Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species.

Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.

Performance of the cobas EBV and cobas BKV assays: multi-site comparison of standardized quantitation.

Guidelines recommend monitoring of Epstein-Barr virus (EBV) and BK virus (BKV) in solid organ and hematopoietic stem cell transplant patients. The majority of quantitative DNA testing for EBV and BKV employs unstandardized individual laboratory-developed testing solutions (LDTs), with implications for accuracy, reproducibility, and comparability between laboratories. The performance of the cobas EBV and cobas BKV assays was assessed across five laboratories, using the World Health Organization International Standards (WHO IS) for EBV and BKV, and the National Institute of Standards and Technology Quantitative Standard for BKV, and results were compared with the LDTs in use at the time. Methods were also compared using locally sourced clinical specimens. Variation was high when laboratories reported EBV or BKV DNA values using LDTs, where quantitative values were observed to differ by up to 1.5 log10 unit/mL between sites. Conversely, results from the cobas EBV and cobas BKV assays were accurate and reproducible across sites and on different testing days. Adjustment of LDTs using the international standards led to closer alignment between the assays; however, day-to-day reproducibility of LDTs remained high. In addition, BKV continued to show bias, indicating challenges with the commutability of the BKV International Standard. The cobas EBV and cobas BKV assays are automated, aligned to the WHO IS, and have the potential to reduce the variability in viral load testing introduced by differences in LDTs. Standardization of reporting values may eventually allow different centers to compare data to allow clinical decision thresholds to be established supporting improvements in patient management.IMPORTANCEThe application of center-specific cut-offs for clinical decisions and the variability of LDTs often hinder interpretation; thus, the findings reported here support the need for standardization in the field of post-transplant monitoring of EBV and BKV to improve patient management. Alongside the choice of assay, it is also important to consider which standard to use when deciding upon a testing methodology. This is a call to action for standardization, as treatment for EBV and BKV is driven by viral load test results, and the more accurate and comparable the test results are across institutions, the more informed and better the treatment decisions can be.

Short, frequent, light-intensity walking activity improves postprandial vascular-inflammatory biomarkers in people with type 1 diabetes: The SIT-LESS randomized controlled trial.

AIM: To examine the effect of interrupting prolonged sitting with short, frequent, light-intensity activity on postprandial cardiovascular markers in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized crossover trial, 32 adults with T1D (mean ± SD age 28 ± 5 years, glycated haemoglobin 67.9 ± 12.6 mmol/mol, 17 women) completed two 7-h laboratory visits separated by >7 days. Participants either remained seated for 7 h (SIT) or interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals commencing 1 h after each meal (SIT-LESS). Physical activity, insulin regimen, experimental start times, and meal consumption were standardized during each arm. Plasma levels of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, plasminogen activator inhibitor (PAI)-1 and fibrinogen were sampled at baseline, 3.5 and 7 h, and assessed for within- and between-group effects using a repeated measures ANOVA. The estimated glucose disposal rate was used to determine the insulin resistance status. RESULTS: Vascular-inflammatory parameters were comparable between SIT and SIT-LESS at baseline (p > .05). TNF-α, IL-1ß, PAI-1 and fibrinogen increased over time under SIT, whereas these rises were attenuated under SIT-LESS (p < .001). Specifically, over the 7 h under SIT, postprandial increases were detected in TNF-α, IL-1ß, PAI-1 and fibrinogen (+67%, +49%, +49% and +62%, respectively; p < .001 for all). Conversely, the SIT-LESS group showed no change in IL-1ß (-9%; p > .50), whereas reductions were observed in TNF-α, PAI-1 and fibrinogen (-22%, -42% and -44%, respectively; p < .001 for all). The intervention showed enhanced effects in insulin-resistant individuals with T1D. CONCLUSIONS: Interrupting prolonged sitting with light-intensity activity ameliorates postprandial increases in vascular-inflammatory markers in T1D. TRIAL REGISTRATION: The trial was prospectively registered (ISRCTN13641847).

PivNG primers and probes set used in the cobas omni Utility Channel is a reliable supplemental test for detection of Neisseria gonorrhoeae in oropharyngeal, urogenital and rectal specimens collected in cobas PCR Media.

OBJECTIVE: To evaluate the clinical performance of the novel PivNG primers and probes set (PivNG test) used in the cobas omni Utility Channel for supplemental testing of Neisseria gonorrhoeae (NG). METHODS: Oropharyngeal, urogenital and rectal samples were self-collected during routine testing at Barts Health sexual health clinics, London, UK. Samples were tested by the cobas CT/NG test and PivNG cobas omni Utility Channel test on cobas 6800/8800 Systems. Supplemental testing was carried out with the Xpert CT/NG test. PivNG overall percent agreements, positive percent agreements (PPAs)/negative percent agreements (NPAs) and positive/negative predictive values were calculated for each sample type. Microscopy and/or culture data were included for a randomised subset of concordant/discordant results, and a composite reference standard (cobas CT/NG, Xpert CT/NG and culture results) adjusted for partial verification bias was used to determine PivNG PPA and NPA. RESULTS: Of 447 evaluable samples with valid results from all three assays (cobas CT/NG, PivNG and Xpert CT/NG), 288 (64.4%) were NG-positive by both PivNG and cobas CT/NG; 117 (26.2%) were NG-negative in both tests; and 42 (9.4%) had discordant results (with NG-negative supplementary Xpert) CT/NG results in 40/42 instances). Of 19 PivNG/Xpert CT/NG-discordant samples, 11 were confirmed NG-positive by microscopy and/or culture results. PivNG PPA and NPA were 100% and 91% for oropharyngeal swabs, 100% and 100% for vaginal swabs, 100% and 100% for male urine samples, and 100% and 97% for rectal swabs, respectively, compared with the partially adjusted composite reference standard. CONCLUSIONS: PivNG is a reliable supplementary test with high sensitivity for confirming NG infection when used in conjunction with the cobas CT/NG test and samples collected in cobas PCR Media. Moreover, the PivNG test offers a convenient, high-throughput solution for supplemental NG testing of various sample types, with the potential to reduce the number of indeterminate reports.

The importance of fat-free mass and constituent tissue-organs in the control of human appetite.

PURPOSE OF REVIEW: Traditional models of human appetite focus on the contribution of adipose tissue and the gastrointestinal tract, both of which exert mainly inhibitory influences. The purpose of this review is to consider the biological factors that influence the drive to eat. RECENT FINDINGS: Fat-free mass is positively associated with objectively measured meal size and daily energy intake. These findings have been replicated in multiple populations across the life-course in laboratory and free-living studies. Studies have shown that the effect of fat-free mass is statistically mediated by resting metabolic rate, suggesting that energy expenditure per se may influence energy intake. A recent MRI study has reported that fasting hunger was associated with high metabolic rate organ (heart, liver, brain, kidneys) and skeletal muscle mass. Integrating measures of body composition at the tissue-organ level and markers of their metabolic function with appetitive measures could provide novel insight into the mechanisms that influence appetite. SUMMARY: These recent findings suggest that fat-free mass and resting metabolic rate are determinants of energy intake. Consideration of fat-free mass and energy expenditure as physiological sources of appetitive signals helps reconcile the mechanisms underpinning the inhibition of eating with those that drive eating.

Interrupting prolonged sitting with frequent short bouts of light-intensity activity in people with type 1 diabetes improves glycaemic control without increasing hypoglycaemia: The SIT-LESS randomised controlled trial.

AIM: To examine the impact of interrupting prolonged sitting with frequent short bouts of light-intensity activity on glycaemic control in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In total, 32 inactive adults with T1D [aged 27.9 ± 4.7 years, 15 men, diabetes duration 16.0 ± 6.9 years and glycated haemoglobin 8.4 ± 1.4% (68 ± 2.3 mmol/mol)] underwent two 7-h experimental conditions in a randomised crossover fashion with >7-day washout consisting of: uninterrupted sitting (SIT), or, interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals (SIT-LESS). Standardised mixed-macronutrient meals were administered 3.5 h apart during each condition. Blinded continuous glucose monitoring captured interstitial glucose responses during the 7-h experimental period and for a further 48-h under free-living conditions. RESULTS: SIT-LESS reduced total mean glucose (SIT 8.2 ± 2.6 vs. SIT-LESS 6.9 ± 1.7 mmol/L, p = .001) and increased time in range (3.9-10.0 mmol/L) by 13.7% (SIT 71.5 ± 9.5 vs. SIT-LESS 85.1 ± 7.1%, p = .002). Hyperglycaemia (>10.0 mmol/L) was reduced by 15.0% under SIT-LESS (SIT 24.2 ± 10.8 vs. SIT-LESS 9.2 ± 6.4%, p = .002), whereas hypoglycaemia exposure (<3.9 mmol/L) (SIT 4.6 ± 3.0 vs. SIT-LESS 6.0 ± 6.0%, p = .583) was comparable across conditions. SIT-LESS reduced glycaemic variability (coefficient of variation %) by 7.8% across the observation window (p = .021). These findings were consistent when assessing discrete time periods, with SIT-LESS improving experimental and free-living postprandial, whole-day and night-time glycaemic outcomes (p < .05). CONCLUSIONS: Interrupting prolonged sitting with frequent short bouts of light-intensity activity improves acute postprandial and 48-h glycaemia in adults with T1D. This pragmatic strategy is an efficacious approach to reducing sedentariness and increasing physical activity levels without increasing risk of hypoglycaemia in T1D.

Fat-Free Mass and Total Daily Energy Expenditure Estimated Using Doubly Labeled Water Predict Energy Intake in a Large Sample of Community-Dwelling Older Adults.

BACKGROUND: Up to 30% of community-based older adults report reduced appetite and energy intake (EI), but previous research examining the underlying physiological mechanisms has focused on the mechanisms that suppress eating rather than the hunger drive and EI. OBJECTIVES: We examined the associations between fat-free mass (FFM), physical activity (PA), total daily energy expenditure (TDEE), and self-reported EI in older adults. METHODS: The present study was a secondary analysis of the Interactive Diet and Activity Tracking in AARP study. Body composition (deuterium dilution), PA (accelerometry), and TDEE (doubly labeled water) were measured in 590 older adults (age, 63.1 ± 5.9 years; BMI, 28.1 ± 4.9 kg/m2). The total daily EI was estimated from a single 24-hour dietary recall (EIsingle; ±1 month of PA and TDEE measurement) and the mean of up to 6 recalls over a 12-month period (EImean), with misreporters classified using the 95% CIs between the EImean and TDEE. RESULTS: After controlling for age and sex, linear regression demonstrated that FFM and TDEE predicted EI when estimated from a single 24-hour dietary recall (P < 0.05), from the mean of up to 6 dietary recalls (P < 0.05), and after the removal of those classified as underreporters (P < 0.001). Age moderated the associations between FFM and EIsingle (P < 0.001), FFM and EImean (P < 0.001), and TDEE with EIsingle (P = 0.016), with associations becoming weaker across age quintiles. CONCLUSIONS: These data suggest that the total daily EI is proportional to the FFM and TDEE, but not fat mass, in older adults. These associations may reflect an underling drive to eat that influences the daily food intake. While the associations between FFM or TDEE and EI existed across all age quintiles, these associations weakened with increasing age.

Fat-Free Mass and Total Daily Energy Expenditure Estimated Using Doubly Labeled Water Predict Energy Intake in a Large Sample of Community-Dwelling Older Adults.

BACKGROUND: Up to 30% of community-based older adults report reduced appetite and energy intake (EI), but previous research examining the underlying physiological mechanisms has focused on the mechanisms that suppress eating rather than the hunger drive and EI. OBJECTIVES: We examined the associations between fat-free mass (FFM), physical activity (PA), total daily energy expenditure (TDEE), and self-reported EI in older adults. METHODS: The present study was a secondary analysis of the Interactive Diet and Activity Tracking in AARP study. Body composition (deuterium dilution), PA (accelerometry), and TDEE (doubly labeled water) were measured in 590 older adults (age, 63.1 ± 5.9 years; BMI, 28.1 ± 4.9 kg/m2). The total daily EI was estimated from a single 24-hour dietary recall (EIsingle; ±1 month of PA and TDEE measurement) and the mean of up to 6 recalls over a 12-month period (EImean), with misreporters classified using the 95% CIs between the EImean and TDEE. RESULTS: After controlling for age and sex, linear regression demonstrated that FFM and TDEE predicted EI when estimated from a single 24-hour dietary recall (P < 0.05), from the mean of up to 6 dietary recalls (P < 0.05), and after the removal of those classified as underreporters (P < 0.001). Age moderated the associations between FFM and EIsingle (P < 0.001), FFM and EImean (P < 0.001), and TDEE with EIsingle (P = 0.016), with associations becoming weaker across age quintiles. CONCLUSIONS: These data suggest that the total daily EI is proportional to the FFM and TDEE, but not fat mass, in older adults. These associations may reflect an underling drive to eat that influences the daily food intake. While the associations between FFM or TDEE and EI existed across all age quintiles, these associations weakened with increasing age.

Increases in physical activity are associated with a faster rate of weight loss during dietary energy restriction in women with overweight and obesity.

This secondary analysis examined the influence of changes in physical activity (PA), sedentary time and energy expenditure (EE) during dietary energy restriction on the rate of weight loss (WL) and 1-year follow-up weight change in women with overweight/obesity.Measurements of body weight and composition (air-displacement plethysmography), resting metabolic rate (indirect calorimetry), total daily (TDEE) and activity EE (AEE), minutes of PA and sedentary time (PA monitor) were taken at baseline, after 2 weeks, after ≥5% WL or 12 weeks of continuous (25% daily energy deficit) or intermittent (75% daily energy deficit alternated with ad libitum day) energy restriction, and at 1-year post-WL. The rate of WL was calculated as total %WL/number of dieting weeks. Data from both groups were combined for analyses.Thirty-seven participants (age=35±10y; BMI=29.1±2.3kg/m2) completed the intervention (WL=-5.9±1.6%) and 18 returned at 1-year post-WL (weight change=+4.5±5.2%). Changes in sedentary time at 2 weeks were associated with the rate of WL during energy restriction (r=-0.38; p=0.03). Changes in total (r=0.54; p<0.01), light (r=0.43; p=0.01) and moderate-to-vigorous PA (r=0.55; p<0.01), sedentary time (r=-0.52; p<0.01), steps per day (r=0.39; p=0.02), TDEE (r=0.46; p<0.01) and AEE (r=0.51; p<0.01) during energy restriction were associated with the rate of WL. Changes in total (r=-0.50; p=0.04) and moderate-to-vigorous PA (r=-0.61; p=0.01) between post-WL and follow-up were associated with 1-year weight change (r=-0.51; p=0.04).These findings highlight that PA and sedentary time could act as modifiable behavioural targets to promote better weight outcomes during dietary energy restriction and/or weight maintenance.

Does adaptive thermogenesis occur after weight loss in adults? A systematic review.

Adaptive thermogenesis (AT) has been proposed to be a compensatory response that may resist weight loss (WL) and promote weight regain. This systematic review examined the existence of AT in adults after a period of negative energy balance (EB) with or without a weight stabilisation phase. Studies published until 15 May 2020 were identified from PubMed, Cochrane Library, EMBASE, MEDLINE, SCOPUS and Web of Science. Inclusion criteria included statistically significant WL, observational with follow-up or experimental studies, age > 18y, sample size ≥10 participants, intervention period ≥ 1week, published in English, objective measures of total daily energy expenditure (EE) (TDEE), resting EE (REE) and sleeping EE(SEE). The systematic review was registered at PROSPERO (2020 CRD42020165348). A total of thirty-three studies comprising 2528 participants were included. AT was observed in twenty-seven studies. Twenty-three studies showed significant values for AT for REE (82·8 %), four for TDEE (80·0 %) and two for SEE (100 %). A large heterogeneity in the methods used to quantify AT and between subjects and among studies regarding the magnitude of WL and/or of AT was reported. Well-designed studies reported lower or non-significant values for AT. These findings suggest that although WL may lead to AT in some of the EE components, these values may be small or non-statistically significant when higher-quality methodological designs are used. Furthermore, AT seems to be attenuated, or non-existent, after periods of weight stabilisation/neutral EB. More high-quality studies are warranted not only to disclose the existence of AT but also to understand its clinical implications on weight management outcomes.

Effects of a 4-month active weight loss phase followed by weight loss maintenance on adaptive thermogenesis in resting energy expenditure in former elite athletes.

PURPOSE: Despite adaptive thermogenesis (AT) being studied as a barrier to weight loss (WL), few studies assessed AT in the resting energy expenditure (REE) compartment after WL maintenance. The aim of this study was twofold: (1) to understand if AT occurs after a moderate WL and if AT persists after a period of WL maintenance; and (2) if AT is associated with changes in body composition, hormones and energy intake (EI). METHODS: Ninety-four participants [mean (SD); BMI, 31.1(4.3)kg/m2; 43.0(9.4)y; 34% female] were randomized to intervention (IG, n = 49) or control groups (CG, n = 45). Subjects underwent a 1-year lifestyle intervention, divided in 4 months of an active WL followed by 8 months of WL maintenance. Fat mass (FM) and fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry and REE by indirect calorimetry. Predicted REE (pREE) was estimated through a model using FM, FFM. EI was measured by the "intake-balance" method. RESULTS: For the IG, the weight and FM losses were - 4.8 (4.9) and - 11.3 (10.8)%, respectively (p < 0.001). A time-group interaction was found between groups for AT. After WL, the IG showed an AT of -85(29) kcal.d-1 (p < 0.001), and remained significant after 1 year [AT = - 72(31)kcal.d-1, p = 0.031]. Participants with higher degrees of restriction were those with an increased energy conservation (R = - 0.325, p = 0.036 and R = - 0.308, p = 0.047, respectively). No associations were found between diet adherence and AT. Following a sub-analysis in the IG, the group with a higher energy conservation showed a lower WL and fat loss and a higher initial EI. CONCLUSION: AT in REE occurred after a moderate WL and remained significant after WL maintenance. More studies are needed to better clarify the mechanisms underlying the large variability observed in AT and providing an accurate methodological approach to avoid overstatements. Future studies on AT should consider not only changes in FM and FFM but also the FFM composition.

Norovirus attribution study: Detection of norovirus from the commercial food preparation environment in outbreak and non-outbreak premises.

AIMS: Norovirus remains the most significant virological risk that is transmitted via food and the environment to cause acute gastroenteritis. This study aimed to investigate the hypothesis that the contamination of the commercial food production environment with norovirus will be higher in premises that have recently reported a foodborne norovirus outbreak than those that have not. METHODS: Sampling of commercial food production environments was carried out across a 16-month period between January 2015 and April 2016 in the South East and the North West of England by local authority environmental health departments as part of routine surveillance visits to premises. A total of 2982 samples, 2038 virological and 944 bacteriological, were collected from 256 premises. Sixteen of these premises, six from South East and ten from North West England, were sampled as part of a public health outbreak investigation. RESULTS & CONCLUSIONS: Overall, 2038 swabs were submitted for norovirus testing, with an average of eight swabs per premises (range 4 to 23) and a median of seven. Of the premises sampled, 11.7% (30/256) yielded at least one norovirus-positive sample (environmental, and/or food handler hand swab), and 2.5% of the swabs were positive for norovirus. A peak in the positivity rate was seen in the South East in April 2016. No associations were found between norovirus positivity and bacteriology indicators, or between bacteriology indicators and hygiene ratings. SIGNIFICANCE AND IMPACT OF STUDY: This study demonstrates that food premises and food handlers remain a potential source of norovirus transmission and outbreaks.

Identification of psychological correlates of dietary misreporting under laboratory and free-living environments.

Errors inherent in self-reported measures of energy intake (EI) are substantial and well documented, but correlates of misreporting remain unclear. Therefore, potential predictors of misreporting were examined. In Study One, fifty-nine individuals (BMI = 26·1 (sd 3·8) kg/m2, age = 42·7 (sd 13·6) years, females = 29) completed a 14-d stay in a residential feeding behaviour suite where eating behaviour was continuously monitored. In Study Two, 182 individuals (BMI = 25·7 (sd 3·9) kg/m2, age = 42·4 (sd 12·2) years, females = 96) completed two consecutive days in a residential feeding suite and five consecutive days at home. Misreporting was directly quantified by comparing covertly measured laboratory weighed intakes (LWI) with self-reported EI (weighed dietary record (WDR), 24-h recall, 7-d diet history, FFQ). Personal (age, sex and %body fat) and psychological traits (personality, social desirability, body image, intelligence quotient and eating behaviour) were used as predictors of misreporting. In Study One, those with lower psychoticism (P = 0·009), openness to experience (P = 0·006) and higher agreeableness (P = 0·038) reduced EI on days participants knew EI was being measured to a greater extent than on covert days. Isolated associations existed between personality traits (psychoticism and openness to experience), eating behaviour (emotional eating) and differences between the LWI and self-reported EI, but these were inconsistent between dietary assessment techniques and typically became non-significant after accounting for multiplicity of comparisons. In Study Two, sex was associated with differences between LWI and the WDR (P = 0·009), 24-h recall (P = 0·002) and diet history (P = 0·050) in the laboratory, but not home environment. Personal and psychological correlates of misreporting identified displayed no clear pattern across studies or dietary assessment techniques and had little utility in predicting misreporting.

A novel RBMX-TFE3 gene fusion in a highly aggressive pediatric renal perivascular epithelioid cell tumor.

We report an Xp11 translocation perivascular epithelioid cell tumor (PEComa) with a novel RBMX-TFE3 gene fusion, resulting from a paracentric X chromosome inversion, inv(X)(p11;q26). The neoplasm occurred in an otherwise healthy 12-year-old boy who presented with a large left renal mass with extension into the inferior vena cava. The patient was found to have multiple pulmonary metastases at diagnosis and died of disease 3 months later. The morphology (epithelioid clear cells with alveolar and nested architecture) and immunophenotype (TFE3 and HMB45 strongly positive; actin, desmin, and PAX8 negative) was typical of an Xp11 translocation PEComa; however, TFE3 rearrangement was initially not detected by routine TFE3 break-apart fluorescence in situ hybridization (FISH). Further RNA sequencing revealed a novel RBMX-TFE3 gene fusion, which was subsequently confirmed by fusion assay FISH, using custom design RBMX and TFE3 come-together probes. This report describes a novel TFE3 gene fusion partner, RBMX, in a pediatric renal PEComa patient associated with a fulminant clinical course. As documented in other intrachromosomal Xp11.2 inversions, such as fusions with NONO, RBM10, or GRIPAP1 genes, the TFE3 break-apart might be below the FISH resolution, resulting in a false negative result.

Consistent high prevalence of undiagnosed blood-borne virus infection in patients attending large urban emergency departments in England.

Understanding local viral hepatitis and HIV epidemiology is essential if WHO elimination targets are to be achieved. We demonstrate a consistently high prevalence of undiagnosed active infection in urban emergency department attendees in England, with variations in local risk groups crucial to informing targeted testing initiatives.

Matched Weight Loss Through Intermittent or Continuous Energy Restriction Does Not Lead To Compensatory Increases in Appetite and Eating Behavior in a Randomized Controlled Trial in Women with Overweight and Obesity.

BACKGROUND: Continuous energy restriction (CER) is purported to be problematic because of reductions in fat-free mass (FFM), compensatory motivation to overeat, and weakened satiety. Intermittent energy restriction (IER) is an alternative behavioral weight loss (WL) strategy that may mitigate some of these limitations. OBJECTIVE: The objective of the DIVA study was to compare the effects of CER and IER on appetite when the degree of WL (≥5%) is matched. METHODS: Women with overweight/obesity (BMI 25.0-34.9 kg/m2; age 18-55 y) were recruited for this controlled-feeding RCT via CER (25% daily energy restriction) or IER (alternating ad libitum and 75% energy restriction days). Probe days were conducted at baseline and post-intervention to assess body composition, ad libitum energy intake and subjective appetite in response to a fixed-energy breakfast, and eating behavior traits. After baseline measurements, participants were allocated to CER (n = 22) or IER (n = 24). Per protocol analyses (≥5% WL within 12 wk) were conducted with use of repeated measures ANOVA. RESULTS: Thirty of 37 completers reached ≥5% WL [CER (n = 18): 6.3 ± 0.8% in 57 ± 16 d, IER (n = 12): 6.6 ± 1.1% in 67 ± 13 d; % WL P = 0.43 and days P = 0.10]. Fat mass [-3.9 (95% CI: -4.3, -3.4) kg] and FFM [-1.3 (95% CI: -1.6, -1.0) kg] were reduced post-WL (P < 0.001), with no group differences. Self-selected meal size decreased post-WL in CER (P = 0.03) but not in IER (P = 0.19). Hunger AUC decreased post-WL (P < 0.05), with no group differences. Satiety quotient remained unchanged and was similar in both groups. Both interventions improved dietary restraint, craving control, susceptibility to hunger, and binge eating (P < 0.001). CONCLUSIONS: Controlled ≥5% WL via CER or IER did not differentially affect changes in body composition, reductions in hunger, and improvements in eating behavior traits. This suggests that neither CER nor IER lead to compensatory adaptations in appetite in women with overweight/obesity. This trial was registered at clinicaltrials.gov as NCT03447600.

Biomarkers of appetite: is there a potential role for metabolomics?

Knowing the biological signals associated with appetite control is crucial for understanding the regulation of food intake. Biomarkers of appetite have been defined as physiological measures that relate to subjective appetite ratings, measured food intake, or both. Several metabolites including amino acids, lipids and glucose were proposed as key molecules associated with appetite control over 60 years ago, and along with bile acids are all among possible appetite biomarker candidates. Additional metabolites that have been associated with appetite include endocannabinoids, lactate, cortisol and ß-hydroxybutyrate. However, although appetite is a complex integrative process, studies often investigated a limited number of markers in isolation. Metabolomics involves the study of small molecules or metabolites present in biological samples such as urine or blood, and may present a powerful approach to further the understanding of appetite control. Using multiple analytical techniques allows the characterisation of molecules, such as carbohydrates, lipids, amino acids, bile acids and fatty acids. Metabolomics has proven successful in identifying markers of consumption of certain foods and biomarkers implicated in several diseases. However, it has been underexploited in appetite control or obesity. The aim of the present narrative review is to: (1) provide an overview of existing metabolites that have been identified in human biofluids and associated with appetite control; and (2) discuss the potential of metabolomics to deepen understanding of appetite control in humans.

Improving energy expenditure estimates from wearable devices: A machine learning approach.

A means of quantifying continuous, free-living energy expenditure (EE) would advance the study of bioenergetics. The aim of this study was to apply a non-linear, machine learning algorithm (random forest) to predict minute level EE for a range of activities using acceleration, physiological signals (e.g., heart rate, body temperature, galvanic skin response), and participant characteristics (e.g., sex, age, height, weight, body composition) collected from wearable devices (Fitbit charge 2, Polar H7, SenseWear Armband Mini and Actigraph GT3-x) as potential inputs. By utilising a leave-one-out cross-validation approach in 59 subjects, we investigated the predictive accuracy in sedentary, ambulatory, household, and cycling activities compared to indirect calorimetry (Vyntus CPX). Over all activities, correlations of at least r = 0.85 were achieved by the models. Root mean squared error ranged from 1 to 1.37 METs and all overall models were statistically equivalent to the criterion measure. Significantly lower error was observed for Actigraph and Sensewear models, when compared to the manufacturer provided estimates of the Sensewear Armband (p < 0.05). A high degree of accuracy in EE estimation was achieved by applying non-linear models to wearable devices which may offer a means to capture the energy cost of free-living activities.

Biological and psychological mediators of the relationships between fat mass, fat-free mass and energy intake.

BACKGROUND: While recent studies in humans indicate that fat-free mass (FFM) is closely associated with energy intake (EI) when in energy balance, associations between fat mass (FM) and EI are inconsistent. OBJECTIVES: The present study used a cross-sectional design to examine the indirect and direct effects of FFM, FM and resting metabolic rate (RMR) on EI in individuals at or close to energy balance. METHODS: Data for 242 individuals (114 males; 128 females; BMI = 25.7 ± 4.9 kg/m2) were collated from the non-intervention baseline conditions of five studies employing common measures of body composition (air-displacement plethysmography), RMR (indirect calorimetry) and psychometric measures of eating behaviours (Dutch Eating Behaviour Questionnaire). Daily EI (weighed dietary records) and energy expenditure (flex heart rate) were measured for 6-7 days. Sub-analyses were conducted in 71 individuals who had additional measures of body composition (dual-energy X-ray absorptiometry) and fasting glucose, insulin and leptin. RESULTS: After adjusting for age, sex and study, linear regression and mediation analyses indicated that the effect of FFM on EI was mediated by RMR (P < 0.05). FM also independently predicted EI, with path analysis indicating a positive indirect association (mediated by RMR; P < 0.05), and a stronger direct negative association (P < 0.05). Leptin, insulin and insulin resistance failed to predict EI, but cognitive restraint was a determinant of EI and partially mediated the association between FM and EI (P < 0.05). CONCLUSIONS: While the association between FFM and EI was mediated by RMR, FM influenced EI via two separate and opposing pathways; an indirect 'excitatory' effect (again, mediated by RMR), and a stronger direct 'inhibitory' effect. Psychological factors such as cognitive restraint remain robust predictors of EI when considered alongside physiological determinants of EI, and indeed, have the potential to play a mediating role in the overall expression of EI.

Activity energy expenditure is an independent predictor of energy intake in humans.

BACKGROUND: There is evidence that the energetic demand of metabolically active tissue is associated with day-to-day food intake (EI). However, the extent to which behavioural components of total daily energy expenditure (EE) such as activity energy expenditure (AEE) are also associated with EI is unknown. Therefore, the present study examined the cross-sectional associations between body composition, resting metabolic rate (RMR), AEE and EI. METHODS: Data for 242 individuals (114 males; 128 females; BMI = 25.7 ± 4.9 kg/m2) were collated from the baseline control conditions of five studies employing common measures of body composition (air displacement plethysmography) and RMR (indirect calorimetry). Daily EI (weighed-dietary records) and EE (FLEX heart rate) were measured over 6-7 days, and AEE was calculated as total daily EE minus RMR. RESULTS: Linear regression indicated that RMR (ß = 0.39; P < 0.001), fat mass (ß = -0.26; P < 0.001) and AEE (ß = 0.18; P = 0.002) were independent predictors of mean daily EI, with AEE adding ≈3% of variance to the model after controlling for age, sex and study (F(10, 231) = 18.532, P < 0.001; R2 = 0.445). Path analyses indicated that the effect of FFM on mean daily EI was mediated by RMR (P < 0.05), while direct (ß = 0.19; P < 0.001) and indirect (ß = 0.20; P = 0.001) associations between AEE and mean daily EI were observed. CONCLUSIONS: When physical activity was allowed to vary under free-living conditions, AEE was associated with mean daily EI independently of other biological determinants of EI arising from body composition and RMR. These data suggest that EE per se exerts influence over daily food intake, with both metabolic (RMR) and behavioral (AEE) components of total daily EE potentially influencing EI via their contribution to daily energy requirements.