Lean Mass Research Articles

Dry lean mass and fecal calprotectin in rheumatoid arthritis, preliminary results showing association with disease activity and functional status

Dry lean mass and fecal calprotectin in rheumatoid arthritis, preliminary results showing association with disease activity and functional status

Lean metabolic dysfunction-associated steatotic disease is reversed by betulinic acid, a therapeutic triterpene from birch bark

The prevalence of metabolic dysfunction-associated steatotic disease (MASLD) in lean individuals has continued to increase. Despite the benefits of betulinic acid in obesity, its role in lean MASLD has not been verified. We investigated whether betulinic acid recovered lean MASLD by rescuing lipid homeostasis in vivo. Lean MASLD disease mice model was established using atherogenic diets on C57BL/6 male mice. Betulinic acid (5, 15, and 25 mg/kg bw) or positive control was provided ad libitum for 12 weeks. Betulinic acid reduced body adiposity (p<0.01) without affecting lean mass. Betulinic acid improved hepatic lipid accumulation (p<0.01). Blood lipid profiles, including triglyceride, total cholesterol, LDL-cholesterol, and non-esterified fatty acids (p<0.001 and p<0.05), were decreased by betulinic acid. RNA transcriptomes and immunoblotting revealed that betulinic acid markedly reduced hepatic de novo lipogenesis by inhibiting Srebp1/Acc/Fas (p<0.05). Betulinic acid increased fatty acid utilization (p<0.05) in skeletal muscle by stimulating Ampk/Acc1/Cpt1. These findings imply that betulinic acid is a potent bioactive compound that prevents lean MASLD and dyslipidemia.

Sex differences in upper and lower strength and their association with body composition among university students.

Sex strongly influences physical performance throughout adolescence, and excess fat mass is associated with several health and performance impairments. This study aimed to evaluate whether variations in strength between men and women dependent on lean mass and body fat content. This cross-sectional, quasi-experimental, non-probabilistic study involved 44 university students (22 men and 22 women, aged 19-29). Handgrip strength (HGS) was measured using an adjustable handgrip dynamometer, body composition was assessed using bioimpedance, and countermovement jumps (CMJ) were measured using a force platform. Data were analyzed using ANOVA to compare HGS and CMJ based on body mass, and the Pearson correlation coefficient was applied to examine the relationships between grip strength, body composition, and jump test performance. Strength is significantly higher in men compared to women, as is countermovement jump. The strength of women corresponded to over 50% of that of men, whereas the quantity of lean mass in women corresponded to 55% of that of men. We found a significant relationship between strength and lean mass. This study supports the idea that both upper- and lower-body strengths are strongly influenced by lean mass, thereby contributing to sex differences. The primary factor in body composition that explains the disparities in HGS and CMJ between sexes is the proportion of fat mass to lean mass. Finally, the sex disparities observed between body composition and strength depend on lean mass content.

Population Pharmacokinetic Modeling of Cefepime, Meropenem, and Piperacillin-Tazobactam in Patients with Cystic Fibrosis.

Patients with cystic fibrosis (CF) experience recurrent bacterial pulmonary exacerbations. Management of these infections is increasingly challenging due to decreased antimicrobial susceptibility to beta-lactam antibiotics. The pharmacokinetics of these agents are inadequately characterized in patients with CF. One hundred fifty-five pediatric and adult participants with CF receiving cefepime (n=82), meropenem (n=42), or piperacillin-tazobactam (n=31) were enrolled. Opportunistic blood samples were obtained during hospitalization. Population PK analysis was conducted using nonlinear mixed-effects modeling. Clinical and demographic characteristics were evaluated as potential covariates. Monte Carlo simulations were performed to evaluate probability of target attainment (PTA) for different dosing regimens. Estimated creatinine clearance, and total or lean body weight, affected the pharmacokinetics of cefepime and meropenem. No covariates were identified for piperacillin and tazobactam. In the cefepime group, a 3-h infusion achieved higher PTA than a 0.5-h infusion for all participants. Estimated breakpoints (the respective minimum inhibitory concentration (MIC) up to which ≥90% of patients are predicted to reach a PK/PD target) were two- to four-fold higher in pediatric participants receiving a 3-h vs. 0.5-h infusion. In the meropenem group, increased creatinine clearance led to reduced PTA. In the piperacillin-tazobactam group, total daily dose and mode of administration were principal drivers of PTA. Standard dosing regimens fail to achieve specific MIC targets in patients with CF. Therefore, clinicians should incorporate local antibiograms and PK models to determine optimal dosing. Further PK optimization to account for interindividual differences could be achieved by real-time beta-lactam therapeutic drug monitoring.

Animal models of haploinsufficiency revealed the isoform-specific role of GSK-3 in HFD-induced obesity and glucose intolerance.

Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase with two isoforms (α and β) is implicated in the pathogenesis of type 2 diabetes mellitus (T2D). Recently, we reported the isoform-specific role of GSK-3 in T2D using homozygous GSK-3α/β knockout mice. Although the homozygous inhibition models are idealistic in a preclinical setting, they do not mimic the inhibition seen with pharmacological agents. Hence, in this study, we sought to investigate the dose-response effect of GSK-3α/β inhibition in the pathogenesis of obesity-induced T2D. Specifically, to gain insight into the dose-response effect of GSK-3 isoforms in T2D, we generated tamoxifen-inducible global GSK-3α/β heterozygous mice. GSK-3α/β heterozygous and control mice were fed a high-fat diet (HFD) for 16 wk. At baseline, the body weight and glucose tolerance of GSK-3α heterozygous and controls were comparable. In contrast, at baseline, a modest but significantly higher body weight (higher lean mass) was seen in GSK-3β heterozygous compared with controls. Post-HFD, GSK-3α heterozygous and controls displayed a comparable phenotype. However, GSK-3β heterozygous were significantly protected against obesity-induced glucose intolerance. Interestingly, the improved glucose tolerance in GSK-3β heterozygous animals was dampened with chronic HFD-feeding, likely due to significantly higher fat mass and lower lean mass in the GSK-3β animals. These findings suggest that GSK-3β is the dominant isoform in glucose metabolism. However, to avail the metabolic benefits of GSK-3β inhibition, it is critical to maintain a healthy weight.NEW & NOTEWORTHY The precise isoform-specific role of GSK-3 in obesity-induced glucose intolerance is unclear. To overcome the limitations of pharmacological GSK-3 inhibitors (not isoform-specific) and tissue-specific genetic models, in the present study, we created novel inducible heterozygous mouse models of GSK-3 inhibition that allowed us to delete the gene globally in an isoform-specific and temporal manner to determine the isoform-specific role of GSK-3 in obesity-induced glucose intolerance.

The natural course of bone mineral density in transgender youth before medical treatment; a cross sectional study.

Bone mineral density (BMD) Z-scores decrease during puberty suppression in transgender youth. Assessment of treatment impact has been based on the assumption that without intervention, BMD Z-scores remain stable. However, the natural course of BMD in this population is unknown. Retrospective cross-sectional study. Dual-energy X-ray absorptiometry scans prior to medical intervention were included from 333 individuals assigned male at birth (AMAB) and 556 individuals assigned female at birth (AFAB) aged 12-25 years. The relationship between age and BMD Z-scores of sex assigned at birth was analysed for the lumbar spine (LS), total hip (TH), femoral neck (FN), and total-body-less-head (TBLH), adjusted for height SDS, height-adjusted lean mass Z-score, and whole body percentage fat Z-score. In individuals AMAB, the BMD Z-score was negatively associated with age between 12 and 22 years: LS -0.13/year (95% confidence interval, CI -0.17; -0.10); TH -0.05/year (95% CI -0.08; -0.02); FN -0.06/year (95% CI -0.10; -0.03); and TBLH -0.12/year (95% CI -0.15; -0.09). Adjusting for height-adjusted lean mass Z-score attenuated the association at the LS and TBLH and eliminated the association at the TH and FN. BMD Z-scores and age were not associated between 22 and 25 years. In individuals AFAB, BMD Z-scores were only associated with age at the TBLH (-0.08/year, 95% CI -0.12; -0.04) between age 12 and 20 years. In individuals AMAB aged 12-22 years prior to any treatment, BMD Z-scores were inversely correlated with age. This could imply that BMD increases less in individuals AMAB than in the general population, and that changes in Z-score during puberty suppression and subsequent hormone supplementation are not necessarily due to treatment, but possibly related to lifestyle factors.

Predictors Of Handgrip Strength And Its Relationship To Physical Performance In Older Irish Adults

Abstract Background Handgrip strength declines with age and predicts poor physical performance and increased risk of falls and mortality. However, the strength of the relationship between handgrip strength and other physical measures is less well studied. We aimed to explore the predictors of handgrip strength in older Irish adults and its relationship to the Timed and Up and Go (TUG). Methods Study participants were from a longitudinal cohort of Irish adults aged &amp;gt;60 years; Trinity Ulster University Department of Agriculture (TUDA) study. Participants on current or long-term steroids, a history of stroke and with MMSE &amp;lt;24 were excluded. Handgrip strength was assessed with a dynamometer and defined as &amp;lt;27 kg for males and &amp;lt;16 kg for females. Abnormal performance in the TUG was defined as &amp;gt;12 seconds. Predictors of impaired handgrip were explored in multivariate logistic regression. Results There were 748 participants (68.9% female, mean age 70.2 years), of whom 33.4% had abnormal handgrip strength, which was more common in female’s vs males (39.4 vs 20.2%, p&amp;lt;0.001). Both abnormal handgrip strength and TUG was present in 13.6%. Normal handgrip strength had a negative predictive value of 76.0% for ruling out poor TUG, while abnormal handgrip had a positive predictive value of 62% for poor TUG. Predictors of impaired handgrip strength were older age (P&amp;lt;0.0001), female sex (p&amp;lt;0.0001), lower protein intake (P=0.024) and higher waist hip ratio (p=0.014). Conclusion Handgrip strength had a modest correlation with TUG A significant proportion had abnormal TUG but normal handgrip. Changes in lower limb muscle strength (affecting TUG) precede muscle loss in the upper limb. Higher protein intake predicted greater grip strength and supports the recommendation to maintain adequate intakes to prevent sarcopenia. Greater waist hip ratio is associated with reduced lean muscle mass which may explain the negative relationship we identified with handgrip strength.

Association of Depression With Handgrip Strength and Muscle Mass in Young and Middle-Aged American Adults From NHANES 2011-2014: A Cross-Sectional Study.

To investigate relationship between depression and handgrip strength (HGS) and appendicular lean mass (ALM) in Young and middle-aged adults. Cross-sectional study. Data from participants aged 20-59 from the 2011-2014 National Health and Nutrition Examination Survey. In a study of 4927 middle-aged Americans, 2564 (52.30%) were men and 2363 (47.7%) were women, with an average age of 38.57 ± 11.72. Among this group, 716 individuals (14.53%) experienced mild depression, while 385 individuals (7.81%) suffered from moderate to severe depression. Data of HGS and ALM were collected by handgrip test, and whole-body dual-energy X-ray absorptiometry scans. Depression was assessed using the Patient Health Questionnaire-9. Linear and logistic regression, restricted cubic spline regression analyses and subgroup analysis were conducted to evaluate the association. Following multivariate logistic regression analysis, the study showed that a 1-point increase in the depression score was associated with a 4% increase in the probability of reduced grip strength for both males (95% CI: 1.01-1.07) and females (95% CI: 1.01-1.06). Additionally, for males, there was a 5% increase in the likelihood of decreased muscle mass (95% CI: 1.01-1.09), whereas the decline in muscle mass for females did not exhibit statistical significance. Subgroup analysis indicated that the inverse relationship between depression and grip strength, along with the negative association between depression and muscle mass among males, remained consistent in the 40-59 age range. This research revealed an inverse relationship between depression and grip strength in middle-aged and young individuals, and a negative association between depression and ALM was only noted in males. Early intervention could be beneficial from age 40.

Effect of Oral Zinc Supplementation on Phase Angle and Bioelectrical Impedance Vector Analysis in Duchenne Muscular Dystrophy: A Non-Randomized Clinical Trial.

Zinc plays a crucial role in cell structure and functionality. Neurodegenerative Duchenne muscular dystrophy (DMD) alters muscle membrane structure, leading to a loss of muscle mass and strength. The objective of this study was to evaluate the changes in phase angle (PA) and bioelectrical impedance vector analysis (BIVA) results in patients with DMD after oral zinc supplementation. This clinical trial included 33 boys aged 5.6 to 24.5 years diagnosed with DMD. They were divided into three groups according to age (G1, G2, and G3) and supplemented with oral zinc. The mean serum zinc concentration was 74 μg/dL, and 29% of patients had concentrations below the reference value. The baseline values (mean (standard deviation)) of the bioelectrical impedance parameters PA, resistance (R), and reactance (Xc) were 2.59° (0.84°), 924.36 (212.31) Ω, and 39.64 (8.41) Ω, respectively. An increase in R and a decrease in PA and lean mass proportional to age were observed, along with a negative correlation (r = -0.614; p < 0.001) between age and PA. The average cell mass in G1 was greater than that in G3 (p = 0.012). There were no significant differences in serum zinc levels or bioelectrical impedance parameters before and after zinc supplementation. We conclude that this population is at risk of zinc deficiency and the proposed dosage of zinc supplementation was not sufficient to alter serum zinc levels, PA and BIVA results.

Differential impacts of body composition on oxygen kinetics and exercise tolerance of HFrEF and HFpEF patients

This study aims to (1) compare the kinetics of pulmonary oxygen uptake (VO2p), skeletal muscle deoxygenation ([HHb]), and microvascular O2 delivery (QO2mv) between heart failure (HF) patients with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF), and (2) explore the correlation between body composition, kinetic parameters, and exercise performance. Twenty-one patients (10 HFpEF and 11 HFrEF) underwent cardiopulmonary exercise testing to assess VO2 kinetics, with near-infrared spectroscopy (NIRS) employed to measure [HHb]. Microvascular O2 delivery (QO2mv) was calculated using the Fick principle. Dual-energy X-ray absorptiometry (DEXA) was performed to evaluate body composition. HFrEF patients exhibited significantly slower VO2 kinetics (time constant [t]: 63 ± 10.8 s vs. 45.4 ± 7.9 s; P < 0.05) and quicker [HHb] response (t: 12.4 ± 9.9 s vs. 25 ± 11.6 s; P < 0.05). Microvascular O2 delivery (QO2mv) was higher in HFrEF patients (3.6 ± 1.2 vs. 1.7 ± 0.8; P < 0.05), who also experienced shorter time to exercise intolerance (281.6 ± 84 s vs. 405.3 ± 96 s; P < 0.05). Correlation analyses revealed a significant negative relationship between time to exercise and both QO2mv (ρ= -0.51; P < 0.05) and VO2 kinetics (ρ= -0.63). Body adiposity was negatively correlated with [HHb] amplitude (ρ= -0.78) and peak VO2 (ρ= -0.54), while a positive correlation was observed between lean muscle percentage, [HHb] amplitude, and tau (ρ= 0.74 and 0.57; P < 0.05), respectively. HFrEF patients demonstrate more severely impaired VO2p kinetics, skeletal muscle deoxygenation, and microvascular O2 delivery compared to HFpEF patients, indicating compromised peripheral function. Additionally, increased adiposity and reduced lean mass are linked to decreased oxygen diffusion capacity and impaired oxygen uptake kinetics in HFrEF patients.

Aerobic capacity and respiratory indices of junior cross-country skiers and biathletes during incremental exercise testing.

The present study compared the isocapnic buffering phase (ICB), hypocapnic hyperventilation phase, ventilatory threshold (VT), respiratory compensation point (RCP), and maximum oxygen uptake (VO2max) among biathlon and cross-country ski athletes during an incremental exercise test. 37 male and 33 female Turkish National Team athletes volunteered to participate in the research. Body fat percentage, lean mass, and fat mass values of athletes were measured using the bioelectrical impedance analysis method, and oxygen consumption (VO2) was measured with a portable cardiopulmonary exercise test system with a ramp protocol on the treadmill. In VT, RCP, and VO2max phases, male athletes had higher VO2 and speed values than female athletes (p < 0.05). In contrast, they had similar values across different categories of sports (biathlon and cross-country skiing) (p > 0.05). Additionally, XC skiers and males had higher absolute (Abs) VO2 and mass-normalized (Rel) VO2 values than biathletes and females in exhaustion times and ICBs (p < 0.05). In contrast, they had similar Abs VO2 and Rel VO2 values in hypocapnic hyperventilation phases (p > 0.05). In addition, XC skiers and males had higher absolute (Abs) VO2 and relative (Rel) VO2 values than biathletes and females in exhaustion times and ICBs (p < 0.05). In contrast, they had similar Abs VO2 and Rel VO2 values in hypocapnic hyperventilation phases (p > 0.05). These results indicate significant differences in physiological profiles between male and female athletes and between XC skiers and biathletes.

Socioeconomic Status and Obesity.

Obesity is a pervasive public health problem that causes debilitating complications across the life course. One opportunity for preventing the onset of obesity is to focus on its social determinants. Socioeconomic status (SES), which includes factors such as income, educational attainment, occupational prestige, and access to resources, is a key determinant of obesity. In this scoping mini-review, we summarized review articles and meta-analyses of the SES-obesity association. From the 1980s to the present, cross-sectional studies have demonstrated a persistent socioeconomic gradient in obesity in which the association is negative in developed countries and positive in developing countries. Longitudinal studies have revealed the bidirectionality of the SES-obesity association; some studies demonstrate that socioeconomic adversity precedes the onset of obesity, while others provide evidence of reverse causality. While earlier studies relied on anthropometric assessments of weight and height to define obesity, the use of modern technologies like dual-energy x-ray absorptiometry and bioelectrical impedance have demonstrated that the socioeconomic gradient in obesity is robust across multiple indicators of body composition, including direct measures of lean and fat mass. More recently, examination of mediators and moderators of the SES-obesity association have highlighted causal pathways and potential intervention targets, with a focus on health behaviors, environmental conditions, psychological factors, and biological processes. We describe current gaps in knowledge and propose opportunities for future innovation to reduce the burden of obesity and related socioeconomic disparities.

Among people on osteoporosis medication, loss of appendicular or total body lean mass is an independent risk factor for hip and major osteoporotic fractures.

Sarcopenia increases fracture risk. If the risk persists after starting osteoporosis medication, patients may need to be encouraged to pursue strategies to prevent loss of lean mass. To estimate the effects of loss in appendicular lean mass (ALM) or total body lean mass (TBLM) on subsequent fracture risk and effect modification with anti-osteoporosis medication use. We conducted a registry-based cohort study linked to population-based data. We identified individuals ≥ 40years of age with two DXA assessments ≥ 1year apart and minimum 0.5years of observation. ALM and TBLM were estimated from weight, sex, and percent fat from DXA (R2 = 0.91 and 0.84 vs total body DXA, respectively). We report hazard ratios (HR) from Cox regression models estimating time to first incident major osteoporotic fracture (MOF) and hip fracture, adjusted for fracture risk; osteoporosis medication was included as an interaction term and used to stratify analyses. We included 21,249 individuals (mean 67 [SD 10] years, 95% female, 37% on osteoporosis medication). The mean follow-up was 7years (SD 4). A total of 1868 and 548 people had incident MOF and hip fracture, respectively. People with prior ALM loss (HR per SD 1.09, 95% CI 1.04-1.15) or TBLM loss (HR per SD 1.09, 95% CI 1.42-1.14) had a higher risk of MOF. Hip fracture risk was greater in people with prior ALM loss (HR per SD 1.22, 95% CI 1.12-1.33) and TBLM loss (HR per SD 1.26, 95% CI 1.16-1.38). There were no interactions with anti-osteoporosis medication use (all p > 0.3). When restricted to people on anti-osteoporosis medication, each SD in ALM or TBLM loss was associated with 8-9% increased MOF risk and 18-23% increased hip fracture risk. Loss of lean mass is associated with increased fracture risk among individuals on anti-osteoporosis medication. Patients should be encouraged to pursue strategies to prevent sarcopenia.

The dose of remimazolam combined with sufentanil for the induction of general anesthesia in obese patients undergoing bariatric surgery: an up-and-down sequential allocation trial.

Background and purpose: Remimazolam is a newly developed benzodiazepine drug with water-soluble, esterase degradation, and ultra-short-acting properties. The dose for general anesthesia induction in obese patients was not known. This study aimed to determine the optimal dose of remimazolam in combination with sufentanil for the induction of general anesthesia in obese patients. Methods: It was a prospective observational study. We recruited 46 patients scheduled for bariatric surgery from October 2022 to December 2023. One patient refused to provide informed consent, and six patients were receiving psychotropic medication. Thirty-nine patients were enrolled. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale was used to assess the patient's response. The dose of sufentanil was 0.5 µg/kg (lean body weight [LBW]). The initial dose of remimazolam was 0.3mg/kg (LBW). The dose of remimazolam was modified using the up-and-down allocation technique. Successful sedation (negative group) was characterized by achieving a MOAA/S score ≤ 1 within 3min of commencing remimazolam infusion. If negative, the next patient received a low-level dose at a ratio of 0.9. Failed sedation (positive group) was defined as a MOAA/S score of >1 within 3min of commencing remimazolam infusion. The patients in the positive group received propofol 0.5mg/kg as a remedial measure, and the next dose was increased to a higher level. The primary outcome was to determine the half-effective dose (ED50) and 95% effective dose (ED95) of remimazolam in combination with sufentanil 0.5 µg/kg for induction in obese patients. The secondary outcome was to determine the occurrence of adverse effects such as hypotension, hypertension, and intraoperative awareness. Results: The ED50 and ED95 values of remimazolam (LBW) combined with sufentanil (0.5 µg/kg) (LBW) were 0.115mg/kg (95% CI: 0.072-0.137) and 0.179mg/kg (95% CI: 0.150-0.434), respectively, and the time of loss of consciousness in the negative group was 120.13 ± 25.03s. The cardiovascular system was stable during the induction period. The incidence of post operative nausea and vomiting (PONV) was 38.5% in 39 patients. Respiratory depression, allergic reaction, intraoperative awareness, and delayed emergence were not observed in any patient. Conclusion: Remimazolam combined with sufentanil (0.5 µg/kg) (LBW) can be effectively used for general anesthesia induction in obese patients. The ED50 and ED95 values of remimazolam (LBW) were 0.115mg/kg and 0.179mg/kg, respectively. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2200065602.

Contributions to forearm desaturation during transient ischemia in healthy adult males and females across the lifespan.

This study investigated skeletal muscle tissue oxygenation (StO2) desaturation in males and females across the adult lifespan. One-hundred-two individuals (51 females) of 41 young, 34 midlife, and 27 older adults completed a vascular occlusion test with near-infrared spectroscopy (NIRS+VOT). This included five minutes of arterial occlusion, inducing transient ischemia in the forearm flexor muscle group while recording StO2. The magnitude of desaturation (StO2mag) was quantified as the difference between baseline StO2 and the minimum StO2 value observed during ischemia. The rate of desaturation was also examined. Forearm adipose tissue thickness (ATT), forearm lean mass, and handgrip muscular strength were measured. A p ≤ 0.05 was considered significant. Two-way between factor ANOVAs indicated that males exhibited significantly (p<0.001) less ATT than females (collapsed across age) and that forearm lean mass (p<0.001) and muscular strength (p<0.001) decreased across the lifespan independent of sex. Bivariate analyses revealed significant (p<0.05) associations for sex, age, ATT, forearm lean mass, and muscular strength with the desaturation metrics. The ATT values demonstrated the strongest relations with StO2mag and desaturation rate (r = -0.620 and 0.618). Using a model comparison approach, ATT plus age offered the best predictive power for StO2mag and desaturation rate (R2 = 0.456 and 0.438) such that the inclusion of sex did not improve the models. These findings suggested differences in desaturation were primarily explained by variations in ATT and, to a lesser extent, age, but biological sex had no meaningful effect. Future studies must determine what other factors influence desaturation during ischemia.

The Oldest of Old Male C57B/6J Mice Are Protected from Sarcopenic Obesity: The Possible Role of Skeletal Muscle Protein Kinase B Expression

The impact of aging on body composition and glucose metabolism is not well established in C57BL/6J mice, despite being a common pre-clinical model for aging and metabolic research. The purpose of this study was to examine the effect of advancing age on body composition, in vivo glucose metabolism, and skeletal muscle AKT expression in young (Y: 4 months old, n = 7), old (O: 17–18 months old, n = 10), and very old (VO: 26–27 month old, n = 9) male C57BL/6J mice. Body composition analysis, assessed by nuclear magnetic resonance, demonstrated O mice had a significantly greater fat mass and body fat percentage when compared to Y and VO mice. Furthermore, VO mice had a significantly greater lean body mass than both O and Y mice. We also found that the VO mice had greater AKT protein levels in skeletal muscle compared to O mice, an observation that explains a portion of the increased lean body mass in VO mice. During glucose tolerance (GT) testing, blood glucose values were significantly lower in the VO mice when compared to the Y and O mice. No age-related differences were observed in insulin tolerance (IT). We also assessed the glucose response to AMPK activation by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). The change in blood glucose following AICAR administration was significantly reduced in VO mice compared to Y and AG mice. Our findings indicate that lean body mass and AKT2 protein expression in muscle are significantly increased in VO mice compared to O mice. The increase in AKT2 likely plays a role in the greater lean body mass observed in the oldest of old mice. Finally, despite the increased GT, VO mice appear to be resistant to AMPK-mediated glucose uptake.

Effect of Nuts Combined with Energy Restriction on the Obesity Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Obesity is a multifactorial disease that is difficult to control worldwide. Although nuts are recognized health foods, the application of food in obesity management is unclear. We systematically reviewed the literature and performed a meta-analysis to evaluate if nut consumption favors people on energy restriction (ER) dietary interventions. Four databases were used to search for eligible articles in May 2024. This review was conducted according to the PRISMA guide, and the bias risk of papers was evaluated. For the meta-analysis, we extracted the endpoint values of the group's variables and estimated the effect sizes by the random-effects model. Sixteen and ten articles were included in the systematic review and meta-analysis, respectively. Almonds were evaluated in the majority of studies (n = 6). The consumption of nuts (28 to 84 g/d, 4 to 72 months) included in ER (-250 to 1000 kcal/d) did not differently affect anthropometry (weight loss, BMI, waist and hip circumferences), body composition (fat mass, fat-free mass, or lean mass), markers of glucose (glycemia and insulinemia), lipid metabolism (total cholesterol, HDL-c, LDL-c, LDL-c/HDL-c, or triglycerides), and systolic and diastolic blood pressure. In most analyses, stratifying studies by type of nut or intervention time did not present different results in the meta-analysis. As there are few studies, in addition to great methodological variability, more high-quality trials are needed to confirm these results. The PROSPERO registration number is CRD42023444878.

The effect of active vitamin D supplementation on body weight and composition: A meta-analysis of individual participant data

Background & aimsObesity is associated with vitamin D (VitD) deficiency. However, previous studies showed mixed effects of VitD (25-hydroxyVitD/calcidiol) supplementation on body weight. The biological actions of VitD require the hydroxylation of inactive VitD into active VitD (1.25-dihydroxyVitD/calcitriol). This step is highly regulated; therefore, supplementing with inactive VitD might not be sufficient to overcome the potential adverse health effects of VitD deficiency. The objective of this study was to conduct a systematic review and individual participant data (IPD) meta-analysis of data acquired from randomised placebo-controlled calcitriol trials (RCTs) to determine the effects of calcitriol on body weight and weight-related parameters. MethodsStudies were identified from MEDLINE, EMBASE, and CENTRAL databases up to January 27, 2024, and excluded those involving dialysis or cancer patients. We obtained IPD from eligible trials and assessed bias using the Cochrane Collaboration risk-of-bias tool and methodological quality using the Heyland Methodological Quality Score. The study was prospectively registered with PROSPERO (CRD42017076202). ResultsAlthough none of the studies reported information regarding our primary objective, we obtained IPD for 411 patients, with 206 randomised to receive calcitriol and 205 to placebo. This dataset enabled us to conduct an IPD meta-analysis with 17,084 person-months of follow-up (median: 11 months). Meta-analysis showed that calcitriol does not alter body weight, BMI, waist circumference, fat mass or lean body mass compared to placebo. Adjusting for age and sex did not alter the outcomes. ConclusionsIn conclusion, this systematic review and IPD meta-analysis indicate that calcitriol does not affect body weight in normal-weight postmenopausal women and lean patients with type 1 diabetes nor in people suffering from obesity, type 2 diabetes and chronic kidney disease. Whether calcitriol lowers body weight in VitD-sufficient people with obesity remains to be elucidated.

Interleukin-15 and high-intensity exercise: relationship with inflammation, body composition and fitness in cancer survivors.

Pre-clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth. These anti-oncogenic effects of exercise were associated with the exercise-mediated release of myokines such as interleukin (IL)-15. However, no study has quantified the acute IL-15 response in human cancer survivors, and whether physiological adaptations to exercise training (i.e. body composition and cardiorespiratory fitness) influence this response. In the present study breast, prostate and colorectal cancer survivors (n=14) completed a single bout of high-intensity interval exercise (HIIE) [4×4min at 85-95% heart rate (HR) peak, 3min at 50-70% HR peak] before and after 7months of three times weekly high-intensity interval training (HIIT) on a cycle ergometer. At each time point venous blood was sampled before and immediately after HIIE to assess the acute myokine (IL-15, IL-6, IL-10, IL-1ra) responses. Markers of inflammation, cardiorespiratory fitness and measures of body composition were obtained at baseline and 7months. An acute bout of HIIE resulted in a significant increase in IL-15 concentrations (pre-intervention: 113%; P=0.013, post-intervention: 102%; P=0.005). Post-exercise IL-15 concentrations were associated with all other post-exercise myokine concentrations, lean mass (P=0.031), visceral adipose tissue (P=0.039) and absolute peak (P=0.032). There was no significant effect of 7months of HIIT on pre- or post-HIIE IL-15 concentrations (P>0.05). This study demonstrates HIIE is a sufficient stimulus to increase circulating IL-15 and other myokines including IL-6, IL-10 and IL-1ra which may be clinically relevant in the anti-oncogenic effect of exercise and repetitive exposure to these effects may contribute to the positive relationship between exercise and cancer recurrence. KEY POINTS: Exercise has been demonstrated to reduce the risk of cancer recurrence. Pre-clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth, mediated by exercise-induced myokines (IL-6 and IL-15). High-intensity interval exercise significantly increased myokines associated with the anti-oncogenic effect of exercise and the magnitude of response was associated with lean mass, but training did not appear to influence this response. Given IL-15 has been implicated in the anti-oncogenic effect of exercise and is being explored as an immunotherapy agent, high-intensity interval exercise may improve outcomes for people living beyond cancer through IL-15-mediated pathways. Interventions that increase lean mass may also enhance this response.

IGF-1 and insulin receptors in LepRb neurons jointly regulate body growth, bone mass, reproduction, and metabolism.

Leptin receptor (LepRb)-expressing neurons are known to link body growth and reproduction, but whether these functions are mediated via insulin-like growth factor 1 receptor (IGF1R) signaling is unknown. IGF-1 and insulin can bind to each other's receptors, permitting IGF-1 signaling in the absence of IGF1R. Therefore, we created mice lacking IGF1R exclusively in LepRb neurons (IGF1RLepRb mice) and simultaneously lacking IGF1R and insulin receptor (IR) in LepRb neurons (IGF1R/IRLepRb mice) and then characterized their body growth, bone morphology, reproductive and metabolic functions. We found that IGF1R and IR in LepRb neurons were required for normal timing of pubertal onset, while IGF1R in LepRb neurons played a predominant role in regulating adult fertility and exerted protective effects against reproductive aging. Accompanying these reproductive deficits, IGF1RLepRb mice and IGF1R/IRLepRb mice had transient growth retardation. Notably, IGF1R in LepRb neurons was indispensable for normal trabecular and cortical bone mass accrual in both sexes. These findings suggest that IGF1R in LepRb neurons is involved in the interaction among body growth, bone development, and reproduction. Though only mild changes in body weight were detected, simultaneous deletion of IGF1R and IR in LepRb neurons caused dramatically increased fat mass composition, decreased lean mass composition, lower energy expenditure, and locomotor activity in both sexes. Male IGF1R/IRLepRb mice exhibited impaired insulin sensitivity. These findings suggest that IGF1R and IR in LepRb neurons jointly regulated body composition, energy balance, and glucose homeostasis. Taken together, our studies identified the sex-dependent complex roles of IGF1R and IR in LepRb neurons in regulating body growth, reproduction, and metabolism.