Is There a Contribution of Structural Brain Phenotypes to the Variance in Resting Energy Expenditure before and after Weight Loss in Overweight Females?

Brain gray (GM) and white matter (WM) are associated with resting energy expenditure (REE). The impact of weight loss on GM and WM masses, as well as on their associations with REE and the ratio between body and brain metabolism, i.e., encephalic measure (EM)), are unknown. Longitudinal data of 69 female Caucasian subjects (age range 19-69 years) with detailed information on fat mass (FM), fat free mas (FFM), GM, WM and REE. Mean weight loss was 14.5 ± 11.9 kg with changes in FM (-12.9 ± 9.8 kg), FFM (-1.7 ± 4.8 kg) and REE (-159 ± 191 kcal/24 h) (all p < 0.05). With weight loss, there were no changes in GM and WM. Before and after weight loss, FFM was the main determinant of REE (r2 = 0.483 and 0.413; p < 0.05). After weight loss, GM added to the variances in REE (3.6%), REEadjFFM (6.1%) and the REE on FFM residuals (6.6%). In addition, before and after weight loss GM explained 25.0% and 10.0% of the variances in EM (p < 0.05). Weight loss had no effect on volumes of GM and WM. After weight loss, both, GM added to the variances of REE, REE on FFM residuals and EM.

Total energy expenditure and body composition of children with developmental disabilities.

BACKGROUND: Obesity prevalence is increased in children with developmental disabilities, specifically in children with spina bifida and Down syndrome. Energy expenditure, a critical aspect of weight management, has been extensively studied in the typically developing population, but not adequately studied in children with developmental disabilities. OBJECTIVE: Determine energy expenditure, fat-free mass and body fat percentile and the impact of these findings on recommended caloric intake in children with spina bifida and Down syndrome. METHODS/MEASURES: This pilot study included 36 children, 18 with spina bifida, 9 with Down syndrome and 9 typically developing children. Half of the children with spina bifida were non-ambulatory. Doubly labeled water was used to measure energy expenditure and body composition. Descriptive statistics described the sample and MANOVA and ANOVA methods were used to evaluate differences between groups. RESULTS: Energy expenditure was significantly less for children with spina bifida who primarily used a wheelchair (p = .001) and children with Down syndrome (p = .041) when compared to children without a disability when adjusted for fat-free mass. However, no significant difference was detected in children with spina bifida who ambulated without assistance (p = .072). CONCLUSIONS: Children with spina bifida and Down syndrome have a significantly decreased energy expenditure which directly impacts recommended caloric intake. No significant difference was detected for children with spina bifida who ambulated, although the small sample size of this pilot study may have limited these findings. Validating these results in a larger study is integral to supporting successful weight management of these children.

Accuracy of octa-polar bioelectrical impedance analysis for the assessment of total and appendicular body composition in children and adolescents with HIV: comparison with dual energy X-ray absorptiometry and air displacement plethysmography.

BACKGROUND: Body composition analysis has been used to investigate fat mass (FM) and bone mineral content (BMC) in children and adolescents diagnosed with HIV. Investigating the validity of bioelectrical impedance analysis (BIA) is interesting with respect to testing useful techniques for monitoring body composition in children and adolescents in clinical practice. The present study aimed to determine the validity of body composition analysis by BIA compared to dual-energy X-ray absorptiometry (DXA) and air displacement plethysmography (ADP) in children and adolescents an HIV diagnosis. METHODS: Sixty-four children and adolescents (35 females and 29 males) with a mean (SD) age of 12.22 (2.13) years and with an HIV diagnosis participated in the study. Fat-free mass (FFM), FM and body fat percentage (%BF) were obtained by BIA for comparison with DXA and ADP. Segmented FM (trunk, legs and arms), lean soft tissue mass (LSTM) (total and segmented) and BMC were obtained by BIA for comparison with DXA. RESULTS: BIA presented a clinically acceptable correlation with DXA and ADP for FFM. Values found by BIA were underestimated compared to ADP, and overestimated compared to DXA. BIA presented a clinically acceptable correlation with DXA for LSTM estimates (total and segmented parameters) in both sexes (underestimating FM and overestimating LSTM). For other components (%BF, FM and BMC), BIA had a clinically unacceptable correlation with the reference methods in both sexes. CONCLUSIONS: BIA was suitable for evaluating FFM and LSTM in children and adolescents with an HIV diagnosis. For FM, %BF and BMC, BIA was not suitable for performing an evaluation in both sexes.

Protein supplements after weight loss do not improve weight maintenance compared with recommended dietary protein intake despite beneficial effects on appetite sensation and energy expenditure: a randomized, controlled, double-blinded trial.

Background: High-protein diets increase weight loss (WL) during energy restriction; therefore, it has been suggested that additional protein intake may improve weight maintenance (WM) after WL.Objective: We investigated the effect of protein supplements from either whey with or without calcium or soy on WM success after WL compared with that of a control.Design: In a randomized, controlled, double-blinded trial, 220 participants aged 18-60 y with body mass index (in kg/m2) from 27.6 to 40.4 were included. The study was initiated with an 8-wk WL period followed by a 24-wk WM period. During WM, participants consumed the following isocaloric supplements (45-48 g/d): whey and calcium (whey+), whey, soy, or maltodextrin (control). Data were collected at baseline, before WM, and after WM (weeks 0, 8, and 32, respectively) and included body composition, blood biochemistry, and blood pressure. Meal tests were performed to investigate diet-induced-thermogenesis (DIT) and appetite sensation. Compliance was tested by 24-h urinary nitrogen excretion.Results: A total of 151 participants completed the WM period. The control and 3 protein supplements did not result in different mean ± SD weight regains (whey+: 2.19 ± 4.6 kg; whey: 2.01 ± 4.6 kg; soy: 1.76 ± 4.7 kg; and control: 2.23 ± 3.8 kg; P = 0.96), fat mass regains (whey+: 0.46 ± 4.5 kg; whey: 0.11 ± 4.1 kg; soy: 0.15 ± 4.1 kg; and control: 0.54 ± 3.3 kg; P = 0.96), or improvements in lean body mass (whey+: 1.87 ± 1.7 kg; whey: 1.94 ± 1.3 kg; soy: 1.58 ± 1.4 kg; and control: 1.74 ± 1.4 kg; P = 0.50) during WM. Changes in blood pressure and blood biochemistry were not different between groups. Compared with the control, protein supplementation resulted in higher DIT (∼30 kJ/2.5 h) and resting energy expenditure (243 kJ/d) and an anorexigenic appetite-sensation profile.Conclusion: Protein supplementation does not result in improved WM success, or blood biochemistry after WL compared with the effects of normal dietary protein intake (0.8-1.0 g · kg-1 · d-1). This trial was registered at clinicaltrials.gov as NCT01561131.

Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans.

Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial.Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P < 0.01). Men in the CR group lost significantly more trunk fat (P = 0.03) and FFM expressed as a percentage of weight loss (P < 0.001) than women in the CR group.Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline. CALERIE was registered at clinicaltrials.gov as NCT00427193.

Relative contribution of organs other than brain to resting energy expenditure is consistent among male power athletes.

We have previously shown that resting energy expenditure (REE) adjusted by fat-free mass (FFM) in male college athletes remains consistent regardless of FFM. The FFM comprises internal organs with high metabolic activity, such as liver and brain, which account for 60 to 80% of REE in adults. The purpose of the present study is to examine the contribution of internal organs to the REE of the FFM fraction among male power athletes. The study included 37 American male college football players. REE was measured by indirect calorimetry and body composition was measured by dual energy X-ray absorptiometry (DXA). Mass of brain, liver, and kidneys was measured by MRI and mass of heart was estimated by echocardiography. Normal levels of thyroid hormone (triiodothyronine: T3) were confirmed in all subjects prior to the analysis. Multiple regression analysis was used to assess the influence of FFM, fat mass (FM), T3, and mass of organs on variance of REE. Average body weight and FFM were 81.2±11.3 kg and 67.7±7.4 kg, respectively. The relative contributions of liver, kidneys, and heart to REE were consistent regardless of FFM, while the REE of brain was negatively correlated with FFM (r=-0.672, p<0.001). Only FFM and T3 were found to be independent factors influencing REE. These results suggest that a steady contribution of internal organs other than the brain is the major reason for the consistency of the REE/FFM ratio in male power athletes.

Male mice that lack the G-protein-coupled receptor GPR41 have low energy expenditure and increased body fat content.

SCFA are produced in the gut by bacterial fermentation of undigested carbohydrates. Activation of the Gαi-protein-coupled receptor GPR41 by SCFA in ß-cells and sympathetic ganglia inhibits insulin secretion and increases sympathetic outflow, respectively. A possible role in stimulating leptin secretion by adipocytes is disputed. In the present study, we investigated energy balance and glucose homoeostasis in GPR41 knockout mice fed on a standard low-fat or a high-fat diet. When fed on the low-fat diet, body fat mass was raised and glucose tolerance was impaired in male but not female knockout mice compared to wild-type mice. Soleus muscle and heart weights were reduced in the male mice, but total body lean mass was unchanged. When fed on the high-fat diet, body fat mass was raised in male but not female GPR41 knockout mice, but by no more in the males than when they were fed on the low-fat diet. Body lean mass and energy expenditure were reduced in male mice but not in female knockout mice. These results suggest that the absence of GPR41 increases body fat content in male mice. Gut-derived SCFA may raise energy expenditure and help to protect against obesity by activating GPR41.

Impact of endogenous and exogenous insulin on basal energy expenditure in patients with type 2 diabetes under standard treatment.

BACKGROUND: Factors that affect resting energy expenditure or basal energy expenditure (BEE) in patients with type 2 diabetes under standard treatment have not been evaluated in detail. OBJECTIVE: We determined the clinical factors that affected BEE in addition to body composition in patients with type 2 diabetes under standard treatment. DESIGN: BEE was measured by using indirect calorimetry under a strict basal condition in 58 Japanese patients with type 2 diabetes after >7 d as inpatients under management of diabetes with medical nutrition therapy and medications. Insulin secretion was measured with a glucagon test. Stepwise regression was applied to explore determinants of BEE. RESULTS: In the stepwise estimation, insulin secretion (P = 0.015), insulin therapy (P = 0.012), and pulse rate (P = 0.011) were selected in addition to fat-free mass (FFM) (P < 0.001) and fat mass (P = 0.006) as significant independent determinants of BEE. Standardized partial regression coefficients of the additional 3 factors were -0.16, -0.15, and 0.15, respectively, whereas those for FFM and fat mass were 0.82 and 0.19, respectively. The additional 3 factors explained another 3.9% of the variability of BEE, and the adjusted coefficient of determination was 83.4%. Age, sex, other medications, and parameters of glycemic control were not significant determinants beyond the combined contribution of body composition, endogenous and exogenous insulin, and pulse rate. CONCLUSION: Endogenous insulin secretion and exogenous insulin administered in treatment have significant independent effects in the lowering of BEE in patients with diabetes under standard management with medical nutrition therapy and medications.

Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antibacterial agents.

The exposure-response relationship of anti-infective agents at the site of infection is currently being re-examined. Epithelial lining fluid (ELF) has been suggested as the site (compartment) of antimicrobial activity against lung infections caused by extracellular pathogens. There have been an extensive number of studies conducted during the past 20 years to determine drug penetration into ELF and to compare plasma and ELF concentrations of anti-infective agents. The majority of these studies estimated ELF drug concentrations by the method of urea dilution and involved either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Antibacterial agents such as macrolides, ketolides, newer fluoroquinolones and oxazolidinones have ELF to plasma concentration ratios of >1. In comparison, ß-lactams, aminoglycosides and glycopeptides have ELF to plasma concentration ratios of ≤1. Potential explanations (e.g. drug transporters, overestimation of the ELF volume, lysis of cells) for why these differences in ELF penetration occur among antibacterial classes need further investigation. The relationship between ELF concentrations and clinical outcomes has been under-studied. In vitro pharmacodynamic models, using simulated ELF and plasma concentrations, have been used to examine the eradication rates of resistant and susceptible pathogens and to explain why selected anti-infective agents (e.g. those with ELF to plasma concentration ratios of >1) are less likely to be associated with clinical treatment failures. Population pharmacokinetic modelling and Monte Carlo simulations have recently been used and permit ELF and plasma concentrations to be evaluated with regard to achievement of target attainment rates. These mathematical modelling techniques have also allowed further examination of drug doses and differences in the time courses of ELF and plasma concentrations as potential explanations for clinical and microbiological effects seen in clinical trials. Further studies are warranted in patients with lower respiratory tract infections to confirm and explore the relationships between ELF concentrations, clinical and microbiological outcomes, and pharmacodynamic parameters.

Preclinical dynamic 18F-FDG PET - tumor characterization and radiotherapy response assessment by kinetic compartment analysis.

BACKGROUND: Non-invasive visualization of tumor biological and molecular processes of importance to diagnosis and treatment response is likely to be critical in individualized cancer therapy. Since conventional static (18)F-FDG PET with calculation of the semi-quantitative parameter standardized uptake value (SUV) may be subject to many sources of variability, we here present an approach of quantifying the (18)F-FDG uptake by analytic two-tissue compartment modeling, extracting kinetic tumor parameters from dynamic (18)F-FDG PET. Further, we evaluate the potential of such parameters in radiotherapy response assessment. MATERIAL AND METHODS: Male, athymic mice with prostate carcinoma xenografts were subjected to dynamic PET either untreated (n=8) or 24 h post-irradiation (7.5 Gy single dose, n=8). After 10 h of fasting, intravenous bolus injections of 10-15 MBq (18)F-FDG were administered and a 1 h dynamic PET scan was performed. 4D emission data were reconstructed using OSEM-MAP, before remote post-processing. Individual arterial input functions were extracted from the image series. Subsequently, tumor (18)F-FDG uptake was fitted voxel-by-voxel to a compartment model, producing kinetic parameter maps. RESULTS: The kinetic model separated the (18)F-FDG uptake into free and bound tracer and quantified three parameters; forward tracer diffusion (k(1)), backward tracer diffusion (k(2)), and rate of (18)F-FDG phosphorylation, i.e. the glucose metabolism (k(3)). The fitted kinetic model gave a goodness of fit (r(2)) to the observed data ranging from 0.91 to 0.99, and produced parametrical images of all tumors included in the study. Untreated tumors showed homogeneous intra-group median values of all three parameters (k(1), k(2) and k(3)), whereas the parameters significantly increased in the tumors irradiated 24 h prior to (18)F-FDG PET. CONCLUSIONS: This study demonstrates the feasibility of a two-tissue compartment kinetic analysis of dynamic (18)F-FDG PET images. If validated, extracted parametrical maps might contribute to tumor biological characterization and radiotherapy response assessment.

Brain and high metabolic rate organ mass: contributions to resting energy expenditure beyond fat-free mass.

BACKGROUND: The degree to which interindividual variation in the mass of select high metabolic rate organs (HMROs) mediates variability in resting energy expenditure (REE) is unknown. OBJECTIVE: The objective was to investigate how much REE variability is explained by differences in HMRO mass in adults and whether age, sex, and race independently predict REE after adjustment for HMRO. DESIGN: A cross-sectional evaluation of 55 women [30 African Americans aged 48.7 +/- 22.2 y (mean +/- SD) and 25 whites aged 46.4 +/- 17.7 y] and 32 men (8 African Americans aged 34.3 +/- 18.2 y and 24 whites aged 51.3 +/- 20.6 y) was conducted. Liver, kidney, spleen, heart, and brain masses were measured by magnetic resonance imaging, and fat and fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry. REE was measured by indirect calorimetry. RESULTS: REE estimated from age (P = 0.001), race (P = 0.006), sex (P = 0.31), fat (P = 0.001), and FFM (P < 0.001) accounted for 70% (adjusted (2)) of the variability in REE. The addition of trunk HMRO (P = 0.001) and brain (P = 0.006) to the model increased the explained variance to 75% and rendered the contributions of age, sex, and race statistically nonsignificant, whereas fat and FFM continued to make significant contributions (both P < 0.05). The addition of brain to the model rendered the intercept (69 kcal . kg(-1) . d(-1)) consistent with zero, which indicated zero REE for zero body mass. CONCLUSIONS: Relatively small interindividual variation in HMRO mass significantly affects REE and reduces the role of age, race, and sex in explaining REE. Decreases in REE with increasing age may be partly related to age-associated changes in the relative size of FFM components.