Time-of-day does not impact skeletal muscle contractile function, fatigability, or contraction-stimulated glucose uptake

Abstract

Time-of-day impacts different aspects of mammalian physiology, such as the sleep/wake cycle, blood pressure, and body temperature. These time-of-day changes, or “circadian cycles”, are regulated by a central clock in the central suprachiasmatic nucleus of the hypothalamus and peripheral clocks located in other tissues, such as the liver, heart, and skeletal muscle. Interestingly, a growing body of data suggests that exercise performance and capacity also vary by time-of-day, with chronobiological effects on skeletal muscle metabolism and contractile function (i.e., force production) being proposed as important mediators. However, to date, no studies have specifically investigated the effect of time-of-day on skeletal muscle contractile function or glucose metabolism. The objective of this work was to assess ex vivo skeletal muscle contractile function, fatigability, and contraction-stimulated glucose uptake in the extensor digitorum longus (EDL) and soleus from 13-week-old female C57BL/6NJ mice at four different times-of-day (Light cycle time-points: Zeitgeber Time [ZT] ZT1 and ZT7; Dark cycle time-points: ZT13 and ZT19). We used an ex vivo approach as it allowed us to study skeletal muscle in isolation, and thus, independent of other factors that might influence contractile function or glucose metabolism (e.g., nerve function, humoral factors, etc.). We hypothesized that skeletal muscle contractile function, fatigability and contraction-stimulated glucose uptake would not be different by time-of-day. To control for meal-timing, mice were orally gavaged with dextrose (2 g/kg) and then fasted (3 hours) before contractile testing, which consisted of a force-frequency test (1-120 Hz, 0.3 ms pulse, 35 volts; 300 ms and 400 ms train for EDL and soleus, respectively) followed by a 15 minute fatigue test in which the muscles were repeatedly stimulated (EDL: 100 Hz stimulation every 15 seconds; Soleus: 30 Hz stimulation every 2 seconds). Glucose uptake was measured during the fatigue test using the [3H]-2-deoxyglucose (2DOG) uptake approach, with the contralateral muscle being the rested control. Significantly, contractile function, including peak twitch tension and maximal tetanic tension (EDL — ZT1: 281±13; ZT7: 300±21; ZT13: 261±28; ZT19: 280±40 kPa, P = 0.7661, one-way ANOVA; Soleus — ZT1: 117±16; ZT7: 115±18; ZT13: 117±11; ZT19: 111±10 kPa, P = 0.9923, one-way ANOVA) were not different by time-of-day. Similarly, fatigability, as measured as the tension·time integral during the 15 min fatigue test was not different by time-of-day (EDL — ZT1: 640±89; ZT7: 686±92; ZT13: 708±110; ZT19: 683±142 kPa·min, P = 0.9803, one-way ANOVA; Soleus — ZT1: 245±42; ZT7: 261±35; ZT13: 200±41; ZT19: 244±34 kPa·min, P = 0.7019, one-way ANOVA). Finally, while contraction significantly increased 2DOG uptake above basal by ~1.6-fold and ~1.8-fold in the soleus and EDL, respectively, this increase was not different by time-of-day. Taken together, these results demonstrate that time-of-day does not impact skeletal muscle contractile function, fatigability, or contraction-stimulated glucose uptake, regardless of muscle type. By extension, skeletal muscle, per se, is unlikely to be a contributing factor to the documented effects of time-of-day on whole-body exercise performance. This was funded by the UC San Diego Medical Scientist Training Program and NIH R21 AG067495. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.