Lean Mass Research Articles

Cumulative effects of H+ and Pi on force and power of skeletal muscle fibres from young and older adults.

The cellular causes of the age-related loss in power output and increased fatigability are unresolved. We previously observed that the depressive effects of hydrogen (H+) (pH 6.2) and inorganic phosphate (Pi) (30mm) did not differ in muscle fibres from young and older men. However, the effects may have been saturated in the severe fatigue-mimicking condition, potentially masking age differences in the sensitivity of the cross-bridge to these metabolites. Thus, we compared the contractile mechanics of muscle fibres from the vastus lateralis of 13 young (20-32years, seven women) and 12 older adults (70-90years, six women) in conditions mimicking quiescent muscle and a range of elevated H+ (pH 6.8-6.6-6.2) and Pi (12-20-30mm). The older adult knee extensor muscles showed hallmark signs of ageing, including 19% lower thigh lean mass, 60% lower power and a greater fatigability compared to young adult muscles. Progressively increasing concentrations of H+ and Pi in the chemically-permeabilized fibre experiments caused a linear decrease in fibre force, velocity and power; however, the effects did not differ with age or sex. Fast fibre cross-sectional area was 41% smaller in older compared to young adults, which corresponded with lower absolute power. Size-specific power was greater in fibres from older compared to young adults, indicating the age-related decline in absolute power was explained by differences in fibre size. These data suggest the age-related loss in power is determined primarily by fast fibre atrophy in men and women, but the age-related increase in fatigability cannot be explained by an increased sensitivity of the cross-bridge to H+ and Pi. KEY POINTS: The causes of the age-related loss in muscle power output and the increase in fatigability during dynamic exercise remain elusive. We show that progressively increasing concentrations of hydrogen (H+) and inorganic phosphate (Pi) causes a linear decrease in muscle fibre force, velocity and power, but the depressive effects of these metabolites on cross-bridge function did not differ in fibres from older compared to young adults across a range of fatigue-mimicking conditions. We also found peak absolute power did not differ in slow fibres from young and older adults but it was ∼33% lower in older adult fast fibres, which was explained entirely by age differences in fibre size. These data suggest that fast fibre atrophy is a major factor contributing to the loss in power of older men and women, but that the age-related increase in fatigability cannot be explained by an increased sensitivity of the cross-bridge to H+ and Pi.

Artificial intelligence modeling of biomarker-based physiological age: Impact on phase 1 drug-metabolizing enzyme phenotypes.

Age and aging are important predictors of health status, disease progression, drug kinetics, and effects. The purpose was to develop ensemble learning-based physiological age (PA) models for evaluating drug metabolism. National Health and Nutrition Examination Survey (NHANES) data were modeled with ensemble learning to obtain two PA models, PA-M1 and PA-M2. PA-M1 included body composition, blood and urine biomarkers, and disease variables as predictors. PA-M2 had blood and urine-derived variables as predictors. Activity phenotypes for cytochrome-P450 (CYP) CYP2E1, CYP1A2, CYP2A6, xanthine oxidase (XO), and N-acetyltransferase-2 (NAT-2) and telomere attrition were assessed. Bayesian networks were used to obtain mechanistic systems pharmacology model structures for PA. The study included n = 22,307 NHANES participants (51.5% female, mean age 46.0 years, range: 18-79 years). The PA-M1 and PA-M2 distributions had greater dispersion across age strata with a right skew for younger age strata and a left skew for older age strata. There was no evidence of algorithmic bias based on sex or race/ethnicity. Klotho, lean body mass, glycohemoglobin, and systolic blood pressure were the top four predictors for PA-M1. Glycohemoglobin, serum creatinine, total cholesterol, and urine creatinine were the top four predictors for PA-M2. The models also performed satisfactorily in independent validation. Model-predicted PA was associated with CYP2E1, CYP1A2, CYP2A6, XO, and NAT-2 activity. Telomere attrition was associated with greater PA-M1 and PA-M2. Ensemble learning models provide robust assessments of PA from easily obtained blood and urine biomarkers. PA is associated with Phase I drug-metabolizing enzyme phenotypes.

Effect of omega-3 fatty acids supplementation on muscle mass, fat mass, and visceral fat of hemodialysis patients; A randomized clinical trial.

Several studies demonstrated the benefits of omega-3 fatty acids supplementation in chronic kidney disease (CKD) patients. The objective of this study was to investigate the effect of omega-3 fatty acids supplementation in body composition, specifically on the lean body mass and fat mass in hemodialysis patients. In this randomized, double-blind, placebo-controlled clinical trial, a total of 120 end-stage renal disease (ESRD) patients were randomly allocated into two groups. The intervention group has taken three grams of omega-3 fatty acids daily while the placebo group received three grams of medium chain triglycerides (MCT) as a placebo for a total of 2months. The changes in the body mass index (BMI) and body composition (fat mass, muscle, and visceral fat) were assessed at baseline and following the intervention. No significant difference was found in the mean of BMI, FAT, muscle, and visceral fat in the intervention group compared to the control group after the intervention. After two months of omega-3 fatty acid supplementation, the study found no statistically significant impact of omega-3 fatty acids supplementation on various indices of body composition. The effect of ω-3 supplementation in reducing visceral fat was close to significant (p=0.08). This study suggests that there is currently inadequate evidence to support the effect of omega-3 fatty acid supplementation in improving anthropometric measurements in patients with CKD, except a partial effect on visceral fat. Further large-scale and long-term clinical trials are needed to confirm the present results.

Utility of fat-free adipose tissue correction formula for tracking body composition changes with dual-energy X-ray absorptiometry.

Fat loss is often the target of weight loss interventions; however, preservation of lean soft tissue (LST) may be more important for health and weight maintenance. Though some LST loss may be inevitable when tracking body composition changes using dual-energy X-ray absorptiometry (DXA), correcting for the fat-free component of adipose tissue (FFAT) in DXA-derived LST (DXALST) has been proposed. This analysis sought to evaluate differences between DXALST and FFAT-corrected LST (FFATLST) amongst varied populations and interventions to understand application of the correction formula on LST outcomes. 226 subjects were analyzed across five prior studies. Three studies evaluated combined nutrition and exercise (high-intensity interval training [HIIT] or high-intensity resistance training [HIRT]) interventions, including HIIT + HIRT with pre- and post-nutrient timing (HIITRT), HIIT + essential amino acids (HIITAA), and HIRT + protein (HIRTPRO). Remaining studies evaluated HIIT (HIITOW) and protein following bariatric surgery (BARPRO). Pre and post total body DXA scans were used to measure DXALST, body mass, and fat mass (FM). The correction formula was applied to calculate FFATLST. Paired sample t-tests were used to evaluate differences between DXALST and FFATLST change scores (Δ) across all subjects, within each study and intervention. Significant differences between ΔDXALST and ΔFFATLST were observed for BARPRO (mean difference [MD; ΔDXALST-ΔFFATLST] ± standard error [SE]: -3.5 ± 1.2 kg, p < 0.001), as well as HIRTPRO (-0.1 ± 0.2 kg, p = 0.004). When evaluating LST, the FFAT correction may be specifically applicable to cases of significant weight loss (>10% of original weight) or body recomposition (≥2% FM loss and ≥2% LST gain).

Diagnostic power of serum creatinine/cystatin C ratio for identifying low MRI-muscle volume and low grip strength: Data from 9,731 to 149,707 UK Biobank older adults.

Biomarkers for sarcopenia are lacking. We examined the diagnostic power of serum creatinine to cystatin C (Cr:Cyc) ratio for identifying low MRI-muscle volume and low grip strength in a large observational study of UK Biobank older adults. Serum creatinine and cystatin C were measured via immunoassays (Beckman Coulter AU5800 and Siemens Advia 1800, respectively) and grip strength by hydraulic hand dynamometer at baseline visit (2008-2010). MRI-thigh fat-free muscle volume (FFMV) and DXA-derived appendicular lean mass were measured at imaging visit (2014-2018). Extreme outliers were removed, and covariates (demographic, lifestyle, and clinical factors, as well as time elapsed between baseline-imaging visit) were adjusted for in statistical models. 12,873 older adults (mean age: 63.5 ± 2.7 years, 44.2% women) were included for FFMV and ALM/BMI; 149,707 older adults (mean age: 64.0 ± 2.9 years, 50.5% women) for grip strength. Despite significant associations (p<0.05), in fully-adjusted models, Cr:Cyc showed poor to acceptable diagnostic power for identifying low FFMV when using cutpoints of 20th percentile (AUC: 0.577 men; 0.622 women) and T scores of -2 (AUC: 0.596 men; 0.659 women) and -2.5 (AUC: 0.609 men; 0.722 women). In fully-adjusted model, Cr:Cyc showed poor diagnostic power (AUCs: <0.70) for identifying low ALM/BMI or low grip strength irrespective of the cutpoint used. Cr:Cyc may not be a suitable biomarker for identifying low muscle volume or low strength in older adults. This finding, drawn from a large sample size and the use of advanced medical imaging, marks an important contribution to the sarcopenia field.

Different contributions of fat and lean indices to bone strength by sex.

Bone strength depends on both bone density and quality. However, the differences in how body composition indices affect bone strength between men and women remains unclear. This study investigated the associations of various fat and lean indices with bone strength by sex. In this cross-sectional study involving 1,419 participants, bone mineral density (BMD) and body composition were measured using dual-energy X-ray absorptiometry. Bone quality was assessed using the trabecular bone score (TBS). Fat indices included total fat mass, body fat percentage, and waist circumference, while lean indices included appendicular lean mass (ALM) and hand grip strength. All fat indices demonstrated a positive association with BMD and a negative association with the TBS in both men and women. Fat indices were more strongly associated with BMD in women than in men. Furthermore, lean indices contributed more to BMD in men than in women. In women, ALM contributed more to BMD than hand grip strength, whereas in men, hand grip strength had a greater impact on BMD than ALM. Hand grip strength was also positively associated with the TBS in men. Overall, fat indices had a greater influence on BMD in women, while lean indices were more positively associated with bone strength in men. Considering different fat indices, ALM was more strongly associated with BMD in women, whereas hand grip strength played a greater role in men. Thus, maintaining both muscle mass and strength is crucial for preserving bone mass.

Lean Mass Longitudinally Confounds Sedentary Time and Physical Activity With Blood Pressure Progression in 2513 Children.

Randomized controlled trials have reported no effect of moderate-to-vigorous physical activity (MVPA) on reducing blood pressure (BP) in youth, probably due to short trial durations. This study examined the longitudinal effect of sedentary time (ST), light PA (LPA) and MVPA on BP in 11-year-old children followed up for 13 years to determine the confounding and mediating role of body composition. Data included 2513 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort who had data on at least one time-point measure of accelerometer-based movement behaviour across the follow-up and complete BP measures at ages 11, 15 and 24 years. Body composition was assessed with dual-energy x-ray absorptiometry at all time points. Multivariate adjusted generalized linear mixed-effect model and structural equation causal mediation model analyses were conducted. Among 2513 participants (61% female, mean [SD] age 11.72 [0.21] years), ST steadily increased from ~6 h/day in childhood (age 11 years) to ~9 h/day in young adulthood (age 24 years), whereas LPA and MVPA decreased, but BP had an inverted U-shaped increase. In the longitudinal analysis, after full adjustment, a 1-min cumulative ST from ages 11 to 24 years was positively associated with increased systolic BP (0.009 mmHg [95% CI 0.007-0.011]; p < 0.001) and diastolic BP. A 1-min cumulative LPA was inversely associated with systolic BP (-0.007 mmHg [-0.009 to -0.004]; p < 0.001), but not diastolic BP. In isotemporal substitution analyses, longitudinal replacement of 10 min of ST with equal time in LPA during childhood, adolescence and young adulthood cumulatively decreased systolic BP by -2.63 mmHg [95% CI -3.17 to -2.08] (p < 0.0001) and diastolic BP by -1.93 mmHg [95% CI -2.36 to -1.50] (p < 0.0001). Replacing 10 min of ST with 10 min of MVPA had no statistically significant effect due to an absolute confounding effect of lean mass. The association of ST with systolic BP was fully mediated by increased lean mass (93% mediation). Increased total fat mass partially mediated (19%-27%) the inverse associations of cumulative MVPA with cumulative systolic and diastolic BP. Theoretically replacing 10 min/day spent sedentary with 10 min/day of LPA during growth from childhood through young adulthood may lower systolic BP by -3 mmHg and diastolic BP by -2 mmHg. Lean mass seems more significant than fat mass in the relations of ST and PA with BP and should be accounted for in future intervention studies in the paediatric and young adult population.

Genetic Influence of the Brain on Muscle Structure: A Mendelian Randomization Study of Sarcopenia.

The association between brain and sarcopenia has not been clarified. We aim to investigate the causal association between brain structure, function, gene expression and sarcopenia-related traits. All participants were Europeans. GWAS data of Brain Imaging Data Structure (BIDs) was from the UK Biobank. Gene expression in 13 brain regions was acquired from the GTEx Consortium. The sarcopenia-related traits, including appendicular lean mass (ALM), whole body lean mass (WBLM), grip strength and sarcopenia diagnosed by the European Working Group on Sarcopenia in Older People (EWGSOP) or Foundation for the National Institutes of Health (FNIH), were from the IEU website. The inverse variance weighted (IVW), MR Egger, weighted median, weighted mode and Wald ratio methods were used for a two-sample Mendelian randomization (MR) analysis between brain structures and sarcopenia-related traits. The summary-data-based MR (SMR) was used to investigate brain genes causally influencing sarcopenia. We calculated the F-value, odds ratio with 95% CI and p-value. For the sensitivity analysis, the heterogeneity I2 statistic, Cochrane's Q test, Egger's intercept test, MR-PRESSO and the leave-one-out sensitivity test were used. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI), transcription factor interaction prediction and miRNA interaction prediction analysis were used to reveal potential signalling pathways and mechanisms. We included 3144 imaging phenotypes from 8428 participants in BIDs data. One hundred forty-one BIDs were identified to causally influence ALM, 160 BIDs showed significant causal effect on the WBLM, and 86 BIDs showed significant causal effect on grip strength. There were 48 or 32 BIDs causally associated with sarcopenia diagnosed by the EWGSOP or FNIH criteria respectively. After FDR correction, there were 35 BIDs showing causal effect on the ALM, 28 BIDs showing causal effect on the WBLM and 7 BIDs showing causal effect on grip strength (p < 0.05). Twelve to forty-eight genes in different brain regions showed causal effect on all the five sarcopenia-related traits. MMP24-AS1, HLA-DRB6, HLA-DQA2, DDX42, BAG6, NUSAP1, LINC00940, NME1-NME2 and AS3MT in the amygdala region showed detrimental effect on all the five sarcopenia-related traits, whereas HLA-DRB1, HLA-DQB1-AS1 and C6ORF3 showed protective effect (p < 0.05). The gene enrichment analysis indicated these screened genes was mainly enriched in immune-related signalling. We discovered the causal effect of BIDs and brain gene expression on sarcopenia. The positive genes were mainly enriched in immune-related signalling, suggesting an immune-based cross-organ regulation mechanism of brain-muscle axis.

Dietary Total Antioxidant Capacity is Closely Associated with Skeletal Muscle Mass: A Cross-Sectional Study.

Skeletal muscle is of great importance for human activity and quality of life, as its loss contributes greatly to immobilization, especially for aged individuals. An increased dietary intake of antioxidant vitamins may be beneficial for muscle loss because of aging. However, the quantitative relationship between total antioxidation capacity (TAC) of antioxidant vitamins and muscle mass is undetermined. 4009 participants from the National Health and Nutrition Examination Survey (NHANES) were included. Multivariate linear regression analysis was performed with demographic, lifestyle and dietary intake adjustment factors. The dose saturation effect was also determined by a saturation effect analysis. Subgroup analysis were performed forage and sex. In the fully adjusted model, per unit increase of dietary TAC was associated with an increase of 0.018 g/kg appendicular lean mass (95% CI: 0.007-0.029), 0.014 g/kg trunk lean mass (95% CI: 0.004-0.024) and 0.035 g/kg total lean mass (95% CI: 0.014-0.055). TAC was associated with an decrease of 0.004 kg/kg total percent fat (95% CI: -0.006--0.002), 0.005 kg/kg trunk percent fat (95% CI: -0.007--0.002) and 0.003 kg/m2 BMI (95% CI: -0.006--0.001) at the same time. Subgroup analysis indicated that women and adults <50 years may experience the most significant association between TAC and skeletal muscle mass. We revealed a positive correlation between TAC and lean body mass, a negative association between TAC and body fat and BMI. Saturation values were found among people aged 40-59. Age and sex mediate these associations.

Regional Body Composition and Strength, Not Total Body Composition, Are Determinants of Performance in Climbers

Objective: To compare the body composition of Chilean climbers of different performance levels and to determine the relation between the forearm and upper-trunk lean mass and the handgrip and upper-body traction strength, respectively. Methods: A cross-sectional study was carried out on thirty Chilean male adult climbers (26.1 ± 4.9 y.): nine of intermediate level (L1), eleven advanced (L2), and ten elite (L3). Through dual-energy X-Ray absorptiometry (DXA; Lunar Prodigy®), fat mass percentage (FM%), total lean mass (LM), forearm lean mass (FLM), and upper-trunk lean mass (UTLM) were measured. Total muscle mass (TMM) was also estimated. Handgrip strength (HGS) was measured with a Jamar® dynamometer. Maximum upper-body traction strength (UBTS) was evaluated with a standardized movement. The level of climbing was assessed according to IRCRA rules. Results: No differences in FM%, total LM, UTLM, or TMM between the groups were found. Left and assistant FLM were significantly higher in L3 (p = 0.047 and 0.041, respectively). HGS absolute, relative, and adjusted by FLM were not different between groups. FLM was associated with HGS in all segments (p ≤ 0.001). UBTS absolute values, and as adjusted by TMM, were significantly higher in L3 (p = 0.047 and p = 0.049, respectively). Conclusions: Left and non-dominant forearm lean mass were significantly higher in elite climbers. Handgrip strength was not significantly higher in elite climbers; however, the upper-body traction strength was significantly higher in elite climbers, independent of total or regional muscle mass.

Effect of nutrition on the nutritional status in preterm infants with very low birth weight

Introduction. Postnatal growth retardation in premature infants with very low birth weight (VLBW) remains an unresolved problem. There are different approaches regarding the duration of use of breast milk fortifiers during breastfeeding and specialized formulas during formula feeding, as well as the timing of the appointment of complementary feeding. Objective: to evaluate the physical development and component body composition in VLBW infants, depending on nutritional support over the first year of life. Materials and methods. The study included ninety three VLBW premature infants of 2 to 11 months postnatal age (PNA). The main (1st) group included infants (n = 74) who received dietary correction depending on the nutritional status, while no such intervention was performed in the (2nd) comparison group (n = 19). Up to 64 weeks of postconceptional age (PCA), weight, body length, and head circumference were assessed using INTERGROWTH-21st international growth standards, then in the software “WHO Anthro (2009)”. Fat and fat-free (lean) mass were determined using the air plethysmography method (PEA POD, LMi, USA). Results. The analysis of the nutritional status revealed a moderate deviation, not exceeding 1 sigma, decrease in indices (Z-scores) of anthropometric indices in infants of the 1st and 2nd groups by PNA of 2–3 months. Further in infants of the 1st group on the background of prolonged use of fortified nutrition (breast milk fortifier or specialized formulas for preterm infants) and timely introduction of complementary foods, nutritional deficiencies throughout the first year of life in general were not revealed. In the 2nd group of infants without additional correction of nutrition by 4–5 months of age, the development of mild nutritional deficiency was noted by 6–7 months of age. By 6–7 months of age, it turned into moderate nutritional deficiency, which persisted until 8–9 months of age and then turned into mild nutritional deficiency. Analysis of the component body composition showed that during the observation period, the fat-free body mass (FFM) gain in infants in the 1st group was 3.40 kg, in Group 2 infants — 2.2 kg. At the same time, % body fat mass (FM) in infants in groups 1 and 2 had no significant differences (%FM 1 = 19.3 [15.3–22.5], %FM 2 = 19.9 [16.7–24.6], p = 0.769) and did not exceed the values characteristic of preterm infants. Conclusion. A comprehensive assessment of the nutritional status of VLBW infants during the first year of life allowed us to eva­luate the positive impact of long-term use of fortified diets and timely introduction of certain complementary foods. Optimization of nutrition made it possible to prevent the development of nutritional deficiency, which can have a significant positive impact on their further growth, development, and health status.

Abstract 4121348: Impairments in Left Atrioventricular Coupling Underpins Reductions in Skeletal Muscle Mass and Function in Ageing Older Adults

Background: Age-related cardiovascular disease (CVD) may manifest with changes in left ventricular (LV) systolic or left atrial (LA) dysfunction. Alterations in functional performance between the LV and LA chambers characterized by LA-LV coupling may be a sensitive marker representative of impairments in global cardiac performance, compared to either chamber alone. The increasing relevance of skeletal muscle function towards cardiac health in ageing, motivated our current work that investigated associations between skeletal muscle function and LA-LV coupling. Aim : Using advanced cardiac magnetic resonance (CMR) that characterizes cardiac volumetric parameters and strain functions, we determined the association between handgrip strength (HGS) and appendicular lean mass (ALM) with left atrioventricular coupling index (LACI). Methods: Community older adults without CVD underwent simultaneous assessment of HGS by hand dynamometer, height-square adjusted ALM by bio-impedance, and LA phasic function (namely reservoir, conduit, booster strain) as well as LA and LV volumetric parameters by CMR feature tracking. LACI is defined as the ratio of the ratio of LA to LV end-diastolic volumes. We performed linear regression and multivariable logistic regression to examine the relationship between HGS/ALM and LACI. Results: Among 251 study participants (mean age: 71 ± 9.1 years, female 44.7%), 149 (59%) had impaired LACI. HGS was linearly associated with LACI (β=-0.004, p=0.003) and LVEDV (β=1.62, p&lt;0.0001), and ALM was linearly associated with LA volume (β=0.55, p=0.018) and LVEDV (β=3.45, p&lt;0.0001) (Figure.1). Participants with impaired LACI (&gt; 25%) had lower HGS (mean=22.8 ± 7.1 kg vs 26.1 ± 6.4 kg, p= 0.0002), lower ALM (16.4 ± 4.2 kg/m2 vs 17.7 ± 3.8 kg/m2, p=0.014), higher LA volume (36.8 ± 15.2 ml vs 22.0 ± 5.5 ml, p &lt; 0.0001) and lower LV end-diastolic volume (101.0 ± 24.2 ml vs 111.9 ± 27.3 ml, p = 0.0011). The association between impaired LA-LV coupling and lower HGS (β=-0.0647, 95%CI -0.0255, -0.1040, p=0.001) and lower ALM (β=-0.0776, 95%CI -0.0107, -0.1444, p=0.011) persisted after adjusting for age. Conclusion: Reduced HGS and ALM among community-dwelling older adults was associated with impaired LA-LV coupling suggestive of underlying early-stage LA remodelling and impairments in left atrioventricular compliance. Detection of reduced HGS and ALM in community cohorts may prompt early identification of older adults at risk of dysfunctional cardiac aging.

Associations of linear growth with body composition of perinatally HIV-infected African adolescents.

The prevalence of poor linear growth among African children with perinatally acquired HIV remains high. There is concern that poor linear growth may to lead to later total and central fat deposition and associated non-communicable disease risks. We investigated associations between height-for-age Z score (HAZ) and total and regional fat and lean mass measured by dual-energy X-ray absorptiometry, expressed as internal population Z scores, among 839 Zimbabwean and Zambian perinatally HIV-infected male and female adolescents aged 11-19 years. Stunting (HAZ < -2) was present in 37 % of males and 23 % of females. HAZ was strongly positively associated with total, trunk, arm and leg fat mass and lean mass Z scores, in analyses controlling for pubertal stage, socio-economic status and HIV viral load. Associations of linear growth with lean mass were stronger than those with fat outcomes; associations with total and regional fat were similar, indicating no preferential central fat deposition. There was no evidence that age of starting antiretroviral therapy was associated with HAZ or body composition. Non-suppressed HIV viral load was associated with lower lean but not fat mass. The results do not support the hypothesis that poor linear growth or stunting are risk factors for later total or central fat deposition. Rather, increased linear growth primarily benefits lean mass but also promotes fat mass, both consistent with larger body size. Nutritional and/or HIV infection control programmes need to address the high prevalence of stunting among perinatally HIV-infected children in order to mitigate constraints on the accretion of lean and fat mass.

Weight loss and metabolic effects of an ALDH1A1-specific inhibitor, FSI-TN42, in a diet induced mouse model of obesity.

Retinoic acid (RA) participates in weight regulation and energy metabolism. Mice lacking ALDH1A1, one of the major enzymes responsible for RA biosynthesis, are resistant to diet-induced obesity. Previously, we identified FSI-TN42 (N42) as an ALDH1A1-specific inhibitor and reported its pharmacokinetics and pharmacodynamics as well as its efficacy in weight suppression. In the first study, C57BL/6 J male mice were fed a high fat diet for 8 weeks to induce obesity. Mice were then divided into three groups and fed (1) moderate fat diet (MFD), (2) MFD + WIN 18,446 (1 g/kg diet), or (3) MFD + N42 (1 g/kg diet) for 8 weeks. A control group of mice were fed a low-fat diet for the entire period. Mice were weighed weekly and fasting glucose was determined every 4 weeks. Tissues were examined for potential toxicity using histopathology and complete blood counts. In the second study, we examined influences of N42 on energy balance and/or appetite by determining food intake, activity and energy expenditure in mice with obesity treated with MFD or MFD + N42. Lastly, we tested fertility with a mating study. N42 significantly accelerated weight loss compared to MFD alone in mice with obesity by reducing fat mass without decreasing lean mass. N42 did not alter food intake or activity levels. While mice treated with N42 lost significantly more weight, they maintained a similar level of energy expenditure compared to mice fed MFD only. Mice fed N42 preferentially used fat postprandially, especially under thermoneutral or mild cold challenge. N42 did not affect male fertility. N42 promotes weight loss when used with MFD in mice with diet-induced obesity without causing significant organ toxicity or male infertility. Future studies will determine if N42 can be used to promote further weight loss if combined with current weight loss drugs.

Morphological and Performance Biomechanics Profiles of Draft Preparation American-Style Football Players

Background/Objectives: Using advanced methodologies may enhance athlete profiling. This study profiled morphological and laboratory-derived performance biomechanics by position of American-style football players training for the draft. Methods: Fifty-five players were categorized into three groups: Big (e.g., lineman; n = 17), Big–skill (e.g., tight end; n = 11), and Skill (e.g., receiver; n = 27). Body fat (BF%), lean body mass (LBM), and total body mass were measured using a bioelectrical impedance device. Running ground reaction force (GRF) and ground contact time (GCT) were obtained using an instrumented treadmill synchronized with a motion capture system. Dual uniaxial force plates captured countermovement jump height (CMJ-JH), normalized peak power (CMJ-NPP), and reactive strength. Asymmetry was calculated for running force, GCT, and CMJ eccentric and concentric impulse (IMP). MANOVA determined between-group differences, and radar plots for morphological and performance characteristics were created using Z-scores. Results: There was a between-group difference (F(26,80) = 5.70, p &lt; 0.001; Wilk’s Λ = 0.123, partial η2 = 0.649). Fisher’s least squares difference post hoc analyses showed that participants in the Skill group had greater JH, CMJ-NPP, reactive strength, and running GRF values versus Big players but not Big–skill players (p &lt; 0.05). Big athletes had greater BF%, LBM, total body mass, and GCT values than Skill and Big–skill athletes (p &lt; 0.05). Big–skill players had greater GCT asymmetry than Skill and Big players (p &lt; 0.05). Asymmetries in running forces, CMJ eccentric, and concentric IMP were not different (p &gt; 0.05). Morphological and performance biomechanics differences are pronounced between Skill and Big players. Big–skill players possess characteristics from both groups. Laboratory-derived metrics offer precise values of running and jumping force strategies and body composition that can aid sports science researchers and practitioners in refining draft trainee profiles.

Paediatric cancer survivors: lean mass attenuates negative impact of watching television on bone.

To investigate the associations of television (TV) watching time with bone parameters and to examine whether high lean mass attenuates the negative impact of watching TV more than one hour per day on bone parameters. This cross-sectional study comprised 116 young paediatric cancer survivors. Dual-energy X-ray Absorptiometry was used to obtain total body and regional areal bone mineral density (g/cm2), and lean mass (kg) outcomes. Hip Structural Analysis was performed at the narrowest point of the femoral neck. Trabecular Bone Score was obtained in the lumbar spine. TV watching time was obtained using the "Youth Activity Profile" questionnaire. Multiple linear regression models showed negative associations of watching TV more than one hour with bone parameters in peri/post pubertal survivors (β = -0.359 to -0.614, P < 0.001 to 0.047). Those survivors watching TV more than one hour per day and with high lean mass presented higher bone parameter Z-score than those with low lean mass. These findings underline the necessity of identifying strategies that promote musculoskeletal development while reducing TV watching time in young paediatric cancer survivors to maximise bone regeneration. The results indicate that watching television (TV) more than one hour (compared to not watching TV) is negatively associated with bone parameters in peri/post pubertal survivors. Survivors with high lean mass counteract these negative associations of watching TV with bone parameters. It is important to promote musculoskeletal development in this vulnerable population to maximise bone regeneration.

Prevalence of Chronic Liver Disease Based on Ultrasound Shear Wave Elastography in an Adult Asian Indian Population Attending Outpatient Preventive Radiology Clinics in India.

To determine the ultrasound shear wave elastography (SWE)-based prevalence of chronic liver disease in an adult Asian Indian population attending preventive radiology outpatient clinics in India. Liver stiffness measures (LSMs) were ascertained using ultrasound SWE and interquartile range/median (IQR/M) ratio ≤ 30% kilopascal (kPa) units were considered a good quality measurement. Details of modifiable risk factors including comorbidity and personal risk behaviors were collected. The liver was graded based on the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement and Grades 4 and 5 indicated compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH). A multivariate logistic regression model was used to analyze associations with chronic advanced liver disease. The median LSM in the study participants (n = 1145) was 8.0 (IQR 6.5, 9.85) kPa units. 10.65% of the study population had advanced chronic liver disease (cACLD and CSPH) and 22.79% had LSM that was suggestive of cACLD. cACLD and CSPH were significantly associated with comorbidities, personal risk behaviors, and lean and obese body mass indices. Modifiable risk factors were present in 20%-50% of participants with LSM between 7 and 13 kPa. Information on the prevalence of LSM-based cACLD and CSPH and modifiable risk factors in persons with LSM between 7 and 13 kPa will help to design preventative strategies using LSM as an objective imaging biomarker.

Association of dietary inflammatory index with sarcopenia in patients with Metabolic dysfunction-associated fatty liver disease: a cross-sectional study

BackgroundSarcopenia is a common complication of fatty liver, and sarcopenia increases the risk of advanced liver fibrosis in patients with Metabolic dysfunction-associated fatty liver disease (MAFLD). Chronic inflammation is the crucial link between sarcopenia and fatty liver. An anti-inflammatory diet is expected to be an essential measure to prevent sarcopenia in patients with fatty liver, and the dietary inflammatory index (DII) is a crucial tool for assessing the inflammatory potential of diets. However, the relationship between DII and sarcopenia in patients with fatty liver is unclear.ObjectiveThis study investigated the correlation between the dietary inflammatory index (DII) and sarcopenia in patients with Metabolic dysfunction-associated fatty liver disease (MAFLD).MethodsData for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2017–2018, with 917 patients with MAFLD participating in the study. Participants were divided into three groups based on DII tertiles: group T1 (n = 305), group T2 (n = 306), and group T3 (n = 306), and binary logistic regression was used to assess the relationship between DII and sarcopenia with stratified analyses based on the weights recommended by the NHANES and multivariate linear regression was used to evaluate the association of DII with total appendicular lean mass.ResultsAfter adjusting for all confounders, DII was significantly and positively associated with the risk of sarcopenia in women [OR: 1.61, 95% CI: (1.226, 2.06), p &amp;lt; 0.001]. The risk of sarcopenia was higher in the T3 group compared to the T1 group [OR: 4.04, 95% CI: (1.66, 9.84), p = 0.002]. DII was negatively associated with appendicular lean mass adjusted for body mass index in both men and women.ConclusionDII was significantly associated with the risk of sarcopenia in female patients with MAFLD, with higher DII scores related to a higher risk of sarcopenia. Higher DII scores related to a higher risk of sarcopenia in men with significant fibrosis.

Total and appendicular body composition comparisons between near-infrared reactance spectroscopy and dual energy X-ray absorptiometry.

Near-infrared reactance spectroscopy (NIRS) has become increasingly popular in personal and professional settings now that it has been adapted to provide comprehensive body composition assessments. However, whether NIRS agrees with criterion methods remains unknown. Thus, this study aimed to determine the agreement between NIRS and DXA-derived body composition estimates. Ninety-seven participants completed body composition assessments using DXA, and first-generation (NIRSG1), second-generation (NIRSG2), and muscle-specific NIRS (NIRSFIT) devices. On a separate day, a subset of participants (n = 63) performed maximal voluntary contractions (MVC) on a handgrip dynamometer, which were used in conjunction with total appendicular lean mass (ALM) estimates to provide ratios (MVC/total ALM or MVC/ALM of the arms only) depicting muscle quality index (MQI). Fat mass, fat-free mass, body fat %, and ALM, from NIRSG2, but not bone mineral content (BMC), and NIRSFIT demonstrated equivalence (using equivalence tests) with DXA with R2 from 0.83 to 0.97; though BMC revealed concordance coefficients of 0.83 and an R2 of 0.88. MQI using total ALM from NIRS was not equivalent to DXA, but demonstrated low root mean squared error (0.08 kg/kg) and 95% limits of agreement (±0.21 kg/kg). Indices of visceral adipose tissue (iVAT) from NIRSG1 and NIRSG2 were significantly different (p < 0.001), but were both significantly associated with DXA VAT (NIRSG1 R2: 0.53; NIRSG2 R2: 0.62; both p < 0.001). NIRS appears to demonstrate acceptable agreement with DXA and continual improvements could make NIRS a viable alternative for comprehensive body composition assessments.

Trajectory Analysis of the Four-Year Changes in Body Composition and Bone Mineral Characteristics Among Highly Competitive Male University Long-Distance Runners.

This study examined long-term changes in body composition and bone mineral characteristics among male long-distance runners from a high-profile university team, focusing on concerns about impaired musculoskeletal development due to extreme leanness and weight management practices in this population. Trajectory analyses were performed using multilevel modeling of 608 dual-energy x-ray absorptiometry datasets from 109 runners (mean age, height, and weight of 18.0 years, 171.4 cm, and 56.8 kg at baseline, respectively) collected biannually over 4 years. Linear increases in total and regional lean mass (LM) were observed on average, with the increase in leg LM being double that of arm LM (0.07 vs. 0.03 kg per occasion, respectively). Similarly, total bone mineral density (BMD) and content (BMC) exhibited linear growth on average, with BMD accrual being greater in the legs than in the arms (0.004 vs. 0.001 g/cm2 per occasion, respectively). However, rib BMD and BMC were predicted to decrease. Individually predicted growth rates in total LM were significantly associated with those in total BMD (r = 0.347, p < 0.001) and BMC (r = 0.424, p < 0.001). These results indicate site-specific musculoskeletal adaptations to intensive long-distance running training. Moreover, a random slope model accurately captured the trajectories of most dependent variables, highlighting the heterogeneity of training responses. The predictive models developed in this study offer practical strategies for identifying runners at risk of suboptimal physical development, thereby facilitating the development of personalized conditioning programs.