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.

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.

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.

Relationships between diet and basal fat oxidation and maximal fat oxidation during exercise in sedentary adults.

BACKGROUND AND AIMS: To study the relationships between different dietary factors (i.e., energy, macronutrient and fatty acid intake, food group consumption, and dietary pattern) and basal fat oxidation (BFox) and maximal fat oxidation during exercise (MFO) in sedentary adults. METHOD AND RESULTS: A total of 212 (n = 130 women; 32.4 ± 15.1 years) sedentary healthy adults took part in the present study. Information on the different dietary factors examined was gathered through a food frequency questionnaire and three nonconsecutive 24 h recalls. Energy and macronutrient intakes and food consumption were then estimated and dietary patterns calculated. BFox and MFO were measured by indirect calorimetry following standard procedures. Our study shows that dietary fiber intake was positively associated with BFox after taking into consideration the age, sex, and energy intake. A significant positive association between nut consumption and BFox was observed, which became nonsignificant after taking into consideration the age and energy intake. Fat intake and the dietary quality index (DQI), and the DQI for the Mediterranean diet were positively associated with MFO, which was attenuated after taking sex, age, and energy intake into consideration. CONCLUSION: A higher dietary fiber intake and fat intake are associated with higher BFox and MFO, respectively, in sedentary adults. CLINICAL TRIALS: ClinicalTrials.gov, ID: NCT02365129 (https://clinicaltrials.gov/ct2/show/study/NCT02365129) & ID: NCT03334357 (https://clinicaltrials.gov/ct2/show/NCT03334357).

The effects of three types of exercise training on steroid hormones in physically inactive middle-aged adults: a randomized controlled trial.

PURPOSE: Physical inactivity and ageing are associated with imbalances in anabolic/catabolic steroid hormones, jeopardizing health. We investigated the effects of three types of training on plasma steroid hormone levels in physically inactive, middle-aged adults. METHODS: A 12-week randomized controlled trial was performed with a parallel-group design. A total of 67 (36 women) middle-aged adults (45-65 years old) were randomly assigned to (1) no exercise (control), (2) concurrent training based on the international physical activity recommendations (PAR), (3) high-intensity interval training (HIIT), or (4) HIIT plus whole-body electromyostimulation (HIIT + EMS). The training volume in the PAR group was 150 min/week at 60-65% of the heart rate reserve for aerobic training and ~ 60 min/week at 40-50% of the one-repetition maximum for resistance training. The training volume in the HIIT and HIIT + EMS groups was 40-65 min/week at > 95% of the maximum oxygen uptake in long interval sessions, and > 120% of the maximum oxygen uptake in short interval sessions. RESULTS: Compared to the control group, dehydroepiandrosterone sulfate increased in the PAR, HIIT, and HIIT + EMS groups (~ 14%, ~ 14%, and ~ 20%, respectively; all P < 0.01). Cortisol decreased in the PAR, HIIT, and HIIT + EMS groups (~ - 17%, ~ - 10%, and ~ - 23%, respectively; all P ≤ 0.05). Testosterone increased in the HIIT and HIIT + EMS groups (~ 28%, and ~ 16%, respectively; all P ≤ 0.01). Free testosterone increased in the HIIT and HIIT + EMS groups (~ 30% and ~ 18% respectively; all P ≤ 0.01). No significant increase in sex hormone-binding globulin was observed (P = 0.869). CONCLUSION: Our findings suggest that HIIT, with or without whole-body EMS, can significantly enhance steroid hormones status in previously physically inactive middle-aged adults. The PAR program led to slight improvements than the HIIT and HIIT + EMS groups despite the application of a higher training volume. CLINICAL TRIAL REGISTRY: NCT03334357 (ClinicalTrials.gov). November 7, 2017 retrospectively registered.

Exercise training improves sleep quality: A randomized controlled trial.

BACKGROUND: Exercise holds promise as a non-pharmacological intervention for the improvement of sleep quality. Therefore, this study investigates the effects of different training modalities on sleep quality parameters. MATERIAL & METHODS: A total of 69 (52.7% women) middle-aged sedentary adults were randomized to (a) control group, (b) physical activity recommendation from the World Health Organization, (c) high-intensity interval training (HIIT) and (d) high-intensity interval training group adding whole-body electromyostimulation training (HIITEMS). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) scale and accelerometers. RESULTS: All intervention groups showed a lower PSQI global score (all P < .022). HIIT-EMS group improved all accelerometer parameters, with higher total sleep time and sleep efficiency, and lower wake after sleep onset (all P < .016). No differences were found between groups in any sleep quality parameter. CONCLUSION: In conclusion, exercise training induced an improvement in subjective sleep quality in sedentary middleaged adults. Moreover, HIIT-EMS training showed an improvement in objective sleep quality parameters (total sleep time, sleep efficiency and wake after sleep onset) after 12 weeks of exercise intervention. The changes observed in the HIIT-EMS group were not statistically different to the other exercise modalities.

Dietary differences between metabolically healthy overweight-obese and metabolically unhealthy overweight-obese adults.

The aim of the study is to determine the differences in dietary parameters (energy and nutrient intake, adherence to the Mediterranean diet and consumption of food groups) in metabolically healthy overweight-obese (MHOO) v. metabolically unhealthy overweight-obese (MUOO) middle-aged adults. A total of fifty-one middle-aged adults were classified as MHOO or MUOO. BMI and blood pressure were evaluated following the recommendations. HDL, TAG and blood glycaemia were measured in blood samples. Blood pressure was also assessed. Dietary factors were assessed through three 24-h recalls, a validated FFQ and the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire. All variables were evaluated between September and October 2016 and 2017. Our results showed that MHOO individuals registered a higher fish consumption (P = 0·035) and higher compliance (lower consumption) in the commercial sweets and confectionery item of the PREDIMED questionnaire (P = 0·036). No differences were noted in other dietary factors including energy and nutrient intake, consumption of other food groups and in the PREDIMED total score. A near-significant trend toward significance was observed in nuts consumption, wine and fish items of the PREDIMED questionnaire. In conclusion, higher fish consumption and a higher compliance in the commercial sweets and confectionery item of the PREDIMED questionnaire were observed in MHOO middle-aged adults.

Effects of different exercise training programs on body composition: A randomized control trial.

We aimed to investigate the effects of different exercise training programs on body composition parameters in sedentary middle-aged adults. A total of 89 middle-aged adults (53.5 ± 4.9 years old; ~53% women) participated in the FIT-AGEING study. A 12-week randomized controlled trial was performed with a parallel group design. The participants were randomly assigned to (a) a concurrent training based on physical activity recommendation from the World Health Organization group (PAR group), (b) a high-intensity interval training group (HIIT group), and (c) a high-intensity interval training group adding whole-body electromyostimulation group (WB-EMS group). A significant decrease of fat body mass, fat body mass index, and visceral adipose tissue was observed in all training modalities compared to the control group (all P ≤ 0.001). There was a significant increase in lean body mass in the HIIT group as well as in the WB-EMS group compared to the control group and the PAR group (all P ≤ 0.044), whereas an increment of lean body mass index was only observed in the WB-EMS group compared to the control group and the PAR group (all P ≤ 0.042). A significant increase of bone mineral content was observed in the WB-EMS group compared to the control group (P = 0.015), while no changes were found in the PAR group and in the HIIT group compared to the control group (all P ≥ 0.2). Our findings suggest that PAR, HIIT, and WB-EMS can be used as a strategy to improve body composition parameters, obtaining slightly better results with the application of WB-EMS.

Assessment of maximal fat oxidation during exercise: A systematic review.

Maximal fat oxidation during exercise (MFO) and the exercise intensity eliciting MFO (Fatmax ) are considered biological markers of metabolic health and performance. A wide range of studies have been performed to increase our knowledge about their regulation by exercise and/or nutritional intervention. However, numerous data collection and analysis approaches have been applied, which may have affected the MFO and Fatmax estimation. We aimed to systematically review the available studies describing and/or comparing different data collection and analysis approach factors that could affect MFO and Fatmax estimation in healthy individuals and patients. Two independent researchers performed the search. We included all original studies in which MFO and/or Fatmax were estimated by indirect calorimetry through an incremental graded exercise protocol published from 2002 to 2019. This systematic review provides key information about the factors that could affect MFO and Fatmax estimation: ergometer type, metabolic cart used, warm-up duration and intensity, stage duration and intensities imposed in the graded exercise protocol, time interval selected for data analysis, stoichiometric equation selected to estimate fat oxidation, data analysis approach, time of the day when the test was performed, fasting time/previous meal before the test, and testing days for MFO/Fatmax and maximal oxygen uptake assessment. We suggest that researchers measuring MFO and Fatmax should take into account these key methodological issues that can considerably affect the accuracy, validity, and reliability of the measurement. Likewise, when comparing different studies, it is important to check whether the above-mentioned key methodological issues are similar in such studies to avoid ambiguous and unacceptable comparisons.

Association between Sleep Quality and Body Composition in Sedentary Middle-Aged Adults.

Background: Ageing is associated with sleep pattern changes and body composition changes, which are related to several diseases. Purpose: This study aimed to analyse the association between sleep quality and an extensive set of body composition parameters (waist-hip ratio, body mass index, bone mineral content, bone mineral density, lean mass, lean mass index, fat mass, fat mass percentage, fat mass index, visceral adipose tissue) and sleep quality in sedentary middle-aged adults. We also aimed to evaluate whether the possible associations accord between subjective and objective measurements of sleep quality. Methods: 74 (39 women) middle-aged sedentary adults (40⁻65 years old) participated in the present study. The sleep quality was assessed using the Pittsburgh sleep quality index (PSQI) scale and accelerometers. A PSQI global score more than 5 indicates poor sleep quality. Weight, height, waist and hip circumferences were measured, and body mass index and waist-hip ratio were also calculated. Body composition was assessed with a dual-energy X-ray absorptiometry scanner. Results: The PSQI global score was negatively associated with bone mineral content, bone mineral density, lean mass, lean mass index and positively associated with fat mass percentage. No association was found between accelerometer parameters and body composition variables. Conclusion: We showed that a subjective poor sleep quality was negatively associated with bone mineral content (BMC), bone mineral density (BMD), lean mass and lean mass index (LMI) whereas was positively associated with fat mass percentage in middle-aged adults. We also observed that these associations did not accord with objective sleep quality measurements.

Effect of a multimodal intervention in breast Cancer patients undergoing neoadjuvant therapy: A study protocol of the multimodal project.

BACKGROUND AND AIMS: To determine the effect of a multimodal intervention (nutritional behavior change and physical exercise) on quality of life, chemotherapy response rate and tolerance, histopathological level of the tumor, body composition, and biochemical parameters, in patients diagnosed with breast cancer during neoadjuvant chemotherapy treatment, and to compare them with the control group. METHODS: Anticipated 80 patients diagnosed with breast cancer aged 18-70 years will be recruited for this randomized, unblinded clinical trial based on a nutritional behavior change and physical exercise in patients during the approximately 6 months in which the patient receives neoadjuvant treatment. Participants will be randomly allocated (1:1) to one of two groups (intervention or control). Primary and secondary outcomes will be assessed before the beginning and after the neoadjuvant treatment (before surgery). The primary outcome is quality of life, whereas secondary outcomes include chemotherapy response rate and tolerance, histopathological level of the tumor and body composition (i.e., visceral adipose tissue activity, bone, lean and fat masses). We will analyze blood parameters (i.e., biochemical, inflammatory, and tumor markers) as exploratory outcomes. CONCLUSION: This study will address the influence of a practical and viable multimodal intervention (i.e., nutritional behavior change and physical exercise) on breast cancer patients undergoing neoadjuvant chemotherapy. Given the practical viability of the intervention in real-world settings, our study holds promise for significant scientific and clinical implications.

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.

Investigating the Alcohol Effects on the Response to Strenuous Exercise Training: Protocol for a Multidisciplinary Intervention Study in Young Healthy Adults-The BEER-HIIT Study.

High-intensity interval training (HIIT) is a time-efficient strategy to improve fitness and performance. Whereas the multiple and negative effects of high intake of alcohol have been widely studied, the effect of moderate alcohol doses after exercise is not clear, and it is currently under debate. For that, a total of 80 young healthy adults are studied and allocated into 5 groups, each including 16 participants. Four groups follow a HIIT program, while the fifth group is a control non-training group. The training groups will be randomized according to the characteristics of the ingested beverage (alcohol beer, beer 0.0%, sparkling water, or ethanol). The effects of HIIT on several aspects of physical performance and mental health in young healthy adults are evaluated, also the concomitant effect of daily and moderate alcohol consumption. The novelty of this study lies in the continuous measurement of the psychological parameters associated with carrying out a highly demanding training program in conjunction with alcohol consumption in moderate quantities, reflecting real-life conditions.

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.

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.

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.

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.