Significant Increase In Muscle Mass Research Articles

Medium-chain triglycerides (8:0 and 10:0) increase muscle mass and function in frail older adults: a combined data analysis of clinical trials.

Three clinical trials have examined the chronic effects of medium-chain triglycerides (MCTs) on muscle mass and function in frail older adults (mean age 85 years old). However, significant increases in muscle mass and some muscle function relative to long-chain triglycerides (LCTs) have yet to be shown, possibly due to the small number of participants in each trial. We re-analyzed these previous clinical trials to clarify whether MCT supplementation can increase muscle mass and function. After adding post hoc tests to the original report, we compared changes in measurement between the MCT and LCT groups in the first 2 trials and conducted a combined data analysis. In a combined data analysis, changes from baseline in measurements at the 3 months intervention in the MCTs- and LCTs-containing groups were assessed by analysis of covariance adjusted for baseline values of each measurement, age, sex, BMI, allocation to trial, habitual intakes in energy, protein, leucine, octanoic acid, decanoic acid, and vitamin D during the baseline period. The Mann-Whitney U test was used to analyze data on right and left knee extension times. MCT supplementation for 3 months increased muscle function relative to LCT supplementation with and without an L-leucine (1.2 g) and vitamin D (cholecalciferol, 20 μg)-enriched supplement. In a combined data analysis (n = 29 in MCTs, n = 27 in LCTs), relative to supplementation with 6 g LCTs/day, supplementation with 6 g MCTs/day at dinner for 3 months significantly increased body weight (adjusted mean change from baseline: MCTs 1.2 vs. LCTs 0.2 kg, p = 0.023), right arm muscle area (MCTs 1.4 vs. LCTs-0.7 cm2, p = 0.002), left calf circumference (p = 0.015), right-hand grip strength (MCTs 1.6 vs. LCTs 0.3 kg, p = 0.017), right knee extension time (p = 0.021), left knee extension time (p = 0.034), walking speed (p = 0.002), and number of iterations in leg open and close test (p < 0.001) and decreased right triceps skinfold thickness (p = 0.016). In frail older adults, supplementation for 3 months with a low dose (6 g/day) of MCTs (C8:0 and C10:0) increased muscle mass and function. These findings indicate the potential for the practical use of MCTs in daily life in treating sarcopenia.

Perch essence prevents cell death to improve skeletal muscle mass and strength: Evidence from in vitro and human model

Background:Fish protein supplementation may maintain muscle strength and prevent sarcopenia as it contains a complex array of macro- and micronutrients essential for building the skeletal muscle. Objective:The aim of this study was to evaluate the influence of perch essence (PE) supplementation on muscle mass and muscle function of through human and cell model. Methods:The open label clinical trial was conducted to assess the therapeutic effect of PE on muscle mass improvement. The mouse skeletal muscle cell (C2C12) model of muscle atrophy was analyzed for cell viability. Results:Our results showed PE contained abundant branched chain amino acid, taurine, hydroxyproline and collagen. After one month of supplementation with PE in our human model, there was a significant increase in muscle mass in the whole body and all parts of the body, with an increase of 1.55 % in the whole body, 1.79% in the trunk, 1.64% in the arms and 1.38% in the legs. The percentage of subcutaneous fat in the trunk, arms and legs also decreased significantly by 2.49%, 3.21% and 3.40% respectively. PE supplementation also improves muscle grip strength, especially with the dominant hand. The cell model results demonstrated that PE could effectively prevent skeletal muscle cell from death induced by dexamethasone. Conclusion:This study suggests that the branched chain amino acids, taurine, hydroxyproline and collagen in PE have the potential to serve as a good source of dietary supplements for the improvement of skeletal muscle mass and strength through cell protection.Keywords:branched chain amino acid, collagen, perch, skeletal muscle, sarcopenia

Impact of an oral nutritional supplement enriched in leucine, EPA, DHA, and β-glucans on the increase of muscle mass in patients with cancer and malnutrition: The alisenoc trial

MethodsA randomized, double-blind, parallel-group, controlled, multicenter clinical trial was conducted in patients with cancer and malnutrition during outpatient treatment. Patients were randomized to receive either a specific high-calorie, high-protein ONS enriched with leucine, EPA, DHA, and β-glucans or an isocaloric, isonitrogenous standard ONS for eight weeks. Malnutrition was diagnosed using the SGA and body composition was evaluated using bioimpedance. Results57 patients were recruited and 37 completed the intervention period. After the nutritional intervention, patients who received the enhanced-ONS showed a significant increase in muscle mass, which was not detected with the standard ONS [1.92 (4.31) kg vs −0.68 (1.45) kg); p = 0.009)], and there was no significant reduction in the percentage of patients with severe and moderate malnutrition. ConclusionAn enhanced ONS enriched in EPA, DHA, leucine, and β-glucans increases muscle mass and could promote nutritional and functional status recovery in patients with cancer and malnourishment.Trial registration: NCT04184713.

The effects of effortless exercise on diabetic status

Treating physicians have consistently recommended exercise to either prevent diabetes or de-escalate symptomatology. Diabetic complications, however, render physical activity undesirable or unattainable. These involve: hypothyroidism leading to substantial weight gain; perpetual fatigue due to accumulation of white adipose tissue serving as fat storage, and inadequate supply of brown fat to generate energy; accumulated toxicity causing hormonal imbalance that increases hunger; chronic pain and wounds on extremities associated with diabetic neuropathy, etc. Recent research with an effortless exercise method demonstrated enhanced fitness and T3 increase, juxtaposed by decreased inflammation, an optimal relationship between leptin and ghrelin that control appetite, and a significant decrease of visceral fat along with VLDL, the very low-density lipoprotein that carries triglycerides to the tissues. We measured the fasting and postprandial glucose and insulin of 21 diabetics and 20 prediabetics respectively, pre and post twenty treatments. Both previously abnormally high fasting and postprandial (PP) glucose decreased considerably in all 21 diabetic subjects (100%). Nine of the diabetic subjects (42.85%) manifested normal fasting glucose levels after 20 treatments, while the fasting glucose of the remaining twelve diabetic subjects (57.2%) dropped down to the prediabetic level. Ten of the diabetic subjects (47.6%) manifested normal PP insulin levels, while the PP insulin of the remaining eleven diabetic subjects (52.38%) dropped to the prediabetic level after the 20 treatments. Prediabetics had more robust results as expected by their baseline healthier status. Eighteen of prediabetics (90%) manifested both normal fasting and PP insulin levels after the 20 treatments, while the fasting and PP insulin of the remaining two subjects (10%) remained within the prediabetic level. All subjects also exhibited a statistically significant increase in muscle mass, normalized T3 levels, decreased visceral and overall fat along with reduced CRP, advocating diminished inflammation. Dyslipidaemia appeared to subside as denoted by suppressed levels of triglycerides contrasted by elevated HDL.

Postoperative inpatient exercise facilitates recovery after laparoscopic surgery in colorectal cancer patients: a randomized controlled trial

BackgroundEarly mobilization is an integral part of an enhanced recovery program after colorectal cancer surgery. The safety and efficacy of postoperative inpatient exercise are not well known. The primary objective was to determine the efficacy of a postoperative exercise program on postsurgical recovery of stage I–III colorectal cancer patients.MethodsWe randomly allocated participants to postoperative exercise or usual care (1:1 ratio). The postoperative exercise intervention consisted of 15 min of supervised exercise two times per day for the duration of their hospital stay. The primary outcome was the length of stay (LOS) at the tertiary care center. Secondary outcomes included patient-perceived readiness for hospital discharge, anthropometrics (e.g., muscle mass), and physical function (e.g., balance, strength).ResultsA total of 52 (83%) participants (mean [SD] age, 56.6 [8.9] years; 23 [44%] male) completed the trial. The median LOS was 6.0 days (interquartile range; IQR 5–7 days) in the exercise group and 6.5 days (IQR 6–7 days) in the usual-care group (P = 0.021). The exercise group met the targeted LOS 64% of the time, while 36% of the usual care group met the targeted LOS (colon cancer, 5 days; rectal cancer, 7 days). Participants in the exercise group felt greater readiness for discharge from the hospital than those in the usual care group (Adjusted group difference = 14.4; 95% CI, 6.2 to 22.6; P < 0.01). We observed a small but statistically significant increase in muscle mass in the exercise group compared to usual care (Adjusted group difference = 0.63 kg; 95% CI, 0.16 to 1.1; P = 0.03).ConclusionPostsurgical inpatient exercise may promote faster recovery and discharge after curative-intent colorectal cancer surgery.Trial registrationThe study was registered at WHO International Clinical Trials Registry Platform (ICTRP; URL http://apps.who.int/trialsearch); Trial number: KCT0003920.

Potential nutritional strategies to prevent and reverse sarcopenia in aging process: Role of fish oil-derived ω-3 polyunsaturated fatty acids, wheat oligopeptide and their combined intervention

IntroductionNutritional support is potentially considered an essential step to prevent muscle loss and enhance physical function in older adults. ObjectivesThis study aimed to assess the role of potential nutritional strategies, i.e., fish oil-derived ω-3 polyunsaturated fatty acids (PUFAs), wheat oligopeptide and their combined intervention, in preventing and reversing sarcopenia in aging process. MethodsOne hundred 25-month-old Sprague-Dawley rats were randomly divided into 10 groups, and 10 newly purchased 6-month-old rats were included in young control group (n = 10). Fish oil (200, 400 or 800 mg/kg body weight), wheat oligopeptide (100, 200 or 400 mg/kg body weight), fish oil + wheat oligopeptide (800 + 100, 400 + 200 or 200 + 400 mg/kg body weight) or the equal volume of solvent were administered daily by gavage for 10 weeks. The effects of these interventions on natural aging rats were evaluated. ResultsAll intervention groups had a significant increase in muscle mass and grip strength and reduction in perirenal fat weight when compared to the aged control group (P < 0.05). The results of biochemical parameters, magnetic resonance imaging, proteomics and western blot suggested that the combination of wheat oligopeptide and fish oil-derived ω-3 PUFA, especially group WFM 2 (400 + 200 mg/kg body weight fish oil + wheat oligopeptide), was found to be more effective against aging-associated muscle loss than single intervention. Additionally, the interventions ameliorated fatty infiltration, muscle atrophy, and congestion in the intercellular matrix, and inflammatory cell infiltration in muscle tissue. The interventions also improved oxidative stress, anabolism, hormone levels, and inflammatory levels of skeletal muscle. ConclusionsThe combination of fish oil-derived ω-3 PUFA and wheat oligopeptide was found to be a promising nutritional support to prevent and reverse sarcopenia. The potential mechanism involved the promotion of protein synthesis and muscle regeneration, as well as the enhancement of muscle strength.

Does a Kegel Exercise Program Prior to Resistance Training Reduce the Risk of Stress Urinary Incontinence?

This comparative pre-post intervention study investigated the feasibility and benefits of Kegel exercises amongst incontinent women, prior to commencing resistance training (RT), to reduce the risk of stress urinary incontinence (SUI) compared to a group of women without prior Kegel exercises (KE). Incontinence severity index (ISI) score, pelvic floor muscle strength (PFMS), and body composition (such as body mass index (BMI), fat, and muscle mass), were obtained pre and post intervention. Results demonstrated that RT reduced SUI to a significantly greater extent only if preceded by KE as was observed in the Kegel exercise plus RT group (KE + RT) over time. The improvements in total ISI in both the KE + RT and RT groups were large (d = 1.50 and d = 1.17 respectively). A two-way ANOVA indicated a statistically significant improvement in average PFMS within the KE + RT group over time and between the two groups. A positive correlation was found between the average strength of pelvic floor muscles and SUI. Participants in KE + RT group demonstrated a significant increase in muscle mass (p ≤ 0.001) and concomitant reduction in fat mass (p = 0.018). This study determined a dedicated program of KE preceding a RT program improved average pelvic floor muscle strength and was effective in reducing SUI among incontinent women.

Acupunch Exercise Improved Muscle Mass, Hand Grip Strength, and Sleep Quality of Institutional Older Adults with Probable Sarcopenia.

This study tested the effectiveness of a 6-month vitality acupunch (VA) exercise program on muscle mass, hand grip strength, and sleep quality in institutional older adults with probable sarcopenia. A cluster randomized controlled trial was conducted. A total of 103 older adults were assigned to the experimental group (n = 52) and control group (n = 51) according to the institution they inhabited. After the 6-month VA exercise intervention, the experimental group showed significant increases in muscle mass (F = 5.93, p = .017), hand grip strength (F = 56.73, p < .001), and improved sleep quality (F = 23.20, p < .001) compared to the control group. Based on the meridian theory that promotes qi and blood circulation, VA exercise has positive effects on muscle mass, hand grip strength, and sleep quality in older adults with probable sarcopenia.

Efficacy of Curcumin on Treating Cancer Anorexia-Cachexia Syndrome in Locally or Advanced Head and Neck Cancer: A Double-Blind, Placebo-Controlled Randomised Phase IIa Trial (CurChexia).

Background Cancer anorexia-cachexia syndrome (CAS) is a significant comorbidity among all patients with cancer, increasing the mortality rate. Almost all patients with head and neck cancer experience this syndrome. CAS causes increased energy expenditure by increasing systemic inflammation and decreasing energy consumption due to anorexia. It leads to skeleton muscle breakdown and reduces the quality of life. Nutritional interventions and primary cancer treatment are the mainstays to manage this situation. However, a vicious cycle causes CAS to persist, especially in head and neck cancer, where tumour location and its treatment interfere with nutritional interventions. Curcumin shows anti-inflammatory effects, including modulated CAS in animal and in vitro studies. Objective The study aimed to determine the effect of curcumin to treat cancer anorexia-cachexia syndrome among current patients with locally advanced or advanced head and neck cancer. Methods This constitutes a randomised, double-blind, placebo-controlled phase IIa study. Twenty patients with CAS in locally advanced or advanced head and neck cancer adequately nourished via a feeding tube were enrolled and randomised in a 1 : 1 ratio to receive oral curcumin (at a dose of 4000 mg daily) (n = 10) or placebo (n = 10) for 8 weeks. The primary endpoint was body composition (muscle mass, body fat mass, and basal metabolic rate). The secondary endpoints were handgrip muscle strength, body mass index, absolute lymphocyte count, and safety and toxicity. Result There was a statistically significant benefit from curcumin on improving muscle mass compared with placebo (2.16% [95% confidence interval; CI, −0.75 to 5.07] vs. −3.82% [95% CI, −8.2 to 0.57]; P=0.019). The other parameters of body composition were not significant but tended to favour curcumin benefit. The body fat mass (−0.51 [95% CI, −21.89 to 20.86] vs. −8.97% [95% CI, −19.43 to 1.49]; P=0.432) and percentage of mean change in the basal metabolic rate were noted (BMR) (0.54% [95% CI, −1.6 to 2.67] vs. −1.61% [95% CI, −4.05 to 0.84]; P=0.153). Notably, patients treated with curcumin exhibited less reduction in handgrip muscle strength and absolute lymphocyte count but was not significant. Similarly, most adverse events were grade 1 in both groups. Conclusion The curcumin add-on resulted in a significant increase in muscle mass than standard nutritional support. Furthermore, it may improve and delay a decrease in the other body composition parameters, handgrip strength, and absolute lymphocyte count. Curcumin was safe and well tolerated. This constitutes an unmet need for clinical trials. This trial is registered with NCT04208334.

Combined high-intensity interval training as an obesity-management strategy for adolescents

ABSTRACT Effective and safe exercise protocols for obesity management in adolescents are imperative. This study aimed to analyse compliance, efficacy, and safety of combined high-intensity interval training circuit (HIIT) in the management of obesity (including overweight) in adolescents, compared to traditional training (TT). Data from 55 adolescents (47.3% girls) (TT n = 31; HIIT n = 24), aged 12–18 (mean age of 14.3 ± 1.7), with overweight and obesity (median BMI z-score of 2.95), were assessed at baseline and month 6 (Clinicaltrials.gov/NCT02941770). During the 6-month intervention, participants in both exercise groups attended two exercise sessions/week (60 min/session) along with a set of appointments with a paediatrician, nutritionist, and exercise physiologist. Forty-six participants completed the intervention (TT n = 23; HIIT n = 23). Exercise session attendance (≥80%) was significantly higher among HIIT participants (73.9 vs. 13.0%, p < .001). HIIT, but not TT, showed a significant decrease in BMI z-score (d = 0.40, p < .001), body fat mass (BFM, %) (d = 0.41, p = .001), and trunk fat mass (d = 0.56, p < .001), as well as a significant increase in muscle mass (MM, %) (d = 0.28, p = .001) between baseline and 6 months. According to generalized estimating equations, time-by-attendance interactions (instead of time-by group) were found in BMI z-score (β = 0.25, 95%CI: 0.17, 0.33), BFM (β = 2.29, 95%CI: 1.02, 3.56), trunk fat mass (β = 2.94, 95%CI: 1.70, 4.18), and MM (β = −1.16, 95%CI: −1.87, −0.45). No adverse events were reported during HIIT sessions. Although compliance may mediate the impact of an exercise protocol on health-related outcomes, HIIT showed to be safe, with higher compliance compared to TT, which may result in improved outcomes overtime.

Effects of a High-Intensity Interval Training Program on Body Composition and Physical Fitness in Female Field Hockey Players

High-intensity interval training (HIIT) is zed by achieving similar effects to conventional physical and physiological training in a shorter time, allowing its dissemination in the sports field. The present study was aimed to analyze the effects of a HIIT program on body composition and general and specific physical fitness in Chilean female field hockey players. Experimental, repeated measures, simple blind, parallel groups, and a quantitative approach were used. The participants were randomized, and distributed into a control group (CG; n= 10) that maintained regular field hockey training and an experimental group (EG; n= 10) that also received complementary training with HIIT. Body composition (muscle mass and adipose mass), general physical fitness (jump performance with countermovement jump [CMJ] and maximum oxygen consumption [VO2max] were evaluated with the test Course-Navette), and specific physical fitness (pushing speed, dribbling speed, and shooting accuracy) were assessed with established protocols. Pre- and post-intervention comparisons were made with Student's t and Wilcoxon tests, considering p<0.05. The main results indicate that the EG presented a significant increase in muscle mass (p = 0.024; d = 0.62), CMJ (p = 0.005; d = 1.10), VO2max (p = 0.001; d = 1.58) and a significant reduction in adipose mass (p = 0.023; d = 0.36) and time in pushing speed (p = 0.028; d = 0.79). The CG did not present significant changes in any of the variables analyzed, and no significant differences were reported between the groups. In conclusion, eight weeks of HIIT significantly increases muscle mass, jump performance, and VO2max and significantly reduces adipose mass and time in pushing speed in Chilean female field hockey players.

Benefits of Adding an Aquatic Resistance Interval Training to a Nutritional Education on Body Composition, Body Image Perception and Adherence to the Mediterranean Diet in Older Women.

The human population is increasing due to lengthening life expectancy, but the quality of life and health of people is moving in the opposite direction. The purpose of this study is to evaluate how aquatic resistance interval training can influence body composition, body image perception and adherence to the Mediterranean diet (MD) in older women participants in a nutrition education program and to study the relation between these variables. Thirty-four participants aged 69 ± 4 years were randomly assigned into two groups: experimental (aquatic resistance interval training plus nutritional intervention) and control (nutritional intervention). The intervention consisted of resistance training in an aquatic environment carried out for 14 weeks (three sessions per week; 60 min each). Body composition, body image perception and adherence to MD diet were evaluated at baseline and 14 weeks. No significant differences were found between groups regarding body image perception and adherence to the MD. There was a significant increase in muscle mass (kg) (p < 0.001) and a significant decrease in fat mass (kg) (p < 0.001) in the intervention group when compared to the control group. The addition of aquatic resistance interval training to a nutritional intervention was not sufficient to change body image perception and adherence to MD but produced improvement in body composition (through an increase in muscle mass and decrease on fat mass) in older women.

Strength Training as an Assistant Tool in the Prevention of Falls in Elderly Sarcopenics: a Review

An elderly society has been growing gradually in Brazil and after retirement some tend to show levels of sedentary behavior index. In addition, the aging process creates a weakness in physical and emotional health, in addition to other things, the increase in the number of falls, caused by dysfunction and loss of muscle mass, called Sarcopenia. Considering all the benefits of strength training for the most varied audiences and that the aging process is gradual and irreversible resulting in the development of Sarcopenia that tends to worsen with the lack of physical exercises, the objective of this study was to investigate how strength training can generate benefits in elderly people who present with Sarcopenia and promote the reduction of falls. From a literature review in the Scielo and PubMed databases, eight articles were selected to compose the results. Thus, it was possible to conclude that this protocol is known as an alternative for the prevention of falls due to Sarcopenia, since it is capable of promoting a significant increase in muscle mass, as well as improving the balance and functional capacity of the elderly.

Indicies of body composition and uric acid metabolism as markers of metabolic phenotype in normouricemic type 2 diabetic man

The purpose of the workisto investigate the relationship between body composition parameters and uric acid metabolism and lipid spectrum in obese type 2 diabetic male compared with non-obese patients. Materials and methods. In 34 patients with type 2 diabetes, aged 45 to 75 years, with unsatisfactory glycemic control (HbA1c from 7.1 to 12.6 %), mainly with abdominal obesity, anthropometric parameters, characteristics of body composition (percentage of total and abdominal fat, segmental distribution of adipose and muscle tissue, by bioimpedance method), level of HbA1c, C-peptide, concentration of uric acid (UA), 24 h UA excretion, and serum lipid fractions were measured. Patients were divided into 2 groups depending on the degree of obesity: group 1—15 men with overweight without obesity (BMI 25.0—29.9 kg/m2); group2—19 obese men (BMI ≥ 30.0 kg/m2). The groups did not differ in age and disease duration. Results and discussion. Normouricemia was observed in almost all examined patients, without a significant difference in uricemia levels between two groups. In 42 % of obese patients, elevated UA excretion was significantly higher than in the non-obese group, which may reflect increased UA production during the day and increased urate elimination, which leads to normal uricemia. Comparison of body composition between groups with different phenotypes showed that obese patients had significantly higher percentages of total fat and visceral fat than non-obese individuals. Adipose tissue in both groups was evenly distributed between body segments. In obese patients, there was a significant increase in muscle mass, especially in the lower extremities, with some dehydration, as indicated by a decrease in the % water content. Conclusions. It has been shown that both variants of metabolic phenotypes in patients with type 2 diabetes (with and without obesity), under conditions of central fat accumulation and normouricemia, in many cases were accompanied by hyperexcretion of UA, which ensured the preservation of normal uricemia.

Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A

Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.

Myostatin inhibition promotes fast fibre hypertrophy but causes loss of AMP-activated protein kinase signalling and poor exercise tolerance in a model of limb-girdle muscular dystrophy R1/2A.

Limb-girdle muscular dystrophy R1 (LGMD R1) is caused by mutations in the CAPN3 gene and is characterized by progressive muscle loss, impaired mitochondrial function and reductions in the slow oxidative gene expression programme. Myostatin is a negative regulator of muscle growth, and its inhibition improves the phenotype in several muscle wasting disorders. The effect of genetic and pharmacological inhibition of myostatin signalling on the disease phenotype in a mouse model of LGMD R1 (CAPN3 knockout mouse-C3KO) was studied. Inhibition of myostatin signalling in C3KO muscles resulted in significant muscle hypertrophy; however, there were no improvements in muscle strength and exacerbation of exercise intolerance concomitant with further reduction of muscle oxidative capacity was observed. Inhibition of myostatin signalling is unlikely to be a valid therapeutic strategy for LGMD R1. Limb-girdle muscular dystrophy R1 (LGMD R1) is caused by mutations in the CAPN3 gene and is characterized by progressive muscle loss, impaired mitochondrial function and reductions in the slow oxidative gene expression programme. There are currently no therapies available to patients. We sought to determine if induction of muscle growth, through myostatin inhibition, represents a viable therapeutic strategy for this disease. Myostatin is a negative regulator of muscle growth, and its inhibition improves the phenotype in several muscle wasting disorders. However, the effect of myostatin depends on the genetic and pathophysiological context and may not be efficacious in all contexts. We found that genetic inhibition of myostatin through overexpression of follistatin (an endogenous inhibitor of myostatin) in our LGMD R1 model (C3KO) resulted in 1.5- to 2-fold increase of muscle mass for the majority of limb muscles. However, muscle strength was not improved and exercise intolerance was exacerbated. Pharmacological inhibition of myostatin, using an anti-myostatin antibody, resulted in statistically significant increases in muscle mass; however, functional testing did not reveal changes in muscle strength nor endurance in treated C3KO mice. Histochemical and biochemical evaluation of follistatin overexpressing mice revealed a reduction in the percentage of oxidative fibres and decreased activation of AMP-activated protein kinase signalling in transgenics compared to C3KO muscles. Our data suggest that muscle hypertrophy, induced by myostatin inhibition, leads to loss of oxidative capacity, which further compromises metabolically impaired C3KO muscles and thus is unlikely to be a valid strategy for treatment of LGMD R1.

Frameshift mutation in myostatin gene by zinc-finger nucleases results in a significant increase in muscle mass in Meishan sows

Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. A significant increase in skeletal muscle was observed in Mstn&lt;sup&gt;−/−&lt;/sup&gt; mice compared with wild-type mice. So far, there has been no report on porcine MSTN mutations leading to skeletal muscle hypertrophy. In this report a MSTN frameshift mutation missing 11 nucleotides in exon 2 was introduced into Meishan pigs by zinc finger nuclease (ZFN) technology. ZFN-edited MSTN&lt;sup&gt;−/−&lt;/sup&gt; Meishan pigs were successfully produced by a cloning method of somatic cell nucleus transfer. Results from slaughter experiments indicated that lean meat yield increased 16.53% in about 80 kg (10-months-old) MSTN&lt;sup&gt;−/−&lt;/sup&gt; Meishan sows compared with their corresponding wild-type counterparts. The lean percentage of carcass from MSTN&lt;sup&gt;−/−&lt;/sup&gt; sows was 61.20% vs 48.25% for MSTN&lt;sup&gt;+/−&lt;/sup&gt; sows and 44.67% for wild-type sows. The fat of MSTN&lt;sup&gt;−/−&lt;/sup&gt; sows was significantly lower than that of MSTN&lt;sup&gt;+/−&lt;/sup&gt; and wild-type sows. The loin eye area of MSTN&lt;sup&gt;−/−&lt;/sup&gt; Meishan sows (56.42 cm&lt;sup&gt;2&lt;/sup&gt;) was greater than that of MSTN&lt;sup&gt;+/−&lt;/sup&gt; (37.39 cm&lt;sup&gt;2&lt;/sup&gt;) and wild-type (26.26 cm&lt;sup&gt;2&lt;/sup&gt;) sows. The muscle fibre area of longissimus muscle in wild-type Meishan sows (1 946 μm&lt;sup&gt;2&lt;/sup&gt;) was significantly greater than that of MSTN&lt;sup&gt;+/−&lt;/sup&gt; (1 324 μm&lt;sup&gt;2&lt;/sup&gt;) and MSTN&lt;sup&gt;−&lt;/sup&gt;&lt;sup&gt;/−&lt;/sup&gt; (1 419 μm&lt;sup&gt;2&lt;/sup&gt;) sows. Moreover the significantly increased skeletal muscle in these MSTN&lt;sup&gt;−/−&lt;/sup&gt; Meishan sows was mainly due to the increase in the number of myofibres rather than to hypertrophy. Compared with wild-type Meishan sows, it was noted that myofibres had transformed from type I to IIB in MSTN&lt;sup&gt;−/−&lt;/sup&gt; Meishan sows. Our present study demonstrated that frameshift mutation in MSTN by ZFN technology led to a significant increase in muscle mass and a significant decrease in fat content in Meishan sows.

Body Composition Changes Resulting from Nutrition Supplementation and Nutrition Education: Results from 2 × 2 Factorial Trial of 600 Rural Indian Women Living with HIV/AIDS

Abstract Objectives People living with HIV/AIDS are at increased risk of nutritional deficiencies. Loss of lean muscle mass has been associated with a more rapid decline of immune function and increased risk of mortality among individuals suffering from HIV. Our objectives were to evaluate the relative contributions of nutrition supplementation and nutrition education on body composition outcomes using a cluster randomized factorial trial among 600 women living with HIV/AIDS in rural Andhra Pradesh, India. Methods We conducted a prospective cluster randomized controlled 2 × 2 factorial design to assess impacts of nutritional education and nutritional supplementation over a six-month period, with follow up at six, twelve and eighteen months post enrollment. Study protocols were approved by Human Subjects Committees at the Universities of California at Los Angeles, Irvine, and San Francisco and the Ministry of Health in India. Interventions were delivered in the Nellore and Prakasam regions of Andhra Pradesh by trained lay village women, Ashas (Accredited Social Health Activists). Interventions included: usual supportive care provided by Ashas; 2) Asha Support plus Nutrition education; 3) Asha support plus Nutrition supplementation; and, 4) Asha support plus Nutrition education plus Nutrition supplementation. We measured body composition using a Bioimpedance Analyzer Model 310e. All data was analyzed using SAS 9.4. Results Mixed models evaluated change in lean muscle mass from baseline as the primary outcome, and fat weight, overall weight and BMI changes as secondary outcomes. Change in muscle mass from baseline was significantly associated with nutrition supplementation (P = 0.001), nutrition education (P = 0.01), with a significant interaction (P = 0.03) for the combined nutrition supplementation and education term. Using the same factorial structure, nutrition supplementation and education were independently associated with changes in BMI and fat mass. Conclusions Interventions that target nutrition may be an important approach to improving the physiologic response to HIV. We observed significant increases in muscle mass resulting from independent contributions of nutrition education and nutrition supplementation, as well as their combined contribution. Funding Sources NIMH R01MH098728.

The role of UBR5 on Mitogen‐activated protein kinase (MAPK) signalling and muscle mass regulation in mice

E3 ubiquitin ligases are commonly studied in skeletal muscle under atrophy‐inducing conditions. However, we recently identified a novel E3 ubiquitin ligase, UBR5 to be involved in skeletal muscle hypertrophy and recovery from atrophy ( Seaborne et al., 2019). Previous literature suggests an interaction between UBR5 and the MAPK signalling cascade (ERK 1/2, p90RSK) in various other tissues. Thus, we sought to investigate the role of UBR5 on MAPK signalling in basal skeletal muscle.Male C57BL/6 mice (12‐week old) were subjected to in vivo electroporation with a mouse specific UBR5 RNAi plasmid (20ug) in the tibialis anterior (TA) muscle with the contralateral leg serving as a vector control (EV). After 7 days, TA muscles were collected, weighed and sectioned for cross‐sectional area (CSA) and GFP visualization. Western blotting was performed to determine phosphorylation of ERK 1/2, p90RSK, MEK1/2 and MSK1 signalling levels in the transfected TA muscles.After 7 days, muscles transfected with the UBR5 RNAi displayed significant increases in muscle mass. Alongside a 50% reduction in UBR5 protein, we observed a significant reduction in phosphorylation of ERK 1/2 and ~2‐fold increase in p90RSK phosphorylation in RNAi transfected muscles compared to the EV. There were no differences observed in the phosphorylation status of MEK1/2 or MSK1 levels.Gene manipulation of UBR5 in basal skeletal muscle lead to alterations in muscle mass and activation of the MAPK signalling pathway. Future studies will seek to explore the effect of chronic UBR5 knockdown on muscle mass regulation.

Influence of Extra Virgin Olive Oil Supplement and Combined Exercise on Health-Related Physical Fitness, Cardiovascular Disease Risk Factors, and Bone Density in Obese Elementary Students

PURPOSE: The purpose of this study was to investigate the influence of combined exercise and extra virgin olive oil supplement on health-related physical fitness, cardiovascular disease risk factors, and bone density in obese elementary school students.METHODS: The participants were 40 obese elementary students over 25 kg/m&lt;sup&gt;2&lt;/sup&gt; to BMI, 10 combined exercise with high olive oil supplement group (HO+CE), 10 combined exercise with low olive oil supplement group (LO+CE), 10 combined exercise with placebo group (PL+CE), and 10 placebo group (PL). The participants have performed the exercise program for 70 minutes a day and 3 times a week with aerobic and resistance exercise during 12 weeks. Also, high and low olive oil supplement group took in 25 g and 10 g respectively at the same time and place.RESULTS: There were significant decreases in body fat to HO+CE compared with PL+CE (&lt;i&gt;p&lt;/i&gt;&lt;.05) and significant increase in muscle mass and muscular endurance compared with PL+CE (&lt;i&gt;p&lt;/i&gt;&lt;.05). However, there were no significant differences in body weight, BMI, muscular strength, and flexibility between groups. For cardiovascular disease risk factors, there is a significant difference to triglyceride, LDL-C, total cholesterol in HO+CE compared with PL+CE (&lt;i&gt;p&lt;/i&gt;&lt;.05) and there were significant differences to HDL-C significantly decreased in HO+CE compared with PL+CE (&lt;i&gt;p&lt;/i&gt;&lt;.05). There is no significant difference in bone density between groups (&lt;i&gt;p&lt;/i&gt;&gt;.05).CONCLUSIONS: In conclusion, there were positive responses for body composition and cardiovascular disease risk factors for the twofold cases through combined exercise and high extra virgin olive oil supplement, but not for bone density.