Neurological-related proteomic profiling in plasma of children with metabolic healthy and unhealthy overweight/obesity.

OBJECTIVE: Children with overweight/obesity (OW/OB) exhibit poor cardiometabolic health, yet mechanisms influencing brain health remain unclear. We examined the differences in neurological-related circulating proteins in plasma among children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) and the association with metabolic syndrome markers. METHODS: In this cross-sectional study, we included 84 Caucasian children (39% girls), aged 10.1 ± 1.1 years, from the ActiveBrains project (NCT02295072). A ninety-two-protein targeted approach using Olink's® technology was used. RESULTS: We identified distinct concentrations of CD38, LAIR2, MANF and NRP2 proteins in MHO compared with MUO. Moreover, individual metabolic syndrome (MS) markers were linked to nine proteins (CD38, CPM, EDA2R, IL12, JAMB, KYNU, LAYN, MSR1 and SMOC2) in children with OW/OB. These proteins play crucial roles in diverse biological processes (e.g., angiogenesis, cholesterol transport, nicotinamide adenine dinucleotide (NAD+) catalysis and maintenance of blood-brain barrier) related to brain health. CONCLUSION: Our proteomics study suggests that cardiometabolic health (represented by MHO/MUO or individual MS markers) is associated with the concentration in plasma of several proteins involved in brain health. Larger-scale studies are needed to contrast/confirm these findings, with CD38 standing out as a particularly noteworthy and robust discovery.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

Multidisciplinary Prehabilitation and Postoperative Rehabilitation for Avoiding Complications in Patients Undergoing Resection of Colon Cancer: Rationale, Design, and Methodology of the ONCOFIT Study.

ONCOFIT is a randomized clinical trial with a two-arm parallel design aimed at determining the influence of a multidisciplinary Prehabilitation and Postoperative Program (PPP) on post-surgery complications in patients undergoing resection of colon cancer. This intervention will include supervised physical exercise, dietary behavior change, and psychological support comparing its influence to the standard care. Primary and secondary endpoints will be assessed at baseline, at preoperative conditions, at the end of the PPP intervention (after 12 weeks) and 1-year post-surgery, and will include: post-surgery complications (primary endpoint); prolonged hospital length of stay; readmissions and emergency department call within 1-year after surgery; functional capacity; patient reported outcome measures targeted; anthropometry and body composition; clinical/tumor parameters; physical activity levels and sedentariness; dietary habits; other unhealthy habits; sleep quality; and fecal microbiota diversity and composition. Considering the feasibility of the present intervention in a real-life scenario, ONCOFIT will contribute to the standardization of a cost-effective strategy for preventing and improving health-related consequences in patients undergoing resection of colon cancer with an important clinical and economic impact, not only in the scientific community, but also in clinical practice.

Acute and long-term exercise differently modulate plasma levels of oxylipins, endocannabinoids, and their analogues in young sedentary adults: A sub-study and secondary analyses from the ACTIBATE randomized controlled-trial.

BACKGROUND: Fatty acid-derived lipid mediators including oxylipins, endocannabinoids (eCBs), and their analogues, have emerged as key metabolites in the inflammatory and immune response to physiological stressors. METHODS: This report was based on a sub-study and secondary analyses the ACTIBATE single-center unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129). The study was performed in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada. Eligible participants were young, sedentary adults with no chronic diseases. Here, we performed both an acute endurance and resistance exercise sub-studies (n.ß=.ß14 and 17 respectively), and a 24-week supervised exercise intervention, combining endurance and resistance exercise training at moderate-intensity (MOD-EX) or vigorous-intensity (VIG-EX) exercise groups, in young sedentary adults. Randomization was performed by unrestricted randomization. Plasma levels of oxylipins, eCBs, and their analogues were measured using liquid chromatography-tandem mass spectrometry. FINDINGS: Both endurance and resistance exercise increased by.ß+50% the plasma levels of dihomo-..-linolenic acid and arachidonic acid (AA) omega-6 derived oxylipins, as well as eicosapentaenoic acid and docosahexaenoic acid omega-3 derived after 3 and 120.ßmin of the bout of exercise (all ..2.ß....ß0.219 and P.ß..±.ß0.039). These exercise modalities also increased the levels of anandamide and eCBs analogues (+25%). 145 young sedentary adults were assigned to a control (CON, n.ß=.ß54), a MOD-EX (n.ß=.ß48) or a VIG-EX (n.ß=.ß43). 102 participants were included in the final long-term analyses (CON, n.ß=.ß36; MOD-EX, n.ß=.ß33; and VIG-EX, n.ß=.ß33) of the trial. After 24-week of supervised exercise, MOD-EX decreased plasma levels of omega-6 oxylipins, concretely linoleic acid (LA) and adrenic acid derived oxylipins, and the eCBs analogues OEA and LEA in comparison to the CON (all P.ß..±.ß0.021). VIG-EX decreased LA-derived oxylipins and LEA compared to CON. No relevant adverse events were recorded. INTERPRETATION: Endurance and resistance exercises acutely increased plasma levels of oxylipins, eCBs, and their analogues, whereas 24 weeks of exercise training decreased fasting plasma levels of omega-6 oxylipins, and eCBs analogues in young, sedentary adults. FUNDING: See Acknowledgments section.

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.

Linoleic acid-derived oxylipins and isoprostanes plasma levels are influenced by 1,25-Dihydroxyvitamin D levels in middle-aged sedentary adults: The FIT-AGEING study.

INTRODUCTION: Vitamin D - concretely its active form 1,25-dihydroxyvitamin D (1,25(OH)2D) - maintains several physiological processes. Oxylipins are oxidized lipids derived from ω-6 and ω-3 polyunsaturated fatty acids involved in inflammation. Little is known about the association of 1,25(OH)2D with inflammatory parameters in middle-aged populations - who could be at risk of vitamin D deficiency -. The aim of this study was to investigate the relationship between 1,25(OH)2D plasma levels with circulating white blood cells, platelets counts and oxylipins levels. MATERIALS AND METHODS: A total of 74 (53 % women) middle-aged (40-65 years old) adults were recruited for this cross-sectional study. 1,25(OH)2D plasma levels were measured using an immunochemiluminometric assay. White blood cells and platelets were analyzed by hemocytometry. ω-6 and ω-3 oxylipins plasma levels were measured using liquid chromatography - tandem mass spectrometry. Simple and multiple linear regression models, and Pearson correlation analyses, were performed to study the association of 1,25(OH)2D levels with WBC and platelets counts, and oxylipins, respectively. RESULTS: 1,25(OH)2D plasma levels were positively related with linoleic acid-derived oxylipins and isoprostanes plasma levels, whereas an inverse relationship with dihomo-γ-linolenic acid/linoleic acid and arachidonic acid/linoleic acid ratios was unveiled. No significant associations were observed for circulating ω-3 oxylipins, white blood cells levels or platelets count. CONCLUSIONS: Linoleic acid-derived oxylipins and isoprostanes plasma levels may be influenced by 1,25(OH)2D plasma levels. Further investigations are needed to elucidate the impact of other vitamin D forms upon circulating oxylipins levels.

No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial.

Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n = 31, and VIG-EX; n = 31). We observed no changes in BAT volume (Δ Control: -22.2 ± 52.6 ml; Δ MOD-EX: -15.5 ± 62.1 ml, Δ VIG-EX: -6.8 ± 66.4 ml; P = 0.771) or 18F-fluorodeoxyglucose uptake (SUVpeak Δ Control: -2.6 ± 3.1 ml; Δ MOD-EX: -1.2 ± 4.8, Δ VIG-EX: -2.2 ± 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.