TY - JOUR
T1 - Burn Trauma Acutely Increases the Respiratory Capacity and Function of Liver Mitochondria
AU - Bohanon, Fredrick J.
AU - Nunez Lopez, Omar
AU - Herndon, David
AU - Wang, Xiaofu
AU - Bhattarai, Nisha
AU - Ayadi, Amina E.
AU - Prasai, Anesh
AU - Jay, Jayson
AU - Rojas-Khalil, Yesenia
AU - Toliver-Kinsky, Tracy E.
AU - Finnerty, Celeste C.
AU - Radhakrishnan, Ravi S.
AU - Porter, Craig
N1 - Publisher Copyright:
© Copyright 2017 by the Shock Society.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Background: A complete understanding of the role of the liver in burn-induced hypermetabolism is lacking. We investigated the acute effect of severe burn trauma on liver mitochondrial respiratory capacity and coupling control as well as the signaling events underlying these alterations. Methods: Male BALB/c mice (8-12 weeks) received full-thickness scald burns on ∼30% of the body surface. Liver tissue was harvested 24h postinjury. Mitochondrial respiration was determined by high-resolution respirometry. Citrate synthase activity was determined as a proxy of mitochondrial density. Male Sprague-Dawley rats received full-thickness scald burns to ∼60% of the body surface. Serum was collected 24h postinjury. HepG2 cells were cultured with serum-enriched media from either sham- or burn-treated rats. Protein levels were analyzed via western blot. Results: Mass-specific (P = 0.01) and mitochondrial-specific (P = 0.01) respiration coupled to ATP production significantly increased in the liver after burn. The respiratory control ratio for ADP (P = 0.04) and the mitochondrial flux control ratio (P = 0.03) were elevated in the liver of burned animals. Complex III and Complex IV protein abundance in the liver increased after burn by 17% and 14%, respectively. Exposure of HepG2 cells to serum from burned rats increased the pAMPKα:AMPKα ratio (P<0.001) and levels of SIRT1 (P = 0.01), Nrf2 (P<0.001), and PGC1α (P = 0.02). Conclusions: Severe burn trauma augments respiratory capacity and function of liver mitochondria, adaptations that augment ATP production. This response may be mediated by systemic factors that activate signaling proteins responsible for regulating cellular energy metabolism and mitochondrial biogenesis.
AB - Background: A complete understanding of the role of the liver in burn-induced hypermetabolism is lacking. We investigated the acute effect of severe burn trauma on liver mitochondrial respiratory capacity and coupling control as well as the signaling events underlying these alterations. Methods: Male BALB/c mice (8-12 weeks) received full-thickness scald burns on ∼30% of the body surface. Liver tissue was harvested 24h postinjury. Mitochondrial respiration was determined by high-resolution respirometry. Citrate synthase activity was determined as a proxy of mitochondrial density. Male Sprague-Dawley rats received full-thickness scald burns to ∼60% of the body surface. Serum was collected 24h postinjury. HepG2 cells were cultured with serum-enriched media from either sham- or burn-treated rats. Protein levels were analyzed via western blot. Results: Mass-specific (P = 0.01) and mitochondrial-specific (P = 0.01) respiration coupled to ATP production significantly increased in the liver after burn. The respiratory control ratio for ADP (P = 0.04) and the mitochondrial flux control ratio (P = 0.03) were elevated in the liver of burned animals. Complex III and Complex IV protein abundance in the liver increased after burn by 17% and 14%, respectively. Exposure of HepG2 cells to serum from burned rats increased the pAMPKα:AMPKα ratio (P<0.001) and levels of SIRT1 (P = 0.01), Nrf2 (P<0.001), and PGC1α (P = 0.02). Conclusions: Severe burn trauma augments respiratory capacity and function of liver mitochondria, adaptations that augment ATP production. This response may be mediated by systemic factors that activate signaling proteins responsible for regulating cellular energy metabolism and mitochondrial biogenesis.
KW - Burns
KW - hypermetabolism
KW - liver
KW - mitochondria
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UR - http://www.scopus.com/inward/citedby.url?scp=85022001687&partnerID=8YFLogxK
U2 - 10.1097/SHK.0000000000000935
DO - 10.1097/SHK.0000000000000935
M3 - Article
C2 - 28682939
AN - SCOPUS:85022001687
SN - 1073-2322
VL - 49
SP - 466
EP - 473
JO - Shock
JF - Shock
IS - 4
ER -