Dimitru Constantin-Teodosiu

PubMed2003

Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo.

Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (LF) or high-fat (HF) diets. Immediately following exercise, blood flow was reinstated, and muscle was sampled after 20, 60, and 120 seconds of recovery. Mitochondrial coupling was assessed by determining the rate of PCr resynthesis during recovery. The HF diet increased UCP3 protein content by approximately 44% compared with the LF diet. However, this HF diet-induced increase in UCP3 expression was not associated with any changes in the rate of muscle PCr resynthesis during conditions of maximal flux through oxidative phosphorylation. Muscle acetylcarnitine, free-creatine, and lactate concentrations during recovery were unaffected by the HF diet. Taken together, our findings demonstrate that increasing muscle UCP3 expression does not diminish the rate of PCr resynthesis, allowing us to conclude that the primary role of UCP3 in humans is not uncoupling.

Adult↗

PubMed2002

Exercise with low muscle glycogen augments TCA cycle anaplerosis but impairs oxidative energy provision in humans.

We tested the hypotheses that: (i) exercise with low muscle glycogen would reduce pyruvate flux through the alanine aminotransferase (AAT) reaction and attenuate the increase in tricarboxylic acid (TCA) cycle intermediates, and (ii) attenuation of tricarboxylic acid cycle intermediate (TCAI) pool expansion would limit TCA cycle flux, thereby accelerating phosphocreatine (PCr) degradation. Eight men cycled for 10 min at 70 % of their (VO(2,max) on two occasions: (i) following their normal diet (CON) and (ii) after cycling to exhaustion and consuming a low carbohydrate diet for approximately 2 days (LG). Biopsies (m. vastus lateralis) confirmed that [glycogen] was lower in LG vs. CON at rest (257 +/- 18 vs. 611 +/- 54 mmol (kg dry mass)(-1); P 0.05); however, net glycogenolysis was not different after 1 or 10 min of exercise. PCr degradation from rest to 1 min was approximately 26 % higher in LG vs. CON (38 +/- 4 vs. 28 +/- 4 mmol (kg dry mass)(-1); P< or =0.05). The sum of five measured TCAIs (approximately 90 % of total pool) was not different between trials at rest and after 1 min, but was higher after 10 min in LG vs. CON (5.51 +/- 0.43 vs. 4.45 +/- 0.49 mmol (kg dry mass)(-1); P 0.05). Pyruvate dehydrogenase complex (PDC) activity was lower during exercise in LG vs. CON (2.2 +/- 0.2 vs. 1.4 +/- 0.2 mmol min(-1) (kg wet weight)(-1) after 10 min; P< or =0.05), and acetylcarnitine was approximately threefold less, implying increased pyruvate availability for flux through AAT. Resting muscle [glutamate] was higher in LG vs. CON (16.1 +/- 0.8 vs. 11.8 +/- 0.4 mmol (kg dry mass)(-1); P< or =0.05) and the net decrease in [glutamate] during exercise was approximately 30 % greater in LG vs. CON. These findings suggest that: (i) contrary to our hypotheses, LG increased anaplerosis by decreasing PDC flux and/or increasing the conversion of glutamate carbon to TCAIs, and (ii) accelerating the rate of muscle TCAI expansion did not affect oxidative energy provision during the initial phase of contraction, since changes in [TCAI] were not temporally related to PCr degradation.

Adult↗