Decrease In Skeletal Muscle Mass Research Articles

Impact of skeletal muscle mass volume on surgical site infection in free flap reconstruction for oral cancer.

Sarcopenia is a disease in which skeletal muscle mass (SMM) and function are progressively lost. Here, we investigate surgical site infection (SSI) as a function of SMM in patients who underwent free flap reconstruction for a defect caused by oral cancer resection. A nonrandomized, retrospective group of 122 patients treated with free flap reconstruction after oral cancer resection was enrolled in the study. All subjects also underwent preoperative abdominal-lumbar computed tomography (CT). Cross-sectional areas (cm2 ) of skeletal muscles in the L3 region were measured by manual outline on CT images. The obtained areas were normalized for height (cm2 /m2 ), and the resulting value is referred to as the skeletal muscle index (SMI). Recipient site SSI occurred in 30 patients (24.6%). Underweight status (body mass index [BMI] < 18.5 kg/m2 ), anemia and lower SMI were significantly related to recipient site SSI in univariate analysis (p < . 05). In multiple logistic regression analysis, lower SMI was an independent significant risk factor for recipient site SSI (p = .015, adjusted odds ratio = 1.41 per 5 cm2 /m2 decrease). These findings suggest that a decrease in SMM might have more impact than a decrease in BMI on SSI in free flap reconstruction after resection of oral cancer.

Benefits of exercise during peri-and postmenopause

Menopause is associated with an increasing risk to develop the so called metabolic syndrome. A major reason is the decrease of circulating estrogen, a sex steroid which is involved in a variety of metabolic processes. Estrogens affect fat metabolism, bone metabolism and protein metabolism. Declining estrogen levels are associated with adverse lipid profiles, a reduced ability o to metabolize fatty acids, reduced bone mass and density and with a decrease in skeletal muscle mass. All this has implications for the development of diseases like cardiovascular disease, sarcopenia, osteoporosis and diabetes type II. Animal experimental studies and human investigations have clearly demonstrated differences in the ability to metabolize fatty acids between pre- and postmenopausal females. In animal experimental studies but also in human intervention studies we have demonstrated that physical activity has a beneficial impact on many physiological parameters associated with the mentioned diseases. Resistance training has been demonstrated to be an important strategy to maintain bone mass in postmenopausal females. Endurance training has strong preventive effects for the development of cardiovascular diseases. Therefore development of individualized training concepts combined with on optimized nutrition and pharmacological treatment concepts a are powerful strategies to overcome negative physiological impacts in peri- or postmenopause.

Sarcopenia Affects Systemic and Local Immune System and Impacts Postoperative Outcome in Patients with Extrahepatic Cholangiocarcinoma.

A decrease in skeletal muscle mass and function, defined as sarcopenia, is associated with poor postoperative outcome in patients with cancers. Although systemic or local immune status impacts cancer progression, the relationship between sarcopenia and these statuses remains unclear. The aim of this study is to investigate the clinical impact of sarcopenia and its relationship to immune systems in patients with extrahepatic cholangiocarcinoma (ECC). A total of 110 consecutive ECC patients with curative resection between 2005 and 2014 were enrolled. Sarcopenia was determined from skeletal muscle index, assessed by a L3 skeletal muscle mass on axial computed tomography images, and their relationships with patients' clinicopathological characteristics and survival were evaluated. Systemic immune status was calculated using preoperative laboratory data, and tumor-infiltrating (TI) immune cells (CD8+ T cells, CD66b+ neutrophils, CD163+ M2 macrophages) assayed by immunohistochemistry, and their relationship to sarcopenia were evaluated. Sarcopenia was present in 31 patients (28.2%). Patients with sarcopenia had a worse recurrence-free survival (HR 1.87, p = 0.009) and overall survival (OS) (HR 2.47, p = 0.0004) than patients without sarcopenia. Moreover, patients with sarcopenia had a higher level of platelet-lymphocyte ratio (159 vs. 119; p = 0.003) and lower number of TI CD8+ T cells (47 vs. 66 cells/spot; p = 0.03) than patients without sarcopenia. On multivariate analysis, the presence of sarcopenia (HR 2.60, p = 0.0008) was an independent predictor of poor OS. Our data showed that sarcopenia and systemic or local immune cells may interact with each other and play a pivotal role in clinical outcomes of patients with ECC.

IPSCs: A powerful tool for skeletal muscle tissue engineering.

Both volumetric muscle loss (VML) and muscle degenerative diseases lead to an important decrease in skeletal muscle mass, condition that nowadays lacks an optimal treatment. This issue has driven towards an increasing interest in new strategies in tissue engineering, an emerging field that can offer very promising approaches. In addition, the discovery of induced pluripotent stem cells (iPSCs) has completely revolutionized the actual view of personalized medicine, and their utilization in skeletal muscle tissue engineering could, undoubtedly, add myriad benefits. In this review, we want to provide a general vision of the basic aspects to consider when engineering skeletal muscle tissue using iPSCs. Specifically, we will focus on the three main pillars of tissue engineering: the scaffold designing, the selection of the ideal cell source and the addition of factors that can enhance the resemblance with the native tissue.

Skeletal muscle loss during anti-EGFR combined chemotherapy regimens predicts poor prognosis in patients with RAS wild metastatic colorectal cancer

We aimed to assess whether anti-EGFR combined chemotherapy regimens are related with loss of skeletal muscle mass and to compare cetuximab and panitumumab therapies in the aspect of skeletal muscle area change as well as to assess whether skeletal muscle mass loss has prognostic significance in the RAS wild mCRC patients. A total of 56 patients (30 patients in cetuximab arm and 26 patients in panitumumab) who had computed tomography images were retrospectively evaluatedat the diagnosis and follow up during the treatment period before progression. During treatment period 24 patients (42.8%) had muscle loss. Of these, 7 (29.2%) patients were treated at first-line and 17 (70.8%) patients were treated at second-line setting. There was no significant difference in the aspect of skeletal muscle loss among cetuximab and panitumumab combined treatment regimens. Median PFS was 9.1 (8.6-9.6) months in muscle loss group and 13.9 (7.2-20.6) months in muscle stable group (p=0.001). Median OS was 23.4 (95% CI 15.8-31.0) months in muscle stable group and 19.1 (95% CI 17.0-21.3) months in muscle loss group (p=0.57) at first-line setting. For second-line, median OS was 21.2 (14.7-27.7) months in muscle stable group and 14.4 (6.0-22.4) months in muscle loss group (p=0.003). Decrease in skeletal muscle mass before progression on CT imaging is an independent indicator for shorter PFS value in RAS WT mCRC patients who received anti-EGFR combined chemotherapy regimens at both the first and second-line settings. Beside that shorter overall survival values also were significantly seen in patients who had muscle loss during anti-EGFR therapy in the second-line setting.

D3 -Creatine dilution and the importance of accuracy in the assessment of skeletal muscle mass.

Sarcopenia has been described as the age‐associated decrease in skeletal muscle mass. However, virtually every study of sarcopenia has measured lean body mass (LBM) or fat free mass (FFM) rather than muscle mass, specifically. In a number of published sarcopenia studies, LBM or FFM is referred to as muscle mass, leading to an incorrect assumption that measuring LBM or FFM is an accurate measure of muscle mass. As a result, the data on the effects of changes in LBM or FFM in older populations on outcomes such as functional capacity, disability, and risk of injurious falls have been inconsistent resulting in the conclusion that muscle mass is only weakly related to these outcomes. We review and describe the assumptions for the most commonly used measurements of body composition. Dual‐energy X‐ray absorptiometry (DXA) has become an increasingly common tool for the assessment of LBM or FFM and appendicular lean mass as a surrogate, but inaccurate, measurement of muscle mass. Other previously used methods (total body water, bioelectric impedance, and imaging) also have significant limitations. D3‐Creatine (D3‐Cr) dilution provides a direct and accurate measurement of creatine pool size and skeletal muscle mass. In a recent study in older men (MrOS cohort), D3‐Cr muscle mass was associated with functional capacity and risk of injurious falls and disability, while assessments of LBM or appendicular lean mass by DXA were only weakly or not associated with these outcomes. Inaccurate measurements of muscle mass by DXA and other methods have led to inconsistent results and potentially erroneous conclusions about the importance of skeletal muscle mass in health and disease. The assessment of skeletal muscle mass using the D3‐Cr dilution method in prospective cohort studies may reveal sarcopenia as a powerful risk factor for late life disability and chronic disease.

Sex-related differences in frailty factors in older persons with type 2 diabetes: a cross-sectional study.

Background:This cross-sectional study aimed to describe sex-related differences in diabetes-specific factors underlying the development of frailty in older persons with type 2 diabetes.Methods:Older persons aged 60–80 years were sequentially enrolled. Frailty and sarcopenia were evaluated using the validated Kihon checklist (KCL) and Asian Working Group for Sarcopenia algorithm, respectively. Physical function and characteristics were measured by trained nurses independently.Results:This study included 213 participants. The mean age, body mass index (BMI), and glycated hemoglobin (HbA1c) level were 70.4 years, 24.3 kg/m2, and 7.4%, respectively. Prevalence of frailty was higher in women. Social and cognitive functions were lower in the prefrailty stage, while physical function was lower in the frailty stage, although there was no decrease in skeletal muscle mass. After adjustment for age, the KCL score was significantly associated with peripheral neuropathy, diet score, and coronary artery disease (CAD); frailty, with CAD and inoccupation; prefrailty, with diet score; and sarcopenia, with living alone in men. Meanwhile, the KCL score was significantly associated with living alone and skeletal muscle percentage; prefrailty, with peripheral neuropathy; and sarcopenia, with diabetes duration, LDL-cholesterol level, diet score, and irregular lifestyle in women.Conclusions:Sex differences in the risk factors of frailty should be considered when selecting preventive strategies for older persons with type 2 diabetes, early in the prefrailty stage. In particular, it is important to evaluate social participation and diet therapy in men and skeletal muscle mass and psychosocial function in women.

Study Protocol for the Effects of Formula Diet with Dapagliflozin on Metabolic Improvement and Body Composition in Type 2 Diabetes Mellitus.

IntroductionSodium-dependent glucose transporter-2 (SGLT2) inhibitors such as dapagliflozin induce weight loss, but the mechanism is thought to involve loss of both body fat and skeletal muscle mass. The decrease in skeletal muscle mass may lead to worsening of insulin resistance in type 2 diabetes patients. On the other hand, formula diet (FD) is a low-calorie food containing low carbohydrates, low fat, and sufficient protein, vitamins, and minerals to support a healthy and balanced diet, and is used for the treatment of obesity or diabetes. Therefore, we examine whether the protein supplementation is superior to the fat supplementation in metabolic improvement of the poorly controlled type 2 diabetes patients treated with SGLT2 inhibitor. We compare the therapeutic effects using two types of FD; a high protein FD and a high fat FD. Patients are prescribed dapagliflozin and replacement of one of three meals with FD. We compare high protein FD and high fat FD with respect to improvement of glycemic control while maintaining skeletal muscle mass.MethodsWe conduct a prospective, multicenter, double-blinded, randomized, controlled, investigator-initiated clinical trial. Patients who satisfy the eligibility criteria will be randomized to two groups (1:1) and prescribed 5 mg of dapagliflozin once daily together with a high protein FD or high fat FD (same number of calories) to replace one of three meals a day (one meal with FD only and two normal meals). The observation period for both groups is 24 weeks. The primary endpoint is the change in HbA1c.Planned OutcomesThis study is ongoing and scheduled to complete in June 2019. The findings of this study will be disseminated through peer-reviewed publications and conference presentations.Trial RegistrationUniversity Hospital Medical Information Network (UMIN) 000024580.FundingThis study was carried out under contract with the specified nonprofit corporation Hokkaido Institute of Health Sciences, based on a grant from AstraZeneca Co., Ltd. and Ono Pharmaceutical Co., Ltd. for an investigator-initiated clinical trial. The authors funded the journals article processing charges.

Aging, physical activity, and diabetic complications related to loss of muscle strength in patients with type 2 diabetes.

Patients with type 2 diabetes may have motor dysfunctions such as loss of muscle strength. Compared with non-diabetic subjects, patients with diabetes show decreased lower extremity muscle strength. The aim of this review was to describe the influence of factors associated with loss of muscle strength in patients with type 2 diabetes. Aging promotes an accelerated loss of muscle strength in patients with diabetes. Physical inactivity may cause a decline in muscle strength in patients with diabetes. Gradual loss of muscle strength is related to the presence and severity of diabetic neuropathy. Diabetic nephropathy may be a factor contributing to loss of muscle strength, because decrease in skeletal muscle mass is a hallmark of end-stage renal disease. Resistance exercise is an essential component of diabetes treatment regimens and also plays a role in the prevention and management of sarcopenia. Intensive physical therapy intervention should be provided to patients with diabetes having decreased muscle strength.

Postoperative Skeletal Muscle Loss Predicts Poor Prognosis of Adenocarcinoma of Upper Stomach and Esophagogastric Junction.

The relationship between postoperative changes in muscle mass and the prognosis of malignancies remains controversial. We aimed to determine whether a decrease in skeletal muscle mass after surgical resection can predict long-term outcomes in patients with adenocarcinoma of upper stomach (AUS) and esophagogastric junction (AEGJ). We reviewed 146 patients who underwent curative surgery for AUS and AEGJ. We assessed the skeletal muscle index pre- and post-surgery and 6months postoperatively. The rate of decrease in skeletal muscle index (SMI) was calculated and its relationship with clinicopathological factors and prognosis was analyzed. Among the 146 patients studied, 115 underwent re-assessment of SMI 6months postoperatively. The mean decrease in SMI was more prominent in patients with recurrence than in those without recurrence (19.0 ± 2.3 vs. 7.4 ± 0.9%, respectively, P < 0.0001). AUS and AEGJ patients with a >19% decrease in SMI showed significantly lower 5-year overall survival and recurrence-free rates than those with a <19% decrease in SMI (recurrence-free survival: 33.4 vs. 89.2%, respectively, P < 0.0001; overall survival: 40.6 vs. 90.0%, respectively, P < 0.0001). Multivariate analyses indicated that a ≥19% decrease in SMI could predict poor overall survival independently in patients with AUS and AEGJ (P = 0.0070). A ≥19% postoperative decrease in SMI was substantially associated with poor survival in patients with AUS and AEGJ.

Juzentaihoto hot water extract alleviates muscle atrophy and improves motor function in streptozotocin-induced diabetic oxidative stress mice.

A decrease in skeletal muscle mass and motor function occurs in diabetic patients. In type 1 diabetic patients, in particular, fast-type fiber-dominated muscle atrophy occurs due to increased oxidative stress and inflammation. Juzentaihoto is a herbal medicine that has been found to be effective in reducing oxidative stress. In this study, juzentaihoto hot water extract (JTT) was administered prophylactically to mice with diabetic oxidative stress, which was induced by an injection of streptozotocin, and the effects on skeletal muscle mass, motor function, and antioxidant activity were evaluated. In mice that were administered JTT, skeletal muscle atrophy and loss of motor function were suppressed. Additionally, the administration of JTT increased the mRNA expression level of Sirt1 and the activity of superoxide dismutase in the gastrocnemius. In addition to skeletal muscle atrophy, atrophy of the liver, spleen and thymus gland, and kidney hypertrophy were also suppressed. Furthermore, in order to evaluate the antioxidant activity of 10 constituent crude drugs that comprise juzentaihoto, Sirt1 transcriptional activity in C2C12 cells was evaluated. The Sirt1 transcriptional activity was increased by Cinnamomi Cortex, Astragali Radix, and Glycyrrhizae Radix extracts. These three constituent crude drugs play an important function in the antioxidant action of juzentaihoto, suggesting that juzentaihoto can prevent muscle atrophy by decreasing oxidative stress.

Effect of Changes in Skeletal Muscle Mass on Oncological Outcomes During First-Line Sunitinib Therapy for Metastatic Renal Cell Carcinoma.

Sarcopenia is a state of degenerative skeletal muscle wasting induced by cancer cachexia. To evaluate the prognostic impact of changes in skeletal muscle mass (SMM) during first-line sunitinib therapy on oncological outcomes in metastatic renal cell carcinoma (mRCC). Sixty-nine patients were evaluated retrospectively. The skeletal muscle index (SMI) was calculated based on computed tomography images obtained before the initiation (pre-treatment SMI) and after two cycles of sunitinib treatment (post-treatment SMI). The change in SMM was evaluated based on the value of ΔSMI, which was calculated as [(posttreatment SMI - pretreatment SMI)/ pretreatment SMI] × 100. Oncological outcomes were compared between patients with ΔSMI <0 (SMM decrease) and ΔSMI ≥0 (SMM maintenance). A decrease in SMM was observed in 38 patients (55.1%). Progression-free survival (PFS) and overall survival (OS) after sunitinib therapy initiation were significantly shorter in patients with ΔSMI <0 than in those with ΔSMI ≥0 (median PFS: 9.53 vs. 28.4months, p < 0.0001; OS: 19.8 vs. 52.6months, p = 0.0001). ΔSMI was an independent predictive factor for PFS (HR 3.25, 95% CI 1.74-6.29, p = 0.0002) and OS (HR 4.53, 95% CI 2.15-10.5, p < 0.0001). The objective response rate was significantly lower in patients with ΔSMI <0 than in those with ΔSMI ≥0 (23.7% vs. 51.6%, p = 0.0164). Decreased SMM during first-line sunitinib therapy can be aneffective markerof outcome prediction for mRCC.

Amino Acid Nutrition in the Prevention and Treatment of Sarcopenia

Sarcopenia is the decrease in skeletal muscle mass and muscular function that occurs with aging. The underlying mechanisms of sarcopenia include anabolic resistance, which is defined as a poor muscle protein synthetic response to previously effective stimuli such as nutrients and exercise. Among the nutrients that humans ingest, amino acids directly trigger the synthesis of muscle proteins. The essential amino acid leucine, in particular, functions as a stimulatory signal. Leucine-enriched essential amino acids help overcome anabolic resistance in elderly individuals to effectively stimulate muscle protein synthesis. Long-term intake of leucine-enriched essential amino acids has a synergistic effect with exercise to increase skeletal muscle mass, strength, and walking speed in elderly individuals, and can be an effective countermeasure to sarcopenia.

Characterization of Changes in Clinical and Metabolic Parameters for Patients in an Intensive Medical Weight Management Program

Introduction: Obesity is linked to multiple comorbid conditions such as hypertension, hyperlipidemia, diabetes mellitus and cardiovascular disease; digestive disorders associated with obesity include gastroesophageal reflux disease symptoms, erosive esophagitis, Barrett's esophagus, cholelithiasis, nonalcoholic fatty liver disease (NAFLD), cirrhosis, precancerous colon polyps and cancers. The aim of this study is to report changes in clinical and metabolic parameters for patients who underwent an intensive medical weight management program (IMWMP). Methods: Our IMWMP involved visits every two to four weeks with medical providers, a low carbohydrate diet with individualized goal carbohydrates often fewer than 100 g per day, encouraging physical activity, pharmacotherapy for some patients and surveillance every three months with bioelectrical impedance analyzer (BIA). The goal of IMWMP was to help patients lose 10% or more weight. We retrospectively chart reviewed the first 225 patients enrolled in our IMWMP starting in 2015; only patients who had three or more visits with medical providers were included. Analyzed clinical and metabolic parameters included blood pressure, pulse, hemoglobin A1C (HgbA1C), liver chemistries AST and ALT, lipids and CRP (Table 1). BIA data is reported only on patients who had at least two BIA studies and included body weight, body mass index, skeletal muscle mass, visceral adipose tissue and others (Table 2). All comparisons are between baseline and most recent values. Results: 160 patients met inclusion criteria, of which 78 were active enrollees. The mean weight at the time of joining IMWMP and most recent office visit were 238.8 lbs and 214.6 lbs, respectively, for a mean weight loss of 24.2 lbs (-10.13%). Changes in blood pressure, pulse and HgbA1C were minimal (Table 1). AST and ALT decreased by mean of 24.18% and 28.89%, respectively (Table 1). On average, triglycerides decreased by 17.3% and HDL increased by 16.26%. BIA analysis is reported on 125 patients; it showed a mean decrease in fat mass of 12.42%, decrease in visceral adipose tissue of 16.88% and decrease in skeletal muscle mass of 5.14% (Table 2). Conclusion: Our IMWMP led to improvements in many clinical and metabolic parameters. Decrease in liver chemistries with associated weight loss highlights the importance of weight loss in managing NAFLD. Patients in weight loss programs are prone to sarcopenia and our use of BIA in providing dietary recommendations minimized the loss of skeletal muscle mass.1041_A Figure 1. compares mean clinical and metabolic parameters between baseline and after intervention.1041_B Figure 2. compares mean bioelectric impedance analyzer data between baseline and after intervention.

Skeletal Muscle Loss during Neoadjuvant Chemotherapy Is an Independent Risk Factor for Postoperative Infectious Complications in Patients with Advanced Esophageal Cancer

Objective: Neoadjuvant therapy followed by surgery has been the standard treatment for advanced esophageal cancer. Severe toxicities may influence body composition, including skeletal muscle mass, and increase postoperative complications. The purpose of this study was to evaluate the influence of sarcopenia, changes in body composition, and adverse events during neoadjuvant chemotherapy (NACT) on postoperative complications in esophageal cancer patients. Methods: A total of 83 patients with esophageal cancer undergoing NACT followed by esophagectomy were included. Body composition was assessed before chemotherapy and before esophagectomy. The relationships between postoperative infectious complications and sarcopenia, changes in body composition, and adverse events during NACT were investigated. Results: Univariate analysis revealed that skeletal muscle loss during NACT, but not preoperative sarcopenia, was significantly higher in the complication (+) group. Febrile neutropenia tended to occur frequently in the complication (+) group. Multivariate analysis demonstrated that skeletal muscle loss was the only factor significantly associated with infectious complications (p = 0.029). Among adverse events, febrile neutropenia was significantly associated with a decrease in skeletal muscle mass. Conclusion: Loss of skeletal muscle mass during NACT was a significant risk factor for postoperative infectious complications in patients with esophageal cancer. Prevention of severe adverse events may reduce postoperative infectious complications.

Profiles Associated with Sarcopenia in Hepatoma Patients Underwent Transcatheter Arterial Chemoembolization: A Data‐Mining Analysis

AbstractAimsSarcopenia is a prognostic factor in patients with hepatocellular carcinoma (HCC). Transcatheter arterial chemoembolization (TACE) may aggravate sarcopenia because of post‐embolization syndrome. The aims of this study are to investigate changes in skeletal muscle mass after TACE and its risk profiles in patients with HCC.Methods and resultsWe enrolled 104 HCC patients (age 73.5 [41.0–88.0] years, female/male 35/69, body mass index 22.4 [16.0–32.7]). Changes in skeletal muscle mass were evaluated by Δskeletal muscle index (SMI) using computed tomography before and after TACE. Factors correlated with ΔSMI were evaluated. Independent factors and profiles associated with a decrease in SMI were evaluated by multivariate analysis and decision‐tree analysis, respectively. SMI was significantly decreased after TACE in patients with HCC (32.8 vs. 30.6 cm2/m2; P=0.0001). However, there was no significant correlation between the ΔSMI and other variables including Δalbumin. In the logistic regression analysis, no factor was significantly associated with a decrease in SMI. In the decision‐tree analysis, sex was selected as the initial split and, in female, 74% of subjects showed a decrease in SMI. While, in male, an estimated glomerular filtration rate (eGFR) ≤81.7 ml/min/1.73 m2 was the second split; of these patients, 74% of subjects had a decreased SMI.ConclusionsWe demonstrated that skeletal muscle mass was decreased after TACE in patients with HCC. “female” and “male who had a lower eGFR” were profile for a decrease in skeletal muscle mass. Thus, such patients who have HCC treated with TACE may benefit from preventive treatment for sarcopenia.

How to Diagnose Sarcopenia in Korean Older Adults?

In 2017, Korea became an aged society, with the percentage of the population aged ≥65 years accounting for 14% of the total Korean population. The increasing number of older adults and the current health status of Korean older adults had led to increased medical expenditure and social problems. Sarcopenia, defined as the progressive decrease in skeletal muscle mass and strength, develops as a consequence of aging. Sarcopenia is also associated with a risk of adverse health outcomes such as frailty, physical disability, poor quality of life, and death. Thus, sarcopenia is a serious clinical problem among older adults. The International Classification of Diseases, Tenth Revision, Clinical Modification code for sarcopenia, M62.84, became available on October 1, 2016, in the United States. The diagnosis and treatment of sarcopenia urgently requires the establishment of an operational definition for sarcopenia in Korean older adults. In this article, I suggest a screening strategy and diagnostic criteria for sarcopenia in this population.

Hyperglycemia Promotes Muscle Atrophy through the WWP1/KLF15 Pathway

Background: Evidence suggests that diabetes is a promoting factor of sarcopenia. Mechanism how the condition accelerates the development of sarcopenia remains ambiguous. Results: In streptozotocin (STZ)-induced diabetic mice, skeletal muscle mass was decreased by ∼15 % within 21 days after the STZ treatment. The protein abundance of transcription factor KLF15 as well as the mRNA abundance of proteins related to muscle atrophy (Foxo3a, Atrogin1 and Murf1) were elevated whereas the mRNA of KLF15 was unaltered in skeletal muscle of STZ-diabetic mice. Decrease in skeletal muscle mass and increase in the mRNA abundance of muscle atrophy-related proteins triggered by STZ-induced diabetes were prevented in muscle-specific KLF15 deficient mice suggesting that KLF15 plays a key role in diabetes-induced muscle atrophy. Treatment of C2C12 cells with high concentration of glucose (25 mmol/l) decreased the ubiquitination of and increased the protein abundance of KLF15. The E3 ubiquitin ligase WWP1 was found to be downregulated in skeletal muscle of STZ- diabetic mice and in C2C12 cells treated with glucose. Overexpression and knockdown of WWP1 in C2C12 cells resulted in the decrease and the increase, respectively, of KLF15 protein without affecting its mRNA expression. The mRNA abundance of WWP1 in skeletal muscle was downregulated and the mass of skeletal muscle was reduced in Akita mice, which develop diabetes due to beta-cell dysfunction. Administration of the SGLT2 inhibitor empagliflozin, which lowers glycemia without affecting insulin levels, to Akita mice upregulated the expression of WWP1 in skeletal muscle and increased the skeletal muscle mass of these mice. Conclusion: Our results suggest that hyperglycemia upregulates the protein abundance of KLF15 via the downregulation of WWP1, which catalyzes the ubiquitination of KLF15. Hyperglycemia-induced upregulation of KLF15 leads to the induction of genes for muscle atrophy-related proteins, which in turn promotes the atrophy of skeletal muscle. Disclosure Y. Hirata: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. K. Nomura: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Y. Senga: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. M. Imamura: None. S. Takeda: None. Y. Okada: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. S.J. Burden: None. T. Hosooka: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. W. Ogawa: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Abbott.

Relationship between oxidative stress and muscle mass loss in early postmenopause: An exploratory study

BackgroundEndocrine changes due to menopause have been associated to oxidative stress and muscle mass loss. The study objective was to determine the relationship between both variables in early postmenopause. Material and methodsAn exploratory, cross-sectional study was conducted in 107 pre- and postmenopausal women (aged 40–57 years). Levels of serum lipid peroxides and uric acid and enzymes superoxide dismutase and glutathione peroxidase, as well as total plasma antioxidant capacity were measured as oxidative stress markers. Muscle mass using bioelectrical impedance and muscle strength using dynamometry were also measured. Muscle mass, skeletal muscle index, fat-free mass, and body mass index were calculated. ResultsMore than 90% of participants were diagnosed with overweight or obesity. Postmenopausal women had lower values of muscle mass and strength markers, with a negative correlation between lipid peroxide level and skeletal muscle index (r=−0.326, p<0.05), and a positive correlation between uric acid and skeletal muscle index (r=0.295, p<0.05). A multivariate model including oxidative stress markers, age, and waist circumference showed lipid peroxide level to be the main contributor to explain the decrease in skeletal muscle mass in postmenopause, since for every 0.1μmol/l increase in lipid peroxide level, skeletal muscle index decreases by 3.03 units. ConclusionOur findings suggest an association between increased oxidative stress and muscle mass loss in early postmenopause.

Exercise and Nutrition Strategies to Counteract Sarcopenic Obesity.

As the population is aging rapidly, there is a strong increase in the number of individuals with chronic disease and physical limitations. The decrease in skeletal muscle mass and function (sarcopenia) and the increase in fat mass (obesity) are important contributors to the development of physical limitations, which aggravates the chronic diseases prognosis. The combination of the two conditions, which is referred to as sarcopenic obesity, amplifies the risk for these negative health outcomes, which demonstrates the importance of preventing or counteracting sarcopenic obesity. One of the main challenges is the preservation of the skeletal muscle mass and function, while simultaneously reducing the fat mass in this population. Exercise and nutrition are two key components in the development, as well as the prevention and treatment of sarcopenic obesity. The main aim of this narrative review is to summarize the different, both separate and combined, exercise and nutrition strategies so as to prevent and/or counteract sarcopenic obesity. This review therefore provides a current update of the various exercise and nutritional strategies to improve the contrasting body composition changes and physical functioning in sarcopenic obese individuals.