Fig. 1
Shorter-term hypoxic exposure enhances hepatic mitochondrial respiratory capacity. A Experimental design. Female Crl:CD(SD) rats (220–300 g) were exposed to normoxia or hypoxia (10% O2) for either 2 days (2 d) or 14 days (14 d), after which an electron transfer system complex III (CIII) inhibitor (GSK932121A, 25 mg kg−1, i.p.) or vehicle (Veh) was administered. B Haemoglobin concentration ([Hb]) (g/L) obtained from the tail vein upon termination. Data set includes both vehicle and GSK932121A-treated groups, n = 18 normoxic, n = 16 for all other groups. C–H Respiration of liver homogenates from Veh and GSK932121A-treated rats in the following states: Octanoyl carnitine and malate-supported (β-oxidation) respiration, without ADP (OctML) (C) and with ADP (OctMP) (D) to assess fatty acid oxidation. Stimulation of complex I-supported respiration with the addition of glutamate (GMP) (E). Stimulation of maximal OXPHOS following the addition of succinate (GMSP) (F) and maximal ETS capacity with the addition of the uncoupler FCCP (GMSE) (G). Finally, inhibition of complex I-supported respiration through the addition of rotenone, restricting electron flux through complex II in the presence of the electron transfer system uncoupler FCCP (SE) (H). Respiration rates are corrected to wet mass of liver tissue added to the chamber. n = 9 Veh normoxic rats, n = 8 Veh 2 d hypoxic, Veh and GSK932121A-treated 14 d hypoxic, n = 7 normoxic and 2 d hypoxic GSK932121A-treated rats. I Transmission electron microscopy of hepatic tissue at × 2500 and × 7000 magnifications. J Number of hepatic mitochondria per tissue area (μm2) using transmission electron microscopy. Data in Veh and GSK932121A-treated rats is combined, n = 5 normoxic, n = 8 hypoxic 2 d, n = 4 hypoxic 14 d. K Hepatic citrate synthase activity normalised to protein concentration. Data in Veh and GSK932121A-treated rats is combined, n = 17 normoxic, n = 16 hypoxic 2 d and 14 d. Data are presented as mean ± SEM, *p < 0.05, ** p ≤ 0.01, *** p ≤ 0.001.