Lactate administration increases mRNA expression of PGC-1α and UCP3 in mouse skeletal muscle

Kitaoka, Yu; Takeda, Kohei; Tamura, Yuki; Hatta, Hideo

doi:10.1139/apnm-2016-0016

Cited by 71 publications

(67 citation statements)

References 20 publications

(19 reference statements)

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“…Accordingly, treatment with lactate elevated PGC‐1α mRNA in myotubes (Hashimoto et al . 2007) and mouse skeletal muscle (Kitaoka et al . 2016), and a restricted exercise‐induced decline in muscle pH blunted the PGC‐1α mRNA upregulation during the early recovery from high‐intensity exercise in humans (Edge et al .…”

Section: Discussionmentioning

confidence: 99%

Metabolic stress‐dependent regulation of the mitochondrial biogenic molecular response to high‐intensity exercise in human skeletal muscle

Fiorenza

Gunnarsson

Hostrup

et al. 2018

The Journal of Physiology

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The aim of the present study was to examine the impact of exercise-induced metabolic stress on regulation of the molecular responses promoting skeletal muscle mitochondrial biogenesis. Twelve endurance-trained men performed three cycling exercise protocols characterized by different metabolic profiles in a randomized, counter-balanced order. Specifically, two work-matched low-volume supramaximal-intensity intermittent regimes, consisting of repeated-sprint (RS) and speed endurance (SE) exercise, were employed and compared with a high-volume continuous moderate-intensity exercise (CM) protocol. Vastus lateralis muscle samples were obtained before, immediately after, and 3 h after exercise. SE produced the most marked metabolic perturbations as evidenced by the greatest changes in muscle lactate and pH, concomitantly with higher post-exercise plasma adrenaline levels in comparison with RS and CM. Exercise-induced phosphorylation of CaMKII and p38 MAPK was greater in SE than in RS and CM. The exercise-induced PGC-1α mRNA response was higher in SE and CM than in RS, with no difference between SE and CM. Muscle NRF-2, TFAM, MFN2, DRP1 and SOD2 mRNA content was elevated to the same extent by SE and CM, while RS had no effect on these mRNAs. The exercise-induced HSP72 mRNA response was larger in SE than in RS and CM. Thus, the present results suggest that, for a given exercise volume, the initial events associated with mitochondrial biogenesis are modulated by metabolic stress. In addition, high-intensity exercise seems to compensate for reduced exercise volume in the induction of mitochondrial biogenic molecular responses only when the intense exercise elicits marked metabolic perturbations.

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Section: Discussionmentioning

confidence: 99%

Metabolic stress‐dependent regulation of the mitochondrial biogenic molecular response to high‐intensity exercise in human skeletal muscle

Fiorenza

Gunnarsson

Hostrup

et al. 2018

The Journal of Physiology

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“…Citrate synthetase (CS), beta-HAD, and COXIV as well as the fatty acid transporter FAT/CD36 expression and protein content are increased with high-intensity interval training; however, when dichloroacetate was administrated (and lactate reduced), these adaptations were attenuated [50]. Moreover, PDK isoform 4 (which inhibits the conversion of lactate to pyruvate) and UCP3 (uncoupling protein 3, which improves mitochondrial oxidative capacity) were also increased with lactate administration in mouse muscle fibers—both proteins that are also upregulated by PGC-1 alpha [51]. …”

Section: Pgc-1 Alpha Mediates Lactate Adaptations In Muscle Fibersmentioning

confidence: 99%

“…Moreover, a recent study showed that in vivo lactate administration (by intraperitoneal injection on mice) upregulated PGC-1 alpha gene expression [51]. This clearly suggests that many possible lactate-induced adaptations are mediated by the upregulation of PGC-1 alpha.…”

Section: Pgc-1 Alpha Mediates Lactate Adaptations In Muscle Fibersmentioning

confidence: 99%

Lactate as a Signaling Molecule That Regulates Exercise-Induced Adaptations

Nalbandian

Takeda

2016

Biology

128

113

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Lactate (or its protonated form: lactic acid) has been studied by many exercise scientists. The lactate paradigm has been in constant change since lactate was first discovered in 1780. For many years, it was unfairly seen as primarily responsible for muscular fatigue during exercise and a waste product of glycolysis. The status of lactate has slowly changed to an energy source, and in the last two decades new evidence suggests that lactate may play a much bigger role than was previously believed: many adaptations to exercise may be mediated in some way by lactate. The mechanisms behind these adaptations are yet to be understood. The aim of this review is to present the state of lactate science, focusing on how this molecule may mediate exercise-induced adaptations.

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“…In vivo lactate administration increases messenger RNA levels of oxidative metabolism‐related genes as PGC‐1 α in skeletal muscle of mouse (Kitaoka et al. ). In skeletal muscle cell lines as L6 and C2C12, lactate activates the ERK1/2 pathway (Li et al.…”

Section: Introductionmentioning

confidence: 99%

Lactate administration activates the ERK1/2, mTORC1, and AMPK pathways differentially according to skeletal muscle type in mouse

et al. 2018

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Skeletal muscle is described as an endocrine organ, constitutively or intermittently secreting bioactive molecules. The signaling pathways by which these molecules mediate changes in skeletal muscle and regulate interorgan crosstalk are only partly understood. Lactate is widely described as a signaling molecule in different cells, but the role of lactate as a signaling molecule in mature skeletal muscle has not been fully unveiled. The aim of this study was to determine the role of lactate on activation of signaling pathways in adult mouse skeletal muscle. Male mice were injected intraperitoneally with lactate or saline, and tissues were dissected after 40 min. Phosphorylation levels of relevant proteins in muscle were assessed by Western blotting. After lactate administration, we found an increase in p‐ERK1/2Thr202/Tyr204 (3.5‐fold; P = 0.004) and p‐p70S6KT hr389 (1.9‐fold; P = 0.01) in quadriceps; and an increase in p‐rpS6Ser235/236 in both quadriceps (6.3‐fold; P = 0.01) and EDL (2.3‐fold; P = 0.01), without changes in soleus. There was a tendency toward an increase in p‐AMPKT hr172 (1.7‐fold; P = 0.08), with a significant increase in p‐ACCS er79 (1.5‐fold; P = 0.04) in soleus, without changes in quadriceps and EDL. These results support the hypothesis that lactate plays a role in the molecular signaling related to hypertrophy and to oxidative metabolism on adult skeletal muscle and suggest that this activation depends on the skeletal muscle type. The mechanisms that underlie the effect of lactate in mature skeletal muscles remain to be established.

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Lactate administration increases mRNA expression of PGC-1α and UCP3 in mouse skeletal muscle

Cited by 71 publications

References 20 publications

Metabolic stress‐dependent regulation of the mitochondrial biogenic molecular response to high‐intensity exercise in human skeletal muscle

Metabolic stress‐dependent regulation of the mitochondrial biogenic molecular response to high‐intensity exercise in human skeletal muscle

Lactate as a Signaling Molecule That Regulates Exercise-Induced Adaptations

Lactate administration activates the ERK1/2, mTORC1, and AMPK pathways differentially according to skeletal muscle type in mouse

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