Training state and fasting-induced PDH regulation in human skeletal muscle

Abstract

The aim of the present study was to examine the influence of training state on fasting-induced skeletal muscle pyruvate dehydrogenase (PDH) regulation, including PDH phosphorylation. Trained and untrained subjects, matched for skeletal muscle CS activity and OXPHOS protein, fasted for 36 h after receiving a standardized meal. Respiratory exchange ratio (RER) was measured and blood as well as vastus lateralis muscle biopsies were obtained 2, 12, 24, and 36 h after the meal. RER decreased with fasting only in untrained individuals, while PDHa activity decreased from 12 h after the meal in untrained, but only tended to decrease at 36 h in trained. PDH-E1α, PDP1 protein, PDH phosphorylation, and PDH acetylation in skeletal muscle was higher in trained than untrained subjects, but did not change with fasting, while PDK4 protein was higher at 36 h than at 2 h after the meal in both groups. In conclusion, the present results suggest that endurance exercise training modifies the fasting-induced regulation of PDHa activity in skeletal muscle and the substrate switch towards fat oxidation. PDH phosphorylation could not explain the fasting-induced regulation of PDHa activity suggesting other post translational modifications.

Suppression of Pyruvate Dehydrogenase Kinase by Dichloroacetate in Cancer and Skeletal Muscle Cells Is Isoform Specific and Partially Independent of HIF-1α

“…Secondly, an isoform-dependent effect of DCA on the abundance of PDK isoenzymes suggests that DCA alters not only the total PDK protein levels, but also the ratios between the four isoenzymes. PDK isoenzymes differ in their responsiveness to acute physiological regulators of enzyme activity, such as pyruvate, NADH, and acetyl-CoA [3], as well as their transcriptional or translational responses to various acute or chronic physiological stimuli, such as fasting, exercise, or hypoxia [41,42,71,72]. Isoform-dependent alterations in the protein abundance of PDK isoenzymes therefore likely have a functional and not only quantitative effect on the regulation of PDC.…”

GDF15 is an exercise-induced hepatokine regulated by glucagon and insulin in humans

“…Blood samples were obtained 2, 12, 24 and 36 hours after the meal intake. To ensure that the subjects did fast, an increase in ketone body production was monitored ( 26 ). HOMA-IR was calculated using plasma glucose and insulin measured after 12 hours of fasting.…”

Training state and skeletal muscle autophagy in response to 36 h of fasting

“…Further inclusion criteria was defined based on skeletal muscle oxidative capacity. Hence, citrate synthase activity and oxidative phosphorylation complex protein content were measured in skeletal muscle biopsies obtained at rest as markers of oxidative capacity to establish two nonoverlapping populations of untrained and trained individuals (14). This led to the exclusion of four subjects and resulted in seven untrained and six trained individuals, with no significant differences between the two groups in the following parameters: age 28 Ϯ 3 and 27 Ϯ 4 yr, height 183 Ϯ 10 and 183 Ϯ 4 cm, body weight 89 Ϯ 19 and 79 Ϯ 5 kg, and body mass index 26 Ϯ 1 and 24 Ϯ 1 (means Ϯ SD) for untrained and trained subjects, respectively.…”

“…All participants provided written informed consent. Tissue and blood samples from the present experiment have been used to address other research questions (3,14). The inclusion criteria used by Bertholdt et al (3) were based solely on V O2max performance because of use of adipose tissue in contrast to skeletal muscle in the present study.…”