Relative Lean Mass Research Articles

Long-term effects of a fat-directed FGF21 gene therapy in aged female mice.

Fibroblast growth factor 21 (FGF21) has been developed as a potential therapeutic agent for metabolic syndromes. Moreover, FGF21 is considered a pro-longevity hormone because transgenic mice overexpressing FGF21 display extended lifespan, raising the possibility of using FGF21 to promote healthy aging. We recently showed that visceral fat directed FGF21 gene therapy improves metabolic and immune health in insulin resistant BTBR mice. Here, we used a fat directed rAAV-FGF21 vector in 17-month-old female mice to investigate whether long-term FGF21 gene transfer could mitigate aging-related functional decline. Animals with FGF21 treatment displayed a steady, significant lower body weight over 7-month of the study compared to age-matched control mice. FGF21 treatment reduced adiposity and increased relative lean mass and energy expenditure associated with almost 100 folds higher serum level of FGF21. However, those changes were not translated into benefits on muscle function and did not affect metabolic function of liver. Overall, we have demonstrated that a single dose of fat-directed AAV-FGF21 treatment can provide a sustainable, high serum level of FGF21 over long period of time, and mostly influences adipose tissue homeostasis and energy expenditure. High levels of FGF21 alone in aged mice is not sufficient to improve liver or muscle functions.

Environmental Enrichment Improves Motor Function and Muscle Transcriptome of Aged Mice.

Aging results in the progressive decline of muscle strength. Interventions to maintain muscle strength may mitigate the age-related loss of physical function, thus maximizing health span. The work on environmental enrichment (EE), an experimental paradigm recapitulating aspects of an active lifestyle, has revealed EE-induced metabolic benefits mediated by a brain-fat axis across the lifespan of mice. EE initiated at 18-month of age shows a trend toward an increased mean lifespan. While previous work described EE's influences on the aging dynamics of several central-peripheral processes, its influence on muscle remained understudied. Here, the impact of EE is investigated on motor function, neuromuscular physiology, and the skeletal muscle transcriptome. EE is initiated in 20-month-old mice for a five-month period. EE mice exhibit greater relative lean mass that is associated with improved mobility and hindlimb grip strength. Transcriptomic profiling of muscle tissue reveals an EE-associated enrichment of gene expression within several metabolic pathways related to oxidative phosphorylation and the TCA cycle. Many mitochondrial-related genes-several of which participate in the electron transport chain-are upregulated. Stress-responsive signaling pathways are downregulated because of EE. The results suggest that EE improves motor function-possibly through preservation of mitochondrial function-even late in life.

Transplantation of gut microbiota from old mice into young healthy mice reduces lean mass but not bone mass

ABSTRACT Aging is associated with low bone and lean mass as well as alterations in the gut microbiota (GM). In this study, we determined whether the reduced bone mass and relative lean mass observed in old mice could be transferred to healthy young mice by GM transplantation (GMT). GM from old (21-month-old) and young adult (5-month-old) donors was used to colonize germ-free (GF) mice in three separate studies involving still growing 5- or 11-week-old recipients and 17-week-old recipients with minimal bone growth. The GM of the recipient mice was similar to that of the donors, demonstrating successful GMT. GM from old mice did not have statistically significant effects on bone mass or bone strength, but significantly reduced the lean mass percentage of still growing recipient mice when compared with recipients of GM from young adult mice. The levels of propionate in the cecum of mice receiving old donor GM were significantly lower than those in mice receiving young adult donor GM. Bacteroides ovatus was enriched in the microbiota of recipient mice harboring GM from young adult donors. The presence of B. ovatus was not only significantly associated with high lean mass percentage in mice, but also with lean mass adjusted for fat mass in the large human HUNT cohort. In conclusion, GM from old mice reduces lean mass percentage but not bone mass in young, healthy, still growing recipient mice. Future studies are warranted to determine whether GM from young mice improves the musculoskeletal phenotype of frail elderly recipient mice.

Association between appendicular lean mass and chronic obstructive pulmonary disease: epidemiological cross-sectional study and bidirectional Mendelian randomization analysis.

The association of BMI with COPD, and sarcopenia in COPD have been both confirmed by several studies, but research on the relationship and causality of body lean mass and the risk of chronic obstructive pulmonary disease (COPD) remains to be discovered. The purpose of this study was to explore the association between lean mass and COPD risk as well as to further examine the causal relationship in the findings. Three thousand four hundred fifty-nine participants from NHANES 2013-2018 were included in the epidemiological cross-sectional study to assess the association between relative lean mass and COPD by restricted spline analysis (RCS) and weighted multiple logistic regression. Furthermore, to verify the causality between lean mass and COPD, a two-sample Mendelian randomization (MR) with inverse variance weighting (IVW) method was used to analyze GWAS data from European ancestry. Genetic data from the United Kindom Biobank for appendicular lean mass (450,243 cases) and lung function (FEV1/FVC) (400,102 cases) together with the FinnGen platform for COPD (6,915 cases and 186,723 controls) were used for MR. Weighted multiple logistic regression showed a significant correlation between relative appendicular lean mass and COPD after adjusting for confounders (OR = 0.985, 95% CI: 0.975-0.995). Compared to the lower mass (155.3-254.7) g/kg, the high mass (317.0-408.5) g/kg of appendicular lean apparently decreases the risk of COPD (OR = 0.214, 95% CI: 0.060-0.767). Besides, in the analysis of MR, there was a forward causality between appendicular lean mass and COPD (IVW: OR = 0.803; 95%CI: 0.680-0.949; p = 0.01), with a weak trend of causality to lung function. Our study not only found an inverse association between appendicular lean mass and COPD but also supported a unidirectional causality. This provided possible evidence for further identification of people at risk for COPD and prevention of COPD based on limb muscle exercise and nutritional supplementation to maintain skeletal muscle mass.

1176-P: Maternal Hyperglycemia Leads to Distinct Differences in Metabolism and Pancreatic Beta-Cell Function in Male and Female Offspring

Maternal hyperglycemia is a major risk factor for future T2D risk in the offspring. To better understand T2D pathogenesis in this context, we used a mouse model of hyperglycemia induced by high-fat, high-sugar (HFHS) feeding from before mating through to weaning. This resulted in increased adiposity, reduced insulin sensitivity, hyperinsulinemia and impaired glucose tolerance pre-pregnancy. Pregnancy further worsened the metabolic health of dams resulting in reduced insulin levels in addition to glucose intolerance at gestational day 16. By weaning, HFHS-fed dams had fasting hyperglycemia. Maternal hyperglycemia had no impact on offspring body weight and composition at postnatal day 2. However, male offspring of HFHS-fed dams experienced decelerated postnatal growth in the first 2 weeks of life followed by catch-up growth by weaning. Despite comparable body weight, relative fat mass was increased and relative lean mass decreased from 3 to 8 weeks of age in exposed offspring. In males, this was not linked to changes in food intake and metabolic activity measured at 7 weeks. In contrast, daily energy expenditure was increased in female offspring of hyperglycemic dams. At 8 weeks old, despite normal glucose tolerance and insulin sensitivity, male offspring of HFHS-fed dams were hyperinsulinemic during a glucose tolerance test. In contrast, female offspring had reduced insulin sensitivity and higher plasma insulin concentration at baseline and 45 min. Interestingly, insulin secretion was increased only in islets from male offspring characterised by a marked increase in 1st phase and a trend towards higher 2nd phase secretion. Insulin secretion in response to potassium chloride was also increased in these islets. Thus, our data suggest that there are sex-specific mechanisms contributing to future T2D risk in offspring exposed to maternal hyperglycemia with primary hyperinsulinemia being an early feature in males and insulin resistance in females. Disclosure S.E.O'hara: None. K.M.Gembus: None. G.S.Clarke: None. A.J.Page: None. L.M.Nicholas: None. Funding National Health and Medical Research Council of Australia (GNT1092158)

Obesity reduced survival with 5-fluorouracil and did not protect against chemotherapy-induced cachexia or immune cell cytotoxicity in mice

ABSTRACT Fluorouracil/5-flourouracil (5FU) is a first-line chemotherapy drug for many cancer types; however, its associated toxicities contribute to poor quality of life and reduced dose intensities negatively impacting patient prognosis. While obesity remains a critical risk factor for most cancers, our understanding regarding how obesity may impact chemotherapy’s toxicities is extremely limited. C56BL/6 mice were given high fat (Obese) or standard diets (Lean) for 4 months and then subjected to three cycles of 5FU (5d-40 mg/kg Lean Mass, 9d rest) or PBS vehicle control. Shockingly, only 60% of Obese survived 3 cycles compared to 100% of Lean, and Obese lost significantly more body weight. Dihydropyrimidine dehydrogenase (DPD), the enzyme responsible for 5FU catabolism, was reduced in obese livers. Total white blood cells, neutrophils, and lymphocytes were reduced in Obese 5FU compared to Lean 5FU and PBS controls. While adipocyte size was not affected by 5FU in Obese, skeletal muscle mass and myofibrillar cross section area were decreased following 5FU in Lean and Obese. Although adipose tissue inflammatory gene expression was not impacted by 5FU, distinct perturbations to skeletal muscle inflammatory gene expression and immune cell populations (CD45+ Immune cells, CD45+CD11b+CD68+ macrophages and CD45+CD11b+Ly6clo/int macrophage/monocytes) were observed in Obese only. Our evidence suggests that obesity induced liver pathologies and reduced DPD exacerbated 5FU toxicities. While obesity has been suggested to protect against cancer/chemotherapy-induced cachexia and other toxicities, our results demonstrate that obese mice are not protected, but rather show evidence of increased susceptibility to 5FU-induced cytotoxicity even when dosed for relative lean mass.

An animal model for Pierpont syndrome: a mouse bearing the Tbl1xr1Y446C/Y446C mutation.

Pierpont syndrome is a rare disorder characterized mainly by global developmental delay, unusual facial features, altered fat distribution in the limbs and hearing loss. A specific mutation (p.Tyr446Cys) in TBL1XR1, encoding a WD40 repeat-containing protein, which is a component of the SMRT/NCoR (silencing mediator retinoid and thyroid hormone receptors/nuclear receptor corepressors), has been reported as the genetic cause of Pierpont syndrome. Here, we used CRISPR-cas9 technology to generate a mutant mouse with the Y446C mutation in Tbl1xr1, which is also present in Pierpont syndrome. Several aspects of the phenotype were studied in the mutant mice: growth, body composition, hearing, motor behavior, thyroid hormone state and lipid and glucose metabolism. The mutant mice (Tbl1xr1Y446C/Y446C) displayed delayed growth, altered body composition with increased relative lean mass and impaired hearing. Expression of several genes involved in fatty acid metabolism differed in white adipose tissue, but not in liver or muscle of mutant mice compared to wild-type mice (Tbl1xr1+/+). No difference in thyroid hormone plasma concentrations was observed. Tbl1xr1Y446C/Y446C mice can be used as a model for distinct features of Pierpont syndrome, which will enable future studies on the pathogenic mechanisms underlying the various phenotypic characteristics.

A cross-sectional comparative study on the effects of body mass index and exercise/sedentary on serum asprosin in male college students.

Adipocytes regulate the body’s metabolism by secreting adipokines to maintain energy homeostasis. Asprosin is a new type of adipokine, and its relationship with obesity remains controversial. There are a few reports on the effect of long-term exercise on serum asprosin level. This study aimed to investigate the effects of body mass index (BMI) and exercise/sedentary habit on serum asprosin in male college students as well as the relationship between serum asprosin and body composition and related metabolic indicators and provided a basis for further exploration of the biological function of asprosin. Ninety-six male college students were classified into the sedentary habit group (SD; 48) and the special training experience group (ET; 48). Both groups included three subgroups of normal BMI, overweight, and obesity, with 16 people in each subgroup. One-way analysis of variance, analysis of covariance, and Pearson correlation analysis were performed. The results showed that serum asprosin levels in the obesity subgroup were significantly higher than those in the normal and overweight subgroups. Excluding BMI interference, there were no significant differences in serum asprosin between the SD and ET groups; however, there were significant differences in body composition, tumor necrosis factor-α, interleukin-6, and interleukin-10. Asprosin was positively correlated with BMI, body fat percentage, visceral fat area, fasting insulin, insulin resistance homeostasis model, total cholesterol, low-density lipoprotein, tumor necrosis factor-α, interleukin-6, and leptin levels and was negatively correlated with relative lean body mass, relative skeletal muscle mass, high-density lipoprotein, and interleukin-10, and adiponectin levels. In conclusion, serum asprosin is closely related to body weight, body composition, glucose and lipid metabolism, inflammatory response, and fat hormones. Long-term exercise training cannot prevent BMI increase from increasing serum asprosin level. If the influence of BMI is excluded, long-term exercise training does not affect serum asprosin.

Body composition changes at 12 months following different surgical weight loss interventions in adults with obesity: A systematic review and meta‐analysis of randomized control trials

SummaryTo determine relative lean mass and fat mass changes in adults with obesity following surgical weight loss interventions, a systematic review and meta‐analysis was conducted. The Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, and Scopus were screened for eligible studies. Inclusion criteria included randomized controlled trials (RCTs) performed in populations with obesity (body mass index ≥30 kg/m2) aged over 18 years, who underwent any type of bariatric surgery and reported body composition measures via dual‐energy X‐ray absorptiometry or bio‐electrical impedance analysis. Authors conducted full text screening and determined that there were six RCTs eligible for inclusion, with data extracted at 12 months post‐surgery. Meta‐analysis revealed that, relative to gastric banding, Roux‐en‐Y gastric bypass (RYGB) led to greater total body mass loss (mean difference [MD]: −9.33 kg [95% CI: −12.10, −6.56]) and greater fat mass loss (MD: −8.86 kg [95% CI: −11.80, −5.93], but similar lean mass loss (MD: −0.55 kg [95% CI: −3.82, 2.71]. RYGB also led to similar changes in total body mass, fat mass, and lean mass compared with sleeve gastrectomy. RYGB results in greater 12‐month weight and fat loss, but similar changes in lean mass, compared with gastric banding. Further RCTs comparing body composition changes following different bariatric surgery procedures are required.

Relative Lean Body Mass and Waist Circumference for the Identification of Metabolic Syndrome in the Korean General Population.

Lean body mass (LBM) comprises organs and muscle, which are the primary determinants of energy expenditure and regulation of glucose and lipid metabolism. Excessive abdominal fat is associated with metabolic abnormality. Little is known about the relationship between metabolic abnormality and LBM and waist circumference (WC), especially in the Asian general population. The aim of this study was to clarify this relationship. We performed a cross-sectional study with 499,648 subjects who received health check-ups at 16 health promotion centers in 13 Korean cities between January 2018 and October 2019. The subjects were categorized into four groups: (a) High (H)-RLBM (relative lean body mass)/Normal (N)-WC, (b) High-RLBM/Abnormal (A)-WC, (c) Low (L)-RLBM/Normal-WC, and (d) Low-RLBM/Abnormal-WC. RLBM was calculated using fat mass data that were estimated via bioelectrical impedance analysis. L-RLBM/A-WC was significantly associated with metabolically unhealthy status (OR: 4.40, 95% CI: 4.326–4.475) compared to H-RLBM/N-WC. L-RLBM/N-WC (OR: 2.170, 95% CI: 2.122–2.218) and H-RLBM/A-WC (OR: 2.713, 95% CI: 2.659–2.769) were also significantly related to metabolic unhealthy status. The cut-offs of RLBM for predicting metabolic syndrome (MetS) were 74.9 in males and 66.4 in females (p < 0.001). L-RLBM and A-WC are associated with metabolic abnormality in the Korean general population. RLBM is an anthropometric index that can be used to predict MetS in primary health care.

Should nutrition therapy be modified to account for mitochondrial dysfunction in critical illness?

Metabolic dysfunction, and its associated muscle atrophy, remains the most common complication of critical care. At the center of this is mitochondrial dysfunction, secondary to hypoxia and systemic inflammation. This leads to a bioenergetic crisis, with decreased intramuscular adenosine triphosphate content and a reduction in the highly energy-dependent process of protein synthesis. Numerous methods have been studied to try and reduce these effects, with only limited success. Trials investigating the use of increased energy and protein administration have instead found a decrease in relative lean body mass and a potential increase in morbidity and mortality. Ketone bodies have been proposed as alternative substrates for metabolism in critical illness, with promising results seen in animal models. They are currently being investigated in critical care patients in the Alternative Substrates in the Critically Ill Subjects trial (ASICS). The evidence to date suggests that individualized feeding regimens may be key in the nutrition approach to critical illness. Consideration of individual patient factors will need to be combined with personalized protein content, total energy load received, and the timing of such feeds. This review covers mitochondrial dysfunction in critical illness, how it contributes to muscle wasting and the resultant morbidity and mortality, and the scientific basis of why current nutrition approaches to date have not been successful in negating this effect. These two factors underpin the need for consideration of alternative nutrition strategies in the critically ill patient.

Muscle function, quality, and relative mass are associated with knee pain trajectory over 10.7 years.

Periarticular muscle plays an important role in the pathogenesis of musculoskeletal pain. We recently reported that pain population consists of distinct subgroups of which the causes and mechanisms may differ. This study aimed to examine the association of lean mass, muscle strength, and quality with 10.7-year pain trajectory. Nine hundred forty-seven participants from a population-based cohort study were analysed. Dual-energy X-ray absorptiometry was used to assess lean and fat mass. Leg strength, knee extensor strength, and lower-limb muscle quality were measured/calculated. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index pain questionnaire. Radiographic knee osteoarthritis was assessed by X-ray. Three distinct pain trajectories were identified: "Minimal pain" (53%), "Mild pain" (34%), and "Moderate pain" (13%). Higher total and lower-limb lean mass were associated with an increased risk of "Mild pain" and "Moderate pain" trajectories relative to the "Minimal pain" trajectory group, but these associations became nonsignificant after further adjustment for fat mass. Total lean mass percentage was associated with a lower risk of "Mild pain" (relative risk ratio [RRR]: 0.95, 95% confidence interval 0.92-0.98) and "Moderate pain" trajectory (RRR: 0.92, 95% confidence interval 0.87-0.96). Greater leg and knee extensor strength and muscle quality were associated with "Mild pain" and "Moderate pain" trajectories (RRR: 0.52-0.65, all P < 0.05). Similar results were found in those with radiographic knee osteoarthritis. Higher lower-limb muscle strength and quality, and relative lean mass, are associated with a reduced risk of severe knee pain trajectories, suggesting that improving muscle function and composition may protect against persistent unfavourable knee pain courses.

The effects of training with high-speed interval running on muscle performance are modulated by slope.

We examined changes in selected muscle performance parameters after 8 weeks of interval training using two opposite running inclinations. We hypothesized that the uphill training will affect endurance muscle performance outcomes, whereas the downhill training will affect power muscle performance outcomes. Fourteen physically active volunteers were randomly assigned into either the Uphill group (UG; n = 7; uphill interval running at +10% incline) or the Downhill group (DG; n = 7; downhill interval running at −10% incline) and completed 16 training sessions. Each session consisted of ten 30 s treadmill runs at 90% of maximum aerobic speed (MAS) with a work to rest ratio of 1:2. Vertical jump performance, isometric (MVC) and isokinetic torque of knee extensors and flexors, and fatigue of knee extensors were evaluated pre and post‐training. Moreover, body composition (via bioimpedance) and vastus lateralis muscle architecture (via ultrasonography) were assessed pre and post‐training. Relative lean tissue mass, relative fat mass, and squat jump (cm) significantly (p < .05) changed from baseline values by +4.5 ± 4.0%, −11.5 ± 9.6%, and +9.5 ± 11.7%, respectively, only in the DG. Similarly, DG improved absolute values of knee extension rate of torque development and impulse (p < .05), whereas knee flexion peak torque angle significantly decreased in both groups (p < .05). On the other hand, the UG increased the number of repetitions achieved during the fatigue protocol and total work by 21.2 ± 32.6% and 13.8 ± 21.2%, respectively (p < .05). No differences were found between groups in muscle architecture. Introducing variations in slope during HIIT could be used to induce specific improvements toward muscle endurance or power performance characteristics.

Frailty in long‐term Dutch adult survivors of childhood acute myeloid leukaemia, neuroblastoma, and Wilms' tumour

AbstractBackgroundSeveral simultaneous impairments in physical ability may be an indication of frailty in adult survivors of childhood cancer (CCS). The aim of our study was to assess the occurrence of frailty and to explore potential determinants in a selected Dutch cohort of long‐term adult CCS.MethodsIn this cross‐sectional study, we used data of 70 very long‐term CCS [median age 28.8 years (interquartile range: 23.9–34.6)] of acute myeloid leukaemia (AML) (n = 17), neuroblastoma (NBL) (n = 25), and Wilms' tumour (WT) (n = 28). Prefrailty and frailty were defined as having, respectively, 2 and ≥3 of the five following components: low relative lean body mass (by dual‐energy X‐ray absorptiometry less than −1.5 standard deviation, SD), self‐reported exhaustion (fatigue, exhaustion, or exertion related complaints), low energy expenditure (men: &lt;383 kcal/week, and women: &lt;270 kcal/week), slow walking speed (less than −2.0 SD on the 6‐min walk test), and weakness (hand grip strength less than −2.0 SD). Potential determinants of prefrailty and frailty (≥2 components), including treatment components, sociodemographic, and lifestyle factors, were evaluated using logistic regression analysis.ResultsRespectively, 6.3% and 28.1% women and 5.3% and 26.3% men were classified as frail and prefrail. Six per cent of the AML, 8% of the NBL, and 3.6% of the WT CCS were frail. Forty‐one per cent of the AML, 28% of the NBL, and 17.9% of the WT CCS were prefrail. No significant associations were found between any of the investigated determinants and frailty or prefrailty.ConclusionOur results confirm previous reports that CCS, in particular intensively treated, have a potential risk of (pre)frailty.

Testing the utility of condition indices in nestling swallows: a quantitative magnetic resonance approach

Nutritional condition is a key factor influencing the survival of migratory birds, and condition indices derived from morphometric measurements are commonly used to assess nutrient and energy stores. The performance and utility of condition indices used to examine energetics of growing juvenile birds remain uncertain. Recently, quantitative magnetic resonance (QMR) has been used to provide a non-invasive and non-lethal way to obtain measures of body composition. We calculated three widely used body condition indices using both wing length and tarsus length for nestling Barn Swallows Hirundo rustica erythrogaster at two ages (Day 8 and 15) and compared them to relative fat and lean mass calculated using QMR measurements. Additionally, we used QMR to develop multiple regression formulas to predict nestling fat mass, lean mass, and fat-free lean body mass (LBM) from easily obtainable body metrics. In Day 8 birds, variation in both relative fat mass and relative lean mass were adequately explained by total body mass alone, but this relationship was strongest for lean mass. Almost every condition index evaluated failed to explain variation in relative fat or lean mass in Day 15 birds. While our best multiple regression formulas for predicting fat mass and LBM had low predictive power, our formulas for predicting lean mass were precise (R2 > 90%) in both ages, providing a method to estimate the lean mass of nestlings from more readily obtainable metrics. Estimates of fat mass calculated from LBM and total body mass showed poor precision (R2 ≤ 30%).

Body Composition, Metabolic Health, and Functional Impairment among Adults Treated for Abdominal and Pelvic Tumors during Childhood.

We aimed to characterize body composition, metabolic impairments, and physical performance among survivors of pediatric abdominal and pelvic solid tumors. Participants included 431 survivors of abdominal or pelvic tumors [median attained age = 29.9 (range: 18.7-55.1) years]. Relative lean mass and fat mass were assessed with dual X-ray absorptiometry. Metabolic outcomes [insulin resistance (IR), high-density lipoprotein (HDL), low-density lipoprotein, and triglycerides] were based on laboratory values and medication usage. General linear regression evaluated associations between treatment and lifestyle with body composition; binomial regression evaluated associations between body composition and metabolic outcomes and physical performance. Lean mass was lower than values from the National Health and Nutrition Examination Survey (NHANES) in males (Z-score = -0.67 ± 1.27; P < 0.001) and females (Z-score = -0.72 ± 1.28; P < 0.001). Higher cumulative abdominal and pelvic radiation doses were associated with lower lean mass among males [abdominal: β = -0.22 (SE) ± 0.07; P = 0.002 and pelvic: β = -0.23 ± 0.07; P = 0.002] and females (abdominal: β = -0.30 ± 0.09; P = 0.001 and pelvic: β = -0.16 ± 0.08; P = 0.037). Prevalence of IR (40.6% vs. 33.8%; P = 0.006), low HDL (28.9% vs. 33.5%; P = 0.046), and high triglycerides (18.4% vs. 10.0%; P < 0.001) was increased among survivors relative to NHANES. Compared with survivors with normal/high lean mass and normal/low fat mass, survivors with normal/high lean mass and high fat mass had an increased risk of IR (P < 0.001), low HDL (P < 0.001), reduced quadriceps strength at 60°/second (P < 0.001) and 300°/second (P < 0.001), and reduced distance covered in the 6-minute walk (P < 0.01). Abdominal/pelvic radiotherapy is associated with body composition changes that can adversely influence metabolic outcomes and performance status among survivors. Interventions targeting body composition may facilitate management of cardiovascular disease risk in this population.

Expressions of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases 1 in skeletal muscles of aged rats with sarcopenia

To investigate the changes of skeletal muscle mass and strength and the expressions of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinases-1 (TIMP-1) and collagen-1 in the skeletal muscle of aged rats with sarcopenia. With 11 young (6-month-old) SD rats as control group, 18 aged (25-month-old) SD rats were divided into two groups (n=9) according to the relative lean mass determined dual X-ray absorptiometry (DXA), namely aged control group and aged sarcopenia group (the relative lean mass was 2SD higher in aged control than in aged sarcopenia group. The forelimb grip strength of the rats was measured using an electronic grip strength meter. The extracellular matrix (ECM) of the rat's gastrocnemius was observed with HE staining and sirius Red staining, and the protein expressions of collagen-1, MMP-1, and TIMP-1 in the muscular tissues were detected with Western blotting. Compared with the young rats, the aged control rats had significantly lower relative grip strength (P < 0.01) and increased expressions of collagen-1 and TIMP-1 (P < 0.05) and ECM content in the skeletal muscles, but the relative lean mass and MMP-1 protein expression were comparable between the two groups (P>0.05). Compared with the aged control rats, the aged sarcopenic rats had significantly lowered relative lean mass (P < 0.01) and MMP-1 expressions of (P < 0.05) and increased expressions of collagen-1 and TIMP-1 proteins and ECM content in the muscular tissues (P < 0.05) without significant changes in the relative grip strength (P>0.05). MMP-1/TIMP-1 imbalance in the skeletal muscle during aging affects ECM metabolism and leads to increased collagen fibers, which in turn affects the skeletal muscle mass and function and contribute to the onset of sarcopenia.

Does lean body mass equal health despite body mass index?

To determine the association between having simultaneously high body mass index (BMI) and high relative lean body mass (LBM) and cardio-metabolic risk factors, metabolic syndrome (MetS), and diabetes in adults. A cross-sectional analysis was performed on 4982 adults aged 19-85years that participated in the National Health and Nutrition Examination Survey (cycles 1999-2000-2005-2006). The primary exposure variable was categorization into four groups: (a) Low-BMI/Low-LBM, (b) Low-BMI/High-LBM, (c) High-BMI/Low-LBM, and (d) High-BMI/High-LBM. LBM was assessed using dual-energy X-ray absorptiometry. The primary outcome measures were cardio-metabolic risk factors, MetS based on the ATP III definition; participants were required to have at least three of the following five criteria: high waist circumference, low HDL cholesterol, elevated triglyceride levels, high resting blood pressure, and self-reported diabetes. Compared to the High-BMI/High-LBM, most cardio-metabolic risk factors were significantly different among groups (P<.05) while no such differences were observed for the High-BMI/Low-LBM (P>.05). Exception of waist circumference (OR [95%]: 21.8 [8.84-53.82]), there was no increased odds of having cardio-metabolic risk factors in the High-BMI/Low-LBM compared with the High-BMI/High-LBM (P>.05). The odds of having MetS and diabetes for the High-BMI/Low-LBM compared with the High-BMI/High-LBM were OR (95% CI): 1.68 (0.84-3.36) and 0.59 (0.26-1.34), respectively. Our results suggest that having a high-BMI as well as high relative LBM levels is not associated with cardio-metabolic risk factors, MetS, and diabetes. Therefore, maintaining a BMI below 30kg/m2 appears to be clinically relevant, regardless of LBM levels.

Beneficial effects of running and milk protein supplements on Sirtuins and risk factors of metabolic disorders in rats with low aerobic capacity

BackgroundPhysical activity and dietary intake of dairy products are associated with improved metabolic health. Dairy products are rich with branched chain amino acids that are essential for energy production. To gain insight into the mechanisms underlying the benefit of the sub-chronic effects of running and intake of milk protein supplements, we studied Low Capacity Runner rats (LCR), a rodent exercise model with risk for metabolic disorders. We especially focused on the role of Sirtuins, energy level dependent proteins that affect many cellular metabolic processes. MethodsForty-seven adult LCR female rats sedentary or running voluntarily in wheels were fed normal chow and given supplements of either whey or milk protein drink (PD)-supplemented water, or water only for 21 weeks. Physiological responses were measured in vivo. Blood lipids were determined from serum. Mitochondrial markers and Sirtuins (Sirt1-7) including downstream targets were measured in plantaris muscle by western blotting. ResultsFor the first 10 weeks whey-drinking rats ran about 50% less compared to other groups; still, in all runners glucose tolerance improved and triglycerides decreased. Generally, running induced a ∼six-fold increase in running capacity and a ∼8% decrease in % body fat. Together with running, protein supplements increased the relative lean mass of the total body weight by ∼11%. In comparison with sedentary controls, running and whey increased HDL (21%) and whey, with or without running, lowered LDL (−34%). Running increased mitochondrial biogenesis and Sirtuins 3 and 4. When combined with exercise, both whey and milk protein drink induced about a 4-fold increase in Sirt3, compared to runners drinking water only, and about a 2-fold increase compared to the respective sedentary group. Protein supplements, with or without running, enhanced the phosphorylation level of the acetyl-coA-carboxylase, suggesting increased fat oxidation. Both supplemented diets increased Sirt5 and Sirt7 without an additional effect from exercise. Running diminished and PD supplement increased Sirt6. ConclusionWe demonstrate in rats new sub-chronic effects of milk proteins on metabolism that involve Sirtuins and their downstream targets in skeletal muscle. The results show that running and milk proteins act on reducing the risk factors of metabolic disorders and suggest that the underlying mechanisms may involve Sirtuins. Notably, we found that milk protein supplements have some favorable effects on metabolism even without running.

Changes in body composition in male adolescents with childhood‐onset GH deficiency during transition

Restarting rhGH in adolescents with childhood-onset (CO-) GHD is usually based on GH retest, IGF-1, additional pituitary hormone deficiencies, pituitary morphology and history. Short-term changes in body composition in adolescents with CO-GHD when off rhGH may contribute to the identification of those in need of treatment continuation. This is a longitudinal single-centre study. The body composition of 90 male adolescents with low-likelihood severe GHD of adolescence was measured by DXA at the time of rhGH discontinuation and 6months thereafter. At diagnosis, mean age was 5.4years, height was -2.68 SDS and stimulated GH peak was 5.1ng/mL. RhGH treatment was stopped at 16.7years at near-final height of -0.44 SDS. The adolescents were re-examined after 3months off rhGH using both IGF-1 and GHRH-arginine tests. Severe GHD of adolescence was defined both by stimulated GH<16ng/mL and by IGF-1<-1.90 SDS. Males with severe GHD of adolescence (n=8) gained more relative and absolute fat mass and lost significantly more relative lean body mass after 6months off rhGH than healthy individuals (n=82; P<0.001). The sum of absolute fat mass gain and lean body mass loss (=body composition changes score; BCC score) correlated highly with the GH peak (R=0.17; P<0.001). A BCC score >7.0kg was 88% sensitive and 94% specific for detecting severe GHD of adolescence (AUC=0.975). Short-term body composition changes when off rhGH are good clinical markers of severe GHD in male adolescents. The novel BBC score is an aggregate of these changes.