-derived oxylipins and body composition and cardiometabolic risk factors in young adults were assessed. Methods Body composition, brown adipose tissue, traditional serum cardiometabolic risk factors, inflammatory markers, and a panel of 83 oxylipins were analyzed in 133 young adults (age 22.1[SD 2.2] years, 67% women). Results Plasma levels of four omega-6 oxylipins (15-HeTrE, 5-HETE, 14,15-EpETrE, and the oxidative stress-derived 8,12-iso-iPF(2 alpha)-VI) correlated positively with adiposity, prevalence of metabolic syndrome, fatty liver index, and homeostatic model assessment of insulin resistance index and lipid parameters. By contrast, the plasma levels of three omega-3 oxylipins (14,15-DiHETE, 17,18-DiHETE, and 19,20-DiHDPA) were negatively correlated with adiposity, prevalence of metabolic syndrome, fatty liver index, homeostatic model assessment of insulin resistance index, and lipid parameters. The panel of seven oxylipins predicted adiposity better than traditional inflammatory markers such as interferon gamma or tumor necrosis factor-alpha. Pathway analyses revealed that individuals with obesity had higher plasma levels of omega-6 and lower plasma levels of omega-3 oxylipins than normal-weight individuals. Conclusion Plasma levels of seven omega-6 and omega-3 oxylipins may have utility as early markers of cardiometabolic risk in young adults.Analytical BioScience

Activation of Brown Adipose Tissue and Promotion ofWhite Adipose Tissue Browning by Plant-based Dietary Components in Rodents: A Systematic Review

Activation of brown adipose tissue (BAT) and promotion of white adipose tissue (WAT) browning is considered a potential tool to combat obesity and cardiometabolic disorders. The use of plant-based dietary components has become one of the most used strategies for activating BAT and promoting WAT browning in rodents. The main reason is because plant-based dietary components are usually recognized as safe when the dose is properly adjusted, and they can easily be administrated by being added to the diet or dissolved in water. The present systematic review aimed to study the effects of plant-based dietary components on activation of BAT and promotion of WAT browning in rodents. A systematic search of PubMed and Scopus (from 1978 to 2019) identified eligible studies. Studies assessing the effects of plant-based dietary components added to diet and/or water on uncoupling protein 1 (UCP1) expression in BAT and/orWAT were included. Studies that used dietary components of animal origin, did not specify the effects on UCP1, or were conducted in other species different from mice or rats were excluded. Of 3919 studies identified in the initial screening, 146 studies were finally included in the review. We found that tea extract catechins, resveratrol, capsaicin and capsinoids, cacao extract flavanols, and quercetin were the most studied components. Scientific evidence suggests that some of these dietary components activate BAT and promote WAT browning via activation of the AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) pathways. These findings reveal that there is strong scientific evidence supporting the use of plant-based dietary components to activate BAT and promote WAT browning in rodents and thus to potentially combat obesity and cardiometabolic disorders.Diabetes mellitus: pathophysiological changes and therap

Role of Human Brown Fat in Obesity, Metabolism and Cardiovascular Disease: Strategies to Turn Up the Heat

Diabetes mellitus: pathophysiological changes and therap

Effect of Different Exercise Training Modalities on Fasting Levels of Oxylipins and Endocannabinoids in Middle-Aged Sedentary Adults: A Randomized Controlled Trial

This study aimed to investigate the effects of different exercise training programs on fasting plasma levels of oxylipins, endocannabinoids (eCBs), and eCBs-like molecules in middle-aged sedentary adults. A 12-week randomized controlled trial was conducted using a parallel group design. Sixty-five middle-aged adults (40???65 years old) were randomly assigned to: (a) no exercise (control group), (b) concurrent training based on international physical activity recommendations (PAR group), (c) highintensity interval training (HIIT group), and (d) HIIT together with whole-body electromyostimulation (HIIT + EMS group). Plasma levels of oxylipins, eCBs, and eCBs-like molecules were determined in plasma samples before and after the intervention using targeted lipidomics. Body composition was assessed through dual-energy X-ray absorptiometry, and dietary intake through a food frequency questionnaire and three nonconsecutive 24-hr recalls. The physical activity recommendations, HIIT, and HIITEMS groups showed decreased plasma levels of omega-6 and omega-3-derived oxylipins, and eCBs and eCBs-like molecules after 12 weeks (all ?? < ???0.12; all p .05). Importantly, after Bonferroni post hoc corrections, the differences in plasma levels of omega-6 and omega-3 oxylipins were not statistically significant compared with the control group (all p .05). However, after post hoc corrections, plasma levels of anandamide and oleoylethanolamide were increased in the physical activity recommendations group compared with the control group (anandamide: ?? = 0.05 vs. ???0.09; oleoylethanolamide: ?? = ???0.12 vs. 0.013, all p < .049). In conclusion, this study reports that a 12-week exercise training intervention, independent of the modality applied, does not modify fasting plasma levels of omega-6 and omega-3 oxylipins, eCBs, and eCBs-like molecules in middle-aged sedentary adults

Effect of different exercise training modalities on fasting levels of oxylipins and endocannabinoids in middle-aged sedentary adults: a randomized controlled trial

This study aimed to investigate the effects of different exercise training programs on fasting plasma levels of oxylipins, endocannabinoids (eCBs), and eCBs-like molecules in middle-aged sedentary adults. A 12-week randomized controlled trial was conducted using a parallel group design. Sixty-five middle-aged adults (40???65 years old) were randomly assigned to: (a) no exercise (control group), (b) concurrent training based on international physical activity recommendations (PAR group), (c) highintensity interval training (HIIT group), and (d) HIIT together with whole-body electromyostimulation (HIIT + EMS group). Plasma levels of oxylipins, eCBs, and eCBs-like molecules were determined in plasma samples before and after the intervention using targeted lipidomics. Body composition was assessed through dual-energy X-ray absorptiometry, and dietary intake through a food frequency questionnaire and three nonconsecutive 24-hr recalls. The physical activity recommendations, HIIT, and HIITEMS groups showed decreased plasma levels of omega-6 and omega-3-derived oxylipins, and eCBs and eCBs-like molecules after 12 weeks (all ?? < ???0.12; all p .05). Importantly, after Bonferroni post hoc corrections, the differences in plasma levels of omega-6 and omega-3 oxylipins were not statistically significant compared with the control group (all p .05). However, after post hoc corrections, plasma levels of anandamide and oleoylethanolamide were increased in the physical activity recommendations group compared with the control group (anandamide: ?? = 0.05 vs. ???0.09; oleoylethanolamide: ?? = ???0.12 vs. 0.013, all p < .049). In conclusion, this study reports that a 12-week exercise training intervention, independent of the modality applied, does not modify fasting plasma levels of omega-6 and omega-3 oxylipins, eCBs, and eCBs-like molecules in middle-aged sedentary adults.Analytical BioScience

Activation of Human Brown Adipose Tissue by Capsinoids, Catechins, Ephedrine, and Other Dietary Components: A Systematic Review

Human brown adipose tissue (BAT) has attracted clinical interest not only because it dissipates energy but also for its potential capacity to counteract obesity and related metabolic disorders (e.g., insulin resistance and dyslipidemia). Cold exposure is the most powerful stimulus for activating and recruiting BAT, and this stimulatory effect is mediated by the transient receptor potential (TRP) channels. BAT can also be activated by other receptors such as the G-protein-coupled bile acid receptor 1 (GPBAR1) or beta-adrenergic receptors. Interestingly, these receptors also interact with several dietary components; in particular, capsinoids and tea catechins appear to mimic the effects of cold through a TRP-BAT axis, and they consequently seem to decrease body fat and improve metabolic blood parameters. This systematic review critically addresses the evidence behind the available human studies analyzing the effect of several dietary components (e.g., capsinoids, tea catechins, and ephedrine) on BAT activity. Even though the results of these studies are consistent with the outcomes of preclinical models, the lack of robust study designs makes it impossible to confirm the BAT-activation capacity of the specified dietary components. Further investigation into the effects of dietary components on BAT is warranted to clarify to what extent these components could serve as a powerful strategy to treat obesity and related metabolic disorders.Diabetes mellitus: pathophysiological changes and therap

A larger brown fat volume and lower radiodensity are related to a greater cardiometabolic risk, especially in young men

Objectives: Brown adipose tissue (BAT) is important in the maintenance of cardiometabolic health in rodents. Recent reports appear to suggest the same in humans, although if this is true remains elusive partly because of the methodological bias that affected previous research. This cross-sectional work reports the relationships of cold-induced BAT volume, activity (peak standardized uptake, SUVpeak), and mean radiodensity (an inverse proxy of the triacylglycerols content) with the cardiometabolic and inflammatory profile of 131 young adults, and how these relationships are influenced by sex and body weight.Design: This is a cross-sectional study.Methods: Subjects underwent personalized cold exposure for 2 h to activate BAT, followed by static F-18-fluorodeoxyglucose PET-CT scanning to determine BAT variables. Information on cardiometabolic risk (CMR) and inflammatory markers was gathered, and a CMR score and fatty liver index (FLI) were calculated.Results: In men, BAT volume was positively related to homocysteine and liver damage markers concentrations (independently of BMI and seasonality) and the FLI (all P 0.05).Conclusions: A larger BAT volume and a lower BAT mean radiodensity are related to a higher CMR, especially in young men, which may support that BAT acts as a compensatory organ in states of metabolic disruption

Exercise-induced changes on exerkines that might influence brown adipose tissue metabolism in young sedentary adults

In rodents, exercise alters the plasma concentration of exerkines that regulate white adipose tissue (WAT) browning or brown adipose tissue (BAT) metabolism. This study aims to analyse the acute and chronic effect of exercise on the circulating concentrations of 16 of these exerkines in humans. Ten young sedentary adults (6 female) performed a maximum walking effort test and a resistance exercise session. The plasma concentration of 16 exerkines was assessed before, and 3, 30, 60, and 120 min after exercise. Those exerkines modified by exercise were additionally measured in another 28 subjects (22 women). We also measured the plasma concentrations of the exerkines before and after a 24-week exercise programme (endurance + resistance; 3-groups: control, moderate-intensity and vigorous-intensity) in 110 subjects (75 women). Endurance exercise acutely increased the plasma concentration of lactate, norepinephrine, brain-derived neurotrophic factor, interleukin 6, and follistatin-like protein 1 (3 min after exercise), and musclin and fibroblast growth factor 21 (30 and 60 min after exercise), decreasing the plasma concentration of leptin (30 min after exercise). Adiponectin, atrial natriuretic peptide (ANP), beta-aminoisobutyric acid, meteorin-like, follistatin, pro-ANP, irisin and myostatin were not modified or not detectable. The resistance exercise session increased the plasma concentration of lactate 3 min after exercise. Chronic exercise did not alter the plasma concentration of these exerkines. In sedentary young adults, acute endurance exercise releases to the bloodstream exerkines that regulate BAT metabolism and WAT browning. In contrast, neither a low-volume resistance exercise session nor a 24-week training programme modified plasma levels of these molecules

Exercise-induced changes on exerkines that might influence brown adipose tissue metabolism in young sedentary adults

In rodents, exercise alters the plasma concentration of exerkines that regulate white adipose tissue (WAT) browning or brown adipose tissue (BAT) metabolism. This study aims to analyse the acute and chronic effect of exercise on the circulating concentrations of 16 of these exerkines in humans. Ten young sedentary adults (6 female) performed a maximum walking effort test and a resistance exercise session. The plasma concentration of 16 exerkines was assessed before, and 3, 30, 60, and 120 min after exercise. Those exerkines modified by exercise were additionally measured in another 28 subjects (22 women). We also measured the plasma concentrations of the exerkines before and after a 24-week exercise programme (endurance + resistance; 3-groups: control, moderate-intensity and vigorous-intensity) in 110 subjects (75 women). Endurance exercise acutely increased the plasma concentration of lactate, norepinephrine, brain-derived neurotrophic factor, interleukin 6, and follistatin-like protein 1 (3 min after exercise), and musclin and fibroblast growth factor 21 (30 and 60 min after exercise), decreasing the plasma concentration of leptin (30 min after exercise). Adiponectin, atrial natriuretic peptide (ANP), beta-aminoisobutyric acid, meteorin-like, follistatin, pro-ANP, irisin and myostatin were not modified or not detectable. The resistance exercise session increased the plasma concentration of lactate 3 min after exercise. Chronic exercise did not alter the plasma concentration of these exerkines. In sedentary young adults, acute endurance exercise releases to the bloodstream exerkines that regulate BAT metabolism and WAT browning. In contrast, neither a low-volume resistance exercise session nor a 24-week training programme modified plasma levels of these molecules.Metabolic health: pathophysiological trajectories and therap