Abnormal whole-body energy metabolism in iron-deficient humans despite preserved skeletal muscle oxidative phosphorylation.

Iron deficiency impairs skeletal muscle metabolism. The underlying mechanisms are incompletely characterised, but animal and human experiments suggest the involvement of signalling pathways co-dependent upon oxygen and iron availability, including the pathway associated with hypoxia-inducible factor (HIF). We performed a prospective, case-control, clinical physiology study to explore the effects of iron deficiency on human metabolism, using exercise as a stressor. Thirteen iron-deficient (ID) individuals and thirteen iron-replete (IR) control participants each underwent 31P-magnetic resonance spectroscopy of exercising calf muscle to investigate differences in oxidative phosphorylation, followed by whole-body cardiopulmonary exercise testing. Thereafter, individuals were given an intravenous (IV) infusion, randomised to either iron or saline, and the assessments repeated ~ 1 week later. Neither baseline iron status nor IV iron significantly influenced high-energy phosphate metabolism. During submaximal cardiopulmonary exercise, the rate of decline in blood lactate concentration was diminished in the ID group (P = 0.005). Intravenous iron corrected this abnormality. Furthermore, IV iron increased lactate threshold during maximal cardiopulmonary exercise by ~ 10%, regardless of baseline iron status. These findings demonstrate abnormal whole-body energy metabolism in iron-deficient but otherwise healthy humans. Iron deficiency promotes a more glycolytic phenotype without having a detectable effect on mitochondrial bioenergetics.

IL-6 deficiency protects against angiotensin II induced endothelial dysfunction and hypertrophy.

OBJECTIVE: The goal of this study was to test the hypothesis that IL-6 mediates the increases in superoxide, vascular hypertrophy, and endothelial dysfunction in response to angiotensin II (Ang II). METHODS AND RESULTS: Responses of carotid arteries from control and IL-6-deficient mice were examined after acute (22-hour) incubation with Ang II (10 nmol/L) or chronic infusion of Ang II (1.4 mg/kg/d for 14 days). The hypertrophic response and endothelial dysfunction produced by Ang II infusion was markedly less in carotid arteries from IL-6-deficient mice than that in control mice. IL-6 deficiency also protected against endothelial dysfunction in response to acute (local) Ang II treatment (eg, 100 mumol/L acetylcholine produced 100+/-4 and 98+/-4% relaxation in vehicle-treated and 51+/-4 and 99+/-4% relaxation in Ang II-treated, control, and IL-6-deficient vessels, respectively). Endothelial dysfunction could be reproduced in vessels from IL-6-deficient mice with combined Ang II plus IL-6 (0.1 nmol/L) treatment. Increases in vascular superoxide and IL-6, as well as reductions in endothelial nitric oxide synthase mRNA expression, produced by Ang II were absent in IL-6-deficient mice. CONCLUSIONS: These data demonstrate that IL-6 is essential for Ang II-induced increases in superoxide, endothelial dysfunction, and vascular hypertrophy.

Energy requirements and body composition in stable pediatric intensive care patients receiving ventilatory support.

Energy requirements of pediatric intensive-care patients are unknown due to the difficulty of measuring total energy expenditure in free-living conditions. We investigated energy expenditure and body composition in stable pediatric intensive-care patients receiving long-term ventilatory support. Total energy expenditure and total body water were measured in 10 such patients using the doubly-labeled water method. The patients had significantly lower energy expenditure than healthy children of the same age. Relative to length, fat-free mass deposition was significantly lower, and fat deposition was significantly greater, than in healthy subjects. In general, total energy requirements of these patients are significantly reduced as compared to healthy children, which can be attributed to their lower activity levels and their reduced muscle mass. Although they gain weight similar to healthy children, their weight gain is disproportionately higher in fat. However, one patient with myofibromatosis contradicted this general pattern.