O'Brien 2017 Abstract IOC122

PPARα 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 (PPARα)[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 PPARα in this response were investigated. Hypoxia induced a 26% decrease (p≤0.001) in mass specific long chain fatty acid LEAK state respiration and a 23% decrease (p≤0.01) in carbohydrate oxidative phosphorylation capacity in control (chloride treated) mice of both PPARα^+/+ and PPARα^-/- 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 PPARα^+/+ and PPARα^-/- mice, suggesting a mechanism acting independently of PPARα. 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 PPARα.

• Bioblast editor: Kandolf G • 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: F HRR: Oxygraph-2k

Affiliations

O’Brien KA(1,2), Horscroft JAH(2), Lindsay RT(2), Philp A(3), Harridge SDR(1), Murray AJ(2)

Centre Human & Aerospace Physiol Sciences, King’s College London
Dept Physiol, Development Neuroscience, Univ Cambridge
MRC Arthritis Research UK Centre Musculoskeletal Ageing Research, School Sport, Exercise Rehabilitation Sciences, Univ Birmingham

United Kingdom. - ko337@cam.ac.uk

References

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.