Acute Oxaloacetate Exposure Enhances Resistance to Fatigue in in vitro Mouse Soleus Muscle

This is the authors' abstract. We don't add key points for this paper.

Oxaloacetate is a four-carbon substrate involved in the rate-determining step of the tricarboxylic acid (TCA) cycle. We tested the hypothesis that supplementary oxaloacetate would improve skeletal muscle fatigue resistance, possibly by enhancing the substrate-level ATP production within the mitochondria. Mouse soleus muscles (n=16) were dissected, mounted in experimental chambers (33–34°C) and separated into a control (C; n=7) and an experimental group (OAA; n=9). Each muscle conducted 2 contractile work bouts (separated by a 60-min rest period) until a set fatigue point (60% of the initial force). The initial time to fatigue was identical for the C and OAA groups. During the 60-min rest period, the OAA group was perfused with oxaloacetate (1 mg/L), with no changes in the control group. There was no significant difference in time to fatigue between the 2 contractile runs in the control group (186.1±12.4 vs. 190.3±13.8 sec). However, the OAA group displayed a greater resistance to fatigue in the second run compared to the first (210±10.1 vs. 236.9±8.0 sec, P<0.05). These results demonstrate that acute exposure to oxaloacetate increases resistance to fatigue in mouse slow-twitch muscle, and potential sources of this improvement may be due to increased substrate-level phosphorylation within the mitochondria or some other enhancement of the TCA cycle function. Supported by NIH grant 1P01HL091830-01A18101