The effect of a physiological increase in temperature on mitochondrial fatty acid oxidation in rat myofibers

Abstract

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°C and 40°C with the physiological substrates pyruvate + 4 mM malate (Pyr) and palmitoyl-CoA (PCoA) + 0.5 mM malate + 2 mM carnitine in permeabilized myofibers under nonphosphorylating ([Formula: see text]) or phosphorylating ([Formula: see text]) conditions. Mitochondrial efficiency was calculated by the respiratory control ratio (RCR = [Formula: see text]/[Formula: see text]). 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 nonphosphorylating 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°C to 40°C increased PCoA-[Formula: see text] and decreased PCoA-RCR, corresponding to the uncoupling of oxidative phosphorylation (OXPHOS). GTP blocked the heat-induced increase of PCoA-[Formula: see text]. Rising temperature moved toward a Pyr-[Formula: see text] 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. NEW & NOTEWORTHY Ex vivo exposure of skeletal myofibers to heat uncouples substrate oxidation from ADP phosphorylation, decreasing the efficiency of mitochondria to produce ATP. This heat effect alters fatty acids (FAs) more than carbohydrate oxidation. Alteration of FA oxidation involves uncoupling proteins without inducing oxidative stress. This alteration in lipid metabolism may underlie the preferential use of carbohydrates in the heat and could decrease aerobic endurance.

Effect of heat acclimation on metabolic adaptations induced by endurance training in soleus rat muscle

“…Sparks et al (2016) showed that training-induced increases in insulin sensitivity were associated with increased FA-induced uncoupling. Nevertheless, such putative training-induced uncoupling for fatty acids was not increased by heat acclimation, as we expected, because of the previously found acute effect of heat on fatty-acid uncoupling (Tardo-Dino et al, 2019). In our study, neither alterations of UCP-3 nor ANT-1 protein expression can explain such a decrease in the RCR.…”

Endurance Is Improved in Female Rats After Living High-Training High Despite Alterations in Skeletal Muscle

“…We used two protocols to study mitochondrial metabolism. The first was a protocol with three aims: (1) determination of the rate of the maximal oxidative capacity (Vmax), (2) determination of the specific oxidation for pyruvate (V maxPyr ), consisting of the successive addition of 2 mM pyruvate, 0.1 mM ADP, 20 mM creatine, 2 mM ADP, 10 mM glutamate, and 12 mM succinate in the presence of 4 mM malate and (3) estimation of the Km for ADP, with or without creatine, using the Michaelis Menten equation (Kuznetsov and Saks, 1986;Kuznetsov et al, 1996;Anflous et al, 2001;Ponsot et al, 2006;Perry et al, 2012): The second protocol, was used to measure the maximal rates of respiration with Palmitoyl-CoA, a long-chain fatty acid (Ponsot et al, 2005;Tardo-Dino et al, 2019) which must be transported across both mitochondrial membranes (via CPT-1 and CPT-2) in the presence of carnitine. We added Palmitoyl-CoA (final concentration of 400 µM) in the presence of 1 mM carnitine, 2 mM ADP, and 0.5 mM malate.…”

Effects of different rearing systems on intramuscular fat content, fatty acid composition, and lipid metabolism–related genes expression in breast and thigh muscles of Nonghua ducks

“…Notably, the significance between NRS and FRS at the same age exhibited a consistent tendency of higher profiles in NRS, indicating a capability of promoting fatty acids profiles in muscles, which was probably because FRS ducks suffered more from the temperature changes than in NRS. For instance, Tardo-Dino et al. (2019) found the temperature increase lead to less efficient oxidative phosphorylation of fatty acids in the soleus of rats.…”