Medium Chain Acylcarnitines Dominate the Metabolite Pattern in Humans under Moderate Intensity Exercise and Support Lipid Oxidation

Background: Exercise is an extreme physiological challenge for skeletal muscle energy metabolism and has notable health benefits. We aimed to identify and characterize metabolites, which are components of the regulatory network mediating the beneficial metabolic adaptation to exercise

Assessment of relevant hepatic steatosis in obese adolescents by rapid fat-selective GRE imaging with spatial-spectral excitation : a quantitative comparison with spectroscopic findings

OBJECTIVE: To test the feasibility of fat-selective GRE imaging using a spectral-spatial excitation technique for determination of intrahepatic lipid content (IHL) in obese adolescents. METHODS: Fat-selective MR imaging (1.5 T) was applied to record a single axial slice through a representative liver region within a single breath-hold. The sequence uses six equidistant slice-selective excitation pulses with binomial amplitude ratios to achieve high selectivity for lipid signals after appropriate shimming. IHL(MRI) content was quantified using signal intensity of adjacent subcutaneous adipose tissue. As the gold standard for IHL quantification, single-voxel stimulated echo magnetic resonance spectroscopy (MRS) was applied. IHL(MRS) was quantified using the water peak as a reference. RESULTS: Forty-five MR examinations could be performed, and IHL(MRS) content ranged from 0.7% to 19.1%. Results from MRS and fat-selective imaging correlated well with Spearman coefficients between r = 0.78 and r = 0.86. There were no relevant regional differences in IHL within the liver parenchyma (p > 0.6359). Fat-selective imaging was able to reliably identify patients with IHL content above 5% with positive/negative likelihood ratio of 11.8 and 0.05, respectively. CONCLUSION: Fat-selective MR imaging provides both a reliable and a convenient method of rapidly quantifying IHL content in obese adolescents

Normal-weight 14-year-old girl with acanthosis nigricans and markedly increased hepatic steatosis : evidence for the important role of ectopic fat deposition in the pathogenesis of insulin resistance in childhood and adolescence

BACKGROUND: A major factor in the development of insulin resistance is obesity. While the contribution of intrahepatic lipids to insulin resistance is well established in adults, there are only few reports in childhood and adolescence. AIM: To investigate the correlation between ectopic fat deposition and insulin sensitivity in a normal-weight girl with acanthosis nigricans before and after lifestyle intervention. METHODS: Variations in body fat composition and intrahepatic lipids were monitored by means of anthropometric measures and by means of methods based on magnetic resonance imaging and magnetic resonance spectroscopy. RESULTS: We present the case of a normal-weight 14-year-old Caucasian girl with pronounced hepatic steatosis together with acanthosis nigricans, increased waist-circumference and increased visceral fat. During a 7-month period of lifestyle intervention, the girl lost 7.1 kg in weight. Acanthosis nigricans, whole-body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA) improved significantly (before intervention: WBISI 0.42, HOMA 22.2; after intervention: WBISI 1.35, HOMA 6.9). Even though all lipid compartments were decreased in size, the intrahepatic lipids showed an extraordinarily great reduction. CONCLUSION: This case presentation of a normal-weight girl with acanthosis nigricans and markedly increased hepatic steatosis provides support for the association between intrahepatic fat deposition and insulin resistance in adolescence

Gene expression in primary human skeletal muscle cells after treatment with acylcarnitines.

<p>mRNA expression of PGC-1α (A), CPT1b (B), CD36 (C), COX1 (D) and AngPL-4 (E) related to β-actin mRNA levels after incubation with 100 µM L-carnitine (L-C), an equimolar mixture of C8:0-, C10:0- and C12:0-acylcarnitine (total 100 µM; AC), 60 µM palmitate (p), or p and AC as indicated. Values are shown as fold changes compared with untreated (L-C, AC) or BSA-treated (p, p+AC) control cells, shown are means ± SEM; * significant increase with p<0.05 vs. control cells, † p = 0.06 vs. control cells; # significant decrease with p<0.05 vs. control cells. The broken black line indicates the 1-fold expression in control cells.</p

Time-course for the acylcarnitine species plasma levels during the exercise phase and under recovery conditions.

<p>(A) Time-dependent changes of acylcarnitine species during the exercise bout and in the recovery phase, based on non-targeted (NT-)metabolomics signal intensity data. The relative amounts of acylcarnitines are based on peak heights. Values are means ±SE. *<i>p<</i>0.05, significantly different from the pre run signal intensity; (<i>n = </i>13). (B) Time-dependent changes of 13 individual C10:0 carnitine levels based on NT-metabolomics data. (C) Quantitative analysis of time-dependent changes of plasma acylcarnitine concentrations investigated in eight individuals performing a continuous 120 min treadmill run at 70% V_IAT in an independent second exercise study. Values are means ±SE. *<i>p<</i>0.05, significantly different from the pre-run concentrations. As a C8- instead of a C18-reversed phase UPLC-column was used to achieve the detection of the long-chain C16 (palmitoyl)-carnitine, the analysis of C2:0-carnitine was not possible in this experiment.</p

Identification of metabolites reflecting changes in the metabolite pattern during moderate intensity exercise and recovery.

<p>Comparison of the time-dependent changes in the plasma metabolome of 13 individuals after a 60 min treadmill run at 93% velocity at individual anaerobic threshold (V_IAT; approximately 75% of VO_2max), showing the metabolome at rest, immediately at the end of the physical activity and at two time points in the recovery phase. The analyses were performed by partial least squares-discriminant analysis (PLS-DA) and OSC-filtering. (A) OSC-filtered PLS-DA score plot showing pre-run (▪), immediately after run (○), three hours after run (Δ) and 24 hours after run (*); (B) OSC-filtered PLS-DA score plot showing pre run (▪) and immediately after run (○). (C,D) The corresponding S-plot to (A) and (B), respectively. The variables are labelled with <i>m/z</i> values. Potential metabolic biomarkers including the corresponding <i>m/z</i> values are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011519#pone-0011519-t003" target="_blank">Table 3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011519#pone-0011519-t004" target="_blank">Table 4</a>.</p

Most influential metabolites contributing to the separation of the clusters of the exercise and recovery phase shown in Figure 1A.

<p>Only metabolites showing significant changes are given.</p><p>*mass (m/z) represents a fragment of this metabolite.</p

¹³C-Acylcarnitine synthesis and release from primary human myotubes.

<p>Comparison of the time course of intracellular (A) and extracellular (B) intensity levels of ¹²C- and ¹³C-palmitoyl-carnitine in an experiment with primary human myotubes incubated with a mixture of 125 µM [U-¹³C₁₆]palmitate/125 µM palmitate for 30 min, 4 h and 20 h. (C) The time course of the ¹²C- and ¹³C-signal intensity of dodecanoyl-carnitine and (D) decanoyl-carnitine. The ¹³C-signal of the respective acylcarnitine is marked by a dash dotted arrow, the ¹²C-signal by a solid arrow.</p

Physical characteristic of the subjects.

<p>V_IAT - velocity at individual anaerobic threshold,</p><p>VO_2max - maximal oxygen consumption.</p