Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded... Show moreExercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n = 31, and VIG-EX; n = 31). We observed no changes in BAT volume (Delta Control: -22.2 +/- 52.6 ml; Delta MOD-EX: -15.5 +/- 62.1 ml, Delta VIG-EX: -6.8 +/- 66.4 ml; P = 0.771) or F-18-fluorodeoxyglucose uptake (SUVpeak Delta Control: -2.6 +/- 3.1 ml; Delta MOD-EX: -1.2 +/- 4.8, Delta VIG-EX: -2.2 +/- 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.Exercise modulates brown adipose tissue (BAT) metabolism in murine models. Here the authors report that there is no evidence that 24 weeks of supervised exercise training modulates BAT volume or function in young sedentary adults in the ACTIBATE randomized controlled trial. Show less
Context: Cold exposure mobilizes lipids to feed thermogenic processes in organs, including brown adipose tissue (BAT). In rodents, BAT metabolic activity exhibits a diurnal rhythm, which is highest... Show moreContext: Cold exposure mobilizes lipids to feed thermogenic processes in organs, including brown adipose tissue (BAT). In rodents, BAT metabolic activity exhibits a diurnal rhythm, which is highest at the start of the wakeful period. Objective: We investigated whether cold-induced thermogenesis displays diurnal variation in humans and differs between the sexes. Methods: This randomized crossover study included 24 young and lean male (n = 12) and female (n = 12) participants who underwent 2.5-hour personalized cooling using water-perfused mattresses in the morning (7:45 am) and evening (7:45 pm), with 1 day in between. We measured energy expenditure (EE) and supraclavicular skin temperature in response to cold exposure. Results: In males, cold-induced EE was higher in the morning than in the evening (+54% +/- 10% vs +30% +/- 7%; P = 0.05) but did not differ between morning and evening in females (+37% +/- 9% vs +30% +/- 10%; P = 0.42). Only in males, supraclavicular skin temperature upon cold increased more in morning than evening (+0.2 +/- 0.1 degrees C vs -0.2 +/- 0.2 degrees C; P = 0.05). In males, circulating free fatty acid (FFA) levels were increased after morning cold exposure, but not evening (+90% +/- 18% vs +9% +/- 8%; P < 0.001). In females, circulating FFA (+94% +/- 21% vs +20% +/- 5%; P = 0.006), but also triglycerides (+42% +/- 5% vs +29% +/- 4%, P = 0.01) and cholesterol levels (+17% +/- 2% vs 11% +/- 2%; P = 0.05) were more increased after cold exposure in morning than in evening. Conclusion: Cold-induced thermogenesis is higher in morning than evening in males; however, lipid metabolism is more modulated in the morning than the evening in females. Show less
Background: Harnessing cold-induced thermogenesis (CIT) and brown adipose tissue (BAT) activity has been proposed as a means of counteracting a positive energy balance, and thus of combating... Show moreBackground: Harnessing cold-induced thermogenesis (CIT) and brown adipose tissue (BAT) activity has been proposed as a means of counteracting a positive energy balance, and thus of combating obesity and its related comorbidities. However, it has remained unclear whether CIT and BAT activity show diurnal variation in humans -knowledge that might allow treatments based on these factors to be time-optimized.Methods: A randomized crossover experiment was designed to examine whether CIT shows morning/evening variation in young, healthy adults (n = 14, 5 women). On the first experimental day, subjects' shivering thresholds were determined following a cooling protocol. After z96 h had elapsed, the sub-jects then returned on two further days (approx. 48 h apart) at 08:00 h or 18:00 in random order. On both the latter days, the resting energy expenditure (REE) was measured before the subjects underwent personalized cold exposure (i.e., according to their shivering threshold). CIT was then assessed for 60 min by indirect calorimetry. In an independent cross-sectional study (n = 133, 88 women), subjects came to the laboratory between 8:00 and 18:00 h and their BAT F-18-fluordeoxyglucose (F-18-FDG) uptake was assessed after personalized cold stimulation.Results: Both the REE and CIT were similar in the morning and evening (all P > 0.05). Indeed, 60 min of personalized-mild cold exposure in the morning or evening elicited a similar change in energy expen-diture (16.8 +/- 12.8 vs. 15.7 +/- 15.1% increase above REE, P = 0.72). BAT F-18-FDG uptake was also similar in the morning, evening and afternoon (all P > 0.05).Conclusion: CIT does not appear to show morning/evening variation in young healthy adults, with the current study design and methodology. BAT F-18-FDG uptake appears not to change across the day either, although experiments with a within-subject study design are needed to confirm these findings. (C) 2021 The Author(s). Published by Elsevier Ltd. Show less
Where people live and work together it is not always possible to modify the ambient temperature; ways must therefore be found that allow individuals to feel thermally comfortable in such settings.... Show moreWhere people live and work together it is not always possible to modify the ambient temperature; ways must therefore be found that allow individuals to feel thermally comfortable in such settings. The Embr Wave (R) is a wrist-worn device marketed as a 'personal thermostat' that can apply a local cooling stimulus to the skin. The aim of the present study was to determine the effect of an intermittent mild cold stimulus of 25 degrees C for 15-20 s every 5 min over 3.5 days under free-living conditions on 1) skin temperature, 2) perception of skin temperature, 3) sleep quality and 4) resting energy expenditure (REE) in young, healthy adults. Ten subjects wore the device for 3.5 consecutive days. This intervention reduced distal skin temperature after correcting for personal ambient temperature (P < 0.05), but did not affect the subjects' the perception of skin temperature, sleep quality or REE (all P >= 0.051). Thus, this intermittent mild cold regime can reduce distal skin temperature, and wearing it under free-living conditions for 3.5 days does not seem to impair the perception of skin temperature and sleep quality or modify REE. Show less
Objective This study aimed to describe the energy expenditure (EE) and macronutrient oxidation response to an individualized nonshivering cold exposure in young healthy adults. Methods Two... Show moreObjective This study aimed to describe the energy expenditure (EE) and macronutrient oxidation response to an individualized nonshivering cold exposure in young healthy adults. Methods Two different groups of 44 (study 1: 22.1 [SD 2.1] years old, 25.6 [SD 5.2] kg/m(2), 34% men) and 13 young healthy adults (study 2: 25.6 [SD 3.0] years old, 23.6 [SD 2.4] kg/m(2), 54% men) participated in this study. Resting metabolic rate (RMR) and macronutrient oxidation rates were measured by indirect calorimetry under fasting conditions in a warm environment (for 30 minutes) and in mild cold conditions (for 65 minutes, with the individual wearing a water-perfused cooling vest set at an individualized temperature adjusted to the individual's shivering threshold). Results In study 1, EE increased in the initial stage of cold exposure and remained stable for the whole cold exposure (P < 0.001). Mean cold-induced thermogenesis (9.56 +/- 7.9 kcal/h) was 13.9% +/- 11.6% of the RMR (range: -14.8% to 39.9% of the RMR). Carbohydrate oxidation decreased during the first 30 minutes of the cold exposure and later recovered up to the baseline values (P < 0.01) in parallel to opposite changes in fat oxidation (P < 0.01). Results were replicated in study 2. Conclusions A 1-hour mild cold exposure individually adjusted to elicit maximum nonshivering thermogenesis induces a very modest increase in EE and a shift of macronutrient oxidation that may underlie a shift in thermogenic tissue activity. Show less
Heart rate variability (HRV) is a non-invasive indicator of autonomic nervous system function. HRV recordings show artefacts due to technical and/or biological issues. The Kubios software is one of... Show moreHeart rate variability (HRV) is a non-invasive indicator of autonomic nervous system function. HRV recordings show artefacts due to technical and/or biological issues. The Kubios software is one of the most used software to process HRV recordings, offering different levels of threshold-based artefact correction (i.e., Kubios filters). The aim of the study was to analyze the impact of different Kubios filters on the quantification of HRV derived parameters from short-term recordings in three independent human cohorts. A total of 312 participants were included: 107 children with overweight/obesity (10.0 +/- 1.1 years, 58% men), 132 young adults (22.2 +/- 2.2 years, 33% men) and 73 middle-aged adults (53.6 +/- 5.2 years, 48% men). HRV was assessed using a heart rate monitor during 10-15 min, and the Kubios software was used for HRV data processing using all the Kubios filters available (i.e., 6). Repeated-measures analysis of variance indicated significant differences in HRV derived parameters in the time-domain (all p < 0.001) across the Kubios filters in all cohorts, moreover similar results were observed in the frequency-domain. When comparing two extreme Kubios filters, these statistical differences could be clinically relevant, e.g. more than 10 ms in the standard deviation of all normal R-R intervals (SDNN). In conclusion, the results of the present study suggest that the application of different Kubios filters had a significant impact on HRV derived parameters obtained from short-term recordings in both time and frequency-domains. Show less
Background & aims: Since the discovery of active brown adipose tissue in human adults, non-shivering cold-induced thermogenesis (CIT) has been regarded as a promising tool to combat obesity.... Show moreBackground & aims: Since the discovery of active brown adipose tissue in human adults, non-shivering cold-induced thermogenesis (CIT) has been regarded as a promising tool to combat obesity. However, there is a lack of consensus regarding the method of choice to analyze indirect calorimetry data from a CIT study. We analyzed the impact of methods for data selection and methods for data analysis on measures of cold-induced energy expenditure (EE) and nutrient oxidation rates.Methods: Forty-four young healthy adults (22.1 +/- 2.1 years old, 25.6 +/- 5.2 kg/m(2), 29 women) participated in the study. Resting metabolic rate (RMR), cold-induced thermogenesis (CIT), and cold-induced nutrient oxidation rates were estimated by indirect calorimetry under fasting conditions during 1 h of cold exposure combining air conditioning (19.5-20 degrees C) and a water perfused cooling vest set at a temperature of 4 degrees C above the individual shivering threshold. We applied three methods for data selection: (i) time intervals every 5 min (5min-TI), (ii) the most stable 5-min period of every forth part of the cold exposure (5min-SS-4P), and (iii) the most stable 5-min period of every half part of the cold exposure (5min-SS-2P). Lately we applied two methods for data analysis: (i) area under the curve as a percentage of the baseline RMR (AUC) and; (ii) the difference between EE at the end of the cold exposure and baseline RMR (Last-RMR).Results: Mean overall CIT estimation ranged from 11.6 +/- 10.0 to 20.1 +/- 17.2 %RMR depending on the methods for data selection and analysis used. Regarding methods for data selection, 5min-SS-2P did not allow to observe physiologically relevant phenomena (e.g. metabolic shift in fuel oxidation; P = 0.547) due to a lack of resolution. The 5min-TI and 5min-SS-4P methods for data selection seemed to be accurate enough to observe physiologically relevant phenomena (all P < 0.014), but not comparable for estimating over-all CIT and cold-induced nutrient oxidation rates (P < 0.01). Regarding methods for data analysis, the AUC seemed to be less affected for data artefacts and to be more representative in participants with a non-stable energy expenditure during cold exposure.Conclusions: The methods for data selection and analysis can have a profound impact on CIT and cold-induced nutrient oxidation rates estimations, and therefore, it is mandatory to unify it across scientific community to allow inter-study comparisons. Based on our findings, 5min-TI should be considered the method of choice to study dynamics (i.e. changes across time) of CIT and cold-induced nutrient oxidation rates, while 5min-SS-4P and AUC should be the method of choice when computing CIT and cold-induced nutrient oxidation rates as a single value. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. Show less
Background Brown adipose tissue (BAT) seems to play a role in bone morphogenesis. A negative association has been reported between BAT and bone mineral density (BMD) in women, but not in men. A... Show moreBackground Brown adipose tissue (BAT) seems to play a role in bone morphogenesis. A negative association has been reported between BAT and bone mineral density (BMD) in women, but not in men. A panel of experts has recently published a set of recommendations for BAT assessment, and thus, to re-address previously reported associations is needed. This study aimed to investigate the association between cold-induced BAT (18) F-Fluorodeoxyglucose (F-18-FDG) uptake and BMD in young healthy adults.Methods Ninety-eight healthy adults (68 women; 22 +/- 2.2 years old; 24.3 +/- 4.5 kg/m(2)) cold-induced BAT was assessed by means of an F-18-FDG positron emission tomography-computed tomography (PET-CT) scan preceded by a personalized cold stimulation. The cold exposure consisted in 2 h in a mild cold room at 19.5-20 degrees C wearing a water perfused cooling vest set 4 degrees C above the individual shivering threshold. Total body and lumbar spine BMD were assessed by a whole-body DXA scan.Results We found no association between BMD and cold-induced BAT volume, mean, and maximal activity (all P>0.1) in neither young and healthy men nor women. These results remained unchanged when adjusting by height, by body composition, and by objectively assessed physical activity. Sensitivity analyses using the criteria to quantify cold-induced BAT-related parameters applied in previous studies did not change the results.Conclusions In summary, our study shows that there is no association between cold-induced BAT and BMD in young healthy adults. Moreover, our data support the notion that previously shown associations between BAT and BMD in healthy non-calorically restricted individuals, could be driven by methodological issues related to BAT assessment and/or sample size limitations. Show less
The time spent in sedentary behaviour represents an important public health burden. To reduce sedentary time in the general population, the simplest, most effective, and most accessible method is... Show moreThe time spent in sedentary behaviour represents an important public health burden. To reduce sedentary time in the general population, the simplest, most effective, and most accessible method is to decrease lying and sitting time. We aimed to compare differences on energy expenditure (EE) across lying, sitting, and standing positions; and to analyse the associations between the change on EE of changing from one position to another and anthropometric and body composition parameters in young healthy adults. A total of 55 (69% women) young healthy adults aged 21.7 +/- 2.2 participated in the study. We measured EE by indirect calorimetry across lying, sitting, and standing positions following the standard procedures. The EE was significantly higher in standing than in both lying and sitting positions (mean difference: 0.121 +/- 0.292 and 0.125 +/- 0.241 kcal/min, respectively; all P<0.001), and no differences were observed between lying and sitting positions (P = 1.000). There was a negative association between the EE differences in sitting vs. standing position and lean body mass (P = 0.048), yet no associations between EE differences with the rest of the anthropometric and body composition parameters were observed in each position pair studied (all P>0.321). Our findings support the fact that increasing the time spent standing could be a simple strategy to slightly increase EE. Therefore, our results have important clinical implications including a better monitoring, characterizing, and promoting countermeasures to sedentariness through low-level physical activities. Show less
Dairy products are thought to improve recovery after both resistance and endurance exercises due to their nutritional proprieties. We systematically reviewed the effects of dairy product intake on... Show moreDairy products are thought to improve recovery after both resistance and endurance exercises due to their nutritional proprieties. We systematically reviewed the effects of dairy product intake on exercise performance and recovery of muscle function in humans. A literature search was conducted in the MEDLINE (via PubMed) and Web of Science databases from their inception to 15th April 2018. The initial search retrieved 7708 articles, and a total of 11 studies were finally included after applying inclusion and exclusion criteria. All the selected studies were conducted with cow's milk. Whereas some studies found significant positive effect of cow's milk on exercise performance and recovery of muscle function, others did not find any effect. These controversies could be due to the heterogeneity of cow's milk ingestion (e.g., amount of cow's milk, timing of consuming the cow's milk), to the type of intervention, and to the large heterogeneity of outcomes measured. Limited studies exist examining the effects of cow's milk consumption and its influence on exercise performance and recovery of muscle function, therefore further studies are needed to draw more definitive conclusions. Show less
Brown adipose tissue (BAT) thermogenic activity is commonly assessed with a positron emission tomography with computed tomography scan (PET/CT). This technique has several limitations and... Show moreBrown adipose tissue (BAT) thermogenic activity is commonly assessed with a positron emission tomography with computed tomography scan (PET/CT). This technique has several limitations and alternative techniques are needed. Supraclavicular skin temperature measured with iButtons and infrared thermography (IRT) has been proposed as an indirect marker of BAT activity. We studied the concurrent validity of skin temperature measured with iButtons vs. IRT and the association of supraclavicular skin temperature measured with iButtons and IRT with BAT. We measured skin temperature upon a shivering threshold test with iButtons and IRT in 6 different regions in 12 participants (n = 2 men). On a separate day, we determined supraclavicular skin temperature with an iButton and IRT after 2 h of a personalized cooling protocol. Thereafter, we quantified BAT volume and activity by PET/CT. We observed that the absolute differences between the devices were statistically different from 0 (all P < 0.05) after the shivering threshold test. Moreover, we did not find any association between supraclavicular skin temperature measured with iButtons or IRT and BAT F-18-FDG activity (r = -0.213; P = 0.530 and r = -0.079; P = 0.817). However, we observed a negative association of supraclavicular skin temperature measured by IRT with BAT F-18-FDG volume (r = -0.764; P = 0.006), but not with supraclavicular skin temperature measured with iButtons (r = -0.546; P = 0.082). In light of these results, we concluded that the measurement of skin temperature obtained by iButtons and IRT are not comparable. Furthermore, it seems that supraclavicular skin temperature is not associated with BAT F-18-FDG activity, but it appears to be negatively associated with BAT F-18-FDG volume in the case of IRT. Show less
PurposeNear-infrared spectroscopy (NIRS) has recently been proposed as an indirect technique to assess brown adipose tissue (BAT) in young men. NIRS arises as a novel technique to avoid the... Show morePurposeNear-infrared spectroscopy (NIRS) has recently been proposed as an indirect technique to assess brown adipose tissue (BAT) in young men. NIRS arises as a novel technique to avoid the limitations of the gold-standard 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]DG) positron emission tomography combined with X-ray computed tomography (PET/CT). The aim of this study was to examine the association between near-infrared spatially resolved spectroscopy (NIRSRS) parameters and BAT volume and activity estimated by [F-18]DG-PET/CT in 18 young healthy women.ProceduresNIR(SRS) parameters [tissue saturation index and concentrations of total haemoglobin, oxy-haemoglobin, and deoxy-haemoglobin] were continuously measured in the supraclavicular and forearm regions, in both warm and cold (2h of personalised cold exposure) conditions. Then, the NIRSRS data were analysed as an average of 5min in 4 different periods: (i) warm period as the baseline record, (ii) cold period I, (iii) cold period II, and (iv) cold period III. The data were then correlated with BAT volume and activity (SUVmean and SUVpeak) estimated by [F-18]DG-PET/CT.ResultsThere was no association between the NIRSRS parameters in the supraclavicular region in warm conditions (no previous cold exposure) and BAT volume and activity (P>0.05). Similarly, the cold-induced changes of the NIRSRS parameters in the supraclavicular region were not associated with BAT volume and activity (P>0.05).ConclusionsNIR(SRS) does not seem to be a valid technique to indirectly assess BAT in young healthy women. Further research is needed to validate this technique against other methods such as PET/CT using different radiotracers or magnetic resonance imaging. Show less
The maximal fat oxidation (MFO), and the exercise intensity that elicits MFO (Fat(max)), are considered excellent markers of fat metabolism during exercise. Besides individual's biological... Show moreThe maximal fat oxidation (MFO), and the exercise intensity that elicits MFO (Fat(max)), are considered excellent markers of fat metabolism during exercise. Besides individual's biological characteristics (e.g. fed state, physical fitness level, sex, or age), data selection and analysis can affect MFO and Fatmax estimations, yet the effect is unknown. We investigated (i) the impact of using a pre-defined time interval on MFO and Fat(max) estimation, and (ii) the impact of applying 2 different data analysis approaches (measured-values vs. polynomial-curve) on MFO and Fat(max) estimations in sedentary adults. A total of 151 (97 women) sedentary adults aged 29.2 +/- 13.2 years old participated in the study. We assessed MFO and Fatmax through a walking graded exercise test using indirect calorimetry. We pre-defined 13 different time intervals for data analysis, and the estimation of MFO and Fat(max) were performed through the measured-values and the polynomial-curve data analysis approaches. There were significant differences in MFO across pre-defined time intervals methods (P < 0.001) applying measured-values data analysis approach, while no statistical differences were observed when using polynomial-curve data analysis approach (P = 0.077). There were no differences in Fat(max) across pre-defined time intervals independently of the data analysis approach (P >= 0.7). We observed significant differences in MFO between measured-values and the polynomial-curve data analysis approaches across the time intervals methods selected (all P <= 0.05), and no differences were observed in Fat(max) (all P >= 0.2). In conclusion, our results revealed that there are no differences in MFO and Fat(max) across different time intervals methods selected using the polynomial-curve data analysis approach. We observed significant differences in MFO between measured-values vs. polynomial-curve data analysis approaches in all the study time intervals, whereas no differences were detected in Fatmax. Therefore, the use of polynomial-curve data analysis approach allows to compare MFO and Fat(max) using different time intervals in sedentary adults. Show less
Purpose: Human brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and type 2 diabetes; however, whether physical activity (PA) might be an... Show morePurpose: Human brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and type 2 diabetes; however, whether physical activity (PA) might be an efficient stimulus to activate and recruit BAT remains to be ascertained. We aimed to examine whether objectively measured PA levels were associated with BAT volume and activity in young sedentary adults. We additionally examined the association of PA levels with the skeletal muscles activity.Methods: A total of 130 young healthy and sedentary adults (67% women; age, 21.9 +/- 2.1 years old; body mass index, 25 +/- 4.8 kg/m(2)) participated in this cross-sectional study. PA was objectively measured with a wrist-worn accelerometer for 7 consecutive days. Age-specific cut points were applied to classify wrist accelerations into sedentary time and different PA intensities (i.e., light, moderate, vigorous, moderate-vigorous). The participants underwent 2 hours of a personalized cold exposure to determine the cold-induced BAT volume and activity and the skeletal muscles activity by means of an F-18 fluorodeoxyglucose positron emission tomography combined with a CT scan.Results: Objectively measured PA intensity levels were neither associated with BAT volume and activity nor with the skeletal muscles activity (all P> 0.05). The results remained after adjusting for sex, waking time, and environmental temperature.Conclusions: Although PA plays an important role in the prevention of obesity and related comorbidities, it seems that other physiological mechanisms rather than brown adipocyte activation or recruitment might moderate its beneficial metabolic effects in young sedentary adults. Show less
Having valid and reliable resting energy expenditure (REE) estimations is crucial to establish reachable goals for dietary and exercise interventions. However, most of the REE predictive equations... Show moreHaving valid and reliable resting energy expenditure (REE) estimations is crucial to establish reachable goals for dietary and exercise interventions. However, most of the REE predictive equations were developed some time ago and, as the body composition of the current population has changed, it is highly relevant to assess the validity of REE predictive equations in contemporary young adults. In addition, little is known about the role of sex and weight status on the validity of these predictive equations. Therefore, this study aimed to investigate the role of sex and weight status in congruent validity of REE predictive equations in young adults. A total of 132 young healthy adults (67.4% women, 18-26 years old) participated in the study. We measured REE by indirect calorimetry strictly following the standard procedures, and we compared it to 45 predictive equations. The most accurate equations were the following: (i) the Schofield and the Food and Agriculture Organization of the United Nations/World Health Organization/United Nations (FAO/WHO/UNU) equations in normal weight men; (ii) the Mifflin and FAO/WHO/UNU equations in normal weight women; (iii) the Livingston and Korth equations in overweight men; (iv) the Johnstone and Frankenfield equations in overweight women; (v) the Owen and Bernstein equations in obese men; and (vi) the Owen equation in obese women. In conclusion, the results of this study show that the best equation to estimate REE depends on sex and weight status in young healthy adults. Show less
