Absence of renal hypoxia in the subacute phase of severe renal ischemia reperfusion injury

 This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this recordTissue hypoxia has been proposed as an important event in renal ischemia reperfusion injury (IRI) particularly during the period of ischemia and in the immediate hours following reperfusion. However, little is known about renal oxygenation during the subacute phase of IRI. We employed four different methods to assess the temporal and spatial changes in tissue oxygenation during the subacute phase (24 h and 5 days after reperfusion) of a severe form of renal IRI in rats. We hypothesized that the kidney is hypoxic 24 h and 5 days after an hour of bilateral renal ischemia, driven by a disturbed balance between renal oxygen delivery (DO2) and oxygen consumption (VO2). Renal DO2 was not significantly reduced in the subacute phase of IRI. In contrast, renal VO2 was 55% less 24 h, and 49% less 5 days after reperfusion than after sham-ischemia. Inner medullary tissue PO2, measured by radiotelemetry was 25 {plus minus} 12% greater 24 h after ischemia than after sham-ischemia. By 5 days after reperfusion, tissue PO2 was similar to that in rats subjected to sham-ischemia. Tissue PO2 measured by Clark electrode was consistently greater 24 h, but not 5 days, after ischemia than after sham-ischemia. Cellular hypoxia, assessed by pimonidazole adduct immunohistochemistry, was largely absent at both time-points and tissue levels of hypoxia inducible factors were downregulated following renal ischemia. Thus, in this model of severe IRI, tissue hypoxia does not appear to be an obligatory event during the subacute phase, likely due to the markedly reduced oxygen consumption.British Heart FoundationBritish Heart FoundationNational Health and Medical Research Council of AustraliaEuropean Union, Seventh Framework Programm

Heat stress causes spatially-distinct membrane re-modelling in K562 leukemia cells

Cellular membranes respond rapidly to various environmental perturbations. Previously we showed that modulations in membrane fluidity achieved by heat stress (HS) resulted in pronounced membrane organization alterations which could be intimately linked to the expression and cellular distribution of heat shock proteins. Here we examine heat-induced membrane changes using several visualisation methods. With Laurdan two-photon microscopy we demonstrate that, in contrast to the enhanced formation of ordered domains in surface membranes, the molecular disorder is significantly elevated within the internal membranes of cells preexposed to mild HS. These results were compared with those obtained by anisotropy, fluorescence lifetime and electron paramagnetic resonance measurements. All probes detected membrane changes upon HS. However, the structurally different probes revealed substantially distinct alterations in membrane heterogeneity. These data call attention to the careful interpretation of results obtained with only a single label. Subtle changes in membrane microstructure in the decision-making of thermal cell killing could have potential application in cancer therapy

Effects of sprint interval training on ectopic lipids and tissue-specific insulin sensitivity in men with non-alcoholic fatty liver disease

Purpose: This study examined the feasibility of sprint interval exercise training (SIT) for men with non-alcoholic fatty liver disease (NAFLD) and its effects on intrahepatic triglyceride (IHTG), insulin sensitivity (hepatic and peripheral), visceral (VAT) and subcutaneous adipose tissue (ScAT). Methods: Nine men with NAFLD (age 41 ± 8 years; BMI 31.7 ± 3.1 kg m−2; IHTG 15.6 ± 8.3%) were assessed at: (1) baseline (2) after a control phase of no intervention (pre-training) and (3) after 6 weeks of SIT (4–6 maximal 30 s cycling intervals, three times per week). IHTG, VAT and ScAT were measured using magnetic resonance spectroscopy or imaging and insulin sensitivity was assessed via dual-step hyperinsulinaemic-euglycaemic clamp with [6,6-D2] glucose tracer. Results: Participants adhered to SIT, completing ≥ 96.7% of prescribed intervals. SIT increased peak oxygen uptake [ V O2peak: + 13.6% (95% CI 8.8–18.2%)] and elicited a relative reduction in IHTG [− 12.4% (− 31.6 to 6.7%)] and VAT [− 16.9% (− 24.4 to − 9.4%); n = 8], with no change in body weight or ScAT. Peripheral insulin sensitivity increased throughout the study (n = 8; significant main effect of phase) but changes from pre- to post-training were highly variable (range − 18.5 to + 58.7%) and not significant (P = 0.09), despite a moderate effect size (g* = 0.63). Hepatic insulin sensitivity was not influenced by SIT. Conclusions: SIT is feasible for men with NAFLD in a controlled laboratory setting and is able to reduce IHTG and VAT in the absence of weight loss

Effect of Exercise Training on Insulin Sensitivity, Mitochondria and Computed Tomography Muscle Attenuation in Overweight Women With and Without Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is an insulin resistant (IR) state. Increased skeletal muscle lipid content and impaired mitochondrial biogenesis have been implicated in the pathogenesis of IR. We investigated whether differences in these variables explain the IR of women affected by PCOS and whether improvements in IR with exercise are reflected by changes in these variables