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Background/Objectives: Food-induced thermogenesis is generally reported to be higher in the morning, although contrasting results exist because of differences in experimental settings related to the preceding fasting, exercise, sleeping and dieting. To definitively answer to this issue, we compared the calorimetric and metabolic responses to identical meals consumed at 0800 hours and at 2000 hours by healthy volunteers, after standardized diet, physical activity, duration of fast and resting. Subjects/Methods: Twenty subjects (age range 20–35 years, body mass index=19–26 kg m − 2 ) were enrolled to a randomized cross-over trial. They randomly received the same standard meal in the morning and, 7 days after, in the evening, or vice versa. A 30-min basal calorimetry was performed; a further 60-min calorimetry was done 120-min after the beginning of the meal. Blood samples were drawn every 30-min for 180-min. General linear models, adjusted for period and carry-over, were used to evaluate the ‘morning effect’, that is, the difference of morning delta (after-meal minus fasting values) minus evening delta (after-meal minus fasting values) of the variables. Results: Fasting resting metabolic rate (RMR) did not change from morning to evening; after-meal RMR values were significantly higher after the morning meal (1916; 95% confidence interval (CI)=1792, 2041 vs 1756; 1648, 1863 kcal; P <0.001). RMR was significantly increased after the morning meal (90.5; 95% CI=40.4, 140.6 kcal; P <0.001), whereas differences in areas-under-the-curve for glucose (−1800; −2564,−1036 mg dl −1 × h, P <0.001), log-insulin (−0.19; −0.30,−0.07  μ U ml −1 × h; P =0.001) and fatty free acid concentrations (−16.1;−30.0,−2.09 mmol l −1 × h; P =0.024) were significantly lower. Delayed and larger increases in glucose and insulin concentrations were found after the evening meals. Conclusions: The same meal consumed in the evening determined a lower RMR, and increased glycemic/insulinemic responses, suggesting circadian variations in the energy expenditure and metabolic pattern of healthy individuals. The timing of meals should probably be considered when nutritional recommendations are given.

Background/Objectives:The MATADOR (Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound) study examined whether intermittent energy restriction (ER) improved weight loss efficiency compared with continuous ER and, if so, whether intermittent ER attenuated compensatory responses associated with ER.Subjects/Methods:Fifty-one men with obesity were randomised to 16 weeks of either: (1) continuous (CON), or (2) intermittent (INT) ER completed as 8 × 2-week blocks of ER alternating with 7 × 2-week blocks of energy balance (30 weeks total). Forty-seven participants completed a 4-week baseline phase and commenced the intervention (CON: N=23, 39.4±6.8 years, 111.1±9.1 kg, 34.3±3.0 kg m-2 ; INT: N=24, 39.8±9.5 years, 110.2±13.8 kg, 34.1±4.0 kg m-2 ). During ER, energy intake was equivalent to 67% of weight maintenance requirements in both groups. Body weight, fat mass (FM), fat-free mass (FFM) and resting energy expenditure (REE) were measured throughout the study.Results:For the N=19 CON and N=17 INT who completed the intervention per protocol, weight loss was greater for INT (14.1±5.6 vs 9.1±2.9 kg; P<0.001). INT had greater FM loss (12.3±4.8 vs 8.0±4.2 kg; P<0.01), but FFM loss was similar (INT: 1.8±1.6 vs CON: 1.2±2.5 kg; P=0.4). Mean weight change during the 7 × 2-week INT energy balance blocks was minimal (0.0±0.3 kg). While reduction in absolute REE did not differ between groups (INT: -502±481 vs CON: -624±557 kJ d-1 ; P=0.5), after adjusting for changes in body composition, it was significantly lower in INT (INT: -360±502 vs CON: -749±498 kJ d-1 ; P<0.05).Conclusions:Greater weight and fat loss was achieved with intermittent ER. Interrupting ER with energy balance 'rest periods' may reduce compensatory metabolic responses and, in turn, improve weight loss efficiency.

The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs) have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown. This study aimed to examine the associations of PFAS exposure with changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. In the 2-year POUNDS Lost randomized clinical trial based in Boston, Massachusetts, and Baton Rouge, Louisiana, that examined the effects of energy-restricted diets on weight changes, baseline plasma concentrations of major PFASs were measured among 621 overweight and obese participants aged 30-70 years. Body weight was measured at baseline and 6, 12, 18, and 24 months. RMR and other metabolic parameters, including glucose, lipids, thyroid hormones, and leptin, were measured at baseline and 6 and 24 months. Participants lost an average of 6.4 kg of body weight during the first 6 months (weight-loss period) and subsequently regained an average of 2.7 kg of body weight during the period of 6-24 months (weight regain period). After multivariate adjustment, baseline PFAS concentrations were not significantly associated with concurrent body weight or weight loss during the first 6 months. In contrast, higher baseline levels of PFASs were significantly associated with a greater weight regain, primarily in women. In women, comparing the highest to the lowest tertiles of PFAS concentrations, the multivariate-adjusted mean weight regain (SE) was 4.0 (0.8) versus 2.1 (0.9) kg for perfluorooctanesulfonic acid (PFOS) (Ptrend = 0.01); 4.3 (0.9) versus 2.2 (0.8) kg for perfluorooctanoic acid (PFOA) (Ptrend = 0.007); 4.7 (0.9) versus 2.5 (0.9) kg for perfluorononanoic acid (PFNA) (Ptrend = 0.006); 4.9 (0.9) versus 2.7 (0.8) kg for perfluorohexanesulfonic acid (PFHxS) (Ptrend = 0.009); and 4.2 (0.8) versus 2.5 (0.9) kg for perfluorodecanoic acid (PFDA) (Ptrend = 0.03). When further adjusted for changes in body weight or thyroid hormones during the first 6 months, results remained similar. Moreover, higher baseline plasma PFAS concentrations, especially for PFOS and PFNA, were significantly associated with greater decline in RMR during the weight-loss period and less increase in RMR during the weight regain period in both men and women. Limitations of the study include the possibility of unmeasured or residual confounding by socioeconomic and psychosocial factors, as well as possible relapse to the usual diet prior to randomization, which could have been rich in foods contaminated by PFASs through food packaging and also dense in energy. In this diet-induced weight-loss trial, higher baseline plasma PFAS concentrations were associated with a greater weight regain, especially in women, possibly explained by a slower regression of RMR levels. These data illustrate a potential novel pathway through which PFASs interfere with human body weight regulation and metabolism. The possible impact of environmental chemicals on the obesity epidemic therefore deserves attention. ClinicalTrials.gov NCT00072995.

Critical among the changes that occur with aging are decreases in muscle mass and metabolic rate and an increase in fat mass. These changes may predispose older adults to chronic disease and functional impairment; ultimately resulting in a decrease in the quality of life. Research has suggested that long chain omega-3 fatty acids, found predominantly in fatty fish, may assist in reducing these changes. The objective of this study was to evaluate the effect of fish oil (FO) supplementation in a cohort of healthy, community-dwelling older females on 1) metabolic rate and substrate oxidation at rest and during exercise; 2) resting blood pressure and resting and exercise heart rates; 3) body composition; 4) strength and physical function, and; 5) blood measures of insulin, glucose, c-reactive protein, and triglycerides. Twenty-four females (66 ± 1 yr) were recruited and randomly assigned to receive either 3g/d of EPA and DHA or a placebo (PL, olive oil) for 12 wk. Exercise measurements were taken before and after 12 wk of supplementation and resting metabolic measures were made before and at 6 and 12 wk of supplementation. The results demonstrated that FO supplementation significantly increased resting metabolic rate by 14%, energy expenditure during exercise by 10%, and the rate of fat oxidation during rest by 19% and during exercise by 27%. In addition, FO consumption lowered triglyceride levels by 29% and increased lean mass by 4% and functional capacity by 7%, while no changes occurred in the PL group. In conclusion, FO may be a strategy to improve age-related physical and metabolic changes in healthy older females. Trial registration: ClinicalTrials.gov NCT01734538.

Addition of capsaicin (CAPS) to the diet has been shown to increase energy expenditure; therefore capsaicin is an interesting target for anti-obesity therapy. We investigated the 24 h effects of CAPS on energy expenditure, substrate oxidation and blood pressure during 25% negative energy balance. Subjects underwent four 36 h sessions in a respiration chamber for measurements of energy expenditure, substrate oxidation and blood pressure. They received 100% or 75% of their daily energy requirements in the conditions '100%CAPS', '100%Control', '75%CAPS' and '75%Control'. CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units (SHU)) with every meal. An induced negative energy balance of 25% was effectively a 20.5% negative energy balance due to adapting mechanisms. Diet-induced thermogenesis (DIT) and resting energy expenditure (REE) at 75%CAPS did not differ from DIT and REE at 100%Control, while at 75%Control these tended to be or were lower than at 100%Control (p = 0.05 and p = 0.02 respectively). Sleeping metabolic rate (SMR) at 75%CAPS did not differ from SMR at 100%CAPS, while SMR at 75%Control was lower than at 100%CAPS (p = 0.04). Fat oxidation at 75%CAPS was higher than at 100%Control (p = 0.03), while with 75%Control it did not differ from 100%Control. Respiratory quotient (RQ) was more decreased at 75%CAPS (p = 0.04) than at 75%Control (p = 0.05) when compared with 100%Control. Blood pressure did not differ between the four conditions. In an effectively 20.5% negative energy balance, consumption of 2.56 mg capsaicin per meal supports negative energy balance by counteracting the unfavorable negative energy balance effect of decrease in components of energy expenditure. Moreover, consumption of 2.56 mg capsaicin per meal promotes fat oxidation in negative energy balance and does not increase blood pressure significantly. Nederlands Trial Register; registration number NTR2944.

The purpose of the work is to investigate the effects of low-dose testosterone replacement therapy (TRT) and evoked resistance training (RT) on body composition and metabolic variables after spinal cord injury (SCI). Twenty-two individuals with chronic motor complete SCI (ages 18–50 years) were randomly assigned to either TRT+RT (n = 11) or TRT (n = 11) for 16 weeks following a 4 -week delayed entry period. TRT+RT men underwent twice weekly progressive RT using electrical stimulation with ankle weights. TRT was administered via testosterone patches (2–6 mg/day). Body composition was tested using anthropometrics, dual energy x-ray absorptiometry, and magnetic resonance imaging. After an overnight fast, basal metabolic rate (BMR), lipid panel, serum testosterone, adiponectin, inflammatory and anabolic biomarkers (insulin-like growth factor-1 and insulin-like growth factor-binding protein 3 [IGFBP-3]), glucose effectiveness (Sg), and insulin sensitivity (Si) were measured. Total body lean mass (LM; 2.7 kg, p < 0.0001), whole muscle (p < 0.0001), and whole muscle knee extensor cross-sectional areas (CSAs; p < 0.0001) increased in the TRT+RT group, with no changes in the TRT group. Visceral adiposity decreased (p = 0.049) in the TRT group, with a trend in the TRT+RT (p = 0.07) group. There was a trend (p = 0.050) of a 14–17% increase in BMR following TRT+RT. Sg showed a trend (p = 0.07) to improvement by 28.5–31.5% following both interventions. IGFBP-3 increased (p = 0.0001) while IL-6 decreased (p = 0.039) following both interventions, and TRT+RT suppressed adiponectin (p = 0.024). TRT+RT resulted in an increase in LM and whole thigh and knee extensor muscle CSAs, with an increase in BMR and suppressed adiponectin. Low-dose TRT may mediate modest effects on visceral adipose tissue, Sg, IGFBP-3, and IL-6, independent of changes in LM.

Abstract 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

We conducted a bidirectional two-sample Mendelian randomization (MR) study to determine whether genetically predicted basal metabolic rate (BMR) was a causal risk factor for colorectal cancer (CRC) or whether a genetically predicted CRC risk can influence the BMR level (i.e., reverse causation). We employed 1,040 genetic variants as proxies for BMR to obtain effect estimates on CRC risk. Another 58 CRC-associated variants were used to estimate effects on BMR levels. Stratified analysis by tumor site was used to examine the causal associations between BMR and colon/rectal cancer risk. The inverse variance weighted (IVW) method indicated a significant causal effect of genetically determined BMR on CRC risk (ORSD = 1.27, 95% CI = 1.07-1.51). No significant reverse causal association was identified between genetically increased CRC risk and BMR levels [IVW (β = 0, 95% CI = -0.01 to 0)]. The results of MR-Egger and the weighted median method were consistent with the IVW method. Stratified analysis by CRC sites identified significant causal associations between BMR and colon cancer [IVW (ORSD = 1.45, 95% CI = 1.16-1-80)], and null evidence of a causal association between BMR and rectal cancer risk was found (p > 0.05). Our findings add to the current literature by validating a positive relationship between high BMR levels and CRC risk instead of reverse causality. The genetically predicted BMR level was causally associated with colon cancer risk but not rectal cancer risk.

Purpose The study compares MET-defined cutpoints used to classify sedentary behaviors in children using a simulated free-living design. Methods A sample of 102 children (54 boys and 48 girls; 7–13 years) completed a set of 12 activities (randomly selected from a pool of 24 activities) in a random order. Activities were predetermined and ranged from sedentary to vigorous intensities. Participant’s energy expenditure was measured using a portable indirect calorimetry system, Oxycon mobile. Measured minute-by-minute VO 2 values (i.e., ml/kg/min) were converted to an adult- or child-MET value using the standard 3.5 ml/kg/min or the estimated child resting metabolic rate, respectively. Classification agreement was examined for both the “standard” (1.5 adult-METs) and an “adjusted” (2.0 adult-METs) MET-derived threshold for classifying sedentary behavior. Alternatively, we also tested the classification accuracy of a 1.5 child-MET threshold. Classification accuracy of sedentary activities was evaluated relative to the predetermined intensity categorization using receiver operator characteristic curves. Results There were clear improvements in the classification accuracy for sedentary activities when a threshold of 2.0 adult-METs was used instead of 1.5 METs (Se 1.5 METs  = 4.7 %, Sp 1.5 METs  = 100.0 %; Se 2.0 METs  = 36.9 %, Sp 2.0 METs  = 100.0 %). The use of child-METs while maintaining the 1.5 threshold also resulted in improvements in classification (Se = 45.1 %, Sp = 100.0 %). Conclusion Adult-MET thresholds are not appropriate for children when classifying sedentary activities. Classification accuracy for identifying sedentary activities was improved when either an adult-MET of 2.0 or a child-MET of 1.5 was used.