Association of insulin resistance with the accumulation of saturated intramyocellular lipid: A comparison with other fat stores.

It has been shown using proton magnetic resonance spectroscopy (1H MRS) that, in a group of females, whole-body insulin resistance was more closely related to accumulation of saturated intramyocellular lipid (IMCL) than to IMCL concentration alone. This has not been investigated in males. We investigated whether age- and body mass index-matched healthy males differ from the previously reported females in IMCL composition (measured as CH2:CH3) and IMCL concentration (measured as CH3), and in their associations with insulin resistance. We ask whether saturated IMCL accumulation is more strongly associated with insulin resistance than other ectopic and adipose tissue lipid pools and remains a significant predictor when these other pools are taken into account. In this group of males, who had similar overall insulin sensitivity to the females, IMCL was similar between sexes. The males demonstrated similar and even stronger associations of IMCL with insulin resistance, supporting the idea that a marker reflecting the accumulation of saturated IMCL is more strongly associated with whole-body insulin resistance than IMCL concentration alone. However, this marker ceased to be a significant predictor of whole-body insulin resistance after consideration of other lipid pools, which implies that this measure carries no more information in practice than the other predictors we found, such as intrahepatic lipid and visceral adipose tissue. As the marker of saturated IMCL accumulation appears to be related to these two predictors and has a much smaller dynamic range, this finding does not rule out a role for it in the pathogenesis of insulin resistance.

Proton magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations.

1 H-MR spectroscopy of skeletal muscle provides insight into metabolism that is not available noninvasively by other methods. The recommendations given in this article are intended to guide those who have basic experience in general MRS to the special application of 1 H-MRS in skeletal muscle. The highly organized structure of skeletal muscle leads to effects that change spectral features far beyond simple peak heights, depending on the type and orientation of the muscle. Specific recommendations are given for the acquisition of three particular metabolites (intramyocellular lipids, carnosine and acetylcarnitine) and for preconditioning of experiments and instructions to study volunteers.

Muscle fat content in the intact infraspinatus muscle correlates with age and BMI, but not critical shoulder angle.

PURPOSE: Muscle fat content of the rotator cuff increases after a tear. In the healthy rotator cuff, the influence of age, body mass index (BMI) and critical shoulder angle (CSA) on muscle fat content is unknown. The primary aim was to correlate muscle fat content with age, BMI and CSA. The secondary aims were (1) to correlate muscle fat content in the entire muscle and slice Y (most lateral sagittal slice with scapular spine) and (2) assessed the reliability for CSA measurement in MRI. METHODS: In 26 healthy shoulders (17 subjects), aged 40-65 years, BMI 20-35 kg/m2, Goutallier grade 0, Dixon MRI was applied. The CSA was > 35° in 14 shoulders and < 30° in 12 shoulders. Muscle fat content was calculated from Dixon MRI. RESULTS: Infraspinatus muscle fat content correlates moderately with age (r = 0.553; p = 0.003) and BMI (r = 0.517; p = 0.007). Supraspinatus muscle fat content does not correlate with age (r = 0.363, p = 0.069) and BMI (r = 0.342, p = 0.087). No correlation between CSA and muscle fat content was found. Muscle fat content measurement in the entire muscle correlates strongly with measurement in slice Y (intraclass correlation coefficient supraspinatus muscle: 0.757; infraspinatus muscle: 0.794). CSA intermethod analysis between radiography and MR images shows very high reliability (intraclass correlation coefficient > 0.9) and no systematical deviation in Bland-Altman analysis. CONCLUSION: Muscle fat content in the healthy infraspinatus muscle does correlate with age and BMI, but not with the CSA. Muscle fat content measurement in the rotator cuff using Dixon MRI showed a high reliability between slice Y and the entire muscle. LEVEL OF EVIDENCE: III.

31 P magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations.

Skeletal muscle phosphorus-31 31 P MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of 31 P MRS in skeletal muscle depend on the research question, and to assess those questions requires understanding both the relevant muscle physiology, and how 31 P MRS methods can probe it. Here we consider basic signal-acquisition parameters related to radio frequency excitation, TR, TE, spectral resolution, shim and localisation. We make specific recommendations for studies of resting and exercising muscle, including magnetisation transfer, and for data processing. We summarise the metabolic information that can be quantitatively assessed with 31 P MRS, either measured directly or derived by calculations that depend on particular metabolic models, and we give advice on potential problems of interpretation. We give expected values and tolerable ranges for some measured quantities, and minimum requirements for reporting acquisition parameters and experimental results in publications. Reliable examination depends on a reproducible setup, standardised preconditioning of the subject, and careful control of potential difficulties, and we summarise some important considerations and potential confounders. Our recommendations include the quantification and standardisation of contraction intensity, and how best to account for heterogeneous muscle recruitment. We highlight some pitfalls in the assessment of mitochondrial function by analysis of phosphocreatine (PCr) recovery kinetics. Finally, we outline how complementary techniques (near-infrared spectroscopy, arterial spin labelling, BOLD and various other MRI and 1 H MRS measurements) can help in the physiological/metabolic interpretation of 31 P MRS studies by providing information about blood flow and oxygen delivery/utilisation. Our recommendations will assist in achieving the fullest possible reliable picture of muscle physiology and pathophysiology.

The effect of exercise on intramyocellular acetylcarnitine (AcCtn) concentration in adult growth hormone deficiency (GHD).

To cover increasing energy demands during exercise, tricarboxylic cycle (TCA) flux in skeletal muscle is markedly increased, resulting in the increased formation of intramyocellular acetylcarnitine (AcCtn). We hypothesized that reduced substrate availability within the exercising muscle, reflected by a diminished increase of intramyocellular AcCtn concentration during exercise, might be an underlying mechanism for the impaired exercise performance observed in adult patients with growth hormone deficiency (GHD). We aimed at assessing the effect of 2 hours of moderately intense exercise on intramyocellular AcCtn concentrations, measured by proton magnetic resonance spectroscopy (1H-MRS), in seven adults with GHD compared to seven matched control subjects (CS). Compared to baseline levels AcCtn concentrations significantly increased after 2 hours of exercise, and significantly decreased over the following 24 hours (ANOVA p for effect of time = 0.0023 for all study participants; p = 0.067 for GHD only, p = 0.045 for CS only). AcCtn concentrations at baseline, as well as changes in AcCtn concentrations over time were similar between GHD patients and CS (ANOVA p for group effect = 0.45). There was no interaction between group and time (p = 0.53). Our study suggests that during moderately intense exercise the availability of energy substrate within the exercising muscle is not significantly different in GHD patients compared to CS.

Accumulation of saturated intramyocellular lipid is associated with insulin resistance.

Intramyocellular lipid (IMCL) accumulation has been linked to both insulin-resistant and insulin-sensitive (athletes) states. Biochemical analysis of intramuscular triglyceride composition is confounded by extramyocellular triglycerides in biopsy samples, and hence the specific composition of IMCLs is unknown in these states. 1H magnetic resonance spectroscopy (MRS) can be used to overcome this problem. Thus, we used a recently validated 1H MRS method to compare the compositional saturation index (CH2:CH3) and concentration independent of the composition (CH3) of IMCLs in the soleus and tibialis anterior muscles of 16 female insulin-resistant lipodystrophic subjects with that of age- and gender-matched athletes (n = 14) and healthy controls (n = 41). The IMCL CH2:CH3 ratio was significantly higher in both muscles of the lipodystrophic subjects compared with controls but was similar in athletes and controls. IMCL CH2:CH3 was dependent on the IMCL concentration in the controls and, after adjusting the compositional index for quantity (CH2:CH3adj), could distinguish lipodystrophics from athletes. This CH2:CH3adj marker had a stronger relationship with insulin resistance than IMCL concentration alone and was inversely related to VO2max The association of insulin resistance with the accumulation of saturated IMCLs is consistent with a potential pathogenic role for saturated fat and the reported benefits of exercise and diet in insulin-resistant states.

Effects of Dietary Protein and Fat Content on Intrahepatocellular and Intramyocellular Lipids during a 6-Day Hypercaloric, High Sucrose Diet: A Randomized Controlled Trial in Normal Weight Healthy Subjects.

Sucrose overfeeding increases intrahepatocellular (IHCL) and intramyocellular (IMCL) lipid concentrations in healthy subjects. We hypothesized that these effects would be modulated by diet protein/fat content. Twelve healthy men and women were studied on two occasions in a randomized, cross-over trial. On each occasion, they received a 3-day 12% protein weight maintenance diet (WM) followed by a 6-day hypercaloric high sucrose diet (150% energy requirements). On one occasion the hypercaloric diet contained 5% protein and 25% fat (low protein-high fat, LP-HF), on the other occasion it contained 20% protein and 10% fat (high protein-low fat, HP-LF). IHCL and IMCL concentrations (magnetic resonance spectroscopy) and energy expenditure (indirect calorimetry) were measured after WM, and again after HP-LF/LP-HF. IHCL increased from 25.0 ± 3.6 after WM to 147.1 ± 26.9 mmol/kg wet weight (ww) after LP-HF and from 30.3 ± 7.7 to 57.8 ± 14.8 after HP-LF (two-way ANOVA with interaction: p < 0.001 overfeeding x protein/fat content). IMCL increased from 7.1 ± 0.6 to 8.8 ± 0.7 mmol/kg ww after LP-HF and from 6.2 ± 0.6 to 6.9 ± 0.6 after HP-LF, (p < 0.002). These results indicate that liver and muscle fat deposition is enhanced when sucrose overfeeding is associated with a low protein, high fat diet compared to a high protein, low fat diet.

Impact of sleep restriction on metabolic outcomes induced by overfeeding: a randomized controlled trial in healthy individuals.

Background: Overconsumption of energy-dense foods and sleep restriction are both associated with the development of metabolic and cardiovascular diseases, but their combined effects remain poorly evaluated. Objective: The aim of this study was to assess whether sleep restriction potentiates the effects of a short-term overfeeding on intrahepatocellular lipid (IHCL) concentrations and on glucose homeostasis. Design: Ten healthy subjects were exposed to a 6-d overfeeding period (130% daily energy needs, with 15% extra energy as sucrose and 15% as fat), with normal sleep (8 h sleep opportunity time) or sleep restriction (4 h sleep opportunity time), according to a randomized, crossover design. At baseline and after intervention, IHCL concentrations were measured by proton magnetic resonance spectroscopy, and a dual intravenous [6,6-2H2]-, oral 13C-labeled glucose tolerance test and a polysomnographic recording were performed. Results: Overfeeding significantly increased IHCL concentrations (Poverfeeding < 0.001; overfeeding + normal sleep: +53% ± 16%). During the oral glucose tolerance test, overfeeding significantly increased endogenous glucose production (Poverfeeding = 0.034) and the oxidation of 13C-labeled glucose load (Poverfeeding = 0.038). Sleep restriction significantly decreased total sleep time, and the duration of stages 1 and 2 and rapid eye movement sleep (all P < 0.001), whereas slow-wave sleep duration was preserved (Poverfeeding × sleep = 0.809). Compared with overfeeding, overfeeding + sleep restriction did not change IHCL concentrations (Poverfeeding × sleep = 0.541; +83% ± 33%), endogenous glucose production (Poverfeeding × sleep = 0.567), or exogenous glucose oxidation (Poverfeeding × sleep = 0.118). Sleep restriction did not significantly alter blood pressure, heart rate, or plasma cortisol concentrations (all Poverfeeding × sleep = NS). Conclusions: Six days of a high-sucrose, high-fat overfeeding diet significantly increased IHCL concentrations and increased endogenous glucose production, suggesting hepatic insulin resistance. These effects of overfeeding were not altered by sleep restriction. This trial was registered at clinicaltrials.gov as NCT02075723. Other study ID numbers: SleepDep 02/14.

Impaired repletion of intramyocellular lipids in patients with growth hormone deficiency after a bout of aerobic exercise.

BACKGROUND: Ectopic lipids such as intramyocellular lipids (IMCL) are depleted by exercise and repleted by diet, whereas intrahepatocellular lipids (IHCL) are increased immediately after exercise. So far, it is unclear how ectopic lipids behave 24 h after exercise and whether the lack of growth hormone (GH) significantly affects ectopic lipids 24 h after exercise. METHODS: Seven male patients with growth hormone deficiency (GHD) and seven sedentary male control subjects (CS) were included. VO2max was assessed by spiroergometry; visceral and subcutaneous fat by whole body MRI. 1H-MR-spectroscopy was performed in M. vastus intermedius and in the liver before and after 2 h of exercise at 50% VO2max and 24 h thereafter, while diet and physical activity were standardized. RESULTS: Sedentary male subjects (7 GHD, 7 CS) were recruited. Age, BMI, waist circumference, visceral and subcutaneous fat mass was not significantly different between GHD and CS. VO2max was significantly lower in GHD vs. CS. IMCL were diminished through aerobic exercise in both groups: (-11.5 ±â€¯21.9% in CS; -8.9% ±19.1% in GHD) and restored after 24 h in CS (-5.5 ±â€¯26.6% compared to baseline) but not in GHD (-17.9 ±â€¯15.3%). IHCL increased immediately after exercise and decreased to baseline within 24 h. CONCLUSION: These findings suggest that GHD may affect repletion of IMCL 24 h after aerobic exercise.

Diffusion-weighted magnetic resonance spectroscopy boosted by simultaneously acquired water reference signals.

PURPOSE: To combine the metabolite-cycling technique with diffusion-weighted 1 H-MR spectroscopy and to use the inherent water reference for compensation of motion-related signal loss for improved estimation of metabolite apparent diffusion coefficients (ADCs). METHODS: Diffusion-weighted spectra of water and metabolites were acquired simultaneously using metabolite-cycling at 3 T. The water information was used for signal correction of phase, frequency, and eddy currents, as well as for compensation of motion-induced signal loss. ADCs were estimated by 2D simultaneous fitting. The quality of ADC restoration was investigated in vitro. Subsequently, the new approach was applied in 13 subjects for enhanced metabolite ADC estimation in gray matter. RESULTS: Metabolite-cycled diffusion 1 H-MRS is suitable to measure metabolite and water ADCs simultaneously. The water reference facilitates signal amplitude restoration, compensating for motion-related artefacts. 2D fitting stabilizes the fitting procedure and allows the estimation of ADCs even for low signal-to-noise metabolites. Use of the motion-compensation scheme leads to estimation of smaller ADCs for virtually all metabolites (44% smaller ADC on average), to a reduction of fitting uncertainties for metabolite ADCs in individual subjects and reduced variance over the cohort (45% smaller SD on average). CONCLUSION: Using the simultaneously acquired water signal as internal reference allows not only for compensation of phase and frequency fluctuations but also for signal amplitude restoration, and thus improved metabolite ADC estimation. Combination with 2D simultaneous fitting promises access to the diffusion properties even for low signal-to-noise metabolites. The combination of both techniques increases the specificity and sensitivity of estimated metabolite ADC values in the cohort.

Compositional marker in vivo reveals intramyocellular lipid turnover during fasting-induced lipolysis.

Intramyocellular lipid (IMCL) is of particular metabolic interest, but despite many proton magnetic resonance spectroscopy (1H MRS) studies reporting IMCL content measured by the methylene (CH2) resonance signal, little is known about its composition. Here we validated IMCL CH3:CH2 ratio as a compositional marker using 1H MRS at short echo time, and investigated IMCL content and composition during a 28-hour fast in 24 healthy males. Increases in IMCL CH2 relative to the creatine and phosphocreatine resonance (Cr) at 3.0 ppm (an internal standard) correlated with circulating free fatty acid (FA) concentrations, supporting the concept of increased FA influx into IMCL. Significant decreases in IMCL CH3:CH2 ratio indicated a less unsaturated IMCL pool after fasting, and this compositional change related inversely to IMCL baseline composition, suggesting a selective efflux of unsaturated shorter-chain FA from the IMCL pool. This novel in vivo evidence reveals IMCL turnover during extended fasting, consistent with the concept of a flexible, responsive myocellular lipid store. There were also differences between soleus and tibialis anterior in basal IMCL composition and in response to fasting. We discuss the potential of this marker for providing insights into normal physiology and mechanisms of disease.

Fitting interrelated datasets: metabolite diffusion and general lineshapes.

OBJECTIVE: Simultaneous modeling of true 2-D spectroscopy data, or more generally, interrelated spectral datasets has been described previously and is useful for quantitative magnetic resonance spectroscopy applications. In this study, a combined method of reference-lineshape enhanced model fitting and two-dimensional prior-knowledge fitting for the case of diffusion weighted MR spectroscopy is presented. MATERIALS AND METHODS: Time-dependent field distortions determined from a water reference are applied to the spectral bases used in linear-combination modeling of interrelated spectra. This was implemented together with a simultaneous spectral and diffusion model fitting in the previously described Fitting Tool for Arrays of Interrelated Datasets (FiTAID), where prior knowledge conditions and restraints can be enforced in two dimensions. RESULTS: The benefit in terms of increased accuracy and precision of parameters is illustrated with examples from Monte Carlo simulations, in vitro and in vivo human brain scans for one- and two-dimensional datasets from 2-D separation, inversion recovery and diffusion-weighted spectroscopy (DWS). For DWS, it was found that acquisitions could be substantially shortened. CONCLUSION: It is shown that inclusion of a measured lineshape into modeling of interrelated MR spectra is beneficial and can be combined also with simultaneous spectral and diffusion modeling.

Metabolic Effects of Replacing Sugar-Sweetened Beverages with Artificially-Sweetened Beverages in Overweight Subjects with or without Hepatic Steatosis: A Randomized Control Clinical Trial.

OBJECTIVE: Addition of fructose to the diet of normal weight and overweight subjects can increase postprandial plasma triglyceride and uric acid concentration. We, therefore, assessed whether replacing sugar-sweetened beverages (SSB) with artificially-sweetened beverages (ASB) in the diet of overweight and obese subjects would decrease these parameters. METHODS: Twenty-six participants of the REDUCS study, which assessed the effects of replacing SSB by ASB over 12 weeks on intra-hepatocellular lipid concentration, were included in this sub-analysis. All were studied after a four-week run-in period during which they consumed their usual diet and SSBs, and after a 12-week intervention in which they were randomly assigned to replace their SSBs with ASBs (ASB arm) or to continue their usual diet and SSBs (control arm, CTRL). At the end of run-in (week 4) and again at the end of intervention (week 16), they took part in an 8.5 h metabolic investigation during which their plasma glucose, insulin, glucagon, lactate, triglyceride (TG), non-esterified fatty acids (NEFA), and uric acid concentrations were measured over a 30 min fasting period (-30-0 min), then every 2 h over 480 min. with ingestion of standard breakfast at time 0 min and a standard lunch at time 240 min. Breakfast and lunch were consumed together with a 3.3 dL SSB at week 4 and with either an ASB (ASB arm) or a SSB (CTRL arm) at week 16. After analyzing the whole group, a secondary analysis was performed on 14 subjects with hepatic steatosis (seven randomized to ASB, seven to CTRL) and 12 subjects without hepatic steatosis (six randomized to ASB and six to CTRL). RESULTS: Ingestion of meals increased plasma glucose, insulin, glucagon, lactate, and TG concentrations and decreased NEFA concentrations, but with no significant difference of integrated postprandial responses between week 4 and week 16 in both ASB and CTRL, except for a slightly decreased glucagon response in ASB. There was, however, no significant postprandial increase in uric acid concentration in both arms. In the secondary analysis, replacing SSBs with ASBs did not significantly change postprandial TG and uric acid concentrations irrespective of the presence or not of hepatic steatosis, Conclusions: In overweight, high SSB consumers, replacing SSBs with ASBs during 12 weeks did not significantly alter post-prandial TG and uric acid concentration, in spite of the lower energy and fructose content of the meals. These effects were globally the same in subjects without and with hepatic steatosis.

Waist circumference is associated with liver fat in black and white adolescents.

We examined whether waist circumference (WC) is associated with liver fat in black and white adolescents. Liver fat was measured using a 3T proton magnetic resonance spectroscopy (1H-MRS) in 152 overweight/obese adolescents (94 black and 58 white, body mass index (BMI) ≥85th percentile, aged 12-18 years) without liver diseases or diabetes. WC was measured at the last rib. Total and visceral adipose tissue (VAT) were measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, respectively. The proportion of fatty liver (defined as liver fat ≥5.0% by 1H-MRS) was lower (P < 0.01) in black adolescents (5.3%) compared with their white peers (24.1%). Despite similar age, BMI, WC, and total adiposity (%), black adolescents had lower (P < 0.01) VAT (59.0% vs. 81.3 cm2), liver fat (1.6% vs. 3.5%), and alanine aminotransferase (17.2 vs. 22.0 IU/L) compared with their white peers. Independent of race, WC was associated with liver fat (black, r = 0.43; white, r = 0.64) in a similar magnitude to the association between VAT and liver fat (black, r = 0.44; white, r = 0.51) and these findings remained significant after controlling for age, sex, Tanner stage, and total adiposity. In blacks, WC and sex (male) were independent (P < 0.01) predictors of liver fat, explaining 17.1% and 5.6% of the variance, respectively, while in whites WC was the single best predictor, explaining 40.8% of the variance in liver fat. These findings suggest that enlarged WC is a marker of increased liver fat in overweight/obese white and black adolescents.

Metabolic Effects of Glucose-Fructose Co-Ingestion Compared to Glucose Alone during Exercise in Type 1 Diabetes.

This paper aims to compare the metabolic effects of glucose-fructose co-ingestion (GLUFRU) with glucose alone (GLU) in exercising individuals with type 1 diabetes mellitus. Fifteen male individuals with type 1 diabetes (HbA1c 7.0% ± 0.6% (53 ± 7 mmol/mol)) underwent a 90 min iso-energetic continuous cycling session at 50% VO2max while ingesting combined glucose-fructose (GLUFRU) or glucose alone (GLU) to maintain stable glycaemia without insulin adjustment. GLUFRU and GLU were labelled with 13C-fructose and 13C-glucose, respectively. Metabolic assessments included measurements of hormones and metabolites, substrate oxidation, and stable isotopes. Exogenous carbohydrate requirements to maintain stable glycaemia were comparable between GLUFRU and GLU (p = 0.46). Fat oxidation was significantly higher (5.2 ± 0.2 vs. 2.6 ± 1.2 mg·kg-1·min-1, p < 0.001) and carbohydrate oxidation lower (18.1 ± 0.8 vs. 24.5 ± 0.8 mg·kg-1·min-1p < 0.001) in GLUFRU compared to GLU, with decreased muscle glycogen oxidation in GLUFRU (10.2 ± 0.9 vs. 17.5 ± 1.0 mg·kg-1·min-1, p < 0.001). Lactate levels were higher (2.2 ± 0.2 vs. 1.8 ± 0.1 mmol/L, p = 0.012) in GLUFRU, with comparable counter-regulatory hormones between GLUFRU and GLU (p > 0.05 for all). Glucose and insulin levels, and total glucose appearance and disappearance were comparable between interventions. Glucose-fructose co-ingestion may have a beneficial impact on fuel metabolism in exercising individuals with type 1 diabetes without insulin adjustment, by increasing fat oxidation whilst sparing glycogen.

Postexercise repletion of muscle energy stores with fructose or glucose in mixed meals.

Background: Postexercise nutrition is paramount to the restoration of muscle energy stores by providing carbohydrate and fat as precursors of glycogen and intramyocellular lipid (IMCL) synthesis. Compared with glucose, fructose ingestion results in lower postprandial glucose and higher lactate and triglyceride concentrations. We hypothesized that these differences in substrate concentration would be associated with a different partition of energy stored as IMCLs or glycogen postexercise.Objective: The purpose of this study was to compare the effect of isocaloric liquid mixed meals containing fat, protein, and either fructose or glucose on the repletion of muscle energy stores over 24 h after a strenuous exercise session.Design: Eight male endurance athletes (mean ± SEM age: 29 ± 2 y; peak oxygen consumption: 66.8 ± 1.3 mL · kg-1 · min-1) were studied twice. On each occasion, muscle energy stores were first lowered by a combination of a 3-d controlled diet and prolonged exercise. After assessment of glycogen and IMCL concentrations in vastus muscles, subjects rested for 24 h and ingested mixed meals providing fat and protein together with 4.4 g/kg fructose (the fructose condition; FRU) or glucose (the glucose condition; GLU). Postprandial metabolism was assessed over 6 h, and glycogen and IMCL concentrations were measured again after 24 h. Finally, energy metabolism was evaluated during a subsequent exercise session.Results: FRU and GLU resulted in similar IMCL [+2.4 ± 0.4 compared with +2.0 ± 0.6 mmol · kg-1 wet weight · d-1; time × condition (mixed-model analysis): P = 0.45] and muscle glycogen (+10.9 ± 0.9 compared with +12.3 ± 1.9 mmol · kg-1 wet weight · d-1; time × condition: P = 0.45) repletion. Fructose consumption in FRU increased postprandial net carbohydrate oxidation and decreased net carbohydrate storage (estimating total, muscle, and liver glycogen synthesis) compared with GLU (+117 ± 9 compared with +135 ± 9 g/6 h, respectively; P < 0.01). Compared with GLU, FRU also resulted in lower plasma glucose concentrations and decreased exercise performance the next day.Conclusions: Mixed meals containing fat, protein, and either fructose or glucose elicit similar repletion of IMCLs and muscle glycogen. Under such conditions, fructose lowers whole-body glycogen synthesis and impairs subsequent exercise performance, presumably because of lower hepatic glycogen stores. This trial was registered at clinicaltrials.gov as NCT01866215.

Elucidation of the downfield spectrum of human brain at 7 T using multiple inversion recovery delays and echo times.

PURPOSE: To characterize the downfield spectrum at 5-10 ppm in the human brain at a high magnetic field of 7 T. Knowledge of relaxation parameters is of interest for spectroscopy as well as chemical exchange-dependent saturation transfer experiments. METHODS: Water-suppressed spectra were recorded as echo time and inversion time series in healthy volunteers to investigate T2 and T1 values of downfield peaks in gray matter at 7T. The spectra were fitted in a two-dimensional fashion to a heuristic model of a series of Voigt lines, and the relaxation times were obtained for 12 peaks of interest. RESULTS: The mean T2 values averaged over the volunteers ranged from 24 to 158 ms, whereas the mean T1 values ranged from 0.22 to 2.40 s. Spectra of specific inversion and echo times revealed superposition of the amide peaks of N-acetylaspartate with short T2 and an inhomogeneously broadened component with longer T2 . CONCLUSIONS: T2 values were shorter than expected for most peaks, whereas T1 values had a very wide range; shorter relaxation times for some peaks suggests the presence of macromolecules. Most of the larger peaks seemed to be composed of overlapping components, because the Gaussian widths in the Voigt line shape descriptions were larger than expected based on field inhomogeneities. Magn Reson Med 78:11-19, 2016. © 2017 International Society for Magnetic Resonance in Medicine.

Test-retest analysis of multiple 31 P magnetization exchange pathways using asymmetric adiabatic inversion.

PURPOSE: A 31 P-MR inversion transfer (IT) method with a short adiabatic inversion pulse is proposed and its test-retest reliability was evaluated for two spectral fitting strategies. METHODS: Assessment in a test-retest design (3 Tesla, vastus muscles, 12 healthy volunteers, 14 inversion times, 22 ms asymmetric adiabatic inversion pulse, adiabatic excitation); spectral fitting in Fitting Tool for Interrelated Arrays of Datasets (FitAID) and Java Magnetic Resonance User Interface (jMRUI); least squares solution of the Bloch-McConnell-Solomon matrix formalism including all 14 measured time-points with equal weighting. RESULTS: The cohort averages of k[PCr→γ-ATP] (phosphocreatine, PCr; adenosine triphosphate, ATP) are 0.246 ± 0.050s-1 versus 0.254 ± 0.050s-1 , and k[Pi→γ-ATP] 0.086 ± 0.033s-1 versus 0.066 ± 0.034s-1 (average ± standard deviation, jMRUI versus FitAID). Coefficients of variation of the differences between test and retest are lowest (9.5%) for k[PCr→γ-ATP] fitted in FitAID, larger (15.2%) for the fit in jMRUI, and considerably larger for k[Pi→γ-ATP] fitted in FitAID (43.4%) or jMRUI (47.9%). The beginning of the IT effect can be observed with magnetizations above 92% for noninverted lines while inversion of the ATP resonances is better than -72%. CONCLUSION: The performance of the asymmetric adiabatic pulse allows an accurate observation of IT effects even in the early phase; the least squares fit of the Bloch-McConnell-Solomon matrix formalism is robust; and the type of spectral fitting can influence the results significantly. Magn Reson Med 78:33-39, 2017. © 2016 International Society for Magnetic Resonance in Medicine.