Hansen 2021 Physiol Rep

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Hansen C, Olsen K, Pilegaard H, Bangsbo J, Gliemann L, Hellsten Y (2021) High metabolic substrate load induces mitochondrial dysfunction in rat skeletal muscle microvascular endothelial cells. Physiol Rep 9:e14855.

» PMID: 34288561 Open Access

Hansen Camilla, Olsen Karina, Pilegaard Henriette, Bangsbo Jens, Gliemann Lasse, Hellsten Ylva (2021) Physiol Rep

Abstract: The influence of glucose and palmitic acid (PA) on mitochondrial respiration and emission of hydrogen peroxide (H2O2) was determined in skeletal muscle-derived microvascular endothelial cells. Measurements were assessed in intact and permeabilized (cells treated with 0.025% saponin) low passage endothelial cells with acute-or prolonged (3 days) incubation with regular (1.7 mM) or elevated (2.2 mM) PA concentrations and regular (5 mM) or elevated (11 mM) glucose concentrations. In intact cells, acute incubation with 1.7 mM PA alone or with 1.7 mM PA + 5 mM glucose (p < .001) led to a lower mitochondrial respiration (p < 0.01) and markedly higher H2O2/O2 emission (p < 0.05) than with 5 mM glucose alone. Prolonged incubation of intact cells with 1.7 mM PA +5 mM glucose led to 34% (p < 0.05) lower respiration and 2.5-fold higher H2O2/O2 emission (p < 0.01) than incubation with 5 mM glucose alone. Prolonged incubation of intact cells with elevated glucose led to 60% lower (p < 0.05) mitochondrial respiration and 4.6-fold higher H2O2/O2 production than incubation with 5 mM glucose in intact cells (p < 0.001). All effects observed in intact cells were present also in permeabilized cells (State 2). In conclusion, our results show that acute and prolonged lipid availability, as well as prolonged hyperglycemia, induces mitochondrial dysfunction as evidenced by lower mitochondrial respiration and enhanced H2O2/O2 emission. Elevated plasma substrate availability may lead to microvascular dysfunction in skeletal muscle by impairing endothelial mitochondrial function. Keywords: Glucose, Mitochondria, Palmitic acid, Reactive oxygen species, Respirometry, Vascular Bioblast editor: Plangger M O2k-Network Lab: DK Copenhagen Pilegaard H


Labels: MiParea: Respiration 


Organism: Rat  Tissue;cell: Skeletal muscle, Endothelial;epithelial;mesothelial cell  Preparation: Permeabilized cells, Intact cells 

Regulation: Substrate  Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k, O2k-Fluorometer 

2021-07, AmR