Relative Contribution Of Fat Mass Research Articles

Normal fat mass cannot be reliably estimated in typical pharmacokinetic studies

PurposeAn influential covariate for pharmacokinetics is (body) size. Recently, the method of estimation of normal fat mass (NFM) has been advocated. Here, the relative contribution of fat mass, estimated as a fraction fat (Ffat), is used to explain differences in pharmacokinetic parameters. This concept is more and more applied. However, it remains unclear whether NFM can be reliably estimated in these typical studies.MethodsWe performed an evaluation of the reliability of NFM estimation in a typical study size (n = 30), otherwise best-case scenario, by means of a pharmacokinetic simulation study. Several values of Ffat were investigated.ResultsIn a typical pharmacokinetic study, high imprecision was observed for NFM parameter estimates over a range of scenarios. For example, in a scenario where the true value of Ffat on clearance was 0.5, we found a 95% confidence interval of − 0.1 to 2.1, demonstrating a low precision. The implications for practice are that one could conclude that fat-free mass best describes the relationship of the pharmacokinetics with body size, while the true relationship was between fat-free mass and total body weight. Consequently, this could lead to incorrect extrapolation of pharmacokinetics to extreme body sizes.ConclusionIn typical pharmacokinetic studies, NFM should be used with caution because the Ffat estimates have low precision. The estimation of Ffat should always be preceded by careful study design evaluation before planning a study, to ensure that the design and sample size is sufficient to apply this potentially useful methodology.

Adipose Tissue Resting Energy Expenditure and Expression of Genes Involved in Mitochondrial Function Are Higher in Women than in Men

Context:Men and women differ in body fat distribution and adipose tissue metabolism as well as in obesity comorbidities and their response to obesity treatment.Objective:The objective of the study was a search for sex differences in adipose tissue function.Design and Setting:This was an exploratory study performed at a university hospital.Participants and Main Outcome Measures:Resting metabolic rate (RMR), body composition, and sc adipose tissue genome-wide expression were measured in the SOS Sib Pair study (n = 732).Results:The relative contribution of fat mass to RMR and the metabolic rate per kilogram adipose tissue was higher in women than in men (P value for sex by fat mass interaction = .0019). Women had increased expression of genes involved in mitochondrial function, here referred to as a mitochondrial gene signature. Analysis of liver, muscle, and blood showed that the pronounced mitochondrial gene signature in women was specific for adipose tissue. Brown adipocytes are dense in mitochondria, and the expression of the brown adipocyte marker uncoupling protein 1 was 5-fold higher in women compared with men in the SOS Sib Pair Study (P = 7.43 × 10−7), and this was confirmed in a cross-sectional, population-based study (n = 83, 6-fold higher in women, P = .00256).Conclusions:The increased expression of the brown adipocyte marker uncoupling protein 1 in women indicates that the higher relative contribution of the fat mass to RMR in women is in part explained by an increased number of brown adipocytes.

Changes in fat mass and fat-free mass during the adiposity rebound: FLAME study

To determine the changes in body composition from 3 to 7 years of age in children undergoing adiposity rebound (AR) at different ages. Body composition was measured bi-annually by bioelectrical impedance in 229 children from a birth cohort. Age at AR was calculated from changes in weight and height velocity over time. Early AR was defined as < 6.1 years (boys) and < 5.6 years (girls). Differences in fat mass (FM) and fat-free mass (FFM) and the velocity of change in these measures were calculated between early and late rebounders. Physical activity (accelerometry), time in sedentary activity, birth factors, and parental weight were compared. Children with early and late AR did not differ in body composition at 3 years of age, except for greater FFM in boys (by 0.8 kg, P = 0.022). In both sexes, change in body mass index (BMI) was significantly higher in early compared with late AR, and was entirely due to differences in the rate of weight gain, rather than any discrepancy in height velocity. This weight differential is predominantly due to increased deposition of FM in girls and FFM in boys. However, in both sexes, children with early rebound have significantly greater increases in FM velocity from 5 years of age. Few differences in any environmental influences were observed. Variation in BMI associated with the timing of AR is due to differences in weight rather than height, and sex differences in the relative contribution of FM and FFM to this additional weight gain are apparent.

Grade of adiposity affects the impact of fat mass on resting energy expenditure in women

Body fat mass (FM) adds to the variance in resting energy expenditure (REE). However, the nature and extent of this relationship remains unclear. Using a database of 1306 women and a linear regression model, we systematically analysed the contribution of FM to the total variance in REE at different grades of adiposity (ranges of body %FM). After adjusting for age, the relative contribution of FM on REE variance increased from low (<or= 10 %FM) to normal (>10- <or= 30 %FM) and moderately elevated (>30- <or= 40 %FM) grades of adiposity but decreased sharply at high (>40- # 50 %FM) and very high (>50 %FM) grades of adiposity according to the ratio between regression coefficients. These data suggest that the specific metabolic rate of fat tissue is reduced at high adiposity. This should be considered when REE is normalized for FM in obesity.

Relationship between body composition and bone mineral density in healthy young and premenopausal Chinese women.

This study investigated the relative contribution of fat mass and lean mass to bone mineral density (BMD) in young and premenopausal healthy Chinese women. The study was performed in 282 young and premenopausal healthy women with regular menstrual cycles. The BMD at lumbar spine (L2-L4), total hip and total body, together with fat mass and lean mass were assessed by dual-energy X-ray absorptiometry (DXA); body height, weight, waist and hip circumference were also measured, and body mass index (BMI) and waist-hip ratio were calculated. Fat mass was a major determinant for BMI, BMI and lean mass were positively related to L2-L4, total hip and total body bone density ( P<0.001 for all), lean mass was the only independent factor contributing to BMD at L2-L4 (standardized coefficient beta=0.282, P<0.001), total hip (beta=0.336, P<0.001) and total body (beta=0.361, P<0.001) in multiple stepwise regression analysis. The correlation between BMI and BMD was improved after adjustment for fat mass, while decreased or even lost when lean mass was adjusted. These data suggested that in the Chinese population, lean mass is an important factor determining BMD in young and premenopausal women.

The relative contribution of body fat and fat pattern to blood pressure level.

Although the association between body weight and blood pressure is irrefutable, body fat mass and blood pressure level may not necessarily be directly related. To clarify the relative contribution of fat mass to blood pressure level, we analyzed data on 399 adults consecutively entering a weight control program. Although most subjects were notably overweight (mean ideal body weight 177%), the population represented a wide spectrum of body weights and blood pressure levels. Study parameters included body fat mass (by total body water, 40K, and Steinkamp formula), lean body mass, body build (chest to height ratio), fat cell number and size from bilateral buttock biopsy specimens, upper fat pattern by arm to thigh circumference ratio, and central fat pattern by subscapular to triceps skinfold ratio. Our results concurred with previously noted correlations between obesity and blood pressure (as mean arterial pressure): weight (r = 0.44), percentage of body fat (r = 0.19), and absolute fat mass (r = 0.38; all p less than 0.01); however, lean body mass, age, and body build correlated highly with both fat mass and mean arterial pressure, thereby confounding this relationship. Multivariate analysis was performed to evaluate the relative contribution of fat mass to mean arterial pressure in the presence of these and other potentially confounding variables. Lean body mass, age, body build, and an upper body fat pattern were found to contribute significantly to the variation in mean arterial pressure (p less than 0.01). In their presence, percentage of body fat, absolute fat mass, central fat pattern, fat cell characteristics, and age of onset of obesity did not significantly improve the predictability of mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)