Schmidt 2015 Abstract MiPschool Greenville 2015

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High-fat diet induced mitochondrial dysfunction exacerbates limb pathology in genetically ischemia protected mice.

Link:

Schmidt CA, Ryan TE, Green TD, Neufer PD, McClung JM (2015)

Event: MiPschool Greenville 2015

Patients with type II diabetes typically present with peripheral arterial disease (PAD) at a younger age and are more likely to suffer tissue loss associated with the most severe manifestation of the disease, critical limb ischemia (CLI). Alterations in limb muscle mitochondrial respiration and reactive oxygen species emission are components of diabetic myopathy and could provide a mechanism for increased morbidity outcomes in CLI patients. We hypothesized that chronic high fat feeding-induced mitochondrial dysfunction would exacerbate the ischemic myopathy in normally ischemia protected BL/6J mice. BL/6J (n=56) mice were placed on a 45% high fat diet (HFD) or a control low fat diet (LFD, 10% fat with matched sucrose) and were subjected to unilateral femoral artery transection (HLI) after 6 or 16-weeks. At HLI d7, mitochondria were isolated from the plantar flexor muscles of both control and ischemic limbs and respiration, hydrogen peroxide (H2O2) emission, and calcium retention capacity were determined. Sixteen weeks of HFD reduced mitochondrial respiration and increased H2O2 emission in contralateral control limb muscle. The pre-existing reductions in mitochondrial respiration were exacerbated by HLI and resulted in increased limb necrosis and reduced limb blood flow recovery during HLI. In parallel, limb muscle myopathy was significantly increased in the normally ischemia protected BL/6J parental strain. Our data suggest that HFD induced mitochondrial dysfunction in limb skeletal muscle tissue creates a local pre-existing metabolic environment that is more conducive to severe ischemic myopathy. Interestingly, this dysfunctional environment dominates over the inherent BL/6J strain dependent genetic protection from ischemia and results in greater tissue necrosis and vascular regression in these mice. These findings demonstrate the complexity of the bio-energetic contributions to ischemic disease pathology and indicate that the diabetic increase in CLI morbidity and mortality outcomes may be a direct result of alterations to the limb tissue mitochondria.


O2k-Network Lab: US NC Greenville Neufer PD


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, mt-Medicine, mt-Awareness  Pathology: Diabetes  Stress:Ischemia-reperfusion  Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Isolated mitochondria 



Event: Poster 


Affiliations

1-Dept Physiol; 2-Diabetes Obesity Inst, East Carolina Univ, Brody Medical Center, Greenville, NC, USA. - mcclungj@ecu.edu