Calf Skeletal Muscle Research Articles

427 Impact of late gestation slow-release nitrogen-enriched diets on energy metabolism in calf skeletal muscle: A proteomic and transcriptomic approach

427 Impact of late gestation slow-release nitrogen-enriched diets on energy metabolism in calf skeletal muscle: A proteomic and transcriptomic approach

Reliability of In Vivo Creatine-Weighted Chemical Exchange Saturation Transfer (CrCEST) MRI in Calf Skeletal Muscle of Healthy Volunteers at 3 T.

Skeletal muscle mitochondrial oxidative phosphorylation (mtOXPHOS) is important for ATP generation and its dysfunction leads to exercise intolerance. Phosphorus magnetic resonance spectroscopy (31P-MRS) is a useful, noninvasive technique for mtOXPHOS assessment but has limitations. Creatine-weighted chemical exchange saturation transfer (CrCEST) MRI is a potential alternative to assess muscle bioenergetics. To evaluate the interscan repeatability, intra- and interobserver reproducibility of CrCEST during mild plantar flexion exercise. Retrospective. Twenty healthy volunteers (age 37.6 ± 12.4 years, 11 females). 3 T/CEST imaging using gradient echo readout. τCrCEST (postexercise Cr recovery time) was assessed in two scans for each participant, following mild plantar flexion exercises targeting the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (Sol) muscles. Three observers measured τCrCEST for interobserver reproducibility. Three readings by one observer were used to measure intraobserver reproducibility. Two scans were used for within-participant interscan repeatability. Paired t tests, intraclass correlation coefficient (ICC), and Pearson correlation were conducted. Bland-Altman plots were used to analyze the interobserver variability. A P-value of 0.05 was considered statistically significant. There was excellent intra- (ICC ) and interobserver (ICC ) reproducibility, with moderate interscan repeatability for τCrCEST in LG and MG (ICC ) and poor-to-moderate interscan repeatability in Sol (ICC ). Excellent interobserver reproducibility was confirmed by Bland-Altman plots (fixed bias P-value ). CrCEST MRI shows promise in assessing muscle bioenergetics by evaluating τCrCEST during mild plantar flexion exercise with reasonable reliability, particularly in LG and MG. 4 TECHNICAL EFFICACY: Stage 1.

Abstract P151: Increased Gain of Skeletal Muscle Adiposity in Middle-Aged African Caribbean Men With Type 2 Diabetes

While type 2 diabetes (T2D) is a known risk factor for the acceleration of muscle loss with aging, less is known about the impact of T2D on skeletal muscle fat infiltration (i.e., myosteatosis) and overall adiposity. Myosteatosis increases with aging, is greater in African as compared to European ancestry individuals, and plays an important role in the development of T2D. Thus, we investigated the association of T2D with changes in body adiposity distribution, with a particular interest in myosteatosis. T2D was identified by self-report, use of hypoglycemic agents, or fasting glucose levels of ≥ 126 mg/dL. Longitudinal changes in computed tomography-measured calf skeletal muscle density [as an inverse surrogate measure of intramuscular adiposity (mg/cm 3 )] and dual-energy X-ray absorptiometry-measured regional and whole body fat were examined by T2D status over an average of 6 years in 724 African-Caribbean men aged 40-54 years from the Tobago Health Study. Total body, arm, leg, and trunk adiposity increased to a significantly greater extent among men without compared to with T2D. In contrast, men with T2D had a 1.6 times greater decrease in calf skeletal muscle density compared with their non-diabetic counterparts (p=0.03). T2D is associated with lower gains in general adiposity, but an increased gain in skeletal muscle adiposity among middle aged African Caribbean men. Our novel findings suggest that middle-aged African Caribbean men with T2D might be at especially high risk for increased gain of myosteatosis. Interventions targeted for men in this age group could focus on controlling diabetes, slowing myosteatosis, and promoting healthy aging.

Assessment of Calf Skeletal Muscle Stiffness in Diabetic Nephropathy Patients with Medial Tibial Stress Syndrome by Two-Dimensional Shear Wave Elastography

Objective: To explore the feasibility of two-dimensional shear wave elastography in evaluating calf skeletal muscle stiffness in diabetic nephropathy patients with medial tibial stress syndrome. Methods: A total of 48 diabetic nephropathy patients with medial tibial stress syndrome from January 2020 to December 2022 were included as the study group, and 48 patients with diabetic nephropathy during the same period were included as the control group. Both groups were detected by two-dimensional shear wave elastography with ultrasonic equipment, and Young‘s modulus of the tibialis anterior muscle, tibialis posterior muscle, and gastrocnemius muscle were observed and analyzed in the two groups. Results: The Young‘s modulus values of tibialis anterior muscle, tibialis posterior muscle, and gastrocnemius muscle in the study group were significantly lower than those in the control group (P < 0.05). Conclusion: Two-dimensional shear wave elastography is feasible for the evaluation of calf skeletal muscle stiffness in diabetic nephropathy patients with medial tibial stress syndrome, and has high accuracy and repeatability. This technique can be used to diagnose, treat and monitor muscle lesions in patients with diabetic nephropathy, and can also be used to assess muscle fatigue and exercise capacity, which has broad application prospects.

Home‐Based Leg Heat Therapy Does Not Improve Vascular Function in Patients with Symptomatic Peripheral Artery Disease

INTRODUCTIONPatients with peripheral artery disease (PAD) suffer from severe exercise intolerance and accelerated rates of functional decline, resulting, in part, from significant endothelial cell dysfunction and the consequent impairment in leg blood flow. Unfortunately, few non‐invasive therapeutic interventions have been shown to ameliorate the microvascular dysfunction in patients with PAD. Repeated exposure to heat therapy (HT) improves endothelial function in sedentary young individuals, but the effects of this therapy on vascular function in patients with PAD remain poorly defined. The objective of the present study was to test the hypothesis that 8 weeks of home‐based leg HT would improve leg vascular function in patients with symptomatic PAD.METHODSThirty‐four patients with symptomatic PAD (66 ± 8 years, ankle‐brachial index: 0.68 ± 0.12) were randomized into one of two groups: home‐based leg HT (HT, n=18) or a control treatment (CON, n=16). Patients in both groups were provided with identical water‐circulating trousers and a portable heating pump and were asked to apply the therapy daily (7 days/week, 90 min per session) for 8 consecutive weeks. The pump issued to participants circulated water through the trousers at 43ºC in the HT group and 33ºC in the control group. Laser‐Doppler flowmetry was used to measure red blood cell flux, an index of skin blood flow, during local skin heating to 39°C for 40 min, followed by 43ºC for 20 min. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure and expressed as a percentage of maximal vasodilation (%CVCmax). Calf skeletal muscle perfusion was assessed using arterial spin labeling magnetic resonance imaging (MRI) following circulatory occlusion of the thigh for 5 min.RESULTSFive participants were either withdrawn prior to study completion or failed to complete the 8‐week follow‐up visit. The remaining 29 participants were included in the final analysis (CON: n=14, HT: n=15). Two participants from CON and 4 from HT were unable to undergo the MRI scans. At baseline, local skin heating to 39ºC increased %CVCmax to 55.8 ± 12.9% in CON and 52.5 ± 18.7% in the HT group. The change from baseline to 8 weeks in %CVCmax was similar between CON and HT (CON: ‐2.6 ± 13.9%, HT: ‐0.7 ± 16.3%, p=0.74). Peak calf blood flow during reactive hyperemia was comparable between groups at baseline (CON: 48.0 ± 24.6 ml/min/100g, HT: 43.8 ± 20.4 ml/min/100g, p=0.76). The change from baseline to 8 weeks in peak calf perfusion was also similar between CON and HT (CON: ‐4.8±21.9 ml/min/100g, HT: ‐2.8±11.0 ml/min/100g, p=0.84).CONCLUSIONEight weeks of home‐based leg HT does not improve leg vascular function in patients with symptomatic PAD.

Abstract MP22: Myosteatosis Is Associated With Worse Cognition In African Caribbean Women

Introduction: Skeletal muscle adipose tissue infiltration (i.e. myosteatosis) increases with aging, and is recognized as a major risk factor for cardio-metabolic diseases. While it is known that visceral adiposity is related to dementia and cognitive decline, the relationship between myosteatosis and cognition is not well understood. Such studies are particularly needed among African ancestry women, who have greater myosteatosis and higher burden of Alzheimer’s Disease and Related Dementias compared with White women. Aim: The objective of this study was to assess if, among African Caribbean middle-aged and older women (aged 40-79), myosteatosis is associated with cognitive function. Methods: Data were collected on women (n=481) from the Tobago Health Study. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a test of information processing speed; DSST is a fast, reliable and sensitive test that predicts onset of dementia. DSST was administered to participants by trained interviewers; scores ranged from 0 to 81 (lower score indicating cognitive decline). Peripheral Quantitative Computed Tomography (Stratec XCT-2000) was used to measure calf skeletal muscle density (MD), which was used as a proxy measure for the myosteatosis (lower MD reflects more adiposity). Linear regression was used to assess the association of muscle density with cognition and was adjusted for age, education, muscle area, waist circumference, alcohol intake, smoking, walking hours, diabetes and hypertension. Results for the primary predictor of interest (MD) were standardized with effects shown per standard deviation (SD). Results: Mean (SD) DSST scores were 38.8 (13.2). Overall, participants were aged 55.2 years and had a BMI of 30.7 kg/m 2 . Mean (SD) MD was 71.7((5.3) (mg/cm 3 ). As expected, in unadjusted analyses, the strongest predictors of lower DSST scores in these women were older age and lower education, higher waist circumference, diabetes and hypertension. After full adjustment, we found that a one SD increase in MD was associated with a 1.48 increase in DSST score (p-value=0.015). Conclusions: Our findings suggest that in African Caribbean women, greater myosteatosis is associated with slower information processing speed, an early indicator of future dementia risk. Future studies using expanded battery of cognitive tests and longitudinal follow-up are warranted to further advance our understanding of the novel role of myosteatosis in dementia risk among African ancestry women.

Predictive Value of Contrast-Enhanced Ultrasound in Chemical Lumbar Sympathectomy for End-Stage Arteriosclerosis Obliterans of the Lower Extremities.

IntroductionThe therapeutic effect of chemical lumbar sympathectomy (CLS) on ischemic diseases of the lower limbs varies greatly among individuals. The time to peak (TTP) response in contrast-enhanced ultrasound (CEUS) can reflect the perfusion disorder of the calf skeletal muscle and the collateral circulation. In this study we evaluated the predictive value of CEUS in patients treated with CLS for end-stage atherosclerotic occlusive disease of the lower extremity (ASO-LE).MethodsThis was a prospective study that included patients with end-stage ASO-LE and moderate to severe pain who had undergone a CEUS examination and CLS procedure and who were observed for 12 months after surgery. The patients’ characteristics and prognostic factors, including lower limb pain score, skin temperature, walking distance, and ulcer and gangrene healing, were recorded.ResultsFifty-eight patients with a mean age of 66.24 (range 58–78) years were included in the study, of whom 42 (71.41%) were men. Following the CLS procedure, the numerical rating scale (NRS)-measured pain decreased significantly, and the skin temperature of the affected limb increased significantly (P < 0.05). The satisfaction rate of lower limb pain relief 1 year after operation was 53.45%. Correlation analysis showed that preoperative TTP response was correlated with the NRS score and skin temperature of the affected limb at 6 months and 12 months post surgery (P < 0.05). The binary logistic regression analysis indicated that a longer preoperative TTP response was associated with a higher risk of poor pain relief after CLS (odds ratio 1.126, 95% confidence interval 1.058–1.205). The receiver operating characteristic curve showed that preoperative TTP response had a certain predictive value on CLS treatment effect, with a sensitivity and specificity of 81.5% and 83.9%, respectively. When the preoperative TTP response was > 77.5, the risk of poor response after CLS increased.ConclusionsPreoperative TTP response was able to predict the therapeutic effect of CLS to a certain extent, and thus may aid physicians in determining the choice of CLS treatment for patients with ASO-LE.Trial RegistrationChinese Clinical Trial Registry: ChicTR1900028424 (principal investigator: Yue Wu; date of registration: 21 December 2019).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00347-9.

Relationship between Calf Circumference and Skeletal Muscle Index among Community-Dwelling Thai Elderly

Background: A strong association between calf circumference (CC) and skeletal muscle index (SMI) has been established worldwide in the elderly, however, these data in the Thai population are lacking. Objective: To evaluate the relationship between CC and SMI, as well as to identify the important predictors of SMI among the community-dwelling Thai elderly. Materials and Methods: The present study was an analytic cross-sectional study performed in 110 community-dwelling adults aged 60 years and older who lived in Sriracha, Chonburi, Thailand. Weight, height, and the maximum CC were measured in standing position. Body composition was measured using the bioelectrical impedance analysis (BIA) and the SMI was calculated as the appendicular skeletal muscle mass (ASM) divided by the height squared (kg/m²). Pearson’s correlation was used to indicate the relationship between CC and SMI. Multiple linear regression was developed to predict SMI. Results: The prevalence of low muscle mass in men and women were 23.5% and 33.3%, respectively. CC had a positive correlation with SMI (r=0.75; p&lt;0.001). The cut-off values for predicting low muscle mass using CC were 34.0 cm (sensitivity 85.5%, specificity 71.8%, AUC 0.895) in women, and 33.4 cm (sensitivity 75.0%, specificity 92.3%, AUC 0.925) in men. Multiple linear regression analysis revealed age, gender, weight, and CC as the key predictors for SMI with adjusted r² of the model equal to 0.80. CC and weight had a direct effect on SMI. On the other hand, age was inversely related to SMI. Women had lower SMI than men. Conclusion: CC was positively associated with SMI, and it could be used as a screening tool to identify the community-dwelling Thai elderly with low muscle mass in the field settings. Important predictors of SMI were age, gender, weight, and CC. Keywords: Calf circumference; Skeletal muscle index; Sarcopenia; Low muscle mass; Aging; Appendicular skeletal muscle mass

Assessment of Calf Skeletal Muscle in Male Type 2 Diabetes Mellitus Patients With Different Courses Using T1ρ Mapping.

The current clinical methods for detecting skeletal muscle complications of type 2 diabetes mellitus (T2DM) are invasive and insensitive. There is an urgent need for noninvasive assessment of skeletal muscle microstructure changes during the disease progression and treatment to assist the clinical management. This work aimed to investigate the T2DM caused changes in the fast-twitch tibialis anterior (TA) and slow-twitch soleus (SOL) skeletal muscles using T1ρ magnetic resonance imaging (MRI). This cross-sectional study took place from December 2014 to December 2020 at Zhongda Hospital Southeast University. A total of 26 new-onset and 15 long-term T2DM patients were enrolled, with the addition of 20 young and 13 older healthy volunteers as age-matched controls. T1ρ relaxation times of SOL and TA muscles in different groups were measured. Parametric and nonparametric tests were used to analyze the relationship between the T1ρ values in SOL and TA muscles and the length of illness, level of fasting blood glucose, and status of homeostasis model assessment of insulin resistance (HOMA-IR). T1ρ relaxation times of SOL and TA muscles both of new-onset and long-term T2DM patients were significantly higher than those of the young (P < .01, P < .05) and older healthy controls (P < .05, P < .01). Positive correlations were observed between the T1ρ relaxation times of the TA or SOL and the duration of T2DM (R2 = 0.420, R2 = 0.326), the level of fasting blood glucose (R2 = 0.253, R2 = 0.071) and HOMA-IR (R2 = 0.232, R2 = 0.414). Quantitative MRI measurement of T1ρ provides a noninvasive tool to assess T2DM-induced changes in the skeletal muscles of T2DM patients.

Pilot study of contrast-free MRI reveals significantly impaired calf skeletal muscle perfusion in diabetes with incompressible peripheral arteries.

Patients with diabetes mellitus (DM) are more likely to have densely calcified lesions in the below-the-knee tibial arteries. However, the relationship between peripheral arterial calcification and local skeletal muscle perfusion has not been explored. Thirty subjects were prospectively recruited into three groups in this pilot study: (1) Non-DM: 10 people without DM; (2) DM, ABI < 1.3: 10 people with DM and normal ankle-brachial index (ABI) (0.9-1.3); and (3) DM, ABI ⩾ 1.3: 10 people with DM and ABI ⩾ 1.3. All subjects underwent calf perfusion measurements at rest and during an isometric plantarflexion contraction exercise within the magnetic resonance imaging (MRI) system. The noncontrast MRI techniques were applied to quantitatively assess skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in medial gastrocnemius and soleus muscles. Both SMBF and SMOEF reserves were calculated as the ratio of the exercise value to the resting value. Exercise SMBF and SMOEF values in the medial gastrocnemius muscle were lower in the two DM groups than in the non-DM group (p < 0.05). The SMBF reserve in medial gastrocnemius was significantly lower in the DM, ABI ⩾ 1.3 group compared to the DM, ABI < 1.3 group (p < 0.05). This study demonstrates that people with DM and calcified arteries had lower perfusion in gastrocnemius muscle compared to those without DM and those with DM and a normal ABI.

Skeletal Muscle Pathology in Peripheral Artery Disease: A Brief Review.

This brief review summarizes current evidence regarding lower extremity peripheral artery disease (PAD) and lower extremity skeletal muscle pathology. Lower extremity ischemia is associated with reduced calf skeletal muscle area and increased calf muscle fat infiltration and fibrosis on computed tomography or magnetic resonance imaging. Even within the same individual, the leg with more severe ischemia has more adverse calf muscle characteristics than the leg with less severe ischemia. More adverse computed tomography-measured calf muscle characteristics, such as reduced calf muscle density, are associated with higher rates of mobility loss in people with PAD. Calf muscle in people with PAD may also have reduced mitochondrial activity compared with those without PAD, although evidence is inconsistent. Muscle biopsy document increased oxidative stress in PAD. Reduced calf muscle perfusion, impaired mitochondrial activity, and smaller myofibers are associated with greater walking impairment in PAD. Preliminary evidence suggests that calf muscle pathology in PAD may be reversible. In a small uncontrolled trial, revascularization improved both the ankle-brachial index and mitochondrial activity, measured by calf muscle phosphocreatine recovery time. A pilot clinical trial showed that cocoa flavanols increased measures of myofiber health, mitochondrial activity, and capillary density while simultaneously improving 6-minute walk distance in PAD. Calf muscle pathological changes are associated with impaired walking performance in people with PAD, and interventions that both increase calf perfusion and improve calf muscle health are promising therapies to improve walking performance in PAD.

Mitochondrial DNA damage in calf skeletal muscle and walking performance in people with peripheral artery disease

BackgroundPeripheral artery disease (PAD) is associated with mitochondrial dysfunction in calf skeletal muscle and a greater abundance of mitochondrial DNA (mtDNA) heteroplasmy. However, it is unknown whether calf skeletal muscle mtDNA of PAD participants harbors a greater abundance of mitochondrial DNA 4977-bp common deletion (mtDNA4977), strand breaks and oxidative damage (i.e., oxidized purines) compared to non-PAD participants and whether these mtDNA abnormalities are associated with poor walking performance in participants with PAD. MethodsCalf muscle biopsies were obtained from 50 PAD participants (ankle-brachial index (ABI) < 0.95) and 25 non-PAD participants (ABI = 0.99–1.40) matched by age, sex, and race. The abundance of mtDNA copy number, mtDNA4977 deletion, strand breaks, and oxidized purines in selected mtDNA regions coding for electron transport chain (ETC) constituents and the non-coding D-Loop region was determined in calf muscle. All participants completed measurement of 6-min walk and usual and fast-paced 4-m walking velocity test. ResultsParticipants with PAD (mean age = 65.4 years, SD = 6.9; 14 (28%) women, 38 (76%) black) and without PAD (mean age = 65.2 years, SD = 6.7; 7 (28%) women, 16 (64%) black) did not differ in the abundance of calf muscle mtDNA4977 deletion, mtDNA strand breaks, and oxidized purines. Though, a greater abundance of mtDNA strand breaks within ND4/5 genes was significantly associated with poorer 6-min walk distance, lower usual-paced 4-m walking velocity, and lower fast-paced 4-m walking velocity in non-PAD participants. Significant associations were also found in the density of strand break damage (i.e., damage per mtDNA copy) within ND1/2, ND4/5 and COII/ATPase 6/8 region with 6-min walk distance, usual-paced 4-m walking velocity and fast-paced 4-m walking velocity in non-PAD participants. Significant interactions were found between PAD presence vs. absence and density of strand break damage within ND1/2, ND4/5, COII/ATPase 6/8 regions for the associations with 6-min walk distance, usual-paced 4-m walking velocity, fast-paced 4-m walking velocity. Conversely, of the three walking performance measures only the usual-paced 4-m walking velocity showed a significant, although modest, negative association with the abundance of oxidized purines in the D-Loop (P = 0.031) and ND4/5 (P = 0.033) regions in the calf skeletal muscle of people with PAD. ConclusionOverall, these data suggest that the abundance of calf muscle mtDNA strand breaks and mtDNA4977 common deletion are not associated with walking performance in people with PAD and may not be directly involved in the pathophysiology of PAD. Conversely, strand breaks in specific mtDNA regions may contribute to poor walking performance in people without PAD. Further study is needed to confirm whether usual-paced 4-m walking velocity is associated significantly with a greater abundance of oxidized purines in the D-loop, a “mutational hotspot” for oxidative damage, and why this association may differ from the association with 6-min walk distance and fast-paced 4-m walking velocity.

Skeletal muscle expression of adipose-specific phospholipase in peripheral artery disease.

Flow-limiting atherosclerotic lesions of arteries supplying the limbs are a cause of symptoms in patients with peripheral artery disease (PAD). Musculoskeletal metabolic factors also contribute to the pathophysiology of claudication, which is manifest as leg discomfort that impairs walking capacity. Accordingly, we conducted a case-control study to determine whether skeletal muscle metabolic gene expression is altered in PAD. Calf skeletal muscle gene expression of patients with PAD and healthy subjects was analyzed using microarrays. The top-ranking gene differentially expressed between PAD and controls (FDR < 0.001) was PLA2G16, which encodes adipose-specific phospholipase A2 (AdPLA) and is implicated in the maintenance of insulin sensitivity and regulation of lipid metabolism. Differential expression was confirmed by qRT-PCR; PLA2G16 was downregulated by 68% in patients with PAD (p < 0.001). Expression of Pla2g16 was then measured in control (db/+) and diabetic (db/db) mice that underwent unilateral femoral artery ligation. There was significantly reduced expression of Pla2g16 in the ischemic leg of both control and diabetic mice (by 51%), with significantly greater magnitude of reduction in the diabetic mice (by 79%). We conclude that AdPLA is downregulated in humans with PAD and in mice with hindlimb ischemia. Reduced AdPLA may contribute to impaired walking capacity in patients with PAD via its effects on skeletal muscle metabolism. Further studies are needed to fully characterize the role of AdPLA in PAD and to investigate its potential as a therapeutic target for alleviating symptoms of claudication.

IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal Muscle.

Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate into α-ketoglutarate with concurrent reduction of NADP+ to NADPH. However, it is not fully understood how IDH2 is intertwined with muscle development and fatty acid metabolism. Here, we examined the effects of IDH2 knockout (KO) on skeletal muscle energy homeostasis. Calf skeletal muscle samples from 10-week-old male IDH2 KO and wild-type (WT; C57BL/6N) mice were harvested, and the ratio of skeletal muscle weight to body and the ratio of mitochondrial to nucleic DNA were measured. In addition, genes involved in myogenesis, mitochondria biogenesis, adipogenesis, and thermogenesis were compared. Results showed that the ratio of skeletal muscle weight to body weight was lower in IDH2 KO mice than those in WT mice. Of note, a noticeable shift in fiber size distribution was found in IDH2 KO mice. Additionally, there was a trend of a decrease in mitochondrial content in IDH2 KO mice than in WT mice (p = 0.09). Further, mRNA expressions for myogenesis and mitochondrial biogenesis were either decreased or showed a trend of decrease in IDH2 KO mice. Moreover, genes for adipogenesis pathway (Pparg, Znf423, and Fat1) were downregulated in IDH2 KO mice. Interestingly, mRNA and protein expression of uncoupling protein 1 (UCP1), a hallmark of thermogenesis, were remarkably increased in IDH2 KO mice. In line with the UCP1 expression, IDH2 KO mice showed higher rectal temperature than WT mice under cold stress. Taken together, IDH2 deficiency may affect myogenesis, possibly due to impairments of muscle generation and abnormal fatty acid oxidation as well as thermogenesis in muscle via upregulation of UCP1.

Associations of Poly (ADP-Ribose) Polymerase1 abundance in calf skeletal muscle with walking performance in peripheral artery disease.

This study investigated associations of markers of oxidative stress and mitochondrial function in calf muscle biopsies with walking performance in people with and without lower extremity peripheral artery disease (PAD). Participants with PAD (ankle-brachial index (ABI) <0.90) and without PAD (ABI: 0.90-1.50) underwent calf muscle biopsy and measurement of 6-min walk and four-meter walking velocity. PARP1 (Poly (ADP-Ribose) Polymerase 1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), silent information regulator 1 (SIRT1) and 4-hydroxynonenal (4HNE) expression were measured in calf muscle using western blot. Among 15 participants with PAD mean age: 66.8years (standard deviation (SD): 6.4) and six without PAD (age: 64.4years, SD: 5.9), mean PARP1-abundance in calf muscle was 1.16±0.92AU and 0.96±0.38AU, respectively (P=0.61). Among participants with PAD after adjustment with ABI, a greater abundance of PARP1 was associated with poorer 6-min walking distance (r=-0.65, P=0.01), usual-paced 4-m walking velocity (r=-0.73, P=0.003) and slower fast-paced four-meter walking velocity (r=-0.51, P=0.07). Among participants with PAD, ABI was not associated with PARP1 abundance in calf muscle (r=0.02, P=0.93). Among participants without PAD, skeletal muscle PARP1 abundance was not significantly associated with 6-min walk distance (r=-0.58; P=0.22), usual-paced walking velocity (r=-0.26; P=0.62), or fast-paced walking velocity (r=-0.21; P=0.69), perhaps due to lack of statistical power. There were no associations of remaining calf muscle measures with walking performance. These findings are consistent with the hypothesis that calf skeletal muscle characteristics are related to walking performance, independently of severity of lower extremity arterial obstruction in people with PAD.

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Meet the First Author.

Assessment of Age-related Oxygenation Changes in Calf Skeletal Muscle by Photoacoustic Imaging: A Potential Tool for Peripheral Arterial Disease.

Peripheral artery disease is often asymptomatic, and various imaging and nonimaging techniques have been used for assessment and monitoring treatments. This study is designed to demonstrate the ability of photoacoustic imaging to noninvasively determine changes in tissue oxygenation that occur in mice's hind limb skeletal muscle as they age. Mice from two age cohorts were scanned bilaterally with a pulsed laser. The photoacoustic signal was unmixed to generate a parametric map of estimated oxygen saturation and then overlaid on grayscale ultrasound images. Tissue oxygenation measured in young and old mice was compared. Photoacoustic imaging visually and quantitatively showed the decrease in skeletal muscle oxygenation that occurs with age. Percent tissue oxygenation decreased from 30.2% to 3.5% (p < 0.05). This reduction corresponded to reduced fractional area of oxygenation, which decreased from 60.6% to 6.0% (p < 0.05). The change in oxygenation capacity of the still active vascular regions was insignificant (p > 0.05). Intrasubject, intra-, and interobserver comparisons showed low variability in measurements, exhibited by high regression and intraclass correlations exceeding 0.81 for all ages. The decrease in oxygenation detected by photoacoustic imaging paralleled the known oxygenation decrease observed in aging tissues, demonstrating that photoacoustic imaging can assess age-related changes in a mouse calf muscle. These intramuscular changes could potentially act as a strong diagnostic marker for peripheral artery disease. This study thus opens the doors for a novel, affordable, noninvasive method of evaluation free of radiation or exogenous material.

633-P: Assessment of Calf Skeletal Muscle in Individuals with Diabetes and a Foot Ulcer Using Diffusion MRI

Aim: This study is to investigate changes in microstructure in the calf muscles of patients with type 2 diabetes mellitus (DM) and foot ulcers. Methods: 42 subjects were recruited: 14 without DM (WDM), 19 DM, and 9 DM and ulcer (DMU). They all underwent non-contrast diffusion imaging scans in a 3T MRI scanner, at rest and during a plantarflexion exercise with a fixed resistance. Results: Reserve data (exercise/rest) of major diffusion indexes for medial gastrocnemius (MG) and soleus (SOL) were calculated for analysis. The indexes were: Fractional Anisotropy (FA), Mean Diffusivity (MD), primary eigenvalue λ1, fiber length, and fiber angle. Diffusional and fiber changes (P&amp;lt;.05) were evident for the MG muscle in the DM and DMU groups (larger diffusional reserve values and larger fiber loss were observed in the DMU group) compared to the WDM group (Figure 1). The DMU was the only group that showed statistically significant diffusional variations (reserve FA, MD, and λ1) for the SOL muscle (P&amp;lt;.05). Conclusion: Diffusion imaging was able to identify DM associated muscle microstructure dysfunction in the calf. Disclosure M. Edalati: None. M. Hastings: None. C.J. Sorensen: None. M.J. Mueller: None. J. Zheng: Consultant; Self; KBI international. Funding National Institutes of Health

Relationship between calf circumference and skeletal muscle mass, strength and function in the elderly

Objective To investigate the relationship between calf circumference and skeletal muscle mass, strength and function in the elderly in Shanghai. Methods A total of 401 old people were recruited from physical examination centers in our hospital with the mean age of (71.8±7.4) years, including 202 males and 199 females.Adipose tissue, skeletal muscle mass (SMM) and appendicular skeletal muscle mass (ASM) were measured by bioelectrical impedance analysis. The ASM index (ASM/height2) and SMM index (SMM/height2) were calculated.Muscle function was measured by testing gait speed (m/s). Muscle strength was measured by handgrip strength(HGS) using an electronic hand dynamometer, with the dominant hand gripping for three times and taking the maximum value.Height, weight, right calf circumference and waist circumference were measured. Results Height, weight, ASM, ASM/height2, SMM, SMM/height2 and HGS were significantly higher in men than in women (P<0.01); adipose tissue was significantly higher in women than in men (P<0.05). The age, body mass index, calf circumference, waist circumference and gait speed were not statistically different (P=0.426, P=0.143, P=0.425, P=0.093, P=0.143). There were linear correlations between calf circumference and height, weight, BMI, waist circumference, ASM, ASM/height2, adipose tissue, grip strength, SMM and SMM/height2 (P=0.001, P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, P=0.003, P<0.001, P<0.001). There was no linear correlation between calf circumference and pace and age (P=0.818, P=0.078). Multiple stepwise regression analysis showed that height, BMI, ASM/height2 and SMM were correlated with the calf circumference. Conclusions Skeletal muscle mass and strength are higher in men than in women, while adipose tissue is higher in women than in men. Skeletal musle mass is an important factor affecting the calf circumference. There is a linear correlation between skeletal muscle strength and calf circumference. Key words: Calf circumference; Hand strength; Skeletal muscle mass

Diffusion Tensor Imaging of the Calf Muscles in Subjects With and Without Diabetes Mellitus.

Diffusion tensor imaging (DTI) has been used to characterize calf skeletal muscle architecture. To assess the diffusional properties of the calf muscles of subjects with and without diabetes, at rest and during isometric plantarflexion exercise. Prospective. Twenty-six subjects in two groups: 13 healthy and 13 subjects with type 2 diabetes (DM); each group consisted of seven females and six males. 3T/2D single-shot spin echo planar imaging. Fractional anisotropy (FA), mean diffusivity (MD), diffusion eigenvalues, and fiber tracking indices were obtained from the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SOL) muscles of the calf at rest and during isometric plantarflexion exercise. We used a combination of nonparametric (Wilcoxon) and parametric (t-test) statistical assessments. The medial gastrocnemius muscle had more indices with significant differences between the two groups (six indices with P < 0.05) than did the lateral gastrocnemius (three indices with P < 0.05) and soleus muscles (only one index with P < 0.05). While the healthy group showed elevated MD values from rest to exercise (MG = 5.83%, LG = 13.45%, and SOL = 11.68%), the diabetic MD showed higher increases (MG = 19.74%, LG = 29.31%, and SOL = 20.84%) that were different between groups (MG: P = 0.009, LG: P = 0.037, and SOL: P = 0.049). Our results indicate considerable diffusional changes between healthy subjects and subjects with diabetes at rest and during isometric plantarflexion exercise in the calf muscles. The medial gastrocnemius muscle displayed the most diffusion sensitivity to diabetes-related microstructural changes. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1285-1295.