Cold-induced changes in plasma signaling lipids are associated with a healthier cardiometabolic profile independently of brown adipose tissue.

Cold exposure activates brown adipose tissue (BAT) and potentially improves cardiometabolic health through the secretion of signaling lipids by BAT. Here, we show that 2 h of cold exposure in young adults increases the levels of omega-6 and omega-3 oxylipins, the endocannabinoids (eCBs) anandamide and docosahexaenoylethanolamine, and lysophospholipids containing polyunsaturated fatty acids. Contrarily, it decreases the levels of the eCBs 1-LG and 2-LG and 1-OG and 2-OG, lysophosphatidic acids, and lysophosphatidylethanolamines. Participants overweight or obese show smaller increases in omega-6 and omega-3 oxylipins levels compared to normal weight. We observe that only a small proportion (∼4% on average) of the cold-induced changes in the plasma signaling lipids are slightly correlated with BAT volume. However, cold-induced changes in omega-6 and omega-3 oxylipins are negatively correlated with adiposity, glucose homeostasis, lipid profile, and liver parameters. Lastly, a 24-week exercise-based randomized controlled trial does not modify plasma signaling lipid response to cold exposure.

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

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

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.

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.

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.

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.

Endometrial whole metabolome profile at the receptive phase: influence of Mediterranean Diet and infertility.

Introduction: Several metabolite classes have been identified in human endometrium, including lipids, nucleotides, amino acids, organic acids, and sugars. The first studies suggest the importance of metabolites in endometrial functions, as imbalance in uterine metabolites has been associated with low implantation rate and endometriosis. Nevertheless, most of studies have put emphasis on specific metabolite classes, and we lack the knowledge of the whole metabolome composition in human uterus. Further, a healthy dietary pattern has been shown to potentially protect against different endometrial dysfunctions and is a potential modulator of metabolomic composition and, consequently, the intrauterine microenvironment. The Mediterranean Diet (MD), characterized by a high intake of fruits, vegetables, cereals, nuts, legumes, fish, and olive oil, and a low consumption of meat, dairy products, and processed foods, has been associated with a wide range of benefits for health. Indeed, the MD pattern has displayed a beneficial role in endometriosis management and fertility; however, the relationship between the MD and the endometrial metabolome is still unknown. In our study, we set out to analyze receptive-phase endometrial metabolome profiles among women with infertility and their associations with MD. Methods: The study included women with male factor infertility (n=8), unexplained infertility (n=10), recurrent implantation failure (n=14), and endometriosis (n=13). The endometrial metabolome was analyzed with ultrahigh-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS). The MD adherence of the participants was assessed using the 14-point MEDAS questionnaire of adherence to the MD. Results: We provide the whole metabolome profile of the endometrium, where 925 different metabolites were identified. Among these metabolites, lipids comprised the largest part, where polyunsaturated fatty acids (PUFAs) prevailed. Women with endometriosis and recurrent implantation failure were found to have lower levels of PUFAs compared to women with male factor and unexplained infertility (i.e., no clear endometrial alterations), identifying a metabolome profile associated with infertility diagnoses where altered endometrial functions are suspected. Moreover, MD adherence seemed to be associated with the endometrial metabolomic profile in a manner dependent on the health status of the uterus. Conclusion: The study findings provide insight into the molecular background of female infertility and lead to identification of potential molecular biomarkers and possibilities for modulating the endometrial microenvironment and, thereby, endometrial functions involved in embryo implantation and infertility.

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.

Reproducibility of the energy metabolism response to an oral glucose tolerance test: influence of a postcalorimetric correction procedure.

PURPOSE: Metabolic flexibility (MetF), which is a surrogate of metabolic health, can be assessed by the change in the respiratory exchange ratio (RER) in response to an oral glucose tolerance test (OGTT). We aimed to determine the day-to-day reproducibility of the energy expenditure (EE) and RER response to an OGTT, and whether a simulation-based postcalorimetric correction of metabolic cart readouts improves day-to-day reproducibility. METHODS: The EE was assessed (12 young adults, 6 women, 27 ± 2 years old) using an Omnical metabolic cart (Maastricht Instruments, Maastricht, The Netherlands) after an overnight fast (12 h) and after a 75-g oral glucose dose on 2 separate days (48 h). On both days, we assessed EE in 7 periods (one 30-min baseline and six 15-min postprandial). The ICcE was performed immediately after each recording period, and capillary glucose concentration (using a digital glucometer) was determined. RESULTS: We observed a high day-to-day reproducibility for the assessed RER (coefficients of variation [CV] < 4%) and EE (CVs < 9%) in the 7 different periods. In contrast, the RER and EE areas under the curve showed a low day-to-day reproducibility (CV = 22% and 56%, respectively). Contrary to our expectations, the postcalorimetric correction procedure did not influence the day-to-day reproducibility of the energy metabolism response, possibly because the Omnical's accuracy was ~ 100%. CONCLUSION: Our study demonstrates that the energy metabolism response to an OGTT is poorly reproducible (CVs > 20%) even using a very accurate metabolic cart. Furthermore, the postcalorimetric correction procedure did not influence the day-to-day reproducibility. Trial registration NCT04320433; March 25, 2020.

Caffeine ingestion attenuates diurnal variation of lower-body ballistic performance in resistance-trained women.

ABSTRACTThe present study investigates the effect of an acute intake of caffeine on the diurnal variation of neuromuscular performance in resistance-trained women. A total of 15 resistance-trained women participated in the current triple-blind, placebo-controlled, crossover experimental study. We assessed neuromuscular performance (i.e. ballistic (countermovement jump [CMJ] height and bench press throw [BPT] peak velocity), maximal strength (squat and bench press [BP] one-repetition maximum [1RM]), and strength-endurance [average velocity of the set during squat and number of repetitions-to-failure in BP]) four times at within 7 days. The participants ingested an acute dose of caffeine (3 mg/kg) or a placebo at 9-11 am and/or 17-19 pm. CMJ height (P = .016) and BP peak velocity (P = .012) were higher in the afternoon than in the morning. Compared to placebo, caffeine intake increased CMJ height by 3.1% in the morning and 1.6% in the afternoon (P = .035), but it had no effect on BPT peak velocity (P = .381). Maximal strength and strength-endurance performances were not affected by the time-of-day or caffeine intake (all P > .3). No significant interaction (time-of-day x substance) was observed in any of the above-mentioned outcomes (all P > .1). In conclusion, an acute dose of caffeine in the morning was effective to restore CMJ performance to levels found in the afternoon, while this effect was not observed neither in BPTpeak velocity nor in lower- and upper-body maximal strength and strength-endurance performance. Moreover, lower- and upper-body ballistic performance were greater in the afternoon than in the morning in resistance-trained women, while the acute intake of caffeine was only effective to increase CMJ height.HighlightsBallistic performance is probably higher in the afternoon than in the morning in resistance-trained women.An acute intake of caffeine is effective to increase countermovement jump performance.The ingestion of an acute dose of caffeine in the morning restored countermovement jump performance to levels found in the afternoon.

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.

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 nutritional intervention for moderate altitude endurance preparation: A case report.

Background: Moderate altitudes carry physiological and metabolic changes that can dampen exercise performance. Fortunately, these changes can be modulated by an optimal nutritional intervention. This case study represents the first nutritional intervention of a moderate altitude athlete. These results may help to establish well-designed nutritional guidelines for moderate altitude sports athletes. Case presentation: This case study examined the effects of a 11-week nutritional intervention on body composition, muscle strength, cardiorespiratory fitness, resting and exercise nutrient oxidation, and subjective sleep quality, in a male high-level moderate altitude athlete with a very light non-exercise activity thermogenesis. During the 11-week of nutritional intervention, 2800-3500 kcal/day, 6.8-8.9 g/kg/day of carbohydrates, 1.2-1.7 g/kg/day of protein, and 1-2.5 g/kg/day of fat were prescribed. Different specific considerations were also included, such as: iron supplementation, antioxidants increment in different phases, and ergogenic aids (i.e. creatine and beta-alanine). Our results demonstrated a decrease in adiposity and an increase in fat-free mass. In parallel, the athlete improved muscle strength, and therefore endurance adaptations after a maximal effort test (i.e. enhancement of the heart rate recovery). After the intervention, the athlete not only increased the carbohydrate oxidation during exercise and resting conditions but also improved his subjective sleep quality. Conclusions: Our results suggest that a nutritional intervention based on the endurance nutritional recommendations and adapted to the altitude physiological peculiarities can induce body re-composition, improve physiological adaptations to effort, and upgrade the substrate oxidation in a moderate altitude high-level athletes.

Cold exposure induces dynamic changes in circulating triacylglycerol species, which is dependent on intracellular lipolysis: A randomized cross-over trial.

BACKGROUND: The application of cold exposure has emerged as an approach to enhance whole-body lipid catabolism. The global effect of cold exposure on the lipidome in humans has been reported with mixed results depending on intensity and duration of cold. METHODS: This secondary study was based on data from a previous randomized cross-over trial (ClinicalTrials.gov ID: NCT03012113). We performed sequential lipidomic profiling in serum during 120 min cold exposure of human volunteers. Next, the intracellular lipolysis was blocked in mice (eighteen 10-week-old male wild-type mice C57BL/6J) using a small-molecule inhibitor of adipose triglyceride lipase (ATGL; Atglistatin), and mice were exposed to cold for a similar duration. The quantitative lipidomic profiling was assessed in-depth using the Lipidyzer platform. FINDINGS: In humans, cold exposure gradually increased circulating free fatty acids reaching a maximum at 60 min, and transiently decreased total triacylglycerols (TAGs) only at 30 min. A broad range of TAG species was initially decreased, in particular unsaturated and polyunsaturated TAG species with ≤5 double bonds, while after 120 min a significant increase was observed for polyunsaturated TAG species with ≥6 double bonds in humans. The mechanistic study in mice revealed that the cold-induced increase in polyunsaturated TAGs was largely prevented by blocking adipose triglyceride lipase. INTERPRETATION: We interpret these findings as that cold exposure feeds thermogenic tissues with TAG-derived fatty acids for combustion, resulting in a decrease of circulating TAG species, followed by increased hepatic production of polyunsaturated TAG species induced by liberation of free fatty acids stemming from adipose tissue. FUNDING: This work was supported by the Netherlands CardioVascular Research Initiative: 'the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences' [CVON2017-20 GENIUS-II] to Patrick C.N. Rensen. Borja Martinez-Tellez is supported by individual postdoctoral grant from the Fundación Alfonso Martin Escudero and by a Maria Zambrano fellowship by the Ministerio de Universidades y la Unión Europea - NextGenerationEU (RR_C_2021_04). Lucas Jurado-Fasoli was supported by an individual pre-doctoral grant from the Spanish Ministry of Education (FPU19/01609) and with an Albert Renold Travel Fellowship from the European Foundation for the Study of Diabetes (EFSD). Martin Giera was partially supported by NWO XOmics project #184.034.019.

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.

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.

Breakfast consumption and its relationship with diet quality and adherence to Mediterranean diet in European adolescents: the HELENA study.

OBJECTIVE: The aim of the current study is to analyze the associations between breakfast consumption and adherence to diet quality index (DQI) and Mediterranean Diet Score (MDS) in European adolescents. METHODS: A multinational cross-sectional study was carried out in 1804 adolescents aged 12.5-17.5 years. The Food Choices and Preferences questionnaire was used to ascertain breakfast consumption (consumers, occasional consumers and skippers), and two non-consecutive 24 h dietary recalls were used to estimate the total daily intake and to calculate the subsequent DQI and MDS. Mixed linear regression models were used to examine the relationship between breakfast consumption and DQI-A and MDS. Age, maternal education, BMI, country and total energy intake were included as covariates. RESULTS: In both sexes, significant differences were observed among the breakfast consumption categories. In both boys and girls, breakfast consumers had significantly higher DQI indices than those adolescents who skipped breakfast regularly (p < 0.001). Regarding total MDS, in both boys and girls, breakfast consumers had a higher total MDS than breakfast skippers (p < 0.001), however, no associations were shown between occasional breakfast consumers and DQI indices and MDS. CONCLUSION: Breakfast consumption has been linked with better dietary quality scores compared with those children who usually skip breakfast. Promotion of regular breakfast consumption in adolescents could be an effective strategy to improve the overall diet quality.

Effect of a Weight Loss and Lifestyle Intervention on Dietary Behavior in Men with Obstructive Sleep Apnea: The INTERAPNEA Trial.

This study investigated the effects of an eight-week interdisciplinary weight loss and lifestyle intervention on dietary behavior in men who were overweight/had obesity and moderate-to-severe obstructive sleep apnea (OSA). It was based on data from INTERAPNEA (ClinicalTrials.gov ID: NCT03851653); a randomized clinical trial conducted from April 2019 to April 2020. Men aged 18-65 years with moderate-to-severe OSA and a body mass index ≥25 kg/m2 were randomly assigned to a usual-care group or an eight-week interdisciplinary weight loss and lifestyle intervention combined with usual-care. Dietary behavior was assessed through the Food Behavior Checklist (FBC) and the Mediterranean Diet Adherence Screener (MEDAS). Of the 89 participants who underwent randomization, 75 completed the intervention endpoint assessment, 89 participants being therefore included in the intention-to-treat analyses, and 75 in the per-protocol approach. As compared with usual-care, the intervention group had greater improvements at intervention endpoint in dietary behavior, as measured by the FBC total score (20% increase in FBC total score, mean between-group difference, 8.7; 95% confidence interval, 5.7 to 11.7), and MEDAS total score (33% increase in MEDAS total score, mean between-group difference, 2.1; 95% CI 1.3 to 2.9). At 6 months after intervention, the intervention group also had greater improvements in both the FBC total score (15% increase) and MEDAS total score (25% increase), with mean between-group differences of 7.7 (CI 95%, 4.4 to 10.9) and 1.7 (CI 95%, 0.9 to 2.6), respectively. An eight-week interdisciplinary weight loss and lifestyle intervention resulted in meaningful and sustainable improvements in dietary behavior, including adherence to the Mediterranean diet in men who were overweight/ had obesity and CPAP-treated moderate-to-severe OSA.