Indirect Calorimetry Data Research Articles

Angiopoietin-like 3 (ANGPTL3) deficiency alters metabolic substrates utilization and reprograms hepatic metabolism

Angiopoietin-like 3 (ANGPTL3) is a lipases-inhibiting hepatokine, thus prevents VLDL and LDL-derived triglycerides, regulating fluxes of triglycerides to the tissues. Aim of this study is to investigate the association between hypolipidemia-induced metabolic alteration, due to ANGPTL3 deficiency, and potential hepatic responses, depending on the source of energetic substrates available. Full-knockout (KO) mice and littermate controls (WT) underwent a standard chow diet or High Fat Diet (HFD, 60% kcal from fat) regimen for 16 weeks. Metabolic responses have been assessed through indirect calorimetry, lipid, glucose and insulin tolerance test, and circulating lipid levels have been evaluated. ANGPTL3 KO mice are hypolipidemic at fasting, postprandially and in fast refeeding, both at chow and HFD. After an oil gavage, ANGPTL3 KO mice absorb less triglycerides both at fasting (area under curve: HO:3320.8mg/dL*min±1214.9vsWT:17303 mg/dL*min±11765.2, p=0.07) and postprandially (area under curve: HO:447.3mg/dL*hr±20.9vsWT: 938.2mg/dL*hr ±294.9, p=0.016), and this associates with a lesser hepatic lipoprotein production, also at HFD. Glucose metabolism is not affected, and liver histology of KO mice at chow and HFD do not show increased steatosis compared to control group. Indirect calorimetry data show an increased trend of oxidative metabolism in the postprandial phase compared to controls (Respiratory Exchange Ratio at ZeitgeberTime21: HO: 0.889±0.102vsWT: 0.969±0.089; p=0.074). Hepatic mTOR activation has been investigated with western blotting, to understand a possible nutrient sensing alteration, by evaluating the phosphorylation of downstream effectors S6K (fold on housekeeping: HO:0.28±0.122vsWT:0.647±0.119; p=0.021) and 4E-BP1 (fold on housekeeping: HO: 0.503±0.193vsWT:1.043±0.270, p=0.048) and a dampened activation is observed. This is associated with a lower protein synthesis. RNA sequencing data confirmed that at chow diet KO mice face the activation of metabolic pathways such as urea cycle and bile acids production. Hepatic signalling pathways, like LXR, are blunted, at chow and HFD. ANGPTL3 deficiency alters the metabolic phenotype, reducing circulating lipemia, and an adaptive metabolic response occurs depending on the metabolic substrate availability.

Effect of carnitine supplementation on energy utilization in patients with type 2 diabetes and long-term tube feeding: A CARE-compliant case report

Introduction: Carnitine is essential for the energy utilization of long-chain fatty acids. However, the effects of carnitine supplementation on patients undergoing tube feeding remain unclear, and some enteral formula products do not contain carnitine. In order to gain insights into the role of carnitine supplementation on energy utilization in patients with long-term tube feeding, we observed the changes in respiratory quotient (RQ) of patients before and after the addition of carnitine due to the renewal of an enteral formula product. Case presentation: We observed 6 patients who continued tube feeding with the same enteral formula product scheduled for renewal. All 6 participants had diabetes, and indirect calorimetry data were available for 4 patients. Participants were observed for 3 months after switching to the new formulation. After the switching, a carnitine supplementation of 120 to 180 mg/day was provided, depending on the intake amount. One month after switching, blood free carnitine and total carnitine levels in all 6 patients increased from below the lower limit to within the range of the Japanese reference standard. In 3 of the 4 patients for whom indirect calorimetry was possible, the fasting RQ at baseline was >0.90, suggesting impaired lipid utilization. The mean fasting RQ significantly decreased 2 months after the switch. The 1- and 2-hour postprandial RQ also showed a significant decrease after switching. Conclusion: Carnitine supplementation of enteral formulas may be important for normal energy utilization of lipids in patients receiving long-term tube feeding. An evaluation using randomized controlled trials with a larger number of patients is required.

Validation of a musculoskeletal model for simulating muscle mechanics and energetics during diverse human hopping tasks.

Computational musculoskeletal modelling has emerged as an alternative, less-constrained technique to indirect calorimetry for estimating energy expenditure. However, predictions from modelling tools depend on many assumptions around muscle architecture and function and motor control. Therefore, these tools need to continue to be validated if we are to eventually develop subject-specific simulations that can accurately and reliably model rates of energy consumption for any given task. In this study, we used OpenSim software and experimental motion capture data to simulate muscle activations, muscle fascicle dynamics and whole-body metabolic power across mechanically and energetically disparate hopping tasks, and then evaluated these outputs at a group- and individual-level against experimental electromyography, ultrasound and indirect calorimetry data. Comparing simulated and experimental outcomes, we found weak to strong correlations for peak muscle activations, moderate to strong correlations for absolute fascicle shortening and mean shortening velocity, and strong correlations for gross metabolic power. These correlations tended to be stronger on a group-level rather than individual-level. We encourage the community to use our publicly available dataset from SimTK.org to experiment with different musculoskeletal models, muscle models, metabolic cost models, optimal control policies, modelling tools and algorithms, data filtering etc. with subject-specific simulations being a focal goal.

Impact of methods for data selection on the day-to-day reproducibility of resting metabolic rate assessed with four different metabolic carts

Background and aimsAccomplishing a high day-to-day reproducibility is important to detect changes in resting metabolic rate (RMR) and respiratory exchange ratio (RER) that may be produced after an intervention or for monitoring patients' metabolism over time. We aimed to analyze: (i) the influence of different methods for selecting indirect calorimetry data on RMR and RER assessments; and, (ii) whether these methods influence RMR and RER day-to-day reproducibility. Methods and resultsTwenty-eight young adults accomplished 4 consecutive RMR assessments (30-min each), using the Q-NRG (Cosmed, Rome, Italy), the Vyntus CPX (Jaeger-CareFusion, Höchberg, Germany), the Omnical (Maastricht Instruments, Maastricht, The Netherlands), and the Ultima CardiO2 (Medgraphics Corporation, St. Paul, Minnesota, USA) carts, on 2 consecutive mornings. Three types of methods were used: (i) short (periods of 5 consecutive minutes; 6–10, 11–15, 16–20, 21–25, and 26–30 min) and long time intervals (TI) methods (6–25 and 6–30 min); (ii) steady state (SSt methods); and, (iii) methods filtering the data by thresholding from the mean RMR (filtering methods). RMR and RER were similar when using different methods (except RMR for the Vyntus and RER for the Q-NRG). Conversely, using different methods impacted RMR (all P ≤ 0.037) and/or RER (P ≤ 0.009) day-to-day reproducibility in all carts. The 6–25 min and the 6–30 min long TI methods yielded more reproducible measurements for all metabolic carts. ConclusionThe 6–25 min and 6–30 min should be the preferred methods for selecting data, as they result in the highest day-to-day reproducibility of RMR and RER assessments.

Carbon dioxide generation rates for children and adolescents

The indoor CO2 concentration in elementary and middle school classrooms is primarily influenced by the CO2 generation rate of the occupants, the outdoor air ventilation rate, and the CO2 concentration in outdoor air. While there have been numerous studies on the CO2 generation rate of adults under different activities, there are limited studies on the CO2 generation rate of children and adolescents during typical activities. It is difficult to obtain data on CO2 generation rates for children and adolescents directly from relevant standards or literature through searching. This paper synthesized CO2 generation rates using indirect calorimetry data in the literature from more than 900 children and adolescents aged 5–18 years under light to vigorous 13 activities, and summarized them into a table so that researchers or designers can easily obtain them. The results show that, as expected, CO2 generation rates increase with activity levels, and age has a highly significant effect on CO2 generation rates in children and adolescents, while gender differences manifest only after age 15. Compared to adults, children aged 5–12 years have significantly lower CO2 generation rates. The findings supplement the missing data on the CO2 generation rate of children and adolescents in the ventilation standard, and also provide basic parameters for the use of CO2 as a tracer gas to quantify the ventilation rates of buildings and spaces in primary and secondary schools classrooms.

Exercise Timing Matters for Glycogen Metabolism and Accumulated Fat Oxidation over 24 h.

Due to increasingly diverse lifestyles, exercise timings vary between individuals: before breakfast, in the afternoon, or in the evening. The endocrine and autonomic nervous systems, which are associated with metabolic responses to exercise, show diurnal variations. Moreover, physiological responses to exercise differ depending on the timing of the exercise. The postabsorptive state is associated with greater fat oxidation during exercise compared to the postprandial state. The increase in energy expenditure persists during the post-exercise period, known as "Excess Post-exercise Oxygen Consumption". A 24 h evaluation of accumulated energy expenditure and substrate oxidation is required to discuss the role of exercise in weight control. Using a whole-room indirect calorimeter, researchers revealed that exercise performed during the postabsorptive state, but not during the postprandial state, increased accumulated fat oxidation over 24 h. The time course of the carbohydrate pool, as estimated by indirect calorimetry, suggests that glycogen depletion after postabsorptive exercise underlies an increase in accumulated fat oxidation over 24 h. Subsequent studies using 13C magnetic resonance spectroscopy confirmed that the variations in muscle and liver glycogen caused by postabsorptive or postprandial exercise were consistent with indirect calorimetry data. These findings suggest that postabsorptive exercise alone effectively increases 24 h fat oxidation.

Identifying the Predictors of Short Term Weight Loss Failure after Roux-En-Y Gastric Bypass.

Gastric bypass surgery is a gold standard therapy for severe obesity. This study aimed to evaluate anthropometric predictors for short-term excess weight loss (EWL) after Roux-en-Y gastric bypass surgery (RYGB) in a sample of severely obese patients. This cohort study was conducted on severely obese candidates for RYGB bariatric surgery in Mashhad, Iran. Indirect calorimetry, anthropometric measurements, and body composition data were collected before, one, and six months after RYGB. Fifty-four participants (43, 79.6% women and 11, 20.4% men) with a mean age of 39.63 ± 9.66 years participated in this study. The mean total weight and BMI loss within six months were 32.89 ± 20.22 kg and 12.37 ± 7.34 kg/m2, respectively. The mean reduction in adipose tissue and fat-free mass was 24.49 kg and 7.46 kg, respectively. The mean resting metabolism rate (RMR) reduction at one and six months after RYGB was 260.49 kcal and 396.07 kcal, respectively. There was a significant difference in mean RMR between the baseline and one and six months after RYGB (p < 0.001). There was no significant gender difference in mean weight and BMI loss percentage at six months post-RYGB (p > 0.05). Baseline skeletal muscle mass (SMM), excess BMI loss (EBMIL) at first month after surgery, and baseline neck circumference (NC) could predict EWL six months after surgery. Reduced RMR shortly after RYGB may be due to FFM reduction. Some anthropometric and their acute changes after RYGB may predict the short-term EWL in RYGB patients.

Pulmonary gas exchange evaluated by machine learning: a computer simulation

Using computer simulation we investigated whether machine learning (ML) analysis of selected ICU monitoring data can quantify pulmonary gas exchange in multi-compartment format. A 21 compartment ventilation/perfusion (V/Q) model of pulmonary blood flow processed 34,551 combinations of cardiac output, hemoglobin concentration, standard P50, base excess, VO2 and VCO2 plus three model-defining parameters: shunt, log SD and mean V/Q. From these inputs the model produced paired arterial blood gases, first with the inspired O2 fraction (FiO2) adjusted to arterial saturation (SaO2) = 0.90, and second with FiO2 increased by 0.1. ‘Stacked regressor’ ML ensembles were trained/validated on 90% of this dataset. The remainder with shunt, log SD, and mean ‘held back’ formed the test-set. ‘Two-Point’ ML estimates of shunt, log SD and mean utilized data from both FiO2 settings. ‘Single-Point’ estimates used only data from SaO2 = 0.90. From 3454 test gas exchange scenarios, two-point shunt, log SD and mean estimates produced linear regression models versus true values with slopes ~ 1.00, intercepts ~ 0.00 and R2 ~ 1.00. Kernel density and Bland–Altman plots confirmed close agreement. Single-point estimates were less accurate: R2 = 0.77–0.89, slope = 0.991–0.993, intercept = 0.009–0.334. ML applications using blood gas, indirect calorimetry, and cardiac output data can quantify pulmonary gas exchange in terms describing a 20 compartment V/Q model of pulmonary blood flow. High fidelity reports require data from two FiO2 settings.

High Energetic Demand of Elite Rowing – Implications for Training and Nutrition

Purpose: Elite rowers have large body dimensions, a high metabolic capacity, and they realize high training loads. These factors suggest a high total energy requirement (TER), due to high exercise energy expenditure (EEE) and additional energetic needs. We aimed to study EEE and intensity related substrate utilization (SU) of elite rowers during rowing (EEEROW) and other (EEENON-ROW) training. Methods: We obtained indirect calorimetry data during incremental (N = 174) and ramp test (N = 42) ergometer rowing in 14 elite open-class male rowers (body mass 91.8 kg, 95% CI [87.7, 95.9]). Then we calculated EEEROW and SU within a three-intensity-zone model. To estimate EEENON-ROW, appropriate estimates of metabolic equivalents of task were applied. Based on these data, EEE, SU, and TER were approximated for prototypical high-volume, high-intensity, and tapering training weeks. Data are arithmetic mean and 95% confidence interval (95% CI). Results: EEEROW for zone 1 to 3 ranged from 15.6 kcal·min−1, 95% CI [14.8, 16.3] to 49.8 kcal·min−1, 95% CI [48.1, 51.6], with carbohydrate utilization contributing from 46.4%, 95% CI [42.0, 50.8] to 100.0%, 95% CI [100.0, 100.0]. During a high-volume, a high-intensity, or a taper week, TER was estimated to 6,775 kcal·day−1, 95% CI [6,651, 6,898], 5,772 kcal·day−1, 95% CI [5,644, 5,900], or 4,626 kcal∙day−1, 95% CI [4,481, 4,771], respectively. Conclusion: EEE in elite open-class male rowers is remarkably high already during zone 1 training and carbohydrates are dominantly utilized, indicating relatively high metabolic stress even during low intensity rowing training. In high-volume training weeks, TER is presumably at the upper end of the sustainable total energy expenditure. Periodized nutrition seems warranted for rowers to avoid low energy availability, which might negatively impact performance, training, and health.

Validation of Resting Energy Expenditure Equations in Older Adults with Obesity

It is unclear which energy expenditure prediction equation should guide weight loss interventions in older adults with obesity. We ascertained the validity of four equations commonly used in practice in a series of weight loss studies of adults aged ≥65 with a body mass index ≥30kg/m2 using indirect calorimetry data. Diagnostic accuracy was defined as <10% discrepancy between predicted and measured resting metabolic rate (RMR). Mean was 73.4 years. RMR using the ReeVue was 1,643 kCal. With 59.0% accuracy, the WHO equation demonstrated the highest accuracy while the Harris-Benedict yielded 53.5% accuracy. The Owens equation demonstrated the least variability (21.5% overprediction, 27.8% underprediction) with 50.7% accuracy. A SECA bioimpedance analyzer noted the second lowest accuracy of 49.6%. Only 43.1% of measurements were within 10% of the gold-standard indirect calorimetry value using the Mifflin equation. All equations demonstrated <60% accuracy suggesting a great need for estimating energy needs.

Analysis of Thermogenesis Experiments with CalR.

Modern indirect calorimetry systems allow for high-frequency time series measurements of the factors affected by thermogenesis: energy intake and energy expenditure. These indirect calorimetry systems generate a flood of raw data recording oxygen consumption, carbon dioxide production, physical activity, and food intake among other factors. Analysis of these data requires time-consuming manual manipulation for formatting, data cleaning, quality control, and visualization. Beyond data handling, analyses of indirect calorimetry experiments require specialized statistical treatment to account for differential contributions of fat mass and lean mass to metabolic rates.Here we describe how to use the software package CalR version 1.2, to analyze indirect calorimetry data from three examples of thermogenesis, cold exposure, adrenergic agonism, and hyperthyroidism in mice, by providing standardized methods for reproducible research. CalR is a free online tool with an easy-to-use graphical user interface to import data files from the Columbus Instruments' CLAMS, Sable Systems' Promethion, and TSE Systems' PhenoMaster. Once loaded, CalR can quickly visualize experimental results and perform basic statistical analyses. We present a framework that standardizes the data structures and analyses of indirect calorimetry experiments to provide reusable and reproducible methods for the physiological data affecting body weight.

POSSIBILITIES OF USING PERIOPERATIVE ENERGY MONITORING IN INTENSIVE CARE IN PATIENTS WITH ACUTE CALCULOUS CHOLECYSTITIS.

The aim: To study possibilities of using perioperative energy monitoring in intensive care in patients with acute calculous cholecystitis (ACC). Materials and methods: 131 patients with ACC, who underwent laparoscopic cholecystectomy (LC) under general anesthesia were studied. Risk of ASA II-IV. Group I (n = 63) - intensive care aimed at maintaining vital functions. Group II (n = 68) - additional use of indirect calorimetry data. Results: At the stages of the reverse position of Trendelenburg, pneumoperitoneum and the beginning of the operation, a decrease in hemodynamic, a violation of the oxygen status and metabolism were observed with more pronounced manifestations in the I group, where there was a longer recovery. In patients of group II, on the background of enhanced infusion therapy and administration of glucocorticoids, their recovery was more intense, they woke up faster and were transferred to the ward. These patients had 2,4 times less nausea and vomiting, and less postoperative pain upon awakening (p<0,05). Conclusions: In patients with ACC, correction of hemodynamic, oxygen status and metabolism, makes LC safer.

Effects of nocturnal light exposure on circadian rhythm and energy metabolism in healthy adults: A randomized crossover trial

ABSTRACT Exposure to continuous light at night, including night-shift work or a nocturnal lifestyle, is emerging as a novel deleterious factor for weight gain and obesity. Here, we examined whether a single bout of bright light (BL) exposure at night affects energy metabolism via changes in circadian rhythm and nocturnal melatonin production. Ten healthy young men were randomized to a two-way crossover experimental design protocol: control (< 50 lux) and BL (approximately 10000 lux) conditions, with at least seven days of interval. The participants were exposed to each condition for 3 h (21:00–24:00) before sleep (0 lux, 00:00–07:00) in a room-type metabolic chamber. On each experimental night (21:00–07:00), energy expenditure, respiratory quotient (RQ), and substrate oxidation were measured to determine the energy metabolism. BL exposure prior to bedtime altered biological rhythms, disrupted the nocturnal decline in body temperature, and suppressed the melatonin level before sleeping, resulting in an increase in sleep latency. Indirect calorimetry data revealed that BL exposure significantly decreased the fat oxidation and increased the RQ, an indicator of the carbohydrate-to-fat oxidation ratio, throughout the whole period (light exposure and sleep). We revealed that acute BL exposure prior to bedtime exacerbated circadian rhythms and substrate oxidations, suggesting that chronic BL exposure at night may lead to obesity risk due to disturbances in circadian rhythms and macronutrient metabolism.

Neither Postabsorptive Resting Nor Postprandial Fat Oxidation Are Related to Peak Fat Oxidation in Men With Chronic Paraplegia

The peak rate of fat oxidation (PFO) achieved during a graded exercise test is an important indicator of metabolic health. In healthy individuals, there is a significant positive association between PFO and total daily fat oxidation (FO). However, conditions resulting in metabolic dysfunction may cause a disconnect between PFO and non-exercise FO. Ten adult men with chronic thoracic spinal cord injury (SCI) completed a graded arm exercise test. On a separate day following an overnight fast (≥ 10 h), they rested for 60 min before ingesting a liquid mixed meal (600 kcal; 35% fat, 50% carbohydrate, 15% protein). Expired gases were collected and indirect calorimetry data used to determine FO at rest, before and after feeding, and during the graded exercise test. Participants had “good” cardiorespiratory fitness (VO2peak: 19.2 ± 5.2 ml/kg/min) based on normative reference values for SCI. There was a strong positive correlation between PFO (0.30 ± 0.08 g/min) and VO2peak (r = 0.86, p = 0.002). Additionally, postabsorptive FO at rest was significantly and positively correlated with postprandial peak FO (r = 0.77, p = 0.01). However, PFO was not significantly associated with postabsorptive FO at rest (0.08 ± 0.02 g/min; p = 0.97), postprandial peak FO (0.10 ± 0.03 g/min; p = 0.43), or incremental area under the curve postprandial FO (p = 0.22). It may be advantageous to assess both postabsorptive FO at rest and PFO in those with SCI to gain a more complete picture of their metabolic flexibility and long-term metabolic health.

Nutritional support for patients in the neurosurgical and neurological intensive care unit: are special guidelines necessary?

The nutritional support for patients in the intensive care unit is an integral component of intensive care. Patients of a neurological and neurosurgical profile who are in the intensive care unit are a special group of patients, whose treatment differs both in the used intensive therapy methods and nutritional support provision.&#x0D; Indirect calorimetry should be used to determine the energy requirements in neurosurgical and neurological patients. The use of calculation equations, such as the Harris-Benedict equation, is impossible due to its large discrepancy with indirect calorimetry data. The need for protein in patients of this category should be made at the rate of 1.22.0 g/kg of body weight per day. The urinary nitrogen loss data should not be used as a routine method for determining protein requirements in these patients. Insufficient energy and protein intake in neurosurgical and neurological patients can lead to increased infectious complications, mechanical ventilation duration, and length of intensive care unit stay, and rehabilitation potential deterioration. Excessive energy intake can lead to increased carbon dioxide production and intra-abdominal pressure, thereby increasing the intracranial pressure and aggravating secondary brain damage.&#x0D; The central nervous system damage leads to increased intestinal permeability, worsens motility, and even changes the microbiota, which requires constant monitoring of the gastrointestinal tract functions to provide adequate nutritional support in neurological and neurosurgical patients who are in the intensive care unit.&#x0D; In modern guidelines, both on intensive care and nutritional support, recommendations for its implementation in these patients are unclear.

P0084 / #397: CRITICALLY ILL INFANTS ARE MORE HYPOMETABOLIC THAN NON INFANTS

Aims & Objectives: The knowledge of the metabolic status of critically ill pediatric patients is fundamental. The assessment of energy expenditure by indirect calorimetry is the gold standard for metabolic assessment of critically ill patients since the equations for determining energy expenditure at rest did not show accuracy for the critically ill patient population. Indirect calorimetry enables proper nutritional management avoiding underfeeding and overfeeding, both harmful. This study aims to evaluate whether there is a difference in the metabolic pattern observed in children undergoing mechanical ventilation in the intensive care unit in relation to age group. Methods: Indirect calorimetry data were collected from children aged 1 month to 84 months of age in the first 72 hours of mechanical ventilation. It was evaluated if there were differences in values according to age group. Results: Energy expenditure and oxygen comsumption results were obtained from 182 patients from 1 month to 84 months of age. A difference was observed in the mean values obtained in infants compared to older children. There was a statistically significant difference (p <0.01) in the median VO2/m2 in children under 2 years (median 125; IQR 100.4-149.2; n = 134) when compared to older children (median 151.9; IQR 135.2-178.4; n = 48). Statistically significant differences (p <0.01) were also observed between the energy expenditure values of children under 2 years (median 259; IQR184-356.5; n = 134) and older children (median 714 (593.8-824, 8). Conclusions: It was observed that infants have a more hypometabolic profile than children older than 2 years.

Effects of acute nutritional ketosis during exercise in adults with glycogen storage disease type IIIa are phenotype-specific: An investigator-initiated, randomized, crossover study.

Glycogen storage disease type IIIa (GSDIIIa) is an inborn error of carbohydrate metabolism caused by a debranching enzyme deficiency. A subgroup of GSDIIIa patients develops severe myopathy. The purpose of this study was to investigate whether acute nutritional ketosis (ANK) in response to ketone‐ester (KE) ingestion is effective to deliver oxidative substrate to exercising muscle in GSDIIIa patients. This was an investigator‐initiated, researcher‐blinded, randomized, crossover study in six adult GSDIIIa patients. Prior to exercise subjects ingested a carbohydrate drink (~66 g, CHO) or a ketone‐ester (395 mg/kg, KE) + carbohydrate drink (30 g, KE + CHO). Subjects performed 15‐minute cycling exercise on an upright ergometer followed by 10‐minute supine cycling in a magnetic resonance (MR) scanner at two submaximal workloads (30% and 60% of individual maximum, respectively). Blood metabolites, indirect calorimetry data, and in vivo 31P‐MR spectra from quadriceps muscle were collected during exercise. KE + CHO induced ANK in all six subjects with median peak βHB concentration of 2.6 mmol/L (range: 1.6‐3.1). Subjects remained normoglycemic in both study arms, but delta glucose concentration was 2‐fold lower in the KE + CHO arm. The respiratory exchange ratio did not increase in the KE + CHO arm when workload was doubled in subjects with overt myopathy. In vivo 31P MR spectra showed a favorable change in quadriceps energetic state during exercise in the KE + CHO arm compared to CHO in subjects with overt myopathy. Effects of ANK during exercise are phenotype‐specific in adult GSDIIIa patients. ANK presents a promising therapy in GSDIIIa patients with a severe myopathic phenotype.Trial registration numberClinicalTrials.gov identifier: NCT03011203.

High-throughput discovery of genetic determinants of circadian misalignment.

Circadian systems provide a fitness advantage to organisms by allowing them to adapt to daily changes of environmental cues, such as light/dark cycles. The molecular mechanism underlying the circadian clock has been well characterized. However, how internal circadian clocks are entrained with regular daily light/dark cycles remains unclear. By collecting and analyzing indirect calorimetry (IC) data from more than 2000 wild-type mice available from the International Mouse Phenotyping Consortium (IMPC), we show that the onset time and peak phase of activity and food intake rhythms are reliable parameters for screening defects of circadian misalignment. We developed a machine learning algorithm to quantify these two parameters in our misalignment screen (SyncScreener) with existing datasets and used it to screen 750 mutant mouse lines from five IMPC phenotyping centres. Mutants of five genes (Slc7a11, Rhbdl1, Spop, Ctc1 and Oxtr) were found to be associated with altered patterns of activity or food intake. By further studying the Slc7a11tm1a/tm1a mice, we confirmed its advanced activity phase phenotype in response to a simulated jetlag and skeleton photoperiod stimuli. Disruption of Slc7a11 affected the intercellular communication in the suprachiasmatic nucleus, suggesting a defect in synchronization of clock neurons. Our study has established a systematic phenotype analysis approach that can be used to uncover the mechanism of circadian entrainment in mice.

Chronic effects of high-intensity interval training on postprandial lipemia in healthy men.

The aim of this study was to determine the chronic (≥72 h postexercise) effects of high-intensity interval training (HIIT) on postprandial lipemia and metabolic markers in healthy volunteers. Eight physically active young men (mean ± SD: age 22 ± 3 yr, height 1.77 ± 0.07 m, body mass 67.7 ± 6.2 kg) underwent two 6-h mixed-meal tolerance tests and resting vastus lateralis muscle biopsies before the first session and ≥72 h after the final session of 4 wk of HIIT [16 sessions in total; 10 × 60-s bouts of cycling at 90% maximal oxygen uptake (V̇o2max), interspersed with 60-s intervals at 45% V̇o2max]. Arterialized and deep venous blood samples from across the forearm, brachial artery blood flow measurements, and whole-body indirect calorimetry data were obtained before, and at regular intervals for 6 h after, consumption of a standardized mixed meal. The main findings revealed that, when assessed ≥72 h postexercise, postprandial free fatty acid (FFA) uptake across the forearm was increased in response to exercise training (P = 0.025). However, 4 wk of HIIT did not alter fasting or postprandial circulating triglyceride concentrations or their tissue uptake, despite a 10.2% ± 7.7% improvement in V̇o2max (P = 0.004). Protein content of adipose triglyceride lipase in the vastus lateralis at rest was reduced by 25% ± 21% (P = 0.01). Collectively, these findings suggest that 4 wk of HIIT enhances postprandial clearance of FFA when assessed ≥72 h postexercise but does not confer persisting (training) adaptations in postprandial triglyceridemia.NEW & NOTEWORTHY When assessed ≥72 h after the last exercise session, 4 wk of high-intensity interval training (HIIT) did not improve triglyceridemia but enhanced free fatty acid uptake into muscle with a concurrent reduction in skeletal muscle adipose triglyceride lipase protein content. This suggests that previously reported acute reductions in postprandial triglyceridemia following a single bout of HIIT do not translate to sustained improvements after 4 wk of HIIT, supporting the concept of frequent exercise for the maintenance of lipemic control.

Estimation of non-shivering thermogenesis and cold-induced nutrient oxidation rates: Impact of method for data selection and analysis

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. Forty-four young healthy adults (22.1±2.1 years old, 25.6±5.2kg/m2, 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 1h of cold exposure combining air conditioning (19.5-20°C) and a water perfused cooling vest set at a temperature of 4°C above the individual shivering threshold. We applied three methods for data selection: (i) time intervals every 5min (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). 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. 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.