Porter 2018 MiP2018b

From Bioblast
Skeletal muscle mitochondrial thermogenesis in hypermetabolic humans.

Link: MiP2018

Porter C, Ogunbileje JO, Fry CS, Bhattarai N, Rontoyianni VG, Capek KD, Bohannon FJ, Reidy PT, Finnerty CC, Suman OE, Rasmussen BB, Herndon DN (2018)

Event: MiP2018


Patients with severe burns become profoundly hypermetabolic. Uncoupling of skeletal muscle mitochondria plays a putative role in burn-induced hypermetabolism, however, a mechanistic understanding of this response is lacking. We hypothesize that uncoupling proteins (UCPs) contribute to mitochondrial thermogenesis in skeletal muscle of hypermetabolic burn patients.

We quantified whole body resting energy expenditure, mitochondrial respiratory capacity and coupling control, and the abundance and function of selected inner mitochondrial membrane carrier proteins in muscle collected from hypermetabolic burn patients and healthy non-burned individuals. Patients with burns were studied twice, at approximately two and four weeks post-injury.

Patients had massive burns, encompassing 54Β±20% of their body surface area. Metabolic rate was elevated by 44% and 47% at 2- and 4-weeks post-injury, respectively (P<0.001). State 3 respiration was similar in healthy controls and burned patients at 2 and 4 weeks post injury. In contrast, both state 2 (P<0.001) and oligomycin insensitive state 4 (P<0.01) leak respiration were elevated in muscle from burned patients at 2- and 4-weeks post burn. Further, respiratory control in response to ADP (P<0.01) and oligomycin (P<0.001) were diminished in muscle mitochondria from burned individuals. The proportion of state 4 respiration sensitive to the UCP inhibitor GDP was greater in burned patients (1.96Β±0.32 vs. 3.62Β±0.26 pmol/s/mg, P<0.001; or 9.5Β±1.0 vs, 3.5Β±0.4% of maximal uncoupled respiration, P<0.001). The response to the adenine nucleotide translocase (ANT) inhibitor bongkrekic acid during state 4 respiration was similar in healthy and burned patients. In line with this, the mRNA (P<0.001) and protein (P<0.05) levels of UCP2 were elevated in muscle of burn victims, whereas ANT gene (P<0.001) and protein (P<0.001) expression were decreased in muscle in response to burns.

Skeletal muscle mitochondria become uncoupled in response to burn trauma, suggesting a role for muscle mitochondrial thermogenesis in burn-induced hypermetabolism. Here, we identify uncoupling proteins as a molecular mediator of uncoupled mitochondrial respiration in the muscle of hypermetabolic humans.

β€’ Bioblast editor: Plangger M, Kandolf G β€’ O2k-Network Lab: US TX Galveston Porter C

Labels: MiParea: Respiration, Patients 

Enzyme: Uncoupling protein 

Coupling state: LEAK, OXPHOS 

HRR: Oxygraph-2k 


Porter C(1,3), Ogunbileje JO(1,3), Fry CS(2), Bhattarai N(1,3), Rontoyianni VG(1,3), Capek KD(1,3), Bohannon FJ(1,3), Reidy PT(2,+), Finnerty CC(1,3), Suman OE(1,3), Rasmussen BB(2), Herndon DN(1,3)

  1. Dept Surgery
  2. Dept Nutrition Metabolism; Univ Texas Medical Branch
  3. Shriners Hospitals Children; Galveston, TX, USA. - [email protected]
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