Body Composition In Obesity Research Articles

8040 Precision-Engineered Activin and GDF Ligand Trap HS235: A Novel Lean Mass-Preserving Treatment for Obesity

Abstract Disclosure: G. Schang: Employee; Self; 35Pharma. M. De Molliens: Employee; Self; 35Pharma. E. Brule: Employee; Self; 35Pharma. C. Chauvet: Employee; Self; 35Pharma. J. Denis: Employee; Self; 35Pharma. A. Sours: Employee; Self; 35Pharma. V. Ganesh: Employee; Self; 35Pharma. G. Tremblay: Employee; Self; 35Pharma. J. Schoelermann: Employee; Self; 35Pharma. M. O'Connor: Employee; Self; 35Pharma. Introduction: Novel anti-obesity medications including incretin mimetics have revolutionized the pharmacotherapy of obesity and type 2 diabetes, leading to unprecedented weight loss and clinically meaningful improvement of glucose metabolism and cardiometabolic health. However, incretins reduce body mass in a non-selective manner; both fat mass and lean mass are lost with incretin treatment. In obese patients treated with incretins, undesirable loss of lean body mass (LBM) can account for up to 40% of overall weight loss. Loss of LBM negatively impacts resting metabolic rate, leading to a weight loss plateau and often unsustainable results. Furthermore, individuals with sarcopenia, characterized by low muscle mass and strength, are at greater risk for heart failure. The preservation, or even increase, of LBM is therefore a desirable treatment goal for obesity pharmacotherapy and overall cardiometabolic health. Activins and growth differentiation factors (GDFs), which are members of the TGF-beta superfamily, are validated targets controlling body composition and metabolism. Specifically, blockade of activins and GDFs has anabolic effects in metabolically active tissues such as skeletal muscle and brown adipose tissue, while reducing white adipose tissue mass. Therefore, specific and selective blockade of activins and GDFs represents a novel anti-obesity treatment strategy which can act orthogonally to current anti-obesity medications. HS235 is an activin receptor ectodomain-based (ActR) Fc-fusion protein that has been rationally designed to attain optimal inhibition of ligands controlling body composition in obesity. Methods: A structure-assisted rational molecular engineering approach coupled with cell-based potency screening was employed to design HS235. To validate the anti-obesogenic potential of HS235, diet-induced obese (DIO) mice were injected with HS235, an incretin mimetic, or a combination of both. Fat mass, LBM, muscle weights, and biomarker readouts were assessed at the end of study. Results: In cell-based assays, HS235 potently and selectively neutralized activins and GDFs implicated in body composition. This translated to complete in vivo target engagement and pharmacodynamic response. In a DIO mouse model, both HS235 and the incretin mimetic significantly improved metabolic parameters and decreased fat mass, but only HS235 increased LBM, while incretin-based treatment led to LBM loss. Importantly, the addition of HS235 to the incretin mimetic lead to a synergistic fat mass loss and prevented loss of LBM. Conclusion: Potent and selective inhibition of activins and GDFs by HS235 represents a novel LBM preserving weight loss strategy orthogonal to incretin mimetics. Collectively, these data support the development of HS235 as a novel anti-obesity agent to complement currently approved incretin-based medications to improve quality of weight loss. Presentation: 6/3/2024

FRI017 Precision-engineered Activin And GDF Ligand Trap HS235: A Novel Lean Mass-preserving Treatment for Obesity

Abstract Disclosure: G. Schang: Employee; Self; 35Pharma Inc. M. Poujol de Molliens: Employee; Self; 35Pharma Inc. E. Brûlé: Employee; Self; 35Pharma Inc. C. Chauvet: Employee; Self; 35Pharma Inc. J. Denis: Employee; Self; 35Pharma Inc. A. Sours: Employee; Self; 35Pharma Inc. V. Ganesh: Employee; Self; 35Pharma Inc. G. Tremblay: Employee; Self; 35Pharma Inc. J. Schoelermann: Employee; Self; 35Pharma Inc. M. O'Connor-McCourt: Employee; Self; 35Pharma Inc. Introduction: Novel anti-obesity medications including incretin mimetics have revolutionized the pharmacotherapy of obesity and type 2 diabetes, leading to unprecedented weight loss and clinically meaningful improvement of glucose metabolism and cardiometabolic health. However, this loss of fat mass is accompanied by undesirable loss of lean body mass (LBM) which can account for 15 - 40% of overall weight loss. Loss of LBM by incretin-based therapies negatively impacts resting metabolic rate, leading to a weight loss plateau and often unsustainable results. The preservation, or even increase, of LBM is therefore a desirable treatment goal for obesity pharmacotherapy and improvement of overall health. Activins and growth differentiation factors (GDFs), which are members of the TGF-beta superfamily, are validated targets controlling body composition and metabolism. Specifically, blockade of activins and GDFs has anabolic effects in metabolically active tissues such as skeletal muscle and brown adipose tissue, while reducing white adipose tissue mass. Therefore, specific and selective blockade of activins and GDFs represents a novel anti-obesity treatment strategy which can act orthogonally to current anti-obesity medications. Aims and objectives: HS235 is an activin receptor ectodomain-based (ActR) Fc-fusion protein that has been rationally designed to attain optimal inhibition of ligands controlling body composition in obesity. Methods: A structure-assisted rational molecular engineering approach coupled with cell-based potency screening was employed to design HS235. In vivo target engagement and pharmacodynamic response to HS235 were assessed in mice by quantifying metabolic biomarkers including muscle hypertrophy, muscle and fat gene expression, as well as plasma metabolites. To further validate the anti-obesogenic potential of HS235, diet-induced obese (DIO) mice were injected with HS235, an incretin mimetic, or a combination of both. Fat mass, LBM, glucose metabolism, exercise tolerance, and biomarker readouts were assessed at the end of study. Results: In cell-based assays, HS235 potently and selectively neutralized activins and GDFs implicated in body composition. This translated to complete in vivo target engagement and pharmacodynamic response. In a DIO mouse model, both HS235 and the incretin mimetic significantly improved metabolic parameters and decreased fat mass, but only HS235 increased LBM, while incretin-based treatment led to LBM loss. Importantly, the addition of HS235 to the incretin mimetic prevented this loss of LBM. Conclusion: Potent and selective inhibition of activins and GDFs by HS235 represents a novel LBM preserving weight loss strategy. Collectively, these data support the development of HS235 as a novel anti-obesity agent that may also complement currently approved incretin-based medications. Presentation: Friday, June 16, 2023

Genome-wide DNA methylation analysis of body composition in Chinese monozygotic twins.

Little is currently known about epigenetic alterations associated with body composition in obesity. Thus, we aimed to explore epigenetic relationships between genome-wide DNA methylation levels and three common traits of body composition as measured by body fat percentage (BF%), fat mass (FM) and lean body mass (LBM) among Chinese monozygotic twins. Generalized estimated equation model was used to regress the methylation level of CpG sites on body composition. Inference about Causation Through Examination Of Familial Confounding was used to explore the evidence of a causal relationship. Gene expression analysis was further performed to validate the results of differentially methylated genes. We identified 32, 22 and 28 differentially methylated CpG sites (p < 10-5 ) as well as 20, 17 and eight differentially methylated regions (slk-corrected p < 0.05) significantly associated with BF%, FM and LBM which were annotated to 65 genes, showing partially overlapping. Causal inference demonstrated bidirectional causality between DNA methylation and body composition (p < 0.05). Gene expression analysis revealed significant correlations between expression levels of five differentially methylated genes and body composition (p < 0.05). These DNA methylation signatures will contribute to increased knowledge about the epigenetic basis of body composition and provide new strategies for early prevention and treatment of obesity and its related diseases.

Thermoluminescence Dosimetry in Abdominal CT for Urinary Stone Detection: Effective Radiation Dose Reduction With Tin Prefiltration at 100 kVp.

Spectral shaping via tin prefiltration has gained recognition for dose saving in high-contrast imaging tasks. The aim of this phantom dosimetry study was to investigate whether the use of tin filters can also reduce the effective radiation dose in 100 kVp abdominal computed tomography (CT) compared with standard low-dose scans for suspected urolithiasis. Using a third-generation dual-source CT scanner, 4 scan protocols each were used on a standard (P1-P4) and a modified obese Alderson-Rando phantom (P5-P8), in which 11 urinary stones of different compositions were placed. Hereby 1 scan protocol represented standard low-dose settings (P1/P5: 110 kVp/120 kVp), whereas 3 experimental protocols used low-kilovoltage spectral shaping (P2/P3/P4 and P6/P7/P8: 100 kVp with tin prefiltration). Radiation dose was recorded by thermoluminescent dosimeters at 24 measurement sites. For objective assessment of image quality, dose-weighted contrast-to-noise ratios were calculated and compared between scan protocols. Additional subjective image quality analysis was performed by 2 radiologists using equidistant 5-point scales for estimation image noise, artifacts, kidney stone detectability, and delineation of bone and soft tissue. Both conventional low-dose protocols without tin prefiltration were associated with the highest individual equivalent doses and the highest effective radiation dose in the experimental setup (P1: 0.29-6.43 mGy, 1.45-1.83 mSv; P5: 0.50-9.35 mGy, 2.33-2.79 mSv). With no false-positive diagnoses, both readers correctly detected each of the 11 urinary calculi irrespective of scan protocol and phantom configuration. Protocols using spectral shaping via tin prefiltration allowed for effective radiation dose reduction of up to 38% on the standard phantom and 18% on the modified obese phantom, while maintaining overall diagnostic image quality. Effective dose was approximately 10% lower in a male versus female anatomy and could be reduced by another 10% if gonadal protection was used ( P < 0.001). Spectral shaping via tin prefiltration at 100 kVp is a suitable means to reduce the effective radiation dose in abdominal CT imaging of patients with suspected urolithiasis. The dose reduction potential is slightly less pronounced in a modified phantom emulating an obese body composition compared with a standard phantom.

Perinatal Obesity Induces Hepatic Growth Restriction with Increased DNA Damage Response, Senescence, and Dysregulated Igf-1-Akt-Foxo1 Signaling in Male Offspring of Obese Mice.

Maternal obesity predisposes for hepato-metabolic disorders early in life. However, the underlying mechanisms causing early onset dysfunction of the liver and metabolism remain elusive. Since obesity is associated with subacute chronic inflammation and accelerated aging, we test the hypothesis whether maternal obesity induces aging processes in the developing liver and determines thereby hepatic growth. To this end, maternal obesity was induced with high-fat diet (HFD) in C57BL/6N mice and male offspring were studied at the end of the lactation [postnatal day 21 (P21)]. Maternal obesity induced an obese body composition with metabolic inflammation and a marked hepatic growth restriction in the male offspring at P21. Proteomic and molecular analyses revealed three interrelated mechanisms that might account for the impaired hepatic growth pattern, indicating prematurely induced aging processes: (1) Increased DNA damage response (γH2AX), (2) significant upregulation of hepatocellular senescence markers (Cdnk1a, Cdkn2a); and (3) inhibition of hepatic insulin/insulin-like growth factor (IGF)-1-AKT-p38-FoxO1 signaling with an insufficient proliferative growth response. In conclusion, our murine data demonstrate that perinatal obesity induces an obese body composition in male offspring with hepatic growth restriction through a possible premature hepatic aging that is indicated by a pathologic sequence of inflammation, DNA damage, senescence, and signs of a possibly insufficient regenerative capacity.

Effect of severe compared with moderate energy restriction on physical activity among postmenopausal female adults with obesity: a prespecified secondary analysis of the Type of Energy Manipulation for Promoting optimum metabolic health and body composition in Obesity (TEMPO) Diet randomized controlled Trial

ABSTRACTBackgroundAn under-explored strategy for increasing physical activity is the dietary treatment of obesity, but empirical evidence is lacking.ObjectivesWe aimed to compare the effects of weight loss via severe as opposed to moderate energy restriction on physical activity over 36 mo.MethodsA total of 101 postmenopausal female adults (45–65 y, BMI 30–40 kg/m2, <180 min/wk of structured exercise) were randomly assigned to either 12 mo of moderate energy restriction (25%–35% of energy requirement) with a food-based diet, or a severe intervention involving 4 mo of severe energy restriction (65%–75% of energy requirement) with a total meal replacement diet, followed by 8 mo of moderate energy restriction. Physical activity was encouraged, but no tailored or supervised exercise prescription was provided. Physical activity was assessed with an accelerometer worn for 7 d before baseline (0 mo) and 0.25, 1, 4, 6, 12, 24, and 36 mo after intervention commencement.ResultsCompared with the moderate group, the severe group exhibited greater mean: total volume of physical activity; duration of moderate-to-vigorous-intensity physical activity (MVPA); duration of light-intensity physical activity; step counts, as well as lower mean duration of sedentary time. All these differences (except step counts) were apparent at 6 mo [e.g., 1006 metabolic equivalent of task (MET)-min/wk; 95% CI: 564, 1449 MET-min/wk for total volume of physical activity], and some were also apparent at 4 and/or 12 mo. There were no differences between groups in the 2 other outcomes investigated (self-efficacy to regulate exercise; and proportion of participants meeting the WHO's 2020 Physical Activity Guidelines for MVPA). When the analyses were adjusted for weight at each time point, the differences between groups were either attenuated or abolished.ConclusionsAmong female adults with obesity, including a dietary component to reduce excess body weight—notably one involving severe energy restriction—could potentially enhance the effectiveness of physical activity interventions.This trial was registered at www.anzctr.org.au as ACTRN12612000651886.

Maternal high-fat diet induces long-term obesity with sex-dependent metabolic programming of adipocyte differentiation, hypertrophy and dysfunction in the offspring.

Maternal obesity determines obesity and metabolic diseases in the offspring. The white adipose tissue (WAT) orchestrates metabolic pathways, and its dysfunction contributes to metabolic disorders in a sex-dependent manner. Here, we tested if sex differences influence the molecular mechanisms of metabolic programming of WAT in offspring of obese dams. To this end, maternal obesity was induced with high-fat diet (HFD) and the offspring were studied at an early phase [postnatal day 21 (P21)], a late phase (P70) and finally P120. In the early phase we found a sex-independent increase in WAT in offspring of obese dams using magnetic resonance imaging (MRI), which was more pronounced in females than males. While the adipocyte size increased in both sexes, the distribution of WAT differed in males and females. As mechanistic hints, we identified an inflammatory response in females and a senescence-associated reduction in the preadipocyte factor DLK in males. In the late phase, the obese body composition persisted in both sexes, with a partial reversal in females. Moreover, female offspring recovered completely from both the adipocyte hypertrophy and the inflammatory response. These findings were linked to a dysregulation of lipolytic, adipogenic and stemness-related markers as well as AMPKα and Akt signaling. Finally, the sex-dependent metabolic programming persisted with sex-specific differences in adipocyte size until P120. In conclusion, we do not only provide new insights into the molecular mechanisms of sex-dependent metabolic programming of WAT dysfunction, but also highlight the sex-dependent development of low- and high-grade pathogenic obesity.

Irisin levels in genetic and essential obesity: clues for a potential dual role

Irisin is conventionally regarded as a myokine involved in the browning of white adipose tissue, energy expenditure and glucose tolerance. Its potential link to fat accumulation and metabolic dysfunction is debated. We sought to explore the relationship between circulating irisin and components of body composition in two different phenotypes of severe obesity. For this purpose, 30 obese adults with Prader-Will syndrome (PWS) (age 35.7 ± 1.5 y, BMI 45.5 ± 1.5 kg/m2) and 30 adult controls with common obesity (age 34.9 ± 1.7 y, BMI 46.8 ± 1.4 kg/m2) underwent analysis of irisin levels, metabolic profile, body composition and resting energy expenditure (REE). Normal irisin levels were obtained from a group of 20 lean donors (age 32.4 ± 1.5 y, BMI 23.8 ± 0.8 kg/m2). Expected differences in body composition and metabolic profile existed between study groups. PWS exhibited lower muscle mass (p < 0.001), FFM (p < 0.001), REE (p < 0.001), as well as insulin (p < 0.05), HOMA-IR (p < 0.05) and triglycerides levels (p < 0.05) than controls with common obesity. In PWS, irisin levels were significantly lower and overall less dispersed than in controls with common obesity (p < 0.05), while being similar to values recorded in lean subjects. To explore the relation between irisin and body composition in obesity, univariate correlation analysis in the obese populations as a whole showed positive associations between irisin and muscle mass (p = 0.03) as well as REE (p = 0.01), which disappeared when controlled for the PWS status. Noticeably, a positive association became evident between irisin and %FM after controlling for the PWS status (p = 0.02). Also positive were associations between irisin and insulin (p = 0.02), HOMA-IR (p = 0.02) and triglycerides (p = 0.04). In stepwise multivariable regression analysis, irisin levels were independently predicted by the PWS status (p = 0.001), %FM (p = 0.004) and triglycerides (p = 0.008). Current results suggest that obese adults with PWS harbor lower irisin levels than individuals with common obesity. The divergent models of obesity herein studied suggest a potential link between circulating irisin and muscle mass and metabolic dysfunction relating to adiposity.

Effect of Weight Loss via Severe vs Moderate Energy Restriction on Lean Mass and Body Composition Among Postmenopausal Women With Obesity

Severely energy-restricted diets are the most effective dietary obesity treatment. However, there are concerns regarding potential adverse effects on body composition. To compare the long-term effects of weight loss via severe vs moderate energy restriction on lean mass and other aspects of body composition. The Type of Energy Manipulation for Promoting Optimum Metabolic Health and Body Composition in Obesity (TEMPO) Diet Trial was a 12-month, single-center, randomized clinical trial. A total of 101 postmenopausal women, aged 45 to 65 years with body mass index (calculated as weight in kilograms divided by height in meters squared) from 30 to 40, who were at least 5 years after menopause, had fewer than 3 hours of structured physical activity per week, and lived in the Sydney metropolitan area of New South Wales, Australia, were recruited between March 2013 and July 2016. Data analysis was conducted between October 2018 and August 2019. Participants were randomized to either 12 months of moderate (25%-35%) energy restriction with a food-based diet (moderate intervention) or 4 months of severe (65%-75%) energy restriction with a total meal replacement diet followed by moderate energy restriction for an additional 8 months (severe intervention). Both interventions had a prescribed protein intake of 1.0 g/kg of actual body weight per day, and physical activity was encouraged but not supervised. The primary outcome was whole-body lean mass at 12 months after commencement of intervention. Secondary outcomes were body weight, thigh muscle area and muscle function (strength), bone mineral density, and fat mass and distribution, measured at 0, 4, 6, and 12 months. A total of 101 postmenopausal women were recruited (mean [SD] age, 58.0 [4.2] years; mean [SD] weight, 90.8 [9.1] kg; mean [SD] body mass index, 34.4 [2.5]). Compared with the moderate group at 12 months, the severe group lost more weight (effect size, -6.6 kg; 95% CI, -8.2 to -5.1 kg), lost more whole-body lean mass (effect size, -1.2 kg; 95% CI, -2.0 to -0.4 kg), and lost more thigh muscle area (effect size, -4.2 cm2; 95% CI, -6.5 to -1.9 cm2). However, decreases in whole-body lean mass and thigh muscle area were proportional to total weight loss, and there was no difference in muscle (handgrip) strength between groups. Total hip bone mineral density (effect size, -0.017 g/cm2; 95% CI, -0.029 to -0.005 g/cm2), whole-body fat mass (effect size, -5.5 kg; 95% CI, -7.1 to -3.9 kg), abdominal subcutaneous adipose tissue (effect size, -1890 cm3; 95% CI, -2560 to -1219 cm3), and visceral adipose tissue (effect size, -1389 cm3; 95% CI, -1748 to -1030 cm3) loss were also greater for the severe group than for the moderate group at 12 months. Severe energy restriction had no greater adverse effect on relative whole-body lean mass or handgrip strength compared with moderate energy restriction and was associated with 2-fold greater weight and fat loss over 12 months. However, there was significantly greater loss of total hip bone mineral density with severe vs moderate energy restriction. Therefore, caution is necessary when implementing severe energy restriction in postmenopausal women, particularly those with osteopenia or osteoporosis. anzctr.org.au Identifier: 12612000651886.

Rationale and Protocol for a Randomized Controlled Trial Comparing Fast versus Slow Weight Loss in Postmenopausal Women with Obesity—The TEMPO Diet Trial

Very low energy diets (VLEDs), commonly achieved by replacing all food with meal replacement products and which result in fast weight loss, are the most effective dietary obesity treatment available. VLEDs are also cheaper to administer than conventional, food-based diets, which result in slow weight loss. Despite being effective and affordable, these diets are underutilized by healthcare professionals, possibly due to concerns about potential adverse effects on body composition and eating disorder behaviors. This paper describes the rationale and detailed protocol for the TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity), in a randomized controlled trial comparing the long-term (3-year) effects of fast versus slow weight loss. One hundred and one post-menopausal women aged 45–65 years with a body mass index of 30–40 kg/m2 were randomized to either: (1) 16 weeks of fast weight loss, achieved by a total meal replacement diet, followed by slow weight loss (as for the SLOW intervention) for the remaining time up until 52 weeks (“FAST” intervention), or (2) 52 weeks of slow weight loss, achieved by a conventional, food-based diet (“SLOW” intervention). Parameters of body composition, cardiometabolic health, eating disorder behaviors and psychology, and adaptive responses to energy restriction were measured throughout the 3-year trial.

Recruitment Strategies for a Randomised Controlled Trial Comparing Fast Versus Slow Weight Loss in Postmenopausal Women with Obesity-The TEMPO Diet Trial.

Current research around effective recruitment strategies for clinical trials of dietary obesity treatments have largely focused on younger adults, and thus may not be applicable to older populations. The TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity) is a randomised controlled trial comparing the long-term effects of fast versus slow weight loss on body composition and cardio-metabolic health in postmenopausal women with obesity. This paper addresses the recruitment strategies used to enrol participants into this trial and evaluates their relative effectiveness. 101 post-menopausal women aged 45–65 years, with a body mass index of 30–40 kg/m2 were recruited and randomised to either fast or slow weight loss. Multiple strategies were used to recruit participants. The total time cost (labour) and monetary cost per randomised participant from each recruitment strategy was estimated, with lower values indicating greater cost-effectiveness and higher values indicating poorer cost-effectiveness. The most cost-effective recruitment strategy was word of mouth, followed (at equal second place) by free publicity on TV and radio, and printed advertorials, albeit these avenues only yielded 26/101 participants. Intermediate cost-effective recruitment strategies were flyer distribution at community events, hospitals and a local tertiary education campus, internet-based strategies, and clinical trial databases and intranets, which recruited a further 40/101 participants. The least cost-effective recruitment strategy was flyer distribution to local health service centres and residential mailboxes, and referrals from healthcare professionals were not effective. Recruiting for clinical trials involving postmenopausal women could benefit from a combination of recruitment strategies, with an emphasis on word of mouth and free publicity via radio, TV, and print media, as well as strategic placement of flyers, supplemented with internet-based strategies, databases and intranets if a greater yield of participants is needed.

Does obesity attenuate the beneficial cardiovascular effects of cardiorespiratory fitness?

Background and aimsHigher cardiorespiratory fitness is associated with lower pulse wave velocity and arterial stiffness in normal weight individuals, and this has not been examined in obese individuals. It is unclear whether an altered body composition acts as a modifier of the association between cardiorespiratory fitness and arterial stiffness. We examined the association between peak oxygen uptake and brachial-ankle pulse wave velocity and analysed whether body composition attenuates this association in obese middle-aged individuals. MethodsBio-impedance analysis-derived body composition assessment in 212 healthy and sedentary either overweight or obese individuals was followed by measurement of brachial-ankle pulse wave velocity and spiroergometric peak oxygen uptake. Multivariate analysis was performed to analyse the association between peak oxygen uptake and brachial-ankle pulse wave velocity and to assess the moderating effect of several body composition-related interaction terms (BMI, total body mass, body fat mass, waist circumference, waist-to-height ratio) on this association. ResultsPeak oxygen uptake was inversely associated with brachial-ankle pulse wave velocity (β = −0.059, 95% CI = −0.099; −0.018, p = 0.005). Testing for the impact of different body composition-related interaction terms on this association showed no significance, 95% CI lateralized towards positivity. ConclusionsThis study shows an inverse association between cardiorespiratory fitness and arterial stiffness in middle-aged obese individuals. We also found a tendency towards an attenuating impact of an obese body composition on this association. Physical fitness seems to be a stronger modulator of cardiovascular risk than body composition but the success of training efforts may be compromised by obesity.

Echocardiographic B-mode evaluation of the right heart in older people: The ActiFE Study

PurposeRight heart B-mode echocardiography reference values have been predominantly obtained in younger age cohorts (<65years). Aims of the study were to describe and evaluate the feasibility of right heart B-mode echocardiography in a large geriatric cohort and to analyze standard parameters in defined subgroups with or without any evidence for structural cardiac disease. MethodsActiFE-Ulm study is a population-based cohort study including a sample of people≥65years old living in the region of Ulm, Germany. Echocardiography including right heart parameters was performed within a cardiovascular follow-up of 688 subjects. Principal resultsNon-obtainability of right heart B-mode data was rather not a consequence of accompanying cardiac diseases or risk factors but of a more obese body composition. Mean values of right heart measurements of our subpopulation of subjects without evidence for structural cardiac disease were continuously higher than those of the guidelines (e.g. mean right ventricular end diastolic area 23.5±5.6cm2 (males), 20.3±5.0cm2 (females)). On an individual basis, guideline-suggested abnormality thresholds were also often exceeded, whereas this situation occurred more often in male than in female subjects. Major conclusionsMethodically, right heart B-mode echocardiography in older subjects is challenging. Our results suggest an ageing-associated right heart enlargement. Utilization of published right heart reference values in older adults seems to be problematic and in clinical practice, they always have to be interpreted within the clinical and functional context and in relation to other right heart echocardiographic parameters.

Fast versus slow weight loss: development process and rationale behind the dietary interventions for the TEMPO Diet Trial.

SummaryObjective and methodsFinding effective solutions to curb the obesity epidemic is a great global public health challenge. The need for long‐term follow‐up necessitates weight loss trials conducted in real‐world settings, outside the confines of tightly controlled laboratory or clinic conditions. Given the complexity of eating behaviour and the food supply, this makes the process of designing a practical dietary intervention that stands up to scientific rigor difficult. Detailed information about the dietary intervention itself, as well as the process of developing the final intervention and its underlying rationale, is rarely reported in scientific weight management publications but is valuable and essential for translating research into practice. Thus, this paper describes the design process and underlying rationale behind the dietary interventions in an exemplar weight loss trial – the TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity). This trial assesses the long‐term effects of fast versus slow weight loss on adiposity, fat free mass, muscle strength and bone density in women with obesity (body mass index 30–40 kg m−2) that are 45–65 years of age, postmenopausal and sedentary.Results and conclusionsThis paper is intended as a resource for researchers and/or clinicians to illustrate how theoretical values based on a hypothesis can be translated into a dietary weight loss intervention to be used in free‐living women of varying sizes.

Macronutrient distribution of the diet–impact on weight and cardiometabolic outcomes in overweight and obese children and adolescents: A systematic review

energy restriction) for up to 12-months. Subjective ratings of appetite before and after a standard meal, physical activity measured via accelerometery, and REE determined by indirect calorimetry, will be measured at baseline, 1-week, 1-month, 4months and 6-months after the start of the dietary interventions. Participants will be followed-up at 12-months to see whether initial compensatory responses return to normal post intervention. Given that the increases in appetite and reductions in energy expenditure that occur due to energy restriction predict subsequent weight regain, the results from this study will inform the relative likelihood of weight regain in response to severe versus moderate energy restriction. This study is a component of the TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimum metabolic health and body composition in Obesity), funded by an NHMRC Project Grant (APP1026005). Trial ID: ACTRN12612000651886.

A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a frequent reproductive and metabolic disorder associated with insulin resistance (IR). Berberine (BBR) is an isoquinoline derivative alkaloid extracted from Chinese medicinal herbs that has been used as an insulin sensitizer. BBR may have a potential therapeutic value for PCOS. The aim of this study was to evaluate the effects of BBR in comparison to metformin (MET) on the metabolic features of women with PCOS. Eighty-nine subjects with PCOS and IR subjects were randomized into one of three treatment groups: BBR+compound cyproterone acetate (CPA; n=31), MET+CPA (n=30), and placebo+CPA (n=28) for 3 months. Clinical characteristics of the women and metabolic and hormonal parameters were assessed before and after the period of treatment. Treatment with BBR in comparison to MET showed decrease in waist circumference and waist-to-hip ratio (WHR; P<0.01), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDLC; P<0.05) as well as increase in high-density lipoprotein cholesterol (HDLC) and sex hormone-binding globulin (SHBG; P<0.05). Similarly, treatment with BBR in comparison to placebo showed decrease in WHR, fasting plasma glucose, fasting insulin, homeostasis model assessment for IR, area under the curve of insulin, TC, LDLC, and TG (P<0.05) as well as increase in HDLC and SHBG (P<0.01). Intake of BBR improved some of the metabolic and hormonal derangements in a group of treated Chinese women with PCOS. Main effects could be related to the changes in body composition in obesity and dyslipidemia. Further controlled studies are needed for the assessment of the potential favorable metabolic effects of BBR in women with PCOS.

Estimating Energy Needs in Nutrition Support Patients

Determination of energy needs is a fundamental part of nutrition support. The amount of metabolically active tissue mass is the major determinant of metabolic rate. The other components of total energy requirement in an adult are physical activity, diet-induced thermogenesis, and illness hypermetabolism. Measurement with indirect calorimetry is possible but not common. Measurement can capture the effect of body size, diet-induced thermogenesis, and illness on metabolic rate but usually not the effect of physical activity. More often, the energy need is calculated based on its association with body weight and composition. Many equations have been proposed over the years, as have adjustments to body weight in an attempt to capture the distorting effect of body composition in obesity and emaciation. Some equations capture the effects of illness and diet-induced thermogenesis without the need for modification; some require multiplication with various factors. None predict the energy expenditure from physical activity. In determining the energy prescription, all of the component parts must be considered, regardless of whether energy expenditure is measured or calculated.

Imaging body composition in obesity and weight loss: challenges and opportunities

Obesity is a threat to public health worldwide primarily due to the comorbidities related to visceral adiposity, inflammation, and insulin resistance that increase risk for type 2 diabetes and cardiovascular disease. The translational research portfolio that originally described these risk factors was significantly enhanced by imaging techniques, such as dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), and magnetic resonance imaging (MRI). In this article, we briefly review the important contributions of these techniques to understand the role of body composition in the pathogenesis of obesity-related complications. Notably, these imaging techniques have contributed greatly to recent findings identifying gender and racial differences in body composition and patterns of body composition change during weight loss. Although these techniques have the ability to generate good-quality body composition data, each possesses limitations. For example, DEXA is unable to differentiate type of fat, CT has better resolution but provides greater ionizing radiation exposure, and MRI tends to require longer imaging times and specialized equipment for acquisition and analysis. With the serious need for efficacious and cost-effective therapies to appropriately identify and treat at-risk obese individuals, there is greater need for translational tools that can further elucidate the interplay between body composition and the metabolic aberrations associated with obesity. In conclusion, we will offer our perspective on the evolution toward an ideal imaging method for body composition assessment in obesity and weight loss, and the challenges remaining to achieve this goal.

Imaging body composition in obesity and weight loss: challenges and opportunities

Imaging body composition in obesity and weight loss: challenges and opportunities Heidi J Silver1, E Brian Welch2, Malcolm J Avison2, Kevin D Niswender1,31Department of Medicine, 2Department of Radiology and Radiological Sciences, Institute of Imaging Sciences, Vanderbilt University, Nashville, TN, USA; 3Tennessee Valley Healthcare System, Nashville, TN, USAAbstract: Obesity is a threat to public health worldwide primarily due to the comorbidities related to visceral adiposity, inflammation, and insulin resistance that increase risk for type 2 diabetes and cardiovascular disease. The translational research portfolio that originally described these risk factors was significantly enhanced by imaging techniques, such as dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), and magnetic resonance imaging (MRI). In this article, we briefly review the important contributions of these techniques to understand the role of body composition in the pathogenesis of obesity-related complications. Notably, these imaging techniques have contributed greatly to recent findings identifying gender and racial differences in body composition and patterns of body composition change during weight loss. Although these techniques have the ability to generate good-quality body composition data, each possesses limitations. For example, DEXA is unable to differentiate type of fat, CT has better resolution but provides greater ionizing radiation exposure, and MRI tends to require longer imaging times and specialized equipment for acquisition and analysis. With the serious need for efficacious and cost-effective therapies to appropriately identify and treat at-risk obese individuals, there is greater need for translational tools that can further elucidate the interplay between body composition and the metabolic aberrations associated with obesity. In conclusion, we will offer our perspective on the evolution toward an ideal imaging method for body composition assessment in obesity and weight loss, and the challenges remaining to achieve this goal.Keywords: obesity, imaging, body composition, visceral fat

Comparison of DXA and water measurements of body fat following gastric bypass surgery and a physiological model of body water, fat, and muscle composition

Measurement of body composition changes following bariatric surgery is complicated because of the difficulty of measuring body fat in highly obese individuals that have increased photon absorption and are too large for the standard dual-energy X-ray absorptiometry (DXA) table. We reproducibly measured body composition from half-body DXA scans and compared the values of total body fat estimated from total body water (TBW) and DXA measurements before and after Roux-en-Y gastric bypass surgery (RYGB). DXA, TBW (deuterium dilution), extracellular water (ECW; bromide dilution), and intracellular water (ICW) measurement (by subtraction) were made before surgery and at 2 wk, 6 wk, 6 mo, and 12 mo after surgery. Twenty individuals completed baseline and at least four follow-up visits. DXA appeared to underestimate the fat and bone mass in extreme obesity (before surgery), whereas at 6 and 12 mo after surgery, the DXA and TBW fat measurements were similar. The ECW-to-ICW ratio was increased in obese individuals and increased slightly more after surgery. We describe a new model that explains this abnormal water composition in terms of the normal physiological changes that occur in body composition in obesity and weight loss. This model is also used to predict the muscle mass loss following RYGB.