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.Netherlands CardioVascular Research Initiative: `the Dutch Heart FoundationDutch Federation of University Medical CentersNetherlands Organization for Health Research and Development Royal Netherlands Academy of Sciences' CVON201720 GENIUS-IIFundacion Alfonso Martin EscuderoMaria Zambrano - Ministerio de Universidades y la Union Europea -NextGenerationEU RR_C_2021_04Spanish Government FPU19/01609European Foundation for the Study of Diabetes (EFSD)NWO XOmics project 184.034.01

Lycopene Supplementation for Patients Under Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Lycopene supplementation has been considered potentially useful as an adjuvant cancer therapy according to its anticancer properties. The present study aimed to investigate the effects of lycopene supplementation on outcome improvement in patients with cancer therapy. As a secondary aim, we conducted a meta analysis to investigate the efficacy of lycopene supplementation on circulating lycopene concentration in patients with cancer therapy.Methods: A systematic and comprehensive search was performed in electronic databases, including PubMed, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, EMBASE, MedNar, and OpenGrey up to March 2023. The inclusion criteria were randomized controlled trials conducted on patients under cancer therapy (i.e., radiotherapy, chemotherapy, surgery, etc.) supplementing with lycopene. Data extraction and analysis: two different evaluators screened and collected literature independently. Information regarding the study design, participants, intervention, and dependent outcomes was extracted, and the bias of the study was assessed. Additionally, separate random-effect meta-analyses were performed to examine the effects of lycopene supplementation on circulating lycopene concentration in patients under cancer therapy.Results: The initial search retrieved 7 565 articles of which eight met the inclusion criteria. Lycopene supplementation did not modify cancer hallmarks in these studies. However, despite the heterogeneity between studies, we show that, compared with control, lycopene supplementation had moderate effects on circulating lycopene concentration in patients under cancer therapy (pooled mean difference, 0.1361; 95% CI [0.0574; 0.2148], P = .0007).Conclusions: Our study shows that lycopene supplementation does not modify the main hallmarks of cancer, but it increases circulating lycopene concentration in patients under cancer therapy, which could have a positive impact on potential clinical and molecular outcomes in cancer patients.Spanish Government FPU19/01609University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Healt

Dietary Inflammatory Index and S-Klotho Plasma Levels in Middle-Aged Adults

Background: Soluble Klotho (S-Klotho) is an aging suppressor with a close link with inflammation. However, it is still unknown whether the dietary inflammatory potential is associated with S-Klotho plasma level. We aimed to investigate the association of the Dietary Inflammatory Index (DII) with S-Klotho plasma levels in middle-aged sedentary adults. Methods: 73 middle-aged sedentary adults (40–65 years old) participated in the present study. DII was determined from 28 dietary items obtained by 24 h recalls and food frequency questionnaires. The S-Klotho plasma levels were measured using a solid-phase sandwich enzyme-linked immunosorbent assay. Results: a weak positive association was observed between DII and S-Klotho plasma levels ( B = 52.223, R2 = 0.057, p = 0.043), which disappeared after controlling for body mass index (p = 0.057). Conclusions: A pro-inflammatory dietary pattern measured with the DII was slightly and positively associated with S-Klotho plasma levels in middle-aged 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 Exercise and Health [UCEES]), by the Regional Government of Andalusia, Regional Ministry of Economy, Knowledge, Enterprises 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

Association between sleep quality and time with energy metabolism in sedentary adults

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

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.Spanish Ministry of Economy and Competitiveness via Retos de la Sociedad grant DEP2016-79512-REuropean CommissionSpanish Government FPU15/04059 FPU19/01609University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and HealthJunta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades via the ERDF SOMM17/6107/UGRFundacion Alfonso Martin EscuderoUniversidad de Granada/CBU

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 steadystate 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

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 receptivephase 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.MCIN/AEI Endo-Map PID2021-12728OB-100 ENDORE SAF2017-87526-R PRE2018-085440 RYC-2016-21199 FPU19/03745 FPU19/01638 FPU19/01609ERFD A way of making EuropeESF Investing in your futureFEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento ROBIN A-CTS-614-UGR20 IRENE P20_00158University of Granada Plan Propio de Investigacion PPJIB2021-02Plan de Recuperacion, Transformacion y resiliencia, Ayudas para la recualificacion del sistema universitario espanol, Ayudas Margarita Sala

Caffeine increases maximal fat oxidation during a graded exercise test: is there a diurnal variation?

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/UG

Omega-6 and omega-3 oxylipins as potential markers of cardiometabolic risk in young adults

This study was supported by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393) and PTA-12264, Retos de la Sociedad (DEP2016-79512-R) and the European Regional Development Fund (ERDF), the Spanish Ministry of Education (FPU16/02828 and FPU19/01609), the Fundacion Iberoamericana de Nutricion (FINUT), the Redes Tematicas de Investigacion Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigacion 2016 Excellence actions: Unit of Excellence on Exercise and Health (UCEES), the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF; ref. SOMM17/6107/UGR and DOC 01151), the Fundacion Alfonso Martin Escudero, 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-2) to PCNR, and the Chinese Scholarship Council (CSC, No. 201707060012).Objective: Omega-6 and omega-3 oxylipins are known to play a role in inflammation and cardiometabolic diseases in preclinical models. The associations between plasma levels of omega-6 and omega-3 polyunsaturated fatty acid–derived oxylipins and body composition and cardiometabolic risk factors in young adults were assessed. Methods: Body composition, brown adipose tissue, traditional serum cardiometabolic risk factors, inflammatory markers, and a panel of 83 oxylipins were analyzed in 133 young adults (age 22.1[SD 2.2] years, 67% women). Results: Plasma levels of four omega-6 oxylipins (15-HeTrE, 5-HETE, 14,15-EpETrE, and the oxidative stress–derived 8,12-iso- iPF2α -VI) correlated positively with adiposity, prevalence of metabolic syndrome, fatty liver index, and homeostatic model assessment of insulin resistance index and lipid parameters. By contrast, the plasma levels of three omega-3 oxylipins (14,15-DiHETE, 17,18-DiHETE, and 19,20-DiHDPA) were negatively correlated with adiposity, prevalence of metabolic syndrome, fatty liver index, homeostatic model assessment of insulin resistance index, and lipid parameters. The panel of seven oxylipins predicted adiposity better than traditional inflammatory markers such as interferon gamma or tumor necrosis factor-alpha. Pathway analyses revealed that individuals with obesity had higher plasma levels of omega-6 and lower plasma levels of omega-3 oxylipins than normal-weight individuals. Conclusion: Plasma levels of seven omega-6 and omega-3 oxylipins may have utility as early markers of cardiometabolic risk in young adults.Spanish Government PI13/01393Retos de la Sociedad DEP2016-79512-REuropean Commission Spanish Government FPU16/02828 FPU19/01609Fundacion Iberoamericana de Nutricion (FINUT)Redes Tematicas de Investigacion Cooperativa RETIC Red SAMID RD16/0022AstraZenecaUniversity of Granada Plan Propio de Investigacion Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Junta de Andalucia Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGR DOC 01151Fundacion Alfonso Martin EscuderoNetherlands CardioVascular Research Initiative: the Dutch Heart FoundationDutch Federation of University Medical CentersNetherlands Organization for Health Research and DevelopmentRoyal Netherlands Academy of Sciences CVON2017-20 GENIUS-2China Scholarship Council 201707060012 PTA-1226

Beer or Ethanol Efects on the Body Composition Response to High-Intensity Interval Training. The BEER-HIIT Study

High-intensity interval training (HIIT) is promoted as a time-effcient strategy to improve body composition but concomitant beer intake, which is common among physically active individuals, may interfere with these effects. The primary aim of this study is to determine the effects of a 10-week (2 days/week) HIIT program on anthropometric and body composition measurements, and to assess whether those effects are influenced by the moderate consumption of beer (at least 5 days/week), or its alcohol equivalent. Young (24 ± 6 years old) healthy adults (n = 72, 35 females) volunteered for a non-training group (Non-Training group) or for HIIT training. Those going for training choose whether they preferred to receive alcohol or not. Those choosing alcohol were randomly allocated for receiving beer (5.4%; T-Beer group) or the equivalent amount of alcohol (vodka; T-Ethanol group) in sparkling water. Those choosing no-alcohol were randomly allocated for receiving alcohol-free beer (0.0%; T-0.0Beer group) or sparkling water (T-Water group). From Monday through Friday, men ingested 330 mL of the beverage with lunch and 330 mL with dinner; women ingested 330 mL with dinner. Before and after the intervention, anthropometry and body composition, through dual-emission X-ray absorptiometry, were measured. No changes in body mass, waist circumference, waist/hip ratio, visceral adipose tissue or bone mineral density occurred in any of the groups. By contrast, in all the training groups, significant decreases in fat mass together with increases in lean mass (all p < 0.05) occurred. These positive effects were not influenced by the regular intake of beer or alcohol. In conclusion, a moderate beer intake does not blunt the positive effect of 10-week HIIT on body composition in young healthy adults.This research was partially funded by an unrestricted grant of the Centro de Información Cerveza y Salud (CICS), Madrid, Spain. F.J.A.-G. and A.D.-l.-O are supported by a training grant from the Spanish Ministry of Education (FPU14/04172 and FPU15/03960)