Chris Boesch

Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes

BACKGROUND Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance. OBJECTIVE The aim was to assess the effects of fructose, a potent stimulator of hepatic de novo lipogenesis, on intrahepatocellular lipids (IHCLs) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)--a subgroup of individuals prone to metabolic disorders. DESIGN Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet (3.5 g x kg FFM(-1) x d(-1), +35% energy intake). Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp (0.3 and 1.0 mU x kg(-1) x min(-1)), together with 6,6-[2H2]glucose. IHCLs and intramyocellular lipids (IMCLs) were measured by 1H-magnetic resonance spectroscopy. RESULTS The OffT2D group had significantly (P < 0.05) higher IHCLs (+94%), total triacylglycerols (+35%), and lower whole-body insulin sensitivity (-27%) than did the control group. The high-fructose diet significantly increased IHCLs (control: +76%; OffT2D: +79%), IMCLs (control: +47%; OffT2D: +24%), VLDL-triacylglycerols (control: +51%; OffT2D: +110%), and fasting hepatic glucose output (control: +4%; OffT2D: +5%). Furthermore, the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group (group x diet interaction: P < 0.05). CONCLUSIONS A 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity. Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group, which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes. This trial was registered at clinicaltrials.gov as NCT00523562.

Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria

Large neutral amino acids (LNAAs), including phenylalanine (Phe), compete for transport across the blood-brain barrier (BBB) via the L-type amino acid carrier. Accordingly, elevated plasma Phe impairs brain uptake of other LNAAs in patients with phenylketonuria (PKU). Direct effects of elevated brain Phe and depleted LNAAs are probably major causes for disturbed brain development and function in PKU. Competition for the carrier might conversely be put to use to lower Phe influx when the plasma concentrations of all other LNAAs are increased. This hypothesis was tested by measuring brain Phe in patients with PKU by quantitative 1H magnetic resonance spectroscopy during an oral Phe challenge with and without additional supplementation with all other LNAAs. Baseline plasma Phe was approximately 1,000 micromol/l and brain Phe was approximately 250 micromol/l in both series. Without LNAA supplementation, brain Phe increased to approximately 400 micromol/l after the oral Phe load. Electroencephalogram (EEG) spectral analysis revealed acutely disturbed brain activity. With concurrent LNAA supplementation, Phe influx was completely blocked and there was no slowing of EEG activity. These results are relevant for further characterization of the LNAA carrier and of the pathophysiology underlying brain dysfunction in PKU and for treatment of patients with PKU, as brain function might be improved by continued LNAA supplementation.

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.

Structural and neurobehavioral delay in postnatal brain development of preterm infants.

Postnatal brain development of healthy prematurely born infants was assessed to study possible influence of premature birth and early extrauterine environment on structural, biochemical, and functional brain development. Myelination and differentiation of gray and white matter were studied byin vivo magnetic resonance (MR) imaging (MRI), changes in cerebral metabolism by 1H MR spectroscopy (MRS), and changes in early human neurobehavior by the assessment of preterm infants behavior (APIB). The stage of intrauterine and extrauterine brain development in prematurely born infants at term was compared with the stage of mainly intrauterine brain development in a group of full-term infants. Eighteen preterm infants unremarkable with respect to neurologic and medical status were studied at approximately 2 wk of postnatal age [gestational age (GA) 1: 32.5 ± 1.2 wk] and again at term(GA 2: 40.0 ± 1.1 wk). For comparison a group of 13 full-term born infants (GA T: 40.6 ± 2.1 wk) were studied by MR and six by APIB. When GA 2 to GA 1 was compared, significant maturational changes were found with MRI in gray and white matter and myelination, with 1H MRS in the concentration of N-acetylaspartate and with all scores of APIB. In preterm infants at term (GA 2) compared with full-term infants (GA T) significantly less gray and white matter differentiation and myelination was observed as well as significantly poorer performance in four neurobehavioral parameters (autonomic reactivity, motoric reactivity, state organization, attentional availability). We conclude that MRI and 1H MRS can be used to study postnatal brain development in preterm infants. Structural and biochemical maturation is accompanied by functional maturation as shown with the neurobehavior assessment. Preterm infants at term compared with full-term infants show a structural as well as a functional delay in brain development assessed at 40 wk of postconceptional age.

Effects of aerobic versus resistance exercise without caloric restriction on abdominal fat, intrahepatic lipid, and insulin sensitivity in obese adolescent boys: a randomized, controlled trial.

The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown. We examined the effects of aerobic exercise (AE) versus resistance exercise (RE) without caloric restriction on abdominal adiposity, ectopic fat, and insulin sensitivity and secretion in youth. Forty-five obese adolescent boys were randomly assigned to one of three 3-month interventions: AE, RE, or a nonexercising control. Abdominal fat was assessed by magnetic resonance imaging, and intrahepatic lipid and intramyocellular lipid were assessed by proton magnetic resonance spectroscopy. Insulin sensitivity and secretion were evaluated by a 3-h hyperinsulinemic-euglycemic clamp and a 2-h hyperglycemic clamp. Both AE and RE prevented the significant weight gain that was observed in controls. Compared with controls, significant reductions in total and visceral fat and intrahepatic lipid were observed in both exercise groups. Compared with controls, a significant improvement in insulin sensitivity (27%) was observed in the RE group. Collapsed across groups, changes in visceral fat were associated with changes in intrahepatic lipid (r = 0.72) and insulin sensitivity (r = −0.47). Both AE and RE alone are effective for reducing abdominal fat and intrahepatic lipid in obese adolescent boys. RE but not AE is also associated with significant improvements in insulin sensitivity.

Fast, noniterative shimming of spatially localized signals. In vivo analysis of the magnetic field along axes

A strategy for localized shimming is described, which is noniterating, fast, and reliable. It is shown that the magnetic field measured along a particular projection that runs through the center of a volume element can be separated into the rn contributions from different orders n of the spherical harmonic functions. The selection of a suitable number of projections with distinctive orientations permits unambiguous determination of the coefficients of each spherical harmonic term by combining the results of polynomial regression analysis along the different axes. Shim coils are generally built to generate a field that corresponds to a single spherical harmonic. The measurement of the magnetic field along projections is used to design a rapid shim procedure that uses simple algorithms. The effect of displacing the localized volume is calculated from the representation of the spherical harmonic functions in Cartesian coordinates. The practicality and speed of the resulting method are demonstrated on a 2.35 T 40 cm bore system for the adjustment of the X, Y, Z, Z2, and X2 - Y2 coils.

Observation of intramyocellular lipids by means of 1H magnetic resonance spectroscopy.

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are being increasingly used for investigations of human muscle physiology. While MRI reveals the morphology of muscles in great detail (e.g. for the determination of muscle volumes), MRS provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the monitoring of high-energy phosphates (31P MRS), glycogen (13C MRS), or intramyocellular lipids (1H MRS), to give only a few examples. The observation of intramyocellular lipids (IMCL) by means of 1H MRS is non-invasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace the biopsy for the monitoring of IMCL levels; however, the biopsy still has the advantage that other methods such as those used in molecular biology can be applied to the sample. The present study describes variations in the IMCL levels (expressed in mmol/kg wet weight and ml/100 ml) in three different muscles before and after (0, 1, 2, and 5 d) marathon runs for a well-trained individual who followed two different recovery protocols varying mainly in the diet. It was shown that the repletion of IMCL levels is strongly dependent on the diet post exercise. The monitoring of IMCL levels by means of 1H MRS is extremely promising, but several methodological limitations and pitfalls need to be considered, and these are addressed in the present review.

Effects of a short-term overfeeding with fructose or glucose in healthy young males

Consumption of simple carbohydrates has markedly increased over the past decades, and may be involved in the increased prevalence in metabolic diseases. Whether an increased intake of fructose is specifically related to a dysregulation of glucose and lipid metabolism remains controversial. We therefore compared the effects of hypercaloric diets enriched with fructose (HFrD) or glucose (HGlcD) in healthy men. Eleven subjects were studied in a randomised order after 7 d of the following diets: (1) weight maintenance, control diet; (2) HFrD (3.5 g fructose/kg fat-free mass (ffm) per d, +35 % energy intake); (3) HGlcD (3.5 g glucose/kg ffm per d, +35 % energy intake). Fasting hepatic glucose output (HGO) was measured with 6,6-2H2-glucose. Intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) were measured by 1H magnetic resonance spectroscopy. Both fructose and glucose increased fasting VLDL-TAG (HFrD: +59 %, P < 0.05; HGlcD: +31 %, P = 0.11) and IHCL (HFrD: +52 %, P < 0.05; HGlcD: +58 %, P = 0.06). HGO increased after both diets (HFrD: +5 %, P < 0.05; HGlcD: +5 %, P = 0.05). No change was observed in fasting glycaemia, insulin and alanine aminotransferase concentrations. IMCL increased significantly only after the HGlcD (HFrD: +24 %, NS; HGlcD: +59 %, P < 0.05). IHCL and VLDL-TAG were not different between hypercaloric HFrD and HGlcD, but were increased compared to values observed with a weight maintenance diet. However, glucose led to a higher increase in IMCL than fructose.

Topographic Electrophysiological Signatures of fMRI Resting State Networks

Background fMRI Resting State Networks (RSNs) have gained importance in the present fMRI literature. Although their functional role is unquestioned and their physiological origin is nowadays widely accepted, little is known about their relationship to neuronal activity. The combined recording of EEG and fMRI allows the temporal correlation between fluctuations of the RSNs and the dynamics of EEG spectral amplitudes. So far, only relationships between several EEG frequency bands and some RSNs could be demonstrated, but no study accounted for the spatial distribution of frequency domain EEG. Methodology/Principal Findings In the present study we report on the topographic association of EEG spectral fluctuations and RSN dynamics using EEG covariance mapping. All RSNs displayed significant covariance maps across a broad EEG frequency range. Cluster analysis of the found covariance maps revealed the common standard EEG frequency bands. We found significant differences between covariance maps of the different RSNs and these differences depended on the frequency band. Conclusions/Significance Our data supports the physiological and neuronal origin of the RSNs and substantiates the assumption that the standard EEG frequency bands and their topographies can be seen as electrophysiological signatures of underlying distributed neuronal networks.

Classification of Intervertebral Disk Degeneration with Axial T2 Mapping

OBJECTIVE The aim of this study was to establish an MRI classification system for intervertebral disks using axial T2 mapping, with a special focus on evaluating early degenerative intervertebral disks. MATERIALS AND METHODS Twenty-nine healthy volunteers (19 men, 10 women; age range, 20-44 years; mean age, 31.8 years) were studied, and axial T2 mapping was performed for the L3-L4, L4-L5, and L5-S1 intervertebral disks. Grading was performed using three classification systems for degenerative disks: our system using axial T2 mapping and two other conventional classification systems that focused on the signal intensity of the nucleus pulposus or the structural morphology in sagittal T2-weighted MR images. We analyzed the relationship between T2, which is known to correlate with change in composition of intervertebral disks, and degenerative grade determined using the three classification systems. RESULTS With axial T2 mapping, differences in T2 between grades I and II were smaller and those between grades II and III, and between grades III and IV, were larger than those with the other grading systems. The ratio of intervertebral disks classified as grade I was higher with the conventional classification systems than that with axial T2 mapping. In contrast, the ratio of intervertebral disks classified as grade II or III was higher with axial T2 mapping than that with the conventional classification systems. CONCLUSION Axial T2 mapping provides a more T2-based classification. The new system may be able to detect early degenerative changes before the conventional classification systems can.