Kinetics of stable isotope and body composition in olive baboons (Papio anubis) estimated by deuterium dilution space: a pilot study

Morphometrics and isotope-labelled water were used to determine body composition [total body water, total body fat and fat-free mass (FFM)] of three captive female olive baboons (Papio anubis). Mean mass was 16.5 kg, comparable with other captive settings but heavier than wild olive baboons. Average water content was 66%; FFM averaged 90.5%. Baboon females have less body fat than human counterparts. Compared with captive or wild baboons, these females were adequately nourished for their energy expenditure. A positive association between total mass and FFM existed, but due to the small sample no general relationship was observed for body fat or FFM and condition or size measures. The kinetics of deuterium equilibration in body fluids for baboons was determined as 3-4 hours after injection, similar to that for humans. Deuterium dilution technique appears to be an appropriate method for studying body composition in baboons, although a larger sample is needed for relationships between morphometric indices and body composition.     

Magnitude and variation of fat-free mass density: a cellular-level body composition modeling study

The mean density of fat-free mass (FFM) is remarkably stable at 1.10 g/cm(3) in healthy adult humans, and this stability is a cornerstone of the widely applied densitometry-based two-compartment model for estimating total body fat. At present, the usual means of exploring FFM density is by in vitro or in vivo experimental studies. The purpose of the present investigation was to develop a cellular-level body composition model that includes seven factors that determine FFM density. The model, when applied with available empirical coefficients, predicted an FFM density similar to that observed in vivo. An analysis of the seven model components indicates that the ratio of extracellular solids to total body water is a major determinant of individual variation in FFM density. The difference in FFM density across sex, race, and age groups was examined with the developed model. The present study thus provides a conceptual framework for the systematic study of FFM density in humans.     

Magnitude and variation of ratio of total body potassium to fat-free mass: a cellular level modeling study

Potassium is an essential element of living organisms that is found almost exclusively in the intracellular fluid compartment. The assumed constant ratio of total body potassium (TBK) to fat-free mass (FFM) is a cornerstone of the TBK method of estimating total body fat. Although the TBK-to-FFM (TBK/FFM) ratio has been assumed constant, a large range of individual and group values is recognized. The purpose of the present study was to undertake a comprehensive analysis of biological factors that cause variation in the TBK/FFM ratio. A theoretical TBK/FFM model was developed on the cellular body composition level. This physiological model includes six factors that combine to produce the observed TBK/FFM ratio. The ratio magnitude and range, as well as the differences in the TBK/FFM ratio between men and women and variation with growth, were examined with the proposed model. The ratio of extracellular water to intracellular water (E/I) is the major factor leading to between-individual variation in the TBK/FFM ratio. The present study provides a conceptual framework for examining the separate TBK/FFM determinants and suggests important limitations of the TBK/FFM method used in estimating total body fat in humans and other mammals.     

Hypothalamic inflammation and thermogenesis: the brown adipose tissue connection

Hypothalamic inflammation and dysfunction are common features of experimental obesity. An imbalance between caloric intake and energy expenditure is generated as a consequence of this inflammation, leading to the progressive increase of body adiposity. Thermogenesis, is one of the main functions affected by obesity-linked hypothalamic dysfunction and the complete characterization of the mechanisms involved in this process may offer new therapeutic perspectives for obesity. The brown adipose tissue is an important target for hypothalamic action in thermogenesis. This tissue has been thoroughly studied in rodents and hibernating mammals; however, until recently, its advocated role in human thermogenesis was neglected due to the lack of substantial evidence of its presence in adult humans. The recent demonstration of the presence of functional brown adipose tissue in adult humans has renovated the interest in this tissue. Here, we review some of the work that shows how inflammation and dysfunction of the hypothalamus can control brown adipose tissue activity and how this can impact on whole body thermogenesis and energy expenditure.     

Metabolic correlates of hominid brain evolution

Large brain sizes in humans have important metabolic consequences as humans expend a relatively larger proportion of their resting energy budget on brain metabolism than other primates or non-primate mammals. The high costs of large human brains are supported, in part, by diets that are relatively rich in energy and other nutrients. Among living primates, the relative proportion of metabolic energy allocated to the brain is positively correlated with dietary quality. Humans fall at the positive end of this relationship, having both a very high quality diet and a large brain size. Greater encephalization also appears to have consequences for aspects of body composition. Comparative primate data indicate that humans are 'under-muscled', having relatively lower levels of skeletal muscle than other primate species of similar size. Conversely, levels of body fatness are relatively high in humans, particularly in infancy. These greater levels of body fatness and reduced levels of muscle mass allow human infants to accommodate the growth of their large brains in two important ways: (1) by having a ready supply of stored energy to 'feed the brain', when intake is limited and (2) by reducing the total energy costs of the rest of the body. Paleontological evidence indicates that the rapid brain evolution observed with the emergence of Homo erectus at approximately 1.8 million years ago was likely associated with important changes in diet and body composition.     

Modeling the influence of body size on V(O2) peak: effects of model choice and body composition.

This study examined the bivariate relationship between peak oxygen uptake (V(O2) peak); l/min) and body size in adult men (n = 1,314, age 17-66 yr), using both "simple" and "full" iterative nonlinear allometric models. The simple model was described by V(O2) peak = M(b) (or FFM(b)) exp(c SR-PA) exp(a + d age) epsilon (where M is body mass in kg; FFM is fat-free mass in kg; SR-PA is self-reported physical activity; epsilon is a multiplicative error term; and exp indicates natural antilogarithms). The full model was described by V(O2) peak = M(b) (or FFM(b)) exp(c SR-PA) exp(a + d age) + e (epsilon), where e is a permitted Y-intercept term. The M exponent obtained from simple allometry was 0.65 [95% confidence interval (CI), 0.59-0.71], suggestive of a curvilinear relationship constrained to pass through the origin. This "zero Y-intercept" assumption was examined via the full allometric model, which revealed an M exponent of 1.00 (95% CI, 0.7-1.31), together with a positive Y-intercept term (e) of 1.13 (95% CI, 0.54-1.73). The FFM exponents were not significantly different from unity in either the simple or full allometric models. It appears that the curvilinearity of the simple allometric model (using total M) is fictitious and is due to the inappropriate forcing of the regression line through the origin. Utilizing FFM as the body-size variable revealed a linear relationship between body size and V(O2) peak, irrespective of model choice. We conclude that the population mass exponent for V(O2) peak is close to unity.     

Metabolically active portion of fat-free mass: a cellular body composition level modeling analysis

The proportion of fat-free mass (FFM) as body cell mass (BCM) is highly related to whole body resting energy expenditure. However, the magnitude of BCM/FFM may have been underestimated in previous studies. This is because Moore's equation [BCM (kg) = 0.00833 x total body potassium (in mmol)], which was used to predict BCM, underestimates BCM by approximately 11%. The aims of the present study were to develop a theoretical BCM/FFM model at the cellular level and to explore the influences of sex, age, and adiposity on the BCM/FFM. Subjects were 112 adults who had the following measurements: total body water by (2)H(2)O or (3)H(2)O dilution; extracellular water by NaBr dilution; total body nitrogen by in vivo neutron activation analysis; and bone mineral by dual-energy X-ray absorptiometry. FFM was calculated using a multicomponent model and BCM as the difference between FFM and the sum of extracellular fluid and solids. The developed theoretical model revealed that the proportion of BCM to FFM is mainly determined by water distribution (i.e., E/I, the ratio of extracellular to intracellular water). A significant correlation (r = 0.90, P < 0.001) was present between measured and model-predicted BCM/FFM for all subjects pooled. Measured BCM/FFM [mean (SD)] was 0.584 +/- 0.041 and 0.529 +/- 0.041 for adult men and women (P < 0.001), respectively. A multiple linear regression model showed that there are independent significant associations of sex, age, and fat mass with BCM/FFM.     

The compositional distribution of coding sequences and DNA molecules in humans and murids

Summary The compositional distributions of coding sequences and DNA molecules (in the 50-100-kb range) are remarkably narrower in murids (rat and mouse) compared to humans (as well as to all other mammals explored so far). In murids, both distributions begin at higher and end at lower GC values. A comparison of homologous coding sequences from murids and humans revealed that their different compositional distributions are due to differences in GC levels in all three codon positions, particularly of genes located at both ends of the distribution. In turn, these differences are responsible for differences in both codon usage and amino acids. When GC levels at first+second codon positions and third codon positions, respectively, of murid genes are plotted against corresponding GC levels of homologous human genes, linear relationships (with very high correlation coefficients and slopes of about 0.78 and 0.60, respectively) are found. This indicates a conservation of the order of GC levels in homologous genes from humans and murids. (The same comparison for mouse and rat genes indicates a conservation of GC levels of homologous genes.) A similar linear relationship was observed when plotting GC levels of corresponding DNA fractions (as obtained by density gradient centrifugation in the presence of a sequence-specific ligand) from mouse and human. These findings indicate that orderly compositional changes affecting not only coding sequences but also noncoding sequences took place since the divergence of murids. Such directional fixations of mutations point to the existence of selective pressures affecting the genome as a whole.     

Fat, muscles, and wages

Recent studies in health economics have generated two important findings: that as a measure of fatness the body mass index (BMI) is biased; and that, when it comes to analyzing wage correlates, both fat-free mass (FFM) and body fat (BF) are better suited to the task. We validate these findings for Germany using the BIAdata Base Project and the German Socio-Economic Panel. While we find no significant correlation between BMI and wages in any of our models, simple linear regression models featuring both contemporary and time-lagged fatness measures indicate that FFM and, to a lesser extent, BF are associated with hourly wages: more specifically, the relationship between FFM/BF and hourly wages is about two to three times higher for females than for males. In contrast, fixed-effects models indicate that there is no correlation between hourly wages and both FFM and BF with one exception: a significant correlation (and one in line with expectations) is found to be the rule among job changers.     

Metabolism and longevity: is there a role for membrane fatty acids?

More than 100 years ago, Max Rubner combined the fact that both metabolic rate and longevity of mammals varies with body size to calculate that "life energy potential" (lifetime energy turnover per kilogram) was relatively constant. This calculation linked longevity to aerobic metabolism which in turn led to the "rate-of-living" and ultimately the "oxidative stress" theories of aging. However, the link between metabolic rate and longevity is imperfect. Although unknown in Rubner's time, one aspect of body composition of mammals also varies with body size, namely the fatty acid composition of membranes. Fatty acids vary dramatically in their susceptibility to peroxidation and the products of lipid peroxidation are very powerful reactive molecules that damage other cellular molecules. The "membrane pacemaker" modification of the "oxidative stress" theory of aging proposes that fatty acid composition of membranes, via its influence on peroxidation of lipids, is an important determinant of lifespan (and a link between metabolism and longevity). The relationship between membrane fatty acid composition and longevity is discussed for (1) mammals of different body size, (2) birds of different body size, (3) mammals and birds that are exceptionally long-living for their size, (4) strains of mice that vary in longevity, (5) calorie-restriction extension of longevity in rodents, (6) differences in longevity between queen and worker honeybees, and (7) variation in longevity among humans. Most of these comparisons support an important role for membrane fatty acid composition in the determination of longevity. It is apparent that membrane composition is regulated for each species. Provided the diet is not deficient in polyunsaturated fat, it has minimal influence on a species' membrane fatty acid composition and likely also on it's maximum longevity. The exceptional longevity of Homo sapiens combined with the limited knowledge of the fatty acid composition of human tissues support the potential importance of mitochondrial membranes in determination of longevity.     

Testosterone,physical activity,and somatic outcomes among Filipino males

Testosterone (T) facilitates male investment in reproduction in part through its anabolic effects on skeletal muscle. Traits like muscle and strength are energetically costly but are believed to enhance competitive ability in humans and other mammals. However, there are limited data on relationships between T and somatic outcomes in lean, non‐western populations. We evaluate relationships between waking and pre‐bed salivary T and adiposity, fat‐free mass (FFM), arm muscle area (AMA), and grip strength (GS) in a large, population‐based birth cohort of young adult Filipino males (20.8–22.6 years, n = 872). Data were collected as part of the Cebu Longitudinal Health and Nutrition Survey. Neither waking nor evening T predicted FFM, AMA, or GS. However, there were borderline or significant interactions between T and basketball playing (the most common team sport) and weight lifting as predictors of outcomes: higher waking T predicted higher FFM (activity × T interaction P < 0.01), AMA (interaction P < 0.1), and GS (interaction P < 0.02) among frequent basketball players, and GS (interaction P < 0.09) among the smaller sample of weight lifters. In contrast to clinical studies, but consistent with findings in several subsistence‐level populations, T was positively related to adiposity in these lean young males, suggesting that energy status might regulate circulating T. Our findings support a role of the prewaking rise in T as a determinant of energetic allocation to lean mass and strength in the context of repeated muscular use and support the hypothesized role of T as a mediator of investment in costly somatic traits in human males. Am J Phys Anthropol 142:590–599, 2010. © 2010 Wiley‐Liss, Inc.     

Scaling the physiological effects of exposure to radiofrequency electromagnetic radiation: consequences of body size

We have demonstrated that a comparative analysis of the physiological effects of exposure of laboratory mammals to radiofrequency electromagnetic radiation (RFR) may be useful in predicting exposure thresholds for humans if the effect is assumed to be due only to heating of tissue. The threshold specific absorption rate (SAR) necessary to affect a thermoregulatory parameter shows an inverse and linear relationship to body mass. The inverse relationship between threshold SAR and body mass is attributed to a surface area: body mass relationship. In comparison to small mammals, relatively large mammals have a reduced capacity to dissipate an internal heat load passively, and are therefore physiologically more sensitive to RFR exposure. The threshold for a thermoregulatory response depends on the type of response measured, species, ambient temperature, etc. By extrapolation, it can be shown that a SAR of only 0.2-0.4 W/kg is required to promote a thermoregulatory response in a mammal with a body mass of 70 kg (e.g. weight of adult human). The specific absorption rate bioeffects data collected from laboratory mammals can be related by means of a simple power formula: threshold SAR (W/kg) = aMb, where M is body mass in kg, a is a constant and b is equal to approximately -0.5. Through this equation we have illustrated that a threshold SAR measured in a species weighing 100 g would be 10 times greater than that of a species weighing 10 000 g. Accordingly, a relatively low SAR that is physiologically ineffective in small mammals may be stressful to larger species.     

Predicting changes of body weight, body fat, energy expenditure and metabolic fuel selection in C57BL/6 mice

The mouse is an important model organism for investigating the molecular mechanisms of body weight regulation, but a quantitative understanding of mouse energy metabolism remains lacking. Therefore, we created a mathematical model of mouse energy metabolism to predict dynamic changes of body weight, body fat, energy expenditure, and metabolic fuel selection. Based on the principle of energy balance, we constructed ordinary differential equations representing the dynamics of body fat mass (FM) and fat-free mass (FFM) as a function of dietary intake and energy expenditure (EE). The EE model included the cost of tissue deposition, physical activity, diet-induced thermogenesis, and the influence of FM and FFM on metabolic rate. The model was calibrated using previously published data and validated by comparing its predictions to measurements in five groups of male C57/BL6 mice (N = 30) provided ad libitum access to either chow or high fat diets for varying time periods. The mathematical model accurately predicted the observed body weight and FM changes. Physical activity was predicted to decrease immediately upon switching from the chow to the high fat diet and the model coefficients relating EE to FM and FFM agreed with previous independent estimates. Metabolic fuel selection was predicted to depend on a complex interplay between diet composition, the degree of energy imbalance, and body composition. This is the first validated mathematical model of mouse energy metabolism and it provides a quantitative framework for investigating energy balance relationships in mouse models of obesity and diabetes.     

Scaling of maximal oxygen uptake by lower leg muscle volume in boys and men.

The aim of this study was to critically examine the influence of body size on maximal oxygen uptake (VO2 max) in boys and men using body mass (BM), estimated fat-free mass (FFM), and estimated lower leg muscle volume (Vol) as the separate scaling variables. VO2 max and an in vivo measurement of Vol were assessed in 15 boys and 14 men. The FFM was estimated after percentage body fat had been predicted from population-specific skinfold measurements. By using nonlinear allometric modeling, common body size exponents for BM, FFM, and Vol were calculated. The point estimates for the size exponent (95% confidence interval) from the separate allometric models were: BM 0.79 (0.53-1.06), FFM 1.00 (0.78-1.22), and Vol 0.64 (0.40-0.88). For the boys, substantial residual size correlations were observed for VO2 max/BM0.79 and VO2 max/FFM1.00, indicating that these variables did not correctly partition out the influence of body size. In contrast, scaling by Vol0.64 led to no residual size correlation in boys or men. Scaling by BM is confounded by heterogeneity of body composition and potentially substantial differences in the mass exponent between boys and men. The FFM is precluded as an index of involved musculature because Vol did not represent a constant proportion of FFM [Vol proportional, variantFFM1.45 (95% confidence interval, 1.13-1.77)] in the boys (unlike the men). We conclude that Vol, as an indicator of the involved muscle mass, is the most valid allometric denominator for the scaling of VO2 max in a sample of boys and men heterogeneous for body size and composition.     

Character phylogeny of the primate forelimb superficial venous system.

The ontogeny and comparative anatomy of the forelimb superficial veins were investigated in humans, non-human primates and other mammals. Adult humans and the orangutan (Pongo) possess two autonomous forelimb veins, one on the lateral (preaxial) margin of the limb, the other on the medial (postaxial) margin. All other adult primates and mammals examined possess a lateral vein alone. In African apes (Pan and Gorilla) and in 24% of human forelimbs the lateral vein is short, being essentially confined to the antebrachial region, whereas in other mammals and in 76% of human limbs the lateral vein runs from the carpus to the clavicular region. In humans the medial vein develops before the lateral vein, whereas in the rabbit and the pig the medial vein is present in early embryos but is subsequently lost. We propose that in humans, and probably also in the orangutan, the possession of a medial vein is a neotenic retention of a primitive tetrapod condition. These animals, which retain their medial vein, are united by losing a late stage in their ontogeny. Other animals subsequently pass through a stage in which the medial vein is lost, but Pongo and Homo retain this vein to adulthood. The loss of an ontogenetic stage can arise independently, and the presence of a medial vein therefore affords only weak evidence for a close phylogenetic relationship between humans and the orangutan. The polymorphic lateral vein of humans may be a character state that is intermediate between the derived (short) lateral vein of the African apes and the primitive long lateral vein of other non-human primates and mammals.     

Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation

A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that “the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy”. However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM), fat mass (FM)], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate), but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.     

Allometric scaling and Bayesian priors for annual survival of birds and mammals

Allometric theory predicts that instantaneous mortality rates scale with body mass with a negative quarter power. Such a relationship would mean that the survival rate of one species is partly predictable from the survival rate of other species. We develop allometric regression models for annual adult survival of birds and mammals, using data collected from the literature. These models conform to the predictions of the allometric theory; the value of negative one-quarter for the scaling parameter is within the 95% credible interval, which is [-0.31, -0.10] for birds and [-0.35, -0.15] for mammals. The predictions are very well supported when evaluated using an independent set of data. The regression models can be used to provide objective and informative Bayesian priors for annual adult survival rates of birds and mammals or to act as a point of comparison in new studies.     

QDR 4500A DXA overestimates fat-free mass compared with criterion methods.

This study evaluated the accuracy with which the dual-energy X-ray absorptiometer (Hologic QDR 4500A) measured fat-free mass (FFM), fat mass (FM), and hydration of FFM. In a study of 58 men and women (ages 70-79 yr), the QDR 4500A was found to provide a systematically higher estimate of FFM and lower estimate of FM than a four-component model of body composition. A correction factor from this study was developed and applied to two other samples (n = 13 and 37). We found mean corrected levels of FFM and FM to be equivalent to that obtained by the four-component model or total body water. In addition, the hydration of the corrected FFM was closer to the established hydration level in adult samples and that obtained from the four-component model. These findings suggest that the current calibration of the fan-beam system of the Hologic QDR 4500A provides an overestimate of FFM and underestimate of FM compared with reference methods.     

Free carnitine and acetyl carnitine plasma levels and their relationship with body muscular mass in athletes

Summary The purpose of the present study was to investigate the relationship between plasma carnitine concentration and body composition variation in relation to muscular and fat masses since there is no experimentally proved correlation between plasma carnitine and body masses. We used bioelectric impedance analysis (BIA), to determine body composition and to have a complete physical fitness evaluation. The post-absorptive plasma free carnitine and acetyl carnitine plasma levels, body composition as Fat-Free Mass (FFM) and Fat Mass (FM) in kg, as well as in percent of body mass, were analysed in 33 healthy subjects. A significant negative correlation was found between plasma acetyl carnitine and FFM in weight (kg) as well as in percent of body mass (respectively p < 0.0001; p < 0.01); a significant positive correlation was found only between FM in percent and plasma acetyl carnitine (p < 0.01). The observed negative correlation between plasma acetyl carnitine and muscular mass variation might reflect an oxidative metabolic muscle improvement in relation to muscular fat free mass increment and might be evidence that muscle metabolism change is in relation to plasma acetyl carnitine concentration.     

Adaptive thermogenesis with weight loss in humans

Adaptive thermogenesis (AT) with weight loss refers to underfeeding‐associated fall in resting and non‐resting energy expenditure (REE, non‐REE); this is independent of body weight and body composition. In humans, the existence of AT was inconsistently shown and its clinical significance has been questioned.

Objectives:

Discrepant findings are mainly due to different definitions of AT, the use of various and nonstandardized study protocols, and the limits of accuracy of methods to assess energy expenditure. With controlled underfeeding, AT takes more than 2 wk to develop. AT accounts to an average of 0.5 MJ (or 120 kcal) with a considerable between subject variance.

Design and Methods:

Low‐sympathetic nervous system activity, 3,5,3′‐tri‐iodothyronine (T3) and leptin are likely to add to AT; however, the kinetic changes of their plasma levels with underfeeding differ from the time course of AT and controlled intervention studies substituting and titrating these hormones are rare in humans. AT in response to underfeeding is independent of thermogenesis in response to either diet or cold. Although fat‐free mass (FFM) and, thus, liver, and skeletal muscle are considered as major sites of AT, cold‐induced nonshivering thermogenesis relates to the metabolism of brown adipose tissue (BAT). In humans, diet‐induced thermogenesis is related to postprandial substrate metabolism of FFM with a questionable role of BAT. Obviously, the REE component of AT differs from and its non‐REE component with respect to organ contribution as well as mechanisms. Thus, AT cannot be considered as unique.

Conclusions:

AT should be characterized based on individual components of daily energy expenditure, detailed body composition analyses, and mathematical modeling. The biological basis of AT as well as the influences of age, sex, obesity, stress, and inflammation remain to be established in humans.