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O'Brien 2017 Abstract IOC122

From Bioblast
PPARĪ± independent effects of nitrate supplementation on skeletal muscle mitochondrial function in hypoxia.

Link: Mitochondr Physiol Network 22.01

O'Brien KA, Horscroft JAH, Lindsay RT, Philp A, Harridge SDR, Murray AJ (2017)

Event: IOC122

Oxygen insufficiency (hypoxia), either in response to environmental exposure or pathological states, induces metabolic stress and remodelling the details of which remain ill-defined. A controversial aspect of acclimation is skeletal muscle metabolic remodelling, a process that may be aided by nitrate supplementation. Mechanisms of nitrate action have been demonstrated previously in skeletal muscle to involve interaction with a master regulator of fat metabolism, peroxisome proliferator-activated receptor alpha (PPARĪ±)[1]. In the present study, the potential for dietary nitrate supplementation to aid hypoxic acclimatisation through protection of skeletal muscle mitochondrial function and the requirement for PPARĪ± in this response were investigated. Hypoxia induced a 26% decrease (pā‰¤0.001) in mass specific long chain fatty acid LEAK state respiration and a 23% decrease (pā‰¤0.01) in carbohydrate oxidative phosphorylation capacity in control (chloride treated) mice of both PPARĪ±+/+ and PPARĪ±-/- genotypes. These significant decreases were not apparent in nitrate supplemented mice, indicating a nitrate dependent recovery of mitochondrial function. A nitrate effect was observed in both PPARĪ±+/+ and PPARĪ±-/- mice, suggesting a mechanism acting independently of PPARĪ±. Our results confirm previous reports of hypoxia suppressing skeletal muscle mitochondrial function and show this effect can be partially alleviated through dietary nitrate supplementation. Whilst the signalling mechanisms remain uncertain, this process appears to occur independently of PPARĪ±.


ā€¢ Bioblast editor: Kandolf G ā€¢ O2k-Network Lab: UK Cambridge Murray AJ


Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Skeletal muscle 


Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k 


Affiliations

Oā€™Brien KA(1,2), Horscroft JAH(2), Lindsay RT(2), Philp A(3), Harridge SDR(1), Murray AJ(2)
  1. Centre Human & Aerospace Physiol Sciences, Kingā€™s College London
  2. Dept Physiol, Development Neuroscience, Univ Cambridge
  3. MRC Arthritis Research UK Centre Musculoskeletal Ageing Research, School Sport, Exercise Rehabilitation Sciences, Univ Birmingham
United Kingdom. - ko337@cam.ac.uk

References

  1. Ashmore T, Roberts LD, Morash AJ, Kotwica AO, Finnerty J, West JA, Murfitt SA, Fernandez BO, Branco C, Cowburn AS, Clarke K, Johnson RS, Feelisch M, Griffin JL, Murray AJ Nitrate enhances skeletal muscle fatty acid oxidation via a nitric oxide-cGMP-PPAR-mediated mechanism. BMC Biol 13:1-17.