Human white-fat thermogenesis: Experimental and meta-analytic findings

© 2020 The Authors. Published by Taylor & Francis. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1080/23328940.2020.1769530White adipose tissue (WAT) thermogenic activity may play a role in whole-body energy balance and two of its main regulators are thought to be environmental temperature (Tenv) and exercise. Low Tenv may increase uncoupling protein one (UCP1; the main biomarker of thermogenic activity) in WAT to regulate body temperature. On the other hand, exercise may stimulate UCP1 in WAT, which is thought to alter body weight regulation. However, our understanding of the roles (if any) of Tenv and exercise in WAT thermogenic activity remains incomplete. Our aim was to examine the impacts of low Tenv and exercise on WAT thermogenic activity, which may alter energy homeostasis and body weight regulation. We conducted a series of four experimental studies, supported by two systematic reviews and meta-analyses. We found increased UCP1 mRNA (p = 0.03; but not protein level) in human WAT biopsy samples collected during the cold part of the year, a finding supported by a systematic review and meta-analysis (PROSPERO review protocol: CRD42019120116). Additional clinical trials (NCT04037371; NCT04037410) using Positron Emission Tomography/Computed Tomography (PET/CT) revealed no impact of low Tenv on human WAT thermogenic activity (p > 0.05). Furthermore, we found no effects of exercise on UCP1 mRNA or protein levels (p > 0.05) in WAT biopsy samples from a human randomized controlled trial (Clinical trial: NCT04039685), a finding supported by systematic review and meta-analytic data (PROSPERO review protocol: CRD42019120213). Taken together, the present experimental and meta-analytic findings of UCP1 and SUVmax, demonstrate that cold and exercise may play insignificant roles in human WAT thermogenic activity. Abbreviations: WAT:White adipose tissue; Tenv: Environmental temperature; UCP1: Uncoupling protein one; BAT: Brown adipose tissue; BMI:Body mass index; mRNA: Messenger ribonucleic acid; RCT: Randomized controlled trial; WHR: Waist-to-hip ratio; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; PET/CT: Positron Emission Tomography and Computed Tomography; REE: Resting energy expenditure; 18F-FDG: F18 fludeoxyglucose; VO2peak:Peak oxygen consumption; 1RM: One repetition maximum; SUVmax: Maximum standardized uptake value; Std: Standardized mean difference.This work was supported by funding from the European Union 7th Framework Program FP7-PEOPLE-2012-IRSES grant no. [319010]; FP7-PEOPLE-2013-IRSES grant no. [612547] and Horizon 2020 ICI-THROUGH grant no [645710].Published versio

Predictors of the experience of a Cytosponge test: analysis of patient survey data from the BEST3 trial

Availability of data and materials: The trial protocol, statistical analysis plan, and statistical report are available via the University of Cambridge data repository (https://www.data.cam.ac.uk/repository). Datasets will be available from R Fitzgerald ([email protected]) on request.Copyright © The Author(s) 2023. Background: The Cytosponge is a cell-collection device, which, coupled with a test for trefoil factor 3 (TFF3), can be used to diagnose Barrett’s oesophagus, a precursor condition to oesophageal adenocarcinoma. BEST3, a large pragmatic, randomised, controlled trial, investigated whether offering the Cytosponge-TFF3 test would increase detection of Barrett’s. Overall, participants reported mostly positive experiences. This study reports the factors associated with the least positive experience. Methods: Patient experience was assessed using the Inventory to Assess Patient Satisfaction (IAPS), a 22-item questionnaire, completed 7–14 days after the Cytosponge test. Study cohort: All BEST3 participants who answered ≥ 15 items of the IAPS (N = 1458). Statistical analysis: A mean IAPS score between 1 and 5 (5 indicates most negative experience) was calculated for each individual. ‘Least positive’ experience was defined according to the 90th percentile. 167 (11.4%) individuals with a mean IAPS score of ≥ 2.32 were included in the ‘least positive’ category and compared with the rest of the cohort. Eleven patient characteristics and one procedure-specific factor were assessed as potential predictors of the least positive experience. Multivariable logistic regression analysis using backwards selection was conducted to identify factors independently associated with the least positive experience and with failed swallow at first attempt, one of the strongest predictors of least positive experience. Results: The majority of responders had a positive experience, with an overall median IAPS score of 1.7 (IQR 1.5–2.1). High (OR = 3.01, 95% CI 2.03–4.46, p < 0.001) or very high (OR = 4.56, 95% CI 2.71–7.66, p < 0.001) anxiety (relative to low/normal anxiety) and a failed swallow at the first attempt (OR = 3.37, 95% CI 2.14–5.30, p < 0.001) were highly significant predictors of the least positive patient experience in multivariable analyses. Additionally, sex (p = 0.036), height (p = 0.032), alcohol intake (p = 0.011) and education level (p = 0.036) were identified as statistically significant predictors. Conclusion: We have identified factors which predict patient experience. Identifying anxiety ahead of the procedure and discussing particular concerns with patients or giving them tips to help with swallowing the capsule might help improve their experience. Trial registration ISRCTN68382401.The BEST3 trial was funded by Cancer Research UK (C14478/A21047), National Institute for Health Research covering service support costs, the UK National Health Service funding excess treatment costs and Medtronic providing funding for Cytosponge devices and TFF3 antibodies. RCF is funded by a Programme Grant from the Medical Research Council (RG84369) and is CI for the BEST3 trial and the Innovate UK funded DELTA study. JO was supported by PDS’s Cancer Research UK programme Grant (C8162/A16892) and is currently supported by the Barts Charity (EMSG1K1R). RM was supported by PDS’ Cancer Research UK Cancer Prevention Clinical Trials Unit funding (Grant No.: C8162/A25356). SGS is supported by a Yorkshire Cancer Research Fellowship. JW is funded by a Cancer Research UK career development fellowship (C7492/A17219). BG was funded as part of the DELTA study by Innovate UK (Grant No. 41162). FW is supported by the Cancer Research UK CanTest Grant [C8640/A23385]. RL is supported by the Intramural Research Program of the US National Institutes of Health/National Cancer Institute

The Effect of Cold Dialysis in Motor and Sensory Symptoms of RLS/WED Occurring During Hemodialysis

Restless legs syndrome/Willis–Ekbom disease (RLS/WED) is a common sensorimotory disorder affecting almost 30% of hemodialysis (HD) patients. RLS/WED induces discomfort during rest hours, and its symptoms have also been observed during HD sessions. Anecdotal reports suggest that cooling the dialysate solution during dialysis could help patients overcome those symptoms and improve restlessness. The aim of this double-blind study was to assess whether a reduction of the dialysate temperature by 1°C could reduce motor and sensory symptoms of RLS/WED occurring during HD. Thirty-two HD patients participated in the study. Patients were divided into two groups: the RLS (N=16) and the non-RLS groups (N=16). Patients were studied on two different scenarios for two consecutive HD sessions, 1 week apart: 1) standard temperature of the dialysate (37°C) and 2) low temperature of the dialysate (36°C cold dialysis scenario). In all sessions, motor (leg movement per hour of HD [LM/hHD]) and sensory symptoms were assessed. The reduction of dialysate temperature by 1°C was effective in reducing motor symptoms as they assessed the LM/hHD by 36% only in patients with RLS, while a significant interaction was found between “LM/hHD affected by temperature” and “RLS status” (p = 0.039). Sensory symptoms also reduced by 10% after the reduction of the dialysate temperature. The reduction of the dialysate temperature by 1°C reduced motor symptoms by 36–54% and sensory symptoms by 10% in HD patients with RLS/WED. Cold dialysis could be considered a safe nonpharmacological approach for the amelioration of RLS/WED symptoms occurring during HD

Long-term intradialytic hybrid exercise training on fatigue symptoms in patients receiving hemodialysis therapy

Purpose: Hemodialysis (HD) patients suffer from generalized weakness, exercise intolerance and muscle atrophy, all leading to generalized fatigue and lack of energy. HD patients spend at least 50% of their time in a functionally “switch off” mode with their fatigue sensations reaching a peak in the immediate hours after the dialysis session. The purpose of the current study was to assess the effectiveness of a nine-month hybrid intradialytic exercise program on fatigue symptoms occurring during and after hemodialysis session. Methods: Twenty stable hemodialysis patients were included in the study (59 ± 13.7 years; 16 males). All patients completed a 9-month supervised exercise training program composed of both aerobic cycling and resistance training during HD. Aspects related to physical and generalized fatigue were assessed via validated questionnaires, while physical performance was assessed by a battery of tests, before and after the intervention period. Results: Exercise capacity and physical performance were increased by an average of 65 and 40%, respectively. Patients reported feeling better during post-dialysis hours in question 1 (p = 0.000), question 3 (p = 0.009) and question 4 (p = 0.003) after the 9-month intervention. In addition, exercise training improved scores in cognitive function (p = 0.037), vitality (p = 0.05), depression (p = 0.000) and fatigue (p = 0.039). Conclusion: The present study showed that a 9-month hybrid (aerobic + resistance) exercise training program improved symptoms of post-dialysis fatigue and overall general perception of fatigue. Hybrid exercise training is a safe and effective non-pharmacological approach to ameliorate fatigue symptoms in HD patients

Effects of 12 months of detraining on health-related quality of life in patients receiving hemodialysis therapy

Purpose: Limited data exist regarding the effects of detraining on functional capacity and quality of life (QoL) in the hemodialysis population. The aim of the current study was to assess whether the discontinuation from a systematic intradialytic exercise training program will affect aspects of health-related QoL and functional capacity in hemodialysis patients. Methods Seventeen hemodialysis patients (12 Males/5 Females, age 60.8 ± 13.6 year) participated in this study. Patients were assessed for functional capacity using various functional capacity tests while QoL, daily sleepiness, sleep quality, depression and fatigue were assessed using validated questionnaires at the end of a 12-month aerobic exercise program and after 12 months of detraining. Results:The detraining significantly reduced patients’ QoL score by 20% (P = 0.01). More affected were aspects related to the physical component summary of the QoL (P < 0.001) rather than those related to the mental one (P = 0.096). In addition, the performance in the functional capacity tests was reduced (P < 0.05), while sleep quality (P = 0.020) and daily sleepiness scores (P = 0.006) were significantly worse after the detraining period. Depressive symptoms (P = 0.214) and the level of fatigue (P = 0.163) did not change significantly. Conclusions: Detraining has a detrimental effect in patients’ QoL, functional capacity and sleep quality. The affected physical health contributed significantly to the lower QoL score. It is crucial for the chronic disease patients, even during emergencies such as lockdowns and restrictions in activities to maintain a minimum level of activity to preserve some of the acquired benefits and maintain their health status

Human white-fat thermogenesis: Experimental and meta-analytic findings

White adipose tissue (WAT) thermogenic activity may play a role in whole-body energy balance and two of its main regulators are thought to be environmental temperature (Tenv) and exercise. Low Tenv may increase uncoupling protein one (UCP1; the main biomarker of thermogenic activity) in WAT to regulate body temperature. On the other hand, exercise may stimulate UCP1 in WAT, which is thought to alter body weight regulation. However, our understanding of the roles (if any) of Tenv and exercise in WAT thermogenic activity remains incomplete. Our aim was to examine the impacts of low Tenv and exercise on WAT thermogenic activity, which may alter energy homeostasis and body weight regulation. We conducted a series of four experimental studies, supported by two systematic reviews and meta-analyses. We found increased UCP1 mRNA (p = 0.03; but not protein level) in human WAT biopsy samples collected during the cold part of the year, a finding supported by a systematic review and meta-analysis (PROSPERO review protocol: CRD42019120116). Additional clinical trials (NCT04037371; NCT04037410) using Positron Emission Tomography/Computed Tomography (PET/CT) revealed no impact of low Tenv on human WAT thermogenic activity (p &gt; 0.05). Furthermore, we found no effects of exercise on UCP1 mRNA or protein levels (p &gt; 0.05) in WAT biopsy samples from a human randomized controlled trial (Clinical trial: NCT04039685), a finding supported by systematic review and meta-analytic data (PROSPERO review protocol: CRD42019120213). Taken together, the present experimental and meta-analytic findings of UCP1 and SUVmax, demonstrate that cold and exercise may play insignificant roles in human WAT thermogenic activity. Abbreviations: WAT:White adipose tissue; Tenv: Environmental temperature; UCP1: Uncoupling protein one; BAT: Brown adipose tissue; BMI:Body mass index; mRNA: Messenger ribonucleic acid; RCT: Randomized controlled trial; WHR: Waist-to-hip ratio; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; PET/CT: Positron Emission Tomography and Computed Tomography; REE: Resting energy expenditure; 18F-FDG: F18 fludeoxyglucose; VO2peak:Peak oxygen consumption; 1RM: One repetition maximum; SUVmax: Maximum standardized uptake value; Std: Standardized mean difference. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group