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Abstract
Concurrent Obesity And Chronic Alcohol Consumption Exacerbates Skeletal Muscle Mitochondrial Dysfunction In A Murine Model Of Peripheral Artery Disease (PAD)
Arteriosclerosis, thrombosis, and vascular biology, Vol.44(Suppl_1), A1151
05/2024
Web of Science ID: WOS:001350237100182
Abstract
Abstract only PAD causes ischemic mitochondrial and consequent muscle damage in the legs, amplifying patient morbidity and mortality. While obesity and alcoholism are common comorbidities, their impact on PAD myopathy is unclear. We sought to determine the effect of concurrent hindlimb ischemia (HLI), obesity and chronic alcohol consumption on muscle oxidative stress, and mitochondrial and limb function.
Methods:
Twenty-four male, 24 female, 8 month old C57BL/6 mice received high-fat-sucrose (HFS) or low-fat-sucrose (LFS) diets for 16 weeks, followed by either 20% ethanol (EtOH) added to the drinking water / continued water access for another 12 weeks (
n
=12 mice/4 groups). The left femoral artery was then ligated to induce HLI, and mice continued their assigned diets for another 4 weeks. The quadriceps from ischemic and non-ischemic limbs were excised at euthanasia. High-resolution respirometry measured muscle mitochondrial respiration and reactive oxygen species (H
2
O
2
) output. Muscle oxidative stress and mitochondrial quality control (mitophagy) were assessed enzymatically and by western blot.
Results:
Compared to LFS animals with/without EtOH access, two-way ANOVA showed post-HLI limb function was lower in HFS+water and HFS+EtOH animals (p<0.05). Mitochondrial respiration was lower in LFS+EtOH, HFS+water, and HFS+EtOH ischemic muscle during electron transport chain Complex I, state 2 (I.2), Complex I, state 3 (I.3) and Complex III versus LFS+water controls (p<0.05), and was further reduced during Complex II and IV in LFS and HFS-ischemic muscle exposed to EtOH (p<0.01). Mitochondrial H
2
O
2
yield was increased in HFS+water and HFS+EtOH ischemic muscle at complexes I.2, I.3, II, III and IV (p<0.05), but not in LFS+EtOH muscle. Oxidative damage (carbonyl accumulation) (p<0.0001) and reduced antioxidant levels (superoxide dismutase (p<0.05) and PGC-1alpha (p<0.001)) was only evident in HFS ischemic muscle with/without EtOH exposure. However, the mitochondrial detoxifying enzyme, aldehyde dehydrogenase-2 (p=0.03), and mitophagy markers LC3II:I ratio (p=0.002) and mitofusins 1 (p=0.02) and 2 (p=0.002), were only reduced in HFS+EtOH muscle.
Conclusion:
Obesity and chronic alcohol consumption exacerbates muscle mitochondriopathy in mice with HLI.
Related links
Details
- Title
- Concurrent Obesity And Chronic Alcohol Consumption Exacerbates Skeletal Muscle Mitochondrial Dysfunction In A Murine Model Of Peripheral Artery Disease (PAD)
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.44(Suppl_1), A1151
- Resource Type
- Abstract
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 1
- Copyright
- © 2024 by American Heart Association, Inc.
- Identifiers
- WOS:001350237100182; 99381273396206600
- Academic Unit
- Usha Kundu, MD College of Health; Public Health
- Language
- English