Lactate administration activates the ERK1/2, mTORC1, and AMPK pathways differentially according to skeletal muscle type in mouse
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Lactate administration activates the ERK1/2, mTORC1, and AMPK pathways differentially according to skeletal muscle type in mouse. / Cerda-Kohler, Hugo; Henríquez Olguín, Carlos Felipe; Casas, Mariana; Jensen, Thomas Elbenhardt; Llanos, Paola; Jaimovich, Enrique.
In: Physiological Reports, Vol. 6, No. 18, e13800, 2018.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Lactate administration activates the ERK1/2, mTORC1, and AMPK pathways differentially according to skeletal muscle type in mouse
AU - Cerda-Kohler, Hugo
AU - Henríquez Olguín, Carlos Felipe
AU - Casas, Mariana
AU - Jensen, Thomas Elbenhardt
AU - Llanos, Paola
AU - Jaimovich, Enrique
N1 - CURIS 2018 NEXS 330
PY - 2018
Y1 - 2018
N2 - 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-p70S6KThr389 (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-AMPKThr172 (1.7-fold; P = 0.08), with a significant increase in p-ACCSer79 (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.
AB - 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-p70S6KThr389 (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-AMPKThr172 (1.7-fold; P = 0.08), with a significant increase in p-ACCSer79 (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.
KW - Faculty of Science
KW - Metabolism
KW - Molecular signaling
KW - Skeletal muscle
U2 - 10.14814/phy2.13800
DO - 10.14814/phy2.13800
M3 - Journal article
C2 - 30230254
VL - 6
JO - Physiological Reports
JF - Physiological Reports
SN - 2051-817X
IS - 18
M1 - e13800
ER -
ID: 202942362