What is the best size descriptor to use for pharmacokinetic studies in the obese?

The prevalence of obesity in the western world is dramatically rising, with many of these individuals requiring therapeutic intervention for a variety of disease states. Despite the growing prevalence of obesity there is a paucity of information describing how doses should be adjusted, or indeed whether they need to be adjusted, in the clinical setting. This review is aimed at identifying which descriptors of body size provide the most information about the relationship between dose and concentration in the obese. The size descriptors, weight, lean body weight, ideal body weight, body surface area, body mass index, fat-free mass, percent ideal body weight, adjusted body weight and predicted normal body weight were considered as potential size descriptors. We conducted an extensive review of the literature to identify studies that have assessed the quantitative relationship between the parameters clearance (CL) and volume of distribution (V) and these descriptors of body size. Surprisingly few studies have addressed the relationship between obesity and CL or V in a quantitative manner. Despite the lack of studies there were consistent findings: (i) most studies found total body weight to be the best descriptor of V. A further analysis of the studies that have addressed V found that total body weight or another descriptor that incorporated fat mass was the preferred descriptor for drugs that have high lipophilicity; (ii) in contrast, CL was best described by lean body mass and no apparent relationship between lipophilicity or clearance mechanism and preference for body size descriptor was found. In conclusion, no single descriptor described the influence of body size on both CL and V equally well. For drugs that are dosed chronically, and therefore CL is of primary concern, dosing for obese patients should not be based on their total weight. If a weight-based dose individualization is required then we would suggest that chronic drug dosing in the obese subject should be based on lean body weight, at least until a more robust size descriptor becomes available.

Studies on the antiobesity effect of zinc-α2-glycoprotein in the ob/ob mouse

OBJECTIVE: To investigate the mechanism of the lipid depletion by zinc-a(2)-glycoprotein (ZAG). DESIGN: Studies were conducted in the ob/ob mouse, or on isolated adipocytes from these animals or their lean counterparts. RESULTS: Treatment of these animals for 15 days with ZAG (100? µg, intravenously, daily) resulted in a reduction of body weight of 6.55? g compared with phosphate-buffered saline-treated controls, without a change in food or water intake, but with a 0.4?°C rise in rectal temperature. ZAG-treated mice had a 30% reduction in carcass fat mass and a twofold increase in weight of brown adipose tissue. Epididymal adipocytes from ZAG-treated mice showed an increased expression of ZAG and hormone-sensitive lipase (HSL), and this was maintained for a further 3 days in the absence of ZAG. There was an increased lipolytic response to isoproterenol, which was retained for 3 days in vitro in the absence of ZAG. Expression of HSL was also increased in subcutaneous and visceral adipose tissue, as was also adipose triglyceride lipase (ATGL). There was a rapid loss of labelled lipid from epididymal adipose tissue of ZAG-treated mice, but not from the other depots, reflecting the difference in sensitivity to lipolytic stimuli. The increased expression of HSL and ATGL may involve the extracellular signal-regulated kinase (ERK) pathway, as the active (phospho) form was upregulated in all adipose depots after ZAG administration, whereas in vitro studies showed induction of HSL and ATGL by ZAG to be attenuated by PD98059, an inhibitor of the ERK pathway. CONCLUSION: These results suggest that ZAG not only induces direct lipolysis, but also sensitizes adipose tissue to other lipolytic stimuli.

Studies on the anti-obesity activity of zinc-α2-glycoprotein in the rat

OBJECTIVE: To investigate the anti-obesity effect of the adipokine zinc-a(2)-glycoprotein (ZAG) in rats and the mechanism of this effect. SUBJECTS: Mature male Wistar rats (540 ± 83 g) were administered human recombinant ZAG (50 µg per 100 g body weight given intravenously daily) for 10 days, while control animals received an equal volume of phosphate-buffered saline (PBS). RESULTS: Animals treated with ZAG showed a progressive decrease in body weight, without a decrease in food and water intake, but with a 0.4 °C rise in body temperature. Body composition analysis showed loss of adipose tissue, but an increase in lean body mass. The loss of fat was due to an increase in lipolysis as shown by a 50% elevation of plasma glycerol, accompanied by increased utilization of non-esterified fatty acids, as evidenced by the 55% decrease in plasma levels. Plasma levels of glucose and triglycerides were also reduced by 36-37% and there was increased expression of the glucose transporter 4 in both skeletal muscle and adipose tissue. Expression of the lipolytic enzymes adipose triglyceride lipase and hormone-sensitive lipase in the white adipose tissue (WAT) were increased twofold after ZAG administration. There was almost a twofold increased expression of uncoupling proteins 1 and 3 in brown adipose tissue and WAT, which would contribute to increased substrate utilization. Administration of ZAG increased ZAG expression twofold in the gastrocnemius muscle, BAT and WAT, which was probably necessary for its biological effect. CONCLUSION: These results show that ZAG produces increased lipid mobilization and utilization in the rat.

Tissue-specific selection of reference genes is required for expression studies in the mouse model of maternal protein undernutrition

Suboptimal maternal nutrition during gestation results in the establishment of long-term phenotypic changes and an increased disease risk in the offspring. To elucidate how such environmental sensitivity results in physiological outcomes, the molecular characterisation of these offspring has become the focus of many studies. However, the likely modification of key cellular processes such as metabolism in response to maternal undernutrition raises the question of whether the genes typically used as reference constants in gene expression studies are suitable controls. Using a mouse model of maternal protein undernutrition, we have investigated the stability of seven commonly used reference genes (18s, Hprt1, Pgk1, Ppib, Sdha, Tbp and Tuba1) in a variety of offspring tissues including liver, kidney, heart, retro-peritoneal and inter-scapular fat, extra-embryonic placenta and yolk sac, as well as in the preimplantation blastocyst and blastocyst-derived embryonic stem cells. We find that although the selected reference genes are all highly stable within this system, they show tissue, treatment and sex-specific variation. Furthermore, software-based selection approaches rank reference genes differently and do not always identify genes which differ between conditions. Therefore, we recommend that reference gene selection for gene expression studies should be thoroughly validated for each tissue of interest. © 2011 Elsevier Inc.

Fat Absorption in Commercial French Fries Depending on Oil Type and Coating

This study examines the effect of edible coatings, type of oil used, and cooking method on the fat content of commercially available French fries. In contrast to earlier studies that examined laboratory prepared French fries, this study assesses commercially available French fries and cooking oils. This study also measured the fat content in oven baked French fries, comparing the two cooking methods in addition to the comparisons of different coatings’ oil uptake. The findings of this study were that the type of oil used did have a significant impact on the final oil content of the uncoated and seasoned fries. The fries coated in modified food starch and fried in peanut and soy oils had what appeared to be significantly higher oil content than those fried in corn oil or baked, but the difference was not statistically significant. Additionally, fat content in French fries with hydrocollidial coatings that were prepared in corn oil were not significantly different than French fries with the same coating that were baked.

Feasibility of MR-Based Body Composition Analysis in Large Scale Population Studies

Introduction Quantitative and accurate measurements of fat and muscle in the body are important for prevention and diagnosis of diseases related to obesity and muscle degeneration. Manually segmenting muscle and fat compartments in MR body-images is laborious and time-consuming, hindering implementation in large cohorts. In the present study, the feasibility and success-rate of a Dixon-based MR scan followed by an intensity-normalised, non-rigid, multi-atlas based segmentation was investigated in a cohort of 3,000 subjects. Materials and Methods 3,000 participants in the in-depth phenotyping arm of the UK Biobank imaging study underwent a comprehensive MR examination. All subjects were scanned using a 1.5 T MR-scanner with the dual-echo Dixon Vibe protocol, covering neck to knees. Subjects were scanned with six slabs in supine position, without localizer. Automated body composition analysis was performed using the AMRA Profiler™ system, to segment and quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT) and thigh muscles. Technical quality assurance was performed and a standard set of acceptance/rejection criteria was established. Descriptive statistics were calculated for all volume measurements and quality assurance metrics. Results Of the 3,000 subjects, 2,995 (99.83%) were analysable for body fat, 2,828 (94.27%) were analysable when body fat and one thigh was included, and 2,775 (92.50%) were fully analysable for body fat and both thigh muscles. Reasons for not being able to analyse datasets were mainly due to missing slabs in the acquisition, or patient positioned so that large parts of the volume was outside of the field-of-view. Discussion and Conclusions In conclusion, this study showed that the rapid UK Biobank MR-protocol was well tolerated by most subjects and sufficiently robust to achieve very high success-rate for body composition analysis. This research has been conducted using the UK Biobank Resource.

Application of body mass index adjusted for fat mass (BMIfat) obtained by bioelectrical impedance in adults

Introduction: Body mass index (BMI) has been one of the methods most frequently used for diagnose obesity, but it isn't consider body composition. Objective: This study intends to apply one new adiposity index, the BMI adjusted for fat mass (BMIfat) developed by Mialich, et al. (2011), in a adult Brazilian sample. Methods: A cross-sectional study with 501 individuals of both genders (366 women, 135 men) aged 17 to 38 years and mean age was 20.4 ± 2.8 years, mean weight 63.0 ± 13.5 kg, mean height 166.9 ± 9.0 cm, and BMI 22.4 ± 3.4 kg/m². Results and discussion: High and satisfactory R2 values were obtained, i.e., 91.1%, 91.9% and 88.8% for the sample as a whole and for men and women, respectively. Considering this BMIfat were developed new ranges, as follows: 1.35 to 1.65 (nutritional risk for malnutrition), > 1.65 and ≤ 2.0 (normal weight) and > 2.0 (obesity). The BMIfat had a more accurate capacity of detecting obese individuals (0.980. 0.993, 0.974) considering the sample as a whole and women and men, respectively, compared to the traditional BMI (0.932, 0.956, 0.95). Were also defined new cut-off points for the traditional BMI for the classification of obesity, i.e.: 25.24 kg/m² and 28.38 kg/m² for men and women, respectively. Conclusion: The BMIfat was applied for the present population and can be adopted in clinical practice. Further studies are needed to determine its application to different ethnic groups and to compare this index to others previously described in the scientific literature.

Associations between liking for fat, sweet or salt and obesity risk in French adults

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A home-based treadmill training reduced epicardial and abdominal fat in postmenopausal women with metabolic syndrome

Introduction: The current study was designed to determine the effect of home-based treadmill training on epicardial and abdominal adipose tissue in postmenopausal women with metabolic syndrome (MS). A secondary objective was to identify significant correlations between imaging and conventional anthropometric parameters. Material and methods: Sixty postmenopausal women with MS volunteered for the current trial. Thirty were randomly assigned to perform a supervised home-based 16-week treadmill training program, 3 sessions/week, consisting of a warm-up, 30-40 min treadmill exercise (increasing 5-minutes each 4-weeks) at a work intensity of 60-75% of peak heart rate (increasing 5% each 4-weeks) and cooling-down. Epicardial fat thickness (EFT) was assessed by echocardiography. Abdominal fat mass in the lumbar regions L1-L4 and L4-L5 was determined by dual X-ray absorptiometry. Results: Epicardial fat thickness and abdominal fat percentages were significantly improved after the completion of the training program. Another striking feature of the current study was the moderate correlation that was found between EFT and waist circumference (WC). Conclusion: Home-based treadmill training reduced epicardial and abdominal fat in postmenopausal women with MS. A secondary finding was that a moderate correlation was found between EFT and WC. While current investigations are promising, future studies are still required to consolidate this approach in clinical application.

Patterns of sedentary behavior : insights from observational and experimental studies on body composition and energy expenditure

It is recognized that sedentary behavior (SB) has deleterious effects on numerous health outcomes and it appears that physiological mechanisms underlying these harms are distinct from the ones explaining moderate-to-vigorous physical activity (MVPA) benefits. Sedentary behavior represents a large portion of human’s life and is increasing with technological development. A new current of opinion supports the idea that the manner SB is accumulated plays an important role. This dissertation presents six research studies conducted under the scope of SB. In the methodological area, the first study highlighted the magnitude of potential errors in estimating SB and its patterns from common alternative methods (accelerometer and heart rate monitor) compared to ActivPAL. This study presented the accelerometer as a valid method at a group level. Two studies (2 and 5) were performed in older adults (the most sedentary group in the population) to test the associations for SB patterns with abdominal obesity using accelerometry. The findings showed positive graded associations for prolonged sedentary bouts with abdominal obesity and showed that those who interrupted SB more frequently were less likely to present abdominal obesity. Therefore, public health recommendations regarding breaking up SB more often are expected to be relevant. The associations between sedentary patterns and abdominal obesity were independent of MVPA in older adults. However, the low MVPA in this group makes it unclear whether this independent relationship still exists if highly active persons are analysed. Study 3 inovates by examining the association of SB with body fatness in highly trained athletes and found SB to predict total fat mass and trunk fat mass, independently of age and weekly training time. Study 4 also brings novelty to this research field by quantifying the metabolic and energetic cost of the transition from sitting to standing and then sitting back down (a break), informing about the modest energetic costs (0.32 kcal·min−1). Finally, from a successful multicomponent pilot intervention to reduce and break up SB (study 6), an important behavioral resistance to make more sit/stand transitions despite successfully reducing sitting time (~ 1.85 hours·day-1) was found, which may be relevant to inform future behavioral modification programs. The present work provides observational and experimental evidence on the relation for SB patterns with body composition outcomes and energy regulation that may be relevant for public health interventions.

Ultramorphology and histochemistry of fat body cells from last Instar larval of the Pachycondyla (=Neoponera) villosa (Fabricius) (Formicidae: Ponerinae)

As células do corpo gorduroso de Pachycondyla (=Neoponera) villosa distribuem-se como uma única camada entre a cutícula e o trato digestivo, formando um conjunto de células agrupadas e recobertas por uma fina membrana. Não foram identificados tipos celulares distintos por meio da ultramorfologia, porém a histologia revelou três tipos celulares distintos: os trofócitos, mais abundantes, as células de urato, distribuídas por entre os trofócitos, e os enócitos, menos abundantes que os demais. Os enócitos são comumente observados próximos da cutícula. Histoquimicamente, os trofócitos apresentaram reação positiva para proteínas básicas no núcleo e no citoplasma e reação fortemente positiva nos grânulos citoplasmáticos. O teste para carboidratos foi fortemente positivo em todo o citoplasma, enquanto para os lipídeos observou-se reação positiva nas vesículas citoplasmáticas. em relação às células de urato, estas apresentaram reação positiva para proteínas básicas no núcleo e citoplasma, por entre as vesículas. Essas células não apresentaram reação para o teste de PAS e Sudan Black B. Quanto aos enócitos, estes apresentaram citoplasma fracamente positivo ao PAS e fortemente positivo ao Sudan Black B e para o azul de bromofenol.

The magnitude of association between overweight and obesity and the risk of diabetes: a meta-analysis of prospective cohort studies

The objectives of this meta-analysis were to examine the magnitude of the relative risk (RR) of developing type 2 diabetes for overweight and obese populations, compared to those with normal weight, and to determine causes of the variation in RR between various cohort studies. The magnitude of the RR was analyzed by combining 18 prospective cohort studies that matched defined criteria. The variance in RR between studies was explored. The overall RR of diabetes for obese persons compared to those with normal weight was 7.19, 95% CI: 5.74, 9.00 and for overweight was 2.99, 95% CI: 2.42, 3.72. The variation in RR among studies was explored and it was found that the effect of heterogeneity was highly related with sample size, method of assessment of body mass index (BMI) and method of ascertainment of type 2 diabetes. By combining only cohort studies with more than 400 cases of incident diabetes (>median), adjusted by at least three main confounding variables (age, family history of type 2 diabetes, physical activity), measured BMI, and diabetes determined by clinical diagnosis, the RR was 7.28, 95% CI: 6.47, 8.28 for obesity and 2.92, 95% CI: 2.57, 3.32 for overweight.

Fat mass is associated with foot pain in men: the Geelong osteoporosis study

OBJECTIVE: Foot pain is a common complaint in adults. Evidence suggests that body composition is involved in the development of foot pain. However, whether this is the case in men remains unclear because previous studies mainly examined women. The aim of this cross-sectional study was to determine the relationship between body composition and foot pain in men while accounting for important risk factors. METHODS: Among 978 men (median age 60 yrs, range 24-98) from the Geelong Osteoporosis Study who participated in a followup study in 2006 to 2011, 796 provided responses to questions on health status and foot pain. Foot pain was determined using the Manchester Foot Pain and Disability Index, and body composition was measured using dual-energy x-ray absorptiometry. RESULTS: Of the 796 respondents, 177 (22%) had foot pain. Risk factors for foot pain were age (OR 1.03, 95% CI 1.02-1.04), self-reported depression (OR 2.05, 95% CI 1.30-3.20), decreased mobility (OR 1.54, 95% CI 1.05-2.24), and lower education (OR 1.47, 95% CI 1.03-2.09). Foot pain was associated with body mass index (OR 1.05, 95% CI 1.00-1.10), fat mass (OR 1.02, 95% CI 1.03-1.05), and fat mass index (OR 1.08, 95% CI 1.01-1.15), but not fat-free mass (OR 1.01, 95% CI 0.98-1.04) or fat-free mass index (OR 1.05, 95% CI 0.95-1.15) after appropriate adjustments were made. CONCLUSION: Fat mass is associated with foot pain in men. These findings complement those in studies that have mainly examined women, and provide further evidence for the relationship between obesity and foot pain.

Fat talk and its relationship with body image disturbance

Although past studies have highlighted fat talk as relevant to body image disturbance, the majority of these have only investigated the link between fat talk and body esteem, to the exclusion of other body image constructs. One hundred and ninety-nine women completed an online survey measuring levels of appearance-based comparisons, body surveillance, thin ideal internalization, body esteem, and fat talk (FT-body concerns and FT-body comparisons). Results showed that fat talk made a significant contribution in explaining additional variance in body esteem above the other three body image factors, with FT-body concerns in particular making the highest unique contribution. Hierarchical regression analyses suggest that fat talk should be viewed as an independent psychosocial predictor of body esteem in both theoretical and therapeutic contexts. Future research should explore these relationships from a longitudinal perspective, and also clarify the nuances in the relationships by investigating the nature of women's everyday body image experiences.

Caffeine Intake and its Association with Disease Progression, Sleep Quality and Anxiety Symptoms and Nutritional Alterations in People Living with HIV in the Miami Adult Studies on HIV Cohort

Miami-Dade County has approximately 27,000 people living with HIV (PLWH), and the highest HIV incidence in the nation. PLWH have reported several types of sleep disturbances. Caffeine is an anorexic and lipolytic stimulant that may adversely affect sleep patterns, dietary intakes and body composition. High caffeine consumption (>250 mg. per day or the equivalent of >4 cups of brewed coffee) may also affect general functionality, adherence to antiretroviral treatment (ART) and HIV care. This study assess the relationship of high caffeine intake with markers of disease progression, sleep quality, insomnia, anxiety, nutritional intakes and body composition. A convenience sample of 130 PLWH on stable ART were recruited from the Miami Adult Studies on HIV (MASH) cohort, and followed for three months. After consenting, questionnaires on Modified Caffeine Consumption (MCCQ), Pittsburg Insomnia Rating Scale (PIRS), Pittsburg Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7), socio-demographics, drug and medication use were completed. CD4 count, HIV viral load, anthropometries, and body composition measures were obtained. Mean age was 47.89±6.37 years, 60.8% were male and 75.4% were African-Americans. Mean caffeine intake at baseline was 337.63 ± 304.97 mg/day (Range: 0-1498 mg/day) and did not change significantly at 3 months. In linear regression, high caffeine consumption was associated with higher CD4 cell count (β=1.532, P=0.049), lower HIV viral load (β=-1.067, P=0.048), higher global PIRS (β=1.776, P=0.046), global PSQI (β=2.587, P=0.038), and GAD-7 scores (β=1.674, P=0.027), and with lower fat mass (β=-0.994, P=0.042), energy intakes (β=-1.643, P=0.042) and fat consumption (β=-1.902, P=0.044), adjusting for relevant socioeconomic and disease progression variables. Over three months, these associations remained significant. The association of high caffeine with lower BMI weakened when excluding users of other anorexic and stimulant drugs such as cocaine and methamphetamine, suggesting that caffeine in combination, but not alone, may worsen their action. In summary, high caffeine consumption was associated with better measures of disease progression; but was also detrimental on sleep quality, nutritional intakes, BMI and body composition and associated with insomnia and anxiety. Large scale studies for longer time are needed to elucidate the contribution of caffeine to the well-being of PLWH.