The Effect of a Physiological Increase in Temperature on Mitochondrial Fatty Acid Oxidation in Rat Myofibers

We investigated the effect of temperature increase on mitochondrial fatty acid (FA) and carbohydrate oxidation in the slow-oxidative skeletal muscles (soleus) of rats. We measured mitochondrial respiration at 35 and 40°C with the physiological substrates pyruvate + 4mM malate (Pyr) and palmitoyl-CoA + 0.5mM malate + 2mM carnitine (PCoA) in permeabilised myofibres under non-phosphorylating ( 0) or phosphorylating ( max) conditions. Mitochondrial efficiency was calculated by the respiratory control ratio (RCR = max/ 0). We used guanosine triphosphate (GTP), an inhibitor of uncoupling protein (UCP), to study the mechanisms responsible for alterations of mitochondrial efficiency. We measured hydrogen peroxide (H2O2) production under non-phosphorylating and phosphorylating conditions at both temperatures and substrates. We studied citrate synthase (CS) and 3-hydroxyl acyl coenzyme A dehydrogenase (3-HAD) activities at both temperatures. Elevating the temperature from 35 to 40°C increased PCoA- 0 and decreased PCoA-RCR, corresponding to the uncoupling of oxidative phosphorylation (OXPHOS). GTP blocked the heat-induced increase of PCoA- 0. Rising temperature moved towards a Pyr- 0 increase, without significance. Heat did not alter H2O2 production resulting from either PCoA or Pyr oxidation. Heat induced an increase in 3-HAD but not in CS activities. In conclusion, heat induced OXPHOS uncoupling for PCoA oxidation which was, at least partially, mediated by UCP and independent of oxidative stress. The classically described heat-induced glucose shift may actually be mostly due to a less efficient FA oxidation. These findings raise questions concerning the consequences of heat-induced alterations in mitochondrial efficiency of FA metabolism on thermoregulation.