Effects of energy loads on energy and nutrient absorption rates and gut microbiome in humans: A randomized crossover trial.

OBJECTIVE: This study aimed to determine the effects of different energy loads on the gut microbiota composition and the rates of energy and nutrient excretion via feces and urine. METHODS: A randomized crossover dietary intervention study was conducted with three dietary conditions: overfeeding (OF), control (CON), and underfeeding (UF). Ten healthy men were subjected to each condition for 8 days (4 days and 3 nights in nonlaboratory and laboratory settings each). The effects of dietary conditions on energy excretion rates via feces and urine were assessed using a bomb calorimeter. RESULTS: Short-term energy loads dynamically altered the gut microbiota at the α-diversity (Shannon index), phylum, and genus levels (p < 0.05). Energy excretion rates via urine and urine plus feces decreased under OF more than under CON (urine -0.7%; p < 0.001, urine plus feces -1.9%; p = 0.049) and UF (urine -1.0%; p < 0.001, urine plus feces -2.1%; p = 0.031). However, energy excretion rates via feces did not differ between conditions. CONCLUSIONS: Although short-term overfeeding dynamically altered the gut microbiota composition, the energy excretion rate via feces was unaffected. Energy excretion rates via urine and urine plus feces were lower under OF than under CON and UF conditions.

Investigation of seasonality of human spontaneous physical activity and energy expenditure in respiratory chamber in Phoenix, Arizona.

OBJECTIVE: The existence of seasonal changes in energy metabolism is uncertain. We investigated the relationship between the seasons and spontaneous physical activity (SPA), energy expenditure (EE), and other components measured in a respiratory chamber. METHODS: Between 1985-2005, 671 healthy adults (aged 28.8 ± 7.1 years; 403 men) in Phoenix, Arizona had a 24-hour stay in the respiratory chamber equipped with radar sensors; SPA (expressed as a percentage over the time interval), the energy cost of SPA, EE, and respiratory exchange ratio (RER) were measured. RESULTS: In models adjusted for known covariates, SPA (%) was lower during summer (7.2 ± 2.9, p = 0.0002), spring (7.5 ± 2.9, p = 0.025), and fall (7.6 ± 3, p = 0.038) compared to winter (8.3 ± 3.5, reference). Conversely, energy cost of SPA (kcal/h/%) was higher during summer (2.18 ± 0.83, p = 0.0008), spring (2.186 ± 0.83, p = 0.017), and fall (2.146 ± 0.75, p = 0.038) compared to winter (2.006 ± 0.76). Protein (292 ± 117 kcal/day, ß = -21.2, p = 0.08) oxidation rates was lower in the summer compared to winter. Carbohydrate and lipid oxidation rates (kcal/day) did not differ across seasons. RER and 24-h EE did not differ by season. CONCLUSION: SPA, representing fidgeting-like behavior in the chamber, demonstrated a winter peak and summer nadir in humans living in a desert climate. These findings indicate that the physiological propensity for movement may be affected by seasonal factors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00340132, NCT00342732.

Cross-sectional association of metrics derived from continuous glucose monitoring with cognitive performance in older adults with type 2 diabetes.

AIM: To examine the association between continuous glucose monitoring (CGM)-derived metrics and cognitive performance in older adults with type 2 diabetes (T2D). MATERIALS AND METHODS: A total of 100 outpatients with T2D aged 70 years or older were analysed. Participants underwent CGM for 14 days. As CGM-derived metrics, mean sensor glucose (SG), glucose coefficient of variation (CV), time in range (TIR; 70-180 mg/dl), time above range (TAR; > 180 mg/dl) and time below range (TBR; < 70 mg/dl), were calculated. Participants underwent cognitive tests, including the Japanese version of the Montreal Cognitive Assessment (MoCA-J), a delayed word-recall test from the Alzheimer's Disease Assessment Scale-cognitive subscale, a digit symbol substitution test, a letter word fluency test, a trail-making test (TMT) and digit span test (DSP). RESULTS: In multiple regression analyses adjusted for confounders, a higher mean SG was associated with a lower performance in MoCA-J and TMT part B (TMT-B) (P < .05). A higher TAR was associated with a lower performance in TMT-B and DSP-backward (P < .05). By contrast, a higher TIR was associated with better function in TMT-B and DSP-backward (P < .05). Furthermore, CV and TBR were not associated with any cognitive function. CONCLUSION: Hyperglycaemia metrics and TIR derived from CGM are associated with cognitive functions, especially with executive function and working memory, in older adults with T2D.

Effects of Short-term Fasting on Ghrelin/GH/IGF-1 Axis in Healthy Humans: The Role of Ghrelin in the Thrifty Phenotype.

CONTEXT: A greater decrease in 24-hour energy expenditure (24hEE) during short-term fasting is indicative of a thrifty phenotype. OBJECTIVE: As ghrelin and the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis are implicated in the regulation of energy intake and metabolism, we investigated whether ghrelin, GH, and IGF-1 concentrations mediate the fasting-induced decrease in 24hEE that characterizes thriftiness. METHODS: In 47 healthy individuals, 24hEE was measured in a whole-room indirect calorimeter both during 24-hour eucaloric and fasting conditions. Plasma total ghrelin, GH, and IGF-1 concentrations were measured by enzyme-linked immunosorbent assay after an overnight fast the morning before and after each 24-hour session. RESULTS: During 24-hour fasting, on average 24hEE decreased by 8.0% (P < .001), GH increased by ~5-fold (P < .001), whereas ghrelin (mean +23 pg/mL) and IGF-1 were unchanged (both P ≥ .19) despite a large interindividual variability in ghrelin change (SD 150 pg/mL). Greater fasting-induced increase in ghrelin was associated with a greater decrease in 24hEE during 24-hour fasting (r = -0.42, P = .003), such that individuals who increased ghrelin by 200 pg/mL showed an average decrease in 24hEE by 55 kcal/day. CONCLUSION: Short-term fasting induced selective changes in the ghrelin/GH/IGF-1 axis, specifically a ghrelin-independent GH hypersecretion that did not translate into increased IGF-1 concentrations. Greater increase in ghrelin after 24-hour fasting was associated with greater decrease in 24hEE, indicating ghrelin as a novel biomarker of increased energy efficiency of the thrifty phenotype.

Associations between motorized transport access, out-of-home activities, and life-space mobility in older adults in Japan.

BACKGROUND: Motorized transport access and out-of-home activities are two potential correlates of Life-space mobility (LSM), a common research topic in mobility studies of older adults. These correlates remain mostly unexplored in previous literature and relating them with LSM can reveal directions for improving the LSM of older adults. METHODS: The associations between motorized transport access, out-of-home activities, and LSM were examined using data from 1,333 older adults (mean age = 70.63) living in 15 cities and towns in Japan. LSM was assessed using composite life-space assessment (LSA) scores. Motorized transport access was measured using dummies showing whether a person had car access (divided into five levels) and used public transport (bus and railway), and out-of-home activities were measured using the number of various activities that were conducted during the most recent weekday and weekend day. Generalized linear models were used to assess the associations. RESULTS: The sample was dominated by males (74.42%), with more than half of the sample had their own cars. On average, each respondent had four activities during two survey days, and shopping was the most common activity. The results showed that owning a car and using railway, as well as various activities were associated with increased composite LSA scores, whereas no cars or only shared cars in home were associated with decreased composite LSA scores. However, these associations differed between males and females. CONCLUSIONS: In this study, different levels of motorized transport access and different types of out-of-home activities were found to associate differently with composite LSA scores. Based on these findings, we suggest that policymakers should provide more transport access, pay more attention to the LSM of older adults with high clinics/hospital activities, and trigger more shopping and daily leisure activities for older adults to improve the LSM of this population.

ApoE4 Is Associated with Lower Body Mass, Particularly Fat Mass, in Older Women with Cognitive Impairment.

A lower body mass is associated with the progression of Alzheimer's disease (AD) and the risk of mortality in patients with AD; however, evidence of genetic determinants of decreased body mass in cognitively impaired older adults is limited. We therefore investigated the genetic effect of APOE-ε4 on body composition in older adults with mild cognitive impairment (MCI) and early-to-moderate-stage AD. A total of 1631 outpatients (aged 65-89 years) with MCI and early-to-moderate-stage AD were evaluated for the association between body composition and APOE-ε4 status. After adjusting for covariates, including cognitive function evaluated with the Mini-Mental State Examination, the presence of the APOE-ε4 was associated with lower weight (ß = -1.116 ± 0.468 kg per presence, p = 0.017), fat mass (ß = -1.196 ± 0.401 kg per presence, p = 0.003), and percentage of body fat (ß = -1.700 ± 0.539% per presence, p = 0.002) in women but not in men. Additionally, the impact of APOE-ε4 on measures of body composition in women was more remarkable in MCI than in AD patients. The presence of the APOE-ε4 allele was associated with lower fat mass, particularly in women with MCI, independent of cognitive decline.

Trends in spontaneous physical activity and energy expenditure among adults in a respiratory chamber, 1985 to 2005.

OBJECTIVE: Fidgeting, a type of spontaneous physical activity (SPA), has substantial thermogenic potential. This research aims to examine secular trends in SPA and energy expenditure (EE) inside a respiratory chamber. METHODS: From 1985 to 2005, healthy adults (n = 678; mean age: 28.8 years; men: 60%; 522 Indigenous American, 129 White, and 27 Black) had a 24-hour stay in the respiratory chamber equipped with radar sensors. Body composition, glucose tolerance, fasting insulin, insulin action (hyperinsulinemic-euglycemic clamp), and insulin secretion (intravenous glucose tolerance test) were measured as covariates. RESULTS: SPA, adjusted for age, sex, race, and body composition, declined (r = -0.30, p < 0.0001), with a concomitant rise in the energy cost of SPA (r = 0.30, p < 0.0001). The 24-hour EE adjusted for covariates increased (r = 0.31, p < 0.0001), which was reflected in increases in EE during sleep (r = 0.18, p < 0.0001) and during the awake, fed condition (r = 0.28, p < 0.0001). The secular trends in SPA or 24-hour EE were unchanged with adjustment for measures related to glucose metabolism. CONCLUSIONS: Secular trend analyses showed a decline in fidgeting. However, this decline in SPA was partially counterbalanced by an increase in energy cost of this activity and a rise in EE. Nevertheless, our results support public health efforts to promote small but sustained changes in these behaviors.

BOLD signal response in primary visual cortex to flickering checkerboard increases with stimulus temporal frequency in older adults.

Many older adults have difficulty seeing brief visual stimuli which younger adults can easily recognize. The primary visual cortex (V1) may induce this difficulty. However, in neuroimaging studies, the V1 response change to the increase of temporal frequency of visual stimulus in older adults was unclear. Here we investigated the association between the temporal frequency of flickering stimuli and the BOLD activity within V1 in older adults, using surface-based fMRI analysis. The fMRI data from 29 healthy older participants stimulated by contrast-reversing checkerboard at temporal flicker frequencies of 2, 4, and 8 Hz were obtained. The participants also performed a useful field of view (UFOV) test. The slope coefficient of BOLD activity regarding the temporal frequency of the visual stimulus averaged within V1 regions of interest was positive and significantly different from zero. Group analysis in the V1 showed significant clusters with positive slope and no significant clusters with a negative slope. The correlation coefficient between the slope coefficient and UFOV performance was not significant. The results indicated that V1 BOLD response to a flickering visual stimulus increases as the stimulus temporal frequency increases from 2 to 8 Hz in older adults.

Eating Dinner Early Improves 24-h Blood Glucose Levels and Boosts Lipid Metabolism after Breakfast the Next Day: A Randomized Cross-Over Trial.

Aim: To examine whether mild early time-restricted eating (eating dinner at 18:00 vs. at 21:00) improves 24-h blood glucose levels and postprandial lipid metabolism in healthy adults. Methods: Twelve participants (2 males and 10 females) were included in the study. In this 3-day (until the morning of day 3) randomized crossover study, two different conditions were tested: eating a late dinner (at 21:00) or an early dinner (at 18:00). During the experimental period, blood glucose levels were evaluated by each participant wearing a continuous blood glucose measuring device. Metabolic measurements were performed using the indirect calorimetry method on the morning of day 3. The study was conducted over three days; day 1 was excluded from the analysis to adjust for the effects of the previous day's meal, and only data from the mornings of days 2 and 3 were used for the analysis. Results: Significant differences were observed in mean 24-h blood glucose levels on day 2 between the two groups (p = 0.034). There was a significant decrease in the postprandial respiratory quotient 30 min and 60 min after breakfast on day 3 in the early dinner group compared with the late dinner group (p < 0.05). Conclusion: Despite a difference of only 3 h, eating dinner early (at 18:00) has a positive effect on blood glucose level fluctuation and substrate oxidation compared with eating dinner late (at 21:00).

Reduced adaptive thermogenesis during acute protein-imbalanced overfeeding is a metabolic hallmark of the human thrifty phenotype.

BACKGROUND: The human thrifty phenotype is characterized by a greater decrease in 24-h energy expenditure (24EE) during fasting due to relatively higher eucaloric 24EE in sedentary conditions, both of which are indicative of greater propensity to weight gain. Thriftiness is also associated with a smaller increase in 24EE (i.e., reduced adaptive thermogenesis) during overfeeding. OBJECTIVES: We investigated whether short-term measures of adaptive thermogenesis during overfeeding with low/normal/high protein content characterize thriftiness. METHODS: In this secondary cross-sectional analysis of a single-arm crossover study, 24EE was measured using whole-room indirect calorimetry during energy balance, fasting, and different overfeeding conditions (low/3% protein, high/30% protein, and 3 normal/20% protein diets) with 200% of eucaloric requirements in 77 healthy individuals [63 men; BMI (in kg/m2): 26.4 ± 4.3; body fat by DXA: 27.7% ± 9.4%, mean ± SD] with normal glucose regulation. Relations between the 24EE during energy balance (adjusted for body composition) and 24EE during each overfeeding diet were analyzed using separate linear regression models. Participants were arbitrarily categorized as thrifty/spendthrift based on the median value (-177 kcal/d) of the difference in 24EE between fasting and energy balance conditions. RESULTS: Differences in 24EE during low/high-protein overfeeding diets (regression line slope = 0.76 and 0.68, respectively, both P < 0.05 compared with slope = 1) but not during the normal-protein overfeeding diets (all P > 0.05 compared with slope = 1) were dependent on baseline 24EE during energy balance. Specifically, individuals with higher eucaloric 24EE (thriftier phenotype) showed smaller increases in 24EE during protein-imbalanced overfeeding. Analyzed by group, thrifty individuals had smaller increases in 24EE by 42 and 237 kcal/d during low- and high-protein overfeeding, respectively, compared with spendthrift individuals who showed greater increases in 24EE by 100 and 302 kcal/d (P ≤ 0.03 compared with thrifty group). CONCLUSIONS: During acute overfeeding conditions with low/high-protein content, thrifty participants have limited capacity to increase 24EE, indicating that impaired adaptive thermogenesis during protein-imbalanced diets further characterizes the thrifty phenotype and its susceptibility to weight gain. This trial was registered at clinicalTrials.gov as NCT00523627.

Reduced Albumin Concentration Predicts Weight Gain and Higher Ad Libitum Energy Intake in Humans.

Objective: Circulating albumin is negatively associated with adiposity but whether it is associated with increased energy intake, lower energy expenditure or weight gain has not been examined. Methods: In study 1 (n=238; 146 men), we evaluated whether fasting albumin concentration was associated with 24-h energy expenditure and ad libitum energy intake. In study 2 (n=325;167 men), we evaluated the association between plasma albumin and change in weight and body composition. Results: After adjustment for known determinants of energy intake lower plasma albumin concentration was associated with greater total daily energy intake (ß= 89.8 kcal/day per 0.1 g/dl difference in plasma albumin, p=0.0047). No associations were observed between plasma albumin concentrations and 24-h energy expenditure or 24-h respiratory quotient (p>0.2). Over 6 years, volunteers gained on average 7.5 ± 11.7 kg (p<0.0001). Lower albumin concentrations were associated with greater weight [ß=3.53 kg, p=0.039 (adjusted for age, sex, follow up time), CI 0.16 to 6.21 per 1 g/dl difference albumin concentration] and fat mass (ß=2.3 kg, p=0.022), respectively, but not with changes in fat free mass (p=0.06). Conclusions: Lower albumin concentrations were associated with increased ad libitum food intake and weight gain, indicating albumin as a marker of energy intake regulation. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT00340132, NCT00342732.

The Relationship between Changes in Organ-Tissue Mass and Sleeping Energy Expenditure Following Weight Change in College Sumo Wrestlers.

Background and objectives: It has been well established that the resting energy expenditure (REE) for the whole body is the sum of the REE for each organ-tissue in young and middle-aged healthy adults. Based on these previous studies, although it is speculated that sleeping energy expenditure (SEE, which has small inter-individual variability) changes with a commensurate gain or reduction in the resting metabolic rate of each organ-tissue, it is unclear whether a change in organ-tissue masses is directly attributed to the fluctuation of SEE at present. This study aimed to assess the relationship between changes in organ-tissue mass and sleeping energy expenditure (SEE) following weight change in college Sumo wrestlers. This included blood analysis, which is related to energy expenditure. Materials and Methods: A total of 16 healthy male college Sumo wrestlers were recruited in this study. All measurements were obtained before and after weight change. Magnetic resonance imaging measurements were used to determine the volume of the skeletal muscle (SM), liver, and kidneys, and an indirect human calorimeter was used to determine SEE before and after weight change. Results: The change in body mass and SEE ranged between -8.7~9.5 kg, and -602~388 kcal/day. Moreover, changes in SM, liver, and kidneys ranged between -3.3~3.6 kg, -0.90~0.77 kg, and -0.12~0.07 kg. The change in SEE was not significantly correlated with the change in SM or liver mass, nor with blood analyses; however, a significant relationship between the change in kidney mass and SEE was observed. Conclusions: Based on our results, there is a possibility that the mass of the kidneys has an effect on the change in SEE following weight change in college Sumo wrestlers.

Procedures for Measuring Excreted and Ingested Calories to Assess Nutrient Absorption Using Bomb Calorimetry.

OBJECTIVE: With the upsurge in interest in the gut microbiome, complete and accurate measurement of ingested calories and calories lost through excreted stool is crucial for assessing the effect of the microbiota on nutrient absorption. METHODS: Measurement of ingested and excreted calories was conducted over 3 days. Meals were made in duplicate: one was given to the participant, and one was used for the measurement of calories. Stool was marked by nonabsorbable dye ingested prior to and at the end of each 3-day diet period and was collected for caloric assessment from the appearance of the first dye marker until the appearance of the second dye marker. RESULTS: Stool calories per gram for pellets were 4.91 ± 0.06 kcal/g. The mean stool calorie loss as a percentage of ingested calories was 7.3% ± 1.6% (range, 6.6%-8.5%). The stool measurement of kilocalories per gram was not associated with the total measured stool calories or with stool weight (P = 0.2 and P = 0.2, respectively) over the 3-day period. However, the weight of stool samples during each dietary intervention was positively associated with the calorie loss in stool (r = 0.58, P < 0.0001). CONCLUSIONS: Our methods provide a direct measure of ingested calories and stool calories needed to accurately assess relative stool calorie loss as a measure of nutrient absorption. The weight of stool samples across the marked diet period is crucial to determining total stool calories.

Early adaptive thermogenesis is a determinant of weight loss after six weeks of caloric restriction in overweight subjects.

BACKGROUND: Adaptive thermogenesis during prolonged energy deficit refers to the greater than expected reduction in energy expenditure (EE) independent of concomitant loss of metabolically active body mass. OBJECTIVE: As inter-individual variability in the magnitude of adaptive thermogenesis may influence the extent of energy deficit thereby predicting the amount of weight reduction, we investigated whether early adaptive thermogenesis is a determinant of weight loss after 6 weeks of daily 50% caloric restriction in an inpatient setting. DESIGN AND METHODS: The current study reports the results of an exploratory, secondary analysis in overweight but otherwise healthy subjects (n = 11, 7 men, 35 ±â€¯9y, BMI = 40 ±â€¯7 kg/m2, body fat = 63.3 ±â€¯5.3%). Body composition and 24-h EE (24hEE) measurement in a whole-room indirect calorimeter were used to calculate the magnitude of adaptive thermogenesis while on caloric restriction after 1, 3 and 6 weeks. Energy deficit during caloric restriction was quantified via food, stool, and urine bomb calorimetry. Fasting hormonal concentrations (FT4, FT3, FGF21, leptin) were obtained at baseline and at weeks 3 and 6 during caloric restriction. RESULTS: The magnitude of adaptive thermogenesis in 24hEE after 1 week of caloric restriction was -178 ±â€¯137 kcal/day (mean ±â€¯SD), was overall stable during and following caloric restriction, and demonstrated remarkable intra-individual consistency. A relatively greater decrease in 24hEE of 100 kcal/d after 1 week of caloric restriction was associated on average with reduced energy deficit by 8195 kcal over 6 weeks and predicted 2.0 kg less weight loss, of which 0.5 kg was fat mass, after 6 weeks. No correlations were found between hormonal concentrations and weight loss. CONCLUSIONS: The extent of weight loss is influenced by the magnitude of adaptive thermogenesis in the early stage of caloric restriction. Although these results need replication in larger study groups with adequate statistical power, targeting adaptive thermogenesis may help to optimize long-term interventions in obesity therapy.

Metabolic Responses to 24-Hour Fasting and Mild Cold Exposure in Overweight Individuals Are Correlated and Accompanied by Changes in FGF21 Concentration.

A greater decrease in 24-h energy expenditure (24 EE) during 24-h fasting defines a "thriftier" metabolic phenotype prone to weight gain during overfeeding and resistant to weight loss during caloric restriction. As the thermogenic response to mild cold exposure (COLD) may similarly characterize this human phenotype identified by acute fasting conditions, we analyzed changes in 24 EE and sleeping metabolic rate (SLEEP) in a whole-room indirect calorimeter during 24-h fasting at thermoneutrality (24°C) and during energy balance both at thermoneutrality (24°C) and mild cold (19°C) in 20 healthy volunteers (80% male; aged 36.6 ± 11.4 years; percentage body fat 34.8 ± 10.5%). Greater decrease in 24 EE during fasting (thriftier phenotype) was associated with less increase in 24 EE during COLD (i.e., less cold-induced thermogenesis). Greater decreases in plasma fibroblast growth factor 21 (FGF21) after 24-h fasting and after COLD were highly correlated and associated with greater decreases in SLEEP in both conditions. We conclude that the metabolic responses to short-term fasting and COLD are associated with and mediated by the liver-derived hormone FGF21. Thus, the 24 EE response to COLD further identifies the "thrifty" versus "spendthrift" phenotype, providing an additional setting to investigate the physiological mechanisms underlying the human metabolic phenotype and characterizing the individual susceptibility to weight change.

Higher Urinary Dopamine Concentration is Associated with Greater Ad Libitum Energy Intake in Humans.

OBJECTIVE: This study aimed to assess the relationship between dopamine, a neurotransmitter involved in feeding behavior, and ad libitum energy intake in humans. METHODS: Healthy individuals (n = 158; 72 Native American, 50 white, 18 black, and 18 Hispanic participants; BMI: 33 [SD 9] kg/m2 ; body fat: 33% [SD 9%]) were admitted for two inpatient studies investigating the determinants of ad libitum energy intake and assessed for 3 days using a highly reproducible, computerized vending machine paradigm. Urine was collected for 24 hours during eucaloric conditions prior to the ad libitum feeding period, and urinary dopamine excretion rate was quantified by high-performance liquid chromatography. RESULTS: Urinary dopamine excretion rate was on average 346 ± 106 µg over 24 hours and was positively correlated with BMI (r = 0.28, P < 0.0001). Higher dopamine concentrations were associated with lower cognitive restraint (ρ = -0.25, P = 0.005) and greater total ad libitum energy intake (r = 0.29, P = 0.0002). However, after adjustment for anthropometrics, in black and white cohorts, higher dopamine concentrations were associated with greater total ad libitum energy intake (r = 0.70, P = 0.001 and r = 0.33, P = 0.02, respectively), whereas no associations were observed in Native American or Hispanic cohorts (all P > 0.3). CONCLUSIONS: Higher urinary dopamine concentrations are associated with greater ad libitum energy intake, indicating a role for dopamine in the reward pathway regulating human feeding behavior.

Recharacterizing the Metabolic State of Energy Balance in Thrifty and Spendthrift Phenotypes.

PURPOSE: The human thrifty phenotype hypothesis presupposes that lower 24-hour (24h) energy expenditure (24EE) during famine preserves body mass and promotes survival. The prevailing view defines thrifty individuals as having a lower 24EE during fasting. However, it is also plausible that the greater decline in 24EE during fasting in thrifty individuals is due to higher 24EE during energy balance conditions (ENBAL). Herein, we provide evidence that this is indeed the case. METHODS: In 108 healthy subjects, 24EE was measured in a whole-room indirect calorimeter both during ENBAL and 24h fasting conditions. Subjects were categorized as thrifty or spendthrift based on the median value (-162 kcal/day) of the difference in 24EE (adjusted for body composition) between fasting and ENBAL conditions. Concomitant 24h urinary catecholamines were assessed by liquid chromatography-mass spectrometry. RESULTS: Compared to ENBAL, 24EE decreased during 24h fasting by 172 kcal/day (standard deviation = 93; range, -470 to 122). A greater-than-median decrease in 24EE ("thriftier" phenotype) was due to higher 24EE during ENBAL (+124 kcal/day; P < 0.0001) but not to lower 24EE during fasting (P = 0.35). Greater fasting-induced increase in epinephrine was associated with concomitant lower decrease in 24EE (r = 0.27; P = 0.006). MAIN CONCLUSION: The greater decrease in 24EE during acute fasting (which characterizes the thrifty phenotype) is not due to reduced metabolic rate during fasting but to a relatively higher 24EE during feeding conditions, and this decrease in 24EE during fasting is accompanied by a smaller increase in epinephrine. These results recharacterize the prevailing view of the short-term 24EE responses that define the human metabolic phenotypes. Clinical Trials: NCT00523627, NCT00687115, NCT02939404.

Effects of cognitive and visual loads on driving performance after take-over request (TOR) in automated driving.

The present study investigated effects of cognitive and visual loads on driving performance after take-over request (TOR) in an automated driving task. Participants completed automated driving in a driving simulator without a non-driving related task, with an easy non-driving related task, and with a difficult non-driving related task. The primary task was to monitor the environment and the system state. An N-back task and a Surrogate Reference Task (SuRT) were adapted to induce cognitive and visual loads respectively. The system followed a front vehicle automatically. Driving performance was measured by responses to a critical event (appearance of a broken-down car) after the automated system issued TOR and then terminated. High subjective difficulty of the N-back task was related to increased time and increased steering angle variance in the time course from onset of steering control to lane change, while high subjective difficulty of SuRT was related to increased steering angle variance in the time course after lane change. This suggests that both cognitive and visual loads affect driving performance after TOR in automated driving, but the effects appear in different time courses.