Mitochondria-targeted dodecyltriphenylphosphonium (C12TPP) combats high-fat-diet-induced obesity in mice.

BACKGROUND: A membrane-penetrating cation, dodecyltriphenylphosphonium (C12TPP), facilitates the recycling of fatty acids in the artificial lipid membrane and mitochondria. C12TPP can dissipate mitochondrial membrane potential and may affect total energy expenditure and body weight in animals and humans. METHODS: We investigated the metabolic effects of C12TPP in isolated brown-fat mitochondria, brown adipocyte cultures and mice in vivo. Experimental approaches included the measurement of oxygen consumption, carbon dioxide production, western blotting, magnetic resonance imaging and bomb calorimetry. RESULTS: In mice, C12TPP (50 µmol per (day•kg body weight)) in the drinking water significantly reduced body weight (12%, P<0.001) and body fat mass (24%, P<0.001) during the first 7 days of treatment. C12TPP did not affect water palatability and intake or the energy and lipid content in feces. The addition of C12TPP to isolated brown-fat mitochondria resulted in increased oxygen consumption. Three hours of pretreatment with C12TPP also increased oligomycin-insensitive oxygen consumption in brown adipocyte cultures (P<0.01). The effects of C12TPP on mitochondria, cells and mice were independent of uncoupling protein 1 (UCP1). However, C12TPP treatment increased the mitochondrial protein levels in the brown adipose tissue of both wild-type and UCP1-knockout mice. Pair-feeding revealed that one-third of the body weight loss in C12TPP-treated mice was due to reduced food intake. C12TPP treatment elevated the resting metabolic rate (RMR) by up to 18% (P<0.05) compared with pair-fed animals. C12TPP reduced the respiratory exchange ratio, indicating enhanced fatty acid oxidation in mice. CONCLUSIONS: C12TPP combats diet-induced obesity by reducing food intake, increasing the RMR and enhancing fatty acid oxidation.

Prognostic markers among Egyptian children with sepsis in the Intensive Care Units, Cairo University Hospitals.

BACKGROUND: Early identification of septic patients at risk of mortality is important in their prognosis. OBJECTIVE: Identification of septic patients at risk of mortality in Pediatric Intensive Care Units (PICUs) at Cairo University Hospitals, through measuring the levels of certain immunological parameters. METHODS: A hospital-based prospective cohort study was conducted in two PICUs at Cairo University Hospitals; all patients with diagnosis of severe sepsis or septic shock on admission were included. A total of 57 patients were prospectively followed at the selected PICUs and their demographic and clinical data were recorded. Microbiological and immunological workup (at days 1 and 7) was conducted for all patients to detect the causative organism of sepsis and to measure the levels of immunoglobulins (IgG, IgM and IgA), complement factors (C3 and C4), mature lymphocyte subpopulations (CD3+) and natural killer (NK) cells (CD3-CD16+CD56+), respectively. RESULTS: Mortality rate was 24.6%; the most frequent causes of death were multi-organ dysfunction and refractory shock. PELOD and PRISM III scores were significantly higher among non-survivors. At day 1, non-survivors had significantly higher levels of IgG, C4 and NK cells than survivors. However, from day 1 to day 7, survivors had a progressive increase in most of the immunological parameters (IgG, IgM, C4and CD3+ T lymphocytes). Survival curve analysis revealed the significant predictive ability of NK cells to detect early mortality. CONCLUSION: Monitoring the levels of cellular and humoral immunological parameters together with assessing PELOD and PRISM III scores can significantly affect prognosis and survival of septic children.