‘Functional’ body composition: differentiating between benign and non-benign obesity

Recent body composition analyses, together with assessments of insulin resistance, aerobic fitness, and intima-media thickness of the common carotid artery, have shown that metabolically-benign obese subjects have a similar BMI, waist circumference, and subcutaneous abdominal fat compared with non-metabolically-benign obese subjects. Research has suggested that 25-30% of the obese population do not need either treatment or prevention of secondary disorders. Therefore, assessment of functional body composition should replace nutritional status-based risk assessments (such as the body mass index) in both metabolic research and clinical decision making. The concept of ‘functional’ body composition gives us a more sophisticated view on nutritional status, metabolism, endocrinology, and diseases. Knowledge of detailed body composition enables characterization of biomedical traits which will give functional evidence relating genetic variants

Relationship between Birth Weight, Early Growth Rate, and Body Composition in 5- to 7-Year-Old Children

Background: Programing of body composition during intrauterine growth may contribute to the higher risk for cardio-metabolic disease in individuals born small or large for gestational age (SGA, LGA). Compensations of intrauterine growth by catch-up or catch-down postnatal growth may lead to adverse consequences like a thin-fat phenotype. Methods: The impact of (i) birth weight as well as (ii) the interaction between birth weight and catch-up or catch-down growth during the first 2 years of life on fat-free mass index (FFMI) and fat mass index (FMI) in 3,204 5–7-year-old children were investigated using Hattori’s body composition chart. Body composition results were compared to appropriate for gestational age (AGA) birth weight with the same body mass index (BMI). Results: In total, 299 children at age 5–7 years were categorized as SGA, 2,583 as AGA, and 322 as LGA. When compared to AGA-children, BMI at 5–7 years of age was higher in LGA-children (15.5 vs. 16.2 kg/m2; p < 0.001) but not different in SGA-children. Compared to AGA with the same BMI, LGA was associated with higher FMI and a lower FFMI in 5–7-year-old girls. This phenotype was also seen for both sexes with catch-down growth during the first 2 years of life whereas catch-up growth prevented the higher FMI and lower FFMI per BMI. By contrast, SGA was associated with a higher FFMI and lower FMI in 5–7-year-old boys compared to AGA boys with the same BMI. This phenotype was also seen with catch-down growth in both genders whereas catch-up growth in girls led to more gain in FMI per BMI. Conclusion: LGA with a compensatory catch-down postnatal growth may be a risk factor for the development of disproportionate gain in fat over lean mass whereas SGA with a catch-down postnatal growth seems to favor the subsequent accretion of lean over fat mass. A higher propensity of lean mass accretion during postnatal growth in boys compared to girls explains sex differences in these phenotypes

Analysis of the adiponectin paradox in healthy older people

Background It remains unknown why adiponectin levels are associated with poor physical functioning, skeletal muscle mass and increased mortality in older populations. Methods In 190 healthy adults (59-86 years, BMI 17-37 kg/m2 , 56.8% female), whole body skeletal muscle mass (normalized by height, SMI, kg/m2 ), muscle and liver fat were determined by magnetic resonance imaging. Bone mineral content (BMC) and density (BMD) were assessed by dual X-ray absorptiometry (n = 135). Levels of insulin-like growth factor 1 (IGF-1), insulin, inflammation markers, leptin and fibroblast growth factor 21 were measured as potential determinants of the relationship between adiponectin and body composition. Results Higher adiponectin levels were associated with a lower SMI (r = -0.23, P < 0.01), BMC (r = -0.17, P < 0.05) and liver fat (r = -0.20, P < 0.05) in the total population and with higher muscle fat in women (r = 0.27, P < 0.01). By contrast, IGF-1 showed positive correlations with SMI (r = 0.33), BMD (r = 0.37) and BMC (r = 0.33) (all P < 0.01) and a negative correlation with muscle fat (r = -0.17, P < 0.05). IGF-1 was negatively associated with age (r = -0.21, P < 0.01) and with adiponectin (r = -0.15, P < 0.05). Stepwise regression analyses revealed that IGF-1, insulin and leptin explained 18% of the variance in SMI, and IGF-1, leptin and age explained 16% of the variance in BMC, whereas adiponectin did not contribute to these models. Conclusions Associations between higher adiponectin levels and lower muscle or bone mass in healthy older adults may be explained by a decrease in IGF-1 with increasing adiponectin levels

Recent advances in understanding body weight homeostasis in humans [version 1; referees: 4 approved]

Presently, control of body weight is assumed to exist, but there is no consensus framework of body weight homeostasis. Three different models have been proposed, with a “set point” suggesting (i) a more or less tight and (ii) symmetric or asymmetric biological control of body weight resulting from feedback loops from peripheral organs and tissues (e.g. leptin secreted from adipose tissue) to a central control system within the hypothalamus. Alternatively, a “settling point” rather than a set point reflects metabolic adaptations to energy imbalance without any need for feedback control. Finally, the “dual intervention point” model combines both paradigms with two set points and a settling point between them. In humans, observational studies on large populations do not provide consistent evidence for a biological control of body weight, which, if it exists, may be overridden by the influences of the obesogenic environment and culture on personal behavior and experiences. To re-address the issue of body weight homeostasis, there is a need for targeted protocols based on sound concepts, e.g. lean rather than overweight subjects should be investigated before, during, and after weight loss and weight regain. In addition, improved methods and a multi-level–multi-systemic approach are needed to address the associations (i) between masses of individual body components and (ii) between masses and metabolic functions in the contexts of neurohumoral control and systemic effects. In the future, simplifications and the use of crude and non-biological phenotypes (i.e. body mass index and waist circumference) should be avoided. Since changes in body weight follow the mismatch between tightly controlled energy expenditure at loosely controlled energy intake, control (or even a set point) is more likely to be about energy expenditure rather than about body weight itself

Validation of energy expenditure and macronutrient oxidation measured by two new whole-room indirect calorimeters

Objective The aim of this study was to validate two new whole-room indirfect calorimeters according to Room Indirect Calorimetry Operating and Reporting Standards (RICORS 1.0). Methods For technical validation, 16 propane combustion tests were performed to determine accuracy and precision of energy expenditure (EE) and ventilation rates of oxygen (VO2 ), carbon dioxide (VCO2 ), and respiratory exchange ratio (VCO2 /VO2 ). For biological validation, eight participants (mean [SD], age 24.1 [2.5] years; BMI 24.3 [3.1] kg/m2 ) underwent four 24-hour protocols under highly standardized conditions: (1) isocaloric sedentary, (2) fasting sedentary, (3) isocaloric active, and (4) fasting active. Reliability (coefficients of variation [CV]) and minimal detectable changes (MDC) were calculated for 24-hour EE, sleeping metabolic rate (SMR), physical activity energy expenditure (PAEE), thermic effect of food (TEF), and macronutrient oxidation rates. Results Technical validation showed high reliability and recovery rates for VO2 (0.75% and 100.8%, respectively), VCO2 (0.49% and 100.6%), and EE (0.54% and 98.2%). Biological validation revealed CV and MDC for active conditions of 1.4% and 4.3% for 24-hour EE, 1.7% and 5.9% for SMR, and 30.2% and 38.4% for TEF, as well as 5.8% and 10.5% for PAEE, respectively. Mean CV and MDC for macronutrient oxidation rates were 9.9% and 22.9%, respectively. Conclusions The precision of 24-hour EE and SMR was high, whereas it was lower for PAEE and poor for TEF

Independence and property in Kant's Rechtslehre

I argue that the freedom which is to coexist with the freedom of choice of others in accordance with a universal law mentioned in Kant's Rechtslehre is not itself freedom of choice. Rather, it is the independence which is a condition of being able to exercise genuine free choice by not having to act in accordance with the choices of others. Kant's distinction between active and passive citizenship appears, however, to undermine this idea of independence, because the possession of a certain type of property right on the part of some citizens makes it possible for them to dominate others. Kant's account of property in this way turns out to be central to the question as to whether his Rechtslehre represents an internally consistent account of how freedom can be guaranteed within a legal and political community. I go on to argue that Kant's attempt to justify a pre-political right of property cannot be viewed as a successful justification of private property, and that he should have abandoned the notion of such a right together with any presumption in favour of private property

FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas

In search of novel genes associated with glioma pathogenesis, we have previously shown frequent deletions of the KIAA1797/FOCAD gene in malignant gliomas, and a tumor suppressor function of the encoded focadhesin impacting proliferation and migration of glioma cells in vitro and in vivo. Here, we examined an association of reduced FOCAD gene copy number with overall survival of patients with astrocytic gliomas, and addressed the molecular mechanisms that govern the suppressive effect of focadhesin on glioma growth. FOCAD loss was associated with inferior outcome in patients with isocitrate dehydrogenase 1 or 2 (IDH)-mutant astrocytic gliomas of WHO grades II-IV. Multivariate analysis considering age at diagnosis as well as IDH mutation, MGMT promoter methylation, and CDKN2A/B homozygous deletion status confirmed reduced FOCAD gene copy number as a prognostic factor for overall survival. Using a yeast two-hybrid screen and pull-down assays, tubulin beta-6 and other tubulin family members were identified as novel focadhesin-interacting partners. Tubulins and focadhesin co-localized to centrosomes where focadhesin was enriched in proximity to centrioles. Focadhesin was recruited to microtubules via its interaction partner SLAIN motif family member 2 and reduced microtubule assembly rates, possibly explaining the focadhesin-dependent decrease in cell migration. During the cell cycle, focadhesin levels peaked in G2/M phase and influenced time-dependent G2/M progression potentially via polo like kinase 1 phosphorylation, providing a possible explanation for focadhesin-dependent cell growth reduction. We conclude that FOCAD loss may promote biological aggressiveness and worsen clinical outcome of diffuse astrocytic gliomas by enhancing microtubule assembly and accelerating G2/M phase progression

Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma

Objective: To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT -> TMZ) by extending TMZ beyond 6 cycles. Methods: The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT -> TMZ and completed >6 cycles of maintenance chemotherapy without progression. Associations of clinical patient characteristics, molecular markers, and residual tumor determined by magnetic resonance imaging after 6 cycles of TMZ with progression-free survival (PFS) and overall survival (OS) were analyzed with the log-rank test. Multivariate analyses using the Cox proportional hazards model were performed to assess associations of prolonged TMZ use with outcome. Results: Sixty-one of 142 identified patients received at least 7 maintenance TMZ cycles (median 11, range 7-20). Patients with extended maintenance TMZ treatment had better PFS (20.5 months, 95% confidence interval [CI] 17.7-23.3, vs 17.2 months, 95% CI 10.2-24.2, p = 0.035) but not OS (32.6 months, 95% CI 28.9-36.4, vs 33.2 months, 95% CI 25.3-41.0, p = 0.126). However, there was no significant association of prolonged TMZ chemotherapy with PFS (hazard ratio [HR] 5 0.8, 95% CI 0.4-1.6, p = 0.559) or OS (HR 5 1.6, 95% CI 0.8-3.3, p = 0.218) adjusted for age, extent of resection, Karnofsky performance score, presence of residual tumor, O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, or isocitrate dehydrogenase (IDH) mutation status. Conclusion: These data may not support the practice of prolonging maintenance TMZ chemotherapy beyond 6 cycles. Classification of evidence: This study provides Class III evidence that in patients with newly diagnosed glioblastoma, prolonged TMZ chemotherapy does not significantly increase PFS or OS

Effect of Constitution on Mass of Individual Organs and Their Association with Metabolic Rate in Humans—A Detailed View on Allometric Scaling

Resting energy expenditure (REE)-power relationships result from multiple underlying factors including weight and height. In addition, detailed body composition, including fat free mass (FFM) and its components, skeletal muscle mass and internal organs with high metabolic rates (i.e. brain, heart, liver, kidneys), are major determinants of REE. Since the mass of individual organs scales to height as well as to weight (and, thus, to constitution), the variance in these associations may also add to the variance in REE. Here we address body composition (measured by magnetic resonance imaging) and REE (assessed by indirect calorimetry) in a group of 330 healthy volunteers differing with respect to age (17–78 years), sex (61% female) and BMI (15.9–47.8 kg/m2). Using three dimensional data interpolation we found that the inter-individual variance related to scaling of organ mass to height and weight and, thus, the constitution-related variances in either FFM (model 1) or kidneys, muscle, brain and liver (model 2) explained up to 43% of the inter-individual variance in REE. These data are the first evidence that constitution adds to the complexity of REE. Since organs scale differently as weight as well as height the “fit” of organ masses within constitution should be considered as a further trait