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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

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.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.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.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.

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., Netherlands CardioVascular Research Initiative: `the Dutch Heart Foundation, Dutch Federation of University Medical Centers, Netherlands Organization for Health Research and Development Royal Netherlands Academy of Sciences' CVON201720 GENIUS-II, Fundacion Alfonso Martin Escudero, Maria Zambrano - Ministerio de Universidades y la Union Europea -NextGenerationEU RR_C_2021_04, Spanish Government FPU19/01609, European Foundation for the Study of Diabetes (EFSD), NWO XOmics project 184.034.019

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 = -0.270, p = -0.263, p = -0.263, p, Spanish Ministry of Economy and Competitiveness via Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III PI13/01393 PTA 12264-I, Retos de la Sociedad DEP2016-79512-R, European Commission Spanish Government FPU16/05159 FPU16/02828 FPU17/01523 FPU19/01609, Fundacion Iberoamericana de Nutricion (FINUT), University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES), AstraZeneca, Junta de Andalucia Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGR, China Scholarship Council 201707060012, Fundacion Alfonso Martin Escudero, Ministerio de Universidades y la Union Europea -NextGenerationEU RR_C_2021_04, European Commission through the "European funds for regional development" (EFRE) regional Ministry of Economy, Science and Digitalization of Saxony-Anhalt as part of the Autonomy in old Age "(AiA) research group for "LiLife" Project ZS/2018/11/95324

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., Spanish Government, China Scholarship Council 201607060017 201707060012

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., Spanish Ministry of Economy and Competitiveness via Retos de la Sociedad grant DEP2016-79512-R, European Commission, Spanish Government FPU15/04059 FPU19/01609, University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health, Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades via the ERDF SOMM17/6107/UGR, Fundacion Alfonso Martin Escudero, Universidad de Granada/CBUA

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 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.

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. 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. Compared to the control group, dehydroepiandrosterone sulfate increased in the PAR, HIIT, and HIIT + EMS groups (~ 14%, ~ 14%, and ~ 20%, respectively; all P

The present work examines the relationships between maximal fat oxidation during a graded exercise test (MFO), the intensity of exercise that elicits MFO (Fatmax), and traditional cardiometabolic r...

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 moderateto- 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., Spanish Government FPU16/01093 FPU14/04172 FPU19/01609, University of Granada-LoMonaco S.L. Sleep Research Cathedra University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES), Regional Ministry of Economy, Knowledge, Enterprise, and Universities (CECEU) of Andalusia (European Regional Development Funds) SOMM17/6107/UGR

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.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.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%.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.

Hector Vazquez-Lorente (FPU18/03655) and Lucas Jurado-Fasoli (FPU19/01609) are under an FPU fellowship from the Spanish Ministry of Education. This study is part of a Ph.D. thesis conducted in the Biomedicine Doctoral Studies of the University of Granada, Spain. The APC was funded by San Cecilio University Hospital, FIBAO, IBS-Granada, Spain., alpha-Klotho protein is a powerful predictor of the aging process and lifespan. Although lowered circulating soluble alpha-Klotho levels have been observed in aged non-healthy individuals, no specific reference values across a wide range of ages and sex using an enzyme-linked immunosorbent assay (ELISA) are available for larger cohorts of healthy individuals. The present analytical cross-sectional study was aimed to establish the reference values of soluble alpha-Klotho serum levels in healthy adults by age and sex groups. A total of 346 (59% women) healthy individuals aged from 18 to 85 years were recruited. Subjects were divided by sex and age as: (i) young (18-34.9 years), (ii) middle-aged (35-54.9 years), and (iii) senior (55-85 years) individuals. The soluble alpha-Klotho levels were measured in serum using ELISA. Senior adults were the age-group that presented the lowest soluble alpha-Klotho serum levels (p < 0.01), with age showing a negative association with soluble alpha-Klotho serum levels (p < 0.001). No differences between sexes were observed. Therefore, soluble alpha-Klotho levels were especially decreased-regardless of sex-in our cohort of healthy individuals because of the physiological decline derived from the aging process. We recommend routine assessments of soluble alpha-Klotho levels using ELISA as a simple and cheap detectable marker of aging that improves quality of life in the elderly., Spanish Government FPU18/03655 FPU19/01609, San Cecilio University Hospital, FIBAO, IBS-Granada, Spain

The ageing process can be influenced by energy intake and different macronutrients within the diet. The soluble form of the α-Klotho gene (called S-Klotho) is widely considered as a powerful anti-ageing biomarker.To analyze the association of energy, dietary energy density and macronutrient intake with S-Klotho plasma levels in middle-aged sedentary adults.A total of 72 (52.8% women) middle-aged sedentary adults (53.7 ± 5.2 years old) participated in the study. Energy and macronutrients intake (i.e. fat, carbohydrate and protein) were assessed using three non-consecutive 24-h recalls. S-Klotho plasma levels were measured in the Ethylenediaminetetraacetic acid (EDTA) plasma using a solid-phase sandwich enzyme-linked immunosorbent assay.No association was observed between energy, dietary energy density or macronutrient intake and S-Klotho plasma levels in men (all P≥ 0.1). We found an inverse association between energy, protein and carbohydrate intake with S-Klotho plasma levels in women (all P≤0.043), which disappeared after controlling for age, lean mass index and sedentary time. An inverse association was observed between dietary energy density and S-Klotho plasma levels in women after controlling for covariates (all P≤0.05).In summary, the present study showed an inverse association of dietary energy density with S-Klotho plasma levels in middle-aged women. In addition, our data suggest that the associations between energy and macronutrient intake could be highly dependent on lean mass and sedentary time.

The authors would like to thank all the participants that took part of the study for their time and effort. This study is part of a Ph.D. Thesis conducted in the Biomedicine Doctoral Studies of the University of Granada, Spain. We are grateful to Dr. Ángel Gutiérrez and Alejandro De la O for all their support in the study. We are grateful to Ms. Ana Yara Postigo-Fuentes for her assistance with the English language., The aim of the present study was to investigate the relationship of sleep quality and time with basal metabolic rate (BMR) and fuel oxidation in basal conditions and during exercise in sedentary middleaged adults. We also studied the mediation role of dietary intake and adherence to the traditional Mediterranean Diet in the relationship between sleep parameters and energy metabolism parameters.A secondary analysis of the FIT-AGEING study was undertaken. 70 middle-aged sedentary adults (40–65 years old) participated in the present study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and wrist accelerometers (ActiSleep, Actigraph, Pensacola, Florida, USA) for 7 consecutive days. BMR was measured with indirect calorimetry and fuel oxidation was estimated through stoichiometric equations. Maximal fat oxidation was determined by a walking graded exercise test and dietary intake with 24 h recalls. Adherence to the traditional Mediterranean diet was assessed through the PREDIMED questionnaire. PSQI global score (poor sleep quality) was associated with lower basal fat oxidation (BFox), both expressed in g/min and as a percentage of BMR, independently of confounders. We did not find any association between other sleep and energy metabolism parameters. No mediating role of the dietary intake or PREDIMED global score was observed in the association of PSQI and BFox. In conclusion, our study showed that a subjective poor sleep quality was associated with lower BFox, which is not mediated by dietary intake in sedentary adults., The study was supported by the Spanish Ministry of Education (FPU14/04172 and FPU15/03960), by the University of Granada UGR Research and Knowledge Transfer Fund (PPIT) 2016 (Excellence Actions Programme. Units of Scientific Excellence: Scientific Unit of Excellence on Excercise and Health [UCEES]) and Plan Propio de Investigación 2019 - Programa Contratos-Puente, by the Regional Government of Andalusia, Regional Ministry of Economy, Knowledge, Entreprises and University, by the European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR and by Redes Temáticas de Investigación Cooperativa RETIC grant Red SAMID RD16/0022.

This cross-sectional study investigates the relationship between the shed form of the Klotho protein (S-Klotho) in plasma, and cardiometabolic risk in healthy, sedentary adults. The study subjects were 214 healthy, sedentary adults (~64% women). Data were collected during the baseline assessments of two randomized controlled trials: The FIT-AGEING study (n=74 [~50% women] middle-aged adults aged 40-65 years) and the ACTIBATE study (n=140 [~70% women] young adults aged 18-25 years). A sex-specific cardiometabolic risk score was calculated for each subject based on waist circumference, systolic and diastolic blood pressure, and plasma glucose, high-density lipoprotein cholesterol and triglycerides. A significant inverse relationship was detected between S-Klotho and the cardiometabolic risk score of both the middle-aged men and women (β=-0.658, R2=0.433, P0.5), nor for the young, healthy men and women when analysed separately (all P>0.1). In conclusion, in healthy, sedentary, middle-aged adults, but not in young, healthy, sedentary adults, higher plasma S-Klotho concentrations are associated with a lower cardiometabolic risk score.

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.

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

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.

S-klotho, the shed form of α-klotho, is thought to be an ageing suppressor with functions related to the physiology of energy metabolism. However, it remains unknown whether ageing biomarkers such as S-klotho and/or chronological ageing are associated in any way with basal metabolic rate (BMR) and fuel oxidation in basal conditions and during exercise. The present work investigates the association of BMR and fuel oxidation in basal conditions and during exercise, with plasma S-klotho in middle-aged, sedentary adults. BMR was measured by indirect calorimetry in 74 such subjects (53% women; age 53.7±5.1 years) following standard procedures, and their fuel oxidation estimated via stoichiometric equations. The maximal fat oxidation during exercise (MFO) and the intensity of exercise that elicits MFO (Fatmax) were determined using a walking graded exercise test. No relationship was seen between BMR and plasma S-klotho (P>0.1), although both basal fat oxidation and MFO showed positive associations with this protein (both P0.1). The present findings suggest that basal fat oxidation and MFO are strongly associated with plasma S-klotho in middle-aged sedentary adults. These results support the idea that metabolic flexibility is a powerful predictor of biological ageing.

Objectives To determine the association between physical activity and physical fitness levels (i.e. cardiorespiratory fitness and muscular strength) and the shed form of the α-Klotho gene (S-Klotho plasma levels) in middle-aged sedentary adults. Study design and main outcome measures A total of 74 middle-aged sedentary adults (52.7% women; 53.7 ± 5.1 years old) were enrolled in the FIT-AGEING study. Physical activity and sedentary time were assessed with a wrist-worn accelerometer. Maximal oxygen uptake (VO2max) was determined by a maximum treadmill test using indirect calorimetry. Lower- and upper-body muscular strength were assessed by an isokinetic strength test and by the hand grip strength test, respectively. The S-Klotho plasma levels were measured in the EDTA plasma using a solid-phase sandwich enzyme-linked immunosorbent assay. Results Based on the principal-component analysis, overall physical activity, moderate and vigorous physical activity levels, and sedentary time (as outcomes included in the ‘sedentary time and physical activity’ category) explained a total of 17.5% of the cumulative variance in S-Klotho plasma levels, while extension peak torque, hand grip strength, and maximal oxygen uptake (as outcomes included in the ‘physical fitness’ category) explained a total of 15.5% of the cumulative variance in S-Klotho plasma levels. Based on the loading of variables in these 2 categories, the percentage of the cumulative variance in S-Klotho plasma level explained was 28.9%s; this reached 33.0% of cumulative variance when sex was included in the model. Conclusions In summary, our results indicate that physical activity and physical fitness levels are associated with S-Klotho plasma levels in middle-aged sedentary adults. Therefore, the S-Klotho protein could be a key factor in the relationship between physical activity and physical fitness and health improvements during the ageing process.

Humans have long sought means to extend longevity and counteract the effects of aging on physical and mental functioning. Exercise is a highly effective way of treating and preventing the main causes of morbidity and mortality, most of which are associated with aging. Interestingly, the Klotho gene is involved in the aging process. Indeed, overexpression of the Klotho gene is associated with longevity, and experimental animals lacking this gene seem to develop multiple disorders resembling human aging and present a shortened lifespan. Three Klotho-related genes have been identified: α-Klotho, β-Klotho, and γ-Klotho. Exercise seems to play a key role on the secreted form of the α-Klotho gene (S-Klotho) in animal models as well as in humans. We systematically reviewed the available evidence on the associations between exercise and S-Klotho protein regulation.

Introduction Alcohol consumption is related to several diseases and injuries that accelerate the ageing process and increase the mortality and morbidity risk. The soluble form of the α-Klotho gene (called S-Klotho) is widely considered as a powerful anti-ageing biomarker. Aim The aim of the present study was to analyze the association between alcohol consumption and S-Klotho plasma levels in sedentary middle-aged adults. Methods 74 (39 women) middle-aged sedentary adults (40–65 years old) participated in the present study. Alcohol consumption was assessed with a food frequency questionnaire previously validated and with three non-consecutive 24-hours recall. The S-Klotho plasma levels were measured by ELISA using a soluble α-Klotho ELISA assay kit. Results Total alcoholic drinks consumption was negatively associated with S-Klotho plasma levels (β=-17.031; R2 = 0.096, P = 0.013). Furthermore, we observed that higher consumption of total alcoholic drinks is associated with lower S-Klotho plasma levels in middle-aged sedentary adults controlling for BMI (β=-16.372; R2 = 0.201, P = 0.011), LMI (β=-31.854; R2 = 0.305, P = 0.010) and for FMI β=-13.337; R2 = 0.075, P = 0.049). Conclusion: In conclusion, our study shows that total alcoholic drinks consumption is negatively associated with the S-Klotho plasma levels in middle-aged sedentary adults.

Objective: To study the association between usual dietary factors (dietary energy density, nutrient intake, food group consumption, and dietary pattern) and brown adipose tissue (BAT) volume/F-18-fluorodeoxyglucose (F-18-FDG) uptake after personalized cold exposure in young healthy adults.Methods: A total of 122 young adults (n = 82 women; 22.0 +/- 2.1 years old; 24.8 +/- 4.8 kg/m(2)) took part in this cross-sectional study. Dietary factors were measured via a food frequency questionnaire and three non-consecutive 24 h recalls. Dietary energy density (foods and caloric beverages included) and macronutrient intakes were subsequently estimated using EvaIFINUT (R) software, food group consumption was estimated from the food frequency questionnaire, and different dietary patterns and quality indices were determined according to the reference methods. BAT volume, BAT F-18-FDG uptake, and skeletal muscle F-18-FDG uptake were assessed by static F-18-FDG positron-emission tomography and computed tomography (PET-CT) scans after a 2 h personalized exposure to cold.Results: A direct association was detected between dietary energy density and BAT Standardized Uptake Value (SUV)mean (beta = 0.215; R-2 = 0.044; P = 0.022), and between ethanol consumption and BAT volume (beta = 0.215; R-2 = 0.044; P = 0.022). The a priori Mediterranean dietary pattern was inversely associated with BAT SUVmean and SUVpeak (beta = -0.273; R-2 = 0.075; P = 0.003 and beta = -0.255; R-2 = 0.066; P = 0.005 respectively). In addition, the diet quality index for a Mediterranean diet and a pro-inflammatory dietary pattern (as determined via the dietary inflammatory index) were directly associated with BAT SUVmean and SUVpeak (SUVmean: beta = 0.238; R-2 = 0.053; P = 0.013 and beta = 0.256; R-2 = 0.052; P = 0.012 respectively; SUVpeak: beta = 0.278; R-2 = 0.073; P = 0.003 and beta = 0.248; R-2 = 0.049; P = 0.016 respectively). After controlling for multiplicity and possible confounders (sex, the evaluation wave and BMI), all the detected associations persisted.Conclusion: Dietary factors are slightly associated with BAT volume and/or F-18-FDG uptake after a personalized cold exposure in young adults. Our results provide an overall picture of the potential relationships between dietary factors and BAT-related variables in humans. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The main active metabolite of vitamin D, the 1,25-dihydroxyvitamin D (1,25(OH)2D), and the shed form of the α-Klotho gene (S-Klotho) play an important role in aging-related physiological processes ...

The study is supported by the Spanish Ministry of Education (FPU14/04172 and FPU15/03960). The authors would like to thank all the participants that take part of the study for their time and effort. This study is part of a Ph.D. Thesis conducted in the Biomedicine Doctoral Studies of the University of Granada, Spain., Background: A growing body of scientific works investigating the physio-pathological mechanisms behind cardiovascular disease has suggested that vitamin D deficiency could play a key role on its development. However, it remains unclear whether its active form (1,25-dihydroxyvitamin D [1,25(OH)(2)D] is associated with cardiometabolic risk factors in healthy individuals. The aim of the present study was to investigate the relationships of 1,25(OH)(2)D plasma levels with cardiometabolic risk factors in a sample of healthy sedentary adults. Methods: A total of 73 adults (similar to 53% women; 54 +/- 5 years old) were included in the current cross-sectional study. A sex-specific cardiometabolic risk score (MetScore) was calculated for each subject based on clinical parameters (i.e., waist circumference, systolic and diastolic blood pressure, plasma glucose, high-density lipoprotein cholesterol, and triglycerides) according to the International Diabetes Federation's clinical criteria. Plasma levels of 1,25(OH)(2)D were measured using a DiaSorin Liaison (R) immunochemiluminometric analyzer. Results: No significant association was detected between 1,25(OH)(2)D and MetScore (beta = 0.037, R-2 = 0.001, p = 0.77), independently of age, sex and fat body mass index. A significant inverse association were observed between 1,25(OH)(2)D and waist circumference (beta = -0,303, R-2 = 0.092, p = 0.01). These results were consistent after controlling by potential confounders. Conclusion: In summary, the present results suggest that 1,25(OH)(2)D plasma levels are not associated with either cardiometabolic risk factors or insulin resistance in healthy sedentary adults. However, an inverse association of 1,25(OH)(2)D plasma levels with central adiposity was observed in our study sample., Spanish Government FPU14/04172 FPU15/03960

Background: There is evidence that caffeine increases the maximal fat oxidation rate (MFO) and aerobic capacity, which are known to be lower in the morning than in the afternoon. This paper examines the effect of caffeine intake on the diurnal variation of MFO during a graded exercise test in active men. Methods: Using a triple-blind, placebo-controlled, crossover experimental design, 15 active caffeine-naïve men (age: 32 ± 7 years) completed a graded exercise test four times at seven-day intervals. The subjects ingested 3 mg/ kg of caffeine or a placebo at 8 am in the morning and 5 pm in the afternoon (each subject completed tests under all four conditions in a random order). A graded cycling test was performed. MFO and maximum oxygen uptake (VO2max) were measured by indirect calorimetry, and the intensity of exercise that elicited MFO (Fatmax) calculated. Results: MFO, Fatmax and VO2max were significantly higher in the afternoon than in the morning (all P < 0.05). Compared to the placebo, caffeine increased mean MFO by 10.7% (0.28 ± 0.10 vs. 0.31 ± 0.09 g/min respectively, P < 0.001) in the morning, and by a mean 29.0% (0.31 ± 0.09 vs. 0.40 ± 0.10 g/min, P < 0.001) in the afternoon. Caffeine also increased mean Fatmax by 11.1% (36.9 ± 14.4 [placebo] vs. 41.0 ± 13.1%, P = 0.005) in the morning, and by 13.1% (42.0 ± 11.6 vs. 47.5 ± 10.8%, P = 0.008) in the afternoon. Conclusion: These findings confirm the previously reported diurnal variation in the whole-body fat oxidation rate during graded exercise in active caffeine-naïve men, and indicate that the acute ingestion of 3 mg/kg of caffeine increases MFO, Fatmax and VO2max independent of the time of day. Trial registration: NCT04320446. Registered 25 March 2020 - Retrospectively registered., University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES), Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGR

This study was supported by grants FPU16/01093 (Dr Carneiro-Barrera), FPU14/04172 (Dr Amaro-Gahete), and FPU19/01609 (Mr Jurado-Fasoli) from the Spanish Ministry of Education and Vocational Training; grant SOMM17/6107/UGR (via European Regional Development Funds) from the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (Dr Ruiz); and funding from the University of GranadaLoMonaco S.L. Sleep Research Cathedra and the University of Granada Plan Propio de Investigacion 2016Excellence Actions: Unit of Excellence on Exercise and Health., IMPORTANCE Obesity is the leading cause of obstructive sleep apnea (OSA); however, the effects of weight loss and lifestyle interventions on OSA and comorbidities remain uncertain. OBJECTIVE To evaluate the effect of an interdisciplinary weight loss and lifestyle intervention on OSA and comorbidities among adults with moderate to severe OSA and overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS The InterdisciplinaryWeight Loss and Lifestyle Intervention for OSA (INTERAPNEA) study was a parallel-group open-label randomized clinical trial conducted at a hospital-based referral center in Granada, Spain, from April 1, 2019, to October 23, 2020. The study enrolled 89 Spanish men aged 18 to 65 years with moderate to severe OSA and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or greater who were receiving continuous positive airway pressure (CPAP) therapy. The sole inclusion of men was based on the higher incidence and prevalence of OSA in this population, the differences in OSA phenotypes between men and women, and the known effectiveness of weight loss interventions among men vs women. INTERVENTIONS Participants were randomized to receive usual care (CPAP therapy) or an 8-week weight loss and lifestyle intervention involving nutritional behavior change, aerobic exercise, sleep hygiene, and alcohol and tobacco cessation combined with usual care. MAIN OUTCOMES AND MEASURES The primary end point was the change in the apnea-hypopnea index (AHI) from baseline to the intervention end point (8 weeks) and 6 months after intervention. Secondary end points comprised changes in other OSA sleep-related outcomes, body weight and composition, cardiometabolic risk, and health-related quality of life. RESULTS Among 89 men (mean [SD] age, 54.1 [8.0] years; all of Spanish ethnicity; mean [SD] AHI, 41.3 [22.2] events/h), 49 were randomized to the control group and 40 were randomized to the intervention group. The intervention group had a greater decrease in AHI (51% reduction; change, –21.2 events/h; 95%CI, –25.4 to –16.9 events/h) than the control group (change, 2.5 events/h; 95% CI, –2.0 to 6.9 events/h) at the intervention end point, with a mean between-group difference of –23.6 events/h (95%CI, –28.7 to –18.5 events/h). At 6 months after intervention, the reduction in AHI was 57%in the intervention group, with a mean between-group difference of –23.8 events/h (95% CI, –28.3 to –19.3 events/h). In the intervention group, 18 of 40 participants (45.0%) no longer required CPAP therapy at the intervention end point, and 6 of 40 participants (15.0%) attained complete OSA remission. At 6 months after intervention, 21 of 34 participants (61.8%) no longer required CPAP therapy, and complete remission of OSA was attained by 10 of 34 participants (29.4%). In the intervention vs control group, greater improvements in body weight (change, –7.1 kg [95%CI, −8.6 to −5.5 kg] vs −0.3 kg [95%CI, −1.9 to 1.4 kg]) and composition (eg, change in fat mass, −2.9 kg [95%CI, −4.5 to −1.3 kg] vs 1.4 kg [95%CI, −0.3 to 3.1 kg]), cardiometabolic risk (eg, change in blood pressure, −6.5mmHg [95%CI, −10.3 to −2.6mmHg] vs 2.2mmHg [95%CI, −2.1 to 6.6mm Hg]), and health-related quality of life (eg, change in Sleep Apnea Quality of Life Index, 0.8 points [95%CI, 0.5-1.1 points] vs 0.1 points [95%CI, −0.3 to 0.4 points]) were also found at the intervention end point. CONCLUSIONS AND RELEVANCE In this study, an interdisciplinary weight loss and lifestyle intervention involving Spanish men with moderate to severe OSA and had overweight or obesity and were receiving CPAP therapy resulted in clinically meaningful and sustainable improvements in OSA severity and comorbidities as well as health-related quality of life. This approach may therefore be considered as a central strategy to address the substantial impact of this increasingly common sleepdisordered breathing condition., Spanish Government FPU16/01093 FPU14/04172 FPU19/01609, Junta de Andalucia SOMM17/6107/UGR, University of GranadaLoMonaco S.L. Sleep Research Cathedra, University of Granada Plan Propio de Investigacion 2016Excellence Actions: Unit of Excellence on Exercise and Health

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.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.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).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.NCT03334357 (ClinicalTrials.gov). November 7, 2017 retrospectively registered.

To study the association between usual dietary factors (dietary energy density, nutrient intake, food group consumption, and dietary pattern) and brown adipose tissue (BAT) volume/A total of 122 young adults (n = 82 women; 22.0 ± 2.1 years old; 24.8 ± 4.8 kg/mA direct association was detected between dietary energy density and BAT Standardized Uptake Value (SUV)mean (β = 0.215; RDietary factors are slightly associated with BAT volume and/or