The relative abundance of fecal bacterial species belonging to the Firmicutes and Bacteroidetes phyla is related to plasma levels of bile acids in young adults.

BACKGROUND: Gut bacteria play a crucial role in the metabolism of bile acids (BA). Whether an association exists between the fecal microbiota composition and circulating BA levels in humans is poorly understood. Here, we investigated the relationship between fecal microbiota diversity and composition with plasma levels of BA in young adults. METHODS: Fecal microbiota diversity/composition was analyzed with 16S rRNA sequencing in 80 young adults (74% women; 21.9 ± 2.2 years old). Plasma levels of BA were measured using liquid chromatography-tandem mass spectrometry. PERMANOVA and Spearman correlation analyses were used to investigate the association between fecal microbiota parameters and plasma levels of BA. RESULTS: Fecal microbiota beta (P = 0.025) and alpha diversity indexes of evenness (rho = 0.237, P = 0.033), Shannon (rho = 0.313, P = 0.004), and inverse Simpson (rho = 0.283, P = 0.010) were positively associated with plasma levels of the secondary BA glycolithocholic acid (GLCA). The relative abundance of genera belonging to the Firmicutes and Bacteroidetes phyla was positively correlated with plasma levels of GLCA (all rho ≥ 0.225, P ≤ 0.049). However, the relative abundance of species from Firmicutes and Bacteroidetes phyla were negatively correlated with plasma levels of primary and secondary BA (all rho ≤ - 0.220, P ≤ 0.045), except for the relative abundance of Bacteroides vulgatus, Alistipes onderdonkii, and Bacteroides xylanisolvens species (Bacteroidetes phylum) that were positively correlated with the plasma levels of GLCA. CONCLUSIONS: The relative abundance of specific fecal bacteria species is associated with plasma levels of BA in young adults. However, further investigations are required to validate whether the composition of the gut microbiota can regulate the plasma concentrations of BA in humans.

A bout of endurance and resistance exercise transiently decreases plasma levels of bile acids in young, sedentary adults.

Circulating bile acids (BA) are signaling molecules that control glucose and lipid metabolism. However, the effects of acute exercise on plasma levels of BA in humans remain poorly understood. Here, we evaluate the effects of a bout of maximal endurance exercise (EE) and resistance exercise (RE) on plasma levels of BA in young, sedentary adults. Concentration of eight plasma BA was measured by liquid chromatography-tandem mass spectrometry before and 3, 30, 60, and 120 min after each exercise bout. Cardiorespiratory fitness (CRF) was assessed in 14 young adults (21.8 ± 2.5 yo, 12 women); muscle strength was assessed in 17 young adults (22.4 ± 2.5 yo, 11 women). EE transiently decreased plasma levels of total, primary, and secondary BA at 3 and 30 min after exercise. RE exerted a prolonged reduction in plasma levels of secondary BA (p < 0.001) that lasted until 120 min. Primary BA levels of cholic acid (CA) and chenodeoxycholic acid (CDCA) were different across individuals with low/high CRF levels after EE (p ≤ 0.044); CA levels were different across individuals with low/high handgrip strength levels. High CRF individuals presented higher levels of CA and CDCA 120 min after exercise vs baseline (+77% and +65%) vs the low CRF group (-5% and -39%). High handgrip strength levels individuals presented higher levels of CA 120 min after exercise versus baseline (+63%) versus the low handgrip strength group (+6%). The study findings indicate that an individual's level of physical fitness can influence how circulating BA respond to both endurance and resistance exercise. Additionally, the study suggests that changes in plasma BA levels after exercising could be related to the control of glucose homeostasis in humans.

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) high-intensity 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 HIIT-EMS groups showed decreased plasma levels of omega-6 and omega-3-derived oxylipins, and eCBs and eCBs-like molecules after 12 weeks (all Δ ≤ -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: Δ = 0.05 vs. -0.09; oleoylethanolamide: Δ = -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.

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 inflammatory 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 fitness 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%), triglycerides (+ 63.9%), C-reactive protein (+ 124.2%), diastolic blood pressure (+ 5.5%), and pro-inflammatory 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 specific pro-inflammatory omega-6 signature pattern and higher VAT levels, and seem to reflect the cardiovascular status of young adults.

Endocrine Mechanisms Connecting Exercise to Brown Adipose Tissue Metabolism: a Human Perspective.

PURPOSE OF REVIEW: To summarize the state-of-the-art regarding the exercise-regulated endocrine signals that might modulate brown adipose tissue (BAT) activity and/or white adipose tissue (WAT) browning, or through which BAT communicates with other tissues, in humans. RECENT FINDINGS: Exercise induces WAT browning in rodents by means of a variety of physiological mechanism. However, whether exercise induces WAT browning in humans is still unknown. Nonetheless, a number of protein hormones and metabolites, whose signaling can influence thermogenic adipocyte's metabolism, are secreted during and/or after exercise in humans from a variety of tissues and organs, such as the skeletal muscle, the adipose tissue, the liver, the adrenal glands, or the cardiac muscle. Overall, it seems plausible to hypothesize that, in humans, exercise secretes an endocrine cocktail that is likely to induce WAT browning, as it does in rodents. However, even if exercise elicits a pro-browning endocrine response, this might result in a negligible effect if blood flow is restricted in thermogenic adipocyte-rich areas during exercise, which is still to be determined. Future studies are needed to fully characterize the exercise-induced secretion (i.e., to determine the effect of the different exercise frequency, intensity, type, time, and volume) of endocrine signaling molecules that might modulate BAT activity and/or WAT browning or through which BAT communicates with other tissues, during exercise. The exercise effect on BAT metabolism and/or WAT browning could be one of the still unknown mechanisms by which exercise exerts beneficial health effects, and it might be pharmacologically mimicked.

Evidence of high 18 F-fluorodeoxyglucose uptake in the subcutaneous adipose tissue of the dorsocervical area in young adults.

NEW FINDINGS: What is the central question of this study? In some studies, biopsies have been performed of the subcutaneous adipose tissue in the abdomen, and they failed to find browning markers. Is the abdomen the right place to take biopsies? What is the main finding and its importance? For first time, we observed that the glucose uptake in the dorsocervical subcutaneous adipose tissue is higher in comparison to other areas of subcutaneous adipose tissue. ABSTRACT: Neonates have subcutaneous brown adipose tissue (BAT) in the dorsocervical area, and it is thought that these depots gradually disappear with age. Here, we determined that young adults have high 18 F-flurodeoxyglucose (18 F-FDG) uptake in the subcutaneous adipose tissue (SAT) of the dorsocervical area. A total of 133 young adults (age 22 ± 2 years; body mass index 25 ± 5 kg m2 ) were included in the study. We performed a shivering threshold test for every participant. Later, we performed 2 h of personalized cold exposure, immediately before a positron emission tomography/computed tomography scan. We showed that 23 of 133 participants had 18 F-FDG uptake in the dorsocervical area that achieved the criteria to be considered BAT, mainly in women (96%, n = 22 of 23). In the whole sample, the glucose uptake in the SAT of the dorsocervical area was positively correlated with BAT volume and activity located in the supraclavicular area. We showed that the 18 F-FDG uptake of the SAT of the dorsocervical area in humans is different from that of other SAT areas. Future studies are warranted to confirm the brown signature of this tissue.

Higher Plasma Levels of Endocannabinoids and Analogues Correlate With a Worse Cardiometabolic Profile in Young Adults.

CONTEXT: The endocannabinoid system (ECS) is a signaling system composed of endocannabinoids (eCBs), their receptors, and the enzymes involved in their synthesis and metabolism. Alterations in the ECS are linked to the development of cardiometabolic diseases. OBJECTIVE: Here, we investigated the relationship between plasma levels of eCBs and their analogues with body composition and cardiometabolic risk factors. METHODS: The study included 133 young adults (age 22.1 ± 2.2 years, 67% women). Fasting plasma levels of eCBs and their analogues were measured using liquid chromatography-tandem mass spectrometry. Body composition, brown adipose tissue (BAT) volume, glucose uptake, and traditional cardiometabolic risk factors were measured. RESULTS: Plasma levels of eCBs and several eCB analogues were positively correlated with adiposity and traditional cardiometabolic risk factors (eg, serum insulin and triacylglyceride levels, all r ≥ 0.17 and P ≤ .045). Plasma levels of 2-arachidonoyl glycerol and N-pentadecenoylethanolamine were negatively correlated with BAT volume and glucose uptake (all r ≤ -0.17 and P ≤ .047). We observed that the plasma levels of eCBs and their analogues were higher in metabolically unhealthy overweight-obese participants than in metabolically healthy overweight-obese participants. CONCLUSION: Our findings show that the plasma levels of eCBs and their analogues are related to higher levels of adiposity and worse cardiometabolic profile.

Cold exposure modulates potential brown adipokines in humans, but only FGF21 is associated with brown adipose tissue volume.

OBJECTIVE: The study objective was to investigate the effect of cold exposure on the plasma levels of five potential human brown adipokines (chemokine ligand 14 [CXCL14], growth differentiation factor 15 [GDF15], fibroblast growth factor 21 [FGF21], interleukin 6 [IL6], and bone morphogenic protein 8b [BMP8b]) and to study whether such cold-induced effects are related to brown adipose tissue (BAT) volume, activity, or radiodensity in young humans. METHODS: Plasma levels of brown adipokines were measured before and 1 h and 2 h after starting an individualized cold exposure in 30 young adults (60% women, 21.9 ± 2.3 y; 24.9 ± 5.1 kg/m2 ). BAT volume, 18 F-fluorodeoxyglucose uptake, and radiodensity were assessed by a static positron emission tomography-computerized tomography scan after cold exposure. RESULTS: Cold exposure increased the concentration of CXCL14 (Δ2h = 0.58 ± 0.98 ng/mL; p = 0.007), GDF15 (Δ2h = 19.63 ± 46.2 pg/mL; p = 0.013), FGF21 (Δ2h = 33.72 ± 55.13 pg/mL; p = 0.003), and IL6 (Δ1h = 1.98 ± 3.56 pg/mL; p = 0.048) and reduced BMP8b (Δ2h = -37.12 ± 83.53 pg/mL; p = 0.022). The cold-induced increase in plasma FGF21 was positively associated with BAT volume (Δ2h: ß = 0.456; R2 = 0.307; p = 0.001), but not with 18 F-fluorodeoxyglucose uptake or radiodensity. None of the changes in the other studied brown adipokines was related to BAT volume, activity, or radiodensity. CONCLUSIONS: Cold exposure modulates plasma levels of several potential brown adipokines in humans, whereas only cold-induced changes in FGF21 levels are associated with BAT volume. These findings suggest that human BAT might contribute to the circulatory pool of FGF21.

The role of sex in the relationship between fasting adipokines levels, maximal fat oxidation during exercise, and insulin resistance in young adults with excess adiposity.

AIM: Previous evidence suggest that a sexual dimorphism in exercise fat oxidation and adipokines levels may explain a lower risk of cardio-metabolic disorders in women. Therefore, we investigated the role of sex in the relationship between adipokines levels, maximal fat oxidation (MFO) during exercise and insulin resistance. METHODS: Fifty young adults with excess adiposity (31 women; body fat: 38.7 ± 5.3%) were included in this study. The fasting levels of leptin, adiponectin, glucose and insulin were determined from blood samples and the homeostatic model assessment of insulin resistance index (HOMA-IR) subsequently calculated. Body fat percentage and visceral adipose tissue (VAT) were assessed through dual-energy X-ray absorptiometry whereas MFO was estimated during an incremental-load exercise test after an overnight fasting through indirect calorimetry. RESULTS: Men had lower levels of body fat (d = 1.80), adiponectin (d = 1.35), leptin (d = 0.43) and MFO (d = 1.25) than women. Conversely, men showed higher VAT (d = 0.85) and fasting glucose levels (d = 0.89). No sex differences were observed in HOMA-IR (d = 0.34). Adipokines levels were not associated with MFO in both sexes (r < 0.30), whereas adiponectin levels were inversely related with HOMA-IR in both men (r = -0.58) and women (r = -0.50). Leptin concentration was associated to HOMA-IR only in men (r = 0.41), while no statistically significant relationships were observed between MFO and HOMA-IR in both sexes (r < 0.44). CONCLUSION: Insulin resistance was similar between sexes regardless of superior levels of adipokines and MFO during exercise in women. Therefore, adiponectin and leptin may regulate glucose homeostasis without altering whole body fat oxidation rate during exercise.

Intra-Assessment Resting Metabolic Rate Variability Is Associated with Cardiometabolic Risk Factors in Middle-Aged Adults.

The intra-assessment resting metabolic rate variability is related to cardiometabolic health, as suggested by previous literature. We studied whether that variability (expressed as coefficient of variation [CV; %]) for oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), and resting energy expenditure (REE) is similar between men and women, and if is similarly associated with cardiometabolic risk factors. Gas exchange in 72 middle-aged adults was measured by indirect calorimetry. Anthropometrics and body composition, cardiorespiratory fitness, circulating cardiometabolic risk factors, and heart rhythm parameters were also determined. Men and women presented similar intra-assessment resting metabolic rate variability (all p > 0.05). Notably, in men, CV for RER was positively associated with BMI and adiposity (both standardized ß = 0.35, Ps ≤ 0.048), while CVs for VO2, VCO2, and REE were negatively associated (standardized ß ranged from -0.37 to -0.46, all p ≤ 0.036) with cardiometabolic risk factors. In women, CVs for VCO2 and REE were negatively associated with adiposity (both standardized ß = -0.36, Ps ≤ 0.041) and cardiometabolic risk Z-score (standardized ß = -0.40 and -0.38, respectively, Ps ≤ 0.05). In conclusion, intra-assessment resting metabolic rate variability could be considered an indicator of cardiometabolic health in middle-aged adults.

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

ABSTRACTIn 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), ß-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.HighlightsAcute endurance exercise increases the plasma concentration of lactate, norepinephrine, brain-derived neurotrophic factor, interleukin 6, follistatin-like protein 1, musclin, and fibroblast growth factor 21, and decrease the plasma concentration of leptin.The exercise-induced change in lactate plasma concentration is positively associated with brown adipose tissue volume, glucose uptake and radiodensity.Neither acute resistance exercise nor chronic exercise significantly alter the plasma concentration of these exerkines.Trial registration: ClinicalTrials.gov identifier: NCT02365129.

A single dose of dihydrocapsiate does not improve neuromuscular performance in resistance-trained young adults: A randomised, triple-blinded, placebo-controlled, crossover trial.

Capsinoids may exert ergogenic effects on resistance exercises. However, the acute effects of capsinoids on neuromuscular performance in humans are unknown. Here, we aimed to investigate the acute effects of dihydrocapsiate on lower- and upper-body neuromuscular performance parameters in resistance-trained individuals. 25 young adults (n = 6 women; age = 26 ± 3 years; body mass index = 24.3 ± 2.8 kg/m2) with ≥ 1-year resistance training experience were included in this triple-blind (participants, intervention researchers, and data analysts were blinded), placebo-controlled, crossover study. Lower- and upper-body ballistic strength (countermovement jump [CMJ] height and bench press throw [BPT] peak velocity), maximum dynamic strength (estimated 1 repetition maximum in squat and bench press [BP]), and strength-endurance (mean set velocity [squat] and number of repetitions to failure [bench press]) were assessed in 2 independent sessions (≥7 days separation). Participants ingested 12 mg of dihydrocapsiate or placebo 30 min before each trial. We found no significant differences between dihydrocapsiate and placebo conditions in ballistic strength, (CMJ height 33.20 ± 8.07 vs 33.32 ± 7.85 cm; BPT peak velocity 2.82 ± 0.77 vs 2.82 ± 0.74 m/s) maximal dynamic strength (estimated squat 1RM: 123.76 ± 40.63 vs 122.66 ± 40.97 kg; estimated BP 1RM: 99.47 ± 43.09 vs 99.60 ± 43.34 kg), and strength-endurance (squat mean set velocity 0.66 ± 0.07 vs 0.66 ± 0.05 m/s; number BP repetitions to failure 13.00 ± 3.56 vs 13.00 ± 4.78) (all P ≥ 0.703). We conclude that dihydrocapsiate does not acutely improve neuromuscular performance in trained young adults.

Capsinoids ­ non-pungent analogs of capsaicin ­ have been recently proposed as potential ergogenic compounds in humans.However, the effects of a single dose of capsinoids on neuromuscular performance parameters in humans remains unknown.12 mg of dihydrocapsiate does not improve neuromuscular performance in resistance-trained young adults.Dihydrocapsiate should not be recommended as an ergogenic aid to acutely increase neuromuscular performance.

Gene-exercise interaction on brain health in children with overweight/obesity: the ActiveBrains randomized controlled trial.

We investigated the interaction between a genetic score and an exercise intervention on brain health in children with overweight/obesity. One hundred one children with overweight/obesity (10.0 ± 1.5 yr, 59% girls) were randomized into a 20-wk combined exercise intervention or a control group. Several cognitive and academic outcomes were measured with validated tests. Hippocampal volume was quantified using magnetic resonance imaging. Six brain health-related polymorphisms [rs6265 (BDNF), rs2253206 (CREB1), rs2289656 (NTRK2), rs4680 (COMT), rs429358, and rs7412 (APOE)] were genotyped. Cognitive flexibility and academic skills improved significantly more in the exercise than in the control group only in the children with a "favorable" genetic profile [mean z-score, 0.41-0.67 (95% CI 0.11 to 1.18)], yet not in those with "less favorable" genetic profile. An individual response analysis showed that children responded to exercise in cognitive flexibility only in the "genetically favorable" group [i.e., 62% of them had a meaningful (≥0.2 Cohen d) increase in the exercise group compared with only 25% in the control group]. This finding was consistent in per-protocol and intention-to-treat analyses (P = 0.01 and P = 0.03, respectively). The results were not significant or not consistent for the rest of outcomes studied. Our findings suggest that having a more favorable genetic profile makes children with overweight/obesity more responsive to exercise, particularly for cognitive flexibility.NEW & NOTEWORTHY Interindividual differences have been reported in brain health-related outcomes in response to exercise interventions in adults, which could be partially explained by genetic background differences. However, the role of genetic polymorphisms on brain health-related outcomes in response to exercise interventions remains unexplored in pediatric population. The current study in children with overweight/obesity showed that a genetic score composed of six brain health-related polymorphisms (BDNF, CREB1, NTRK2, COMT, and APOE) regulated the exercise-induced response on several brain health outcomes, yet mainly and more consistently on cognitive flexibility.

High omega-6/omega-3 fatty acid and oxylipin ratio in plasma is linked to an adverse cardiometabolic profile in middle-aged adults.

Omega-6 and omega-3 oxylipins may be surrogate markers of systemic inflammation, which is one of the triggers for the development of cardiometabolic disorders. In the current study, we investigated the relationship between plasma levels of omega-6 and omega-3 oxylipins with body composition and cardiometabolic risk factors in middle-aged adults. Seventy-two 72 middle-aged adults (39 women; 53.6±5.1 years old; 26.7±3.8 kg/m2) were included in this cross-sectional study. Plasma levels of omega-6 and omega-3 fatty acids and oxylipins were determined using targeted lipidomic. Body composition, dietary intake, and cardiometabolic risk factors were assessed with standard methods. The plasma levels of the omega-6 fatty acids and derived oxylipins, the hydroxyeicosatetraenoic acids (HETEs; arachidonic acid (AA)-derived oxylipins) and dihydroxy-eicosatrienoic acids (DiHETrEs; AA-derived oxylipins), were positively associated with glucose metabolism parameters (i.e., insulin levels and homeostatic model assessment of insulin resistance index (HOMA); all r≥0.21, P<.05). In contrast, plasma levels of omega-3 fatty acids and derived oxylipins, specifically hydroxyeicosapentaenoic acids (HEPEs; eicosapentaenoic acid-derived oxylipins), as well as series-3 prostaglandins, were negatively associated with plasma glucose metabolism parameters (i.e., insulin levels, HOMA; all r≤0.20, P<.05). The plasma levels of omega-6 fatty acids and derived oxylipins, HETEs and DiHETrEs were also positively correlated with liver function parameters (i.e., glutamic pyruvic transaminase, gamma-glutamyl transferase (GGT), and fatty liver index; all r≥0.22 and P<.05). In addition, individuals with higher omega-6/omega-3 fatty acid and oxylipin ratio showed higher levels of HOMA, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, and GGT (on average +36%), as well as lower levels of high-density lipoprotein cholesterol (-13%) (all P<.05). In conclusion, the omega-6/omega-3 fatty acid and oxylipin ratio, as well as specific omega-6 and omega-3 oxylipins plasma levels, reflect an adverse cardiometabolic profile in terms of higher insulin resistance and impaired liver function in middle-aged adults.

Effects of phenylcapsaicin on aerobic capacity and physiological parameters in active young males: a randomized, triple-blinded, placebo-controlled, crossover trial.

Objective: Phenylcapsaicin (PC) is a new capsaicin analog which has exhibited a higher bioavailability. This sudy assessed the effects of a low dose (LD) of 0.625 mg and a high dose (HD) of 2.5 mg of PC on aerobic capacity, substrate oxidation, energy metabolism and exercise physiological variables in young males. Materials and methods: Seventeen active males (age = 24.7 ± 6.0 years) enrolled to this randomized, triple-blinded, placebo-controlled, crossover trial. Participants attended the laboratory on 4 sessions separated by 72-96 h. A submaximal exercise test [to determine maximal fat oxidation (MFO) and the intensity at MFO (FATmax)] followed by a maximal incremental test (to determine VO2max) were performed in a preliminary session. The subsequent sessions only differed in the supplement ingested [LD, HD or placebo (PLA)] and consisted of a steady-state test (60 min at FATmax) followed by a maximal incremental test. Energy metabolism, substrate oxidation, heart rate, general (gRPE) and quadriceps (RPEquad) rate of perceived exertion, skin temperature and thermal perception were tested. Results: Clavicle thermal perception was lower in HD compared to PLA and LD (p = 0.04) across time. HD reduced maximum heart rate in comparison to PLA and LD (p = 0.03). LD reported higher general RPE (RPEg) values during the steady-state test compared to PLA and HD across time (p = 0.02). HD and LD elicited higher peak of fat oxidation during the steady-state test compared with PLA (p = 0.05). Intra-test analyses revealed significant differences for fat oxidation (FATox) in favor of HD and LD compared to PLA (p = 0.002 and 0.002, respectively), and for carbohydrate oxidation (CHOox) (p = 0.05) and respiratory exchange ratio (RER) (p = 0.03) for PLA. In the incremental test, only general RPE at 60% of the maximal intensity (W) differed favoring HD (p ≤ 0.05). Conclusion: Therefore, PC may contribute to increase aerobic capacity through the improvement of fat oxidation, maximum heart rate and perceptual responses during exercise.

Associations between Intra-Assessment Resting Metabolic Rate Variability and Health-Related Factors.

In humans, the variation in resting metabolic rate (RMR) might be associated with health-related factors, as suggested by previous studies. This study explored whether the intra-assessment RMR variability (expressed as a coefficient of variation (CV; %)) is similar in men and women and if it is similarly associated with diverse health-related factors. The RMR of 107 young, and relatively healthy adults, was assessed using indirect calorimetry. Then, the CV for volumes of oxygen consumption (VO2) and carbon dioxide production (VCO2), respiratory exchange ratio (RER), and resting energy expenditure (REE) were computed as indicators of intra-assessment RMR variability. Body composition, cardiorespiratory fitness (peak VO2 uptake), circulating cardiometabolic risk factors, and heart rate and its variability (HR and HRV) were assessed. Men presented higher CVs for VO2, VCO2, and REE (all p ≤ 0.001) compared to women. Furthermore, in men, the intra-assessment RER variability was associated with vagal-related HRV parameters and with mean HR (standardized ß = −0.36, −0.38, and 0.41, respectively; all p < 0.04). In contrast, no associations were observed in women. In conclusion, men exhibited higher variability (CVs for VO2, VCO2, and REE) compared to women. The CV for RER could be a potential marker of cardiometabolic risk in young men.

Plasma Levels of Bile Acids Are Related to Cardiometabolic Risk Factors in Young Adults.

CONTEXT: Bile acids (BA) are known for their role in intestinal lipid absorption and can also play a role as signaling molecules to control energy metabolism. Prior evidence suggests that alterations in circulating BA levels and in the pool of circulating BA are linked to an increased risk of obesity and a higher incidence of type 2 diabetes in middle-aged adults. OBJECTIVE: We aimed to investigate the association between plasma levels of BA with cardiometabolic risk factors in a cohort of well-phenotyped, relatively healthy young adults. METHODS: Body composition, brown adipose tissue, serum classical cardiometabolic risk factors, and a set of 8 plasma BA (including glyco-conjugated forms) in 136 young adults (age 22.1 ± 2.2 years, 67% women) were measured. RESULTS: Plasma levels of chenodeoxycholic acid (CDCA) and glycoursodeoxycholic acid (GUDCA) were higher in men than in women, although these differences disappeared after adjusting for body fat percentage. Furthermore, cholic acid (CA), CDCA, deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA) levels were positively, yet weakly associated, with lean body mass (LBM) levels, while GDCA and glycolithocholic acid (GLCA) levels were negatively associated with 18F-fluorodeoxyglucose uptake by brown adipose tissue. Interestingly, glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), and GUDCA were positively associated with glucose and insulin serum levels, HOMA index, low-density lipoprotein cholesterol, tumor necrosis factor alpha, interleukin (IL)-2, and IL-8 levels, but negatively associated with high-density lipoprotein cholesterol, ApoA1, and adiponectin levels, yet these significant correlations partially disappeared after the inclusion of LBM as a confounder. CONCLUSION: Our findings indicate that plasma levels of BA might be sex dependent and are associated with cardiometabolic and inflammatory risk factors in young and relatively healthy adults.

Plasma Levels of Omega-3 and Omega-6 Derived Oxylipins Are Associated with Fecal Microbiota Composition in Young Adults.

Pre-clinical studies suggest that circulating oxylipins, i.e., the oxidation products of polyunsaturated fatty acids (PUFAs), modulate gut microbiota composition in mice, but there is no information available in humans. Therefore, this study aimed to investigate the relationship between omega-3 and omega-6 derived oxylipins plasma levels and fecal microbiota composition in a cohort of young adults. 80 young adults (74% women; 21.9 ± 2.2 years old) were included in this cross-sectional study. Plasma levels of oxylipins were measured using liquid chromatography-tandem mass spectrometry. Fecal microbiota composition was analyzed by V3-V4 16S rRNA gene sequencing. We observed that plasma levels of omega-3 derived oxylipins were positively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho ≥ 0.415, p ≤ 0.009) and negatively associated with the relative abundance of Sutterella genus (Proteobacteria phylum; rho ≥ -0.270, p ≤ 0.041), respectively. Moreover, plasma levels of omega-6 derived oxylipins were negatively associated with the relative abundance of Acidaminococcus and Phascolarctobacterium genera (Firmicutes phylum; all rho ≥ -0.263, p ≤ 0.024), as well as Sutterella, Succinivibrio, and Gemmiger genera (Proteobacteria phylum; all rho ≥ -0.263, p ≤ 0.024). Lastly, the ratio between omega-6 and omega-3 oxylipins plasma levels was negatively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho = -0.334, p = 0.004) and Butyricimonas genus (Bacteroidetes phylum; rho = -0.292, p = 0.014). In conclusion, our results show that the plasma levels of omega-3 and omega-6 derived oxylipins are associated with the relative abundance of specific fecal bacteria genera.

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 18F-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). In men, BAT mean radiodensity was negatively related to the glucose and insulin concentrations, alanine aminotransferase activity, insulin resistance, total cholesterol/HDL-C, LDL-C/HDL-C, the CMR score, and the FLI (all P ≤ 0.02). In women, it was only negatively related to the FLI (P < 0.001). These associations were driven by the results for the overweight and obese subjects. No relationship was seen between BAT and inflammatory markers (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.