Bradley R. Newcomer

Evaluation of the strength-size relationship in vivo using various muscle size indices.

PURPOSE It is well accepted that maximum strength is related to muscle size. The primary purpose of this study was to determine whether anthropometric or dual-energy x-ray absorptiometry (DEXA) estimates of muscle size were valid predictors of plantar flexor maximum voluntary contraction (MVC) strength and could be used in lieu of more sophisticated techniques (e.g., magnetic resonance imaging (MRI)). Additionally, we compared the relationship among MVC and three MRI-determined muscle size measures; anatomical (ACSA) and physiological (PCSA) cross-sectional areas; and muscle volume (VOLm). METHODS We measured plantar flexor MVC at 1.83 rad and various indices of muscle size: 1) body weight, 2) total body lean mass (LM) (DEXA), 3) lower leg LM (DEXA), 4) lower leg circumference, 5) estimated muscle+bone cross-sectional area (CSA) from circumference and calf skin-fold, 6) triceps surae ACSA, 7) triceps surae PCSA, and (8) triceps surae volume (VOLm), in 39 premenopausal women (mean +/- SD: 36 +/- 8 yr, 165 +/- 6 cm, and 65 +/- 9 kg). RESULTS Zero-order correlations showed significant (P < 0.05) associations between MVC and total body LM (r = 0.365), lower leg LM (r = 0.381), circumference (r = 0.584), estimated muscle+bone CSA (r = 0.447), ACSA (r = 0.733), PCSA (r = 0.715), and VOLm (r = 0.649). By using the Fisher Z-transformation, ACSA and PCSA correlated significantly higher with MVC (P < 0.05) than anthropometric and DEXA indices. Further, only ACSA and PCSA regressed to the origin, indicating the ability to predict MVC was greatest with these two measures. CONCLUSIONS The MRI-determined muscle size indices, which were specific to the triceps surae, correlated with strength better than whole limb anthropometric and DEXA indices. In this group of women, both ACSA and PCSA appeared superior to VOLm for predicting strength. PCSA was not found to be more precise than ACSA. ACSA appears to provide adequate precision for estimating plantar flexor specific tension in vivo.

Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction

Peak oxygen uptake (VO2) is diminished in patients with heart failure with preserved ejection fraction (HFpEF) suggesting impaired cardiac reserve. To test this hypothesis, we assessed the haemodynamic response to exercise in HFpEF patients.

Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function.

Objective: Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures.

Muscle‐associated Triglyceride Measured by Computed Tomography and Magnetic Resonance Spectroscopy

Objective: Muscle triglyceride can be assessed in vivo using computed tomography (CT) and 1H magnetic resonance spectroscopy (MRS), two techniques that are based on entirely different biophysical principles. Little is known, however, about the cross‐correlation between these techniques and their test—retest reliability.

Measurement of the Tricarboxylic Acid Cycle Rate in Human Grey and White Matter in Vivo by 1H-[13C] Magnetic Resonance Spectroscopy at 4.1T

13C isotopic labeling data were obtained by 1H-observed/13C-edited magnetic resonance spectroscopy in the human brain in vivo and analyzed using a mathematical model to determine metabolic rates in human grey matter and white matter. 22,5-cc and 56-cc voxels were examined for grey matter and white matter, respectively. When partial volume effects were ignored, the measured tricarboxylic acid cycle rate was 0.72 ± 0.22 (mean ± SD) and 0.29 ± 0.09 μmol min–1 g–1(mean ± SD) in voxels of ∼70% grey and ∼70% white matter, respectively. After correction for partial volume effects using a model with two tissue compartments, the tricarboxylic acid cycle rate in pure grey matter was higher (0.80 ± 0.10 mol min–1 g–1; mean ± SD) and in white matter was significantly lower (0.17 ± 0.01 μmol min–1 g–1; mean ± SD). In 1H-observed/13C-edited magnetic resonance spectroscopy labeling studies, the larger concentrations of labeled metabolites and faster metabolic rates in grey matter biased the measurements heavily toward grey matter, with labeling time courses in 70% grey matter appearing nearly identical to labeling in pure grey matter.

31P MRS measurement of mitochondrial function in skeletal muscle : reliability, force-level sensitivity and relation to whole body maximal oxygen uptake

The reliability, relation to whole‐body maximal oxygen uptake (VO2max), and force‐level sensitivity of 31P MRS markers of mitochondrial function were studied in 39 normal‐weight women. Following 90 s isometric plantar‐flexion exercises at 45, 70 and 100% of maximum voluntary contraction, skeletal muscle mitochondrial function was determined from the phosphocreatine recovery time constant (TCPCr), the ADP recovery time constant (TCADP), and the rate of change in PCr during the first 14 s of recovery (OxPhos). VO2max was measured on a treadmill. Test–retest measurements were obtained in a subset of seven women. Overall, TCPCr, TCADP and OxPhos were reproducible for all exercises (coefficients of variation = 2.3–19.3%). With increasing force‐level, TCPCr was prolonged (29.0 ± 8.2, 31.9 ± 9.0 and 35.4 ± 9.5 s), OxPhos was increased (0.159 ± 0.081, 0.247 ± 0.090 and 0.310 ± 0.114), and TCADP was shortened (22.4 ± 7.9, 21.3 ± 6.2, and 19.5 ± 6.7; p < 0.01). All MRS markers of mitochondrial function were correlated with VO2max (r = 0.41–0.72; p < 0.05). These results suggest that measurements of TCPCr, TCADP and OxPhos yield reproducible results that correlate with whole‐body VO2max and that vary in force‐level sensitivity. Copyright

Biological and clinical MRS at ultra-high field

The advantages of performing spectroscopic studies at higher field strengths include increased SNR, improved spectral resolution for J‐coupled resonances, and improvements in the selectivity of spectral editing schemes. By using pulse sequences that minimize the required echo time, refocus J‐evolution, employ low peak B1 requiring pulses and take advantage of spectroscopic imaging methods, these advantages can also be utilized in clinical applications of spectroscopy at high field. In addition to the static measurements measurements of N‐acetyl aspartate (NAA), creatine (CR) and choline (CH) which can be performed at 1.5 T, high resolution measurements of glutamate, glutamine, GABA and the incorporation of 13C labeled glucose into glutamate are possible with improved spatial and spectral resolution. These methods have been utilized in patients with seizure disorders and multiple sclerosis to identify, characterize and map the metabolic changes associated with these diseases and their treatment.

Relation between in vivo and in vitro measurements of skeletal muscle oxidative metabolism

The relationships between in vivo 31P magnetic resonance spectroscopy (MRS) and in vitro markers of oxidative capacity (mitochondrial function) were determined in 27 women with varying levels of physical fitness. Following 90‐s isometric plantar flexion exercises, calf muscle mitochondrial function was determined from the phosphocreatine (PCr) recovery time constant, the adenosine diphosphate (ADP) recovery time constant, the rate of change of PCr during the initial 14 s of recovery, and the apparent maximum rate of oxidative adenosine triphosphate (ATP) synthesis (Qmax). Muscle fiber type distribution (I, IIa, IIx), citrate synthase (CS) activity, and cytochrome c oxidase (COX) activity were determined from a biopsy sample of lateral gastrocnemius. MRS markers of mitochondrial function correlated moderately (P < 0.05) with the percentage of type IIa oxidative fibers (r = 0.41 to 0.66) and CS activity (r = 0.48 to 0.64), but only weakly with COX activity (r = 0.03 to 0.26, P > 0.05). These results support the use of MRS to determine mitochondrial function in vivo.

Impaired Insulin Sensitivity and Elevated Ectopic fat in Healthy Obese vs. Nonobese Prepubertal Children

Insulin sensitivity is impaired and ectopic fat (accretion of lipids outside of typical adipose tissue depots) increased in obese adults and adolescents. It is unknown how early in life this occurs; thus, it is important to evaluate young children to identify potential factors leading to the development of metabolic syndrome. We examined an ethnically diverse cohort of healthy, exclusively prepubertal children (N = 123; F = 57, M = 66; age 8.04 ± 0.77 years) to examine differences in insulin sensitivity and ectopic and visceral fat deposition between obese and nonobese youth. Obesity was categorized by age‐ and sex‐adjusted BMI z‐scores (nonobese = z‐score <2 (N = 94) and obese = z‐score ≥2 (N = 29)). Insulin sensitivity was assessed by both a frequently sampled intravenous glucose tolerance test (Si) and the homeostatic model assessment of insulin resistance (HOMAIR). Intramyocellular lipids (IMCLs) from soleus and intrahepatic lipids (IHLs) were assessed by magnetic resonance spectroscopy, visceral adipose tissue (VAT) by magnetic resonance imaging, and total body fat by dual‐energy X‐ray absorptiometry. We also examined serum lipids (total cholesterol, triglycerides, high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol) and blood pressure (diastolic and systolic). Obese children exhibited significantly lower Si (5.9 ± 5.98 vs. 13.43 ± 8.18 (mµ/l)−1·min−1, P = 0.01) and HDL‐C and higher HOMAIR (1.68 ± 1.49 vs. 0.63 ± 0.47, P < 0.0001), IMCL (0.74 ± 0.39 vs. 0.44 ± 0.21% water peak, P < 0.0001), IHL (1.49 ± 1.13 vs. 0.54 ± 0.42% water peak, P < 0.0001), VAT (20.16 ± 8.01 vs. 10.62 ± 5.44 cm2, P < 0.0001), total cholesterol, triglycerides, low‐density lipoprotein cholesterol, and systolic blood pressure relative to nonobese children. These results confirm significantly increased ectopic fat and insulin resistance in healthy obese vs. nonobese children prior to puberty. Excessive adiposity during early development appears concomitant with precursors of type 2 diabetes and the metabolic syndrome.

PPAR-α agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial

BackgroundInsulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat β-oxidation. It was unknown if this relationship was present in patients with acute insulin resistance induced by trauma.MethodsA double blind placebo controlled trial was conducted in 18 children with severe burn injury. Metabolic studies to assess whole body palmitate oxidation and insulin sensitivity, muscle biopsies for mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl carnitine concentrations, and magnetic resonance spectroscopy for muscle and liver triglycerides were compared before and after two weeks of placebo or PPAR-α agonist treatment.ResultsInsulin sensitivity and basal whole body palmitate oxidation as measured with an isotope tracer increased significantly (P = 0.003 and P = 0.004, respectively) after PPAR-α agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-α treatment (P = 0.002). However, the concentrations of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and liver triglycerides did not change with either treatment. PKC-θ activation during hyper-insulinemia decreased significantly following PPAR-α treatment.ConclusionPPAR-α agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.